1 00:00:05,280 --> 00:00:10,480 WELCOME BACK TO DAY TWO OF THE 2 00:00:10,480 --> 00:00:15,400 PRECISION PROBIOTICS THERAPIES 3 00:00:15,400 --> 00:00:26,440 AND CHALLENGES AND WORK SHOPS. 4 00:00:26,440 --> 00:00:29,160 AND ON BEHALF OF THE NIH 5 00:00:29,160 --> 00:00:32,560 PLANNING COMMITTEE FOR THE 6 00:00:32,560 --> 00:00:34,360 WORKSHOP WE WANT TO WELCOME 7 00:00:34,360 --> 00:00:37,000 EVERYONE BACK FOR DAY TWO. 8 00:00:37,000 --> 00:00:39,880 BEFORE WE BEGIN I WOULD LIKE TO 9 00:00:39,880 --> 00:00:41,760 REVIEW A FEW LOGISTICS. 10 00:00:41,760 --> 00:00:46,600 A REMINDER TO MUTE YOURSELVES 11 00:00:46,600 --> 00:00:48,160 WHEN NOT SPEAKING AND DO MAKE 12 00:00:48,160 --> 00:00:49,960 SURE YOUR VIDEO IS ON DURING 13 00:00:49,960 --> 00:00:51,360 YOUR SESSION OR PARTICULARLY 14 00:00:51,360 --> 00:00:52,600 WHEN SPEAKING OR IF YOU HAVE 15 00:00:52,600 --> 00:00:54,160 COMMENTS DURING THE PANEL 16 00:00:54,160 --> 00:00:54,800 DISCUSSION. 17 00:00:54,800 --> 00:00:57,520 FOR OUR NIH VIDEO CAST VIEWERS 18 00:00:57,520 --> 00:01:01,120 YOU ARE WELCOME TO SUBMIT A 19 00:01:01,120 --> 00:01:02,680 QUESTION AT ANY TIME USING THE 20 00:01:02,680 --> 00:01:03,080 FORM. 21 00:01:03,080 --> 00:01:04,840 THE LINK IS GOING TO BE RIGHT 22 00:01:04,840 --> 00:01:06,560 BELOW THE SCREEN WHERE YOU'RE 23 00:01:06,560 --> 00:01:07,760 VIEWING THE LIVE STREAM. 24 00:01:07,760 --> 00:01:10,960 WE WILL TRY TO GET TO AT LEAST A 25 00:01:10,960 --> 00:01:12,520 FEW OF THE QUESTIONS FROM THE 26 00:01:12,520 --> 00:01:14,640 AUDIENCE DURING OUR PANEL 27 00:01:14,640 --> 00:01:16,160 DISCUSSION TIMES BUT WE'RE 28 00:01:16,160 --> 00:01:18,160 UNLIKELY TO GET TO ALL OF YOUR 29 00:01:18,160 --> 00:01:18,840 QUESTIONS. 30 00:01:18,840 --> 00:01:20,160 HOWEVER ALL QUESTIONS SUBMITTED 31 00:01:20,160 --> 00:01:21,320 WILL BE COLLECTED AND SHARED 32 00:01:21,320 --> 00:01:24,160 WITH THE PLANNING TEAM. 33 00:01:24,160 --> 00:01:26,160 FINALLY THE BULK OF THE MEETING 34 00:01:26,160 --> 00:01:29,840 IS BEING RECORDED AND WILL BE 35 00:01:29,840 --> 00:01:30,440 ARE SO, I HAVE HAD FOR FUTURE 36 00:01:30,440 --> 00:01:30,840 VIEWING. 37 00:01:30,840 --> 00:01:33,360 WE ASK THAT YOU BE RESPECTFUL BY 38 00:01:33,360 --> 00:01:35,560 THE FACT THAT SOME OF OUR FOLKS 39 00:01:35,560 --> 00:01:39,600 MIGHT BE SHARING EARLY DATA 40 00:01:39,600 --> 00:01:41,560 REFRAIN FROM TAKING SCREEN 41 00:01:41,560 --> 00:01:42,120 SHOTS. 42 00:01:42,120 --> 00:01:45,760 I'M NOW PLEASED TO TURN IT OVER 43 00:01:45,760 --> 00:01:51,080 TO OUR COCHAIRS DR. HYE-SOOK KIM 44 00:01:51,080 --> 00:01:57,960 AND DR. BARBARA SORKIN. 45 00:01:57,960 --> 00:02:02,480 WELCOME YOU TODAY AND WILL TURN 46 00:02:02,480 --> 00:02:04,560 IT OVER TO OUR SPEAKERS. 47 00:02:04,560 --> 00:02:06,000 TAKE IT AWAY 48 00:02:06,000 --> 00:02:07,440 >> THANK YOU, KATHERINE AND 49 00:02:07,440 --> 00:02:10,800 THANK YOU EVERYONE AND WELCOME 50 00:02:10,800 --> 00:02:13,360 TO EVERYONE. 51 00:02:13,360 --> 00:02:15,280 I WOULD LIKE TO START WITH THANK 52 00:02:15,280 --> 00:02:16,400 YOU TO ALL OF THE SPEAKERS 53 00:02:16,400 --> 00:02:18,640 YESTERDAY AND THE MODERATORS OF 54 00:02:18,640 --> 00:02:20,520 THE BOTH SESSIONS ONE AND TWO 55 00:02:20,520 --> 00:02:22,200 FOR THE FABULOUS TALK AND VERY 56 00:02:22,200 --> 00:02:23,440 EXCITING DISCUSSIONS. 57 00:02:23,440 --> 00:02:26,320 DURING THE SESSIONS WE ACTUALLY 58 00:02:26,320 --> 00:02:27,760 HAD IDENTIFIED CHALLENGES AND 59 00:02:27,760 --> 00:02:31,840 GAPS IN OUR CURRENT TECHNOLOGY 60 00:02:31,840 --> 00:02:34,440 IN PRECISION PROBIOTICS. 61 00:02:34,440 --> 00:02:36,440 FOR INSTANCE DEFINING 62 00:02:36,440 --> 00:02:40,400 CLARIFICATIONS OF MECHANISMS 63 00:02:40,400 --> 00:02:42,760 ACTIONS. 64 00:02:42,760 --> 00:02:47,520 AND WE ALSO FOUND A NONINVASIVE 65 00:02:47,520 --> 00:02:50,080 METHOD IS VERY CHALLENGING AND 66 00:02:50,080 --> 00:02:53,400 VERY IMPORTANT. 67 00:02:53,400 --> 00:02:55,120 SO FOR CONTINUE OUR JOURNEY 68 00:02:55,120 --> 00:02:57,120 TODAY WE'LL HEAR MORE ABOUT THE 69 00:02:57,120 --> 00:02:57,760 TECHNOLOGY. 70 00:02:57,760 --> 00:02:59,120 AND WE'LL HAVE THE DISCUSSION 71 00:02:59,120 --> 00:03:00,720 AROUND WHERE THIS TECHNOLOGIES 72 00:03:00,720 --> 00:03:11,000 SHOULD BE ADVANCED AND WHAT 73 00:03:11,000 --> 00:03:15,960 HURDLES ARE THERE. 74 00:03:15,960 --> 00:03:16,520 BARBARA. 75 00:03:16,520 --> 00:03:17,920 7 76 00:03:17,920 --> 00:03:20,280 >> THANK YOU SO MUCH HYE-SOOK 77 00:03:20,280 --> 00:03:22,280 FOR THAT QUICK SUMMARY OF 78 00:03:22,280 --> 00:03:22,720 YESTERDAY. 79 00:03:22,720 --> 00:03:26,720 MY THANKS AS WELL TO THE 80 00:03:26,720 --> 00:03:28,000 SPEAKERS AND ORGANIZERS AND ALL 81 00:03:28,000 --> 00:03:30,920 OF THE PEOPLE WHO SUBMITTED 82 00:03:30,920 --> 00:03:32,680 GREAT QUESTIONS. 83 00:03:32,680 --> 00:03:34,760 IT WAS VIGOROUS AND INFORMATIVE 84 00:03:34,760 --> 00:03:36,200 AND THOUGHT PROVOKING DISCUSSION 85 00:03:36,200 --> 00:03:38,960 AND LET'S KEEP UP THE MOMENTUM 86 00:03:38,960 --> 00:03:39,360 TODAY. 87 00:03:39,360 --> 00:03:41,160 BUT BEFORE WE MOVE TO THE 88 00:03:41,160 --> 00:03:43,520 SCIENCE TALKS PER SAY IT IS MY 89 00:03:43,520 --> 00:03:46,080 GREAT PLEASURE TO INTRODUCE THE 90 00:03:46,080 --> 00:03:51,640 ACTING DIRECTOR DR. JOSEPH 91 00:03:51,640 --> 00:03:52,160 BETTS. 92 00:03:52,160 --> 00:03:54,120 JOE BRINGS TO THE DIRECTOR SHIP 93 00:03:54,120 --> 00:03:59,560 OF ODS IN ADDITION TO HIS GREAT 94 00:03:59,560 --> 00:04:01,320 INTERPERSONAL SKILLS A WEALTH OF 95 00:04:01,320 --> 00:04:01,800 EXPERIENCE. 96 00:04:01,800 --> 00:04:04,680 HE WAS THE VICE PRESIDENT FOR 97 00:04:04,680 --> 00:04:09,840 SCIENTIFIC AND TECHNICAL AFFAIRS 98 00:04:09,840 --> 00:04:13,280 -- AND WORKED AFTER THAT FOR 99 00:04:13,280 --> 00:04:20,920 MANY YEARS AS THE FOOD AND DRUG 100 00:04:20,920 --> 00:04:22,520 ADMINISTRATION AND THEN AS A 101 00:04:22,520 --> 00:04:23,680 RESEARCH COUNCIL. 102 00:04:23,680 --> 00:04:24,040 HE BRINGS A WEALTH OF 103 00:04:24,040 --> 00:04:25,040 INFORMATION AND IT IS -- I'M 104 00:04:25,040 --> 00:04:26,760 VERY, VERY GLAD TO INTRODUCE 105 00:04:26,760 --> 00:04:28,200 HIM. 106 00:04:28,200 --> 00:04:29,760 JOE, TAKE IT AWAY. 107 00:04:29,760 --> 00:04:31,200 THANKS FOR THE GREAT SESSION 108 00:04:31,200 --> 00:04:32,160 YESTERDAY. 109 00:04:32,160 --> 00:04:34,040 IT WAS WONDER SON. 110 00:04:34,040 --> 00:04:36,440 AND I LOOK FORWARD TO MORE 111 00:04:36,440 --> 00:04:38,520 SAME. 112 00:04:38,520 --> 00:04:42,040 WHAT I BRING TO THIS VERY QUICK 113 00:04:42,040 --> 00:04:44,600 HOPEFULLY TALK IS KIND OF MY 114 00:04:44,600 --> 00:04:46,720 PERSONAL PERSPECTIVE FROM HAVING 115 00:04:46,720 --> 00:04:49,360 BEEN A REGULATOR IN INDUSTRY AND 116 00:04:49,360 --> 00:04:52,440 ALSO DIRECTOR OF ODS AND WHY 117 00:04:52,440 --> 00:04:55,080 THIS WORK IS SO IMPORTANT. 118 00:04:55,080 --> 00:04:59,200 SO I JUST START OFF QUICKLY -- 119 00:04:59,200 --> 00:05:03,440 WITH A LITTLE BIT BOILERPLATE 120 00:05:03,440 --> 00:05:05,200 ABOUT THE DIETARY SUPPLEMENT 121 00:05:05,200 --> 00:05:05,720 ACT. 122 00:05:05,720 --> 00:05:10,440 A COUPLE OF THINGS. 123 00:05:10,440 --> 00:05:13,640 DEFINE DIETARY SUPPLEMENTS AS A 124 00:05:13,640 --> 00:05:15,000 CATEGORY OF GOODS AS HAS NOT 125 00:05:15,000 --> 00:05:16,440 BEEN THE CASE IN THE PAST. 126 00:05:16,440 --> 00:05:19,840 IT CREATED THE DIETARY SUB 127 00:05:19,840 --> 00:05:28,040 ELEMENTS BY AMENDIN AMEND AMENDING. 128 00:05:28,040 --> 00:05:30,440 WHY IS THIS IMPORTANT? 129 00:05:30,440 --> 00:05:32,440 * I'M GOING TO READ THIS WHOLE 130 00:05:32,440 --> 00:05:35,960 SLIDE BUT I WILL SAY THAT THE 131 00:05:35,960 --> 00:05:37,960 REGULATORY PROVISIONS OF FOOD 132 00:05:37,960 --> 00:05:42,000 AND DRUG -- ACT DEFINE THE 133 00:05:42,000 --> 00:05:43,680 PRODUCTS PLACED IN THE 134 00:05:43,680 --> 00:05:45,920 MARKETPLACE BY THE INTENDED USE. 135 00:05:45,920 --> 00:05:48,360 DRUGS ARE INTENDED TO CURE, 136 00:05:48,360 --> 00:05:51,120 TREAT, MITIGATE DISEASE IN MAN 137 00:05:51,120 --> 00:05:52,320 OR ANIMALS. 138 00:05:52,320 --> 00:05:54,120 SUPPLEMENTS ARE INTENDED TO 139 00:05:54,120 --> 00:05:55,280 SUPPLEMENT THE DIET. 140 00:05:55,280 --> 00:05:58,360 THAT IS THE WHOLE DEFINITION. 141 00:05:58,360 --> 00:06:01,640 THERE IS SOME OTHER STUFF AROUND 142 00:06:01,640 --> 00:06:03,440 IT ABOUT WHAT CAN GO INTO THE 143 00:06:03,440 --> 00:06:05,640 MANUFACTURING OF A DIETARY 144 00:06:05,640 --> 00:06:07,200 SUPPLEMENT BUT THAT IS THE GIST 145 00:06:07,200 --> 00:06:09,160 OF IT. 146 00:06:09,160 --> 00:06:10,720 ANYTHING THAT WE CAN INGEST TO 147 00:06:10,720 --> 00:06:13,400 SUPPLEMENT THE DIET IS A DIETARY 148 00:06:13,400 --> 00:06:14,920 SUPPLEMENT. 149 00:06:14,920 --> 00:06:16,360 SUPPLEMENTS ARE CONSIDERED FOODS 150 00:06:16,360 --> 00:06:18,680 AND FOODS ARE SAFE BY DEFINITION 151 00:06:18,680 --> 00:06:21,040 UNLESS THEY ARE DIETARY 152 00:06:21,040 --> 00:06:21,640 INGREDIENTS. 153 00:06:21,640 --> 00:06:25,040 SO, THAT IS ALSO AN IMPORTANT 154 00:06:25,040 --> 00:06:29,760 INGREDIENT. 155 00:06:29,760 --> 00:06:31,920 SOME OTHER STUFF INTENDED TO BE 156 00:06:31,920 --> 00:06:33,240 TAKEN BY MOUTH. 157 00:06:33,240 --> 00:06:36,360 IT CONTAINS ONE OF SEVERAL 158 00:06:36,360 --> 00:06:38,000 INGREDIENTS WHICH IF YOU HAVE 159 00:06:38,000 --> 00:06:42,440 GONE INTO A WHOLE FOODS OR CBS 160 00:06:42,440 --> 00:06:44,080 YOU'LL RECOGNIZE VITAMINS AND 161 00:06:44,080 --> 00:06:47,040 MINERALS AND AMINO ACIDS BUT 162 00:06:47,040 --> 00:06:52,600 ALSO PRO-BIOTICS. 163 00:06:52,600 --> 00:06:57,440 ALSO DIETARY SUPPLEMENTS HAS A 164 00:06:57,440 --> 00:06:59,840 DATABASE -- LABELED DATABASE. 165 00:06:59,840 --> 00:07:03,520 THERE IS OVER 136,000 INDIVIDUAL 166 00:07:03,520 --> 00:07:05,720 LABELS OR PRODUCTS FOR DIETARY 167 00:07:05,720 --> 00:07:06,400 SUPPLEMENTS. 168 00:07:06,400 --> 00:07:09,120 THAT IS A LOT OF PRODUCTS. 169 00:07:09,120 --> 00:07:14,480 IT'S SEARCH ARTICLE. 170 00:07:14,480 --> 00:07:17,240 -- SEARCHABLE. 171 00:07:17,240 --> 00:07:20,080 AND THERE IS NOT QUITE 6,000 172 00:07:20,080 --> 00:07:22,840 LABELS USING THE BROAD TERM 173 00:07:22,840 --> 00:07:23,480 PRO-BIOTIC. 174 00:07:23,480 --> 00:07:26,720 THAT IS 4.5% OF THE DATABASE AND 175 00:07:26,720 --> 00:07:28,400 JUST BY WAY OF COMPARISON THE 176 00:07:28,400 --> 00:07:30,840 NUMBER OF FDA APPROVED 177 00:07:30,840 --> 00:07:32,080 PRO-BIOTIC DRUGS WHICH ARE 178 00:07:32,080 --> 00:07:34,280 REGULATED BY THE CENTER OF 179 00:07:34,280 --> 00:07:35,640 BIOLOGICALS IS ZERO. 180 00:07:35,640 --> 00:07:38,480 SO, THAT IS WHY ALL OF THIS 181 00:07:38,480 --> 00:07:40,040 WONDERFUL SCIENTIFIC EXPLORATION 182 00:07:40,040 --> 00:07:41,680 IS NECESSARY. 183 00:07:41,680 --> 00:07:44,040 WHY IS THAT THE CASE? 184 00:07:44,040 --> 00:07:47,040 ONE CAN MAKE THE ARGUMENT 185 00:07:47,040 --> 00:07:48,600 ECONOMICALLY THAT IT'S CHEAP TO 186 00:07:48,600 --> 00:07:49,920 BRING A DIETARY SUPPLEMENT TO 187 00:07:49,920 --> 00:07:52,160 THE MARKET OR SOMETHING LIKE 188 00:07:52,160 --> 00:07:52,360 THAT. 189 00:07:52,360 --> 00:07:57,280 REALLY ASIDE FROM MAINTAINING 190 00:07:57,280 --> 00:08:03,480 GUT HEALTH WHY ARE WE LOOKING AT 191 00:08:03,480 --> 00:08:06,240 PRO-BIOTICS IN THE FIRST PLACE? 192 00:08:06,240 --> 00:08:08,280 IT'S -- SOME OF THE TALKS WE 193 00:08:08,280 --> 00:08:11,240 HEARD YESTERDAY WERE TALKING 194 00:08:11,240 --> 00:08:15,160 ABOUT ULCER -- COLITIS. 195 00:08:15,160 --> 00:08:19,640 IT'S NOT A DRUG CLAIM. 196 00:08:19,640 --> 00:08:23,440 SO ODS PROVIDES A FACT SHEET 197 00:08:23,440 --> 00:08:25,080 AMONG OUR MANY FACT SHEETS 198 00:08:25,080 --> 00:08:28,120 DEALING WITH THE SUBJECT OF 199 00:08:28,120 --> 00:08:28,440 PRO-BIOTICS. 200 00:08:28,440 --> 00:08:29,880 WE HAVE FACT SHEETS FOR 201 00:08:29,880 --> 00:08:34,320 CONSUMERS FOR PROFESSIONAL 202 00:08:34,320 --> 00:08:37,080 PRACTITIONERS AND ALSO A SPANISH 203 00:08:37,080 --> 00:08:39,000 LANGUAGE FACT SHEET. 204 00:08:39,000 --> 00:08:42,200 AND IT'S ABOUT PRO-BIOTICS IS 205 00:08:42,200 --> 00:08:43,520 DIETARY SUPPLEMENTS. 206 00:08:43,520 --> 00:08:47,680 AN ATTEMPT TO SUMMARIZE THE 207 00:08:47,680 --> 00:08:51,000 USES. 208 00:08:51,000 --> 00:08:52,560 ODS DOES HAVE IT'S NOT AN 209 00:08:52,560 --> 00:08:56,080 ENORMOUS A AMOUNT OF MONEY IN 210 00:08:56,080 --> 00:08:58,320 OUR PORTFOLIO BUT WE DO HAVE 211 00:08:58,320 --> 00:09:01,960 SOME INVESTMENT IN PREBIOTICS 212 00:09:01,960 --> 00:09:05,760 AND PRO-BIOTICS RESEARCH. 213 00:09:05,760 --> 00:09:08,200 IN 2020 THAT WAS NORTH OF HALF A 214 00:09:08,200 --> 00:09:10,040 MILLION DOLLARS. 215 00:09:10,040 --> 00:09:13,800 WE CO-FOUND DRAFT APPLICATIONS. 216 00:09:13,800 --> 00:09:16,760 I DO WANT TO GIVE AN 217 00:09:16,760 --> 00:09:18,640 INTRODUCTION BY WAY OF PROVIDING 218 00:09:18,640 --> 00:09:21,960 MY OWN REASON THAT WE NEED TO DO 219 00:09:21,960 --> 00:09:23,440 THIS RESEARCH AND ALSO TO 220 00:09:23,440 --> 00:09:25,200 PROVIDE A A LITTLE BIT OF 221 00:09:25,200 --> 00:09:27,640 BACKGROUND IN ADS's STAKE IN 222 00:09:27,640 --> 00:09:28,840 THIS AREA. 223 00:09:28,840 --> 00:09:30,840 SO I WILL END THAT THERE. 224 00:09:30,840 --> 00:09:33,120 * SO THAT WE CAN MOVE ON TO OUR 225 00:09:33,120 --> 00:09:34,360 NEXT SPEAKER. 226 00:09:34,360 --> 00:09:36,360 WE HAVE WONDERFUL SPEAKERS WHO 227 00:09:36,360 --> 00:09:38,680 ARE WAY MORE EXPERT IN THIS AREA 228 00:09:38,680 --> 00:09:42,520 THAN I AM AND I WOULD RATHER 229 00:09:42,520 --> 00:09:44,880 DEVOTE OUR TIME TO THEM RATHER 230 00:09:44,880 --> 00:09:46,880 THAN TO ME. 231 00:09:46,880 --> 00:09:47,920 SO THANK YOU. 232 00:09:47,920 --> 00:09:51,120 AND WE'LL MOVE ON TO OUR KEYNOTE 233 00:09:51,120 --> 00:09:59,600 FOR THE DAY. 234 00:09:59,600 --> 00:10:03,600 SO WE'LL MOVE ON TO OUR KEYNOTE. 235 00:10:03,600 --> 00:10:08,520 AND THAT IS DR. GARY WU. 236 00:10:08,520 --> 00:10:09,840 HE IS FROM THE UNIVERSITY OF 237 00:10:09,840 --> 00:10:10,760 PENNSYLVANIA. 238 00:10:10,760 --> 00:10:19,040 HE IS THE FORWARD INNOCENT -- 239 00:10:19,040 --> 00:10:25,760 PROFESSOR GASTROINTESTINAL. 240 00:10:25,760 --> 00:10:27,800 DIRECTOR OF THE PAN CENTER FOR 241 00:10:27,800 --> 00:10:29,080 NUTRITIONAL SCIENTISTS AND 242 00:10:29,080 --> 00:10:33,600 MEDICINE AND CO-DIRECTOR -- GO 243 00:10:33,600 --> 00:10:37,160 MOLECULAR STUDIES AND CHILDREN'S 244 00:10:37,160 --> 00:10:39,240 HOSPITAL IN PENNSYLVANIA 245 00:10:39,240 --> 00:10:39,840 MICROBIOME PROGRAM. 246 00:10:39,840 --> 00:10:42,520 HE WAS THE INAUGURAL DIRECTOR 247 00:10:42,520 --> 00:10:46,160 AND CHAIR OF THE BOARD FOR THE 248 00:10:46,160 --> 00:10:48,680 AMERICAN GASTRO INTEREST LOGICAL 249 00:10:48,680 --> 00:10:50,640 ASSOCIATION * AND EDUCATION. 250 00:10:50,640 --> 00:10:53,320 AND IS AN ELECTED MEMBER OF BOTH 251 00:10:53,320 --> 00:10:55,240 THE AMERICAN SOCIETY FOR 252 00:10:55,240 --> 00:10:56,840 CLINICAL INVESTIGATION AND THE 253 00:10:56,840 --> 00:10:57,440 ASSOCIATION OF AMERICAN 254 00:10:57,440 --> 00:11:00,720 PHYSICIANS. 255 00:11:00,720 --> 00:11:05,200 RESEARCH IN THE WU LAB -- AND 256 00:11:05,200 --> 00:11:08,920 THE RELATIONSHIP OF SEVERAL 257 00:11:08,920 --> 00:11:16,280 ASPECTS OF METABOLISM -- -- -- 258 00:11:16,280 --> 00:11:20,040 HIS TALK TODAY IS THE GUT 259 00:11:20,040 --> 00:11:22,240 MICROBIOME AS A PROTOTYPE FOR 260 00:11:22,240 --> 00:11:24,440 THE OPPORTUNITIES THAT 261 00:11:24,440 --> 00:11:26,560 CHALLENGES IN THE DEVELOPMENT OF 262 00:11:26,560 --> 00:11:27,200 PRO-BIOTICS. 263 00:11:27,200 --> 00:11:28,720 THE NEXT STEP. 264 00:11:28,720 --> 00:11:29,160 DR. WU. 265 00:11:29,160 --> 00:11:31,080 TAKE IT AWAY 266 00:11:31,080 --> 00:11:31,400 >> GREAT. 267 00:11:31,400 --> 00:11:33,040 THANK YOU SO MUCH FOR THAT 268 00:11:33,040 --> 00:11:33,640 INTRODUCTION. 269 00:11:33,640 --> 00:11:45,440 LET ME SHARE MY SCREEN HERE. 270 00:11:45,440 --> 00:11:47,000 AM I ALL GOOD HERE? 271 00:11:47,000 --> 00:11:48,160 >> YOU ARE INDEED. 272 00:11:48,160 --> 00:11:49,360 >> ALL RIGHT. 273 00:11:49,360 --> 00:11:49,600 AWESOME. 274 00:11:49,600 --> 00:11:52,440 THANK YOU VERY MUCH FOR INVITING 275 00:11:52,440 --> 00:11:55,040 ME TO PARTICIPATE IN THIS 276 00:11:55,040 --> 00:11:57,000 SYMPOSIUM. 277 00:11:57,000 --> 00:11:59,120 WHEN I SORT OF REFLECTED ABOUT 278 00:11:59,120 --> 00:12:00,600 WHAT I WOULD SPEAK ABOUT OVER 279 00:12:00,600 --> 00:12:03,320 THE NEXT 35 MINUTES OR SO I 280 00:12:03,320 --> 00:12:06,720 THOUGHT INSTEAD OF SPEAKING WITH 281 00:12:06,720 --> 00:12:08,160 GRANULARITY ABOUT ONE OR TWO 282 00:12:08,160 --> 00:12:09,440 PROJECTS THAT I WOULD GIVE YOU 283 00:12:09,440 --> 00:12:12,280 AN OVER-ALL PERSPECTIVE 284 00:12:12,280 --> 00:12:13,960 CONCEPTUAL FRAMEWORK FROM THE 285 00:12:13,960 --> 00:12:15,440 VIEWPOINT OF A PHYSICIAN 286 00:12:15,440 --> 00:12:18,440 SCIENTISTS AND WHAT IT MEANS TO 287 00:12:18,440 --> 00:12:20,200 HAVE A PHYSICIAN PRO-BIOTIC FOR 288 00:12:20,200 --> 00:12:24,440 THE TREATMENT OF DISEASE. 289 00:12:24,440 --> 00:12:27,120 AND I WILL USE INFLAMMATORY 290 00:12:27,120 --> 00:12:29,880 BOWEL DISEASE AS THAT CONCEPTUAL 291 00:12:29,880 --> 00:12:31,040 FRAMEWORK. 292 00:12:31,040 --> 00:12:33,040 AND WITHIN THAT NOTION I WANTED 293 00:12:33,040 --> 00:12:34,280 TO HIGHLIGHT BOTH THE 294 00:12:34,280 --> 00:12:35,640 OPPORTUNITIES AND CHALLENGES IN 295 00:12:35,640 --> 00:12:37,000 THE FIELD BUT JUST AS 296 00:12:37,000 --> 00:12:38,520 IMPORTANTLY HIGHLIGHT THE 297 00:12:38,520 --> 00:12:42,440 SPEAKERS AND SESSIONS 3 AND 4. 298 00:12:42,440 --> 00:12:44,680 THE TOPICS AND THEIR EXPERTISE 299 00:12:44,680 --> 00:12:49,000 TO GIVE YOU A FLAVOR OF HOW THIS 300 00:12:49,000 --> 00:12:51,000 IS INTEGRATED TOGETHER WHEN 301 00:12:51,000 --> 00:12:52,560 THINKING ABOUT THE DEVELOPMENT 302 00:12:52,560 --> 00:12:54,880 OF NEW TYPES OF THERAPEUTIC 303 00:12:54,880 --> 00:12:55,440 MODALITIES. 304 00:12:55,440 --> 00:12:58,440 SO THESE ARE MY DISCLOSURES NONE 305 00:12:58,440 --> 00:13:02,040 OF WHICH ARE RELEVANT TO MY TALK 306 00:13:02,040 --> 00:13:02,680 TODAY. 307 00:13:02,680 --> 00:13:03,680 WHEN THINKING ABOUT PRECISION 308 00:13:03,680 --> 00:13:06,080 PROBIOTICS THERAPY I WANT TO 309 00:13:06,080 --> 00:13:07,680 HIGHLIGHT THE PRECISION MEDICINE 310 00:13:07,680 --> 00:13:10,120 INITIATIVE THAT WAS STARTED BY 311 00:13:10,120 --> 00:13:11,960 BARACK OBAMA. 312 00:13:11,960 --> 00:13:14,720 IT WAS FUNDAMENTAL IN LAUNCHING 313 00:13:14,720 --> 00:13:16,440 THE PROGRAM HERE AND THE 314 00:13:16,440 --> 00:13:19,040 STATEMENT -- BELOW IS ACTUALLY 315 00:13:19,040 --> 00:13:21,440 GERMAIN TO THE NOTION OF 316 00:13:21,440 --> 00:13:23,560 PRECIPITATION THERAPIES. 317 00:13:23,560 --> 00:13:26,040 UNTIL NOW MOST MEDICAL THERAPIES 318 00:13:26,040 --> 00:13:27,320 HAVE BEEN DESIGNED FOR THE 319 00:13:27,320 --> 00:13:27,840 AVERAGE PATIENT. 320 00:13:27,840 --> 00:13:30,280 AS A RESULT OF THIS ONE SIZE 321 00:13:30,280 --> 00:13:31,840 FITS ALL APPROACH TREATMENTS CAN 322 00:13:31,840 --> 00:13:34,280 BE SUCCESSFUL FOR SOME PATIENTS 323 00:13:34,280 --> 00:13:36,400 BUT NOT FOR OTHERS. 324 00:13:36,400 --> 00:13:37,840 PRECISION MEDICINE IS AN IN 325 00:13:37,840 --> 00:13:39,320 VACATE I'VE APPROACH THAT TAKES 326 00:13:39,320 --> 00:13:40,720 INTO ACCOUNT INDIVIDUAL 327 00:13:40,720 --> 00:13:43,080 DIFFERENCES IN PEOPLE'S GENES, 328 00:13:43,080 --> 00:13:47,160 ENVIRONMENTS AND LIFESTYLES. 329 00:13:47,160 --> 00:13:49,440 SO THIS IS THE PROGRESSION OF 330 00:13:49,440 --> 00:13:51,160 SCIENCE AND REDUCTION OF 331 00:13:51,160 --> 00:13:52,160 PRACTICE THINKING ABOUT NEW 332 00:13:52,160 --> 00:13:53,840 TYPES OF PRODUCTS THAT WOULD 333 00:13:53,840 --> 00:13:57,600 TREAT PATIENTS WITH DISEASE. 334 00:13:57,600 --> 00:14:00,240 THERE ARE PROCESS -- FECAL 335 00:14:00,240 --> 00:14:03,640 PRODUCTS AND DEFINED MICROBIAL 336 00:14:03,640 --> 00:14:06,040 CONSORTIA. 337 00:14:06,040 --> 00:14:10,200 WE KNOW THAT RECURRENT CDI IS 338 00:14:10,200 --> 00:14:12,280 EFFECTIVELY TREATED BY FMT AND 339 00:14:12,280 --> 00:14:15,200 WE'RE HOPEFUL THAT THESE OTHER 340 00:14:15,200 --> 00:14:16,400 MODALITIES CAN BE SUCCESSFUL. 341 00:14:16,400 --> 00:14:18,960 FOR OTHER DISEASES IT'S POSSIBLE 342 00:14:18,960 --> 00:14:25,400 THAT FMT MIGHT HAVE A ROLE. 343 00:14:25,400 --> 00:14:28,480 BUT CERTAINLY IS THE FOCUS OF 344 00:14:28,480 --> 00:14:29,440 TECHNOLOGY DEVELOPMENT 345 00:14:29,440 --> 00:14:36,240 ESPECIALLY WHEN THINKING ABOUT 346 00:14:36,240 --> 00:14:39,120 MICROBIAL CONSORTIA DEVELOPMENT. 347 00:14:39,120 --> 00:14:42,720 WE BETTER DEFINE WHAT WE'RE IN 348 00:14:42,720 --> 00:14:44,160 ACCUMULATING PATIENTS WITH THE 349 00:14:44,160 --> 00:14:45,480 SAFER IT'S GOING TO BE. 350 00:14:45,480 --> 00:14:47,560 WE BEGIN WITH FMT. 351 00:14:47,560 --> 00:14:49,680 THAT IS WHERE WE ARE NOW BUT 352 00:14:49,680 --> 00:14:51,560 WE'RE HOPEFUL THAT FOR 353 00:14:51,560 --> 00:14:53,600 SUSTAINABILITY WE'LL BE MOVING 354 00:14:53,600 --> 00:14:54,920 ON TO BETTER TYPES OF 355 00:14:54,920 --> 00:14:56,600 TECHNOLOGIES BASED ON WONDERFUL 356 00:14:56,600 --> 00:14:58,040 SCIENCE IN THE FIELD. 357 00:14:58,040 --> 00:14:59,480 SO THESE ARE THE VARIOUS 358 00:14:59,480 --> 00:15:01,400 SESSIONS OBVIOUSLY IN THE 359 00:15:01,400 --> 00:15:02,640 SYMPOSIUM. 360 00:15:02,640 --> 00:15:06,720 I'M GOING TO HIGHLIGHT SECTION 361 00:15:06,720 --> 00:15:13,480 THREE AND SECTION FOUR. 362 00:15:13,480 --> 00:15:16,400 SO WHERE VERY BE BEEN AND WHERE 363 00:15:16,400 --> 00:15:17,440 ARE WE CURRENTLY? 364 00:15:17,440 --> 00:15:19,840 THE MOTION OF PRO-BIOTICS WHICH 365 00:15:19,840 --> 00:15:24,880 ARE DEFINED AS LIVE MICRO 366 00:15:24,880 --> 00:15:27,120 ORGANISMS -- CONFER A HEALTH 367 00:15:27,120 --> 00:15:31,400 BENEFIT TO THE HOST. 368 00:15:31,400 --> 00:15:33,440 AND JUST PULL OUT ONE PARTICULAR 369 00:15:33,440 --> 00:15:35,040 QUOTE FROM THIS. 370 00:15:35,040 --> 00:15:43,400 WHERE THE AUTHOR STATES ALL-PRO ALL-PRO 371 00:15:43,400 --> 00:15:45,400 BIOTICS HAVE BECOME AN INTEGRAL 372 00:15:45,400 --> 00:15:49,160 PART. 373 00:15:51,360 --> 00:15:53,120 SO I THINK WE'VE LEARNED A LOT 374 00:15:53,120 --> 00:15:55,440 ABOUT THE PROCESSING AND 375 00:15:55,440 --> 00:15:57,800 DEVELOPMENT OF PRO-BIOTICS 376 00:15:57,800 --> 00:16:05,240 KEEPING ORGANIZ -- ORGANISMS LIVE AT 377 00:16:05,240 --> 00:16:06,440 SCALE. 378 00:16:06,440 --> 00:16:10,640 FROM THE FDA STANDPOINT LIVE 379 00:16:10,640 --> 00:16:12,760 PRODUCTS WHICH ARE DEFINED AS 380 00:16:12,760 --> 00:16:17,400 LIVE ORGANISMS THAT FOR EXAMPLE 381 00:16:17,400 --> 00:16:20,480 BACTERIA THAT TREAT, PREVENT OR 382 00:16:20,480 --> 00:16:22,600 CARRY DISEASE CONDITION IN 383 00:16:22,600 --> 00:16:24,640 HUMANS AND IS NOT A VACCINE. 384 00:16:24,640 --> 00:16:25,960 THESE ARE THE FOUR LARGE AREAS 385 00:16:25,960 --> 00:16:27,760 THAT I WANT TO COVER. 386 00:16:27,760 --> 00:16:29,200 IN MY TALK. 387 00:16:29,200 --> 00:16:31,800 WHAT IS THE ACTIVE COMPONENT? 388 00:16:31,800 --> 00:16:33,880 DOES IT NEED TO BE ALIVE. 389 00:16:33,880 --> 00:16:35,480 CAN IT BE DEAD? 390 00:16:35,480 --> 00:16:38,800 DOES IT INVOLVE DRUG METABOLISM. 391 00:16:38,800 --> 00:16:41,240 DOES IT INVOLVE METABOLITE 392 00:16:41,240 --> 00:16:43,360 PRODUCTION AND MAYBE FUNGI AND 393 00:16:43,360 --> 00:16:46,720 VIRUSES ARE ACTUALLY IMPORTANT. 394 00:16:46,720 --> 00:16:49,720 IN A LIVE ORGANISM IS NECESSARY 395 00:16:49,720 --> 00:16:53,640 -- WE HEARD A LOT ABOUT THAT. 396 00:16:53,640 --> 00:16:54,040 YESTERDAY. 397 00:16:54,040 --> 00:16:57,640 I WILL REPEAT SOME OF THIS MAYBE 398 00:16:57,640 --> 00:16:59,280 FROM A SLIGHTLY DIFFERENT 399 00:16:59,280 --> 00:17:00,040 PERSPECTIVE TODAY. 400 00:17:00,040 --> 00:17:01,000 THE IMPORTANCE OF THE 401 00:17:01,000 --> 00:17:03,840 ENVIRONMENT OF THE CONTEXT OF 402 00:17:03,840 --> 00:17:08,440 THE MICRO BIOTA. 403 00:17:08,440 --> 00:17:13,040 AND THEN IS THERE A NEED FOR 404 00:17:13,040 --> 00:17:15,680 COMPANION DIAGNOSTIC RESEARCH. 405 00:17:15,680 --> 00:17:19,520 WHAT IS THE ACTIVE COMPONENT? 406 00:17:19,520 --> 00:17:21,440 OBVIOUSLY NOVEMBER ALE BACTERIAL 407 00:17:21,440 --> 00:17:23,320 STRAINS ARE IMPORTANT AND ERWIN 408 00:17:23,320 --> 00:17:26,840 IS GOING TO BE SPEAKING ABOUT 409 00:17:26,840 --> 00:17:29,800 NOVEL PRO-BIOTICS. 410 00:17:29,800 --> 00:17:32,840 DRUG METABOLISM. 411 00:17:32,840 --> 00:17:36,040 ANDY GOOD MAN GAVE A GREAT TALK. 412 00:17:36,040 --> 00:17:38,560 EMILY WILL BE TALKING ABOUT 413 00:17:38,560 --> 00:17:42,240 DECIPHERING THE HUMAN MICROBIOME 414 00:17:42,240 --> 00:17:43,640 WITH CHEMISTRY. 415 00:17:43,640 --> 00:17:45,240 WE HEARD A BIT ABOUT THIS 416 00:17:45,240 --> 00:17:49,000 YESTERDAY. 417 00:17:49,000 --> 00:17:52,000 A NICE ARTICLE IN CELL. 418 00:17:52,000 --> 00:17:54,920 TO IDENTIFY SMALL MOLECULES THAT 419 00:17:54,920 --> 00:17:56,040 HAVE AN IMPACT. 420 00:17:56,040 --> 00:17:59,400 I'M GOING TO COME BACK TO THE 421 00:17:59,400 --> 00:18:00,960 TOPIC THAT WHICH IS GOING TO BE 422 00:18:00,960 --> 00:18:07,000 DIFFERENT BUT THIS IS A 423 00:18:07,000 --> 00:18:10,960 MARVELOUS ARTICLE. 424 00:18:10,960 --> 00:18:12,360 ENGINEERED FUNCTION. 425 00:18:12,360 --> 00:18:14,320 TO DELIVER THERAPEUTICS. 426 00:18:14,320 --> 00:18:16,920 MAYBE IT'S NOT JUST BACTERIA. 427 00:18:16,920 --> 00:18:21,040 MIC ROW -- AND FUNGI AND YEAST 428 00:18:21,040 --> 00:18:21,880 ARE IMPORTANT. 429 00:18:21,880 --> 00:18:24,240 AND JUNE HAS DONE SOME REALLY 430 00:18:24,240 --> 00:18:25,560 IMPORTANT WORK IN THIS AREA AND 431 00:18:25,560 --> 00:18:26,800 SHE IS GOING TO BE TALKING ABOUT 432 00:18:26,800 --> 00:18:29,680 THE IMMUNE SYSTEM TO IDENTIFY 433 00:18:29,680 --> 00:18:32,240 RELEVANT MICROBES AND I SUSPECT 434 00:18:32,240 --> 00:18:35,880 THAT SHE WILL BE TOUCHING UPON 435 00:18:35,880 --> 00:18:36,320 FUNGI. 436 00:18:36,320 --> 00:18:37,800 BUT NOBODY IS TALKING ABOUT 437 00:18:37,800 --> 00:18:39,440 VIRUSES THAT I KNOW OF FOR 438 00:18:39,440 --> 00:18:42,080 EXAMPLE BACTERIA AGE BUT I WANT 439 00:18:42,080 --> 00:18:46,040 TO HIGHLIGHT THIS WORK ABOUT 440 00:18:46,040 --> 00:18:50,040 TARGETING BACTERIA TO ATTENUATE 441 00:18:50,040 --> 00:18:51,440 ALCOHOLIC LIVER DISEASE AND THEN 442 00:18:51,440 --> 00:18:54,000 THE NOTION OF WHETHER OR NOT IT 443 00:18:54,000 --> 00:18:58,120 COULD BE A POST BIOTIC. 444 00:18:58,120 --> 00:19:00,240 THE ORGANISM DOESN'T NECESSARILY 445 00:19:00,240 --> 00:19:02,720 NEED TO BE VIABLE AND THIS IS 446 00:19:02,720 --> 00:19:04,040 INTERESTING. 447 00:19:04,040 --> 00:19:08,000 SHOWING PAST OUR RISED -- 448 00:19:08,000 --> 00:19:11,120 READING * TO A BIGGER EFFECT 449 00:19:11,120 --> 00:19:13,200 THAN THE LIVE ORGANISMS ITSELF. 450 00:19:13,200 --> 00:19:16,320 SO IT'S A WIDE RANGE OF TOPICS 451 00:19:16,320 --> 00:19:18,560 THAT WE CAN TALK ABOUT IN 452 00:19:18,560 --> 00:19:21,200 TERMING WHAT IS THE ACTIVE 453 00:19:21,200 --> 00:19:24,640 COMPONENT THAT CAN BE UTILIZED 454 00:19:24,640 --> 00:19:28,040 OR TREAT DISEASE. 455 00:19:28,040 --> 00:19:30,240 THIS BI-DIRECTION ALL THE OF 456 00:19:30,240 --> 00:19:32,880 MICROBIOME INVESTIGATION. 457 00:19:32,880 --> 00:19:42,560 BASIBASIC RESEARCHERS DEFINE -- AND 458 00:19:42,560 --> 00:19:45,200 FOR THAT REASON THERE IS A HIGH 459 00:19:45,200 --> 00:19:46,600 SIGNAL TO NOISE RATIO. 460 00:19:46,600 --> 00:19:49,240 FOR THOSE PURPOSES WE CAN DEFINE 461 00:19:49,240 --> 00:19:51,680 PROOF OF CONCEPT CAUSE AND 462 00:19:51,680 --> 00:19:53,240 EFFECT RELATIONSHIPS IN A MODEST 463 00:19:53,240 --> 00:19:54,720 SIDE COHORT. 464 00:19:54,720 --> 00:19:56,920 ON THE OTHER HAND ULTIMATELY WE 465 00:19:56,920 --> 00:19:58,480 WANT TO BE DOING THINGS THAT ARE 466 00:19:58,480 --> 00:20:00,720 RELEVANT TO HUMANS BUT THE 467 00:20:00,720 --> 00:20:03,760 CHALLENGE IS THAT HUMANS LIVE IN 468 00:20:03,760 --> 00:20:05,840 A FREE LIVING AND I HIGHLY 469 00:20:05,840 --> 00:20:07,200 VARIABLE ENVIRONMENT. 470 00:20:07,200 --> 00:20:09,840 HIGH LEVEL GENETIC DIVERSITY AND 471 00:20:09,840 --> 00:20:11,240 VARIABLE DIET. 472 00:20:11,240 --> 00:20:14,040 AND FOR THAT REASON THERE IS A 473 00:20:14,040 --> 00:20:17,280 LOWER SIGNAL TO NOISE RATIO. 474 00:20:17,280 --> 00:20:19,480 BUT WE DO HAVE TO KEEP IN MIND 475 00:20:19,480 --> 00:20:21,200 THAT SMALL EFFECT SIZE OVER 476 00:20:21,200 --> 00:20:24,400 LARGE POPULATIONS CAN BE 477 00:20:24,400 --> 00:20:25,880 IMPACTFUL. 478 00:20:25,880 --> 00:20:28,440 ALSO IT EMPHASIZES THE NEED FOR 479 00:20:28,440 --> 00:20:32,200 THE APPROACH TO THERAPEUTICS. 480 00:20:32,200 --> 00:20:34,080 SO AS AN EXAMPLE OF THIS THIS IS 481 00:20:34,080 --> 00:20:36,000 JUST WORK WE PUBLISHED A NUMBER 482 00:20:36,000 --> 00:20:37,760 OF YEARS AGO LOOKING AT THE 483 00:20:37,760 --> 00:20:39,240 IMPACT OF DIET. 484 00:20:39,240 --> 00:20:41,600 THIS WAS A CONTROLLED FEEDING 485 00:20:41,600 --> 00:20:42,040 EXPERIMENT. 486 00:20:42,040 --> 00:20:45,080 10 HEALTHY VOLUNTEERS. 487 00:20:45,080 --> 00:20:47,640 RANDOMIZED TO HIGH FIBER VERSUS 488 00:20:47,640 --> 00:20:49,560 LOW FIBER DIET. 489 00:20:49,560 --> 00:20:51,440 WE COLLECTED FECAL SAMPLES. 490 00:20:51,440 --> 00:20:53,360 EACH BALL IS A DIFFERENT 491 00:20:53,360 --> 00:21:02,080 COMPOSITION OF A MICR MICRO BOTA. 492 00:21:02,080 --> 00:21:04,840 EACH INDIVIDUAL OR EACH COLOR IS 493 00:21:04,840 --> 00:21:06,400 VERY DIFFERENT FROM THE OTHER 494 00:21:06,400 --> 00:21:06,840 COLORS. 495 00:21:06,840 --> 00:21:09,040 SO, THAT IS HOW DIFFERENT WE ARE 496 00:21:09,040 --> 00:21:09,840 FROM EACH OTHER. 497 00:21:09,840 --> 00:21:11,440 THE ARROWS POINT TO DAY ONE OF 498 00:21:11,440 --> 00:21:13,360 THE STUDY. 499 00:21:13,360 --> 00:21:15,040 FOR EACH ONE OF THE -- FOR A 500 00:21:15,040 --> 00:21:16,160 NUMBER OF DIFFERENT COLORS AND 501 00:21:16,160 --> 00:21:18,360 YOU CAN SEE THAT DAY ONE OF THE 502 00:21:18,360 --> 00:21:20,600 STUDY IS DIFFERENT FROM ALL THE 503 00:21:20,600 --> 00:21:21,840 OTHER DAYS OF THAT PARTICULAR 504 00:21:21,840 --> 00:21:23,840 COLOR MEANING THAT YES DIET DOES 505 00:21:23,840 --> 00:21:30,880 HAVE AN IMPACT ON THE -- ON THE 506 00:21:30,880 --> 00:21:32,640 -- COMPOSITION. 507 00:21:32,640 --> 00:21:34,520 THE OTHER POINT IS THAT THE 508 00:21:34,520 --> 00:21:36,520 VECTOR FROM DAY ONE TO ALL OF 509 00:21:36,520 --> 00:21:40,640 THE OTHER DAYS SEEMS TO BE -- 510 00:21:40,640 --> 00:21:41,240 STOCASTIC. 511 00:21:41,240 --> 00:21:42,040 NOT CONSISTENT. 512 00:21:42,040 --> 00:21:43,920 EVEN THOUGH PEOPLE WERE EATING 513 00:21:43,920 --> 00:21:44,880 SIMILAR THINGS. 514 00:21:44,880 --> 00:21:46,800 PEOPLE DIDN'T CONVERGE IN TERMS 515 00:21:46,800 --> 00:21:49,880 OF THEIR COMPOSITION OF MICRO 516 00:21:49,880 --> 00:21:56,640 GOT A WITHIN 10 DAYS. 517 00:21:56,640 --> 00:21:58,920 * SO ONE COULD SAYS THERE IS A 518 00:21:58,920 --> 00:22:00,840 LOT OF NOISE. 519 00:22:00,840 --> 00:22:03,240 BUT IT'S INFORMATION THAT CAN BE 520 00:22:03,240 --> 00:22:05,200 MINED AND HAS UTILITY FOR THE 521 00:22:05,200 --> 00:22:06,760 PURPOSES OF PERSONALIZATION. 522 00:22:06,760 --> 00:22:08,440 SO THIS IS SOME OF THE WORK THAT 523 00:22:08,440 --> 00:22:10,520 YOU ALL KNOW OF BY AARON AND 524 00:22:10,520 --> 00:22:12,960 OTHERS AT THE WEISMAN INSTITUTE 525 00:22:12,960 --> 00:22:15,000 WHO TOOK ADVANTAGE OF THAT 526 00:22:15,000 --> 00:22:16,840 INTEREST SUBJECT VARIABILITY IN 527 00:22:16,840 --> 00:22:20,840 THE MICROBIOME TO COME UP WITH A 528 00:22:20,840 --> 00:22:25,480 PERSONALIZED NUTRITION PREDICTOR 529 00:22:25,480 --> 00:22:29,240 THAT WOULD IMPROVE GLYCEMIC 530 00:22:29,240 --> 00:22:29,640 RESPONSES. 531 00:22:29,640 --> 00:22:31,680 THIS IS EARLY DAYS BUT IT'S AN 532 00:22:31,680 --> 00:22:34,160 INTERESTING CONCEPT AND IN TOTAL 533 00:22:34,160 --> 00:22:36,480 THAT WHOLE NOTION OF 534 00:22:36,480 --> 00:22:38,040 PERSONALIZATION AND PRECISION IS 535 00:22:38,040 --> 00:22:41,240 REALLY THE CORNERSTONE FOR THE 536 00:22:41,240 --> 00:22:43,800 PRECISION FOR NUTRITION HEALTH 537 00:22:43,800 --> 00:22:45,560 INITIATIVE THAT WAS JUST 538 00:22:45,560 --> 00:22:47,240 LAUNCHED BY THE ALL OF US 539 00:22:47,240 --> 00:22:50,440 PROGRAM AT NIH WHERE THE GUT 540 00:22:50,440 --> 00:22:52,000 MICROBIOME IS A VERY IMPORTANT 541 00:22:52,000 --> 00:22:53,640 COMPONENT OF THAT. 542 00:22:53,640 --> 00:22:56,520 SO WHAT ACTUALLY IS RESPONSIBLE 543 00:22:56,520 --> 00:22:57,640 FOR THAT INTER-SUBJECT 544 00:22:57,640 --> 00:22:59,680 VARIABILITY? 545 00:22:59,680 --> 00:23:01,360 THERE IS EVIDENCE THAT THIS IS 546 00:23:01,360 --> 00:23:03,720 AT THE STRAIN LEVEL OF MICROBES. 547 00:23:03,720 --> 00:23:06,200 SO I'M SHOWING YOU SOME WORK 548 00:23:06,200 --> 00:23:09,040 FROM NICOLE AND CURTIS -- 549 00:23:09,040 --> 00:23:12,360 SHOWING YOU DOMINANT FREQUENCY A 550 00:23:12,360 --> 00:23:16,640 CONGRESS ALL SITES -- AND 551 00:23:16,640 --> 00:23:18,880 MICROBIAL SPECIES AND BIOMARKERS 552 00:23:18,880 --> 00:23:21,320 AND THE POINT IS THAT SINGLE 553 00:23:21,320 --> 00:23:23,960 STRAINS FROM A SEQUENCING 554 00:23:23,960 --> 00:23:26,400 STANDPOINT TEND TO DOMINATE MOST 555 00:23:26,400 --> 00:23:27,160 SPECIES. 556 00:23:27,160 --> 00:23:29,920 BUT THAT GENETIC DIVERSITY IS 557 00:23:29,920 --> 00:23:31,280 SOMEWHAT DIFFERENT BETWEEN 558 00:23:31,280 --> 00:23:33,960 DIFFERENT TYPES OF SPECIES WHERE 559 00:23:33,960 --> 00:23:36,480 STRAIN DOMINANCE IS SOMEWHAT 560 00:23:36,480 --> 00:23:37,880 DIFFERENT. 561 00:23:37,880 --> 00:23:39,800 NEVERTHELESS THE MICROBIAL 562 00:23:39,800 --> 00:23:42,120 STABILITY AND UNIQUENESS THAT WE 563 00:23:42,120 --> 00:23:43,880 SEE EXTEND DOWN TO THE STRAIN 564 00:23:43,880 --> 00:23:45,440 LEVEL. 565 00:23:45,440 --> 00:23:47,640 SO WE HEARD A LOT ABOUT 566 00:23:47,640 --> 00:23:49,080 DIFFERENT STRAINS YESTERDAY. 567 00:23:49,080 --> 00:23:50,760 WE'LL BE HEARING MORE ABOUT THAT 568 00:23:50,760 --> 00:23:51,200 TODAY. 569 00:23:51,200 --> 00:23:55,480 THIS IS JUST A REVIEW BY CURTIS 570 00:23:55,480 --> 00:23:57,920 EXAMINING DIFFERENT MODALITIES 571 00:23:57,920 --> 00:24:00,440 BY WHICH YOU CAN LOOK AT STRAIN 572 00:24:00,440 --> 00:24:01,720 LEVEL EPIDEMIOLOGY. 573 00:24:01,720 --> 00:24:05,160 I WANT TO HIGHLIGHT THIS CORNER 574 00:24:05,160 --> 00:24:05,640 HERE. 575 00:24:05,640 --> 00:24:07,480 ALTHOUGH THERE IS A DOMINANT 576 00:24:07,480 --> 00:24:09,080 STRAIN AND SOMETIMES VERY 577 00:24:09,080 --> 00:24:10,960 DOMINANT IN A PARTICULAR SPECIES 578 00:24:10,960 --> 00:24:15,600 WHEN YOU ACTUALLY ISOLATE 579 00:24:15,600 --> 00:24:17,160 ORGANISMS AND CULTURE THEM YOU 580 00:24:17,160 --> 00:24:19,040 CAN PICK OUT MANY DIFFERENT 581 00:24:19,040 --> 00:24:21,040 TYPES OF STRAINS FOR PARTICULAR 582 00:24:21,040 --> 00:24:22,600 SPECIES IN MOST CASES. 583 00:24:22,600 --> 00:24:25,680 SO WHAT THAT MEANS IS THAT 584 00:24:25,680 --> 00:24:27,040 SEQUENCING TELLS US PART OF THE 585 00:24:27,040 --> 00:24:27,240 PICTURE. 586 00:24:27,240 --> 00:24:30,560 YOU CAN PICK UP THE DOMINANCE OF 587 00:24:30,560 --> 00:24:32,320 ONE PARTICULAR ORGANISM BUT 588 00:24:32,320 --> 00:24:34,560 THERE MAY BE LESS DOMINANT 589 00:24:34,560 --> 00:24:36,760 STRAINS THAT CAN BE EQUALLY 590 00:24:36,760 --> 00:24:40,480 IMPORTANT IF NOT MORE IMPORTANT 591 00:24:40,480 --> 00:24:40,960 THAN PHYSIOLOGY. 592 00:24:40,960 --> 00:24:44,480 WE DO NEED TO BE DOING BASIC 593 00:24:44,480 --> 00:24:46,800 MICROBIOLOGY AND CULTIVATION 594 00:24:46,800 --> 00:24:49,640 GROWING ORGANISMS TO LOOK AT 595 00:24:49,640 --> 00:24:49,920 PHYSIOLOGY. 596 00:24:49,920 --> 00:24:52,760 ANOTHER THING THAT WE HAVE TO BE 597 00:24:52,760 --> 00:24:55,280 COGNIZANT OF IS LATERAL GENE 598 00:24:55,280 --> 00:24:55,960 TRANSFER. 599 00:24:55,960 --> 00:24:58,520 MAKING THE POINT THAT ON HUMAN 600 00:24:58,520 --> 00:25:01,160 BODY SURFACE THAT'S THERE COULD 601 00:25:01,160 --> 00:25:04,520 BE SUBSTANTIAL -- IN TRANSFER. 602 00:25:04,520 --> 00:25:06,440 THEY ARE NOT ENTIRELY STABLE 603 00:25:06,440 --> 00:25:08,400 OVER TIME. 604 00:25:08,400 --> 00:25:09,840 THIS IS WORK THAT WAS 605 00:25:09,840 --> 00:25:12,840 HIGHLIGHTED BY JUSTIN -- 606 00:25:12,840 --> 00:25:15,040 YESTERDAY. 607 00:25:15,040 --> 00:25:16,640 JUST BEARS REPEATING. 608 00:25:16,640 --> 00:25:19,440 LOOKING AT A PRO-BIOTIC DELIVERY 609 00:25:19,440 --> 00:25:21,120 TO INDIVIDUALS WHERE SOME 610 00:25:21,120 --> 00:25:26,680 INDIVIDUALS ACTUALLY SHOWED 611 00:25:26,680 --> 00:25:28,160 ENGRAPHMENT VERSUS INDIVIDUALS 612 00:25:28,160 --> 00:25:30,280 THAT DID NOT SHOW ENGRAPHMENT 613 00:25:30,280 --> 00:25:33,920 AND THIS WAS OR LATE WITH UNDER 614 00:25:33,920 --> 00:25:38,840 REPRESENTATION OF CARBO HIGH 615 00:25:38,840 --> 00:25:41,400 RATE UTILIZATION. 616 00:25:41,400 --> 00:25:44,280 THE NICHE IS OPEN FOR THE 617 00:25:44,280 --> 00:25:46,640 ENGRAPHMENT OF A PRO-BIOTIC 618 00:25:46,640 --> 00:25:48,760 BACTERIA BECAUSE OF HIGHER 619 00:25:48,760 --> 00:25:50,520 RESOURCE AVAILABILITY. 620 00:25:50,520 --> 00:25:52,120 THE BIOLOGICAL BASES FOR THIS 621 00:25:52,120 --> 00:25:55,040 HAS BEEN SHOWN BY A NUMBER OF 622 00:25:55,040 --> 00:25:59,160 INVESTIGATORS FIRST OF ALL BY -- 623 00:25:59,160 --> 00:26:01,400 -- JUSTIN SHOWED THIS YESTERDAY 624 00:26:01,400 --> 00:26:04,320 AND ENGRAPHMENT AND PERSISTENCE 625 00:26:04,320 --> 00:26:07,720 OF -- IS SOMEWHAT DEPENDENT UPON 626 00:26:07,720 --> 00:26:11,800 THE -- WHICH IS INVOLVED IN -- 627 00:26:11,800 --> 00:26:12,560 METABOLISM. 628 00:26:12,560 --> 00:26:18,440 SO WHEN MUTATED IT CAN NO LONGER 629 00:26:18,440 --> 00:26:19,840 OUTCOMPETE THE WILD TYPE. 630 00:26:19,840 --> 00:26:23,680 THIS IS A LOSS OF FUNCTION -- 631 00:26:23,680 --> 00:26:26,680 BUT -- THIS IS A GAIN OF 632 00:26:26,680 --> 00:26:29,040 FUNCTION -- WHERE THE STRAIN CAN 633 00:26:29,040 --> 00:26:33,440 ACTUALLY PERSIST IN THE NEW 634 00:26:33,440 --> 00:26:36,720 NICHE DEVELOPED. 635 00:26:36,720 --> 00:26:38,920 SO WORK BY ALLEN AND OTHERS AT 636 00:26:38,920 --> 00:26:42,920 THE WEISMAN INSTITUTE UTILIZED A 637 00:26:42,920 --> 00:26:44,680 PRO-BIOTIC CONSORTIUM TO REALLY 638 00:26:44,680 --> 00:26:47,480 LOOK AT THIS IN BOTH ANIMAL 639 00:26:47,480 --> 00:26:49,440 MODELS AND HUMANS. 640 00:26:49,440 --> 00:26:51,240 AND IT'S A VERY IMPORTANT 641 00:26:51,240 --> 00:26:52,640 OBSERVATION FOR THE FIELD HERE. 642 00:26:52,640 --> 00:26:55,920 THE FIRST POINT IS THAT STOOL 643 00:26:55,920 --> 00:26:57,480 DOESN'T NECESSARILY REPRESENT 644 00:26:57,480 --> 00:27:00,600 THE MUCOSAL SURFACE. 645 00:27:00,600 --> 00:27:01,840 WE KNOW THAT. 646 00:27:01,840 --> 00:27:04,600 KNOWING THAT -- AND CERTAIN 647 00:27:04,600 --> 00:27:07,160 CIRCUMSTANCES OCCURS AT THE 648 00:27:07,160 --> 00:27:08,600 MUCOSAL SURFACE. 649 00:27:08,600 --> 00:27:09,840 WHEN THINKING ABOUT TRANSLATION 650 00:27:09,840 --> 00:27:15,840 OF MICE TO HUMANS IS MICE HAVE 651 00:27:15,840 --> 00:27:17,680 RESISTANCE TO PRO-BIOTICS. 652 00:27:17,680 --> 00:27:20,040 SO HIGHLIGHTING THE ADVANTAGES 653 00:27:20,040 --> 00:27:20,920 AND SOME OF THE OPPORTUNITIES 654 00:27:20,920 --> 00:27:23,240 YET CHALLENGES IN THE FIELD. 655 00:27:23,240 --> 00:27:25,120 SO THERE ARE A NUMBER OF 656 00:27:25,120 --> 00:27:26,160 INVESTIGATORS THAT ARE GOING TO 657 00:27:26,160 --> 00:27:28,680 BE TALKING ABOUT I THINK TOPIC 658 00:27:28,680 --> 00:27:30,800 THAT'S ARE RELEVANT TO 659 00:27:30,800 --> 00:27:32,560 INTER-SUBJECT VARIABILITY. 660 00:27:32,560 --> 00:27:34,840 I'VE LISTED THEM HERE. 661 00:27:34,840 --> 00:27:36,680 I WANT TO MENTION THAT -- 662 00:27:36,680 --> 00:27:41,360 TALKING ABOUT SMALL INTESTINAL 663 00:27:41,360 --> 00:27:42,120 MICROBIOTA WHICH IS NOT SO MUCH 664 00:27:42,120 --> 00:27:45,840 IN THE LITERATURE BECAUSE OF 665 00:27:45,840 --> 00:27:46,800 TECHNOLOGIC ISSUES. 666 00:27:46,800 --> 00:27:52,800 I DO WANT TO MENTION JULIA OH. 667 00:27:52,800 --> 00:27:54,840 FACTORS THAT ARE RELEVANT TO THE 668 00:27:54,840 --> 00:27:58,160 GUT SO WE'VE GOT TO BE COGNIZANT 669 00:27:58,160 --> 00:28:01,240 THAT THE SKIN IS ALSO VERY 670 00:28:01,240 --> 00:28:03,600 IMPORTANT AND WE CAN LEARN A LOT 671 00:28:03,600 --> 00:28:05,320 FROM LESSONS THAT JULIA IS GOING 672 00:28:05,320 --> 00:28:08,480 TO BE TALKING ABOUT ALSO. 673 00:28:08,480 --> 00:28:10,800 SO THAT COLONIZATION RESISTANCE 674 00:28:10,800 --> 00:28:12,440 COULD BE A RELATIVELY SMALL 675 00:28:12,440 --> 00:28:14,360 NICHE BUT THERE ARE OBVIOUSLY 676 00:28:14,360 --> 00:28:15,720 OPPORTUNITIES TO OPEN UP THE 677 00:28:15,720 --> 00:28:19,040 NICHE TO ALLOW ENGRAPHMENT OF 678 00:28:19,040 --> 00:28:21,560 PRECISION PRO-BIOTICS AT A 679 00:28:21,560 --> 00:28:23,440 LARGER SCALE AND WE HEARD ABOUT 680 00:28:23,440 --> 00:28:24,960 THIS YESTERDAY. 681 00:28:24,960 --> 00:28:26,320 ESSENTIALLY HIGHLIGHTING THE 682 00:28:26,320 --> 00:28:28,320 FACT THAT PRETREATMENT WITH MICE 683 00:28:28,320 --> 00:28:30,760 AND ALLOWS ENGRAPHMENT OF 684 00:28:30,760 --> 00:28:33,120 ORGANISMS AND THERE IS A DOSE 685 00:28:33,120 --> 00:28:35,120 DEPENDENT RESPONSE MULTI-DAY 686 00:28:35,120 --> 00:28:37,960 DOSING WOULD LEAD TO MORE 687 00:28:37,960 --> 00:28:40,760 PERSISTENT ENGRAVE WANT OVER 688 00:28:40,760 --> 00:28:44,720 TIME * IF TREATED WITH AN 689 00:28:44,720 --> 00:28:47,400 ANTIBIOTIC TO FACILITATE 690 00:28:47,400 --> 00:28:54,080 ENGRAFTMENT. 691 00:28:54,080 --> 00:28:55,640 SO IS THE ENVIRONMENT 692 00:28:55,640 --> 00:28:56,680 GUT IMPORTANT WHEN THINKING 693 00:28:56,680 --> 00:28:59,040 ABOUT THE MICROBIOTA. 694 00:28:59,040 --> 00:29:03,080 AND HERE I'M GOING TO PUT ON 695 00:29:03,080 --> 00:29:06,920 MORE OF MY PHYSICIAN HAT. 696 00:29:06,920 --> 00:29:09,320 SO INFLAMMATORY BOWEL DISEASE 697 00:29:09,320 --> 00:29:14,120 CAN BE GUIDED INTO TWO DISEASES. 698 00:29:14,120 --> 00:29:16,000 REASONS DISEASE WHICH IS CHRONIC 699 00:29:16,000 --> 00:29:17,960 INFLAMMATION INVOLVING ANY 700 00:29:17,960 --> 00:29:23,560 REGION OF THE ENTRUSTAL TRACT. 701 00:29:23,560 --> 00:29:29,200 THESE ARE CHRONIC DISEASES THAT 702 00:29:29,200 --> 00:29:31,400 REQUIRE LIFELONG IMMUNO 703 00:29:31,400 --> 00:29:32,040 SUPPRESSION. 704 00:29:32,040 --> 00:29:33,920 IT'S COMPLEX. 705 00:29:33,920 --> 00:29:37,120 A GENETIC PREDICTION AND WE 706 00:29:37,120 --> 00:29:38,600 THINK THE MOST IMPORTANT 707 00:29:38,600 --> 00:29:40,120 ENVIRONMENTAL TRIGGERS IS 708 00:29:40,120 --> 00:29:43,600 PROBABLY THE GUT MICROBIOTA 709 00:29:43,600 --> 00:29:46,240 WHICH LEAD TO A REGULATORY 710 00:29:46,240 --> 00:29:48,560 DEFECT RESPONSIBLE FOR THAT 711 00:29:48,560 --> 00:29:50,160 CONNICK INFLAMMATORY RESPONSE. 712 00:29:50,160 --> 00:29:53,040 IF WE WERE TO ASK HOW MUCH IS US 713 00:29:53,040 --> 00:29:54,440 VERSES THE ENVIRONMENT WE THINK 714 00:29:54,440 --> 00:29:57,240 THAT THE GENETIC CONTRIBUTION TO 715 00:29:57,240 --> 00:29:58,480 THE DEVELOPMENT OF REASONS 716 00:29:58,480 --> 00:30:00,920 DISEASE IS 30% TO 40%. 717 00:30:00,920 --> 00:30:05,280 AND THIS IS BASED ON THE STUDY 718 00:30:05,280 --> 00:30:07,440 IN IDENTICAL TWINS. 719 00:30:07,440 --> 00:30:10,120 ENVIRONMENTAL FACTORS ARE THE 720 00:30:10,120 --> 00:30:11,360 LARGEST CONTRIBUTOR. 721 00:30:11,360 --> 00:30:13,120 AND THAT IS WHY I WANTED TO 722 00:30:13,120 --> 00:30:14,880 HIGHLIGHT THIS AS A PARADIGM. 723 00:30:14,880 --> 00:30:19,680 AND EVIDENCE FOR THIS -- IS THE 724 00:30:19,680 --> 00:30:28,920 INCREASING IN DENSE ASSOCIATED WITH 725 00:30:28,920 --> 00:30:29,760 WESTERNIZATION. 726 00:30:29,760 --> 00:30:31,680 WE'RE SEEING A RAPID RISE IN 727 00:30:31,680 --> 00:30:36,040 ASIA AND THIS IS PRIMARILY IN 728 00:30:36,040 --> 00:30:37,920 INDIA AND IN CHINA AND OTHER 729 00:30:37,920 --> 00:30:38,400 COUNTRIES. 730 00:30:38,400 --> 00:30:41,400 SO THIS IS A VERY, VERY POWERFUL 731 00:30:41,400 --> 00:30:43,280 ENVIRONMENTAL EFFECT THAT 732 00:30:43,280 --> 00:30:45,680 EXTENDS WELL BEYOND INFLAMMATORY 733 00:30:45,680 --> 00:30:46,360 BOWEL DISEASE. 734 00:30:46,360 --> 00:30:48,440 OTHER TYPES OF DISEASES THAT ARE 735 00:30:48,440 --> 00:30:49,960 VERY IMPORTANT IN THE HEALTH OF 736 00:30:49,960 --> 00:30:52,680 THE HUMAN POPULATIONS ARE SEEING 737 00:30:52,680 --> 00:30:55,880 A RAPID INCREASE BECAUSE OF 738 00:30:55,880 --> 00:30:57,320 ENVIRONMENTAL INFLUENCES. 739 00:30:57,320 --> 00:31:00,320 SO WE'RE FOCUSED ON THE 740 00:31:00,320 --> 00:31:00,840 MICROBIAL ENVIRONMENT. 741 00:31:00,840 --> 00:31:05,520 WE DO KNOW THAT THE ENVIRONMENT 742 00:31:05,520 --> 00:31:11,280 IT IS VERY, VERY DIFFERENT WHEN 743 00:31:11,280 --> 00:31:13,520 COMPARED WITH HEALTH. 744 00:31:13,520 --> 00:31:16,840 SO WHAT IS RESPONSIBLE FOR THIS? 745 00:31:16,840 --> 00:31:20,440 I USE DYSBIOSIS US AS A GENERAL 746 00:31:20,440 --> 00:31:22,120 TERM -- ASSOCIATED WITH DISEASE. 747 00:31:22,120 --> 00:31:25,320 THIS IS NOT NECESSARILY A 748 00:31:25,320 --> 00:31:26,880 COMPLETELY POPULAR TERM BUT I 749 00:31:26,880 --> 00:31:29,760 USE THIS AS A WAY TO EXPRESS 750 00:31:29,760 --> 00:31:33,080 THIS IDEA ABOUT AN ALTERNATIVE 751 00:31:33,080 --> 00:31:34,040 CONFIGURATION. 752 00:31:34,040 --> 00:31:36,960 WORK ABOUT ANDREA AND OTHERS 753 00:31:36,960 --> 00:31:38,920 HAVE HELPED TO DEFINE REASON WHY 754 00:31:38,920 --> 00:31:41,040 THE MICROBIAL COMMUNITY IS 755 00:31:41,040 --> 00:31:42,640 DIFFERENT AND IT'S LARGELY 756 00:31:42,640 --> 00:31:46,160 BECAUSE OF HOST DERIVED FACTORS. 757 00:31:46,160 --> 00:31:48,240 INFLAMMATION IS AN OXIDATIVE 758 00:31:48,240 --> 00:31:50,960 PROCESS THAT CAN LEAD TO AN 759 00:31:50,960 --> 00:31:52,040 OXIDATIVE ENVIRONMENT IN THE GUT 760 00:31:52,040 --> 00:31:57,120 AND A LOT OF THESE ORGANISMS ARE 761 00:31:57,120 --> 00:31:59,560 MORE -- TOLERANT. 762 00:31:59,560 --> 00:32:02,240 THE HOST CAN PRODUCE SMALL 763 00:32:02,240 --> 00:32:04,840 MOLECULES THAT PROMOTE AN ROBE 764 00:32:04,840 --> 00:32:06,680 ARREST PERFORATION. 765 00:32:06,680 --> 00:32:13,400 * TOGETHER IT REALLY MEANS THAT 766 00:32:13,400 --> 00:32:15,000 IT'S THE HOST ITSELF. 767 00:32:15,000 --> 00:32:17,040 THE INFLAMMATORY PROCESS THAT IS 768 00:32:17,040 --> 00:32:19,600 LEADING TO AN ENVIRONMENTAL 769 00:32:19,600 --> 00:32:22,880 PRESSURE OTICON PLEX MICROBIAL 770 00:32:22,880 --> 00:32:24,760 COMMUNITY THAT FAVORS THE 771 00:32:24,760 --> 00:32:25,680 OUTGROWTH OF PARTICULAR 772 00:32:25,680 --> 00:32:26,120 ORGANISMS. 773 00:32:26,120 --> 00:32:40,320 SO WE CAUSED THIS DISBOSE US. 774 00:32:40,320 --> 00:32:43,000 -- WE HEARD A LOT ABOUT FROM A 775 00:32:43,000 --> 00:32:44,000 NUMBER OF INVESTIGATORS 776 00:32:44,000 --> 00:32:44,640 YESTERDAY. 777 00:32:44,640 --> 00:32:48,520 SO YOU HAVE A MOUSE THAT 778 00:32:48,520 --> 00:32:51,600 SPONTANEOUSLY DEVELOPED COLITIS 779 00:32:51,600 --> 00:32:55,680 -- A HEALTHY MOUSE CAN LEAD TO 780 00:32:55,680 --> 00:32:57,840 DEVELOPMENT OF DISEASE. 781 00:32:57,840 --> 00:33:01,600 SO THAT TRANSFERABILITY OF THAT 782 00:33:01,600 --> 00:33:05,520 MICROBIOTA COMMUNITY AND THE 783 00:33:05,520 --> 00:33:07,080 RECAPITULATION -- PROVIDES CAUSE 784 00:33:07,080 --> 00:33:08,520 AND EFFECT INFORMATION. 785 00:33:08,520 --> 00:33:13,160 PROVING THAT IN FACT THE -- 786 00:33:13,160 --> 00:33:13,600 PATHOGENESIS. 787 00:33:13,600 --> 00:33:14,920 THAT IS IN ANIMALS. 788 00:33:14,920 --> 00:33:19,400 WHAT ABOUT IN HUMANS. 789 00:33:19,400 --> 00:33:22,040 LET ME GIVE YOU ONE POTENTIAL 790 00:33:22,040 --> 00:33:23,440 EXAMPLE. 791 00:33:23,440 --> 00:33:25,600 HERE ARE THREE CLINICAL TRIALS 792 00:33:25,600 --> 00:33:31,080 SHOWING BENEFIT FOR FECAL 793 00:33:31,080 --> 00:33:38,200 TRANSFER. 794 00:33:38,200 --> 00:33:43,080 I'M NOT SAYING AND I'M NOT 795 00:33:43,080 --> 00:33:48,000 ADVOCATING FOR STANDARD F MT AS 796 00:33:48,000 --> 00:33:51,920 THE TREATMENT FOR THIS. 797 00:33:51,920 --> 00:33:53,960 IT'S A WINDOW INTO THE 798 00:33:53,960 --> 00:33:55,200 OPPORTUNITIES THAT MIGHT BE 799 00:33:55,200 --> 00:33:57,320 AVAILABLE FOR CHANGE IN THE 800 00:33:57,320 --> 00:34:01,040 MICROBIOTA IN HUMANS WITH 801 00:34:01,040 --> 00:34:02,440 INFLAMMATORY BOWEL DISEASE. 802 00:34:02,440 --> 00:34:05,080 THERE IS A CAUSE AND EFFECT 803 00:34:05,080 --> 00:34:08,720 RELATIONSHIP AND THE DISEASE 804 00:34:08,720 --> 00:34:10,000 PATHOGENESIS SPECIFICALLY IN 805 00:34:10,000 --> 00:34:10,440 HUMANS. 806 00:34:10,440 --> 00:34:13,680 SO GETTING BACK TO THE BASIS OF 807 00:34:13,680 --> 00:34:15,960 THE DYSBIOSIS US I WANT TO MAKE 808 00:34:15,960 --> 00:34:18,040 A POINT. 809 00:34:18,040 --> 00:34:22,400 ONE OF THE MECHANISMS IS 810 00:34:22,400 --> 00:34:24,720 AEROBIC. 811 00:34:24,720 --> 00:34:30,120 THE LOSS OF MITOCHONDRIAL -- AND 812 00:34:30,120 --> 00:34:33,560 ALLOW THE DYNAMIC FLOW OF OXYGEN 813 00:34:33,560 --> 00:34:34,800 THAT WOULD FAVOR THE OUTGROWTH 814 00:34:34,800 --> 00:34:37,560 OF ORGANISMS SUCH AS -- -- SO, 815 00:34:37,560 --> 00:34:39,440 THAT IS ONE PARTICULAR 816 00:34:39,440 --> 00:34:40,680 MECHANISM. 817 00:34:40,680 --> 00:34:44,520 THE OTHER IS ANAEROBIC. 818 00:34:44,520 --> 00:34:48,480 IN THE ABSENCE OF OXYGEN 819 00:34:48,480 --> 00:34:50,680 INFLAMMATION IN THE GUT COULD 820 00:34:50,680 --> 00:34:53,360 PRODUCE ALTERNATIVE RECEPTORS 821 00:34:53,360 --> 00:34:57,440 THAT WOULD FACILITATE ANAEROBIC 822 00:34:57,440 --> 00:34:59,320 REST PERFECT RAISING AND THAT 823 00:34:59,320 --> 00:35:01,560 WOULD LEAD TO THE DYSBIOSIS US 824 00:35:01,560 --> 00:35:09,560 ALSO. 825 00:35:09,560 --> 00:35:12,040 ONE IS OXYGEN AND THE OTHER IS 826 00:35:12,040 --> 00:35:17,000 AN ALTERNATIVE ELECTRONIC 827 00:35:17,000 --> 00:35:18,280 RECEPTOR TO OXYGEN. 828 00:35:18,280 --> 00:35:19,600 HOW CAN THAT HAPPEN? 829 00:35:19,600 --> 00:35:21,120 THIS IS JUST A THOUGHT 830 00:35:21,120 --> 00:35:23,480 EXPERIMENT ON MY OWN PART SO I 831 00:35:23,480 --> 00:35:25,720 CAN TAKE THE BLAME BUT LET ME 832 00:35:25,720 --> 00:35:28,040 TELL YOU THE THOUGHT AND THAT IS 833 00:35:28,040 --> 00:35:30,920 THE IMPORTANCE OF SPATIAL 834 00:35:30,920 --> 00:35:32,480 DISCRIMINATION OR SPATIAL 835 00:35:32,480 --> 00:35:33,400 CHARACTERIZATION WHEN THINKING 836 00:35:33,400 --> 00:35:35,600 ABOUT BIOLOGY IN THE GUT. 837 00:35:35,600 --> 00:35:40,640 BUT WHAT I PUT ALONG THE Y AXIS 838 00:35:40,640 --> 00:35:42,640 IS A RATE AND THIS IS THE 839 00:35:42,640 --> 00:35:44,560 SPATIAL RESOLUTION INCREASING 840 00:35:44,560 --> 00:35:45,680 DISTANCE. 841 00:35:45,680 --> 00:35:47,240 SO MAYBE ORGANISMS THAT ARE 842 00:35:47,240 --> 00:35:50,000 CLOSER TO THE SURFACE THAT ARE 843 00:35:50,000 --> 00:35:52,320 IN A MORE MICRO AEROBIC 844 00:35:52,320 --> 00:35:53,120 ENVIRONMENT THAT IS THE 845 00:35:53,120 --> 00:35:54,880 OPPORTUNITY TO HAVE A MORE 846 00:35:54,880 --> 00:35:56,560 AEROBIC RESPONSE THAT PLAYS A 847 00:35:56,560 --> 00:35:58,640 ROLE IN THE DEVELOPMENT OF 848 00:35:58,640 --> 00:36:00,800 DYSBIOSIS US BUT AS YOU MOVE 849 00:36:00,800 --> 00:36:04,920 AWAY MORE IN ANN AEROBIC 850 00:36:04,920 --> 00:36:06,400 ENVIRONMENT THAT IS PERHAPS 851 00:36:06,400 --> 00:36:08,400 WHERE MORE RECEPTORS PLAY A 852 00:36:08,400 --> 00:36:09,920 GREATER ROLE IN THE DEVELOPMENT 853 00:36:09,920 --> 00:36:12,320 OF DYSBIOSIS US. 854 00:36:12,320 --> 00:36:18,840 AND * JUST A CONCEPT -- OF THE 855 00:36:18,840 --> 00:36:21,880 MICRMICROBIOTA IN ITS ENVIRONMENT IN 856 00:36:21,880 --> 00:36:23,840 THE GUT MAY BE IMPORTANT. 857 00:36:23,840 --> 00:36:26,040 WE HAVE A HINT THIS MAY BE THE 858 00:36:26,040 --> 00:36:30,000 CASE IN HOOP ANS. 859 00:36:30,000 --> 00:36:37,000 -- IN HUMANS. 860 00:36:37,000 --> 00:36:40,160 -- -- BASED ON A SWAB OR 861 00:36:40,160 --> 00:36:43,160 BIOPSIES ARE DIFFERENT IN 862 00:36:43,160 --> 00:36:44,440 COMPOSITION. 863 00:36:44,440 --> 00:36:47,440 AND THE ORGANISMS THAT ARE 864 00:36:47,440 --> 00:36:50,440 ADHERENT TO THE MUCOS A IN PART 865 00:36:50,440 --> 00:36:54,000 ARE MORE ARROW TOLERANT. 866 00:36:54,000 --> 00:36:55,520 WE HAD DEVELOPED A TECHNOLOGY 867 00:36:55,520 --> 00:36:57,520 WITH THE NOTION THAT THE HOST 868 00:36:57,520 --> 00:36:59,960 ACTUALLY PROVIDES OXYGEN IN TO 869 00:36:59,960 --> 00:37:03,080 THE GUT ENVIRONMENT. 870 00:37:03,080 --> 00:37:06,240 WE DEVELOPED A TECHNOLOGY USING 871 00:37:06,240 --> 00:37:10,480 -- AND NANO PROBES THAT WOULD 872 00:37:10,480 --> 00:37:14,720 ALLOW US TO QUANTIFY -- 873 00:37:14,720 --> 00:37:16,640 NONINVASIVELY AND IN REALTIME. 874 00:37:16,640 --> 00:37:19,200 WE COULD SHOW THAT IF YOU 875 00:37:19,200 --> 00:37:23,280 QUANTIFY OXYGEN IN HUMAN -- IN 876 00:37:23,280 --> 00:37:26,640 MOUSE TISSUE IN THE LIVER THAT 877 00:37:26,640 --> 00:37:29,040 -- IT IS ABOUT 40TOR. 878 00:37:29,040 --> 00:37:33,000 BUT IF YOU NOW SWITCH THE MOUSE 879 00:37:33,000 --> 00:37:37,200 INSPIRING AMBIENT AIR TO 100% 880 00:37:37,200 --> 00:37:39,000 OXYGEN THERE IS AN IMMEDIATE 881 00:37:39,000 --> 00:37:41,200 RISE AND WHEN YOU TURN BACK ON 882 00:37:41,200 --> 00:37:48,400 THE AMBIENT AIR REDUCES. 883 00:37:48,400 --> 00:37:54,760 AS YOU HYPER OXYGENATE -- YOU 884 00:37:54,760 --> 00:37:58,400 CAN NOW SEE A DYNAMIC RESPONSE. 885 00:37:58,400 --> 00:38:01,840 IF YOU REDUCE OXYGEN BACK DOWN 886 00:38:01,840 --> 00:38:03,960 JUST LIKE IN TISSUE THE OXYGEN 887 00:38:03,960 --> 00:38:04,960 LEVELS BEGIN TO DROP. 888 00:38:04,960 --> 00:38:06,680 HOWEVER THEY DON'T REDUCE DOWN 889 00:38:06,680 --> 00:38:09,160 TO THE BASELINE AND YOU CAN DO 890 00:38:09,160 --> 00:38:12,920 THE SUCCESSIVELY BUT THERE IS 891 00:38:12,920 --> 00:38:15,440 ALWAYS A LITTLE BIT OF OXYGEN 892 00:38:15,440 --> 00:38:16,440 LEFT IN THE ENVIRONMENT. 893 00:38:16,440 --> 00:38:18,120 THIS SHOWS THAT IN FACT WE 894 00:38:18,120 --> 00:38:22,200 PROVIDE OXYGEN INTO THE -- GUT 895 00:38:22,200 --> 00:38:27,880 THAT IS CONSUMED BY -- MICROBES. 896 00:38:27,880 --> 00:38:30,520 THERE IS IS COMPLEXITY IN TERMS 897 00:38:30,520 --> 00:38:34,240 OF THE CHEMISTRY THAT MAY BE 898 00:38:34,240 --> 00:38:36,440 RELEVANT TO THE OXYGEN DYNAMICS 899 00:38:36,440 --> 00:38:40,120 BETWEEN THE HOST AND THE LUMEN 900 00:38:40,120 --> 00:38:43,440 OF THE GUT. 901 00:38:43,440 --> 00:38:46,760 WE DEMONSTRATED THIS BOOK 902 00:38:46,760 --> 00:38:50,440 LOOKING ATROPHIESES. 903 00:38:50,440 --> 00:38:51,800 -- AT -- FECES. 904 00:38:51,800 --> 00:39:02,680 7 * EVEN GERMFREE FECES -- WILL 905 00:39:02,680 --> 00:39:05,680 CONSUME OXYGEN DOWNTOWN AN -- 906 00:39:05,680 --> 00:39:07,560 AEROBIC STATE IN A COUPLE OF 907 00:39:07,560 --> 00:39:08,640 AREAS. 908 00:39:08,640 --> 00:39:10,480 STRESSING THAT FECAL MATERIAL IS 909 00:39:10,480 --> 00:39:14,240 A VERY COMPLEX AND BIOLOGICALLY 910 00:39:14,240 --> 00:39:19,440 ACTIVE MATRIX AND WE KNOW THAT 911 00:39:19,440 --> 00:39:21,520 FECAL MATERIALS VERY GOOD 912 00:39:21,520 --> 00:39:22,960 INSULATOR AGAINST OXYGEN. 913 00:39:22,960 --> 00:39:28,240 SO WHY IS THAT RELEVANT? 914 00:39:28,240 --> 00:39:30,400 I JUST SHOWED YOU ONE RESULT 915 00:39:30,400 --> 00:39:33,480 FROM CHRIS . 916 00:39:33,480 --> 00:39:37,040 WE SHOWED THAT -- AS IT MOVES 917 00:39:37,040 --> 00:39:40,000 TOWARD THE MUCOSAL SURFACE WILL 918 00:39:40,000 --> 00:39:43,920 ACTUALLY ACTIVATE A TYPE THREE 919 00:39:43,920 --> 00:39:46,400 SECRETION SYSTEM THAT PROMOTES 920 00:39:46,400 --> 00:39:48,440 PATHO AGAIN US TEE. 921 00:39:48,440 --> 00:39:50,880 * MEANING THAT THE OXYGEN 922 00:39:50,880 --> 00:39:52,440 GRADIENT IS NOT ONLY IMPORTANT 923 00:39:52,440 --> 00:39:54,880 FOR WHAT IS ACTUALLY LIVING IN 924 00:39:54,880 --> 00:39:56,680 THESE VARIOUS TYPES OF 925 00:39:56,680 --> 00:39:57,920 ENVIRONMENTS BUT IT'S IMPORTANT 926 00:39:57,920 --> 00:40:00,640 FOR THE BIOLOGICAL FUNCTION. 927 00:40:00,640 --> 00:40:03,840 IT WILL CHANGE GENE 928 00:40:03,840 --> 00:40:08,560 REPRESENTATION, ACTIVITY -- AND 929 00:40:08,560 --> 00:40:14,240 VARIOUS LI -- BIOLOGICAL FUNCTIONS. 930 00:40:14,240 --> 00:40:15,280 THERE ARE GROWING TECHNOLOGIES 931 00:40:15,280 --> 00:40:17,920 TO LOOK AT SPATIAL RESOLUTION OF 932 00:40:17,920 --> 00:40:20,160 THE MICROBIOTA SO THIS IS WORK 933 00:40:20,160 --> 00:40:25,080 USING FLUORESCE ANC -- * ALONG 934 00:40:25,080 --> 00:40:28,640 WITH I THINK A VERY SPECIALIZED 935 00:40:28,640 --> 00:40:31,240 OPTICS AND MACHINE LEARNING 936 00:40:31,240 --> 00:40:34,000 ALGORITHMS THAT ALLOW THESE 937 00:40:34,000 --> 00:40:36,320 INVESTIGATORS TO CHARACTERIZE AT 938 00:40:36,320 --> 00:40:39,760 HIGH LEVEL OF COMPLEXITY THE 939 00:40:39,760 --> 00:40:42,200 COMPOSITION OF THE MICROBIOTA AT 940 00:40:42,200 --> 00:40:43,520 BODY SURFACES. 941 00:40:43,520 --> 00:40:46,480 SO, THAT IS THE COMPOSITION OF 942 00:40:46,480 --> 00:40:48,840 MICROBIOTA BUT WE HEARD ABOUT 943 00:40:48,840 --> 00:40:50,680 METABOLITES AND THEY CAN BE 944 00:40:50,680 --> 00:40:54,840 SPATIALLY RESOLVED USING ALL OF 945 00:40:54,840 --> 00:41:01,000 THE MASS SPECTORMETRY IMAGING. 946 00:41:01,000 --> 00:41:08,240 THEY DID -- MSI ON CONTROLLED 947 00:41:08,240 --> 00:41:08,840 SECUM. 948 00:41:08,840 --> 00:41:11,400 YOU CAN SEE THE COLORS ARE VERY 949 00:41:11,400 --> 00:41:13,480 DIFFERENT FOR THESE THREE SMALL 950 00:41:13,480 --> 00:41:16,240 MONTHLY SCHOOLS AND IT'S NOT 951 00:41:16,240 --> 00:41:18,040 JUST THE GUT. 952 00:41:18,040 --> 00:41:20,560 NOT * JUST THE FECES BUT THE 953 00:41:20,560 --> 00:41:21,480 TISSUE ITSELF. 954 00:41:21,480 --> 00:41:25,120 SO THIS IS VERY INTERESTING 955 00:41:25,120 --> 00:41:25,440 INFORMATION. 956 00:41:25,440 --> 00:41:27,880 THERE ARE HUNDREDS OF DIFFERENT 957 00:41:27,880 --> 00:41:29,480 FEATURES THAT CAN BE SPATIALLY 958 00:41:29,480 --> 00:41:31,560 RESOLVED IN TERMS OF 959 00:41:31,560 --> 00:41:32,040 METABOLITES. 960 00:41:32,040 --> 00:41:34,680 SPATIAL RESOLUTION OF THE 961 00:41:34,680 --> 00:41:36,120 MICROBIOTA TOGETHER WITH THE 962 00:41:36,120 --> 00:41:38,560 METABOLITES ARE PRODUCING AND 963 00:41:38,560 --> 00:41:41,320 COULD BE IMPORTANT FOR THING 964 00:41:41,320 --> 00:41:43,000 ABOUT FUNCTIONALITY OF THE MICRO 965 00:41:43,000 --> 00:41:46,080 BUY OAT A. TALKING ABOUT THINGS 966 00:41:46,080 --> 00:41:47,720 * THAT ARE RELEVANT. 967 00:41:47,720 --> 00:41:50,240 SOME ARE TALKING ABOUT LAB ON A 968 00:41:50,240 --> 00:41:53,440 PILL FOR SPATIALLY TARGETED -- 969 00:41:53,440 --> 00:41:54,320 THINKING ABOUT SPATIAL 970 00:41:54,320 --> 00:41:55,000 RESOLUTION. 971 00:41:55,000 --> 00:42:00,520 AND DR. KIM HAS DEVELOPED A 972 00:42:00,520 --> 00:42:03,440 DISEASE ON A CHIP TYPE MODALITY 973 00:42:03,440 --> 00:42:05,320 THAT WOULD BE ACTUALLY VERY WELL 974 00:42:05,320 --> 00:42:07,760 SUITED TO LOOK AT 975 00:42:07,760 --> 00:42:09,240 CHARACTERIZATION AT SPATIAL 976 00:42:09,240 --> 00:42:11,440 RESOLUTION. 977 00:42:11,440 --> 00:42:16,120 SO I USE OXYGEN. 978 00:42:16,120 --> 00:42:19,560 WE DO HAVE TO THINK ABOUT HOW 979 00:42:19,560 --> 00:42:21,040 ADDITIONAL WAYS BY WHICH THE 980 00:42:21,040 --> 00:42:23,480 HOST AND MICROBE ACTUALLY 981 00:42:23,480 --> 00:42:25,160 INTERACT IN THINKING ABOUT 982 00:42:25,160 --> 00:42:26,280 THERAPEUTIC PRODUCTS AND WEARING 983 00:42:26,280 --> 00:42:28,600 MY HAT AS A PHYSICIAN I NEED TO 984 00:42:28,600 --> 00:42:30,200 EMPHASIZE AND GIVE YOU A LITTLE 985 00:42:30,200 --> 00:42:32,480 BIT OF PRIMER HOW WE CURRENTLY 986 00:42:32,480 --> 00:42:34,120 TREAT INFLAMMATORY BOWEL 987 00:42:34,120 --> 00:42:35,120 DISEASE. 988 00:42:35,120 --> 00:42:37,640 THE FIRST APPROACH IS INDUCE 989 00:42:37,640 --> 00:42:38,200 REMISSION. 990 00:42:38,200 --> 00:42:40,440 TREAT THE DISEASE TO TURN OFF 991 00:42:40,440 --> 00:42:43,280 THE INFLAMMATION SO PATIENTS 992 00:42:43,280 --> 00:42:45,800 FEEL WELL AND YOU NORMALIZE 993 00:42:45,800 --> 00:42:47,040 LABORATORY VALUES. 994 00:42:47,040 --> 00:42:49,240 ONCE YOU INDUCE REMISSION THE 995 00:42:49,240 --> 00:42:51,240 NEXT STEP IS TO PREVENT THE 996 00:42:51,240 --> 00:42:52,800 DISEASE FROM COMING BACK OVER 997 00:42:52,800 --> 00:42:54,000 TIME. 998 00:42:54,000 --> 00:42:57,280 AND SADLY INFLAMMATORY BOWEL 999 00:42:57,280 --> 00:43:00,600 DISEASE PROBABLY REQUIRES 1000 00:43:00,600 --> 00:43:02,440 LIFELONG IMMUNO SUPPRESSION. 1001 00:43:02,440 --> 00:43:04,360 HOWEVER THERE IS A NOTION THAT 1002 00:43:04,360 --> 00:43:07,240 YOU CAN CHANGE THE DISEASE. 1003 00:43:07,240 --> 00:43:09,360 WE HAVE A HINT OF THIS AND THE 1004 00:43:09,360 --> 00:43:10,920 NOTION OF CHANGING THE 1005 00:43:10,920 --> 00:43:12,440 ENVIRONMENT OF THE GUT MAY 1006 00:43:12,440 --> 00:43:13,480 ACTUALLY PROVIDE AN OPPORTUNITY 1007 00:43:13,480 --> 00:43:15,800 TO CHANGE THE COURSE OF DISEASE 1008 00:43:15,800 --> 00:43:17,440 AND WE HAVE TO MONITOR THESE 1009 00:43:17,440 --> 00:43:20,360 PATIENTS LONG-TERM FOR POTENTIAL 1010 00:43:20,360 --> 00:43:21,840 SERIOUS OUTCOMES LIKE 1011 00:43:21,840 --> 00:43:23,640 DEVELOPMENT OF CANCER AS WELL AS 1012 00:43:23,640 --> 00:43:25,840 MONITORING OUTCOMES WITH IN 1013 00:43:25,840 --> 00:43:27,400 TERMS OF THERAPY. 1014 00:43:27,400 --> 00:43:30,440 SO IN TREATING WE HAVE -- 1015 00:43:30,440 --> 00:43:33,240 DIFFERENT TYPES OF DRUGS 1016 00:43:33,240 --> 00:43:34,440 BEGINNING FROM THE SIMPLE TO 1017 00:43:34,440 --> 00:43:36,240 MUCH MORE ADVANCED TREATMENTS 1018 00:43:36,240 --> 00:43:39,040 AND THESE ARE LARGELY TARGETED 1019 00:43:39,040 --> 00:43:39,760 BIOLOGICS. 1020 00:43:39,760 --> 00:43:42,040 AND IF YOU DON'T RESPOND 1021 00:43:42,040 --> 00:43:43,200 UNFORTUNATELY YOU MAY NEED TO 1022 00:43:43,200 --> 00:43:44,160 HAVE SURGERY. 1023 00:43:44,160 --> 00:43:45,840 BUT THERE IS A WHOLE APPROACH 1024 00:43:45,840 --> 00:43:48,640 THAT WE USED TO TREAT AND WE 1025 00:43:48,640 --> 00:43:50,840 HAVE TO BE COGNIZANT OF THIS 1026 00:43:50,840 --> 00:43:52,520 WHEN WE THINK ABOUT COMING ONE 1027 00:43:52,520 --> 00:43:55,200 NEW THERAPEUTICS FROM THE 1028 00:43:55,200 --> 00:43:57,240 MICROBIOTA STANDPOINT. 1029 00:43:57,240 --> 00:44:00,040 THE HOST EXERTS AN ENVIRONMENTAL 1030 00:44:00,040 --> 00:44:03,400 PRESSURE ON THE MICROBIOTA AND 1031 00:44:03,400 --> 00:44:05,080 OUR HOPE IS THAT WE WILL COME UP 1032 00:44:05,080 --> 00:44:07,040 WITH BETTER STRATEGIES TO CHANGE 1033 00:44:07,040 --> 00:44:08,840 THE CONFIGURATION THAT WILL HELP 1034 00:44:08,840 --> 00:44:10,400 THE HOST. 1035 00:44:10,400 --> 00:44:11,760 BUT THAT ACTUALLY BRINGS UP A 1036 00:44:11,760 --> 00:44:13,560 COUPLE OF VERY IMPORTANT POINTS. 1037 00:44:13,560 --> 00:44:14,920 WHAT ARE YOU TRYING TO DO WHEN 1038 00:44:14,920 --> 00:44:18,120 YOU TARGET A PRECISION 1039 00:44:18,120 --> 00:44:18,920 PRO-BIOTIC. 1040 00:44:18,920 --> 00:44:21,240 ARE YOU TRYING TO ACTUALLY TREAT 1041 00:44:21,240 --> 00:44:23,000 ACTIVE DISEASE UP HERE OR ARE 1042 00:44:23,000 --> 00:44:26,440 YOU GOING TO PREVENT 1043 00:44:26,440 --> 00:44:32,600 REOCCURRENCE. 1044 00:44:32,600 --> 00:44:34,840 BUT IT IS VERY DIFFICULT TO 1045 00:44:34,840 --> 00:44:37,040 DEMONSTRATE PREVENTION OF 1046 00:44:37,040 --> 00:44:37,560 RECURRENCE. 1047 00:44:37,560 --> 00:44:39,040 MAYBE THAT'S AN OPPORTUNITY TO 1048 00:44:39,040 --> 00:44:41,640 BE THINKING B. THE OTHER IS DO 1049 00:44:41,640 --> 00:44:45,800 YOU WANT TO HAVE A STAND ALONE 1050 00:44:45,800 --> 00:44:47,160 THERAPEUTIC OR MAYBE A 1051 00:44:47,160 --> 00:44:47,840 COMBINATION THERAPY. 1052 00:44:47,840 --> 00:44:49,400 MAYBE YOU NEED TO BE TREATING 1053 00:44:49,400 --> 00:44:52,880 THE HOST USING SOME LEVEL OF 1054 00:44:52,880 --> 00:44:54,880 IMMUNO SUPPRESSION FOR CHANGING 1055 00:44:54,880 --> 00:44:55,640 THE GUT. 1056 00:44:55,640 --> 00:44:58,000 MIGHT MAKE THE DRUGS THAT WE 1057 00:44:58,000 --> 00:45:00,600 CURRENTLY USE BETTER. 1058 00:45:00,600 --> 00:45:01,840 >> DR. WU, YOU HAVE ABOUT FIVE 1059 00:45:01,840 --> 00:45:02,320 MINUTES 1060 00:45:02,320 --> 00:45:03,320 >> OKAY. 1061 00:45:03,320 --> 00:45:06,080 >> SO WE HAVE A NUMBER OF 1062 00:45:06,080 --> 00:45:08,000 INVESTIGATORS TALKING ABOUT 1063 00:45:08,000 --> 00:45:10,280 HOSTESS, MICROBIOTA REACTIONS. 1064 00:45:10,280 --> 00:45:11,920 I WON'T GET INTO DETAILS. 1065 00:45:11,920 --> 00:45:14,640 IT'S GOING TO BE VERY IMPORTANT. 1066 00:45:14,640 --> 00:45:17,520 BARBARA HAS A VERY NICE MODEL 1067 00:45:17,520 --> 00:45:20,240 SYSTEM ABOUT THE WILD MICROBIOTA 1068 00:45:20,240 --> 00:45:21,520 THAT IS GOING TO BE VERY 1069 00:45:21,520 --> 00:45:22,120 IMPORTANT. 1070 00:45:22,120 --> 00:45:25,880 SO WE DO HAVE AN EXAMPLE WHERE 1071 00:45:25,880 --> 00:45:28,840 TARGETED THERAPEUTIC IN THIS 1072 00:45:28,840 --> 00:45:32,040 CASE -- WERE ATTEMPTED TO BE 1073 00:45:32,040 --> 00:45:39,960 USED AS A TREATMENT FOR US 1074 00:45:39,960 --> 00:45:44,160 CERTIFY COLITIS. 1075 00:45:44,160 --> 00:45:44,680 *. 1076 00:45:44,680 --> 00:45:47,160 THE INDIVIDUALS THAT WERE 1077 00:45:47,160 --> 00:45:49,560 ENROLLED WERE REFRACTORY TO 1078 00:45:49,560 --> 00:45:53,640 STANDARD THERAPEUTICS. 1079 00:45:53,640 --> 00:45:55,840 THIS TRIAL WAS TERMINATED FOR 1080 00:45:55,840 --> 00:45:58,680 LACK OF CLINICAL EFFICACY. 1081 00:45:58,680 --> 00:46:00,160 NEVERTHELESS I THINK WE'LL LEARN 1082 00:46:00,160 --> 00:46:02,040 A LOT FROM THIS AND THIS IS JUST 1083 00:46:02,040 --> 00:46:04,120 THE START OF MANY DIFFERENT 1084 00:46:04,120 --> 00:46:07,560 TYPES OF OPPORTUNITIES. 1085 00:46:07,560 --> 00:46:10,640 THE FINAL THING IS COME PANS 1086 00:46:10,640 --> 00:46:11,280 DIAGNOSTICS. 1087 00:46:11,280 --> 00:46:17,240 CAN YOU COME UP WITH A 1088 00:46:17,240 --> 00:46:20,520 DIAGNOSTIC TO FIND OUT WHO WOULD 1089 00:46:20,520 --> 00:46:25,960 RESPOND TO THE TREATMENT. 1090 00:46:25,960 --> 00:46:29,040 SO IF YOU TANG ALL -- PATIENTS 1091 00:46:29,040 --> 00:46:31,560 WHO ACHIEVE REMISSION THERE IS 1092 00:46:31,560 --> 00:46:35,360 NO RESPONSE COMPARED TO PLACEBO. 1093 00:46:35,360 --> 00:46:37,040 HOWEVER YOU STRATIFY INDIVIDUALS 1094 00:46:37,040 --> 00:46:43,000 USING A COME PANS DIAGNOSTIC -- 1095 00:46:43,000 --> 00:46:44,080 BASICALLY A BLOOD TEST. 1096 00:46:44,080 --> 00:46:45,960 YOU CAN SEE THERE IS A DOSE 1097 00:46:45,960 --> 00:46:47,840 DEPENDENT RESPONSE IN RESPONSE 1098 00:46:47,840 --> 00:46:51,840 TO THE ANTITMF DRUG. 1099 00:46:51,840 --> 00:46:53,680 TRYING TO DEFINE WHO'S GOING TO 1100 00:46:53,680 --> 00:46:55,360 RESPOND IS GOING TO BE IMPORTANT 1101 00:46:55,360 --> 00:46:57,680 AND THERE IS ARE OTHER EXAMPLES 1102 00:46:57,680 --> 00:46:59,680 IN ONCOLOGY AND THIS IS BREAST 1103 00:46:59,680 --> 00:47:02,040 CANCER -- TREATING WITH 1104 00:47:02,040 --> 00:47:06,800 INHIBITORS. 1105 00:47:06,800 --> 00:47:12,000 AS A MODALITY FOR A COME PANS 1106 00:47:12,000 --> 00:47:12,440 DIAGNOSTIC. 1107 00:47:12,440 --> 00:47:13,720 WE HAVE EVIDENCE FOR THIS. 1108 00:47:13,720 --> 00:47:15,640 THIS IS A PHASE II CLINICAL 1109 00:47:15,640 --> 00:47:18,000 TRIAL LOOKING AT TREATMENT ON 1110 00:47:18,000 --> 00:47:21,240 PREVENTION OF RECURRENCE OF -- 1111 00:47:21,240 --> 00:47:21,680 INFECTION. 1112 00:47:21,680 --> 00:47:24,360 THIS CLINICAL TRIAL DID NOT SHOW 1113 00:47:24,360 --> 00:47:25,880 A SIGNIFICANT BENEFIT. 1114 00:47:25,880 --> 00:47:28,440 DID NOT REACH STATISTICAL 1115 00:47:28,440 --> 00:47:29,320 SIGNIFICANCE BUT THESE 1116 00:47:29,320 --> 00:47:31,640 INVESTIGATORS DID THE FIELD A 1117 00:47:31,640 --> 00:47:35,920 FAVOR BY DOING A POST HOCK 1118 00:47:35,920 --> 00:47:38,360 ANALYSIS SHOWING THEY USED PCR 1119 00:47:38,360 --> 00:47:40,280 TESTING TO DETERMINE ELIGIBILITY 1120 00:47:40,280 --> 00:47:44,240 IN THE STUDY AND THAT CANNOT 1121 00:47:44,240 --> 00:47:47,240 DIFFERENTIATE. 1122 00:47:47,240 --> 00:47:50,040 TOXIN TESTING CAN MAKE THAT 1123 00:47:50,040 --> 00:47:52,440 DISTINCTION BETWEEN INFECTION 1124 00:47:52,440 --> 00:47:53,160 VERSUS COLONIZATION. 1125 00:47:53,160 --> 00:47:54,480 THEY ALSO DETERMINED THAT THE 1126 00:47:54,480 --> 00:47:56,320 DOSE MAY NOT HAVE BEEN OPTIMAL. 1127 00:47:56,320 --> 00:48:01,720 SO THIS SAME APPROACH WAS 1128 00:48:01,720 --> 00:48:04,200 UTILIZED AND WAS PUBLISHED IN 1129 00:48:04,200 --> 00:48:05,760 THE NEW ENGLAND JOURNAL OF 1130 00:48:05,760 --> 00:48:06,400 MEDICINE. 1131 00:48:06,400 --> 00:48:16,840 THEY USED THE COME PANS 1132 00:48:16,840 --> 00:48:18,480 DIAGNOSING -- *. 1133 00:48:18,480 --> 00:48:21,480 AGAIN EMPHASIZING THE IMPORTANCE 1134 00:48:21,480 --> 00:48:37,040 OF A COMPANION DIAGNOSIS. 1135 00:48:37,040 --> 00:48:41,640 AND WE KNOW FROM THE HOST 1136 00:48:41,640 --> 00:48:44,400 STANDPOINT -- DEFINING -- HOST 1137 00:48:44,400 --> 00:48:46,960 IMMUNE PATTERNS THAT PREDICT 1138 00:48:46,960 --> 00:48:49,400 OUTCOME TO THE TREATMENT OF 1139 00:48:49,400 --> 00:48:50,040 ANTITMF. 1140 00:48:50,040 --> 00:48:51,280 WE'RE SEEING INFORMATION THAT 1141 00:48:51,280 --> 00:48:54,160 MINING THE MICROBIOTA CAN BE 1142 00:48:54,160 --> 00:48:57,440 USED AS A PROGNOSTIC FACTOR. 1143 00:48:57,440 --> 00:49:01,080 AND MAYBE THINKING FORWARD 1144 00:49:01,080 --> 00:49:02,000 MICROBES THEMSELVES PRECISION 1145 00:49:02,000 --> 00:49:04,680 PROBIOTICS COULD BE PART OF A 1146 00:49:04,680 --> 00:49:10,120 CELL-BASED BIOSENSOR -- AGAIN AS 1147 00:49:10,120 --> 00:49:11,640 ANOTHER MICROBIOLOGICAL 1148 00:49:11,640 --> 00:49:12,560 PREDICTIVE MARKER. 1149 00:49:12,560 --> 00:49:14,320 HERE IS MY LAST SLIDE. 1150 00:49:14,320 --> 00:49:16,240 IN THE FIELD RIGHT NOW WE HAVE 1151 00:49:16,240 --> 00:49:18,800 ANIMAL MODEL STATUS SHOWING 1152 00:49:18,800 --> 00:49:19,560 CAUSE AND EFFECT. 1153 00:49:19,560 --> 00:49:21,440 AND WE HAVE HUMAN ASSOCIATION 1154 00:49:21,440 --> 00:49:21,880 STUDIES. 1155 00:49:21,880 --> 00:49:24,800 WE WANT TO GET DOWN TO A LIVE 1156 00:49:24,800 --> 00:49:26,920 THERAPEUTIC PRODUCTS. 1157 00:49:26,920 --> 00:49:28,960 AND WHAT WE'RE CURRENTLY DOING 1158 00:49:28,960 --> 00:49:33,800 IS FMT -- -- AND WE DO NEED TO 1159 00:49:33,800 --> 00:49:36,240 BE MOVING DOWN THIS AXIS HERE 1160 00:49:36,240 --> 00:49:40,320 AND WE'RE SEEING THIS EVOLUTION. 1161 00:49:40,320 --> 00:49:42,440 AND THAT INCLUDES HUMAN 1162 00:49:42,440 --> 00:49:44,560 INTERVENTION STUDIES TO 1163 00:49:44,560 --> 00:49:46,440 DETERMINE WHETHER OR NOT WHAT WE 1164 00:49:46,440 --> 00:49:48,360 OBSERVE IN ANIMAL MODELS IS 1165 00:49:48,360 --> 00:49:50,760 RELEVANT TO HUMAN PHYSIOLOGY. 1166 00:49:50,760 --> 00:49:53,560 THERE IS NO GOOD MODEL FOR 1167 00:49:53,560 --> 00:49:56,280 INFLAMATORY BOWEL DISEASE THAT 1168 00:49:56,280 --> 00:49:58,200 ACTUALLY RECAPITULATES THE HUMAN 1169 00:49:58,200 --> 00:50:00,440 RESPONSE TO OUR THERAPEUTIC 1170 00:50:00,440 --> 00:50:01,000 INTERVENTIONS. 1171 00:50:01,000 --> 00:50:03,520 SO IT'S A TALL TASK BUT VERY 1172 00:50:03,520 --> 00:50:04,040 IMPORTANT. 1173 00:50:04,040 --> 00:50:07,040 ALSO IMPORTANT TO KNOW THAT ONLY 1174 00:50:07,040 --> 00:50:09,600 ABOUT 30% OF INDIVIDUALS RESPOND 1175 00:50:09,600 --> 00:50:12,480 TO CURRENT THERAPIES AND 30% OF 1176 00:50:12,480 --> 00:50:14,840 INDIVIDUALS LOSE RESPONSIVENESS. 1177 00:50:14,840 --> 00:50:16,840 SO THERE IS AN IMPORTANT NEED 1178 00:50:16,840 --> 00:50:19,920 FOR BETTER AND ALTERNATIVE 1179 00:50:19,920 --> 00:50:20,840 THERAPEUTICS. 1180 00:50:20,840 --> 00:50:23,920 A QUOTE -- PERFECT IS THE ENEMY 1181 00:50:23,920 --> 00:50:26,480 OF GOOD SO WE TALKED ABOUT A LOT 1182 00:50:26,480 --> 00:50:28,160 OF GRANULAR CONCEPTS. 1183 00:50:28,160 --> 00:50:30,640 WOULD IT BE GREAT IF WE KNEW ALL 1184 00:50:30,640 --> 00:50:32,880 OF THESE THINGS ABOUT THE 1185 00:50:32,880 --> 00:50:33,640 MICROBIOTA. 1186 00:50:33,640 --> 00:50:35,200 A LOT OF INTERACTIONS. 1187 00:50:35,200 --> 00:50:37,200 BUT THE NOTION IS THAT MAYBE WE 1188 00:50:37,200 --> 00:50:39,440 DON'T NEED TO KNOW EVERYTHING TO 1189 00:50:39,440 --> 00:50:40,320 MAKE FORWARD PROGRESS IN THE 1190 00:50:40,320 --> 00:50:40,760 FIELD. 1191 00:50:40,760 --> 00:50:45,040 SO IT'S IMPORTANT TO BE 1192 00:50:45,040 --> 00:50:47,160 HYPOTHESIS DRIVEN BUT THE 1193 00:50:47,160 --> 00:50:48,960 COMPLEXITY MEANS THAT WE MAY NOT 1194 00:50:48,960 --> 00:50:49,600 KNOW EVERYTHING. 1195 00:50:49,600 --> 00:50:52,840 AND I USE AN EXAMPLE -- WHICH IS 1196 00:50:52,840 --> 00:50:55,240 THE STANDARD DRUG USED. 1197 00:50:55,240 --> 00:50:55,960 VERY SAFE. 1198 00:50:55,960 --> 00:50:57,840 VERY EFFECTIVE. 1199 00:50:57,840 --> 00:51:00,040 HOWEVER, WE DON'T KNOW HOW IT 1200 00:51:00,040 --> 00:51:00,600 WORKS. 1201 00:51:00,600 --> 00:51:03,080 THE LIST OF THINGS THAT IT 1202 00:51:03,080 --> 00:51:06,760 INHIBITS OR INDUCES IS RELONG 1203 00:51:06,760 --> 00:51:09,040 BUT WE KNOW THAT IT WORKS. 1204 00:51:09,040 --> 00:51:10,240 SO THERE ARE OPPORTUNITIES I 1205 00:51:10,240 --> 00:51:11,880 THINK TO MOVE FORWARD. 1206 00:51:11,880 --> 00:51:13,440 AND THINK ABOUT HUMAN 1207 00:51:13,440 --> 00:51:14,440 INTERVENTION STUDIES. 1208 00:51:14,440 --> 00:51:16,320 THAT WILL TEACH US A LOT OF 1209 00:51:16,320 --> 00:51:17,440 IMPORTANT THINGS. 1210 00:51:17,440 --> 00:51:20,120 EVEN WHEN WE DON'T KNOW 1211 00:51:20,120 --> 00:51:21,120 PRECISELY EVERYTHING ABOUT THE 1212 00:51:21,120 --> 00:51:21,600 SYSTEM. 1213 00:51:21,600 --> 00:51:24,040 SO WITH THAT I TOLD YOU ABOUT 1214 00:51:24,040 --> 00:51:26,520 THE OXYGEN DYNAMICS. 1215 00:51:26,520 --> 00:51:28,520 HIGHLIGHTING THE GROUP OF 1216 00:51:28,520 --> 00:51:29,880 INDIVIDUALS IN RED THAT DID THAT 1217 00:51:29,880 --> 00:51:31,440 WORK AND I THANK YOU AGAIN VERY 1218 00:51:31,440 --> 00:51:33,560 MUCH FOR THE OPPORTUNITY TO GIVE 1219 00:51:33,560 --> 00:51:34,840 YOU THIS PRESENTATION TODAY AND 1220 00:51:34,840 --> 00:51:36,240 I LOOK FORWARD TO THE PANEL 1221 00:51:36,240 --> 00:51:36,560 DISCUSSION. 1222 00:51:36,560 --> 00:51:40,160 THANK YOU. 1223 00:51:40,160 --> 00:51:43,000 >> THANK YOU SO MUCH, DR. WU. 1224 00:51:43,000 --> 00:51:45,880 A GREAT TALK AND ALSO THANK YOU 1225 00:51:45,880 --> 00:51:48,280 TO DR. BETZ FOR HIS OPENING 1226 00:51:48,280 --> 00:51:48,880 REMARKS. 1227 00:51:48,880 --> 00:51:52,400 NOW I'M PLEASED TO TURN THINGS 1228 00:51:52,400 --> 00:51:56,080 OVER TO DR. PADMA MARUVADA. 1229 00:51:56,080 --> 00:52:06,120 AND DR. RYAN RANALLO. 1230 00:52:06,120 --> 00:52:09,240 NEXT GENERATION PRO-BIOTICS, NEW 1231 00:52:09,240 --> 00:52:10,600 TRAIN IDENTIFICATION AND 1232 00:52:10,600 --> 00:52:12,600 DEVELOPMENT. 1233 00:52:12,600 --> 00:52:15,680 THEY WILL ALTERNATE AND 1234 00:52:15,680 --> 00:52:16,720 INTRODUCING THEIR SPEAKERS AND 1235 00:52:16,720 --> 00:52:19,480 I'M GOING TO BRING UP A QUICK 1236 00:52:19,480 --> 00:52:20,920 SLIDE THAT SHARES WITH YOU WHO 1237 00:52:20,920 --> 00:52:24,240 THE SPEAKERS WILL BE. 1238 00:52:24,240 --> 00:52:26,120 DR. RANALLO IS GOING TO LEAD OFF 1239 00:52:26,120 --> 00:52:28,200 IN INTRODUCING THE SPEAKERS. 1240 00:52:28,200 --> 00:52:31,720 AND SO I WILL TURN IT OVER TO 1241 00:52:31,720 --> 00:52:33,280 DR. RANALLO WHO WILL INTRODUCE 1242 00:52:33,280 --> 00:52:37,480 THE FIRST SPEAKER OF SECTION 3. 1243 00:52:37,480 --> 00:52:38,440 THANK YOU. 1244 00:52:38,440 --> 00:52:39,840 TAKE IT AWAY. 1245 00:52:39,840 --> 00:52:40,920 >> THANK YOU, KATHERINE. 1246 00:52:40,920 --> 00:52:44,880 I ALSO WANT TO THANK GARY FOR AN 1247 00:52:44,880 --> 00:52:46,360 INCREDIBLY THOUGHTFUL KEYNOTE 1248 00:52:46,360 --> 00:52:49,080 AND THE WAY IN WHICH HE 1249 00:52:49,080 --> 00:52:50,640 ARTICULATED TODAY'S SESSIONS AND 1250 00:52:50,640 --> 00:52:52,440 PUT THEM INTO CONTEXT. 1251 00:52:52,440 --> 00:52:54,160 IT'S JUST GOING TO MAKE OUR JOBS 1252 00:52:54,160 --> 00:52:55,320 SO MUCH EASIER. 1253 00:52:55,320 --> 00:52:57,080 SO WITH THAT GOOD MORNING, 1254 00:52:57,080 --> 00:52:58,760 EVERYBODY AND WELCOME TO THE 1255 00:52:58,760 --> 00:53:01,280 THIRD SESSION OF OUR WORKSHOP. 1256 00:53:01,280 --> 00:53:03,880 AND AS KATHERINE SAID IT'S NEXT 1257 00:53:03,880 --> 00:53:09,200 GENERATION PRO-BIOTICS STRAIN, 1258 00:53:09,200 --> 00:53:10,200 NEW DEVELOPMENT. 1259 00:53:10,200 --> 00:53:13,400 ALONG WITH MY COLLEAGUE PADMA 1260 00:53:13,400 --> 00:53:14,160 MARUVADA. 1261 00:53:14,160 --> 00:53:16,560 WE WILL BE YOUR MODERATORS. 1262 00:53:16,560 --> 00:53:18,560 AND WE WILL BE HOSTING YOUR 1263 00:53:18,560 --> 00:53:19,800 PANEL DISCUSSION. 1264 00:53:19,800 --> 00:53:25,160 AS A REMINDER SPEAKERS, -- THE 1265 00:53:25,160 --> 00:53:26,760 LIST OF SPEAKERS FOR THE SECTION 1266 00:53:26,760 --> 00:53:28,160 IS IN YOUR PROGRAM GUIDE ALONG 1267 00:53:28,160 --> 00:53:30,640 WITH THE BIOS AND ABSTRACTS. 1268 00:53:30,640 --> 00:53:32,960 FOR THOSE OF YOU WATCHING PLEASE 1269 00:53:32,960 --> 00:53:34,440 REMEMBER TO SUBMIT QUESTIONS FOR 1270 00:53:34,440 --> 00:53:36,440 THE PANEL DISCUSSION AS I SAID 1271 00:53:36,440 --> 00:53:38,080 WE'LL TRY TO GET TO SOME OF 1272 00:53:38,080 --> 00:53:38,560 THOSE. 1273 00:53:38,560 --> 00:53:43,720 AND WITH THAT I WOULD LIKE TO 1274 00:53:43,720 --> 00:53:53,480 INTRODUCE DR. JULIA OH. 1275 00:53:53,480 --> 00:53:54,560 JULIA. 1276 00:53:54,560 --> 00:53:55,600 IT'S ALL YOURS. 1277 00:53:55,600 --> 00:54:11,480 >> ALL RIGHT. 1278 00:54:11,480 --> 00:54:15,360 >> SO JUST BY WAY OF CONTEXT -- 1279 00:54:15,360 --> 00:54:17,600 A LOT ABOUT HEALTHY VERSUS 1280 00:54:17,600 --> 00:54:19,360 DISEASE MICROBIOMES AND HOW WE 1281 00:54:19,360 --> 00:54:21,560 MIGHT TARGET THESE DIFFERENCES 1282 00:54:21,560 --> 00:54:23,440 TO DEVELOP THERAPEUTICS. 1283 00:54:23,440 --> 00:54:26,240 THE SKIN MICROBIOME. 1284 00:54:26,240 --> 00:54:28,440 WE'VE DEFINED SOME OF THE 1285 00:54:28,440 --> 00:54:29,080 CHARACTERISTICS. 1286 00:54:29,080 --> 00:54:31,720 THERE MIGHT BE HEALTHY 1287 00:54:31,720 --> 00:54:33,000 CONFIGURATIONS THAT DIFFER 1288 00:54:33,000 --> 00:54:34,880 BETWEEN INDIVIDUALS BUT WHOSE 1289 00:54:34,880 --> 00:54:37,280 OVER-ALL PARAMETERS ARE DEFINED 1290 00:54:37,280 --> 00:54:42,040 BY THE SKIN SITE. 1291 00:54:42,040 --> 00:54:46,400 AND THESE DEFINE. 1292 00:54:46,400 --> 00:54:49,240 IN TERMS OF DIVERSITY AND 1293 00:54:49,240 --> 00:54:50,440 STABILITY OVER TIME. 1294 00:54:50,440 --> 00:54:53,120 WHEN YOU HAVE A -- TO THE SYSTEM 1295 00:54:53,120 --> 00:54:58,520 WHETHER IT'S IN THINKSIC -- OR * 1296 00:54:58,520 --> 00:55:01,040 EXTRINSIC -- IT CAN BE DRIVEN 1297 00:55:01,040 --> 00:55:06,080 INTO A DISEASE MINIMUM THAT IS 1298 00:55:06,080 --> 00:55:10,840 CHARACTERIZED -- AS PATHOGENS 1299 00:55:10,840 --> 00:55:12,360 TAKE OVER. 1300 00:55:12,360 --> 00:55:18,840 AND I SHOW THIS TO YOU BECAUSE 1301 00:55:18,840 --> 00:55:20,560 -- IT SHOWS THE TARGETS. 1302 00:55:20,560 --> 00:55:23,560 THERE ARE SOME KEY UNRESOLVED 1303 00:55:23,560 --> 00:55:27,480 KNOWLEDGE GAPS. 1304 00:55:27,480 --> 00:55:33,360 AND ONE THAT I'LL TALK ABOUT IS 1305 00:55:33,360 --> 00:55:38,160 STRAIN DIVERSITY. 1306 00:55:38,160 --> 00:55:40,480 DIFFERENT STRAINS HAVE DRAMATIC 1307 00:55:40,480 --> 00:55:41,600 PHENOTYPIC DIFFERENCES. 1308 00:55:41,600 --> 00:55:45,760 AND FROM A MICROBIAL PERSPECTIVE 1309 00:55:45,760 --> 00:55:51,120 WE NEED TO CARE ABOUT STRAINS. 1310 00:55:51,120 --> 00:55:53,880 SO FOR EXAMPLE THE SINGLE TOXIN 1311 00:55:53,880 --> 00:55:56,320 -- E. COLI CAN TURN OUR CLONING 1312 00:55:56,320 --> 00:55:58,960 FRIEND INTO A PATHOGEN THAT 1313 00:55:58,960 --> 00:56:04,720 CAUSES KIDNEY FAILURE. 1314 00:56:04,720 --> 00:56:07,920 AND DEPENDING ON WHICH STRAIN 1315 00:56:07,920 --> 00:56:12,640 YOU HAVE GREEN OR RED YOUR 1316 00:56:12,640 --> 00:56:13,880 DISEASE SUSCEPTIBILITY OR 1317 00:56:13,880 --> 00:56:16,640 TREATMENT RESPONSE CAN BE 1318 00:56:16,640 --> 00:56:19,520 DIFFERENT. 1319 00:56:19,520 --> 00:56:21,840 BUT IT GETS MORE COMPLICATED. 1320 00:56:21,840 --> 00:56:24,480 DO WE ACQUIRE AND MAINTAIN JUST 1321 00:56:24,480 --> 00:56:26,840 ONE STRAIN WITHIN AN INDIVIDUAL 1322 00:56:26,840 --> 00:56:28,960 SO ALL RED OR ALL GREEN? 1323 00:56:28,960 --> 00:56:33,360 OR DO WE HARBOR MIXTURES WHICH 1324 00:56:33,360 --> 00:56:34,680 CHANGESES THE PICTURE. 1325 00:56:34,680 --> 00:56:39,200 SO EVEN HEALTHY PEOPLE MIGHT BE 1326 00:56:39,200 --> 00:56:40,280 RESERVOIRS. 1327 00:56:40,280 --> 00:56:41,840 DIFFERENT STRAINS MIGHT COMPETE 1328 00:56:41,840 --> 00:56:43,840 AGAINST EACH OTHER. 1329 00:56:43,840 --> 00:56:45,240 PREVENT COLONIZATION. 1330 00:56:45,240 --> 00:56:57,200 THE LOCATION MIGHT BE IMPORTANT. 1331 00:56:57,200 --> 00:56:58,640 LARGELY UNANSWERED QUESTION WAS 1332 00:56:58,640 --> 00:56:59,400 CRITICAL. 1333 00:56:59,400 --> 00:57:01,040 WHETHER WE HAVE ONE OR MANY 1334 00:57:01,040 --> 00:57:02,880 STRAINS OF THE GIVEN SPECIES AND 1335 00:57:02,880 --> 00:57:03,800 THEN ASSOCIATED QUESTIONS. 1336 00:57:03,800 --> 00:57:06,080 HOW DO WE ACQUIRE THEM AND WHAT 1337 00:57:06,080 --> 00:57:07,440 HAPPENS TO THEM OVER THEIR 1338 00:57:07,440 --> 00:57:10,520 TENURE IN OUR BODIES. 1339 00:57:10,520 --> 00:57:14,440 SO WE USE METRO GENOMIC 1340 00:57:14,440 --> 00:57:15,520 SEQUENCES. 1341 00:57:15,520 --> 00:57:18,600 AND A LIMITATION -- WHICH IS FAR 1342 00:57:18,600 --> 00:57:21,680 MORE COMPREHENSIVE IN TERMS OF 1343 00:57:21,680 --> 00:57:23,120 RECOVERING DIVERSITY. 1344 00:57:23,120 --> 00:57:25,120 A LIMITATION IS THAT IT HAS 1345 00:57:25,120 --> 00:57:28,520 LIMITED ACCURACY. 1346 00:57:28,520 --> 00:57:32,160 AND ALGORITHMS TEND TO 1347 00:57:32,160 --> 00:57:36,520 UNDERESTIMATE STRAIN DIVERSITY. 1348 00:57:36,520 --> 00:57:38,840 AS WE SEQUENCE INDIVIDUAL 1349 00:57:38,840 --> 00:57:40,440 GENOMES AND THIS PROVIDES US THE 1350 00:57:40,440 --> 00:57:42,040 RESOLUTION THAT WE NEED TO 1351 00:57:42,040 --> 00:57:43,360 UNDERSTAND SOME OF OUR BASIC 1352 00:57:43,360 --> 00:57:44,640 QUESTIONS. 1353 00:57:44,640 --> 00:57:47,080 -- LOOKING AT WITHIN AN 1354 00:57:47,080 --> 00:57:49,440 INDIVIDUAL STRAIN DIVERSITY WE 1355 00:57:49,440 --> 00:57:52,960 LOOKED AT STAPH -- WE ALL HAVE 1356 00:57:52,960 --> 00:57:54,640 IT AND IT'S PRETTY MUCH 1357 00:57:54,640 --> 00:57:56,240 EVERYWHERE ON OUR SKIN. 1358 00:57:56,240 --> 00:58:00,840 AND WHILE IT'S ESSENTIAL -- IT'S 1359 00:58:00,840 --> 00:58:06,240 LOW IN ABUNDANCE. 1360 00:58:06,240 --> 00:58:10,160 NOW THE FLIP SIDE IS ALSO THE 1361 00:58:10,160 --> 00:58:14,000 COMMON CAUSE OF BLOOD INFECTION. 1362 00:58:14,000 --> 00:58:15,760 SO UNDERSTANDING HOW CERTAIN 1363 00:58:15,760 --> 00:58:17,480 TRAINS ARE ASSOCIATED WITH 1364 00:58:17,480 --> 00:58:19,480 DISEASE WILL PROVIDE INSIGHTS 1365 00:58:19,480 --> 00:58:23,320 INTO THE TRANSITION. 1366 00:58:23,320 --> 00:58:28,960 8 AND SO IN OUR FIRST PASS WE 1367 00:58:28,960 --> 00:58:32,360 CULTIVATED AND SEQUENCED 1500 1368 00:58:32,360 --> 00:58:34,680 ISOLATES FROM FIVE HEALTHY 1369 00:58:34,680 --> 00:58:36,160 INDIVIDUALS AND THEN COMPARED 1370 00:58:36,160 --> 00:58:38,680 THEIR GENOMES TO ANSWER BASIC 1371 00:58:38,680 --> 00:58:39,600 QUESTIONS. 1372 00:58:39,600 --> 00:58:41,520 JUST RECAPPING THEM HERE. 1373 00:58:41,520 --> 00:58:44,240 SO TO ANSWER THE FIRST QUESTION 1374 00:58:44,240 --> 00:58:45,840 OUR FIRST EXTRAORDINARY RESULT 1375 00:58:45,840 --> 00:58:49,600 WITH THAT BASICALLY -- EVERY 1376 00:58:49,600 --> 00:58:52,560 ISOLATE WAS A DIFFERENT 1377 00:58:52,560 --> 00:58:54,520 GENETICALLY STRAIN. 1378 00:58:54,520 --> 00:58:57,320 SO THE HEAT MAP OF GENE 1379 00:58:57,320 --> 00:59:00,400 PREVALENCES WERE REPRESENTATIVE. 1380 00:59:00,400 --> 00:59:03,200 THIS IS GENE CONTENT DIFFERENCES 1381 00:59:03,200 --> 00:59:06,080 WITH SKIN SITE ON THE X AXIS. 1382 00:59:06,080 --> 00:59:13,760 7 SO FIRST OFF THE HETEROGENEITY 1383 00:59:13,760 --> 00:59:17,600 -- CAN HAVE DIFFERENT 1384 00:59:17,600 --> 00:59:20,280 COMPILATION OF GENES. 1385 00:59:20,280 --> 00:59:22,280 IT CAN BE UNIQUE TO THE SKIN 1386 00:59:22,280 --> 00:59:26,640 SITE. 1387 00:59:26,640 --> 00:59:28,880 SUGGESTING A STRONG SKIN SITE 1388 00:59:28,880 --> 00:59:33,120 SPECIALIZATION. 1389 00:59:33,120 --> 00:59:36,760 BUT AGAIN THE OVER-ALL 1390 00:59:36,760 --> 00:59:37,880 HETEROGENEITY SUGGEST THAT THERE 1391 00:59:37,880 --> 00:59:40,080 ARE ADDITIONAL FACTORS CAUSING 1392 00:59:40,080 --> 00:59:41,560 THIS. 1393 00:59:41,560 --> 00:59:43,240 WHAT COULD BE SOME OF THE 1394 00:59:43,240 --> 00:59:43,640 FACTORS? 1395 00:59:43,640 --> 00:59:45,200 FOR EXAMPLE MAYBE WHERE THESE 1396 00:59:45,200 --> 00:59:46,520 DIFFERENT STRAINS COME FROM. 1397 00:59:46,520 --> 00:59:48,720 THESE STRAINS ARE SO DIVERSE 1398 00:59:48,720 --> 00:59:50,400 THAT IT'S UNLIKELY FOR ALL OF 1399 00:59:50,400 --> 00:59:53,480 THESE DIVERSE STRAINS TO DIVERGE 1400 00:59:53,480 --> 00:59:58,080 FROM A SINGLE PARENT STRAIN. 1401 00:59:58,080 --> 01:00:00,480 IT'S THOUGHT THAT WE GET OUR 1402 01:00:00,480 --> 01:00:02,800 MICROBIOME FROM OUR MOMS AND 1403 01:00:02,800 --> 01:00:05,760 THEN TRANSMISSION EVENTS, THESE 1404 01:00:05,760 --> 01:00:11,960 MIGHT BRING NEW STRAINS IN OR 1405 01:00:11,960 --> 01:00:15,360 EVOLUTION. 1406 01:00:15,360 --> 01:00:21,920 AS WE -- -- TO INFER THE SOURCE 1407 01:00:21,920 --> 01:00:24,840 OF THE STRAIN -- BECAUSE SNIPS 1408 01:00:24,840 --> 01:00:27,600 CAN ACT LIKE A MOLECULAR CLOCK 1409 01:00:27,600 --> 01:00:31,440 AND THAT IS REFLECTED BY THE 1410 01:00:31,440 --> 01:00:43,480 CLOSESTHE --CLOSENESS. 1411 01:00:43,480 --> 01:00:47,120 -- -- THIS WAS SURPRISING 1412 01:00:47,120 --> 01:00:51,640 BECAUSE THE ONLY OTHER STUDY 1413 01:00:51,640 --> 01:01:04,000 LOOKING AT FRAGILIS -- DIVERGES 1414 01:01:04,000 --> 01:01:07,480 OVER TIME. 1415 01:01:07,480 --> 01:01:09,520 BUT THEN WHAT OTHER OTHER 1416 01:01:09,520 --> 01:01:13,520 FACTORS? 1417 01:01:13,520 --> 01:01:15,200 TRANSMISSION BETWEEN BODY SITES 1418 01:01:15,200 --> 01:01:16,680 WITHIN AN INDIVIDUAL. 1419 01:01:16,680 --> 01:01:19,240 SO BY TRACKING SNIPS WE CAN 1420 01:01:19,240 --> 01:01:21,240 MOUNT THE MOST COMMON WAYS FOR 1421 01:01:21,240 --> 01:01:22,680 STRAINS TO TRAVEL WHICH IS BY 1422 01:01:22,680 --> 01:01:23,120 TOUCH. 1423 01:01:23,120 --> 01:01:26,440 THE LINES SHOW THE PREVALENT 1424 01:01:26,440 --> 01:01:28,360 TRANSMISSION ROUTES FROM THE 1425 01:01:28,360 --> 01:01:34,360 HANDS TO THE FACE. 1426 01:01:34,360 --> 01:01:36,680 THE GENES AS WELL IN A MECHANISM 1427 01:01:36,680 --> 01:01:39,440 CALLED MORE ZONE TAN GENE 1428 01:01:39,440 --> 01:01:41,640 TRANSFER. 1429 01:01:41,640 --> 01:01:49,560 * SO A FICK EXAMPLE -- AND ALSO 1430 01:01:49,560 --> 01:01:50,040 *. 1431 01:01:50,040 --> 01:01:51,440 THE 1432 01:01:53,480 --> 01:01:57,240 WHICH CAN MAKE PATHOGENS 1433 01:01:57,240 --> 01:02:01,400 RESISTANT TO TREATMENT. 1434 01:02:01,400 --> 01:02:04,320 AND THEN WE LOOK FOR EVIDENCE OF 1435 01:02:04,320 --> 01:02:06,680 DISSEMINATION OF THESE GENETIC 1436 01:02:06,680 --> 01:02:07,120 ELEMENTS. 1437 01:02:07,120 --> 01:02:12,600 ON THE LEFT IS AN EXAMPLE. 1438 01:02:12,600 --> 01:02:15,240 ON THE RIGHT WE SEE A MAP OF 1439 01:02:15,240 --> 01:02:16,080 DISSEMINATION WITHIN AN 1440 01:02:16,080 --> 01:02:17,200 INDIVIDUAL. 1441 01:02:17,200 --> 01:02:21,600 THE DARKNESS OF THE BLUE DOTS 1442 01:02:21,600 --> 01:02:22,680 REFLECT IS PREVALENCE. 1443 01:02:22,680 --> 01:02:28,080 WE SEE THE RESISTANCE GAMES HAVE 1444 01:02:28,080 --> 01:02:32,800 DISSEMINATED TO DIFFERENT SITES. 1445 01:02:32,800 --> 01:02:36,560 HORIZONTAL GENE TRANSFER -- AND 1446 01:02:36,560 --> 01:02:40,000 SO NOW WE HAVE AN EMERGING 1447 01:02:40,000 --> 01:02:44,560 PORTRAIT. 1448 01:02:44,560 --> 01:02:46,240 IT STARTS WITH OUR COLONIZATION 1449 01:02:46,240 --> 01:02:50,800 OF A GENETICALLY DIVERSE 1450 01:02:50,800 --> 01:02:59,640 STRAINS. 1451 01:02:59,640 --> 01:03:01,320 AND BEING REALLY SURPRISED BY 1452 01:03:01,320 --> 01:03:03,400 THE DEGREE WITHIN AN INDIVIDUAL 1453 01:03:03,400 --> 01:03:05,040 STRAIN DIVERSITY THAT WE FOUND 1454 01:03:05,040 --> 01:03:11,000 WE WONDERED IF THIS DIVERSITY 1455 01:03:11,000 --> 01:03:13,840 WAS A NECESSARY CONSEQUENCE. 1456 01:03:13,840 --> 01:03:16,600 AND TO EXPLAIN ONE CONSEQUENCE 1457 01:03:16,600 --> 01:03:22,080 OF STRAIN DIVERSITY -- QUORUM 1458 01:03:22,080 --> 01:03:24,040 SENSING ENDED UP BEING RELEVANT 1459 01:03:24,040 --> 01:03:24,640 HERE. 1460 01:03:24,640 --> 01:03:29,240 SOME BACTERIA PRODUCES A 1461 01:03:29,240 --> 01:03:34,240 CHEMICAL. 1462 01:03:34,240 --> 01:03:36,000 AND TURN ON A SPECIAL SET OF 1463 01:03:36,000 --> 01:03:39,920 GENES. 1464 01:03:39,920 --> 01:03:42,240 AND THERE IS MORE AUTO INDUCER 1465 01:03:42,240 --> 01:03:44,600 AND THESE CAN BE TURNED ON AND 1466 01:03:44,600 --> 01:03:46,240 ALL OF THE CELLS IN THE 1467 01:03:46,240 --> 01:03:50,440 POPULATION. 1468 01:03:50,440 --> 01:03:53,280 SO WHAT HAPPENS WITH THE 1469 01:03:53,280 --> 01:03:57,800 DIFFERENT MIXTURES. 1470 01:03:57,800 --> 01:04:00,080 BASED ON THE LITERATURE WE 1471 01:04:00,080 --> 01:04:02,080 THOUGHT THAT IT MIGHT CAUSE 1472 01:04:02,080 --> 01:04:05,760 INTERFERENCE IN THE POPULATION. 1473 01:04:05,760 --> 01:04:07,880 AND THAT IS EXACTLY WHAT WE 1474 01:04:07,880 --> 01:04:10,040 OBSERVED ENVY TOE. 1475 01:04:10,040 --> 01:04:12,360 -- *. 1476 01:04:12,360 --> 01:04:14,600 AND WE MADE THEM IN DIFFERENT 1477 01:04:14,600 --> 01:04:24,560 PROPORTIONS. 1478 01:04:24,560 --> 01:04:27,640 TRANSCRIPTION AS MEASURED WAS 1479 01:04:27,640 --> 01:04:30,840 VERY STRONGLY REPRESSED COMPARED 1480 01:04:30,840 --> 01:04:34,840 TO WHEN YOU GIVE IT TO -- THAT 1481 01:04:34,840 --> 01:04:40,440 IS STRONGLY INDUCED. 1482 01:04:40,440 --> 01:04:43,760 AS A COROLLARY STRAIN DIVERSITY 1483 01:04:43,760 --> 01:04:46,600 CAN BE AN IMPORTANT DETERMINANT. 1484 01:04:46,600 --> 01:04:48,800 AND NOW WE'RE TESTING THIS IN 1485 01:04:48,800 --> 01:04:50,480 MOUSE MODELS. 1486 01:04:50,480 --> 01:04:55,840 SO ADDING VERY PLANTS. 1487 01:04:55,840 --> 01:04:56,440 *. 1488 01:04:56,440 --> 01:05:02,440 NOW DIGGING DEEPER -- IT BEGS 1489 01:05:02,440 --> 01:05:04,960 FOR QUESTIONS LIKE WHICH STRAINS 1490 01:05:04,960 --> 01:05:07,280 IS WITHIN AN INFECTION AND WHICH 1491 01:05:07,280 --> 01:05:09,680 STRAINS DO WE USE FOR AN 1492 01:05:09,680 --> 01:05:10,440 ANTIBIOTIC. 1493 01:05:10,440 --> 01:05:13,320 WOULD IT BE BETTER TO USE A 1494 01:05:13,320 --> 01:05:16,080 GENETICALLY SIMILAR OR MORE 1495 01:05:16,080 --> 01:05:22,040 DISTANT STRAIN. 1496 01:05:22,040 --> 01:05:24,320 AND THEN YOU HAVE WHAT ARE THE 1497 01:05:24,320 --> 01:05:26,960 FUNCTION, CONSEQUENCES OF STRAIN 1498 01:05:26,960 --> 01:05:29,040 DIVERSITY IN THE SKIN? 1499 01:05:29,040 --> 01:05:30,920 WE'VE BEEN TAKING A FEW 1500 01:05:30,920 --> 01:05:34,640 APPROACHES. 1501 01:05:34,640 --> 01:05:36,640 SO FOR EXAMPLE TAKING IN MIND TO 1502 01:05:36,640 --> 01:05:39,280 ALL OF THE UNKNOWN FUNCTIONS OF 1503 01:05:39,280 --> 01:05:42,480 ALL OF THE STRAIN SPECIFIC GENES 1504 01:05:42,480 --> 01:05:46,560 -- WE DEVELOP GENOME WIDE CRISPR 1505 01:05:46,560 --> 01:05:51,000 INTERFERENCE -- TO PROBE -- 1506 01:05:51,000 --> 01:05:53,520 PLASTICITY IN DIFFERENT 1507 01:05:53,520 --> 01:05:55,080 ENVIRONMENTAL CONDITIONS 1508 01:05:55,080 --> 01:05:59,800 RELEVANT TO THE SKIN. 1509 01:05:59,800 --> 01:06:02,280 WE DEVELOPED A PLATFORM 1510 01:06:02,280 --> 01:06:06,120 PROFILING THE RESPONSE OF SKIN 1511 01:06:06,120 --> 01:06:08,360 ORGANOIDS TO COLONIZATION BY 1512 01:06:08,360 --> 01:06:11,240 DIFFERENT STRAINS WITH DIFFERENT 1513 01:06:11,240 --> 01:06:18,680 HOST READOUTS. 1514 01:06:18,680 --> 01:06:25,240 AND TO SHOWING A SNAPSHOT. 1515 01:06:25,240 --> 01:06:28,200 SO HERE WE'RE LOOKING AT A FEW 1516 01:06:28,200 --> 01:06:30,520 OF THE DIFFERENTIALLY EXPRESSED 1517 01:06:30,520 --> 01:06:35,240 GENES. 1518 01:06:35,240 --> 01:06:38,680 AND THEY ARE BOXED IN RED WITH A 1519 01:06:38,680 --> 01:06:40,320 TIME SERIES. 1520 01:06:40,320 --> 01:06:42,640 AND YOU CAN SEE CLEARLY THERE IS 1521 01:06:42,640 --> 01:06:48,680 TIME EFFECTS. 1522 01:06:48,680 --> 01:06:50,800 AND SECOND YOU CAN SEE THE 1523 01:06:50,800 --> 01:06:53,040 EFFECTS OF THE CATHETER 1524 01:06:53,040 --> 01:06:56,600 ASSOCIATED STRAIN. 1525 01:06:56,600 --> 01:06:59,240 SO A STRAIN SPECIFIC EFFECT IN 1526 01:06:59,240 --> 01:07:01,560 THESE ORGANOIDS. 1527 01:07:01,560 --> 01:07:03,400 AND WE'RE ALSO SEEKING TO 1528 01:07:03,400 --> 01:07:06,160 UNDERSTAND HOW GENETIC DIVERSITY 1529 01:07:06,160 --> 01:07:14,680 LINK CANS TO THE ME LA -- METABOLITES. 1530 01:07:14,680 --> 01:07:16,440 WE'RE USING COME FEW 1531 01:07:16,440 --> 01:07:36,880 INDICATIONAL PREDICTIONS -- -- SO HERE 1532 01:07:36,880 --> 01:07:43,800 WE'RE LOOKING AT THE SCORES. 1533 01:07:43,800 --> 01:07:47,640 AND IN CATEGORIES OF INTEREST. 1534 01:07:47,640 --> 01:07:49,520 METABOLITES THAT ACTIVATE AGE 1535 01:07:49,520 --> 01:07:52,240 SIGNALING THAT MEDIATES SKIN 1536 01:07:52,240 --> 01:07:54,000 BARRIER REPAIR AS WELL AS 1537 01:07:54,000 --> 01:07:55,880 DIFFERENT FACETS OF THE IMMUNE 1538 01:07:55,880 --> 01:07:57,280 SYSTEM. 1539 01:07:57,280 --> 01:07:59,360 MAJOR DIFFERENCES BETWEEN THE 1540 01:07:59,360 --> 01:08:00,840 TWO STRAINS IN SOME OF THESE 1541 01:08:00,840 --> 01:08:03,920 PATHWAYS. 1542 01:08:03,920 --> 01:08:05,720 AND THAT IS MY TWO BIG TAKE 1543 01:08:05,720 --> 01:08:07,120 AWAYS HERE. 1544 01:08:07,120 --> 01:08:09,240 THIS IS GOING TO BE HIGHLY 1545 01:08:09,240 --> 01:08:10,080 SPECIES SPECIFIC. 1546 01:08:10,080 --> 01:08:14,280 WE SEE EXTENSIVE WITHIN AND 1547 01:08:14,280 --> 01:08:16,840 INDIVIDUAL STRAIN DIVERSITY. 1548 01:08:16,840 --> 01:08:20,120 SO DESIGNING THERAPEUTICS WE 1549 01:08:20,120 --> 01:08:22,640 NEED TO THINK NOT ONLY AT THE 1550 01:08:22,640 --> 01:08:25,440 SPECIES LEVEL BUT AT THE STRAIN 1551 01:08:25,440 --> 01:08:29,640 LEVEL. 1552 01:08:29,640 --> 01:08:32,440 NOW WITH THAT JUST THANKING MY 1553 01:08:32,440 --> 01:08:34,520 FANTASTIC GROUP AT THE JACKSON 1554 01:08:34,520 --> 01:08:36,640 LABORATORY AND MY WONDERFUL 1555 01:08:36,640 --> 01:08:39,960 COLLABORATORS AS WELL. 1556 01:08:39,960 --> 01:08:41,120 >> THANK YOU. 1557 01:08:41,120 --> 01:08:42,840 THANK YOU, JULIA. 1558 01:08:42,840 --> 01:08:44,960 THAT WAS A WONDERFUL 1559 01:08:44,960 --> 01:08:45,440 PRESENTATION. 1560 01:08:45,440 --> 01:08:51,800 OUR NEXT SPEAKER IS DR. JUNE 1561 01:08:51,800 --> 01:08:53,480 ROUND FROM THE UNIVERSITY OF 1562 01:08:53,480 --> 01:09:02,240 UTAH. 1563 01:09:02,240 --> 01:09:06,880 >> GOOD MORNING, EVERYONE. 1564 01:09:06,880 --> 01:09:08,440 AND CAN YOU SEE THIS? 1565 01:09:08,440 --> 01:09:09,840 >> YES. 1566 01:09:09,840 --> 01:09:11,480 >> RIGHT IN THE MIDDLE OF THE 1567 01:09:11,480 --> 01:09:11,840 PRESENTATION. 1568 01:09:11,840 --> 01:09:13,720 WHICH IS ALWAYS GOOD. 1569 01:09:13,720 --> 01:09:15,520 >> YOU ARE IN SPEAKER 1570 01:09:15,520 --> 01:09:17,520 PRESENTATION MODE SO MAYBE IF 1571 01:09:17,520 --> 01:09:18,840 YOU CAN SWAP MONITORS. 1572 01:09:18,840 --> 01:09:22,200 THAT IS WHAT WE SEE. 1573 01:09:22,200 --> 01:09:26,880 PERFECT. 1574 01:09:26,880 --> 01:09:28,680 >> THANK YOU SO MUCH FOR PUTTING 1575 01:09:28,680 --> 01:09:30,240 TOGETHER THIS MEETING. 1576 01:09:30,240 --> 01:09:35,640 IT'S BEEN A WONDERFUL AND 1577 01:09:35,640 --> 01:09:37,840 INVITING -- ME TO PRESENT SOME 1578 01:09:37,840 --> 01:09:38,480 OF OUR WORK. 1579 01:09:38,480 --> 01:09:40,320 I'M GOING TO TALK ABOUT 1580 01:09:40,320 --> 01:09:41,280 ORGANISMS THAT WE HAVE NOT 1581 01:09:41,280 --> 01:09:43,400 MENTIONED IN THIS MEETING YET. 1582 01:09:43,400 --> 01:09:46,280 BUT ARE STILL AN IMPORTANT 1583 01:09:46,280 --> 01:09:49,040 ALBEIT SMALL PROPORTION OF OUR 1584 01:09:49,040 --> 01:09:49,520 MICROBIOTA. 1585 01:09:49,520 --> 01:09:51,200 IN KEEPING WITH THE FOCUS OF 1586 01:09:51,200 --> 01:09:53,720 THIS MEETING I THOUGHT I WOULD 1587 01:09:53,720 --> 01:09:56,040 TELL YOU A STORY THAT WE 1588 01:09:56,040 --> 01:09:59,040 PUBLISHED LAST YEAR REGARDING 1589 01:09:59,040 --> 01:10:04,400 HOW THE FUNGI REACTS TO PROMOTE 1590 01:10:04,400 --> 01:10:06,840 COLONIZATION AND ALSO PROMOTING 1591 01:10:06,840 --> 01:10:09,160 INTESTINAL HEALTH AND EXPLORING 1592 01:10:09,160 --> 01:10:12,000 THAT IN AN THERAPEUTIC WAY. 1593 01:10:12,000 --> 01:10:25,400 IGA HAS BEEN WELL APPRECIATED. 1594 01:10:25,400 --> 01:10:32,920 IGA CAN NEUTRA -- NEUTRALIZE TOXINS. 1595 01:10:32,920 --> 01:10:34,840 IT'S ALSO REALLY IMPORTANT IN 1596 01:10:34,840 --> 01:10:41,280 STRUCTURING THE MICROBIOTA 1597 01:10:41,280 --> 01:10:41,960 COMPOSITION. 1598 01:10:41,960 --> 01:10:43,760 AND IN A VARIETY OF WAYS BUT 1599 01:10:43,760 --> 01:10:45,640 MOST OF THE STUDIES EVER LARGELY 1600 01:10:45,640 --> 01:10:48,200 FOCUS ENDS AGAIN ON THE 1601 01:10:48,200 --> 01:10:50,560 BACTERIAL COMPONENT. 1602 01:10:50,560 --> 01:10:55,000 78 SO AS I'VE MENTIONED THE 1603 01:10:55,000 --> 01:10:56,000 MICROBIOTA IS COMPLEX. 1604 01:10:56,000 --> 01:10:59,400 A LOT OF BACTERIAL DIVERSITY BUT 1605 01:10:59,400 --> 01:11:04,000 ALSO HOME TO VIRAL AS WELL AS 1606 01:11:04,000 --> 01:11:05,640 FUNGAL ORGANISMS. 1607 01:11:05,640 --> 01:11:08,640 WE WONDERED WHETHER OR NOT IGA 1608 01:11:08,640 --> 01:11:11,720 WAS IMPORTANT. 1609 01:11:11,720 --> 01:11:14,600 SO WE STARTED WITH SOME VERY 1610 01:11:14,600 --> 01:11:17,360 SIMPLE QUESTIONS REGARDING IGA 1611 01:11:17,360 --> 01:11:20,240 AND ITS INTERACTION WITH FUNGAL 1612 01:11:20,240 --> 01:11:21,800 SPECIES. 1613 01:11:21,800 --> 01:11:26,720 BUT WE GOT INTERESTED IN FUNGI 1614 01:11:26,720 --> 01:11:30,440 APPROXIMATELY 10 YEARS AGO 1615 01:11:30,440 --> 01:11:32,680 BECAUSE THERE WAS A CLINICAL 1616 01:11:32,680 --> 01:11:36,480 TEST THAT WAS ABLE TO 1617 01:11:36,480 --> 01:11:37,240 DISTINGUISH BETWEEN REASONS 1618 01:11:37,240 --> 01:11:39,240 DISEASE AND YOU WILLER RATE I 1619 01:11:39,240 --> 01:12:00,120 HAVE COLITIS. 1620 01:12:00,120 --> 01:12:02,040 AT THE TIME THIS HINTED TO US 1621 01:12:02,040 --> 01:12:05,400 THAT FUNGAL SPECIES AND THE 1622 01:12:05,400 --> 01:12:07,680 IMMUNE RESPONSE MIGHT BE 1623 01:12:07,680 --> 01:12:10,840 RELEVANT IN DISEASES SUCH AS 1624 01:12:10,840 --> 01:12:12,680 INFLAMMATORY BOWEL DISEASE. 1625 01:12:12,680 --> 01:12:14,920 SO TO ASK THE SIMPLE QUESTION OF 1626 01:12:14,920 --> 01:12:17,240 WHETHER OR NOT FUNGAL SPECIES 1627 01:12:17,240 --> 01:12:22,120 WERE EVEN RECOGNIZED BY IGA WE 1628 01:12:22,120 --> 01:12:24,600 COLLABORATED WITH -- WHO 1629 01:12:24,600 --> 01:12:27,360 PROVIDED US SOME FECAL SAMPLES 1630 01:12:27,360 --> 01:12:30,080 FROM HEALTHY INDIVIDUALS AND 1631 01:12:30,080 --> 01:12:33,120 ALSO FROM THOSE WITH DISEASE. 1632 01:12:33,120 --> 01:12:35,640 WE INCUBATED THEM WITH KNOWN 1633 01:12:35,640 --> 01:12:37,440 FUNGAL STRAINS THAT ARE 1634 01:12:37,440 --> 01:12:41,680 PREVALENT IN THE HUMAN GUT 1635 01:12:41,680 --> 01:12:55,600 MICROBIOTA. 1636 01:12:55,600 --> 01:13:00,240 -- WE DID SEE IGA SEEMS TO HAVE 1637 01:13:00,240 --> 01:13:10,120 SOME SORT OF SPECIFICITY. 1638 01:13:10,120 --> 01:13:13,000 BUT WE SAW LITTLE REACTIVE 1639 01:13:13,000 --> 01:13:15,040 AGAINST ORGANISMS. 1640 01:13:15,040 --> 01:13:17,840 SO THIS DATA DEMONSTRATED THAT 1641 01:13:17,840 --> 01:13:20,600 INDEED IGA DOES BIND AND 1642 01:13:20,600 --> 01:13:25,880 RECOGNIZE FUNGAL -- ORGANISMS IN 1643 01:13:25,880 --> 01:13:28,120 THE GUT BUT IT DOES SEEM TO HAVE 1644 01:13:28,120 --> 01:13:34,120 SOME SELECTIVITY. 1645 01:13:34,120 --> 01:13:35,800 WE SEE VERY SIMILAR RESULTS. 1646 01:13:35,800 --> 01:13:38,960 SO HERE WE'VE TAKEN GERMFREE 1647 01:13:38,960 --> 01:13:41,840 ANIMALS AND WE'VE MONO 1648 01:13:41,840 --> 01:13:46,040 ASSOCIATED THEM WITH -- THAT 1649 01:13:46,040 --> 01:13:58,360 WE'VE ENGINEERED. 1650 01:13:58,360 --> 01:14:02,080 AND WE LOOK AT THE RESPONSE AS 1651 01:14:02,080 --> 01:14:02,840 MEASURED. 1652 01:14:02,840 --> 01:14:08,760 AND WE SEE SIMILAR RESULTS. 1653 01:14:08,760 --> 01:14:12,240 WHERE CALBICANS IS HIGHLY 1654 01:14:12,240 --> 01:14:16,960 TARGETED. 1655 01:14:16,960 --> 01:14:18,520 DESPITE BEING THE ONLY THING 1656 01:14:18,520 --> 01:14:24,240 PRESENT IN THE GERMFREE ANIMAL. 1657 01:14:24,240 --> 01:14:26,240 I WANT TO MAKE SURE YOU CAN 1658 01:14:26,240 --> 01:14:28,880 STILL HEAR ME BECAUSE MY 1659 01:14:28,880 --> 01:14:30,840 COMPUTER JUST BLIPPED OUT. 1660 01:14:30,840 --> 01:14:32,160 >> YOU'RE STILL LOOKING AND 1661 01:14:32,160 --> 01:14:33,640 SOUNDING VERY GOOD. 1662 01:14:33,640 --> 01:14:34,240 >> GREAT. 1663 01:14:34,240 --> 01:14:36,040 I'M SORRY. 1664 01:14:36,040 --> 01:14:37,440 IT JUST FREAKED OUT AND I DON'T 1665 01:14:37,440 --> 01:14:39,240 KNOW WHAT HAPPENED. 1666 01:14:39,240 --> 01:14:43,320 SO IT SEEMS LIKE IGA ROBUSTLY 1667 01:14:43,320 --> 01:14:47,000 TARGETS -- BUT NOT NECESSARILY 1668 01:14:47,000 --> 01:14:51,480 -- -- -- SO WE WONDERED WHAT IGA 1669 01:14:51,480 --> 01:14:54,040 WAS DOING TO THE -- FUNGI. 1670 01:14:54,040 --> 01:14:55,640 AND IN ORDER TO ANSWER THE 1671 01:14:55,640 --> 01:15:00,440 QUESTION WE EXPLORED THE FIRM 1672 01:15:00,440 --> 01:15:03,720 FREE MOUSE SYSTEM. 1673 01:15:03,720 --> 01:15:07,160 THEY DO NOT HAVE AN ADAPTIVE 1674 01:15:07,160 --> 01:15:12,000 RESPONSE AND WE ASSOCIATED AGAIN 1675 01:15:12,000 --> 01:15:16,680 ENGINEERED WITH GFP. 1676 01:15:16,680 --> 01:15:19,360 WE PULLED THOSE SPECIES OUT OF 1677 01:15:19,360 --> 01:15:23,280 THE ANIMALS AND WE PERFORMED AN 1678 01:15:23,280 --> 01:15:28,880 RNA SEEK ON THE FUNGI ITSELF. 1679 01:15:28,880 --> 01:15:32,720 IT LOOKED VERY DIFFERENT 1680 01:15:32,720 --> 01:15:34,440 TRANSCRIPTIONALLY WHEN COMPARED 1681 01:15:34,440 --> 01:15:37,440 TO YEAST PULLED OUT OF WILD TYPE 1682 01:15:37,440 --> 01:15:39,280 ANIMAL AND ONE OF THE MAJOR 1683 01:15:39,280 --> 01:15:41,840 PATHWAYS THAT WAS CHANGED OR UP 1684 01:15:41,840 --> 01:15:43,640 REGULATED IN YEAST THAT CAME 1685 01:15:43,640 --> 01:15:46,080 FROM AN ANIMAL THAT LACKED 1686 01:15:46,080 --> 01:15:50,160 ADAPTIVE IMMUNITY WERE GENES 1687 01:15:50,160 --> 01:15:52,360 THAT WERE ASSOCIATED WITH HYPO 1688 01:15:52,360 --> 01:15:54,000 TRANSITION. 1689 01:15:54,000 --> 01:15:56,440 IF YOU'RE UNFAMILIAR WITH THE 1690 01:15:56,440 --> 01:15:59,000 BIOLOGY THIS YEAST IS ABLE TO 1691 01:15:59,000 --> 01:16:00,840 EXIST IN MULTIPLE FORMS. 1692 01:16:00,840 --> 01:16:01,960 THE DOMINANT FORMS THAT ARE 1693 01:16:01,960 --> 01:16:04,120 FOUND WITHIN THE GUT ARE THE 1694 01:16:04,120 --> 01:16:06,240 YEAST FORM WHICH IT LOOKS MUCH 1695 01:16:06,240 --> 01:16:10,080 LIKE A BUDDING YEAST. 1696 01:16:10,080 --> 01:16:13,640 BUT UNDER CERTAIN ENVIRONMENTAL 1697 01:16:13,640 --> 01:16:16,760 CONDITIONS -- THEY CAN UNDERGO A 1698 01:16:16,760 --> 01:16:18,840 PROCESS AND IT CAN FORM THESE 1699 01:16:18,840 --> 01:16:24,560 VERY ELONGATED -- NOW -- STUDIED 1700 01:16:24,560 --> 01:16:26,640 IN DEPTH BY MANY INVESTIGATORS 1701 01:16:26,640 --> 01:16:31,440 FOR VAGINAL INFECTIONS AS WELL 1702 01:16:31,440 --> 01:16:36,560 AS SYSTEMATIC INFECTIONS AND THE 1703 01:16:36,560 --> 01:16:39,440 HYPHAE ARE ASSOCIATED WITH 1704 01:16:39,440 --> 01:16:40,160 INVASIVENESS. 1705 01:16:40,160 --> 01:16:42,240 ASSOCIATED WITH GREATER DISEASE. 1706 01:16:42,240 --> 01:16:45,440 SO SINCE WE SAW THAT THE 1707 01:16:45,440 --> 01:16:47,680 TRANSCRIPTIONAL PROGRAM WAS UP 1708 01:16:47,680 --> 01:16:50,920 REGULATED IN -- THAT WERE COMING 1709 01:16:50,920 --> 01:16:53,440 FROM MICE THAT LACKED ADAPTIVE 1710 01:16:53,440 --> 01:16:56,080 IMMUNITY WE WANTED TO 1711 01:16:56,080 --> 01:16:57,440 COLLABORATE WHAT THESE YEAST 1712 01:16:57,440 --> 01:16:59,400 LOOK LIKE IN THE GUTS OF 1713 01:16:59,400 --> 01:17:02,440 ANIMALS. 1714 01:17:02,440 --> 01:17:06,920 SO AGAIN WE COLONIZED IN THIS 1715 01:17:06,920 --> 01:17:11,600 CASE WE COLONIZED AND WE ALSO 1716 01:17:11,600 --> 01:17:15,040 INCORPORATED A B CELL 1717 01:17:15,040 --> 01:17:16,680 DEFIBRILLATORS ANIMAL SO WE 1718 01:17:16,680 --> 01:17:20,400 COULD PINPOINT THIS RESPONSE TO 1719 01:17:20,400 --> 01:17:21,280 POTENTIALLY ANTIBODIES. 1720 01:17:21,280 --> 01:17:25,480 AND WHEN WE PERFORM FISH ON THE 1721 01:17:25,480 --> 01:17:28,440 CANADAAL BY CANS WE SEE A PRETTY 1722 01:17:28,440 --> 01:17:29,440 STRIKING PHENOTYPE. 1723 01:17:29,440 --> 01:17:34,360 WE SEE THAT CANADA ALBICANS 1724 01:17:34,360 --> 01:17:35,920 EXIST MORE IN THE YEAST FORM. 1725 01:17:35,920 --> 01:17:38,480 WE SEE THAT MOST OF THE CANADA 1726 01:17:38,480 --> 01:17:47,040 EXIST IN THE ELONGATED HYPHAEA. 1727 01:17:47,040 --> 01:17:48,960 MORE OVER IF YOU USE IMAGE 1728 01:17:48,960 --> 01:17:57,640 STREAM ANALYSIS CLASS A -- 1729 01:17:57,640 --> 01:17:59,640 COMBINATION THIS IS AN VIDEOS 1730 01:17:59,640 --> 01:18:06,880 CELL WHERE WE STAINED IT -- -- 1731 01:18:06,880 --> 01:18:10,400 ALSO COME IN WITH ANTI IGA THAT 1732 01:18:10,400 --> 01:18:12,040 IS PHYSICALLY BINDING TO THE 1733 01:18:12,040 --> 01:18:13,960 YEAST AND WHAT WE CONSISTENTLY 1734 01:18:13,960 --> 01:18:17,840 FIND IS THAT IGA IS TARGETING 1735 01:18:17,840 --> 01:18:21,560 THE HYPHAL FORM OF THE YEAST AS 1736 01:18:21,560 --> 01:18:24,360 OPPOSED TO THE YEAST FORM OF THE 1737 01:18:24,360 --> 01:18:26,840 FUNGI AND THIS CAN BE 1738 01:18:26,840 --> 01:18:29,440 QUANTITATIVE BECAUSE -- THIS IS 1739 01:18:29,440 --> 01:18:31,800 AN APPROACH WHERE WE SEE MORE OF 1740 01:18:31,800 --> 01:18:34,000 THE POSITIVE FRACTION IS BINDING 1741 01:18:34,000 --> 01:18:39,560 TO THE HYHH AL FORM 1742 01:18:39,560 --> 01:18:44,760 THE IGA RESPONSE IS SUPPRESSING 1743 01:18:44,760 --> 01:18:48,040 THE TRANSITIONAL PROGRAM. 1744 01:18:48,040 --> 01:18:50,240 AND THAT IGA IS PHYSICALLY 1745 01:18:50,240 --> 01:18:53,760 BINDING TO THINGS THAT ARE 1746 01:18:53,760 --> 01:18:56,520 ASSOCIATED WITH HYPHAL WITHIN 1747 01:18:56,520 --> 01:18:58,040 THE GUT OF ANIMALS. 1748 01:18:58,040 --> 01:18:59,640 SO WE WANTED TO UNDERSTAND WHAT 1749 01:18:59,640 --> 01:19:03,360 ARE THESE THAT ARE BEING BOUND 1750 01:19:03,360 --> 01:19:08,160 BY IGA. 1751 01:19:08,160 --> 01:19:10,640 SO WE TOOK A BIOCHEMICAL 1752 01:19:10,640 --> 01:19:11,080 APPROACH. 1753 01:19:11,080 --> 01:19:13,480 WE TRIED A LOT OF THINGS. 1754 01:19:13,480 --> 01:19:16,400 BUT WE TOOK A BIOCHEMICAL 1755 01:19:16,400 --> 01:19:16,800 APPROACH. 1756 01:19:16,800 --> 01:19:19,800 7 SO THE WAY THAT THIS WAS DONE 1757 01:19:19,800 --> 01:19:25,520 WE GREW UP -- CABLICANS IN MEDIA 1758 01:19:25,520 --> 01:19:31,480 THAT PROMOTES YEAST FORMATION -- 1759 01:19:31,480 --> 01:19:33,320 AND THEN TAKE THOSE AND RUN THEM 1760 01:19:33,320 --> 01:19:35,880 ON A GEL AND WE PROBE THAT GEL 1761 01:19:35,880 --> 01:19:39,200 WITH IGA THAT IS ISOLATED FROM 1762 01:19:39,200 --> 01:19:40,960 GERMFREE MICE AND WHEN DO YOU 1763 01:19:40,960 --> 01:19:42,920 THIS AGAIN WHAT YOU FIND IS THAT 1764 01:19:42,920 --> 01:19:45,960 THE IGA ACTIVITY TENDS TO BIND 1765 01:19:45,960 --> 01:19:49,600 TO PROTEINS THAT ARE ASSOCIATED 1766 01:19:49,600 --> 01:19:55,640 WITH HY PHI. 1767 01:19:55,640 --> 01:19:58,040 AND WHAT WE IDENTIFIED IS THAT 1768 01:19:58,040 --> 01:20:01,640 IGA TENDS TO BIND ADD MOTIONS 1769 01:20:01,640 --> 01:20:07,400 SUCH AS ALS3 AS WELL AS HYR1. 1770 01:20:07,400 --> 01:20:11,040 7 SO THIS HELPED US TO IDENTIFY 1771 01:20:11,040 --> 01:20:14,440 WHAT EPITOPES WERE BEING 1772 01:20:14,440 --> 01:20:15,720 RECOGNIZED. 1773 01:20:15,720 --> 01:20:17,720 SO AS I SHOWED YOU EARLIER IN 1774 01:20:17,720 --> 01:20:22,360 THE TALK -- IT DOES NOT SEEM TO 1775 01:20:22,360 --> 01:20:24,840 BE TARGETED BY IGA. 1776 01:20:24,840 --> 01:20:28,840 SO WE WONDERED IF THESE 1777 01:20:28,840 --> 01:20:31,120 ADHESIONS WERE SUFFICIENT FOR AN 1778 01:20:31,120 --> 01:20:33,600 ORGANISM TO NOW BE TARGETED BY 1779 01:20:33,600 --> 01:20:35,240 IGA. 1780 01:20:35,240 --> 01:20:39,120 SO WE ENGINEERED -- TO EXPRESS 1781 01:20:39,120 --> 01:20:47,440 SOME OF THESE ADD -- ADHESIONS. 1782 01:20:47,440 --> 01:20:52,720 AND INDEED -- YOU CAN NOW SEE 1783 01:20:52,720 --> 01:21:06,280 THE EMERGENCE OF IGA REACTIVITY. 1784 01:21:06,280 --> 01:21:07,920 THIS IS JUST TO SHOW YOU THAT 1785 01:21:07,920 --> 01:21:11,160 WHEN YOU LOOK AT REACTIVITY IN 1786 01:21:11,160 --> 01:21:14,640 HUMANS WHEN YOU ISOLATE THAT 1787 01:21:14,640 --> 01:21:16,280 FECAL WASH AND ASK WHETHER OR 1788 01:21:16,280 --> 01:21:19,000 NOT THERE IS IGA IN THE GUTS OF 1789 01:21:19,000 --> 01:21:21,320 HUMAN THAT'S REACTS AGAINST 1790 01:21:21,320 --> 01:21:24,000 THESE SPECIFIC ISOTOPES WE FIND 1791 01:21:24,000 --> 01:21:25,800 HUMANS ALSO POSSESS REACTIVITY 1792 01:21:25,800 --> 01:21:28,000 TO MANY OF THESE ADHESION 1793 01:21:28,000 --> 01:21:32,640 INCLUDING ALS1 AND ALS3 IN 1794 01:21:32,640 --> 01:21:33,080 PARTICULAR. 1795 01:21:33,080 --> 01:21:35,280 SO IT IDENTIFIES THAT THESE 1796 01:21:35,280 --> 01:21:37,080 EPITOPES ARE RELEVANT IN HUMANS 1797 01:21:37,080 --> 01:21:37,840 AS WELL. 1798 01:21:37,840 --> 01:21:38,960 SO THE MORE IMPORTANT QUESTION 1799 01:21:38,960 --> 01:21:43,040 IS DOES THIS MATTER FOR INTEST 1800 01:21:43,040 --> 01:21:44,680 NATURAL HEALTH AND INTESTINAL 1801 01:21:44,680 --> 01:21:46,120 DISEASE. 1802 01:21:46,120 --> 01:21:49,000 WE WANTED TO ASK THE QUESTION OF 1803 01:21:49,000 --> 01:21:51,000 WHETHER OR NOT THIS FILL MEN 1804 01:21:51,000 --> 01:21:53,560 TAKES PROCESS WAS IMPORTANT FOR 1805 01:21:53,560 --> 01:21:55,640 * INTESTINAL DISEASE. 1806 01:21:55,640 --> 01:21:58,960 A LOT OF COOL GENETIC TOOLS THAT 1807 01:21:58,960 --> 01:22:01,080 WE EXPLOITED AND ONE IS THAT YOU 1808 01:22:01,080 --> 01:22:05,320 CAN FORCE YEAST TO STAY THE 1809 01:22:05,320 --> 01:22:07,400 FUNGI TO STAY IN THEIR YEAST 1810 01:22:07,400 --> 01:22:11,240 FORM BY FORCING EXPRESSION OF A 1811 01:22:11,240 --> 01:22:13,640 TRANSCRIPTION FACTOR CALLED 1812 01:22:13,640 --> 01:22:17,240 NRG1. 1813 01:22:17,240 --> 01:22:19,520 WHEN YOU FORCE THE TRANSCRIPTION 1814 01:22:19,520 --> 01:22:21,360 FACTOR TO BE OFF THE YEAST WILL 1815 01:22:21,360 --> 01:22:24,960 THEN FORMER LONG GATED -- 1816 01:22:24,960 --> 01:22:27,240 >> YOU HAVE ABOUT TWO AND A HALF 1817 01:22:27,240 --> 01:22:27,760 MINUTES. 1818 01:22:27,760 --> 01:22:28,200 >> PERFECT. 1819 01:22:28,200 --> 01:22:28,800 THANK YOU. 1820 01:22:28,800 --> 01:22:31,600 YOU THEN TAKE THESE ORGANISMS -- 1821 01:22:31,600 --> 01:22:37,200 AND WE INDUCED -- AS A MODEL OF 1822 01:22:37,200 --> 01:22:43,440 INFLAMMATORY BOWEL DISEASE. 1823 01:22:43,440 --> 01:22:46,200 WHEN WE DID THIS WE SEE THAT 1824 01:22:46,200 --> 01:22:51,400 THIS ENHANCES AND WHEN YOU FORCE 1825 01:22:51,400 --> 01:22:54,680 THOSE ORGANISMS TO STAY IN THEIR 1826 01:22:54,680 --> 01:22:56,680 YEAST FORM IT REDUCES THEIR 1827 01:22:56,680 --> 01:22:57,240 DISEASE. 1828 01:22:57,240 --> 01:23:00,800 HOWEVER WHEN YOU PAUSE THOSE 1829 01:23:00,800 --> 01:23:03,040 ORGANISMS THAT EXACERBATES THE 1830 01:23:03,040 --> 01:23:04,480 INTESTINAL DISEASE. 1831 01:23:04,480 --> 01:23:06,640 SO THIS SAYS THAT THE FORM OF 1832 01:23:06,640 --> 01:23:10,400 THE FUNGI IS REALLY PROMOTING 1833 01:23:10,400 --> 01:23:12,440 DISEASE IN THIS ANIMAL MODEL. 1834 01:23:12,440 --> 01:23:14,240 SO THE FINAL DATA SLIDE THAT 1835 01:23:14,240 --> 01:23:16,160 I'LL SHARE WITH YOU IS THAT WE 1836 01:23:16,160 --> 01:23:20,120 WONDERED IF WE CAN EXPLOIT THIS 1837 01:23:20,120 --> 01:23:21,920 NATURAL PRUNING THAT THE IMMUNE 1838 01:23:21,920 --> 01:23:24,880 SYSTEM DOES TO THE GUN GAS TO 1839 01:23:24,880 --> 01:23:27,440 PREVENT * OR PROTECT FROM 1840 01:23:27,440 --> 01:23:29,480 INTESTINAL DISEASE IN MICE. 1841 01:23:29,480 --> 01:23:44,200 AND WE COLLABORATE CO-LAB -- COLLABORATED -- 1842 01:23:44,200 --> 01:23:45,840 AND WE WERE PROVIDED WITH THE 1843 01:23:45,840 --> 01:23:48,640 VACCINE AGAINST ALS3 AND WE 1844 01:23:48,640 --> 01:23:53,240 IMMUNIZED ANIMALS WITH -- -- 1845 01:23:53,240 --> 01:23:57,640 ALUM AND WE INDUCED AS PER MY 1846 01:23:57,640 --> 01:23:59,320 PREVIOUS SLIDE. 1847 01:23:59,320 --> 01:24:03,520 NOW WHEN CANDICE NOT AROUND THIS 1848 01:24:03,520 --> 01:24:06,400 VACCINATION PROTOCOL THIS IS 1849 01:24:06,400 --> 01:24:08,600 LITTLE AS ONE WOULD PREDICT. 1850 01:24:08,600 --> 01:24:10,160 AGAIN WE SEE THAT THE PRESENCE 1851 01:24:10,160 --> 01:24:13,400 OF CANADA -- WORSENS DISEASE BUT 1852 01:24:13,400 --> 01:24:16,120 IN ANIMALS THAT WERE GIVEN THE 1853 01:24:16,120 --> 01:24:19,000 VACCINE AGAINST ALS3 TO PROMOTE 1854 01:24:19,000 --> 01:24:22,960 THIS IGA RESPONSE THESE ANIMALS 1855 01:24:22,960 --> 01:24:25,880 DIDN'T DEVELOP DSS COLITIS. 1856 01:24:25,880 --> 01:24:30,520 SO REALLY THIS IS AN EXAMPLE OF 1857 01:24:30,520 --> 01:24:33,640 WHEN WE'RE STUDYING THE 1858 01:24:33,640 --> 01:24:34,840 INTERACTION BETWEEN MIKE ROBES 1859 01:24:34,840 --> 01:24:39,320 AND THE IMMUNE * SYSTEM WE CAN 1860 01:24:39,320 --> 01:24:40,800 EXEMPLOYED WHAT NATURE HAS 1861 01:24:40,800 --> 01:24:41,640 EVOLVED. 1862 01:24:41,640 --> 01:24:43,680 AND IN THIS PARTICULAR INSTANCE 1863 01:24:43,680 --> 01:24:45,680 WE'VE IDENTIFIED EPITOPES ON THE 1864 01:24:45,680 --> 01:24:47,800 ORGANISMS THAT CAN BE USED IN 1865 01:24:47,800 --> 01:24:49,040 VACCINATION STRATEGIES TO 1866 01:24:49,040 --> 01:24:51,880 PREVENT THE DISEASE CAPABILITIES 1867 01:24:51,880 --> 01:24:53,960 OF THESE PARTICULAR ORGANISMS. 1868 01:24:53,960 --> 01:24:56,720 AND ONE CAN IMAGINE USING IGA 1869 01:24:56,720 --> 01:24:59,280 JUST AS ONE EXAMPLE TO IDENTIFY 1870 01:24:59,280 --> 01:25:04,320 A RELEVANT BACTERIA, FUNGI EVEN 1871 01:25:04,320 --> 01:25:06,960 VIRUSES AND THEIR MOLECULES AND 1872 01:25:06,960 --> 01:25:10,800 USE THIS TO DESIGN THERAPEUTIC. 1873 01:25:10,800 --> 01:25:13,040 SO WITH THAT I'LL END AND I'LL 1874 01:25:13,040 --> 01:25:15,080 ACKNOWLEDGE ALL OF THE WONDERFUL 1875 01:25:15,080 --> 01:25:16,080 COLLABORATORS. 1876 01:25:16,080 --> 01:25:19,440 WE HAVE GREAT COLLABORATORS AND 1877 01:25:19,440 --> 01:25:22,520 THEN ALL OF THE WONDERFUL WORK 1878 01:25:22,520 --> 01:25:25,040 WAS DONE BY A TALENTED POSTDOC 1879 01:25:25,040 --> 01:25:27,600 WHO'S GOING TO START HER OWN LAB 1880 01:25:27,600 --> 01:25:28,600 HERE IN JULY. 1881 01:25:28,600 --> 01:25:30,760 AND THE FUNDING TO SUPPORT THIS 1882 01:25:30,760 --> 01:25:30,960 WORK. 1883 01:25:30,960 --> 01:25:32,040 THANK YOU VERY MUCH AND I LOOK 1884 01:25:32,040 --> 01:25:33,440 FORWARD TO THE PANEL DISCUSSION 1885 01:25:33,440 --> 01:25:35,000 >> THAT WAS A REALLY GREAT TALK 1886 01:25:35,000 --> 01:25:37,640 AND IT MAKES ME WONDER IF 1887 01:25:37,640 --> 01:25:39,080 SIMILAR THINGS ARE HAPPENING 1888 01:25:39,080 --> 01:25:43,040 WITH BACTERIA SPORE FARMERS BUT 1889 01:25:43,040 --> 01:25:46,120 WE'LL SAVE THAT FOR THE PANEL. 1890 01:25:46,120 --> 01:25:49,640 THE NEXT SPEAKER IS FROM JANUARY 1891 01:25:49,640 --> 01:25:53,440 PETER VAN PIJKEREN. 1892 01:25:53,440 --> 01:26:05,640 TAKE IT AWAY JP. 1893 01:26:05,640 --> 01:26:07,640 >> SO SCREEN IS THERE AND YOU 1894 01:26:07,640 --> 01:26:08,960 CAN HEAR ME OKAY. 1895 01:26:08,960 --> 01:26:09,400 SUPER. 1896 01:26:09,400 --> 01:26:11,200 THANK YOU VERY MUCH FOR THE 1897 01:26:11,200 --> 01:26:14,480 INTRODUCTION AND THANK YOU TO 1898 01:26:14,480 --> 01:26:15,760 THE ORGANIZERS FOR PUTTING 1899 01:26:15,760 --> 01:26:17,720 TOGETHER A NICE WORKSHOP AND I'M 1900 01:26:17,720 --> 01:26:18,920 DELIGHTED TO SHARE SOME OF THE 1901 01:26:18,920 --> 01:26:20,120 WORK THAT WE'VE BEEN DOING. 1902 01:26:20,120 --> 01:26:24,840 SO OUR LAB IS INTERESTED TO 1903 01:26:24,840 --> 01:26:27,240 UNDERSTAND PRO-BIOTIC MECHANISMS 1904 01:26:27,240 --> 01:26:29,520 AS IT PERTAINS TO GUT FITNESS 1905 01:26:29,520 --> 01:26:32,840 AND THE ABILITY OF PRO-BIOTIC TO 1906 01:26:32,840 --> 01:26:34,760 INTERACT WITH THE HOST AND 1907 01:26:34,760 --> 01:26:38,240 LEVERAGE THE KNOWLEDGE TO THE 1908 01:26:38,240 --> 01:26:42,560 DEVELOPMENT OF MICROBIAL 1909 01:26:42,560 --> 01:26:43,440 THERAPEUTICS. 1910 01:26:43,440 --> 01:26:46,280 MOST OF THE WORK THAT WE DO WE 1911 01:26:46,280 --> 01:26:51,640 USE THE GUT SYMBIONT. 1912 01:26:51,640 --> 01:26:53,040 A SPECIES THAT CAN BE FOUND IN 1913 01:26:53,040 --> 01:26:55,560 THE GUT OF A LARGE NUMBER OF 1914 01:26:55,560 --> 01:26:56,840 VERTEBRATES INCLUDING IN HUMANS. 1915 01:26:56,840 --> 01:27:00,040 IT'S NOT A DOMINANT SPECIES IN 1916 01:27:00,040 --> 01:27:01,640 HUMANS BUT IT CAN BE FOUND AND 1917 01:27:01,640 --> 01:27:04,520 IT IS AN ORGANISM THAT HAS 1918 01:27:04,520 --> 01:27:06,240 EVOLVED TO THRIVE WITHIN THE GUT 1919 01:27:06,240 --> 01:27:07,080 ECOSYSTEM. 1920 01:27:07,080 --> 01:27:09,440 WITHIN THE LAST 10 YEARS WE'VE 1921 01:27:09,440 --> 01:27:14,960 INVESTED HEAVILY IN THE USE OF 1922 01:27:14,960 --> 01:27:15,680 TOOLS. 1923 01:27:15,680 --> 01:27:18,360 WORK STARTED WHEN I WAS A 1924 01:27:18,360 --> 01:27:18,920 POSTDOC. 1925 01:27:18,920 --> 01:27:25,200 OUR LAB LATER DEVELOPED CRISPR 1926 01:27:25,200 --> 01:27:28,280 -- -- -- I WILL NOT GO INTO THE 1927 01:27:28,280 --> 01:27:31,560 DETAILS TALKING ABOUT 10 MINUTES 1928 01:27:31,560 --> 01:27:33,360 IS ENOUGH TO PUT EVERYBODY TO 1929 01:27:33,360 --> 01:27:35,240 SLEEP BUT THE TAKE AWAY MESSAGE 1930 01:27:35,240 --> 01:27:39,120 IS WE HAVE A CART BRANCH FOR OUR 1931 01:27:39,120 --> 01:27:40,600 ABILITY AND THESE TOOLS ARE 1932 01:27:40,600 --> 01:27:42,240 ESSENTIAL AND CRITICAL TO 1933 01:27:42,240 --> 01:27:43,400 UNDERSTAND GENE FUNCTION AND 1934 01:27:43,400 --> 01:27:46,600 SPECIFICALLY WITH THE WORK IN 1935 01:27:46,600 --> 01:27:50,440 RELATION TO GUT FITNESS. 1936 01:27:50,440 --> 01:27:56,840 IT HAS PROVEN FRUITFUL. 1937 01:27:56,840 --> 01:28:00,720 SO -- IT IS NOT UNIQUE IN THE 1938 01:28:00,720 --> 01:28:02,720 FACT THAT IT IS ACTUALLY IN THE 1939 01:28:02,720 --> 01:28:06,200 GENOME -- EMBEDDED BACTERIAL 1940 01:28:06,200 --> 01:28:06,640 DNA. 1941 01:28:06,640 --> 01:28:07,720 MOST HAVE THAT. 1942 01:28:07,720 --> 01:28:09,960 AND WHAT WE FOUND IS THAT WHEN 1943 01:28:09,960 --> 01:28:12,040 ACTUALLY -- PASSES THROUGH THE 1944 01:28:12,040 --> 01:28:13,800 GI TRACT AND WE USE MICE FOR 1945 01:28:13,800 --> 01:28:15,600 THIS WHAT WE SEE IS THAT THIS 1946 01:28:15,600 --> 01:28:18,840 VIRAL DNA IS NOW BECOMING 1947 01:28:18,840 --> 01:28:21,440 ACTIVATED LEADING TO THE -- 1948 01:28:21,440 --> 01:28:23,440 VIRAL DNA. 1949 01:28:23,440 --> 01:28:25,080 ULTIMATELY LEADING TO THE 1950 01:28:25,080 --> 01:28:27,760 RELEASE OF THESE VIRUS PARTICLES 1951 01:28:27,760 --> 01:28:29,600 IN THE GUT ECOSYSTEM. 1952 01:28:29,600 --> 01:28:31,480 AND WHILE THIS IS A BURDEN 1953 01:28:31,480 --> 01:28:33,360 BECAUSE PART OF THE POPULATION 1954 01:28:33,360 --> 01:28:35,240 IS BEING KILLED -- AT THE SAME 1955 01:28:35,240 --> 01:28:38,560 TIME WE FOUND THAT IN THE 1956 01:28:38,560 --> 01:28:42,120 VARIETY -- THAT THESE PROVIDE A 1957 01:28:42,120 --> 01:28:43,840 COMPETITIVE ADVANTAGE. 1958 01:28:43,840 --> 01:28:46,320 BECAUSE STRAINS THAT ARE IN THE 1959 01:28:46,320 --> 01:28:48,560 SAME NICHE AND COMPETING FOR THE 1960 01:28:48,560 --> 01:28:50,440 SAME NUTRIENTS CAN BE KILLED BY 1961 01:28:50,440 --> 01:28:56,520 THESE VIRUSES GIVING THE STRAIN 1962 01:28:56,520 --> 01:28:57,600 A COMPETITIVE ADVANTAGE. 1963 01:28:57,600 --> 01:28:59,840 AND FURTHER STUDIES TRY TO 1964 01:28:59,840 --> 01:29:00,720 UNDERSTAND WHAT THE TRIGGERS IN 1965 01:29:00,720 --> 01:29:02,520 THE GUT ARE THAT ACTUALLY LEAD 1966 01:29:02,520 --> 01:29:05,040 TO THE ACTIVATION OF THESE VIEW 1967 01:29:05,040 --> 01:29:05,600 VIRUSES. 1968 01:29:05,600 --> 01:29:08,880 WE FOUND THAT ACTUALLY DIETARY 1969 01:29:08,880 --> 01:29:12,440 -- FRUCTOSE AND ALSO FATTY ACIDS 1970 01:29:12,440 --> 01:29:15,000 PRESENT IN THE GUT ARE TRIGGERS 1971 01:29:15,000 --> 01:29:24,280 THAT ACTIVATE THESE VIRUSES. 1972 01:29:24,280 --> 01:29:28,080 LEADING TO THE -- -- -- WHAT WE 1973 01:29:28,080 --> 01:29:29,800 SEE IS THAT WHEN THIS HAPPENS 1974 01:29:29,800 --> 01:29:31,800 AND WHEN -- IT PASSES THROUGH 1975 01:29:31,800 --> 01:29:34,440 THE GI TRACT THAT APPROXIMATELY 1976 01:29:34,440 --> 01:29:39,600 80% OF THE BACTERIA ARE BEING -- 1977 01:29:39,600 --> 01:29:45,640 LYSED BY THESE VIRUSES. 1978 01:29:45,640 --> 01:29:49,960 AND THAT WAS TO US INTRIGUING 1979 01:29:49,960 --> 01:29:53,240 SPECIFICALLY IN THE LIGHT THAT 1980 01:29:53,240 --> 01:29:55,120 THIS PROVIDES AN OPPORTUNITY TO 1981 01:29:55,120 --> 01:30:01,400 LEVERAGE VIRUSES. 1982 01:30:01,400 --> 01:30:05,240 WE HAVE A BACTERIAL STRAIN THAT 1983 01:30:05,240 --> 01:30:12,240 IS ENGINEERED VIRUSES ARE BEING 1984 01:30:12,240 --> 01:30:16,040 PRODUCED THEREBY RELEASING THE 1985 01:30:16,040 --> 01:30:27,760 THEY AR-- THERAPEUTIC PROTEIN. 1986 01:30:27,760 --> 01:30:33,680 WHEN WE USE A CHEMICAL WE SEE 1987 01:30:33,680 --> 01:30:36,240 THAT VIRUSES ARE PRODUCED AND 1988 01:30:36,240 --> 01:30:39,640 THE MORE CELLS THAT ARE LYSED 1989 01:30:39,640 --> 01:30:41,360 LEAD TO AN INCREASE IN THE 1990 01:30:41,360 --> 01:30:43,600 RELEASE OF THE PROTEIN AND THIS 1991 01:30:43,600 --> 01:30:47,320 IS DRIVEN BY VIRUSES BECAUSE IF 1992 01:30:47,320 --> 01:30:50,520 WE DO THIS SAME EXPERIMENT IN 1993 01:30:50,520 --> 01:30:53,200 BACTERIA THAT LACK THE VIRUSES 1994 01:30:53,200 --> 01:30:55,640 THAT DO PRODUCE THE PROTEINS 1995 01:30:55,640 --> 01:30:58,320 NOTHING HAPPENS. 1996 01:30:58,320 --> 01:31:01,080 SO TO USE VIRUSES NOW AND TO USE 1997 01:31:01,080 --> 01:31:06,000 THIS CONCEPT OF LYSIS HAS AN 1998 01:31:06,000 --> 01:31:10,520 ADVANTAGE OVER USING THE 1999 01:31:10,520 --> 01:31:18,840 CONVENTIONAL PATHWAY. 2000 01:31:18,840 --> 01:31:20,840 SO SINCE THE PATHWAY IS 2001 01:31:20,840 --> 01:31:22,920 ESSENTIAL TO THE BACTERIA CELL 2002 01:31:22,920 --> 01:31:24,560 YOU CAN IMAGINE NOW IF YOU ASK 2003 01:31:24,560 --> 01:31:27,760 THE CELL TO PRODUCE A LOT OF 2004 01:31:27,760 --> 01:31:31,200 PROTEIN THIS BECOMES A METABOLIC 2005 01:31:31,200 --> 01:31:31,640 BURDEN. 2006 01:31:31,640 --> 01:31:33,960 ANOTHER ADVANTAGE IS THAT THE 2007 01:31:33,960 --> 01:31:37,640 DESIGN IS SIMPLIFIED. 2008 01:31:37,640 --> 01:31:39,040 HAVING THE RIGHT PEPTIDE AND 2009 01:31:39,040 --> 01:31:43,360 HAVE THE DESIGN SUCH LEADING TO 2010 01:31:43,360 --> 01:31:54,440 EFFICIENCY CORRECTIOSUFFICIENT -- SECRETIO N. 2011 01:31:54,440 --> 01:31:56,880 WHAT THEY'VE SHOWN AND WE SEE 2012 01:31:56,880 --> 01:32:01,680 SIMILAR THINGS WITH OTHER CITO 2013 01:32:01,680 --> 01:32:02,200 KINDS. 2014 01:32:02,200 --> 01:32:04,760 THIS APPROACH WILL AVOID THAT 2015 01:32:04,760 --> 01:32:07,000 AND ALTHOUGH WE'RE QUITE A FEW 2016 01:32:07,000 --> 01:32:11,600 STEPS REMOVED FROM ALL 2017 01:32:11,600 --> 01:32:13,840 CONTAINMENT -- IT'S A STEP 2018 01:32:13,840 --> 01:32:14,720 TOWARDS CONTAINMENT. 2019 01:32:14,720 --> 01:32:19,560 8 SO WE HAVE THE LUXURY TO WORK 2020 01:32:19,560 --> 01:32:22,560 WITH SEVERAL -- COLLABORATORS 2021 01:32:22,560 --> 01:32:25,440 WHO ARE KNOWLEDGEABLE AND ONE OF 2022 01:32:25,440 --> 01:32:28,200 THESE COLLABORATORS IS FROM THE 2023 01:32:28,200 --> 01:32:29,080 UNIVERSITY OF CALIFORNIA SAN 2024 01:32:29,080 --> 01:32:31,240 DIEGO AND ONE OF THE EXPERTISE 2025 01:32:31,240 --> 01:32:32,760 WAS LIVER DISEASE. 2026 01:32:32,760 --> 01:32:34,480 IN THIS PARTICULAR MODEL WHAT 2027 01:32:34,480 --> 01:32:36,160 THEY ARE DOING IS THAT THEY HAVE 2028 01:32:36,160 --> 01:32:38,160 MICE THAT THEY FIELD A DIET THAT 2029 01:32:38,160 --> 01:32:41,000 IS ENRICHED IN ETHANOL. 2030 01:32:41,000 --> 01:32:43,440 THIS CONTINUOUS ETHANOL 2031 01:32:43,440 --> 01:32:45,440 CONSUMPTION LEADS TO THE -- 2032 01:32:45,440 --> 01:32:47,760 DAMAGE TO THE LIVER CELLS AND A 2033 01:32:47,760 --> 01:32:52,840 PROXY FOR DAMAGED LIVER IS TO 2034 01:32:52,840 --> 01:32:56,640 MEASURE THE PRESENCE IN THE 2035 01:32:56,640 --> 01:32:57,400 BLOOD SCREAM. 2036 01:32:57,400 --> 01:33:00,120 THE MORE YOU HAVE IN THE 2037 01:33:00,120 --> 01:33:01,240 BLOODSTREAM THE MORE LIVER 2038 01:33:01,240 --> 01:33:03,080 DAMAGE THAT CAN BE LINKED TO 2039 01:33:03,080 --> 01:33:03,280 THAT. 2040 01:33:03,280 --> 01:33:07,240 IF YOU LOOK AT MICE THAT ARE 2041 01:33:07,240 --> 01:33:10,120 BEING FED WE SEE THAT THE LEVELS 2042 01:33:10,120 --> 01:33:13,240 ARE COMPARABLE BUT WHEN THEY ARE 2043 01:33:13,240 --> 01:33:17,080 PROVIDED WITH AN ENGINEERED -- 2044 01:33:17,080 --> 01:33:19,920 WE SEE A SIGNIFICANT REDUCTION 2045 01:33:19,920 --> 01:33:24,760 IN THE AMOUNT OF ALT HERE. 2046 01:33:24,760 --> 01:33:27,600 THIS IS BASED ON LOCAL DELIVERY. 2047 01:33:27,600 --> 01:33:31,320 THIS IS LOCAL DELIVERY. 2048 01:33:31,320 --> 01:33:35,720 THEY WENT ON AND -- I'LL GO OVER 2049 01:33:35,720 --> 01:33:37,760 THAT HERE. 2050 01:33:37,760 --> 01:33:39,520 BUT OUR APPROACH HERE IS 2051 01:33:39,520 --> 01:33:42,160 FUNCTIONAL. 2052 01:33:42,160 --> 01:33:46,560 -- -- -- AS RADIATION ONCOLOGY 2053 01:33:46,560 --> 01:33:50,240 -- THEY HAVE A MODEL FOR TOTAL 2054 01:33:50,240 --> 01:33:51,080 BODIY RADIATION. 2055 01:33:51,080 --> 01:33:53,000 THIS IS THE SECOND EXAMPLE WHERE 2056 01:33:53,000 --> 01:33:55,880 THE ENGINEERED PRO-BIOTIC HAS 2057 01:33:55,880 --> 01:33:57,880 PROVEN FRUITFUL HERE AND IN THIS 2058 01:33:57,880 --> 01:33:59,560 PARTICULAR MODEL WHAT THEY DO IS 2059 01:33:59,560 --> 01:34:02,640 THEY EXPOSE MICE TO RADIATION, 2060 01:34:02,640 --> 01:34:04,640 THE RADIATION IS TO TISSUE 2061 01:34:04,640 --> 01:34:06,840 DAMAGE AND IF YOU DON'T DO 2062 01:34:06,840 --> 01:34:09,040 ANYTHING THIS TISSUE DAMAGE IS 2063 01:34:09,040 --> 01:34:11,600 EXPECTED TO REDUCE THE LIFE 2064 01:34:11,600 --> 01:34:13,440 EXPECTANCY OF THE ANIMAL. 2065 01:34:13,440 --> 01:34:15,360 RADIATION CAN BE ONE OF THE 2066 01:34:15,360 --> 01:34:17,360 TREATMENTS IN CANCER AND TO HAVE 2067 01:34:17,360 --> 01:34:22,320 MEANS TO REDUCE THE 6 -- THE 2068 01:34:22,320 --> 01:34:23,880 IMPACTS OF TISSUE DAMAGE ON 2069 01:34:23,880 --> 01:34:28,160 HEALTHY CELLS AND SPECIFICALLY 2070 01:34:28,160 --> 01:34:30,480 ON HEALTHY CELLS MEASURES ARE 2071 01:34:30,480 --> 01:34:33,920 NEEDED TO BASICALLY REDUCE THAT. 2072 01:34:33,920 --> 01:34:35,800 SO TO THE EXTENT IF YOU LOOK AT 2073 01:34:35,800 --> 01:34:38,120 THE DATA FROM THIS YOU SEE THAT 2074 01:34:38,120 --> 01:34:41,160 MICE LEFT UNTREATED AFTER 30 2075 01:34:41,160 --> 01:34:43,760 DAYS NEARLY ALL OF THE MICE 2076 01:34:43,760 --> 01:34:46,240 SUCCUMB TO THE RADIATION. 2077 01:34:46,240 --> 01:34:47,800 THE CONTROL HERE DOES NOT DO 2078 01:34:47,800 --> 01:34:49,440 MUCH TO THE SURVIVAL OF THE 2079 01:34:49,440 --> 01:34:52,760 ANIMALS BUT THE ENGINEERED 2080 01:34:52,760 --> 01:34:54,600 PRO-BIOTIC WE SEE HERE THERE IS 2081 01:34:54,600 --> 01:34:57,000 A SIGNIFICANT INCREASE IN THE 2082 01:34:57,000 --> 01:34:57,680 SURVIVAL. 2083 01:34:57,680 --> 01:34:59,960 AS A THIRD EXAMPLE -- WE HAVE 2084 01:34:59,960 --> 01:35:01,080 DONE THIS IN HOUSE. 2085 01:35:01,080 --> 01:35:05,640 AND WE SEE HERE THAT -- 22 IN A 2086 01:35:05,640 --> 01:35:09,520 MODEL OF DIET AND OH DEESE TEE 2087 01:35:09,520 --> 01:35:13,400 THE RELEASE -- LEADS TO THE 2088 01:35:13,400 --> 01:35:16,360 REDUCTION OF LIVER 2089 01:35:16,360 --> 01:35:16,840 TRIGLYCERIDES. 2090 01:35:16,840 --> 01:35:19,840 SO OVER-ALL I THINK IT'S PRETTY 2091 01:35:19,840 --> 01:35:22,400 EVIDENT THAT MAKING USE OF THE 2092 01:35:22,400 --> 01:35:26,240 MATERIAL VIRUSES TO -- PROTEIN 2093 01:35:26,240 --> 01:35:28,240 AND THE ENVIRONMENT IS 2094 01:35:28,240 --> 01:35:29,920 EFFICACIOUS IN THESE PRECLINICAL 2095 01:35:29,920 --> 01:35:30,720 MODELS. 2096 01:35:30,720 --> 01:35:32,480 HOWEVER FOR MOST OF THE 2097 01:35:32,480 --> 01:35:34,600 EXPERIMENTS THAT I'VE SHOWN YOU 2098 01:35:34,600 --> 01:35:37,040 HERE WE'RE RELYING ON THE 2099 01:35:37,040 --> 01:35:38,360 ENVIRONMENTAL TRIGGERS IN THE 2100 01:35:38,360 --> 01:35:40,880 GUT TO RELEASE THE THERAPEUTIC. 2101 01:35:40,880 --> 01:35:42,600 AND REALLY WE WOULD LIKE TO BE 2102 01:35:42,600 --> 01:35:44,600 IN A SITUATION THAT WE WOULD BE 2103 01:35:44,600 --> 01:35:47,240 IN CONTROL OF THE DETONATORS AND 2104 01:35:47,240 --> 01:35:50,800 ARE NOT RELIANT ON THE DIET OF 2105 01:35:50,800 --> 01:35:53,000 SUGAR OR FATTY ACIDS IN THE GUT 2106 01:35:53,000 --> 01:35:55,440 OR OTHER COMPONENTS IN THE GUT 2107 01:35:55,440 --> 01:35:55,840 ECOSYSTEM. 2108 01:35:55,840 --> 01:35:58,840 WE HAVE IDENTIFIED WHAT WE REFER 2109 01:35:58,840 --> 01:36:02,800 TO AS A -- AND THIS IS A SINGLE 2110 01:36:02,800 --> 01:36:04,560 GENE WHOSE ACTIVATION IS ENOUGH 2111 01:36:04,560 --> 01:36:06,400 TO ACTIVATE THE VIRUSES. 2112 01:36:06,400 --> 01:36:10,040 AND LEADING TO LYSIS. 2113 01:36:10,040 --> 01:36:12,120 AND THIS IS INDEPENDENT OF ANY 2114 01:36:12,120 --> 01:36:14,000 ENVIRONMENTAL TRIGGER OR 2115 01:36:14,000 --> 01:36:15,720 ACTIVATE OR BUT THIS EXPRESSION 2116 01:36:15,720 --> 01:36:19,440 OF THE SINGLE GENE AND TO SHOW 2117 01:36:19,440 --> 01:36:22,720 YOU A PROOF OF CONCEPT HOW WE'VE 2118 01:36:22,720 --> 01:36:24,200 LEVERAGED THAT WHAT WE'VE DONE 2119 01:36:24,200 --> 01:36:28,240 IS THAT WE HAVE CREATED A TRAINS 2120 01:36:28,240 --> 01:36:30,480 DESCRIPTIONAL INFUSION -- AND * 2121 01:36:30,480 --> 01:36:32,160 THIS IS A GENE OF INTEREST 2122 01:36:32,160 --> 01:36:35,240 LOOKED UP TO THE -- AND THIS IS 2123 01:36:35,240 --> 01:36:36,240 IN THE OFF STATUS. 2124 01:36:36,240 --> 01:36:39,680 WHAT WE SEE IS THAT IT NICELY 2125 01:36:39,680 --> 01:36:41,760 GROWS UP OVER TIME INCREASING 2126 01:36:41,760 --> 01:36:43,240 CELL DENSITY AND IF YOU LOOK AT 2127 01:36:43,240 --> 01:36:47,520 THE AMOUNT OF THE PROTEIN -- 2128 01:36:47,520 --> 01:36:50,520 BARELY ANY LIE SIS AND THEREFORE 2129 01:36:50,520 --> 01:37:00,360 BARELY ANY RELEASE. 2130 01:37:00,360 --> 01:37:02,840 -- THE NICE THING ABOUT THIS IS 2131 01:37:02,840 --> 01:37:05,040 THAT IT TAKES ABOUT THREE HOURS 2132 01:37:05,040 --> 01:37:08,040 UPON THE ACTIVATION TO LEAD TO 2133 01:37:08,040 --> 01:37:11,440 LICE US OF THE CELLS AND THIS 2134 01:37:11,440 --> 01:37:14,920 THREE HOUR TIME WINDOW IS ENOUGH 2135 01:37:14,920 --> 01:37:16,600 PROTEIN BEING PRODUCED INSIDE 2136 01:37:16,600 --> 01:37:23,840 THE CELL. 2137 01:37:23,840 --> 01:37:26,040 AND WHAT WE SEE IS THAT AFTER 2138 01:37:26,040 --> 01:37:28,720 THREE HOURS THE CELL DENSITY 2139 01:37:28,720 --> 01:37:29,760 GREATLY DECREASES. 2140 01:37:29,760 --> 01:37:33,200 7 AND WHAT WE NOW SEE IS THAT WE 2141 01:37:33,200 --> 01:37:35,640 HAVE MICRO GRAM LEVELS OF 2142 01:37:35,640 --> 01:37:37,640 PROTEIN BEING RELEASED. 2143 01:37:37,640 --> 01:37:40,280 AND I THINK THIS IS ACTUALLY 2144 01:37:40,280 --> 01:37:41,840 EXCITING BECAUSE THIS PROVIDES 2145 01:37:41,840 --> 01:37:44,240 OPPORTUNITIES AND NOT ONLY TO 2146 01:37:44,240 --> 01:37:47,680 CONTROL THE RELEASE OF A 2147 01:37:47,680 --> 01:37:50,000 THERAPEUTIC UPON SENSING 2148 01:37:50,000 --> 01:37:51,360 ENVIRONMENTAL FACTOR WHETHER 2149 01:37:51,360 --> 01:37:53,920 THAT IS INFLAMMATION IN THE GUT 2150 01:37:53,920 --> 01:37:56,280 OR IN THE PRESENCE OF A TOXIN 2151 01:37:56,280 --> 01:37:58,240 FOR EXAMPLE THAT CAN ACTIVATE A 2152 01:37:58,240 --> 01:38:00,240 PROMOTER LEADING TO THE RELEASE 2153 01:38:00,240 --> 01:38:04,440 OF A PROTEIN AND I THINK THIS 2154 01:38:04,440 --> 01:38:05,640 MAY PROVIDE OPPORTUNITIES IF YOU 2155 01:38:05,640 --> 01:38:09,840 THINK OF DIAGNOSTICS THAT 2156 01:38:09,840 --> 01:38:12,320 PROMOTE OR LOOK FOR A PARTICULAR 2157 01:38:12,320 --> 01:38:14,440 DISEASE STATE IF YOU LIKE. 2158 01:38:14,440 --> 01:38:16,400 >> YOU HAVE ABOUT THREE MINUTES. 2159 01:38:16,400 --> 01:38:16,920 >> OKAY. 2160 01:38:16,920 --> 01:38:17,120 GREAT. 2161 01:38:17,120 --> 01:38:20,240 THANK YOU. 2162 01:38:20,240 --> 01:38:22,600 THESE ARE OPPORTUNITIES HERE 2163 01:38:22,600 --> 01:38:27,000 THAT WE'RE LOOKING FORWARD TO 2164 01:38:27,000 --> 01:38:27,640 LEVERAGE. 2165 01:38:27,640 --> 01:38:29,840 IN TERMS OF EFFICACY AND SAFETY 2166 01:38:29,840 --> 01:38:32,080 WE ARE WORKING WITH A GMO AND 2167 01:38:32,080 --> 01:38:33,880 ONE OF THE APPROACHES THAT WE 2168 01:38:33,880 --> 01:38:36,760 TAKE IS THAT WE'VE NOW DEVELOPED 2169 01:38:36,760 --> 01:38:39,760 A LINE -- WHICH DELETED 10 GAMES 2170 01:38:39,760 --> 01:38:41,840 AND THIS SO-CALLED -- IS 2171 01:38:41,840 --> 01:38:44,840 EXPECTED TO HAVE REDUCED 2172 01:38:44,840 --> 01:38:45,840 COLONIZATION POTENTIAL AND THIS 2173 01:38:45,840 --> 01:38:48,840 IS A PLATFORM WE WANT TO PREFER 2174 01:38:48,840 --> 01:38:50,720 TO DEVELOP TO DELIVER A 2175 01:38:50,720 --> 01:38:51,800 THERAPEUTIC MOLECULES. 2176 01:38:51,800 --> 01:38:56,320 AND I CAN SHARE THAT THIS -- 2177 01:38:56,320 --> 01:38:59,280 MUTE ANNUAL AT LEAST IN A MODEL 2178 01:38:59,280 --> 01:39:02,840 OF IRRADIATION FOR OVARIAN 2179 01:39:02,840 --> 01:39:04,640 CANCER IN MICE HAS PROVEN 2180 01:39:04,640 --> 01:39:06,400 SUCCESSFUL AND IS COMPARABLE TO 2181 01:39:06,400 --> 01:39:08,680 THE EFFICACY OF THE WILD TYPES 2182 01:39:08,680 --> 01:39:11,400 SO THIS IS VERY EXCITING. 2183 01:39:11,400 --> 01:39:14,600 I ALREADY TOUCHED A BIT ON 2184 01:39:14,600 --> 01:39:17,240 BIOSENSORS SO I WILL NOT GO OVER 2185 01:39:17,240 --> 01:39:18,120 THAT IN DETAIL. 2186 01:39:18,120 --> 01:39:20,640 AND I ALSO WANT TO MENTION THAT 2187 01:39:20,640 --> 01:39:22,840 IN THE NEAR FUTURE BECAUSE WE 2188 01:39:22,840 --> 01:39:24,440 HAVE BEEN USING MICE FOR MOST OF 2189 01:39:24,440 --> 01:39:26,480 THE STUDIES WE HOPE TO LEVERAGE 2190 01:39:26,480 --> 01:39:28,480 THIS TO USE SOME LARGER ANIMALS 2191 01:39:28,480 --> 01:39:30,960 TO LOOK FOR PROOF OF CONCEPT AND 2192 01:39:30,960 --> 01:39:33,720 TO BETTER UNDERSTAND PHYSIOLOGY 2193 01:39:33,720 --> 01:39:36,920 AND THERAPEUTIC OF THE 2194 01:39:36,920 --> 01:39:38,440 PRO-BIOTIC AND FOR THAT WE WILL 2195 01:39:38,440 --> 01:39:40,440 BE USING A MINIATURE SWINE THAT 2196 01:39:40,440 --> 01:39:43,680 WE HAVE AVAILABLE ON CAMPUS. 2197 01:39:43,680 --> 01:39:46,400 VERY EXCITED TO SEE ONE OF OUR 2198 01:39:46,400 --> 01:39:48,760 PARTNERS -- WHO IS USING SOME OF 2199 01:39:48,760 --> 01:39:50,480 THE STRAINS THAT WE'VE DEVELOPED 2200 01:39:50,480 --> 01:39:55,640 AND THESE WILL BE TESTED SOON IN 2201 01:39:55,640 --> 01:39:57,080 NONHUMAN PRIMATES. 2202 01:39:57,080 --> 01:39:59,040 AND I'M REALLY LOOKING FORWARD 2203 01:39:59,040 --> 01:40:01,320 TO SEE WHAT WILL BE HAPPENING 2204 01:40:01,320 --> 01:40:03,080 WITH THESE EFFECTS AND LASTLY 2205 01:40:03,080 --> 01:40:05,080 BECAUSE I'VE BEEN BLOWING THE 2206 01:40:05,080 --> 01:40:05,640 HORN. 2207 01:40:05,640 --> 01:40:07,520 I THINK ONCE WE START TO LEARN 2208 01:40:07,520 --> 01:40:10,080 MORE ABOUT THE IMPACT OF 2209 01:40:10,080 --> 01:40:12,080 SPECIFIC ORGANISMS IN HEALTH AND 2210 01:40:12,080 --> 01:40:15,200 DISEASE ULTIMATELY THERE WILL BE 2211 01:40:15,200 --> 01:40:16,680 THE NEED TO INNER. 2212 01:40:16,680 --> 01:40:20,960 >> BACTERIA AND THERE WILL BE -- 2213 01:40:20,960 --> 01:40:22,960 A GAP TO OVERCOME THERE IN TERMS 2214 01:40:22,960 --> 01:40:25,000 OF LACK OF TOOLS THAT ARE 2215 01:40:25,000 --> 01:40:27,120 AVAILABLE TO DO SO. 2216 01:40:27,120 --> 01:40:30,320 SO WITH THAT I AM FIRST OF ALL 2217 01:40:30,320 --> 01:40:32,120 GRATEFUL TO A GREAT TEAM OF 2218 01:40:32,120 --> 01:40:33,800 PEOPLE THAT I HAVE IN THE LAB 2219 01:40:33,800 --> 01:40:36,240 BECAUSE WITHOUT THEM I WOULD NOT 2220 01:40:36,240 --> 01:40:37,680 BE GIVEN THE OPPORTUNITY TO TELL 2221 01:40:37,680 --> 01:40:38,880 YOU THE STORY HERE. 2222 01:40:38,880 --> 01:40:41,120 I'M ALSO GRATEFUL FORth 2223 01:40:41,120 --> 01:40:42,440 ACADEMIC COLLABORATORS THAT I 2224 01:40:42,440 --> 01:40:45,120 MENTIONED EARLIER IN MY TIME 2225 01:40:45,120 --> 01:40:47,640 HERE. 2226 01:40:47,640 --> 01:40:49,720 FUNDING FROM INDUSTRY AND 2227 01:40:49,720 --> 01:40:52,040 GRATEFUL TO BE IN THE POSITION 2228 01:40:52,040 --> 01:40:54,800 TO DO WHAT WE LIKE TO DO AND 2229 01:40:54,800 --> 01:40:56,840 HOPEFULLY TO PUSH THINGS FORWARD 2230 01:40:56,840 --> 01:40:59,000 AND I'M THE OWNER AND FOUNDER OF 2231 01:40:59,000 --> 01:41:02,040 A CONSULTING COMPANY. 2232 01:41:02,040 --> 01:41:04,440 NONE OF THE WORK DISCLOSED HERE 2233 01:41:04,440 --> 01:41:05,960 TODAY IS RELATED TO THAT. 2234 01:41:05,960 --> 01:41:06,960 I THANK YOU VERY MUCH FOR YOUR 2235 01:41:06,960 --> 01:41:07,360 ATTENTION. 2236 01:41:07,360 --> 01:41:08,280 7 2237 01:41:08,280 --> 01:41:11,040 >> THANK YOU SO MUCH, J.P. 2238 01:41:11,040 --> 01:41:12,480 THAT WAS A GREAT TALK. 2239 01:41:12,480 --> 01:41:14,560 I'M GOING TO HAND IT OVER TO 2240 01:41:14,560 --> 01:41:16,120 KATHERINE AS WE HEAD INTO A 2241 01:41:16,120 --> 01:41:16,520 SHORT BREAK. 2242 01:41:16,520 --> 01:41:18,440 7 2243 01:41:18,440 --> 01:41:19,160 >> YES. 2244 01:41:19,160 --> 01:41:20,640 WE'RE GOING TO TAKE A QUICK 2245 01:41:20,640 --> 01:41:22,240 BREAK AND WE'RE GOING TO HEAD 2246 01:41:22,240 --> 01:41:24,640 OUT FOR A FIVE MINUTE BREAK. 2247 01:41:24,640 --> 01:41:28,000 AND SO WE'RE GOING TO COME BACK 2248 01:41:28,000 --> 01:41:30,960 VERY SPECIFICALLY AT 2249 01:41:30,960 --> 01:41:31,040 11:46 2250 01:41:31,040 --> 01:41:32,120 >> WELCOME BACK. 2251 01:41:32,120 --> 01:41:36,400 WE'RE READY TO START THE SECOND 2252 01:41:36,400 --> 01:41:38,640 HALF OF SESSION THREE AND I'M 2253 01:41:38,640 --> 01:41:40,960 GOING TO TURN IT OVER TO 2254 01:41:40,960 --> 01:41:44,040 DR. PADMA MARUVADA. 2255 01:41:44,040 --> 01:41:44,800 DR. MARUVADA, PLEASE TAKE IT 2256 01:41:44,800 --> 01:41:46,760 AWAY. 2257 01:41:46,760 --> 01:41:47,640 >> THANK YOU. 2258 01:41:47,640 --> 01:41:49,040 AND GOOD MORNING. 2259 01:41:49,040 --> 01:41:52,240 IT'S MY PLEASURE TO CO-LEAD THIS 2260 01:41:52,240 --> 01:41:56,640 SESSION WITH MY COLLEAGUE -- 2261 01:41:56,640 --> 01:41:58,760 RYAN RANALLO AND I'M PLEASED AND 2262 01:41:58,760 --> 01:42:00,560 EXCITED ABOUT ALL OF THIS TALK 2263 01:42:00,560 --> 01:42:04,000 THAT WE'VE IN THE LAST -- -- 2264 01:42:04,000 --> 01:42:06,080 YESTERDAY AND ALSO THIS MORNING. 2265 01:42:06,080 --> 01:42:08,320 SO WE ARE NOW CONTINUING WITH 2266 01:42:08,320 --> 01:42:09,960 THE CURRENT SESSION. 2267 01:42:09,960 --> 01:42:12,520 AND WE HAVE THE FIRST SPEAKER 2268 01:42:12,520 --> 01:42:15,640 TAMI LIEBERMAN FROM 2269 01:42:15,640 --> 01:42:17,960 MASSACHUSETTS AND SHE WILL BE 2270 01:42:17,960 --> 01:42:22,480 TALKING ABOUT INFERRING INHUMANE 2271 01:42:22,480 --> 01:42:25,240 BIOLOGY BY RECONSTRUCTING WITHIN 2272 01:42:25,240 --> 01:42:33,960 PERSON BACTERIAL EVOLUTION. 2273 01:42:33,960 --> 01:42:38,960 >> THANK YOU ALL. 2274 01:42:38,960 --> 01:42:42,680 AND THANK YOU TO THE ORGANIZERS 2275 01:42:42,680 --> 01:42:43,800 FOR HAVING ME HERE. 2276 01:42:43,800 --> 01:42:47,280 I ENJOYED THE TALKS. 2277 01:42:47,280 --> 01:42:50,400 MY LAB STARTED IN 2018 AND WE 2278 01:42:50,400 --> 01:42:55,320 FOCUSED ON HOW BACTERIA EVOLVE 2279 01:42:55,320 --> 01:42:58,000 AND I'M NOT TALKING ABOUT HOW 2280 01:42:58,000 --> 01:42:59,120 COMMUNITY COMPOSITION IS 2281 01:42:59,120 --> 01:43:00,920 CHANGING OVER TIME BUT HOW 2282 01:43:00,920 --> 01:43:04,200 INDIVIDUAL MICROBES ARE EVOLVING 2283 01:43:04,200 --> 01:43:05,440 AND MUTATING. 2284 01:43:05,440 --> 01:43:07,520 I DON'T HAVE ANY CONFLICTS TO 2285 01:43:07,520 --> 01:43:09,720 DECLARE. 2286 01:43:09,720 --> 01:43:13,240 AND THERE IS A LOT OF POTENTIAL 2287 01:43:13,240 --> 01:43:16,120 WITH EVOLUTION. 2288 01:43:16,120 --> 01:43:19,560 EACH OF US HAS ABOUT 10 TRILLION 2289 01:43:19,560 --> 01:43:20,840 BACTERIA IN AND ON US. 2290 01:43:20,840 --> 01:43:24,760 EACH HAS ABOUT A MILLION BASE 2291 01:43:24,760 --> 01:43:27,800 PAIRS AND EACH TIME ONE 2292 01:43:27,800 --> 01:43:29,440 REPLICATES THERE IS ABOUT A ONE 2293 01:43:29,440 --> 01:43:32,880 IN A BILL CHANCE OF CREATING A 2294 01:43:32,880 --> 01:43:34,280 MUTATION. 2295 01:43:34,280 --> 01:43:38,600 EVERY TIME THEY REPLICATE WHICH 2296 01:43:38,600 --> 01:43:40,240 IS MAYBE ONCE A DAY THERE ARE 2297 01:43:40,240 --> 01:43:43,440 BILLIONS OF MUTATIONS UPON WHICH 2298 01:43:43,440 --> 01:43:47,120 SELECTION CAN ACT AND IN MY LAB 2299 01:43:47,120 --> 01:43:50,120 WE USE THIS TO UNDERSTAND THIS 2300 01:43:50,120 --> 01:43:53,040 ADAPTATION BUT ALSO AS A GENERAL 2301 01:43:53,040 --> 01:43:56,640 LENS TO UNDERSTANDING 2302 01:43:56,640 --> 01:43:58,640 MICROBIOLOGY IN VIVO. 2303 01:43:58,640 --> 01:44:00,280 AND WE DO THIS BECAUSE LIKE A 2304 01:44:00,280 --> 01:44:02,760 LOT OF FOLKS HERE TODAY WE'RE 2305 01:44:02,760 --> 01:44:05,160 INTERESTED IN THIS BIG GOAL OF 2306 01:44:05,160 --> 01:44:09,360 HOW CAN WE ADD A MICROBE TO AN 2307 01:44:09,360 --> 01:44:13,880 ESTABLISHED MICROBIOME WITHOUT 2308 01:44:13,880 --> 01:44:20,280 BOMBING IT WITH -- ANTIBIOTICS. 2309 01:44:20,280 --> 01:44:26,400 . 2310 01:44:26,400 --> 01:44:30,240 AND IT COULD BE GENETICALLY 2311 01:44:30,240 --> 01:44:31,720 ENGINEERED OR NATURALLY 2312 01:44:31,720 --> 01:44:33,600 OCCURRING BUT THE BIG CHALLENGE 2313 01:44:33,600 --> 01:44:35,720 IS BEYOND AFTER IDENTIFICATION 2314 01:44:35,720 --> 01:44:39,680 WOULD BE UNDERSTANDING MY 2315 01:44:39,680 --> 01:44:45,520 COMMUNITY -- ECOLOGY TO PREDICT 2316 01:44:45,520 --> 01:44:48,240 THESE MICRO BIOMES. 2317 01:44:48,240 --> 01:44:50,600 WE'RE IN THE EARLY DAYS AND NOW 2318 01:44:50,600 --> 01:44:52,680 IS THE THIRD TIME YOU'VE SEEN 2319 01:44:52,680 --> 01:44:55,360 THIS GREAT EXPERIMENT WHERE -- 2320 01:44:55,360 --> 01:44:58,240 IT IS GIVEN TO HEALTHY HUMANS 2321 01:44:58,240 --> 01:45:01,360 AND AFTER REMOVAL THIS BACTERIA 2322 01:45:01,360 --> 01:45:04,040 WAS NOT DETECTED IN MORE THAN 2323 01:45:04,040 --> 01:45:05,560 HALF OF THE PARTICIPANTS. 2324 01:45:05,560 --> 01:45:09,000 AND WHILE POST TALK THE AUTHORS 2325 01:45:09,000 --> 01:45:11,440 ARE ABLE TO SHOW SOME POSSIBLE 2326 01:45:11,440 --> 01:45:14,760 REASONS WHY THESE STRAINS -- 2327 01:45:14,760 --> 01:45:15,640 WERE GRAFTED IN THESE 2328 01:45:15,640 --> 01:45:17,320 INDIVIDUALS AND NOT THESE IT'S 2329 01:45:17,320 --> 01:45:17,920 GOING TO BE IMPORTANT. 2330 01:45:17,920 --> 01:45:21,520 7 AND UNDERSTANDING WHEN SINGLE 2331 01:45:21,520 --> 01:45:25,080 STRAINS VERSUS MULTIPLE STRAINS 2332 01:45:25,080 --> 01:45:26,640 CO-EXIST IS ALSO GOING TO BE 2333 01:45:26,640 --> 01:45:27,400 IMPORTANT. 2334 01:45:27,400 --> 01:45:30,640 FOR SOME SPECIES EVERYBODY IS 2335 01:45:30,640 --> 01:45:32,600 COLONIZED BY A SINGLE STRAIN OF 2336 01:45:32,600 --> 01:45:34,480 THAT SPECIES BUT FOR A LOT OF 2337 01:45:34,480 --> 01:45:40,080 THE SPECIES IT'S MORE OFTEN THE 2338 01:45:40,080 --> 01:45:43,520 CASE THAT MULTIPLE STRAINS ARE 2339 01:45:43,520 --> 01:45:48,360 QUITE COMMON AND ON THE SKIN -- 2340 01:45:48,360 --> 01:45:51,360 FOR THE TWO MOST DOMINANT 2341 01:45:51,360 --> 01:45:52,720 BACTERIA ON THE SKIN MULTIPLE IT 2342 01:45:52,720 --> 01:45:54,600 WILL STRAIN COLONIZATION IS THE 2343 01:45:54,600 --> 01:45:57,840 NORM. 2344 01:45:57,840 --> 01:46:00,840 AND ONE COULD SAY WHY ARE THERE 2345 01:46:00,840 --> 01:46:03,680 NOT INFINITE STRAINS ON THE 2346 01:46:03,680 --> 01:46:06,400 SKIN? 2347 01:46:06,400 --> 01:46:08,280 BEYOND THAT THERE IS A NUMBER OF 2348 01:46:08,280 --> 01:46:10,640 BASIC QUESTIONS WE STILL NEED TO 2349 01:46:10,640 --> 01:46:13,280 UNDERSTAND TO MANIPULATE MICRO 2350 01:46:13,280 --> 01:46:13,840 BIOMES. 2351 01:46:13,840 --> 01:46:15,960 WE NEED TO KNOW WHAT THE NICHE 2352 01:46:15,960 --> 01:46:16,840 RANGE IS. 2353 01:46:16,840 --> 01:46:20,480 DOES A BACTERIA HAVE ANY CHANCE 2354 01:46:20,480 --> 01:46:23,280 OF LIVING ON ME THAT LIVES ON 2355 01:46:23,280 --> 01:46:23,440 YOU. 2356 01:46:23,440 --> 01:46:25,240 WE KNOW THAT THE BIG PLAYERS ARE 2357 01:46:25,240 --> 01:46:27,960 GOING TO BE DIET AND IMMUNE 2358 01:46:27,960 --> 01:46:34,240 SYSTEM ARE GOING TO PLAY ROLES. 2359 01:46:34,240 --> 01:46:37,200 AND LASTLY IS WE DON'T KNOW WHAT 2360 01:46:37,200 --> 01:46:42,120 THE ROLE IS WITHIN EVOLUTION. 2361 01:46:42,120 --> 01:46:44,560 THEY ARE ALREADY ADAPTED TO SOME 2362 01:46:44,560 --> 01:46:46,520 UNIQUE SET OF FORCES WITHIN ME 2363 01:46:46,520 --> 01:46:49,560 AND SO MICROBE FROM THE OUTSIDE 2364 01:46:49,560 --> 01:46:50,640 ENVIRONMENT IS NOT GOING TO 2365 01:46:50,640 --> 01:46:53,440 STAND A CHANCE AGAINST THE 2366 01:46:53,440 --> 01:46:54,640 PREADAPTED MICROBE. 2367 01:46:54,640 --> 01:46:58,680 AND THE UPSIDE IS BY TRACKING IT 2368 01:46:58,680 --> 01:47:00,480 NOT ONLY DO WE LEARN ABOUT THIS 2369 01:47:00,480 --> 01:47:01,840 IMPORTANT FORCE BUT WE LEARN 2370 01:47:01,840 --> 01:47:03,440 SOME OF THE ANSWERS TO OTHER 2371 01:47:03,440 --> 01:47:04,640 QUESTIONS AS WELL. 2372 01:47:04,640 --> 01:47:07,840 AND IN PARTICULAR BY 2373 01:47:07,840 --> 01:47:10,040 RECONSTRUCTING WITHIN PERSON 2374 01:47:10,040 --> 01:47:14,520 EVOLUTION WE CAN RECONSTRUCT HAS 2375 01:47:14,520 --> 01:47:15,360 BACTERIA SPREADS WITHIN 2376 01:47:15,360 --> 01:47:17,640 INDIVIDUALS OR WITHIN A PERSON 2377 01:47:17,640 --> 01:47:20,320 AS JULIA MENTIONED AND ALSO BY 2378 01:47:20,320 --> 01:47:21,640 LOOKING AT WHAT GENES THEMSELVES 2379 01:47:21,640 --> 01:47:23,120 ARE CHANGING WE CAN UNDERSTAND 2380 01:47:23,120 --> 01:47:27,520 THE CHALLENGES TO BACTERIA 2381 01:47:27,520 --> 01:47:33,080 SURVIVORRAL IN VIVO. 2382 01:47:33,080 --> 01:47:35,000 GIVEN THIS GREAT POTENTIAL AND 2383 01:47:35,000 --> 01:47:37,200 MAYBE WHAT I'M SELLING IS THIS 2384 01:47:37,200 --> 01:47:39,440 GREAT TOOL YOU MIGHT BE ASKING 2385 01:47:39,440 --> 01:47:41,760 WHY YOU HAVE NOT HEARD ABOUT 2386 01:47:41,760 --> 01:47:47,440 MORE STUDIES ABOUT IN PERSON 2387 01:47:47,440 --> 01:47:48,240 EVOLUTION. 2388 01:47:48,240 --> 01:47:51,200 IF WE WANT TO STUDY EVOLUTION WE 2389 01:47:51,200 --> 01:47:54,160 MIGHT NEED TO GET DIFFERENT TIME 2390 01:47:54,160 --> 01:47:57,000 POINT SAMPLES. 2391 01:47:57,000 --> 01:47:59,560 AND WHILE LONGITUDINAL DATASETS 2392 01:47:59,560 --> 01:48:01,000 ARE GREAT WHAT WE'VE LEARNED 2393 01:48:01,000 --> 01:48:07,120 OVER TIME IS THAT CROSS SAMPLING 2394 01:48:07,120 --> 01:48:10,360 -- FROM A SINGLE PERSON CAN HELP 2395 01:48:10,360 --> 01:48:12,240 US PROJECT BACK INTO THE RECENT 2396 01:48:12,240 --> 01:48:12,640 PAST. 2397 01:48:12,640 --> 01:48:17,640 AND THE REASON THIS HAPPENS AS 2398 01:48:17,640 --> 01:48:20,480 -- BASED ON LESSONS WE'VE 2399 01:48:20,480 --> 01:48:21,840 LEARNED FROM FINISH FISHES 2400 01:48:21,840 --> 01:48:25,560 DISEASE WHEN ADAPTIVE MUTATIONS 2401 01:48:25,560 --> 01:48:26,840 ARISE WITHIN INDIVIDUALS THEY 2402 01:48:26,840 --> 01:48:29,280 OFTEN RISE IN FREQUENCY AND 2403 01:48:29,280 --> 01:48:31,720 REMOVE THEIR AN SEVENS FOR BUT 2404 01:48:31,720 --> 01:48:34,040 THEY COEXIST WITH OTHER ADAPTIVE 2405 01:48:34,040 --> 01:48:36,280 MUTANTS AND THIS COEXISTENCE 2406 01:48:36,280 --> 01:48:40,120 ALLOWS US TO PROJECT BACK INTO 2407 01:48:40,120 --> 01:48:42,840 THE PAST AND FOR RECENT WITHIN 2408 01:48:42,840 --> 01:48:43,440 PERSON EVOLUTION. 2409 01:48:43,440 --> 01:48:45,640 THERE IS A SECOND REASON AS WELL 2410 01:48:45,640 --> 01:48:47,800 WHICH IS TECHNICAL. 2411 01:48:47,800 --> 01:48:50,440 USING SEQUENCING WE'RE NOT GOING 2412 01:48:50,440 --> 01:48:52,520 TO GET THE WHOLE GENOME 2413 01:48:52,520 --> 01:48:54,240 RESOLUTION THAT WE NEED FOR 2414 01:48:54,240 --> 01:48:55,640 STUDYING EVOLUTION. 2415 01:48:55,640 --> 01:48:59,560 BUT ALSO METAGENOMICS IS QUITE 2416 01:48:59,560 --> 01:49:01,040 DIFFICULT AND I WANT TO 2417 01:49:01,040 --> 01:49:02,560 HIGHLIGHT THAT MORE. 2418 01:49:02,560 --> 01:49:05,320 WHEN WE'RE LOOKING FOR MUTATIONS 2419 01:49:05,320 --> 01:49:07,000 IN EVOLUTION WE WANT TO FIND 2420 01:49:07,000 --> 01:49:09,560 THESE VARIANTS THAT HAVE EMERGED 2421 01:49:09,560 --> 01:49:12,520 WITHIN A PERSON DUE TO DENOVO 2422 01:49:12,520 --> 01:49:12,920 MUTATIONS. 2423 01:49:12,920 --> 01:49:16,040 . 2424 01:49:16,040 --> 01:49:17,800 BECAUSE TWO DIFFERENT STRAINS 2425 01:49:17,800 --> 01:49:20,440 HAPPEN TO COLONIZE ON THE SAME 2426 01:49:20,440 --> 01:49:22,840 PERSON OR TWO DIFFERENT STRAINS 2427 01:49:22,840 --> 01:49:24,440 OF DIFFERENT SPECIES SHARE THE 2428 01:49:24,440 --> 01:49:25,560 SAME MOBILE ELEMENT. 2429 01:49:25,560 --> 01:49:28,080 AND THEN ONCE WE IDENTIFIED THE 2430 01:49:28,080 --> 01:49:30,440 MUTATIONS WE WANT TO KNOW WHICH 2431 01:49:30,440 --> 01:49:32,320 ONES IN THEIR THE SAME CELL AND 2432 01:49:32,320 --> 01:49:35,400 THIS CAN BE A HARD COMPUTATIONAL 2433 01:49:35,400 --> 01:49:43,480 PROBLEM. 2434 01:49:43,480 --> 01:49:47,800 SO WE DO OLD SCHOOL STUFF -- OF 2435 01:49:47,800 --> 01:49:49,800 SEQUENCING THEM INDIVIDUALLY. 2436 01:49:49,800 --> 01:49:52,360 WE PERFORM EVE LOSING NARY 2437 01:49:52,360 --> 01:49:57,240 RECONSTRUCTION. 2438 01:49:57,240 --> 01:49:59,920 THEY ARE INFERRED TO HAVE HAD 2439 01:49:59,920 --> 01:50:01,880 HAPPENED RECENTLY. 2440 01:50:01,880 --> 01:50:04,960 WE'VE GOTTEN THE LAB PROCESSES 2441 01:50:04,960 --> 01:50:08,280 DOWN PRETTY WELL AND IT'S LESS 2442 01:50:08,280 --> 01:50:10,400 THAN $20 FOR SEQUENCES AND 2443 01:50:10,400 --> 01:50:16,760 SAMPLE SET PERFECT ISOLETTE. 2444 01:50:16,760 --> 01:50:19,280 AND IN MY POSTDOC WE SET OUT TO 2445 01:50:19,280 --> 01:50:22,040 ANSWER ANY OF THESE MUTATIONS 2446 01:50:22,040 --> 01:50:24,280 THAT PROVIDE A SIGNIFICANT 2447 01:50:24,280 --> 01:50:26,840 BENEFIT AND WHEN WE LOOKED AT 2448 01:50:26,840 --> 01:50:33,000 THE COMMON GUT BUGS WE DEFINED 2449 01:50:33,000 --> 01:50:36,640 IN VIVO -- AND WITHIN THESE 12 2450 01:50:36,640 --> 01:50:39,480 PEOPLE WE IDENTIFIED MANY CASES 2451 01:50:39,480 --> 01:50:42,040 WHERE THERE WAS IN PERSON 2452 01:50:42,040 --> 01:50:43,040 EVOLUTION. 2453 01:50:43,040 --> 01:50:46,240 WITHIN PERSON -- SO ALL OF THESE 2454 01:50:46,240 --> 01:50:48,160 TIPS ARE ISOLETTES FROM THE SAME 2455 01:50:48,160 --> 01:50:49,240 PERSON. 2456 01:50:49,240 --> 01:50:51,360 WE IDENTIFIED GENES THAT WERE 2457 01:50:51,360 --> 01:50:53,240 MUTE INDICATED MULTIPLE TIMES ON 2458 01:50:53,240 --> 01:50:54,680 INDEPENDENT BRANCHES OF THESE 2459 01:50:54,680 --> 01:50:58,160 TREES AND THIS IS A STRONG 2460 01:50:58,160 --> 01:51:04,320 SIGNATURE OF ADAPTATION. 2461 01:51:04,320 --> 01:51:06,840 AND SO WE IDENTIFIED A BUNCH OF 2462 01:51:06,840 --> 01:51:09,240 GENES THAT HAD THE SIGNATURE OF 2463 01:51:09,240 --> 01:51:11,000 PARALLEL EVOLUTION AND IT TOLD 2464 01:51:11,000 --> 01:51:16,080 US THAT OURER MEMBRANE SYNTHESIS 2465 01:51:16,080 --> 01:51:21,600 GENES ARE GETTING DENOVO POINT 2466 01:51:21,600 --> 01:51:24,240 MUTATIONS THAT ARE PROVIDING 2467 01:51:24,240 --> 01:51:27,440 STRONG -- AND THIS WORK TELLS US 2468 01:51:27,440 --> 01:51:30,440 THAT IT'S IMPORTANT -- A PATHWAY 2469 01:51:30,440 --> 01:51:32,560 NOW WHERE WE CAN IDENTIFY GENES 2470 01:51:32,560 --> 01:51:35,880 THAT ARE IMPORTANT FOR SURVIVAL 2471 01:51:35,880 --> 01:51:39,280 IN VIVO BUT THESE BACTERIA MUST 2472 01:51:39,280 --> 01:51:41,640 BE EXPERIENCING SOME NEW 2473 01:51:41,640 --> 01:51:45,440 SELECTIVE FORCES. 2474 01:51:45,440 --> 01:51:50,240 AND THERE IS REALLY STRONG 2475 01:51:50,240 --> 01:51:51,680 SELECTIVE PRESSURES. 2476 01:51:51,680 --> 01:51:54,560 AND WHAT THIS MEANS THAT IS FOR 2477 01:51:54,560 --> 01:51:56,560 BACTERIA THAT HAS THIS PATTERN 2478 01:51:56,560 --> 01:51:58,720 WE MIGHT NEED TO HAVE 2479 01:51:58,720 --> 01:52:01,920 PERSONALIZED APPROACHES TO DRIVE 2480 01:52:01,920 --> 01:52:03,480 ENGRAPHMENT. 2481 01:52:03,480 --> 01:52:07,280 FOR EXAMPLE -- DRIVING THE 2482 01:52:07,280 --> 01:52:09,440 CHANGES MAYBE BEFORE WE GET 2483 01:52:09,440 --> 01:52:11,760 SOMEBODY A PRO-BIOTIC WE WANT TO 2484 01:52:11,760 --> 01:52:14,520 FIRST PROFILE WHICH ARE IN THEIR 2485 01:52:14,520 --> 01:52:15,840 GUT MICROBIOME. 2486 01:52:15,840 --> 01:52:19,840 IN THE COURSE OF THE STORY WE 2487 01:52:19,840 --> 01:52:24,440 WERE FORTUNATE YOU HAVE TO BEGIN 2488 01:52:24,440 --> 01:52:27,640 WITH EVERY DAY METRO GENOMICS TO 2489 01:52:27,640 --> 01:52:29,120 GET THIS DIAGRAM. 2490 01:52:29,120 --> 01:52:33,400 THERE ARE TWO COEXISTING SUB 2491 01:52:33,400 --> 01:52:35,400 LINEAGES -- WHICH COEXIST 2492 01:52:35,400 --> 01:52:38,000 THROUGHOUT THIS WHOLE TWO-YEAR 2493 01:52:38,000 --> 01:52:39,440 TIME PERIOD DESPITE THE FACT 2494 01:52:39,440 --> 01:52:42,840 THAT ONE HAS A LOT OF 2495 01:52:42,840 --> 01:52:44,840 COMPETITIVE DYNAMICS WITHIN IT. 2496 01:52:44,840 --> 01:52:47,440 SO THIS BLUE GENOTYPE IS ABLE TO 2497 01:52:47,440 --> 01:52:51,160 OUT PERFORM THE PURPLE WITHOUT 2498 01:52:51,160 --> 01:52:53,680 AFFECTING THE ORANGE. 2499 01:52:53,680 --> 01:52:57,000 HOWEVER BECAUSE WE'RE SAMPLING 2500 01:52:57,000 --> 01:52:58,600 FROM STOOL WE CANNOT TELL IF 2501 01:52:58,600 --> 01:53:00,600 THESE ARE NOT COMPETING BECAUSE 2502 01:53:00,600 --> 01:53:03,440 THEY ARE SEPARATING IN SPACE. 2503 01:53:03,440 --> 01:53:09,040 WE WERE FOCUSING ON THE SKIN 2504 01:53:09,040 --> 01:53:11,280 MICROBIOME. 2505 01:53:11,280 --> 01:53:14,840 AND WE'RE INTERESTED IN THE SKIN 2506 01:53:14,840 --> 01:53:17,360 BECAUSE IT ALLOWS US TO ANSWER 2507 01:53:17,360 --> 01:53:19,120 THESE QUESTIONS BUT ALSO A LOT 2508 01:53:19,120 --> 01:53:21,640 OF DISEASES WITHOUT GOOD ANIMAL 2509 01:53:21,640 --> 01:53:22,560 MODELS. 2510 01:53:22,560 --> 01:53:26,440 WE'VE BEEN FOCUSING ON THE OILY 2511 01:53:26,440 --> 01:53:28,440 SKIN OF YOUR FACE AND BACK AND 2512 01:53:28,440 --> 01:53:30,520 CHEST BECAUSE IT'S EASY TO 2513 01:53:30,520 --> 01:53:31,120 SAMPLE. 2514 01:53:31,120 --> 01:53:33,840 IT'S RELATIVELY LOW DIVERSITY. 2515 01:53:33,840 --> 01:53:36,600 WHERE WE CAN SEE -- A COUPLE OF 2516 01:53:36,600 --> 01:53:42,000 GENE US US DOMINATING. 2517 01:53:42,000 --> 01:53:44,760 AND IT'S REALLY A STABLE 2518 01:53:44,760 --> 01:53:45,280 MICROBIOME. 2519 01:53:45,280 --> 01:53:47,320 NOT JUST SOME SAMPLING FROM THE 2520 01:53:47,320 --> 01:53:48,520 ENVIRONMENT. 2521 01:53:48,520 --> 01:53:53,480 AND WE'VE BEEN FOCUSING ON -- A 2522 01:53:53,480 --> 01:53:56,280 DOMINANT BACTERIA IN SKIN WHICH 2523 01:53:56,280 --> 01:53:58,040 LIVES IN YOUR PORES. 2524 01:53:58,040 --> 01:54:00,480 IT'S ON EVERYONE. 2525 01:54:00,480 --> 01:54:02,880 AND IT'S ANAEROBIC. 2526 01:54:02,880 --> 01:54:04,360 SO IT PREFERS TO GROW ON THE 2527 01:54:04,360 --> 01:54:05,600 BOTTOM OF THE PORES WHERE THERE 2528 01:54:05,600 --> 01:54:08,040 IS A LOT OF NUTRIENTS. 2529 01:54:08,040 --> 01:54:10,960 AND WE PERFORMED A STUDY W WHERE 2530 01:54:10,960 --> 01:54:12,840 SET OUT TO ASK IF DIFFERENT 2531 01:54:12,840 --> 01:54:14,280 STRAINS ARE COEXISTING BECAUSE 2532 01:54:14,280 --> 01:54:18,680 OF ADAPTIVE OR NEUTRAL FORCES. 2533 01:54:18,680 --> 01:54:25,640 WE PERFORMED LARGE SAMPLING AND 2534 01:54:25,640 --> 01:54:28,320 FINE FACIAL SCALES. 2535 01:54:28,320 --> 01:54:30,120 AND USING THIS APPROACH WE WERE 2536 01:54:30,120 --> 01:54:33,320 ABLE TO SHOW AGAIN -- WHAT IS 2537 01:54:33,320 --> 01:54:36,240 ALREADY KNOWN IS THERE ARE MANY 2538 01:54:36,240 --> 01:54:39,160 C ACNES EXISTING. 2539 01:54:39,160 --> 01:54:41,840 YOU CAN SEE THERE ARE SIX 2540 01:54:41,840 --> 01:54:44,160 DIFFERENT STRAINS COEXISTING ON 2541 01:54:44,160 --> 01:54:46,400 THIS PERSON. 2542 01:54:46,400 --> 01:54:50,840 AND SHARE SIMILAR GENE CONTENT. 2543 01:54:50,840 --> 01:54:52,320 >> YOU HAVE ABOUT TWO AND A HALF 2544 01:54:52,320 --> 01:54:52,760 MINUTES 2545 01:54:52,760 --> 01:54:53,200 >> OKAY. 2546 01:54:53,200 --> 01:54:54,840 I'M GOING TO GO FAST. 2547 01:54:54,840 --> 01:54:58,240 THIS IS COMMON ACROSS ALL OF OUR 2548 01:54:58,240 --> 01:54:59,360 SUBJECTS. 2549 01:54:59,360 --> 01:55:01,840 WHEN WE SEE WHERE THESE LINEAGES 2550 01:55:01,840 --> 01:55:05,400 ARE -- WE DON'T SEE ANY SIG 2551 01:55:05,400 --> 01:55:07,280 GOINGS OR STRONG SEGREGATION FOR 2552 01:55:07,280 --> 01:55:10,680 THE SURFACE OR DEEPER WITHIN 2553 01:55:10,680 --> 01:55:12,920 PORES BUT WHEN WE ZOOM IN AND 2554 01:55:12,920 --> 01:55:16,280 LOOK AT THE LEVEL OF INDIVIDUAL 2555 01:55:16,280 --> 01:55:17,360 PORES WE SEE SOMETHING MORE 2556 01:55:17,360 --> 01:55:20,240 STRIKING. 2557 01:55:20,240 --> 01:55:23,560 -- -- WE EXPECT TWO RANDOM 2558 01:55:23,560 --> 01:55:26,280 COLONIES FROM THE SAME FOR TO BE 2559 01:55:26,280 --> 01:55:29,560 FROM THE SAME LINEAGE OR SAME 2560 01:55:29,560 --> 01:55:30,880 STRAIN ABOUT HALF OF THE TIME 2561 01:55:30,880 --> 01:55:33,080 BUT IN FACT WHAT WE FIND IS THAT 2562 01:55:33,080 --> 01:55:35,640 WE PICKED TWO COLONIES FROM THE 2563 01:55:35,640 --> 01:55:37,440 SAME POOR THEY ARE ALMOST FROM 2564 01:55:37,440 --> 01:55:38,640 THE SAME STRAIN. 2565 01:55:38,640 --> 01:55:40,640 SUGGESTING THAT THERE ARE 2566 01:55:40,640 --> 01:55:42,720 DIFFERENT MICROBIAL COMMUNITIES 2567 01:55:42,720 --> 01:55:45,240 ON EACH OF THESE ISLANDS ON OUR 2568 01:55:45,240 --> 01:55:48,600 FACE AND WHEN WE LOOK -- IF 2569 01:55:48,600 --> 01:55:51,680 NEARBY ISLANDS HAVE SAME 2570 01:55:51,680 --> 01:55:56,000 LINEAGE'S THEY DON'T. 2571 01:55:56,000 --> 01:55:57,440 SO MAYBE THIS IS SUGGESTING THAT 2572 01:55:57,440 --> 01:55:59,680 EACH CORE IS SELECTING THROUGH A 2573 01:55:59,680 --> 01:56:01,840 DIFFERENT TYPE OF STRAIN. 2574 01:56:01,840 --> 01:56:03,600 AND TO UNDERSTAND THIS WE CAN 2575 01:56:03,600 --> 01:56:05,480 ZOOM IN MORE TO LOOK WITHIN 2576 01:56:05,480 --> 01:56:08,480 STRAIN DIVERSITY AND THIS IS TO 2577 01:56:08,480 --> 01:56:10,800 A SCALE BAR THAT IS VERY SMALL. 2578 01:56:10,800 --> 01:56:12,600 DOZENS OF MUTATIONS AND WE CAN 2579 01:56:12,600 --> 01:56:14,680 SEE THAT EACH FOR IS QUITE 2580 01:56:14,680 --> 01:56:15,760 SEGREGATED ON THE TREE. 2581 01:56:15,760 --> 01:56:17,720 SUGGESTING THAT IT'S NOT JUST 2582 01:56:17,720 --> 01:56:19,960 FILTERING BUT THERE IS A VERY 2583 01:56:19,960 --> 01:56:23,360 RECENT ANCESTOR WITHIN EACH FOR. 2584 01:56:23,360 --> 01:56:26,320 AND WHERE ACROSS LINEAGES -- WE 2585 01:56:26,320 --> 01:56:29,200 SEE LOTS OF DIVERSITY AT THE 2586 01:56:29,200 --> 01:56:31,200 LINEAGE LEVEL WITHIN THE LINEAGE 2587 01:56:31,200 --> 01:56:33,000 LEVEL BUT A SMALL SEGMENT OF 2588 01:56:33,000 --> 01:56:35,480 THAT DIVERSITY WITHIN EACH FOR. 2589 01:56:35,480 --> 01:56:37,520 AND SO THIS TELLS US THAT THERE 2590 01:56:37,520 --> 01:56:39,960 IS SOME RECENT BOTTLENECK WITHIN 2591 01:56:39,960 --> 01:56:41,080 EACH FOR AND WE DETERMINE THAT 2592 01:56:41,080 --> 01:56:42,520 THIS IS NOT ADAPTIVE. 2593 01:56:42,520 --> 01:56:45,960 WE DO NOT SEE ANY SIGNATURES OF 2594 01:56:45,960 --> 01:56:47,640 ADAPTIVE EVOLUTION WHICH WE 2595 01:56:47,640 --> 01:56:50,840 WOULD EXPECT TO SEE. 2596 01:56:50,840 --> 01:56:52,320 SO THERE HAS GOT TO BE SOME 2597 01:56:52,320 --> 01:56:54,880 NEUTRAL DRIVER AND IT'S NOT JUST 2598 01:56:54,880 --> 01:56:59,640 TRIVIAL. 2599 01:56:59,640 --> 01:57:03,240 SO WE THINK WHAT WAS GOING ON -- 2600 01:57:03,240 --> 01:57:05,120 PORES ARE CREATING STRONG 2601 01:57:05,120 --> 01:57:08,840 PRIORITY EFFECTS AND STRONG 2602 01:57:08,840 --> 01:57:11,080 BOTTLENECKS BECAUSE PERHAPS OF 2603 01:57:11,080 --> 01:57:14,480 THEIR PHYSIOLOGY. 2604 01:57:14,480 --> 01:57:16,680 AND BY THE TIME THE SECOND CELL 2605 01:57:16,680 --> 01:57:19,240 CAN COME IN THE FIRST CELL IS 2606 01:57:19,240 --> 01:57:21,840 ALREADY OCCLUDED THE SPACE. 2607 01:57:21,840 --> 01:57:25,280 WHAT THIS MEANS IS THAT THE 2608 01:57:25,280 --> 01:57:27,320 BACTERIA YOU GROWING FASTER EACH 2609 01:57:27,320 --> 01:57:29,440 OF THESE STRAINS AND EACH 2610 01:57:29,440 --> 01:57:32,840 GENOTYPE HAS ITS OWN LITTLE TEST 2611 01:57:32,840 --> 01:57:34,640 TUBE TO WORK IN AND DOESN'T 2612 01:57:34,640 --> 01:57:36,080 REALLY COMPETE WITH OTHER 2613 01:57:36,080 --> 01:57:39,280 STRAINS WHICH MIGHT BE MORE 2614 01:57:39,280 --> 01:57:40,720 ADVANTAGEOUS AND WHAT THIS MEANS 2615 01:57:40,720 --> 01:57:42,920 IN TERMS OF IMPLICATION FOR 2616 01:57:42,920 --> 01:57:46,600 POTENTIAL THERAPY IS THAT -- MAY 2617 01:57:46,600 --> 01:57:48,680 NOT MATTER SO MUCH AND WHAT WE 2618 01:57:48,680 --> 01:57:53,000 WANT TO DO -- IS FOCUS ON 2619 01:57:53,000 --> 01:57:56,480 REMOVAL OF THE STRAINS. 2620 01:57:56,480 --> 01:58:01,200 WE DON'T KNOW YET -- WE SEE 2621 01:58:01,200 --> 01:58:02,840 DIFFERENCES AND WHAT WE'RE 2622 01:58:02,840 --> 01:58:06,600 PROTECTS POSING IS THAT FACIAL 2623 01:58:06,600 --> 01:58:09,720 STRUCTURE IS ONE COMPONENTS BUT 2624 01:58:09,720 --> 01:58:11,320 THERE ARE OTHERS TOO AND 2625 01:58:11,320 --> 01:58:13,840 DETERMINING WHICH OF THESE 2626 01:58:13,840 --> 01:58:15,640 FACTORS IS IMPORTANT FOR HOW 2627 01:58:15,640 --> 01:58:20,120 MUCH ADAPTATION IS GOING ON WILL 2628 01:58:20,120 --> 01:58:22,360 HELP US UNDERSTAND WHEN WE MIGHT 2629 01:58:22,360 --> 01:58:24,320 USE PERSONALIZED APPROACHES IN 2630 01:58:24,320 --> 01:58:26,120 THE MICROBIOME. 2631 01:58:26,120 --> 01:58:29,560 I TRIED TO THANK THE KEY PLAYERS 2632 01:58:29,560 --> 01:58:31,440 BUT THIS WORK WAS HIGHLY 2633 01:58:31,440 --> 01:58:33,680 COLLABORATIVE AND THERE ARE MANY 2634 01:58:33,680 --> 01:58:34,120 INVOLVED. 2635 01:58:34,120 --> 01:58:36,440 AND I'M HAPPY TO TAKE QUESTIONS 2636 01:58:36,440 --> 01:58:38,320 DURING THE PANEL DISCUSSION. 2637 01:58:38,320 --> 01:58:41,040 THANK YOU. 2638 01:58:41,040 --> 01:58:42,200 >> THANK YOU, TAMI. 2639 01:58:42,200 --> 01:58:44,680 THAT WAS A POWERFUL TALK. 2640 01:58:44,680 --> 01:58:48,640 NOW WE'LL GO ON TO THE NEXT 2641 01:58:48,640 --> 01:59:00,520 SPEAKER DR. ERWIN ZOE ZANIDAKIS. 2642 01:59:00,520 --> 01:59:01,160 >> THANK YOU VERY MUCH. 2643 01:59:01,160 --> 01:59:08,240 . 2644 01:59:08,240 --> 01:59:09,120 >> THANK YOU VERY MUCH. 2645 01:59:09,120 --> 01:59:12,560 AND I WOULD LIKE TO THANK THE 2646 01:59:12,560 --> 01:59:14,600 ORGANIZERS FOR A FANTASTIC 2647 01:59:14,600 --> 01:59:17,440 PROGRAM THAT THEY ASSEMBLED AND 2648 01:59:17,440 --> 01:59:19,160 INVITED ME TO GIVE THE TALK AND 2649 01:59:19,160 --> 01:59:28,240 I WOULD LIKE TO FOCUS ON THE 2650 01:59:28,240 --> 01:59:29,480 NOVEL MICROBIOME. 2651 01:59:29,480 --> 01:59:33,000 YOU HAVE TO LOOK AT THE STRAINS 2652 01:59:33,000 --> 01:59:34,840 AND UNDERSTAND THEM AND SEE IF 2653 01:59:34,840 --> 01:59:39,360 THEY HAVE A POTENTIAL TO BE USED 2654 01:59:39,360 --> 01:59:40,400 IN THE FUTURE. 2655 01:59:40,400 --> 01:59:42,720 THIS IS WHAT WE'VE HEARD THESE 2656 01:59:42,720 --> 01:59:45,840 DAYS THAT GUT MICROBIOME IS VERY 2657 01:59:45,840 --> 01:59:47,040 IMPORTANT FOR US. 2658 01:59:47,040 --> 01:59:51,280 WE CREATE ABOUT 500 GRAMS OF GUT 2659 01:59:51,280 --> 01:59:53,840 MICROBIOTA WITH US. 2660 01:59:53,840 --> 01:59:56,760 EACH INDIVIDUAL HAS A UNIQUE 2661 01:59:56,760 --> 01:59:58,000 COMPOSITION AND THAT IS 2662 01:59:58,000 --> 01:59:59,920 RELATIVELY STABLE OVER TIME BUT 2663 01:59:59,920 --> 02:00:11,160 OF COURSE -- -- ISN' ---ANTIBIOTICS CAN 2664 02:00:11,160 --> 02:00:14,800 HAVE A HUGE EFFECT AND OF COURSE 2665 02:00:14,800 --> 02:00:18,400 DIETS. 2666 02:00:18,400 --> 02:00:24,440 BUT ALSO -- ---THAT -- YOU SEE 2667 02:00:24,440 --> 02:00:31,440 DISTANT MICR -- ---THERE ARE MANY 2668 02:00:31,440 --> 02:00:32,320 DEFINITIONS. 2669 02:00:32,320 --> 02:00:35,520 BUT IT COMES BACK TO THAT YOU 2670 02:00:35,520 --> 02:00:37,280 INGEST LIVE MICROBES AND THEY 2671 02:00:37,280 --> 02:00:39,320 HAVE ACTIVITY IN YOUR INTESTINE 2672 02:00:39,320 --> 02:00:42,720 THAT IS SUPPOSED TO BE 2673 02:00:42,720 --> 02:00:48,520 BENEFICIAL AND SOME STUDIES HAVE 2674 02:00:48,520 --> 02:00:49,800 SHOWN THE RESTRAINTS. 2675 02:00:49,800 --> 02:00:52,120 BUT IF YOU LOOK AT THE CURRENT 2676 02:00:52,120 --> 02:00:53,840 STRAIN COLLECTIONS THE MAJORITY 2677 02:00:53,840 --> 02:00:57,840 IS DERIVED FROM FOOD AND FOOD 2678 02:00:57,840 --> 02:01:01,720 COMPONENTS BECAUSE OF THE -- 2679 02:01:01,720 --> 02:01:04,240 THAT WE CAN SAFELY USE THEM. 2680 02:01:04,240 --> 02:01:06,680 BUT THEY ARE SELECTED ON 2681 02:01:06,680 --> 02:01:07,560 SCALABILITY. 2682 02:01:07,560 --> 02:01:09,240 BECAUSE WHERE YOU HAVE TO MARKET 2683 02:01:09,240 --> 02:01:10,720 THEM YOU HAVE TO DELIVER THEM IN 2684 02:01:10,720 --> 02:01:11,640 BIG AMOUNTS. 2685 02:01:11,640 --> 02:01:13,160 SO THEY HAVE TO BE CULTURED AND 2686 02:01:13,160 --> 02:01:15,840 THEREFORE MANY OF THEM ARE -- 2687 02:01:15,840 --> 02:01:18,640 TOLERANT. 2688 02:01:18,640 --> 02:01:22,840 OR SOMETIMES EVEN -- -- ---OR 2689 02:01:22,840 --> 02:01:24,720 EVEN SOME YEAST. 2690 02:01:24,720 --> 02:01:28,880 BUT WE'VE ALSO SEEN THAT THAT 2691 02:01:28,880 --> 02:01:32,080 THE EFFICACY IN TRIALS IT IS NOT 2692 02:01:32,080 --> 02:01:34,640 CONSISTENT AND ALSO -- -- 2693 02:01:34,640 --> 02:01:37,400 DISEASES YOU SEE THE PRO-BIOTICS 2694 02:01:37,400 --> 02:01:40,680 ARE NOT REALLY HELPFUL OR CANNOT 2695 02:01:40,680 --> 02:01:43,680 DO -- -- THE ACTIVITY THAT'S YOU 2696 02:01:43,680 --> 02:01:44,360 HOPE FOR. 2697 02:01:44,360 --> 02:01:48,400 BUT WE ALSO KNOW THAT -- THERE 2698 02:01:48,400 --> 02:01:50,760 ARE MANY MICROBIOMES THAT HAVE 2699 02:01:50,760 --> 02:01:51,480 BEEN ASSOCIATED. 2700 02:01:51,480 --> 02:01:54,960 SO THERE IS A NEED FOR WHAT WE 2701 02:01:54,960 --> 02:01:56,200 CALL NEXT GENERATION PRO-BIOTICS 2702 02:01:56,200 --> 02:01:59,160 AND THAT IS WHY IN 2019 WE 2703 02:01:59,160 --> 02:02:02,920 ASSEMBLED A CONSORTIUM THAT WE 2704 02:02:02,920 --> 02:02:05,440 FOCUSED ON. 2705 02:02:05,440 --> 02:02:07,760 THE RESTRAINTS OF THE 2706 02:02:07,760 --> 02:02:09,560 MICROBIOMES IN THAT WE HAVE IN 2707 02:02:09,560 --> 02:02:14,240 THE GUT. 2708 02:02:14,240 --> 02:02:16,560 AND THE CONSORTIUM IS BASED ON 2709 02:02:16,560 --> 02:02:24,600 THE NUMBER OF ENTERPRISES -- -- 2710 02:02:24,600 --> 02:02:33,920 AND -- WE STUDY DIFFERENT 2711 02:02:33,920 --> 02:02:35,400 ASPECTS OF THIS FOR EXAMPLE 2712 02:02:35,400 --> 02:02:37,240 GENERATION OF PRO-BIOTICS 2713 02:02:37,240 --> 02:02:37,680 CANDIDATES. 2714 02:02:37,680 --> 02:02:41,640 7 AND NEXT GENERATION 2715 02:02:41,640 --> 02:02:43,880 PRO-BIOTICS THAT ARE -- HUMAN 2716 02:02:43,880 --> 02:02:46,080 DERIVED BACTERIA THEY'VE BEEN 2717 02:02:46,080 --> 02:02:48,520 ASSOCIATED WITH A VARIETY OF 2718 02:02:48,520 --> 02:03:00,040 BENEFICIAL HEALTH EFFECTS. 2719 02:03:00,040 --> 02:03:03,640 AND THE SAME IS FOR -- WHICH WAS 2720 02:03:03,640 --> 02:03:05,720 MENTIONED BEFORE. 2721 02:03:05,720 --> 02:03:12,960 BUT YOU CAN LOOK AT -- EQOUL 2722 02:03:12,960 --> 02:03:13,440 PRODUCERS. 2723 02:03:13,440 --> 02:03:15,200 AND THE SAME OF THIS PROJECT IS 2724 02:03:15,200 --> 02:03:18,800 THAT WE ISOLATE AND CORRECT -- 2725 02:03:18,800 --> 02:03:21,960 FROM THE HUMAN INTESTINE THAT 2726 02:03:21,960 --> 02:03:24,040 CAN BE USED IN THE NEXT 2727 02:03:24,040 --> 02:03:26,160 GENERATION OF PRO-BIOTIC. 2728 02:03:26,160 --> 02:03:27,400 THERE ARE SOME THINGS THAT YOU 2729 02:03:27,400 --> 02:03:29,520 HAVE TO KEEP IN MIND AND I'LL 2730 02:03:29,520 --> 02:03:30,880 BRIEFLY DISCUSS THEM AND THE 2731 02:03:30,880 --> 02:03:34,760 FIRST THING IS THAT YOU -- DEAL 2732 02:03:34,760 --> 02:03:37,640 WITH ANAEROBIC MICROORGANISMS. 2733 02:03:37,640 --> 02:03:39,520 YOU HAVE TO ISOLATE THEM. 2734 02:03:39,520 --> 02:03:43,640 AND THEN YOU WANT TO KNOW THEIR 2735 02:03:43,640 --> 02:03:46,240 ACTIVITY IN THE INTESTINE. 2736 02:03:46,240 --> 02:03:48,120 SAFETY ISSUES IN ORDER TO MARKET 2737 02:03:48,120 --> 02:03:50,160 THEM AND THEN PRODUCE THEM IN 2738 02:03:50,160 --> 02:03:53,840 LARGE SCALE AND WHAT MAKES ITS 2739 02:03:53,840 --> 02:03:56,240 COMPLEX IS THAT YOU NEED WAYS OF 2740 02:03:56,240 --> 02:03:59,440 STORING AND PACKAGING THEM AND 2741 02:03:59,440 --> 02:04:04,480 THAT IS SOME CHALLENGES. 2742 02:04:04,480 --> 02:04:08,000 -- FORGETTING THE ISOLATES THIS 2743 02:04:08,000 --> 02:04:11,680 IS THE WORK OF THE -- -- THE 2744 02:04:11,680 --> 02:04:14,440 APPROACH WHICH IS REALLY NICE 2745 02:04:14,440 --> 02:04:16,000 APPROACH WHERE YOU TRY TO 2746 02:04:16,000 --> 02:04:18,880 ISOLATE AS MANY AS POSSIBLE IN 2747 02:04:18,880 --> 02:04:21,560 THE -- HIGH THROUGH PUTNAMER AND 2748 02:04:21,560 --> 02:04:25,520 IT STARTS WITH USING -- A MEDIAN 2749 02:04:25,520 --> 02:04:29,360 THAT ALLOWSES MANY DIFFERENT 2750 02:04:29,360 --> 02:04:31,480 MICROBES TO GROW AND PICK UP THE 2751 02:04:31,480 --> 02:04:34,600 COLONIES AND IDENTIFY THEM -- 2752 02:04:34,600 --> 02:04:38,840 BUT ALSO FOLLOWED BY -- -- 2753 02:04:38,840 --> 02:04:43,400 SEQUENCE WHICH ENABLE YOU TO GET 2754 02:04:43,400 --> 02:04:48,240 AN IDEA -- AND IN THAT GROUP 2755 02:04:48,240 --> 02:04:50,640 THEY'VE MORE THAN A THOUSAND 2756 02:04:50,640 --> 02:04:54,840 ISOLATES FROM FECAL SAMPLES WITH 2757 02:04:54,840 --> 02:04:57,600 A LOT OF BACTERIA. 2758 02:04:57,600 --> 02:05:00,000 A HUGE DIVERSE COLLECTION. 2759 02:05:00,000 --> 02:05:02,760 THEY HAVE A LARGE COLLECTION OF 2760 02:05:02,760 --> 02:05:05,200 -- THE STRAINS WHICH WE SEE AS A 2761 02:05:05,200 --> 02:05:07,560 MODEL ORGANISMS FOR OUR PROJECT. 2762 02:05:07,560 --> 02:05:11,960 7 WELL IN OUR GROUP WE HAVE 2763 02:05:11,960 --> 02:05:15,400 ANOTHER WAY OF -- ISOLATING 2764 02:05:15,400 --> 02:05:18,240 MICROBES AND THAT IS A TARGETED 2765 02:05:18,240 --> 02:05:18,840 APPROACH. 2766 02:05:18,840 --> 02:05:22,640 WE TRY TO ENRICH MICROBES BASED 2767 02:05:22,640 --> 02:05:24,840 ON A FUNCTION. 2768 02:05:24,840 --> 02:05:26,640 8 AND SOME PREVIOUS WORK THAT 2769 02:05:26,640 --> 02:05:31,360 WE'VE DONE WAS FIRST WHEN I WAS 2770 02:05:31,360 --> 02:05:35,280 A STUDENT I WAS ABLE TO ISOLATE 2771 02:05:35,280 --> 02:05:41,600 AN ORGANISM -- WHICH -- ENDED UP 2772 02:05:41,600 --> 02:05:45,000 BEING AN ISOLATE FROM A PHYLUM 2773 02:05:45,000 --> 02:05:47,080 THAT WAS NOT KNOWN YET. 2774 02:05:47,080 --> 02:05:50,840 BUT WE HAVE 96 SAMPLES WHICH WAS 2775 02:05:50,840 --> 02:05:54,040 ISOLATED FROM TARGETING FROM 2776 02:05:54,040 --> 02:05:57,520 MUCUS -- IT WAS BEEN FREQUENTLY 2777 02:05:57,520 --> 02:06:03,520 STUDIED. 2778 02:06:03,520 --> 02:06:05,840 TRIALS HAVE BEEN ONGOING AND 2779 02:06:05,840 --> 02:06:07,560 IT'S TOWARDS LET'S SAY ONE OF 2780 02:06:07,560 --> 02:06:09,840 THE NEXT GENERATION OF 2781 02:06:09,840 --> 02:06:24,080 PRO-BIOTICS. 2782 02:06:24,080 --> 02:06:33,640 IT WAS RECENTLY ISOLATED -- LICE LICE 2783 02:06:33,640 --> 02:06:43,440 IN. 2784 02:06:43,440 --> 02:06:45,200 -- AND TO SEE THEIR POTENTIAL 2785 02:06:45,200 --> 02:06:50,320 FOR THIS NOVEL NEXT GENERATION 2786 02:06:50,320 --> 02:06:53,240 PRO-BIOTICS. 2787 02:06:53,240 --> 02:06:55,880 IN THIS PROJECT WE ALSO LOOKED 2788 02:06:55,880 --> 02:06:59,240 AT -- CAPACITY AND WHAT WE DID 2789 02:06:59,240 --> 02:07:02,360 HERE WAS WE USED ONE TYPE OF 2790 02:07:02,360 --> 02:07:05,800 MEDIUM AND WE ADDED A SINGLE OR 2791 02:07:05,800 --> 02:07:09,560 A MIX OF -- CARBON AND ENERGY 2792 02:07:09,560 --> 02:07:12,320 SOURCES THAT I BELIEVED WERE 2793 02:07:12,320 --> 02:07:15,160 ABLE TO -- IN THE BEAUT RATE 2794 02:07:15,160 --> 02:07:15,600 PRODUCTION. 2795 02:07:15,600 --> 02:07:28,240 AND ALSO PH CAN HAVE AN EFFECT. 2796 02:07:28,240 --> 02:07:31,000 WHEN YOU LOOK AT BUTYRATE 2797 02:07:31,000 --> 02:07:33,640 PRODUCTION, IT WAS REPORTED -- 2798 02:07:33,640 --> 02:07:35,760 THAT YOU HAVE LOWER PH BUT WE 2799 02:07:35,760 --> 02:07:37,040 DID NOT SEE THAT. 2800 02:07:37,040 --> 02:07:41,880 WE SAW -- AN -- EFFECT ON THE PH 2801 02:07:41,880 --> 02:07:47,720 AND ALSO THE -- YOU SEE 2802 02:07:47,720 --> 02:07:48,640 DIFFERENCE THIS IS SOMETHING 2803 02:07:48,640 --> 02:07:50,480 THAT WE'RE WORKING ON AND WE'RE 2804 02:07:50,480 --> 02:07:53,520 TRYING TO ISOLATE SOME OF THESE 2805 02:07:53,520 --> 02:07:54,720 THAT WERE ENRICHED HERE. 2806 02:07:54,720 --> 02:07:57,880 AND NOW I WANT TO COME BACK TO 2807 02:07:57,880 --> 02:07:58,880 THE STRAIN COLLECTION THAT WE 2808 02:07:58,880 --> 02:08:02,680 HAVE IN OUR CONSORTIUM AND FOCUS 2809 02:08:02,680 --> 02:08:04,200 ON THIS. 2810 02:08:04,200 --> 02:08:08,080 AND -- I FIND IT NICE TO SHOW 2811 02:08:08,080 --> 02:08:10,360 SOME MICROSCOPIC PICTURES. 2812 02:08:10,360 --> 02:08:13,000 YOU SEE TWO STRAINS IN THE TWO 2813 02:08:13,000 --> 02:08:15,840 PICTURES AND YOU CAN SEE HOW 2814 02:08:15,840 --> 02:08:18,400 COMPLETELY DIFFERENT THEY LOOK. 2815 02:08:18,400 --> 02:08:20,400 IF YOU WOULD HAVE SAID THESE 2816 02:08:20,400 --> 02:08:22,400 WERE TWO DIFFERENT SPECIES 2817 02:08:22,400 --> 02:08:23,840 PEOPLE WOULD HAVE BELIEVED ME 2818 02:08:23,840 --> 02:08:25,880 BUT THESE ARE TWO STRAINS OF THE 2819 02:08:25,880 --> 02:08:27,080 SAME SPECIES. 2820 02:08:27,080 --> 02:08:29,480 SO I BELIEVE THAT THE STRAIN 2821 02:08:29,480 --> 02:08:31,520 DIVERSITY IS VERY IMPORTANT AND 2822 02:08:31,520 --> 02:08:34,960 WHEN YOU CULTIVATE THEM -- AND 2823 02:08:34,960 --> 02:08:37,280 HARVEST THEM AFTER 24 HOURS YOU 2824 02:08:37,280 --> 02:08:39,840 SEE THE METABOLIC PATHWAYS ARE 2825 02:08:39,840 --> 02:08:40,480 DIFFERENT. 2826 02:08:40,480 --> 02:08:42,360 WITH THE SECOND STRAIN PRODUCING 2827 02:08:42,360 --> 02:08:44,440 MUCH MORE BUTYRATE THAN THE 2828 02:08:44,440 --> 02:08:48,080 FIRST STRAIN. 2829 02:08:48,080 --> 02:08:49,240 INDICATING THE HUGE DIFFERENCE 2830 02:08:49,240 --> 02:08:51,840 IN THE CAPACITY OF JUST THE SAME 2831 02:08:51,840 --> 02:08:53,320 SPECIES BUT TWO DIFFERENT 2832 02:08:53,320 --> 02:08:53,920 STRAINS. 2833 02:08:53,920 --> 02:08:55,520 ONE EXPERIMENT THAT WE PERFORMED 2834 02:08:55,520 --> 02:08:57,160 IS THAT WE LOOKED AT WHAT 2835 02:08:57,160 --> 02:09:00,440 HAPPENS IF THE -- WE ADD THEM TO 2836 02:09:00,440 --> 02:09:03,280 THE FECAL -- CAN THEY ADAPT TO A 2837 02:09:03,280 --> 02:09:08,600 NEW ECOSYSTEM OR ARE THEY UNABLE 2838 02:09:08,600 --> 02:09:13,760 TO -- IN THESE COMMUNITIES. 2839 02:09:13,760 --> 02:09:16,680 WE -- THE SAME CONDITIONS. 2840 02:09:16,680 --> 02:09:27,360 WE MIMIX EDIT. 2841 02:09:27,360 --> 02:09:34,960 AND AND YOU CAN SEE THE PICTURES 2842 02:09:34,960 --> 02:09:38,160 -- YOU CLEARLY SEE THE 2843 02:09:38,160 --> 02:09:39,840 INDIVIDUALITY ON THE -- 2844 02:09:39,840 --> 02:09:41,520 PRODUCTION BUT YOU SEE COMPARED 2845 02:09:41,520 --> 02:09:43,320 TO CONTROLS YOU DO NOT SEE A LOT 2846 02:09:43,320 --> 02:09:45,280 OF DIFFERENCES. 2847 02:09:45,280 --> 02:09:48,200 THAT IS SOMETHING THAT YOU DON'T 2848 02:09:48,200 --> 02:09:52,120 EXPECT -- BUT WHAT WE'RE NOW 2849 02:09:52,120 --> 02:09:55,120 TRYING TO SEE IS THE FOLLOWING 2850 02:09:55,120 --> 02:09:58,840 -- AND THAT IS BASED ON LET'S 2851 02:09:58,840 --> 02:10:02,320 SAY IN THE NICE PAPER FROM THE 2852 02:10:02,320 --> 02:10:04,760 GROUP THAT WAS PUBLISHED 2853 02:10:04,760 --> 02:10:05,200 RECENTLY. 2854 02:10:05,200 --> 02:10:08,480 YOU CAN CLASSIFY THEM IN THE 2855 02:10:08,480 --> 02:10:10,360 INTESTINE IN FOUR GROUPS. 2856 02:10:10,360 --> 02:10:13,240 BASED ON WHETHER THEY OCCUPY THE 2857 02:10:13,240 --> 02:10:16,840 NICHE OR IF THEY ARE ACTIVE. 2858 02:10:16,840 --> 02:10:19,640 WHICH IS SHOWN IN THIS PICTURE 2859 02:10:19,640 --> 02:10:23,400 -- WITH THE ORGANISMS -- -- AND 2860 02:10:23,400 --> 02:10:25,440 THE METABOLIC CAPACITY OR THEY 2861 02:10:25,440 --> 02:10:29,680 CAN BE -- -- AND HARDLY DO 2862 02:10:29,680 --> 02:10:30,120 ANYTHING. 2863 02:10:30,120 --> 02:10:40,440 8 CLEARLY FROM THE -- AT TH ---METABOLIC 2864 02:10:40,440 --> 02:10:42,760 LEVEL THEY ARE ON THE LOW LEVEL 2865 02:10:42,760 --> 02:10:45,840 BUT WE DON'T KNOW IF THEY ARE IN 2866 02:10:45,840 --> 02:10:47,680 HIGH NUMBERS OR LOW NUMBERS AND 2867 02:10:47,680 --> 02:10:48,840 THAT IS SOMETHING THAT WE STILL 2868 02:10:48,840 --> 02:10:50,960 HAVE TO FIND OUT BECAUSE MAYBE 2869 02:10:50,960 --> 02:10:54,000 THIS STRAINS TAKE OVER IN AN 2870 02:10:54,000 --> 02:10:55,840 EXISTING -- BACTERIA THAT IS IN 2871 02:10:55,840 --> 02:10:59,280 THE INTESTINE OF THE ORIGINAL 2872 02:10:59,280 --> 02:11:00,480 SAMPLE. 2873 02:11:00,480 --> 02:11:01,400 BUT THAT IS SOMETHING THINGS 2874 02:11:01,400 --> 02:11:03,160 THAT WE DON'T KNOW AND WE HAVE 2875 02:11:03,160 --> 02:11:05,000 TO STILL STUDY. 2876 02:11:05,000 --> 02:11:08,160 OTHER THINGS THAT WE ARE 2877 02:11:08,160 --> 02:11:09,240 STUDYING IS OF COURSE WHAT IS 2878 02:11:09,240 --> 02:11:11,240 THE IMPACT OF THE STRAINS AND 2879 02:11:11,240 --> 02:11:14,120 THE METABOLITES ON WHOLE CELL 2880 02:11:14,120 --> 02:11:15,640 VIABILITY AND ACTIVITY. 2881 02:11:15,640 --> 02:11:19,640 THAT IS DONE BY FECAL CELL -- 2882 02:11:19,640 --> 02:11:24,040 AND WE WANT TO KNOW WHAT IS THE 2883 02:11:24,040 --> 02:11:34,880 ANTIBIOTIC RESISTANCE PROFILE. 2884 02:11:34,880 --> 02:11:37,640 SO THESE ARE ALL MORE TYPE OF 2885 02:11:37,640 --> 02:11:39,080 SAFETY THINGS THAT YOU HAVE TO 2886 02:11:39,080 --> 02:11:40,440 CONSIDER WHEN YOU WANT TO 2887 02:11:40,440 --> 02:11:42,600 GENERATE THE NEXT GENERATION 2888 02:11:42,600 --> 02:11:43,760 PRO-BIOTICS. 2889 02:11:43,760 --> 02:11:45,760 OTHER THINGS TO CONSIDER IS OF 2890 02:11:45,760 --> 02:11:48,080 COURSE THE PRODUCTION -- THAT 2891 02:11:48,080 --> 02:11:51,200 YOU NORMALLY WHEN WE STUDY THESE 2892 02:11:51,200 --> 02:11:57,160 MICROBES WE HAVE A MAXIMUM OF 2893 02:11:57,160 --> 02:12:04,880 50. 2894 02:12:04,880 --> 02:12:07,360 AND THE QUESTION IS OF COURSE DO 2895 02:12:07,360 --> 02:12:11,520 THE STRAINS BEHAVE THE SAME. 2896 02:12:11,520 --> 02:12:16,160 BECAUSE -- ANAEROBIC MICROBES 2897 02:12:16,160 --> 02:12:21,240 DON'T LIKE TO BE SHAKEN. 2898 02:12:21,240 --> 02:12:22,600 AND THIS IS SOMETHING THAT WE 2899 02:12:22,600 --> 02:12:25,960 WILL STUDY OF COURSE. 2900 02:12:25,960 --> 02:12:28,640 WHEN -- LONG TIME FOR HUMAN 2901 02:12:28,640 --> 02:12:31,480 CONSUMPTION YOU CANNOT USE AN 2902 02:12:31,480 --> 02:12:34,080 UNDEFINED MEDIUM SO YOU NEED TO 2903 02:12:34,080 --> 02:12:36,640 DEFINE A MEDIUM WITH SAFE 2904 02:12:36,640 --> 02:12:39,200 COMPONENTS AND THAT IS SOMETIMES 2905 02:12:39,200 --> 02:12:41,600 NOT EASY TO DO WHERE YOU HAVE 2906 02:12:41,600 --> 02:12:43,720 ISOLATES BECAUSE YOU HAVE NO 2907 02:12:43,720 --> 02:12:45,240 KNOW WHAT THEY NEED FOR THE 2908 02:12:45,240 --> 02:12:46,240 GROWTH ENVIRONMENT AND THAT IS 2909 02:12:46,240 --> 02:12:48,800 QUITE A LOT OF TESTING. 2910 02:12:48,800 --> 02:12:50,000 AND THEN OF COURSE IF YOU WANT 2911 02:12:50,000 --> 02:12:53,760 TO PUT THEM ON THE MARKET THERE 2912 02:12:53,760 --> 02:12:59,800 ARE STRICT -- HOW CAN WE PACKAGE 2913 02:12:59,800 --> 02:13:02,720 THEM AND HOW CAN THEY SURVIVE ON 2914 02:13:02,720 --> 02:13:05,840 THE SHELF OR EVEN WHEN THEY PASS 2915 02:13:05,840 --> 02:13:07,960 THE INTESTINE SO THESE ARE ALL 2916 02:13:07,960 --> 02:13:11,160 QUESTIONS THAT WE ARE STILL 2917 02:13:11,160 --> 02:13:12,720 BRAINSTORMING ABOUT AND DOING 2918 02:13:12,720 --> 02:13:15,560 THE FIRST EXPERIMENTS ABOUT WHAT 2919 02:13:15,560 --> 02:13:16,600 WE CAN DO HERE. 2920 02:13:16,600 --> 02:13:22,640 IN SUMMARY I THINK I SHOW THAT 2921 02:13:22,640 --> 02:13:24,760 -- A NICE SUCCESSFUL COLLECTION 2922 02:13:24,760 --> 02:13:29,160 OF MICROBES AND APPROACHES TO 2923 02:13:29,160 --> 02:13:31,400 HAVE SOME -- THAT ARE PROMISING 2924 02:13:31,400 --> 02:13:33,520 IN THE NexGenATION 2925 02:13:33,520 --> 02:13:33,960 PRO-BIOTICS. 2926 02:13:33,960 --> 02:13:38,040 THE PATH TO GET FROM AN ISOLATE 2927 02:13:38,040 --> 02:13:41,760 -- -- HAS SOME CHALLENGES. 2928 02:13:41,760 --> 02:13:44,840 78 ESPECIALLY SINCE THEY ARE 2929 02:13:44,840 --> 02:13:47,360 OFTEN ANAEROBIC. 2930 02:13:47,360 --> 02:13:52,560 AND THE FIRST SELECTION -- IS 2931 02:13:52,560 --> 02:13:54,320 NOW TAKEN AND VERY EXCITED ABOUT 2932 02:13:54,320 --> 02:13:58,240 IT AND ALSO IT'S NICE ALSO FROM 2933 02:13:58,240 --> 02:14:00,600 THE EXPERIENCE TO LEARN ABOUT 2934 02:14:00,600 --> 02:14:04,760 MICROBES ITSELF BECAUSE I FEELY 2935 02:14:04,760 --> 02:14:06,120 AGREE THAT IN ORDER TO 2936 02:14:06,120 --> 02:14:09,720 UNDERSTAND THE GUT MICROBIOME UM 2937 02:14:09,720 --> 02:14:12,720 WE NEED TO UNDERSTAND WHY WE 2938 02:14:12,720 --> 02:14:15,920 HAVE CERTAIN STRAINS PRESENT IN 2939 02:14:15,920 --> 02:14:19,800 SOME AND NOT OTHERS AND DIVE 2940 02:14:19,800 --> 02:14:21,240 INTO THIS TO UNDERSTAND WHAT IS 2941 02:14:21,240 --> 02:14:24,000 HAPPENING IN OUR GUT. 2942 02:14:24,000 --> 02:14:27,200 AND MY LAST SLIDE I WANT TO 2943 02:14:27,200 --> 02:14:28,760 THANK ALL OF THE PEOPLE WHO WERE 2944 02:14:28,760 --> 02:15:00,840 INVOLVED IN THE STUDY. 2945 02:15:00,840 --> 02:15:03,400 I WOULD LIKE TO THANK YOU FOR 2946 02:15:03,400 --> 02:15:05,840 YOUR ATTENTION AND WILL BE HAPPY 2947 02:15:05,840 --> 02:15:08,080 TO ADDRESS QUESTIONS. 2948 02:15:08,080 --> 02:15:10,200 >> THANK YOU, THAT WAS A VERY 2949 02:15:10,200 --> 02:15:20,560 NICE TALK. 2950 02:15:20,560 --> 02:15:22,800 SO NOW WE'LL MOVE ON TO THE LAST 2951 02:15:22,800 --> 02:15:29,240 BUT NOT THE LEAST TALK FROM 2952 02:15:29,240 --> 02:15:31,480 DR. RUSTEM ISMAGILOV AND HE WILL 2953 02:15:31,480 --> 02:15:33,400 BE TALKING ABOUT SMALL INTESTINE 2954 02:15:33,400 --> 02:15:36,720 AND MICROBES THAT ARE ESSENTIAL 2955 02:15:36,720 --> 02:15:45,280 FOR HUMAN HEALTH. 2956 02:15:45,280 --> 02:15:48,280 >> THANK YOU VERY MUCH. 2957 02:15:48,280 --> 02:15:49,840 CAN YOU CONFIRM THAT YOU CAN 2958 02:15:49,840 --> 02:15:52,280 HEAR ME AND SEE THE SCREEN? 2959 02:15:52,280 --> 02:15:52,800 >> YES. 2960 02:15:52,800 --> 02:15:54,600 VERY WELL. 2961 02:15:54,600 --> 02:15:55,000 >> WONDERFUL. 2962 02:15:55,000 --> 02:15:56,640 I'M ABSOLUTELY DELIGHTED TO BE 2963 02:15:56,640 --> 02:15:58,280 HERE AND HONORED TO BE HERE. 2964 02:15:58,280 --> 02:16:00,240 AND EVERYTHING I'M GOING TO SAY 2965 02:16:00,240 --> 02:16:01,440 IS ONLY POSSIBLE BECAUSE OF THE 2966 02:16:01,440 --> 02:16:03,640 GROUP OF TALENTED COLLABORATORS 2967 02:16:03,640 --> 02:16:07,280 IN THE LAB WHO REALLY DO ALL OF 2968 02:16:07,280 --> 02:16:11,400 THIS WORK AND ALSO FABULOUS 2969 02:16:11,400 --> 02:16:13,840 COLLABORATORS THAT WE'VE BEEN 2970 02:16:13,840 --> 02:16:15,520 FORTUNATE TO WORK WITH OVER THE 2971 02:16:15,520 --> 02:16:17,960 YEARS AND I'M EXTREMELY GRATEFUL 2972 02:16:17,960 --> 02:16:19,240 TO ALL OF THEM. 2973 02:16:19,240 --> 02:16:22,080 I WANT TO START OUT BY POINTING 2974 02:16:22,080 --> 02:16:26,080 OUT THE SIMPLE HYPE CYCLE THAT 2975 02:16:26,080 --> 02:16:27,840 APPLIES TO ANY NEW IDEA AND 2976 02:16:27,840 --> 02:16:28,240 TECHNOLOGY. 2977 02:16:28,240 --> 02:16:32,360 IT STARTS OUT AND GETS TO THE 2978 02:16:32,360 --> 02:16:34,240 EXPECTATIONS -- WHERE IT WAS 2979 02:16:34,240 --> 02:16:36,280 GOING TO CURE EVERY POSSIBLE 2980 02:16:36,280 --> 02:16:39,240 DISEASE AND SOLVE ALL KINDS OF 2981 02:16:39,240 --> 02:16:45,040 PROBLEMS AND THEN THE TROUGH OF 2982 02:16:45,040 --> 02:16:45,560 DISALLUSIONMENT. 2983 02:16:45,560 --> 02:16:47,880 AND SO, THAT IS ALL NORMAL AND 2984 02:16:47,880 --> 02:16:50,240 THEN THE REALLY INTERESTING 2985 02:16:50,240 --> 02:16:51,960 USEFUL PART HAPPENS HERE. 2986 02:16:51,960 --> 02:16:54,920 THE SLOPE WHERE YOU START -- 2987 02:16:54,920 --> 02:16:56,120 WHAT IS POSSIBLE AND NOT 2988 02:16:56,120 --> 02:16:57,880 POSSIBLE AND HOW TO GET THERE. 2989 02:16:57,880 --> 02:16:59,560 AND I WOULD LIKE TO ARGUE THAT 2990 02:16:59,560 --> 02:17:01,800 THERE ARE SIX THINGS OR ADD TO 2991 02:17:01,800 --> 02:17:03,760 THIS LIST -- OF THE SIX THINGS 2992 02:17:03,760 --> 02:17:04,920 THAT I THINK ARE REALLY 2993 02:17:04,920 --> 02:17:06,440 IMPORTANT TO KEEP IN MIND AS 2994 02:17:06,440 --> 02:17:08,600 WE'RE CLIMBING UP THE SLOPE AND 2995 02:17:08,600 --> 02:17:10,600 MAKING PROGRESS. 2996 02:17:10,600 --> 02:17:12,440 JUST TO HIGHLIGHT DIFFERENT 2997 02:17:12,440 --> 02:17:14,200 PARTS OF IT AND THE FIRST POINT 2998 02:17:14,200 --> 02:17:17,760 IS IT'S REALLY SMALL INTESTINE 2999 02:17:17,760 --> 02:17:20,520 AND THE GUT MUCOSAL INTERFACE 3000 02:17:20,520 --> 02:17:23,040 THAT WE HAVE TO THINK ABOUT IN 3001 02:17:23,040 --> 02:17:25,120 ADDITION TO POOP. 3002 02:17:25,120 --> 02:17:27,560 IT'S REALLY A SIMPLE ARGUMENT. 3003 02:17:27,560 --> 02:17:31,880 ALL OF THE FOOD AND NUTRITION 3004 02:17:31,880 --> 02:17:34,040 THAT IS PROCESSED IN THE SMALL 3005 02:17:34,040 --> 02:17:35,000 INTESTINE. 3006 02:17:35,000 --> 02:17:36,840 THE FOOD IS ABSORBED HERE. 3007 02:17:36,840 --> 02:17:39,640 THE IMMUNE SYSTEM -- IS HERE AS 3008 02:17:39,640 --> 02:17:40,000 WELL. 3009 02:17:40,000 --> 02:17:42,600 AND IF YOU THINK ABOUT THE 3010 02:17:42,600 --> 02:17:45,120 SURFACE AREA IT'S OF THE SMALL 3011 02:17:45,120 --> 02:17:46,080 ENTRUSTMENT. 3012 02:17:46,080 --> 02:17:47,440 ABOUT 30 SQUARE METERS. 3013 02:17:47,440 --> 02:17:50,800 ABOUT THE SURFACE AREA OF A 3014 02:17:50,800 --> 02:17:51,840 TENNIS COURT. 3015 02:17:51,840 --> 02:17:53,720 IT'S ABSOLUTELY CRITICAL. 3016 02:17:53,720 --> 02:17:55,320 TO BE THINKING ABOUT THIS PART 3017 02:17:55,320 --> 02:17:57,240 OF THE SYSTEM NOT ONLY WHAT 3018 02:17:57,240 --> 02:18:00,440 COMES OUT HERE. 3019 02:18:00,440 --> 02:18:02,760 ALONG THESE LINES IF YOU WANT TO 3020 02:18:02,760 --> 02:18:04,800 THINK ABOUT HUMAN SMALL 3021 02:18:04,800 --> 02:18:06,240 INTESTINE YOU HAVE TO BE CAREFUL 3022 02:18:06,240 --> 02:18:08,640 WITH INTERPRETING MOUSE MODEL 3023 02:18:08,640 --> 02:18:09,280 RESULTS. 3024 02:18:09,280 --> 02:18:12,360 BECAUSE THEY EAT THEIR OWN POOP. 3025 02:18:12,360 --> 02:18:14,800 IT'S BEEN KNOWN FOR VERY LONG 3026 02:18:14,800 --> 02:18:18,000 TIME 50 YEARS OR MORE THAT THERE 3027 02:18:18,000 --> 02:18:19,320 ARE OLD PAPERS THAT DESCRIBE 3028 02:18:19,320 --> 02:18:22,840 THIS THAT EVEN IN THE STROMS OF 3029 02:18:22,840 --> 02:18:24,640 RODENTS THEY HAVE A VERY HIGH 3030 02:18:24,640 --> 02:18:26,720 LOAD AND IT DOESN'T DROP VERY 3031 02:18:26,720 --> 02:18:30,920 MUCH AND HUMANS -- YOUNG HEALTHY 3032 02:18:30,920 --> 02:18:34,440 HUMANS ARE DIFFERENT. 3033 02:18:34,440 --> 02:18:35,520 VERY LOW LOAD. 3034 02:18:35,520 --> 02:18:38,400 7 THAT IS KEY FOR US TO KEEP IN 3035 02:18:38,400 --> 02:18:41,000 MIND AS YOU CAN IMAGINE. 3036 02:18:41,000 --> 02:18:46,760 AND I ALSO WANT TO EMPHASIZE -- 3037 02:18:46,760 --> 02:18:49,160 ONE POINT HERE IS OF COURSE THIS 3038 02:18:49,160 --> 02:18:51,560 CAN BE -- OLD LITERATURE OF HOW 3039 02:18:51,560 --> 02:18:52,320 TO DO IT. 3040 02:18:52,320 --> 02:18:55,160 IT'S NOT WHAT WE DO NOW -- 3041 02:18:55,160 --> 02:18:57,480 DEVELOPED REALLY IMPORTANT WAY 3042 02:18:57,480 --> 02:19:02,640 OF TESTING THESE HYPOTHESIS BY 3043 02:19:02,640 --> 02:19:06,880 DEVELOPING THESE MECHANICAL TAIL 3044 02:19:06,880 --> 02:19:10,240 CUPS THAT PREVENT THE MICE FROM 3045 02:19:10,240 --> 02:19:12,040 EATING THEIR POOP. 3046 02:19:12,040 --> 02:19:14,000 AND WHAT IS NOT SHOWN HERE BUT 3047 02:19:14,000 --> 02:19:16,080 SHOWN IN THE PAPER -- WHICH I 3048 02:19:16,080 --> 02:19:18,520 ENCOURAGE TO YOU READ IS THAT 3049 02:19:18,520 --> 02:19:20,840 THE MICROBIOTA LOOKS VERY MUCH 3050 02:19:20,840 --> 02:19:23,440 MORE LIKE HUMAN. 3051 02:19:23,440 --> 02:19:28,040 RATHER THAN FECAL MICR MICROBIOTA IN 3052 02:19:28,040 --> 02:19:28,640 THE MOUSE. 3053 02:19:28,640 --> 02:19:30,640 WHAT IS REALLY IMPORTANT IS THAT 3054 02:19:30,640 --> 02:19:34,760 THE -- PROFILES COMPLETELY 3055 02:19:34,760 --> 02:19:37,000 DIFFERENT IN THESE MICE. 3056 02:19:37,000 --> 02:19:38,640 AND THE STANDARD APPROACH IS 3057 02:19:38,640 --> 02:19:43,440 SINGLE HOUSING OR WIRE FLOORS 3058 02:19:43,440 --> 02:19:47,080 ARE QUITE INEFFECTIVE AT LEAST 3059 02:19:47,080 --> 02:19:48,720 IN OUR HANDS. 3060 02:19:48,720 --> 02:19:53,040 THAT IS NOT A GLAMOROUS BUT 3061 02:19:53,040 --> 02:19:55,360 IMPORTANT RESULT. 3062 02:19:55,360 --> 02:19:58,120 ONE MORE POINT IS IF YOU ARE 3063 02:19:58,120 --> 02:20:00,520 DEALING WITH SYMPTOMS LIKE THIS 3064 02:20:00,520 --> 02:20:02,440 -- WHERE THE LOADS CHANGE BY 3065 02:20:02,440 --> 02:20:05,000 ORDERS OF MAGNITUDE YOU HAVE TO 3066 02:20:05,000 --> 02:20:06,000 BE QUANTITATIVE. 3067 02:20:06,000 --> 02:20:07,800 IT'S NOT ENOUGH TO SAY THAT 3068 02:20:07,800 --> 02:20:09,520 SOMETHING CHANGES FROM 2% TO 3069 02:20:09,520 --> 02:20:10,040 35%. 3070 02:20:10,040 --> 02:20:11,720 WE NEED TO KNOW HOW MUCH. 3071 02:20:11,720 --> 02:20:13,720 LET ME ILLUSTRATE BY A SIMPLE 3072 02:20:13,720 --> 02:20:14,280 POINT. 3073 02:20:14,280 --> 02:20:16,840 WE'RE DOING A STUDY WHERE IN A 3074 02:20:16,840 --> 02:20:20,040 HEALTHY COHORT -- IT'S 50/50 AND 3075 02:20:20,040 --> 02:20:24,440 THEN IN DISEASE IT'S 80/20. 3076 02:20:24,440 --> 02:20:26,080 THIS COULD MEAN LOTS OF THINGS. 3077 02:20:26,080 --> 02:20:31,000 AND IN FACT IT COULD MEAN THAT 3078 02:20:31,000 --> 02:20:34,320 TAX ON A WENT UP AND B DIDN'T 3079 02:20:34,320 --> 02:20:37,360 CHANGE. 3080 02:20:37,360 --> 02:20:39,000 OR IT COULD MEAN THAT BOTH OF 3081 02:20:39,000 --> 02:20:40,400 THEM WENT DOWN. 3082 02:20:40,400 --> 02:20:42,840 JUST THAT B WENT DOWN MORE THAN 3083 02:20:42,840 --> 02:20:43,360 A. 3084 02:20:43,360 --> 02:20:44,840 SO, THAT IS IMPORTANT WHEN 3085 02:20:44,840 --> 02:20:49,240 YOU'RE TRYING TO FORMULATE 3086 02:20:49,240 --> 02:20:55,120 HYPOTHESIS FROM YOUR ANALYSIS. 3087 02:20:55,120 --> 02:21:00,440 SO JUST TO SOLVE THIS PROBLEM -- 3088 02:21:00,440 --> 02:21:03,440 THEY DEVELOPED A NICE METHOD 3089 02:21:03,440 --> 02:21:06,200 THAT ALLOWS YOU TO GET 3090 02:21:06,200 --> 02:21:08,880 QUANTITATIVE SEQUENCING DATA AT 3091 02:21:08,880 --> 02:21:11,240 LOW COST AND LOW EFFORT AND IS 3092 02:21:11,240 --> 02:21:13,920 PRACTICAL. 3093 02:21:13,920 --> 02:21:16,240 THEY'VE CHARACTERIZE EDIT VERY 3094 02:21:16,240 --> 02:21:16,680 WELL. 3095 02:21:16,680 --> 02:21:19,880 IT WORKS IN ORDERS OF MAGNITUDE 3096 02:21:19,880 --> 02:21:21,240 QUANTITATIVELY WITH HIGH 3097 02:21:21,240 --> 02:21:23,440 PRECISION OF ACCURACY AND WHAT 3098 02:21:23,440 --> 02:21:25,760 WAS IMPORTANT * TO KEEP IN MIND 3099 02:21:25,760 --> 02:21:31,120 THAT IT'S NOT A PROBLEM BECAUSE 3100 02:21:31,120 --> 02:21:33,120 HUMAN MITOCHONDRIAL DNA 3101 02:21:33,120 --> 02:21:34,880 OVERLAPS. 3102 02:21:34,880 --> 02:21:37,240 SO THERE IS INTERFERENCE MAKING 3103 02:21:37,240 --> 02:21:45,640 IT DIFFICULT. 3104 02:21:45,640 --> 02:21:47,440 I ENCOURAGE YOU IF YOU'RE 3105 02:21:47,440 --> 02:21:51,200 WORKING WITH SAMPLES TO USE THIS 3106 02:21:51,200 --> 02:21:54,480 METHOD TO LEARN MORE. 3107 02:21:54,480 --> 02:21:57,000 AND OF COURSE I WANT TO 3108 02:21:57,000 --> 02:21:59,120 ILLUSTRATE THIS WITH A COUPLE OF 3109 02:21:59,120 --> 02:22:01,640 EXAMPLES WHEN THINKING ABOUT THE 3110 02:22:01,640 --> 02:22:02,080 HUMAN. 3111 02:22:02,080 --> 02:22:07,200 ANOTHER REALLY NICE ASPECT IS 3112 02:22:07,200 --> 02:22:11,240 BECAUSE WE -- KNOW THE ASPECTS 3113 02:22:11,240 --> 02:22:15,120 OF THE HUMAN MITOCHONDRIAL DNA 3114 02:22:15,120 --> 02:22:19,280 -- -- QUITE LOW MASS CULTURAL 3115 02:22:19,280 --> 02:22:21,760 SAMPLES AND ONE EXAMPLE OF THIS 3116 02:22:21,760 --> 02:22:27,000 WAS -- A COLLABORATION -- IN THE 3117 02:22:27,000 --> 02:22:33,040 LAB -- AND HELPING TO GET 3118 02:22:33,040 --> 02:22:35,480 QUANTITATIVE HIGH QUALITY DATA. 3119 02:22:35,480 --> 02:22:37,920 FROM BIOPSIES FROM THESE 3120 02:22:37,920 --> 02:22:40,480 PATIENTS AND FOUND INTERESTING 3121 02:22:40,480 --> 02:22:43,240 ASSOCIATIONS BETWEEN -- ACTIVE 3122 02:22:43,240 --> 02:22:47,440 BASILLE AS -- * AND CELIAC 3123 02:22:47,440 --> 02:22:48,240 DISEASE. 3124 02:22:48,240 --> 02:22:52,480 THIS IS ALL PUBLICLY AVAILABLE 3125 02:22:52,480 --> 02:23:11,000 AND THERE IS AN PRINTOUT THERE. 3126 02:23:11,000 --> 02:23:12,320 FORTUNATE TO BE ABLE TO WORK 3127 02:23:12,320 --> 02:23:15,000 WITH THEM AND AS YOU PROBABLY 3128 02:23:15,000 --> 02:23:17,640 KNOW THEY HAVE THIS INCREDIBLE 3129 02:23:17,640 --> 02:23:21,480 STUDY WHERE THEY ARE ANALYZING 3130 02:23:21,480 --> 02:23:25,400 MICROBIOTA AND MANY OTHER -- 3131 02:23:25,400 --> 02:23:26,040 THAN HUMANS. 3132 02:23:26,040 --> 02:23:29,720 THIS IS A STUDY OF 250 3133 02:23:29,720 --> 02:23:35,240 MICROBIOMES -- WITH QUANTITATIVE 3134 02:23:35,240 --> 02:23:36,240 MEASUREMENTS WHICH FOUND THERE 3135 02:23:36,240 --> 02:23:38,320 IS A SPREAD OF BACTERIAL LOADS 3136 02:23:38,320 --> 02:23:41,960 IN HUMANS AND YOU AS YOU MAY BE 3137 02:23:41,960 --> 02:23:42,520 WOULD EXPECT. 3138 02:23:42,520 --> 02:23:47,160 8 AND OF COURSE KNOWING THESE 3139 02:23:47,160 --> 02:23:49,560 NUMBERS ARE REALLY IMPORTANT 3140 02:23:49,560 --> 02:23:52,000 BECAUSE WE OFTEN THINK ABOUT A 3141 02:23:52,000 --> 02:23:55,920 REALLY PAY A LOT OF ATTENTION -- 3142 02:23:55,920 --> 02:24:00,760 AND HOW CAN WE NOT PAY ATTENTION 3143 02:24:00,760 --> 02:24:03,120 TO -- SITES REALLY IMPORTANT TO 3144 02:24:03,120 --> 02:24:05,080 THINK ABOUT QUANTITATIVE 3145 02:24:05,080 --> 02:24:07,440 MEASUREMENTS IN THESE CONTEXT. 3146 02:24:07,440 --> 02:24:09,960 THERE IS HUGE DISTRIBUTION OF 3147 02:24:09,960 --> 02:24:13,680 LOADS OF INDIVIDUAL TAX OM. 3148 02:24:13,680 --> 02:24:15,640 AND THAT MANY OF THEM APPEAR TO 3149 02:24:15,640 --> 02:24:20,320 BE ORALLY THRIVED AND IT'S NOT 3150 02:24:20,320 --> 02:24:21,280 CONTAMINATION. 3151 02:24:21,280 --> 02:24:23,080 GONE TO GREAT PAINS TOGETHER TO 3152 02:24:23,080 --> 02:24:25,720 MAKE SURE IT'S NOT THE MODEL OF 3153 02:24:25,720 --> 02:24:26,160 CONTAMINATION. 3154 02:24:26,160 --> 02:24:32,000 8 AND THIS IS DESCRIBED IN THE 3155 02:24:32,000 --> 02:24:33,400 PAPER. 3156 02:24:33,400 --> 02:24:35,440 WE FOUND THIS QUANTITATIVE 3157 02:24:35,440 --> 02:24:39,680 MEASUREMENTS ALLOWED US TO LOOK 3158 02:24:39,680 --> 02:24:42,440 AT NEW TYPES OF ANALYSIS. 3159 02:24:42,440 --> 02:24:44,880 SO-CALLED DISRUPT OR ORGANISMS 3160 02:24:44,880 --> 02:24:48,200 THAT OVER GROW SIGNIFICANTLY -- 3161 02:24:48,200 --> 02:24:50,960 -- AND DISRUPT THE REST OF THE 3162 02:24:50,960 --> 02:24:59,240 MICRMICRO BUYMIKE-- MICROBIOTA. 3163 02:24:59,240 --> 02:25:03,000 AND THERE WAS ANOTHER GROUP OF 3164 02:25:03,000 --> 02:25:04,520 DISRUPTORS THAT ARE RARE BUT 3165 02:25:04,520 --> 02:25:06,640 WHEN THEY HAPPEN THEY HAPPEN AT 3166 02:25:06,640 --> 02:25:09,200 HIGH LEVELS AND ALMOST ALL OF 3167 02:25:09,200 --> 02:25:13,040 THEM WERE -- -- SO REALLY NOT 3168 02:25:13,040 --> 02:25:16,120 SOMETHING THAT WAS -- HOPING TO 3169 02:25:16,120 --> 02:25:18,240 FIND IN THE HUMANS THAT WERE 3170 02:25:18,240 --> 02:25:19,640 WALKING AROUND BUT THAT IS WHAT 3171 02:25:19,640 --> 02:25:22,040 IT IS AND WE HAVE TO TO BE 3172 02:25:22,040 --> 02:25:23,680 THINKING ABOUT HOW THESE KINDS 3173 02:25:23,680 --> 02:25:27,840 OF LIKELY PATHOGENIC ORGANISMS 3174 02:25:27,840 --> 02:25:35,840 AFFECT HUMAN HEALTH. 3175 02:25:35,840 --> 02:25:38,000 AND JUST ONE GLIMPSE OF THESE 3176 02:25:38,000 --> 02:25:40,600 RESULTS WERE WE SHOW THAT AGAIN 3177 02:25:40,600 --> 02:25:45,760 THESE DISRUPT OR O I WILLS BOTH 3178 02:25:45,760 --> 02:25:49,720 DRIVE THE GI SYMPTOMS AND THE 3179 02:25:49,720 --> 02:25:52,160 DETAILS ARE DESCRIBED IN THE 3180 02:25:52,160 --> 02:25:52,640 PAPER. 3181 02:25:52,640 --> 02:25:56,240 AND THAT WAS IN COLLABORATION 3182 02:25:56,240 --> 02:25:58,640 AND -- WONDERFUL STUDY. 3183 02:25:58,640 --> 02:26:00,680 I WANT TO COME BACK TO THE POINT 3184 02:26:00,680 --> 02:26:03,480 THAT GARY WAS MAKING EARLIER 3185 02:26:03,480 --> 02:26:06,240 ABOUT -- BALANCE AND TALK ABOUT 3186 02:26:06,240 --> 02:26:07,640 THIS FOR A SECOND. 3187 02:26:07,640 --> 02:26:10,960 WE DO FIND THAT IN THESE SYSTEMS 3188 02:26:10,960 --> 02:26:16,440 THERE IS A VERY GOOD CONCORDANCE 3189 02:26:16,440 --> 02:26:21,640 BETWEEN AEROBE -- AND THESE ARE 3190 02:26:21,640 --> 02:26:23,640 MIXED COMMUNITIES. 3191 02:26:23,640 --> 02:26:25,720 THIS GETS ME TO THE FOURTH POINT 3192 02:26:25,720 --> 02:26:27,640 THAT IS THE CONTROL OF THESE 3193 02:26:27,640 --> 02:26:29,320 SYSTEMS CAN BE REALLY DIFFICULT 3194 02:26:29,320 --> 02:26:32,640 BECAUSE THEY CAN SHOW BIZARRE 3195 02:26:32,640 --> 02:26:35,920 BEHAVIORS THAT DEFY OUR LOGIC 3196 02:26:35,920 --> 02:26:38,000 AND SCIENTIFIC APPROACH. 3197 02:26:38,000 --> 02:26:45,600 TAMI -- WORKING WITH MANY OTHER 3198 02:26:45,600 --> 02:26:49,000 -- PEOPLE -- DEMONSTRATED THAT 3199 02:26:49,000 --> 02:26:51,840 EVEN SIMPLE COMMUNITIES CAN SHOW 3200 02:26:51,840 --> 02:26:57,400 THIS WEIRD BEHAVIOR -- AND THESE 3201 02:26:57,400 --> 02:27:00,240 SYSTEMS ESSENTIALLY REALLY GET 3202 02:27:00,240 --> 02:27:02,800 STUCK AT HIGH OR LOW LEVEL AND 3203 02:27:02,800 --> 02:27:04,800 THERE IS ALMOST NOTHING THAT YOU 3204 02:27:04,800 --> 02:27:07,240 CAN DO TO PUSH IT BETWEEN THESE 3205 02:27:07,240 --> 02:27:08,920 TWO STATES AND I DON'T HAVE TIME 3206 02:27:08,920 --> 02:27:10,800 TO DESCRIBE IT IN DETAIL BUT 3207 02:27:10,800 --> 02:27:13,520 IT'S PUBLISHED IN THIS PAPER. 3208 02:27:13,520 --> 02:27:15,560 BUT IT HAS IMPORTANT 3209 02:27:15,560 --> 02:27:16,320 IMPLICATIONS ABOUT THINKING 3210 02:27:16,320 --> 02:27:20,640 ABOUT CONTROL AND STUDY OF HUMAN 3211 02:27:20,640 --> 02:27:23,280 MICRMICROBIOTA BECAUSE CONTROL IS 3212 02:27:23,280 --> 02:27:23,840 DIFFICULT. 3213 02:27:23,840 --> 02:27:25,840 THERE IS ALMOST NOTHING THAT CAN 3214 02:27:25,840 --> 02:27:27,520 GET YOU TO PUSH THE SYSTEM 3215 02:27:27,520 --> 02:27:29,080 BETWEEN THESE TWO STATES UNLESS 3216 02:27:29,080 --> 02:27:32,080 YOU TAKE IT WAY OUTSIDE AND THE 3217 02:27:32,080 --> 02:27:34,080 SCIENTIFIC STUDY BECOMES VERY 3218 02:27:34,080 --> 02:27:36,440 DIFFICULT BECAUSE SMALL 3219 02:27:36,440 --> 02:27:39,440 PROHIBITIONS IN A WE DOO-DOO 3220 02:27:39,440 --> 02:27:40,640 NOTHING AND WE'LL MISS THE 3221 02:27:40,640 --> 02:27:44,160 IMPORTANT FACTORS THAT CONTROL 3222 02:27:44,160 --> 02:27:47,000 THE SYSTEMS FOR THIS REASON. 3223 02:27:47,000 --> 02:27:48,760 *. 3224 02:27:48,760 --> 02:27:53,040 DEMONSTRATED THAT -- THAT THESE 3225 02:27:53,040 --> 02:27:59,800 ARISE FROM CARBON/OXYGEN 3226 02:27:59,800 --> 02:28:00,040 BALANCE. 3227 02:28:00,040 --> 02:28:00,800 NEED TO UNDERSTAND WHAT WAS 3228 02:28:00,800 --> 02:28:02,680 HAPPENING AND IT'S NOT ENOUGH TO 3229 02:28:02,680 --> 02:28:04,680 HAVE NAMES OF MICROBES. 3230 02:28:04,680 --> 02:28:06,920 WE NEED TO HAVE GENOMES AND HAVE 3231 02:28:06,920 --> 02:28:07,920 MORE MUCH INFORMATION. 3232 02:28:07,920 --> 02:28:09,440 AND THAT IS CHALLENGING. 3233 02:28:09,440 --> 02:28:11,400 THERE IS GREAT WORK THAT HAS 3234 02:28:11,400 --> 02:28:14,320 BEEN DUNGEONING TO GET METRO 3235 02:28:14,320 --> 02:28:21,840 GENOMES OUT OF POOP AND 90% -- 3236 02:28:21,840 --> 02:28:23,720 HOWEVER IF IT'S SOMETHING THAT A 3237 02:28:23,720 --> 02:28:25,760 BIOPSY THAT THE LAB CAN OBTAIN 3238 02:28:25,760 --> 02:28:29,640 FROM A PATIENT -- AND IT'S 3239 02:28:29,640 --> 02:28:31,840 MOSTLY HOST AND THIS IS 3240 02:28:31,840 --> 02:28:33,720 TECHNICALLY VERY CHALLENGING BUT 3241 02:28:33,720 --> 02:28:35,840 EXCITED TO SAY THAT -- THEY'VE 3242 02:28:35,840 --> 02:28:38,640 BEEN ABLE TO SOLVE THESE 3243 02:28:38,640 --> 02:28:39,040 PROBLEMS. 3244 02:28:39,040 --> 02:28:42,240 THEY ARE NOW BEGINNING TO GET 3245 02:28:42,240 --> 02:28:44,920 SHOTGUN DATA FROM THESE BIOPSIES 3246 02:28:44,920 --> 02:28:49,800 THAT ARE ECONOMICAL AND WE CAN 3247 02:28:49,800 --> 02:28:51,040 DO LODGE TIED NATURAL STUDIES 3248 02:28:51,040 --> 02:28:54,440 ALONG THE GI TRACT AND WE CAN 3249 02:28:54,440 --> 02:28:57,160 SEE -- A LOT ABOUT STRAINS AND 3250 02:28:57,160 --> 02:28:59,800 HOW STRAINS VARY ACROSS 3251 02:28:59,800 --> 02:29:02,040 PATIENTS. 3252 02:29:02,040 --> 02:29:05,920 AND THIS IS JUST A QUICK 3253 02:29:05,920 --> 02:29:06,920 ANALYSIS. 3254 02:29:06,920 --> 02:29:09,440 WE CAN ALSO GET TO THESE VERY 3255 02:29:09,440 --> 02:29:11,680 EXCITING RESULTS WHERE WE START 3256 02:29:11,680 --> 02:29:14,320 RECONSTRUCTING GENOMES. 3257 02:29:14,320 --> 02:29:18,720 8 BUT JEFF WAS TALKING YESTERDAY 3258 02:29:18,720 --> 02:29:22,360 -- AND IT'S A COLLABORATION -- 3259 02:29:22,360 --> 02:29:25,080 VERY EXCITING AT MANY LEVELS. 3260 02:29:25,080 --> 02:29:28,240 THIS IS SHOWING THAT THE 3261 02:29:28,240 --> 02:29:34,320 RECONSTRUCTION -- -- META 3262 02:29:34,320 --> 02:29:36,800 GENOMES FROM HUMAN BIOPSIES THAT 3263 02:29:36,800 --> 02:29:39,840 ALLOW US TO LOOK AT THE STRAINS. 3264 02:29:39,840 --> 02:29:42,440 AND WHAT IS GOING TO BE REALLY 3265 02:29:42,440 --> 02:29:44,320 EXCITING IS GOING BACK TO THE 3266 02:29:44,320 --> 02:29:46,800 CELIAC DATA AND SAYING WE KNOW 3267 02:29:46,800 --> 02:29:50,440 THERE IS ACTING BASILLE ARIAS. 3268 02:29:50,440 --> 02:29:53,400 -- HOW DO WE REALLY BEGIN TO 3269 02:29:53,400 --> 02:30:03,440 FORM MAK -- A MAKE USIC -- -- *. 3270 02:30:03,440 --> 02:30:06,480 THIS BRINGS ME TO MY LAST POINT 3271 02:30:06,480 --> 02:30:08,200 -- ABOUT SPATIAL STRUCTURE AND 3272 02:30:08,200 --> 02:30:08,600 IMAGING. 3273 02:30:08,600 --> 02:30:11,280 . 3274 02:30:11,280 --> 02:30:13,840 AND AGAIN VERY CHALLENGING -- 3275 02:30:13,840 --> 02:30:15,840 PROBLEMS THAT WE'VE BEEN 3276 02:30:15,840 --> 02:30:17,400 THINKING ABOUT THIS AND IT TOOK 3277 02:30:17,400 --> 02:30:18,960 A LONG TIME BUT IT'S MOVING 3278 02:30:18,960 --> 02:30:22,240 FORWARD. 3279 02:30:22,240 --> 02:30:23,480 THEY'VE DEVELOPED APPROACHES 3280 02:30:23,480 --> 02:30:28,040 THAT ALLOW US TO DO 3-D -- 3281 02:30:28,040 --> 02:30:31,120 IMAGING WHILE PRESERVING THE 3282 02:30:31,120 --> 02:30:33,120 MICROBIAL GOLD THAT IS ATTACHED 3283 02:30:33,120 --> 02:30:54,080 TO THE SURFACE. 3284 02:30:54,080 --> 02:30:57,120 THE LAYERS -- AND UNDERSTAND THE 3285 02:30:57,120 --> 02:30:58,320 SPATIAL GRADING THAT GARY WAS 3286 02:30:58,320 --> 02:30:59,920 TALKING ABOUT. 3287 02:30:59,920 --> 02:31:01,960 THAT PAPER JUST CAME OUT AND I 3288 02:31:01,960 --> 02:31:04,120 ENCOURAGE TO YOU LOOK AT IT. 3289 02:31:04,120 --> 02:31:06,040 WE ALSO OF COURSE THESE METHODS 3290 02:31:06,040 --> 02:31:09,040 ALLOW TO YOU LOOK AT THE HOST 3291 02:31:09,040 --> 02:31:09,480 CELLS 3292 02:31:09,480 --> 02:31:12,120 THE IMMUNE CELLS AND THE ANATOMY 3293 02:31:12,120 --> 02:31:14,120 DAMAGE AND THE INFRASTRUCTURE 3294 02:31:14,120 --> 02:31:15,880 AND THE MICROBES AS WELL. 3295 02:31:15,880 --> 02:31:26,040 AND I'M EXTREMELY GRATEFUL FOR 3296 02:31:26,040 --> 02:31:27,680 THEIR WORK. 3297 02:31:27,680 --> 02:31:31,520 MY LAST SLIDE. 3298 02:31:31,520 --> 02:31:33,240 THE POINTS THAT WE NEED TO KEEP 3299 02:31:33,240 --> 02:31:33,960 IN MIND. 3300 02:31:33,960 --> 02:31:39,480 THINK ABOUT THE SMALL INTESTINE. 3301 02:31:39,480 --> 02:31:42,600 THE GUT MUCOSAL INTERFACE. 3302 02:31:42,600 --> 02:31:47,000 IF THE TOTAL LOAD CHANGES YOU 3303 02:31:47,000 --> 02:31:50,240 MUST USE QUANTITATIVE TOOLS. 3304 02:31:50,240 --> 02:31:52,280 CONTROL IS DIFFICULT BECAUSE 3305 02:31:52,280 --> 02:31:54,640 THERE ARE ALL KIND OF CRAZY 3306 02:31:54,640 --> 02:31:56,120 BEHAVIORS THAT WE WILL SEE. 3307 02:31:56,120 --> 02:31:59,160 WE HAVE TO THINK ABOUT THEM WHEN 3308 02:31:59,160 --> 02:32:01,640 WE DESIGN PRO-BIOTICS. 3309 02:32:01,640 --> 02:32:04,240 WE NEED TO LOOK AT STRAINS AND 3310 02:32:04,240 --> 02:32:05,640 GENOMES. 3311 02:32:05,640 --> 02:32:07,320 AND OF COURSE 3-D STRUCTURE IS 3312 02:32:07,320 --> 02:32:10,440 GOING TO GIVE US AN INCREDIBLE 3313 02:32:10,440 --> 02:32:13,520 VIEW OF HOW THE INTERACTION IS 3314 02:32:13,520 --> 02:32:14,280 TAKING PLACE. 3315 02:32:14,280 --> 02:32:15,840 I APPRECIATE YOUR ATTENTION AND 3316 02:32:15,840 --> 02:32:19,520 THE CHANCE TO SPEAK. 3317 02:32:19,520 --> 02:32:21,720 >> A FANTASTIC TALK. 3318 02:32:21,720 --> 02:32:24,600 I REALLY GIVE A BIG SHOUT OUT TO 3319 02:32:24,600 --> 02:32:28,160 THE SPEAKERS IN THIS SESSION AND 3320 02:32:28,160 --> 02:32:29,840 NOW WE WOULD LIKE TO MOVE TO THE 3321 02:32:29,840 --> 02:32:30,480 DISCUSSION PART. 3322 02:32:30,480 --> 02:32:32,680 THAT IS THE MOST EXCITING PART 3323 02:32:32,680 --> 02:32:34,400 OF THE WHOLE THING. 3324 02:32:34,400 --> 02:32:42,440 SO RYAN WILL LEAD THE -- 3325 02:32:42,440 --> 02:32:43,000 DISCUSSION 3326 02:32:43,000 --> 02:32:43,720 >> THANK YOU EVERYONE. 3327 02:32:43,720 --> 02:32:46,320 THAT WAS REALLY GREAT. 3328 02:32:46,320 --> 02:32:48,640 PADMA AND I ARE GOING TO GO BACK 3329 02:32:48,640 --> 02:32:51,560 AND FORTH AND ASK QUESTIONS. 3330 02:32:51,560 --> 02:32:53,480 AND AGAIN I'LL ENCOURAGE THE 3331 02:32:53,480 --> 02:32:55,480 VIDEO CAST FOLKS TO SUBMIT 3332 02:32:55,480 --> 02:32:55,960 QUESTIONS. 3333 02:32:55,960 --> 02:32:57,440 THEY'VE BEEN ENTERED INTO THE 3334 02:32:57,440 --> 02:32:57,840 CHAT. 3335 02:32:57,840 --> 02:32:59,640 I'M GOING TO START OFF WITH A 3336 02:32:59,640 --> 02:33:05,840 REALLY A GENERAL QUESTION THAT I 3337 02:33:05,840 --> 02:33:07,360 THINK ENCAPSULATES THIS 3338 02:33:07,360 --> 02:33:09,000 WORKSHOP. 3339 02:33:09,000 --> 02:33:11,840 AND WHAT I'M GOING TO DO IS I'M 3340 02:33:11,840 --> 02:33:14,200 GOING TO ENCOURAGE OUR PANELISTS 3341 02:33:14,200 --> 02:33:17,000 AND I WON'T CALL ON YOU IF YOU 3342 02:33:17,000 --> 02:33:18,800 DON'T FEEL LIKE SAYING ANYTHING 3343 02:33:18,800 --> 02:33:21,680 BUT THEY ALL HAVE DIFFERENT 3344 02:33:21,680 --> 02:33:23,640 PERSPECTIVES OR SIMILAR 3345 02:33:23,640 --> 02:33:24,840 PERSPECTIVES AND IT'S THE 3346 02:33:24,840 --> 02:33:26,320 QUESTION THAT ONE OF OUR 3347 02:33:26,320 --> 02:33:27,640 PREVIOUS SPEAKERS HAD TALKED 3348 02:33:27,640 --> 02:33:28,560 ABOUT. 3349 02:33:28,560 --> 02:33:31,440 AND HIS QUESTION IS AND MY 3350 02:33:31,440 --> 02:33:32,920 QUESTION TO EVERYBODY AND YOU 3351 02:33:32,920 --> 02:33:36,480 CAN RAISE YOUR HAND OR JUMP 3352 02:33:36,480 --> 02:33:40,800 RIGHT IN -- HOW DO WE DEFINE 3353 02:33:40,800 --> 02:33:42,960 NEXT GENERATION PRO-BIOTICS? 3354 02:33:42,960 --> 02:33:47,360 AND THERE HAS BEEN SOME UNIQUE 3355 02:33:47,360 --> 02:33:49,760 PERSPECTIVES IN THE CHAT AND I'M 3356 02:33:49,760 --> 02:33:52,160 GOING TO OPEN IT UP WITH THIS 3357 02:33:52,160 --> 02:33:52,720 QUESTION. 3358 02:33:52,720 --> 02:33:54,640 >> MAYBE I CAN JUMP IN BECAUSE I 3359 02:33:54,640 --> 02:33:57,640 THINK IT WAS MENTIONED IN MY 3360 02:33:57,640 --> 02:34:03,840 TALK -- I SEE NEXT GENERATION 3361 02:34:03,840 --> 02:34:08,120 PRO-BIOTICS IS THAT -- IT'S 3362 02:34:08,120 --> 02:34:10,240 STRAIN DERIVED FROM THE HUMAN 3363 02:34:10,240 --> 02:34:12,040 INTESTINE OR THE HUMAN SKIN AND 3364 02:34:12,040 --> 02:34:14,520 THAT YOU FOCUS ON TARGETING MORE 3365 02:34:14,520 --> 02:34:17,440 OF THE FUNCTION OF HEALTH OR 3366 02:34:17,440 --> 02:34:19,080 RELATED TO HEALTH. 3367 02:34:19,080 --> 02:34:21,520 CLASSICALLY IT WAS MORE FOOD 3368 02:34:21,520 --> 02:34:23,400 DERIVED ORGANISMS THAT MIGHT 3369 02:34:23,400 --> 02:34:25,120 HAVE AN IMPACT AND NOW IT'S MORE 3370 02:34:25,120 --> 02:34:27,840 I THINK TARGETED FOCUSED ON THE 3371 02:34:27,840 --> 02:34:29,480 FUNCTION AND THAT THEY ARE FROM 3372 02:34:29,480 --> 02:34:31,040 THE ECOSYSTEM. 3373 02:34:31,040 --> 02:34:32,920 BUT YOU WANT THEM TO HAVE A 3374 02:34:32,920 --> 02:34:34,920 FUNCTION. 3375 02:34:34,920 --> 02:34:36,560 >> THAT IS GREAT. 3376 02:34:36,560 --> 02:34:37,840 GO AHEAD, GARY. 3377 02:34:37,840 --> 02:34:40,000 PLEASE. 3378 02:34:40,000 --> 02:34:42,440 >> SO SO MY COMMENTS ACTUALLY A 3379 02:34:42,440 --> 02:34:44,000 LITTLE BIT MORE SIMPLE. 3380 02:34:44,000 --> 02:34:46,440 I WOULD LIKE TO SEE PROOF OF 3381 02:34:46,440 --> 02:34:48,200 CONCEPT THAT THIS ACTUALLY IS 3382 02:34:48,200 --> 02:34:49,080 GOOD FOR HEALTH. 3383 02:34:49,080 --> 02:34:51,120 THAT IT ACTUALLY IMPROVES 3384 02:34:51,120 --> 02:34:51,640 HEALTH. 3385 02:34:51,640 --> 02:34:54,040 JUST THE NOTION OF A PRO-BIOTIC 3386 02:34:54,040 --> 02:34:56,280 WHETHER ALIVE OR DEAD OR 3387 02:34:56,280 --> 02:34:56,920 METABOLITE. 3388 02:34:56,920 --> 02:34:59,600 I THINK WE AGAIN I TRY TO 3389 02:34:59,600 --> 02:35:05,240 EMPHASIZE THE FACT -- WONDERFUL 3390 02:35:05,240 --> 02:35:07,040 SCIENCE AND WE'VE LEARNED A LOT 3391 02:35:07,040 --> 02:35:10,200 AS A FIELD LARGELY IN ANIMAL 3392 02:35:10,200 --> 02:35:12,760 MODEL SYSTEMS BUT EXAMPLES IN 3393 02:35:12,760 --> 02:35:15,840 HUMAN PHYSIOLOGY WHERE CHANGING 3394 02:35:15,840 --> 02:35:19,840 THE MICROBIOTA IS BENEFICIAL ARE 3395 02:35:19,840 --> 02:35:21,640 LARGELY LACKING SO MY MOTIONS 3396 02:35:21,640 --> 02:35:23,840 THAT THE CORNER STONE OF A 3397 02:35:23,840 --> 02:35:25,960 DEFINITION FOR NEXT GENERATION 3398 02:35:25,960 --> 02:35:28,400 ROW BIOTIC IS SOMETHING THAT 3399 02:35:28,400 --> 02:35:30,640 ACTUALLY IMPROVES HUMAN HEALTH. 3400 02:35:30,640 --> 02:35:32,440 TREATS OR PREVENTS THE DISEASE 3401 02:35:32,440 --> 02:35:34,640 IN A WAY THAT THE CURRENT 3402 02:35:34,640 --> 02:35:36,560 GENERATION OF PRO-BIOTICS ARE 3403 02:35:36,560 --> 02:35:39,040 NOT ABLE TO DO. 3404 02:35:39,040 --> 02:35:40,640 >> THANK YOU, GARY. 3405 02:35:40,640 --> 02:35:43,600 TAMI. 3406 02:35:43,600 --> 02:35:45,640 >> MAYBE I'M THINKING THIRD A 3407 02:35:45,640 --> 02:35:48,960 GENERATION AFTER THAT. 3408 02:35:48,960 --> 02:35:52,240 SO I TOTALLY AGREE WITH WHAT HAS 3409 02:35:52,240 --> 02:35:53,480 BEEN SAID SO FAR. 3410 02:35:53,480 --> 02:35:55,880 BUT GOING FORWARD I THINK THERE 3411 02:35:55,880 --> 02:35:58,320 ARE A BUNCH OF MICROBE THAT'S 3412 02:35:58,320 --> 02:35:59,800 WERE DISCUSSED YESTERDAY THAT 3413 02:35:59,800 --> 02:36:03,440 ARE NOT GOING TO CURE DISEASES 3414 02:36:03,440 --> 02:36:05,760 BUT WOULD MAYBE PROMOTE HEALTH 3415 02:36:05,760 --> 02:36:08,200 AND PREVENTS DISEASES. 3416 02:36:08,200 --> 02:36:10,320 BACTERIAS THAT CAN PREVENT 3417 02:36:10,320 --> 02:36:10,880 KIDNEY STONES. 3418 02:36:10,880 --> 02:36:12,840 THERE IS A LARGE NUMBER OF THESE 3419 02:36:12,840 --> 02:36:14,880 OUT THERE THAT IF WE HAVE A 3420 02:36:14,880 --> 02:36:17,360 LITTLE BIT OF EACH OF THESE 3421 02:36:17,360 --> 02:36:19,680 DIFFERENT MICROBES MAYBE THEY 3422 02:36:19,680 --> 02:36:22,000 WOULD PROMOTE HEALTH. 3423 02:36:22,000 --> 02:36:23,920 A SYSTEM IN WHICH WE TAKE EACH 3424 02:36:23,920 --> 02:36:27,800 OF THOSE LARGE COCKTAILS EVERY 3425 02:36:27,800 --> 02:36:33,640 DAY TO PREVENT DISEASES THAT IS 3426 02:36:33,640 --> 02:36:35,400 PROBABLY NOT GOING TO HAPPEN OR 3427 02:36:35,400 --> 02:36:37,480 AT LEAST WOULD BE VERY 3428 02:36:37,480 --> 02:36:38,240 EXPENSIVE. 3429 02:36:38,240 --> 02:36:42,680 SO DRIVING ENGRAPHMENT AND 3430 02:36:42,680 --> 02:36:43,560 HAVING MIKE JOBS THAT LIVE 3431 02:36:43,560 --> 02:36:44,920 LONG-TERM IS GOING TO BE 3432 02:36:44,920 --> 02:36:45,360 IMPORTANT. 3433 02:36:45,360 --> 02:36:46,840 IT'S GOING TO INVOLVE SCIENCE 3434 02:36:46,840 --> 02:36:49,840 AND POLICY AND HOW TO ENCOURAGE 3435 02:36:49,840 --> 02:36:51,960 THE DEVELOPMENT OF DRUGS THAT 3436 02:36:51,960 --> 02:36:54,080 ARE NOT TAKEN ON A DAILY BASES 3437 02:36:54,080 --> 02:36:55,440 BUT I THINK THAT CAN HAPPEN. 3438 02:36:55,440 --> 02:36:57,560 7 3439 02:36:57,560 --> 02:36:58,280 >> THAT'S GREAT. 3440 02:36:58,280 --> 02:37:00,360 THANKS, TAMI. 3441 02:37:00,360 --> 02:37:03,000 J.P. 3442 02:37:03,000 --> 02:37:05,280 >> SO I THINK WHEN I THINK ABOUT 3443 02:37:05,280 --> 02:37:12,280 THE TERM NexGen ROW BIOTICS 3444 02:37:12,280 --> 02:37:13,640 MY NEXT THOUGHT WOULD BE WHAT IS 3445 02:37:13,640 --> 02:37:15,960 A PRO-BIOTIC. 3446 02:37:15,960 --> 02:37:18,040 THE HEALTH BENEFITS. 3447 02:37:18,040 --> 02:37:19,400 IT SHOULD HAVE BEEN ESTABLISHED 3448 02:37:19,400 --> 02:37:21,840 AND WHEN I THINK OF THE NEXT 3449 02:37:21,840 --> 02:37:22,840 GENERATION THIS IS ACTUALLY 3450 02:37:22,840 --> 02:37:25,640 STARTING FROM THE ORIGINAL 3451 02:37:25,640 --> 02:37:29,280 PRO-BIOTIC WHEREBY THE ORGANISM 3452 02:37:29,280 --> 02:37:32,160 EATER IS ENGINEERED TO HAVE A 3453 02:37:32,160 --> 02:37:33,480 MORE BENEFICIAL EFFECT OR TAKING 3454 02:37:33,480 --> 02:37:35,080 SOME OF THE ECOLOGICAL 3455 02:37:35,080 --> 02:37:37,120 PRINCIPLES AND TAKING IT INTO 3456 02:37:37,120 --> 02:37:38,080 CONSIDERATION FOR THE EFFECT OF 3457 02:37:38,080 --> 02:37:40,000 THE PRO-BIOTIC. 3458 02:37:40,000 --> 02:37:42,400 BRIEFLY COMMENTING ON WHAT -- 3459 02:37:42,400 --> 02:37:45,240 WAS SAYING IN TERMS OF 3460 02:37:45,240 --> 02:37:47,640 ENGRAPHMENT AND IT DEPENDS ON 3461 02:37:47,640 --> 02:37:49,360 WHO YOU ASK. 3462 02:37:49,360 --> 02:37:52,120 ENGRAPHMENT IS NOT A REQUIREMENT 3463 02:37:52,120 --> 02:37:55,240 FOR PRO-BIOTIC EFFICACY. 3464 02:37:55,240 --> 02:37:57,920 LOOKING AT THE PRECLINICAL 3465 02:37:57,920 --> 02:38:01,000 MODELS WHEREBY MOST PRO-BIOTICS 3466 02:38:01,000 --> 02:38:03,480 THAT YOU FEED THE ANIMAL WILL 3467 02:38:03,480 --> 02:38:05,360 PASS THROUGH AND DO NOT 3468 02:38:05,360 --> 02:38:06,040 COLONIZE. 3469 02:38:06,040 --> 02:38:07,640 YET THERE ARE THESE FUNCTIONS 3470 02:38:07,640 --> 02:38:10,800 THAT YOU SEE IN RELATION TO 3471 02:38:10,800 --> 02:38:12,600 LIVER DISEASE ETC. 3472 02:38:12,600 --> 02:38:15,680 SO ENGRAPHMENT WOULD NOT BE A 3473 02:38:15,680 --> 02:38:17,840 REQUIREMENT FOR BEING A 3474 02:38:17,840 --> 02:38:18,920 PRO-BIOTIC. 3475 02:38:18,920 --> 02:38:22,840 BUT THAT IS JUST MY TWO CENTS. 3476 02:38:22,840 --> 02:38:24,960 >> EVERYBODY IS GOING TO COME AT 3477 02:38:24,960 --> 02:38:26,640 THIS DIFFERENTLY SO THIS IS A 3478 02:38:26,640 --> 02:38:27,440 GREAT QUESTION. 3479 02:38:27,440 --> 02:38:28,600 GO AHEAD, JUNE. 3480 02:38:28,600 --> 02:38:31,040 PLEASE. 3481 02:38:31,040 --> 02:38:32,440 >> AS THE I'M 3482 02:38:32,440 --> 02:38:36,920 >> JUST OF THE GROUP I THINK -- 3483 02:38:36,920 --> 02:38:41,240 * NexGen PRO-BIOTICS IT 3484 02:38:41,240 --> 02:38:45,040 SHOULD CONSIDER THE IMMUNE 3485 02:38:45,040 --> 02:38:45,480 EFFECT. 3486 02:38:45,480 --> 02:38:48,360 ONE OF THE MAJOR THINGS THAT IGA 3487 02:38:48,360 --> 02:38:50,600 DOES TO CANADA IS THAT IT HELPS 3488 02:38:50,600 --> 02:38:52,480 CANADA STICK AROUND IN THE GUT 3489 02:38:52,480 --> 02:38:55,040 SO YOU NEED THE APPROPRIATE IGA 3490 02:38:55,040 --> 02:38:58,480 RESPONSE TO STAY THERE AND IT 3491 02:38:58,480 --> 02:39:00,040 DOESN'T NECESSARILY AFFECT 3492 02:39:00,040 --> 02:39:02,160 CANADA LOADS BUT IT EFFECTS THE 3493 02:39:02,160 --> 02:39:03,480 LOADS OF CANADA. 3494 02:39:03,480 --> 02:39:06,360 SO WHEN THERE IS A CERTAIN IGA 3495 02:39:06,360 --> 02:39:08,840 RESPONSE THAT KEEPS CANADA AWAY 3496 02:39:08,840 --> 02:39:13,120 FROM THE MUCOS A BUT IT CAN 3497 02:39:13,120 --> 02:39:14,720 STILL COLONIZE -- MOST PEOPLE 3498 02:39:14,720 --> 02:39:19,240 ARE FAMILIAR WITH -- THE WORK -- 3499 02:39:19,240 --> 02:39:21,760 IT REQUIRES AN IGA RESPONSE. 3500 02:39:21,760 --> 02:39:25,600 8 IN MY OPINION I THINK THAT WE 3501 02:39:25,600 --> 02:39:27,160 REALLY NEED TO THINK ABOUT HOW 3502 02:39:27,160 --> 02:39:29,280 THE IMMUNE SYSTEM IS GOING TO 3503 02:39:29,280 --> 02:39:31,400 PRUNE THAT PARTICULAR PRO-BIOTIC 3504 02:39:31,400 --> 02:39:34,040 THAT WE'RE GOING TO GIVE AND IN 3505 02:39:34,040 --> 02:39:36,880 FACT WE MIGHT BE ABLE TO NOT 3506 02:39:36,880 --> 02:39:38,600 ONLY USE VACCINATION STRATEGIES 3507 02:39:38,600 --> 02:39:41,440 TO GET RID OF MICROBES THAT WE 3508 02:39:41,440 --> 02:39:43,320 DON'T WANT BUT WE MIGHT BE ABLE 3509 02:39:43,320 --> 02:39:46,400 TO USE VACCINATION STRATEGIES TO 3510 02:39:46,400 --> 02:39:48,840 ENHANCE COLONIZATION OF MICRO 3511 02:39:48,840 --> 02:39:50,320 THAT'S WE WANT TO STAY IN THE 3512 02:39:50,320 --> 02:39:51,880 GUT. 3513 02:39:51,880 --> 02:39:53,440 >> THAT IS WONDERFUL. 3514 02:39:53,440 --> 02:40:10,720 WE HAVE AN IGA QUESTION CUED UP. 3515 02:40:10,720 --> 02:40:16,520 >> LET'S FINISH UP WITH JULIA. 3516 02:40:16,520 --> 02:40:18,520 >> BEING PURE MICROBIOLIGIST I 3517 02:40:18,520 --> 02:40:21,080 HAD A POINT SIMILAR TO JUNE'S 3518 02:40:21,080 --> 02:40:22,440 THAT I THINK THERE IS A LOT MORE 3519 02:40:22,440 --> 02:40:24,440 THAT NEEDS TO GO INTO THE MODEL 3520 02:40:24,440 --> 02:40:25,880 INSTEAD OF JUST THINKING ABOUT 3521 02:40:25,880 --> 02:40:28,240 THE SKIN STATUS OF SKIN BARRIER 3522 02:40:28,240 --> 02:40:30,440 THE RESIDENT IMMUNE CELLS. 3523 02:40:30,440 --> 02:40:33,720 I THINK OF PRO-BIOTICS AS EVEN 3524 02:40:33,720 --> 02:40:35,280 MORE DIFFICULT IN MANY WAYS THAN 3525 02:40:35,280 --> 02:40:38,160 THE HUMAN PRECISION MEDICINE 3526 02:40:38,160 --> 02:40:44,440 TARGETING OF THE CLASSICAL 3527 02:40:44,440 --> 02:40:45,440 GWINNETT CALL VARIANCE. 3528 02:40:45,440 --> 02:40:50,400 THERE SHOULD BE A * DIAGNOSTIC 3529 02:40:50,400 --> 02:40:53,920 PANEL OF SOME OF KIND TBD THAT 3530 02:40:53,920 --> 02:40:56,800 ALLOWS BETTER SELECTION OF A 3531 02:40:56,800 --> 02:40:59,120 PRO-BIOTIC STRAIN -- I'M A GAIN 3532 02:40:59,120 --> 02:41:03,440 OF SOME OF THESE EMERGING 3533 02:41:03,440 --> 02:41:04,080 TRANSPLANTS. 3534 02:41:04,080 --> 02:41:05,840 ENGINEERING MICROBES OBTAINED 3535 02:41:05,840 --> 02:41:09,160 FROM AN INDIVIDUAL TO RESTORE 3536 02:41:09,160 --> 02:41:10,800 MISSING FUNCTIONS BUT AN 3537 02:41:10,800 --> 02:41:11,240 IMPLANT. 3538 02:41:11,240 --> 02:41:13,680 SO YOU'RE NOT PERFECT TUBING A 3539 02:41:13,680 --> 02:41:15,840 LOT OF THE ASPECTS OF THE 3540 02:41:15,840 --> 02:41:16,760 SYSTEM. 3541 02:41:16,760 --> 02:41:18,280 BUT GIVING SOMETHING THAT IS 3542 02:41:18,280 --> 02:41:20,840 SIMILAR TO WHAT THE ECOSYSTEM 3543 02:41:20,840 --> 02:41:23,880 HARD HAS. 3544 02:41:23,880 --> 02:41:25,520 -- ALREADY HAS. 3545 02:41:25,520 --> 02:41:27,920 8 I AGREE WITH GARY'S POINT. 3546 02:41:27,920 --> 02:41:30,360 SOMETHING THAT WORKS PLEASE. 3547 02:41:30,360 --> 02:41:33,120 THAT IS THE FIRST -- THAT I HAVE 3548 02:41:33,120 --> 02:41:35,280 TO AGREE WITH TOO BEFORE WE GET 3549 02:41:35,280 --> 02:41:37,040 INTO THE SCIENCE PROJECT 3550 02:41:37,040 --> 02:41:37,880 >> YOU THANK YOU. 3551 02:41:37,880 --> 02:41:39,240 I APPRECIATE THAT. 3552 02:41:39,240 --> 02:41:41,800 TAKING THE MODERATOR ROLE A 3553 02:41:41,800 --> 02:41:42,560 LITTLE TOO FAR. 3554 02:41:42,560 --> 02:41:44,120 HOW THEY ARE USED. 3555 02:41:44,120 --> 02:41:45,560 TO YOUR LAST POINT. 3556 02:41:45,560 --> 02:41:49,040 HOW ARE THEY USED? 3557 02:41:49,040 --> 02:41:53,560 AND I'LL HAVE A PREAMBLE TO A 3558 02:41:53,560 --> 02:41:56,680 QUESTION ABOUT SEQUENTIAL 3559 02:41:56,680 --> 02:41:59,880 ADMINISTRATION OF PRO-BIOTICS. 3560 02:41:59,880 --> 02:42:04,440 RIGHT IN THAT REALM OF WHAT A 3561 02:42:04,440 --> 02:42:07,440 NEXT GENERATION PRO BUY OATIC 3562 02:42:07,440 --> 02:42:10,320 MAY OR MAY NOT BE 3563 02:42:10,320 --> 02:42:14,240 *. 3564 02:42:14,240 --> 02:42:19,600 >> SO -- -- ---A FEW POTENTIAL 3565 02:42:19,600 --> 02:42:21,800 PRO-BIOTIC IN THE MAKING. 3566 02:42:21,800 --> 02:42:31,960 -- -- CAN WE EXPECT THIS TO BE 3567 02:42:31,960 --> 02:42:36,640 THE -- THE LOW HANGING FRUIT. 3568 02:42:36,640 --> 02:42:38,400 PRO-BIOTICS THAN -- IN THE NEAR 3569 02:42:38,400 --> 02:42:42,880 FUTURE. 3570 02:42:42,880 --> 02:42:45,400 OR ARE THERE OTHER PRO-BIOTICS 3571 02:42:45,400 --> 02:42:49,440 IN THE WORKS. 3572 02:42:49,440 --> 02:42:52,480 -- ANYBODY WANT TO CHIME IN 3573 02:42:52,480 --> 02:42:59,240 THERE? 3574 02:42:59,240 --> 02:42:59,360 -- 3575 02:42:59,360 --> 02:43:02,920 >> I CAN START OFF WITH JUST MY 3576 02:43:02,920 --> 02:43:03,440 VIEW. 3577 02:43:03,440 --> 02:43:06,760 IN GENERAL THIS FIELD IS NOT 3578 02:43:06,760 --> 02:43:09,400 REALLY LOW HANGING FRUIT EXCEPT 3579 02:43:09,400 --> 02:43:13,520 FOR OUR FOR EXAMPLE JUST -- 3580 02:43:13,520 --> 02:43:14,840 INFECTION WHERE WE HAVE A ROAD 3581 02:43:14,840 --> 02:43:18,120 MAP BECAUSE WE KNOW IT'S A 3582 02:43:18,120 --> 02:43:19,120 PROBLEM. 3583 02:43:19,120 --> 02:43:20,000 FMT WORKS. 3584 02:43:20,000 --> 02:43:22,080 YOU WANT TO REDUCE IT TO 3585 02:43:22,080 --> 02:43:23,560 SOMETHING THAT CAN BE 3586 02:43:23,560 --> 02:43:25,240 MANUFACTURED FOR THE REVENGE OF 3587 02:43:25,240 --> 02:43:26,120 THE INFECTION. 3588 02:43:26,120 --> 02:43:28,600 I ALSO THINK THERE ARE OTHER 3589 02:43:28,600 --> 02:43:30,440 EXAMPLES IN HUMAN DISEASE. 3590 02:43:30,440 --> 02:43:33,640 SMALL INTESTINAL BACTERIAL OVER 3591 02:43:33,640 --> 02:43:35,320 GROWTH. 3592 02:43:35,320 --> 02:43:37,480 COLONIZATION WITH ANTIBIOTIC 3593 02:43:37,480 --> 02:43:38,680 RESISTANT ORGANISMS. 3594 02:43:38,680 --> 02:43:41,880 WE KNOW THAT THESE ARE PROBLEMS 3595 02:43:41,880 --> 02:43:44,880 AND THERE ARE SOME EXAMPLES FOR 3596 02:43:44,880 --> 02:43:48,040 TREATMENT OF THESE DISORDERS BUT 3597 02:43:48,040 --> 02:43:49,720 MAYBE A POSITION PRO-BIOTIC 3598 02:43:49,720 --> 02:43:50,600 WOULD BE BETTER. 3599 02:43:50,600 --> 02:43:54,560 SO WE USE THEM TO TREAT SMALL 3600 02:43:54,560 --> 02:43:56,680 BACTERIAL INTESTINAL OVER 3601 02:43:56,680 --> 02:43:58,160 GROWTH. 3602 02:43:58,160 --> 02:44:00,160 COLONIZING INDIVIDUALS THAT HAVE 3603 02:44:00,160 --> 02:44:01,120 ORGANISMS. 3604 02:44:01,120 --> 02:44:03,920 SO, THAT IS SORT OF LOW HANGING 3605 02:44:03,920 --> 02:44:06,120 FRUIT BUT NOT BECAUSE WE DON'T 3606 02:44:06,120 --> 02:44:09,640 HAVE THE POSITION PRO-BIOTIC TO 3607 02:44:09,640 --> 02:44:12,760 TREAT THAT BUT WE KNOW THAT IS A 3608 02:44:12,760 --> 02:44:14,080 MICROBIAL PROBLEM AND WE KNOW 3609 02:44:14,080 --> 02:44:17,400 THAT CHANGING THE MICROBIOTA IN 3610 02:44:17,400 --> 02:44:19,880 SOME WAY CAN BE BENEFICIAL. 3611 02:44:19,880 --> 02:44:22,880 SO I THINK LIKE THE NEXT 3612 02:44:22,880 --> 02:44:24,800 GENERATION BEYOND THE TREATMENT 3613 02:44:24,800 --> 02:44:28,800 OF -- WOULD BE ALONG THAT TIER. 3614 02:44:28,800 --> 02:44:31,640 THINGS THAT ARE MORE DIFFICULT 3615 02:44:31,640 --> 02:44:34,000 -- AND I USED IT BECAUSE IT'S 3616 02:44:34,000 --> 02:44:35,640 MUCH MORE COMPLEX AND PROBABLY 3617 02:44:35,640 --> 02:44:39,160 MUCH MORE CHALLENGING . 3618 02:44:39,160 --> 02:44:41,640 IT DOESN'T MEAN THAT IT'S NOT -- 3619 02:44:41,640 --> 02:44:44,360 -- AND THAT IS MY COMMENT. 3620 02:44:44,360 --> 02:44:46,040 WE CAN PROBABLY MOVE FORWARD 3621 02:44:46,040 --> 02:44:47,720 WITHOUT KNOWING EVERYTHING ABOUT 3622 02:44:47,720 --> 02:44:48,400 THE SYSTEM. 3623 02:44:48,400 --> 02:44:50,640 YOU JUST HAVE TO KNOW ENOUGH TO 3624 02:44:50,640 --> 02:44:53,520 MAKE AN EDUCATED HYPOTHESIS 3625 02:44:53,520 --> 02:44:55,840 ABOUT WHAT THE NEXT STEP WOULD 3626 02:44:55,840 --> 02:44:57,040 BE. 3627 02:44:57,040 --> 02:44:59,640 >> I AGREE WITH WHAT GARY WAS 3628 02:44:59,640 --> 02:45:00,560 JUST SAYING. 3629 02:45:00,560 --> 02:45:03,200 THAT IT'S -- I ALSO DON'T SEE IT 3630 02:45:03,200 --> 02:45:05,520 AS A LOW HANGING FRUIT. 3631 02:45:05,520 --> 02:45:08,120 ALSO BECAUSE OF THE POINTS HE 3632 02:45:08,120 --> 02:45:10,560 MENTIONED BUT IN ADDITION TO WE 3633 02:45:10,560 --> 02:45:14,040 ARE DEALING WITH 8 SOME TIME 3634 02:45:14,040 --> 02:45:17,200 STRICT -- ANAEROBIC MICROBES. 3635 02:45:17,200 --> 02:45:21,280 7 THE CLASSICAL PRO-BIOTICS IF 3636 02:45:21,280 --> 02:45:22,960 YOU WANT TO PRODUCE THEM AND 3637 02:45:22,960 --> 02:45:25,160 KEEP THEM ALIVE IT'S MUCH EASIER 3638 02:45:25,160 --> 02:45:29,120 AND ALSO THE SCALABILITY. 3639 02:45:29,120 --> 02:45:32,600 BUT THAT IS REALLY A CHALLENGE. 3640 02:45:32,600 --> 02:45:38,640 7 A CLASSICAL WAY OF -- TURN 3641 02:45:38,640 --> 02:45:39,840 THEM KNEEPADERS THAT YOU CAN 3642 02:45:39,840 --> 02:45:40,320 USE. 3643 02:45:40,320 --> 02:45:42,960 SO THERE ARE REALLY A LOT OF 3644 02:45:42,960 --> 02:45:45,040 CHALLENGES SO KEEPING THEM ALIVE 3645 02:45:45,040 --> 02:45:48,280 IF THAT IS NEEDED. 3646 02:45:48,280 --> 02:45:49,640 ALSO ONE OF THE THINGS THAT WE 3647 02:45:49,640 --> 02:45:52,000 SHOULD LOOK AT THIS FOR EXAMPLE 3648 02:45:52,000 --> 02:45:55,920 THAT WAS ALSO GARY SAYING THAT 3649 02:45:55,920 --> 02:45:59,160 FOR INSTANCE -- PASTEURIZED THAT 3650 02:45:59,160 --> 02:46:01,200 WORKED VERY WELL. 3651 02:46:01,200 --> 02:46:03,640 THERE IS STILL A LOT -- IT'S 3652 02:46:03,640 --> 02:46:06,240 PROMISING AND WE'RE ON THE WAY 3653 02:46:06,240 --> 02:46:08,440 BUT THERE IS A LONG ROAD TO GO 3654 02:46:08,440 --> 02:46:10,200 TO COME TO REALLY SOMETHING THAT 3655 02:46:10,200 --> 02:46:15,480 YOU CAN APPLY TO LET'S SAY A 3656 02:46:15,480 --> 02:46:17,280 LARGE HUMAN POPULATION. 3657 02:46:17,280 --> 02:46:21,600 THE HOLY GRAIL TO PREVENT OR 3658 02:46:21,600 --> 02:46:28,280 CURE SOMETHING. 3659 02:46:28,280 --> 02:46:29,320 >> IT MIGHT BE TAKING SOME OF 3660 02:46:29,320 --> 02:46:34,040 THE PRO-BIOTICS THAT HAVE NOT 3661 02:46:34,040 --> 02:46:37,680 WORKED SO FAR IN IBD AND START 3662 02:46:37,680 --> 02:46:38,720 ADMINISTERING THEM DURING 3663 02:46:38,720 --> 02:46:39,840 REMISSION. 3664 02:46:39,840 --> 02:46:42,600 GARY WOULD MENTIONED THIS THIS 3665 02:46:42,600 --> 02:46:43,920 MORNING DURING HIS TALK IN 3666 02:46:43,920 --> 02:46:46,480 TRYING TO CHANGE THE MICROBIOTA 3667 02:46:46,480 --> 02:46:51,120 WHEN THE HOST IS ACTIVELY 3668 02:46:51,120 --> 02:46:52,600 SCULPTING THE ENVIRONMENT 3669 02:46:52,600 --> 02:46:54,400 AGAINST PRO-BIOTIC THAT YOU'RE 3670 02:46:54,400 --> 02:46:57,440 TRYING TO ADMINISTER. 3671 02:46:57,440 --> 02:46:59,480 IS NOT SURPRISING BUT THAT HAS 3672 02:46:59,480 --> 02:47:01,680 NOT WORKED. 3673 02:47:01,680 --> 02:47:03,360 TRYING TO CHANGE THE PARADIGM 3674 02:47:03,360 --> 02:47:05,680 AND DO THE HARD CLINICAL TRIALS 3675 02:47:05,680 --> 02:47:09,040 OF ADMINISTERING PRO-BIOTICS 3676 02:47:09,040 --> 02:47:12,520 DURING REMISSION SOUNDS TO ME I 3677 02:47:12,520 --> 02:47:13,760 DON'T KNOW IF ANYONE IS DOING 3678 02:47:13,760 --> 02:47:14,440 IT. 3679 02:47:14,440 --> 02:47:17,000 I'M NOT AWARE IF THAT IS BEING 3680 02:47:17,000 --> 02:47:19,640 DONE YET AND I WANT TO ECHO WHAT 3681 02:47:19,640 --> 02:47:21,840 GARY MENTIONED THIS MORNING. 3682 02:47:21,840 --> 02:47:24,680 >> THANK YOU. 3683 02:47:24,680 --> 02:47:28,000 >> I ALSO WANTED TO JUST REMIND 3684 02:47:28,000 --> 02:47:30,040 EVERYONE OF THE SLIDE THAT GARY 3685 02:47:30,040 --> 02:47:33,760 HAD IN HIS MARVELOUS KEYNOTE. 3686 02:47:33,760 --> 02:47:36,240 I UNDERSTAND STANDARD WHAT 3687 02:47:36,240 --> 02:47:38,440 KEYNOTE MEANS ONCE I HEARD HIS 3688 02:47:38,440 --> 02:47:38,840 TALK. 3689 02:47:38,840 --> 02:47:40,200 SO THIS WAS PERFECT. 3690 02:47:40,200 --> 02:47:43,360 THE POINT ABOUT COME PANS 3691 02:47:43,360 --> 02:47:45,080 DIAGNOSTICS AND MATCHING THE 3692 02:47:45,080 --> 02:47:47,720 RIGHT PERSON WITH THE RIGHT 3693 02:47:47,720 --> 02:47:50,240 PRO-BIOTIC COULD BE EXTREMELY 3694 02:47:50,240 --> 02:47:51,080 POWERFUL. 3695 02:47:51,080 --> 02:47:52,040 FINDING THE MATCH. 3696 02:47:52,040 --> 02:47:57,200 SO, ITS JUST LIKE IN CANCER ON 3697 02:47:57,200 --> 02:47:59,280 AVERAGE THINGS DON'T WORK BUT 3698 02:47:59,280 --> 02:48:01,520 FOR SPECIFIC PEOPLE THAT YOU CAN 3699 02:48:01,520 --> 02:48:03,640 IDENTIFY THEY WORK PRETTY WELL. 3700 02:48:03,640 --> 02:48:05,440 SO ONE OF THE SCIENTIFIC 3701 02:48:05,440 --> 02:48:09,280 QUESTIONS IS TO ME IS ARE WE IN 3702 02:48:09,280 --> 02:48:12,000 THAT SITUATION OF PRO-BIOTICS. 3703 02:48:12,000 --> 02:48:13,560 IS THERE SOMETHING OUT THERE. 3704 02:48:13,560 --> 02:48:15,720 WE JUST DON'T KNOW HOW TO MAKE 3705 02:48:15,720 --> 02:48:17,800 THE MATCH. 3706 02:48:17,800 --> 02:48:19,640 AND OPTIMISTICALLY THAT WOULD BE 3707 02:48:19,640 --> 02:48:21,880 GREAT BECAUSE MEASURING THINGS 3708 02:48:21,880 --> 02:48:25,400 IS EASIER THAN DOING MEDICINE 3709 02:48:25,400 --> 02:48:27,960 FROM SCRATCH AND FINDING MATCHES 3710 02:48:27,960 --> 02:48:30,040 IS EASIER THAN DEVELOPING 3711 02:48:30,040 --> 02:48:31,160 THERAPEUTICS. 3712 02:48:31,160 --> 02:48:32,280 IT'S AN OPEN QUESTION THAT 3713 02:48:32,280 --> 02:48:33,440 SHOULD BE ANSWERED. 3714 02:48:33,440 --> 02:48:33,880 >> RYAN. 3715 02:48:33,880 --> 02:48:37,360 7 3716 02:48:37,360 --> 02:48:39,240 >> I WANT TO GO BACK TO WHAT 3717 02:48:39,240 --> 02:48:41,240 GARY SAID AS WELL IN A DIFFERENT 3718 02:48:41,240 --> 02:48:41,680 WAY. 3719 02:48:41,680 --> 02:48:44,760 BUT TO THINK ABOUT WHAT WE'RE 3720 02:48:44,760 --> 02:48:46,680 TALKING ABOUT -- I MENTIONED THE 3721 02:48:46,680 --> 02:48:49,240 WAY IN WHICH WE USE THEM IN AND 3722 02:48:49,240 --> 02:48:52,680 THE IDEA OF STAGING THE 3723 02:48:52,680 --> 02:48:54,360 INTERVENTION IF YOU WILL FOR 3724 02:48:54,360 --> 02:48:57,560 ACTIVE DISEASE AND TO WHAT TAMI 3725 02:48:57,560 --> 02:48:59,280 SAID DISEASE REMISSION. 3726 02:48:59,280 --> 02:49:02,200 SO AGAIN THINKING ABOUT IT'S NOT 3727 02:49:02,200 --> 02:49:03,280 LOW HANGING FRUIT. 3728 02:49:03,280 --> 02:49:05,720 I TOTALLY AGREE BUT IT WAS 3729 02:49:05,720 --> 02:49:08,480 REALLY STIMULATING TO HEAR THAT 3730 02:49:08,480 --> 02:49:10,400 BECAUSE WE DO HAVE SITUATIONS 3731 02:49:10,400 --> 02:49:11,600 WHERE THERE IS ACTIVE DISEASE 3732 02:49:11,600 --> 02:49:14,920 AND CLEAR PRESSURE FROM THE HOST 3733 02:49:14,920 --> 02:49:19,120 TO EITHER REJECT OR ACCEPT 3734 02:49:19,120 --> 02:49:21,040 DEPENDING ON THE ECOLOGY OF THE 3735 02:49:21,040 --> 02:49:23,680 STRAIN BUT THAT ECOLOGY IS NOT 3736 02:49:23,680 --> 02:49:26,560 GOING TO BE THE SAME OVER TIME. 3737 02:49:26,560 --> 02:49:29,440 DO WE THINK AND CHECK-IN WITH 3738 02:49:29,440 --> 02:49:31,320 DIAGNOSTICS OR POINT OF CARE TO 3739 02:49:31,320 --> 02:49:34,720 CHANGE THE REGIMEN TO EITHER -- 3740 02:49:34,720 --> 02:49:37,160 SO I DON'T KNOW IF ANYONE HAS 3741 02:49:37,160 --> 02:49:38,160 THOUGHTS ON THAT. 3742 02:49:38,160 --> 02:49:39,640 BUT IT DOES -- 3743 02:49:39,640 --> 02:49:41,400 >> LET'S HEAR FROM GARY. 3744 02:49:41,400 --> 02:49:42,800 HE HAS HIS HAND UP. 3745 02:49:42,800 --> 02:49:45,560 7 THE CLOSING COMMENT ON THIS 3746 02:49:45,560 --> 02:49:48,960 QUESTION. 3747 02:49:48,960 --> 02:49:53,360 MAYBE I USED THE LOW HANGING 3748 02:49:53,360 --> 02:49:56,280 FRUIT AS A MISNOMER BUT I 3749 02:49:56,280 --> 02:49:59,480 THOUGHT MAYBE WHAT KIND OF A 3750 02:49:59,480 --> 02:50:01,280 NexGen PRO-BIOTIC COULD BE 3751 02:50:01,280 --> 02:50:03,040 EXPECT IN THE NEXT FIVE OR 10 3752 02:50:03,040 --> 02:50:04,080 YEARS. 3753 02:50:04,080 --> 02:50:06,360 GARY. 3754 02:50:06,360 --> 02:50:08,440 >> I ACTUALLY JUST HAD A COMMENT 3755 02:50:08,440 --> 02:50:21,480 -- TO RUSTEM'S -- IN ONE OF MY 3756 02:50:21,480 --> 02:50:24,680 FIRST SLIDES I SAID PRO-BIOTICS 3757 02:50:24,680 --> 02:50:27,680 ARE NOT -- DON'T HAVE AN 3758 02:50:27,680 --> 02:50:28,440 INDICATION FOR MEDICAL 3759 02:50:28,440 --> 02:50:29,040 TREATMENT. 3760 02:50:29,040 --> 02:50:31,120 IN CLINIC WHEN WE SEE OUR 3761 02:50:31,120 --> 02:50:35,120 PATIENTS THAT HAVE GI SYMPTOMS 3762 02:50:35,120 --> 02:50:37,200 THERE ARE PATIENTS THAT SWEAR BY 3763 02:50:37,200 --> 02:50:39,920 CERTAIN TYPES OF PRO-BIOTICS. 3764 02:50:39,920 --> 02:50:41,320 THEY SAY THIS DEFINITELY MAKES 3765 02:50:41,320 --> 02:50:43,040 ME FEEL BETTER AND I HAVE NO 3766 02:50:43,040 --> 02:50:44,760 REASON NOT TO BELIEVE THEM. 3767 02:50:44,760 --> 02:50:47,640 IN GENERAL ON AVERAGE WE CANNOT 3768 02:50:47,640 --> 02:50:50,040 REALLY SHOW THAT THERE IS A 3769 02:50:50,040 --> 02:50:51,200 DEMONSTRATED EFFECT. 3770 02:50:51,200 --> 02:50:52,640 I THINK THAT MAYBE AN 3771 02:50:52,640 --> 02:50:55,840 OPPORTUNITY IS TO ACTUALLY 3772 02:50:55,840 --> 02:50:57,720 LISTEN TO OUR PATIENTS. 3773 02:50:57,720 --> 02:50:59,840 PATIENTS WHO REALLY DO DERIVE 3774 02:50:59,840 --> 02:51:02,280 SOME TYPE OF BENEFIT FROM EVEN 3775 02:51:02,280 --> 02:51:04,200 THE CURRENT PRO-BIOTICS THAT WE 3776 02:51:04,200 --> 02:51:04,840 USE. 3777 02:51:04,840 --> 02:51:06,920 WHAT MAKES THEM DIFFERENT IN 3778 02:51:06,920 --> 02:51:09,480 TERMS OF THEIR MICRO BUY OAT 3779 02:51:09,480 --> 02:51:10,920 COME. 3780 02:51:10,920 --> 02:51:13,280 THEIR LIFESTYLES AND THEIR DIET 3781 02:51:13,280 --> 02:51:15,080 AND THAT MAKES THEM HAVE A 3782 02:51:15,080 --> 02:51:16,080 BENEFIT THAT IN GENERAL WE 3783 02:51:16,080 --> 02:51:17,960 CANNOT SEE ACROSS EVERYBODY. 3784 02:51:17,960 --> 02:51:20,200 THAT IS A DIFFERENT WAY OF 3785 02:51:20,200 --> 02:51:21,760 THINKING ABOUT PERSONALIZATION. 3786 02:51:21,760 --> 02:51:23,360 BUT I THINK AT THE END OF THE 3787 02:51:23,360 --> 02:51:24,920 DAY WE'RE TRYING TO MAKE OUR 3788 02:51:24,920 --> 02:51:26,480 PATIENTS BETTER AND WHEN OUR 3789 02:51:26,480 --> 02:51:28,400 PATIENTS ARE TELLING US I 3790 02:51:28,400 --> 02:51:30,200 DEFINITELY FEEL BETTER IF I USE 3791 02:51:30,200 --> 02:51:31,280 THIS PRO-BIOTIC. 3792 02:51:31,280 --> 02:51:33,480 WE MIGHT WANT TO PAY MORE 3793 02:51:33,480 --> 02:51:34,320 ATTENTION TO THAT. 3794 02:51:34,320 --> 02:51:35,920 >> THANK YOU. 3795 02:51:35,920 --> 02:51:39,520 THAT IS VERY HELPFUL. 3796 02:51:39,520 --> 02:51:41,720 >> RYAN WILL YOU TAKE THE NEXT 3797 02:51:41,720 --> 02:51:42,200 QUESTION? 3798 02:51:42,200 --> 02:51:43,680 >> I HAVE A LOT OF QUESTIONS BUT 3799 02:51:43,680 --> 02:51:46,600 I WANT TO KEEP THE MOMENTUM 3800 02:51:46,600 --> 02:51:52,160 GOING AND PICK OUT SOME A ASPECTS. 3801 02:51:52,160 --> 02:51:56,640 THE ASPECTS OF THE HOST THAT PUT 3802 02:51:56,640 --> 02:51:58,600 PRECIOUS ON THE MICRO ROW BUY 3803 02:51:58,600 --> 02:52:01,920 OAT UM AS WE INTRODUCE STRAINS 3804 02:52:01,920 --> 02:52:05,240 OR TRYING TO MODIFY THE * THE 3805 02:52:05,240 --> 02:52:06,120 COMMUNITY IN GENERAL. 3806 02:52:06,120 --> 02:52:08,360 THIS COMES FROM A QUESTION FROM 3807 02:52:08,360 --> 02:52:10,720 THE VIDEO CAST AND IT'S SIMPLE 3808 02:52:10,720 --> 02:52:15,440 AND THEN I'LL MAYBE ELABORATE. 3809 02:52:15,440 --> 02:52:17,240 IGA HOST IMMUNITY. 3810 02:52:17,240 --> 02:52:21,360 AND THINK ABOUT HOW IGA IS AND 3811 02:52:21,360 --> 02:52:23,680 JUNE CORRECT ME IF I'M WRONG BUT 3812 02:52:23,680 --> 02:52:25,440 IS DESIGNED TO BE SHORT-LIVED 3813 02:52:25,440 --> 02:52:28,360 AND NOT HAVE LONG-TERM MEMORY IN 3814 02:52:28,360 --> 02:52:30,240 THAT SENSE. 3815 02:52:30,240 --> 02:52:33,640 AND THE QUESTION REALLY IS IN 3816 02:52:33,640 --> 02:52:35,720 TERMS OF THE HOST IMMUNE 3817 02:52:35,720 --> 02:52:38,640 RESPONSE ARE THERE WAYS IN WHICH 3818 02:52:38,640 --> 02:52:41,000 YOU CAN ENVISION -- 3819 02:52:41,000 --> 02:52:43,760 CO-ADMINISTERING ASPECTS OF THE 3820 02:52:43,760 --> 02:52:51,560 HOST TO EITHER ACCEPT OR TO 3821 02:52:51,560 --> 02:52:54,320 MODIFY THE MIKE ROPIAL COMMUNITY 3822 02:52:54,320 --> 02:52:57,440 AND -- AND WHETHER OR NOT THAT 3823 02:52:57,440 --> 02:52:58,800 IS A FEATURE WE SHOULD BE 3824 02:52:58,800 --> 02:53:01,000 BUILDING INTO THE DESIGN' 3825 02:53:01,000 --> 02:53:03,240 NexGen PRO-BIOTICS. 3826 02:53:03,240 --> 02:53:06,840 AND I * I CALLED OUT JUNE BUT 3827 02:53:06,840 --> 02:53:10,000 OTHERS WITH ANSWER AS WELL. 3828 02:53:10,000 --> 02:53:11,800 >> I'LL COMMENT ON IT SINCE YOU 3829 02:53:11,800 --> 02:53:12,560 CALLED ME OUT. 3830 02:53:12,560 --> 02:53:18,280 BUT SO I THINK I ELUDED TO THIS 3831 02:53:18,280 --> 02:53:21,280 WHEN I JUST SPOKE. 3832 02:53:21,280 --> 02:53:23,440 AND THAT IS I GUESS THE WAY I 3833 02:53:23,440 --> 02:53:24,920 ENVISION ONE WAY IN WHICH YOU 3834 02:53:24,920 --> 02:53:27,680 COULD THINK ABOUT INCORPORATING 3835 02:53:27,680 --> 02:53:29,880 HOW THE HOST INFLUENCES THAT 3836 02:53:29,880 --> 02:53:33,080 PRO-BIOTIC IS IS THERE HAVE BEEN 3837 02:53:33,080 --> 02:53:36,280 A FEW STUDIES INCLUDING THE 3838 02:53:36,280 --> 02:53:39,480 FUNGI STUDY THAT I JUST TALKED 3839 02:53:39,480 --> 02:53:42,920 ABOUT THAT DO ATTEST TO A ROLE 3840 02:53:42,920 --> 02:53:47,640 FOR IGA IN PARTICULAR IN HELPING 3841 02:53:47,640 --> 02:53:49,320 AN ORGANISM COLONIZE AND STAY 3842 02:53:49,320 --> 02:53:50,640 WITHIN THE GUT. 3843 02:53:50,640 --> 02:53:52,840 SO THERE HAVE NOT BEEN ANY 3844 02:53:52,840 --> 02:53:55,320 EXPERIMENTS TO DO THIS BUT I 3845 02:53:55,320 --> 02:53:57,240 ENVISION AND I HOPE WE'LL TEST 3846 02:53:57,240 --> 02:54:00,240 ONE DAY THAT YOU COULD VACCINATE 3847 02:54:00,240 --> 02:54:03,000 YOU COULD ELICIT SOME SORT OF 3848 02:54:03,000 --> 02:54:06,640 IMMUNE RESPONSE RIGHT BEFORE OR 3849 02:54:06,640 --> 02:54:09,840 AS YOU'RE GIVING A PRO-BIOTIC TO 3850 02:54:09,840 --> 02:54:12,480 HELP IT TO COLONIZE OR MAYBE GET 3851 02:54:12,480 --> 02:54:14,000 TO THE APPROPRIATE LOCATION. 3852 02:54:14,000 --> 02:54:15,600 WE'VE TALKED ABOUT LOCATION 3853 02:54:15,600 --> 02:54:17,720 ESPECIALLY IN THE SI AND THEN 3854 02:54:17,720 --> 02:54:21,400 THE S II G IS VERY PREVALENT. 3855 02:54:21,400 --> 02:54:23,720 SO I CAN IMAGINE THAT IT IS 3856 02:54:23,720 --> 02:54:25,760 BOOSTING AN IGA RESPONSE AS 3857 02:54:25,760 --> 02:54:28,720 YOU'RE GIVING THAT PRO-BIOTIC 3858 02:54:28,720 --> 02:54:30,280 MIGHT HELP IT STICK WHERE YOU 3859 02:54:30,280 --> 02:54:31,280 WANT IT TO BE. 3860 02:54:31,280 --> 02:54:32,600 SO, THAT IS MY THOUGHTS ON THAT. 3861 02:54:32,600 --> 02:54:36,240 7 3862 02:54:36,240 --> 02:54:38,240 >> I SAW YOU NODDING A LITTLE 3863 02:54:38,240 --> 02:54:38,680 BIT. 3864 02:54:38,680 --> 02:54:43,520 ANYTHING TO ADD MORE ON THAT? 3865 02:54:43,520 --> 02:54:45,840 >> I ABSOLUTELY AGREE WITH WHAT 3866 02:54:45,840 --> 02:54:46,560 JUNE SAID. 3867 02:54:46,560 --> 02:54:53,520 THAT IS -- REALLY INTERESTING. 3868 02:54:53,520 --> 02:54:57,920 AND -- THE TOOLBOX THAT WE HAVE 3869 02:54:57,920 --> 02:55:00,040 AND I ALSO WANTED TO ECHO WHAT 3870 02:55:00,040 --> 02:55:04,200 YOU SAID ABOUT MORE COMPLEX 3871 02:55:04,200 --> 02:55:05,080 APPROACHES. 3872 02:55:05,080 --> 02:55:09,240 7 COMING BACK TO THE POINT ABOUT 3873 02:55:09,240 --> 02:55:11,000 SIMPLE SYSTEMS AND STRONG 3874 02:55:11,000 --> 02:55:11,440 BEHAVIORS. 3875 02:55:11,440 --> 02:55:15,960 IF YOU YOU'RE TRYING TO LAND A 3876 02:55:15,960 --> 02:55:20,120 PLANE YOU JUST DON'T POINT IT 3877 02:55:20,120 --> 02:55:20,400 DOWNWARDS. 3878 02:55:20,400 --> 02:55:22,040 8 THERE IS TURBULENCE AND ALL 3879 02:55:22,040 --> 02:55:23,840 KINDS OF STUFF AND WE DON'T 3880 02:55:23,840 --> 02:55:29,520 UNDERSTAND THE PHYSICS TO FIND 3881 02:55:29,520 --> 02:55:31,920 SIGNIFICANT DIGITS. 3882 02:55:31,920 --> 02:55:33,640 BUT WE CAN STILL LAND THE PLANE 3883 02:55:33,640 --> 02:55:35,440 AND THAT IS DONE BY A SERIES OF 3884 02:55:35,440 --> 02:55:36,000 STEPS. 3885 02:55:36,000 --> 02:55:37,440 THIS QUESTION IF YOU HAVE A 3886 02:55:37,440 --> 02:55:38,960 SYSTEM THAT IS STUCK LET'S SAY 3887 02:55:38,960 --> 02:55:41,320 IN AN UNFAVORABLE STATE. 3888 02:55:41,320 --> 02:55:43,000 WHAT WAS THE NUMBER OF STEPS 3889 02:55:43,000 --> 02:55:45,000 THAT YOU NEED TO TAKE. 3890 02:55:45,000 --> 02:55:46,760 THE SIMPLEST STEPS THAT YOU NEED 3891 02:55:46,760 --> 02:55:47,640 TO TAKE. 3892 02:55:47,640 --> 02:55:51,200 AND IF THE ANSWER IS IT'S 20 3893 02:55:51,200 --> 02:55:55,240 IT'S PROBABLY GOING TO BE 3894 02:55:55,240 --> 02:55:58,080 IMPRACTICAL BUT IF THE ANSWER IS 3895 02:55:58,080 --> 02:56:00,360 TWO THAT COULD BE ACTIONABLE. 3896 02:56:00,360 --> 02:56:02,680 7 SO A APPRECIATE YOU RAISING 3897 02:56:02,680 --> 02:56:03,360 THE QUESTION. 3898 02:56:03,360 --> 02:56:06,000 THAT IS GOING TO BE AN IMPORTANT 3899 02:56:06,000 --> 02:56:08,240 POINT TO THINK THROUGH. 3900 02:56:08,240 --> 02:56:08,840 >> THANK YOU. 3901 02:56:08,840 --> 02:56:11,240 7 JULIA. 3902 02:56:11,240 --> 02:56:11,840 7 3903 02:56:11,840 --> 02:56:13,520 >> SO BUILDING ON BOTH OF THOSE 3904 02:56:13,520 --> 02:56:14,400 COMMENTS. 3905 02:56:14,400 --> 02:56:15,840 AGAIN THINKING ABOUT THE SKIN 3906 02:56:15,840 --> 02:56:19,160 SPECIFICALLY SO THE STRAT YUM -- 3907 02:56:19,160 --> 02:56:21,720 IS DESIGNED TO KEEP STUFF OUT SO 3908 02:56:21,720 --> 02:56:25,040 THAT INHERENTLY IS A BARRIER TO 3909 02:56:25,040 --> 02:56:28,280 ANY PRO-BIOTIC COLONIZATION. 3910 02:56:28,280 --> 02:56:32,160 AND NONCOLONIZING PRO-BIOTICS 3911 02:56:32,160 --> 02:56:35,920 THE DISSEMINATION -- -- AND SO 3912 02:56:35,920 --> 02:56:38,040 AS YOU KNOW THINGS I'VE BEEN 3913 02:56:38,040 --> 02:56:40,560 THINKING ABOUT THAT. 3914 02:56:40,560 --> 02:56:42,400 VARYING IN PRACTICALITY. 3915 02:56:42,400 --> 02:56:44,440 IF YOU BRIEF THE SKIN BARRIER 3916 02:56:44,440 --> 02:56:46,280 WHEN YOU GET A WOUND THAT IS THE 3917 02:56:46,280 --> 02:56:53,920 MOST POWERFUL DRIVER FOR STAPH. 3918 02:56:53,920 --> 02:56:56,080 THAT IS ONE WAY I'VE BEEN 3919 02:56:56,080 --> 02:56:59,560 THINKING THAT ONE COULD INTEREST 3920 02:56:59,560 --> 02:57:02,360 MORE STABLY OR MAKE MORE 3921 02:57:02,360 --> 02:57:05,040 ACCESSIBLE THE IMMUNE CELLS. 3922 02:57:05,040 --> 02:57:07,280 TO ASSIST THE COLONIZATION AND 3923 02:57:07,280 --> 02:57:17,480 THAT IS A COMBINATION. 3924 02:57:17,480 --> 02:57:21,880 TO TARGET THE COLONIZATION. 3925 02:57:21,880 --> 02:57:23,840 BUT THEN AGAIN YOU HAVE TO 3926 02:57:23,840 --> 02:57:26,480 CHANGE THE WAY THAT YOU THINK 3927 02:57:26,480 --> 02:57:29,200 ABOUT THE DELIVERY -- OF YOUR 3928 02:57:29,200 --> 02:57:31,280 PRO-BIOTIC OF CHOICE BECAUSE 3929 02:57:31,280 --> 02:57:32,560 THEN YOU ALTER THE ENVIRONMENT 3930 02:57:32,560 --> 02:57:34,080 AND THAT IS A WHOLE DIFFERENT 3931 02:57:34,080 --> 02:57:36,560 SET OF CRITERIA FOR JUDGING A 3932 02:57:36,560 --> 02:57:38,200 STRAIN TO BE PRO-BIOTIC. 3933 02:57:38,200 --> 02:57:42,280 IS HOW DOES IT BEHAVE IN BREACH 3934 02:57:42,280 --> 02:57:46,440 SKIN BARRIER VERSUS -- SKIN 3935 02:57:46,440 --> 02:57:49,320 BARRIER VERSUS A BARON CONTACT 3936 02:57:49,320 --> 02:57:54,040 WITH THE EPITHELIAL CELLS. 3937 02:57:54,040 --> 02:57:54,920 ANTIBIOTIC CLEARANCE IS ANOTHER 3938 02:57:54,920 --> 02:57:56,560 THOUGHT. 3939 02:57:56,560 --> 02:57:59,160 AN AGGRESSIVE WAY TO REDUCE THE 3940 02:57:59,160 --> 02:58:00,640 COLONIZATION RESISTANCE OF A 3941 02:58:00,640 --> 02:58:01,040 COMMUNITY. 3942 02:58:01,040 --> 02:58:05,760 2 WHAT HAS BEEN PUBLISHED IT HAS 3943 02:58:05,760 --> 02:58:09,280 VARYING EFFICACY IN SKIN BUT 3944 02:58:09,280 --> 02:58:13,960 THOSE KINDS OF I WOULD SAY 3945 02:58:13,960 --> 02:58:16,080 DISTURBANCES OF THE ECOSYSTEM -- 3946 02:58:16,080 --> 02:58:17,680 THEY SHOULD NOT BE DISCOUNTED 3947 02:58:17,680 --> 02:58:21,560 BUT IT DOES ADD ANOTHER LAYER OF 3948 02:58:21,560 --> 02:58:23,120 COMPLEXITY IN UNDERSTANDING THE 3949 02:58:23,120 --> 02:58:25,640 6 EFFICACY. 3950 02:58:25,640 --> 02:58:27,480 >> ONE QUESTION I HAVE FOR YOU 3951 02:58:27,480 --> 02:58:31,240 AS YOU WERE -- SPEAKING AND IT 3952 02:58:31,240 --> 02:58:33,560 RELATES TO THE TOPIC OF YOUR 3953 02:58:33,560 --> 02:58:36,040 TALK AND IT STRUCK ME THAT 3954 02:58:36,040 --> 02:58:37,920 MULTIPLE FOUNDERS MIGHT BE THE 3955 02:58:37,920 --> 02:58:39,560 STARTING POINT. 3956 02:58:39,560 --> 02:58:43,720 FOR PARTICULARLY FOR SKIN 3957 02:58:43,720 --> 02:58:44,040 MICROBIOMES. 3958 02:58:44,040 --> 02:58:45,520 THE WAY IN WHICH YOU WATCH THE 3959 02:58:45,520 --> 02:58:47,320 DISTRIBUTION AND HOW YOU MIGHT 3960 02:58:47,320 --> 02:58:49,560 DELIVER THAT IT SEEMS TO ME THAT 3961 02:58:49,560 --> 02:58:51,240 IT'S SLIGHTLY DIFFERENT THAN 3962 02:58:51,240 --> 02:58:54,200 PERHAPS WHAT WE SEE IN THE GUT. 3963 02:58:54,200 --> 02:58:57,000 AND AS A STARTING POINT FOR 3964 02:58:57,000 --> 02:58:59,040 CONSORT WHY OF MULTIPLE GENRE 3965 02:58:59,040 --> 02:59:01,240 WHERE I GET THE SENSE FROM YOUR 3966 02:59:01,240 --> 02:59:03,320 TALK IN PARTICULAR THAT IT WOULD 3967 02:59:03,320 --> 02:59:07,520 NOT BE REALLY THAT COMPLEX AT 3968 02:59:07,520 --> 02:59:09,520 THE GENRE LEVEL BUT AT THE 3969 02:59:09,520 --> 02:59:10,200 STRAIN LEVEL. 3970 02:59:10,200 --> 02:59:12,920 JUST THROWING THAT OUT THERE 3971 02:59:12,920 --> 02:59:14,920 >> I WOULD LOVE TO TALK ABOUT 3972 02:59:14,920 --> 02:59:17,120 HOW EVERY DIFFERENT SKIN SITE 3973 02:59:17,120 --> 02:59:19,760 YOU'LL NEED A DIFFERENT SET OF 3974 02:59:19,760 --> 02:59:22,040 ORGANISMS AND TARGETS. 3975 02:59:22,040 --> 02:59:24,840 VERY NAIVE ABOUT THE GUT 3976 02:59:24,840 --> 02:59:25,720 ECOSYSTEM. 3977 02:59:25,720 --> 02:59:29,880 THE CRIBS AT THE MICRO LEVEL AND 3978 02:59:29,880 --> 02:59:32,640 THERE ARE INTESTINAL CRIPS. 3979 02:59:32,640 --> 02:59:34,600 I SUSPECT IT WOULD BE TRUE IN 3980 02:59:34,600 --> 02:59:35,600 THE GUT AS WELL. 3981 02:59:35,600 --> 02:59:37,760 YOU CAN SEE IT MORE READILY IN 3982 02:59:37,760 --> 02:59:38,920 THE SKIN. 3983 02:59:38,920 --> 02:59:39,640 >> THANK YOU SO MUCH. 3984 02:59:39,640 --> 02:59:43,680 7 3985 02:59:43,680 --> 02:59:47,760 >> I JUST WONDERED -- AND I 3986 02:59:47,760 --> 02:59:58,920 UNDERSTAND -- -- ----- -- -- 3987 02:59:58,920 --> 03:00:04,840 SOME OF THE ASPECTS -- CAN WE -- 3988 03:00:04,840 --> 03:00:10,560 EYE OF ---THAT WE CAN IDENTIFY 3989 03:00:10,560 --> 03:00:16,040 TO DETERMINE WHETHER OR NOT 3990 03:00:16,040 --> 03:00:19,040 BACTERIA -- CAN -- IS IT 3991 03:00:19,040 --> 03:00:21,200 SOMETHING THAT WHEN YOU SEE LIKE 3992 03:00:21,200 --> 03:00:27,320 THE CONDITIONS OR THE BACTERIA 3993 03:00:27,320 --> 03:00:37,840 -- THIS MAY OR MAY NOT. 3994 03:00:37,840 --> 03:00:39,800 >> I'M HAPPY TO JUMP NCATS I 3995 03:00:39,800 --> 03:00:42,120 THINK WE'RE QUITE FAR FROM THAT. 3996 03:00:42,120 --> 03:00:43,080 *. 3997 03:00:43,080 --> 03:00:44,880 THERE ARE PRINCIPLES THAT WERE 3998 03:00:44,880 --> 03:00:46,360 BROUGHT UP YESTERDAY THAT HAVE 3999 03:00:46,360 --> 03:00:48,640 SHOWN TO BE SOMEWHAT TRUE WHICH 4000 03:00:48,640 --> 03:00:55,840 IS THAT IF THERE IS A NICHE THAT 4001 03:00:55,840 --> 03:00:59,200 IS NOT YET OCCUPIED THAT IS NOT 4002 03:00:59,200 --> 03:01:02,280 YET BEING USED THEN ADDING 4003 03:01:02,280 --> 03:01:05,400 SOMETHING IN MIGHT BE TRIVIAL. 4004 03:01:05,400 --> 03:01:07,840 BUT BEYOND THAT -- WE'RE REALLY 4005 03:01:07,840 --> 03:01:08,880 IN EARLY STAGES. 4006 03:01:08,880 --> 03:01:16,200 7 4007 03:01:16,200 --> 03:01:18,160 >> YEAH. 4008 03:01:18,160 --> 03:01:21,640 CAN WE HAVE STRAINS TO HAVE THEM 4009 03:01:21,640 --> 03:01:23,640 ADAPT BETTER OR TO ADHERE BETTER 4010 03:01:23,640 --> 03:01:26,400 AND TO DO BETTER AND WHAT I 4011 03:01:26,400 --> 03:01:28,720 STRONGLY AGREE WITH WHAT WITH 4012 03:01:28,720 --> 03:01:30,960 WHAT CARE GARY WAS SAYING WE DO 4013 03:01:30,960 --> 03:01:32,800 NOT NEED TO KNOW EVERYTHING TO 4014 03:01:32,800 --> 03:01:35,240 MAKE USE OF THESE STRAINS AND TO 4015 03:01:35,240 --> 03:01:37,440 IMPLEMENT THEM AND TO HAVE AND 4016 03:01:37,440 --> 03:01:39,040 EFFECT. 4017 03:01:39,040 --> 03:01:41,640 UNDERSTANDING MECHANISM FROM 4018 03:01:41,640 --> 03:01:43,200 PRO-BIOTICS WILL GREATLY HELP TO 4019 03:01:43,200 --> 03:01:44,640 ANSWER THE QUESTION THAT YOU 4020 03:01:44,640 --> 03:01:46,880 WERE ASKING AND IF WE BETTER 4021 03:01:46,880 --> 03:01:49,760 UNDERSTAND THE UNDERLYING 4022 03:01:49,760 --> 03:01:51,880 MECHANISMS -- ULTIMATELY AND 4023 03:01:51,880 --> 03:01:53,680 THESE STUDIES ARE HARD AND THAT 4024 03:01:53,680 --> 03:01:55,440 TAKES A LOT OF TIME AND ENERGY 4025 03:01:55,440 --> 03:01:57,160 AND A LOT OF RESTRICTIONS IN 4026 03:01:57,160 --> 03:01:58,440 ORDER TO IMPLEMENT THAT. 4027 03:01:58,440 --> 03:02:00,840 IF YOU THINK ABOUT WE TALKED 4028 03:02:00,840 --> 03:02:06,160 ABOUT STRAIN -- -- AND IT'S 4029 03:02:06,160 --> 03:02:06,680 RESTRICTIVE. 4030 03:02:06,680 --> 03:02:10,920 AND IF YOU THINK ABOUT ISOLATING 4031 03:02:10,920 --> 03:02:12,680 MICROBES FROM THE GUT THESE ARE 4032 03:02:12,680 --> 03:02:15,120 NOT GENETICALLY AMENABLE. 4033 03:02:15,120 --> 03:02:17,200 SO THERE ARE BARRIERS TO 4034 03:02:17,200 --> 03:02:19,720 OVERCOME BUT ONCE WE HAVE A 4035 03:02:19,720 --> 03:02:22,400 BETTER MECHANISTIC UNDERSTANDING 4036 03:02:22,400 --> 03:02:30,440 WE WILL BE IN A BETTER ABLE. 4037 03:02:30,440 --> 03:02:33,440 7 4038 03:02:33,440 --> 03:02:36,080 >> SO WHEN I'M THINKING ABOUT 4039 03:02:36,080 --> 03:02:38,120 ENGRAPHMENT OR PERSISTENCE AND 4040 03:02:38,120 --> 03:02:41,120 THE NICHE THERE IS SOME THINGS 4041 03:02:41,120 --> 03:02:42,360 THAT WE NEED TO KNOW. 4042 03:02:42,360 --> 03:02:46,040 WE HAVE AN IN TUITION ABOUT IT. 4043 03:02:46,040 --> 03:02:48,520 FOR EXAMPLE IN THE GUT THE 4044 03:02:48,520 --> 03:02:51,040 MICROBIOTA THAT IS ADHERENT TO 4045 03:02:51,040 --> 03:02:55,040 THE MUCOUS OR IS IN AFFIX WITH 4046 03:02:55,040 --> 03:02:56,640 THE HOST. 4047 03:02:56,640 --> 03:02:59,400 BECAUSE THINGS THAT DON'T -- 4048 03:02:59,400 --> 03:03:01,200 BASICALLY FLOW THROUGH AND GIVEN 4049 03:03:01,200 --> 03:03:03,240 WINDOWS THEY WILL DISAPPEAR 4050 03:03:03,240 --> 03:03:04,840 AFTER A CERTAIN PERIOD OF TIME. 4051 03:03:04,840 --> 03:03:06,480 THAT IS A CURRENT NOTION. 4052 03:03:06,480 --> 03:03:10,720 I DON'T KNOW IF IT'S ABSOLUTELY 4053 03:03:10,720 --> 03:03:12,680 PROVEN BUT THERE ARE HUMAN 4054 03:03:12,680 --> 03:03:13,840 OBSERVATIONS THAT WOULD SUGGEST 4055 03:03:13,840 --> 03:03:16,360 THAT IS TRUE. 4056 03:03:16,360 --> 03:03:18,400 SINCE I'M A GASTROENTEROLOGIST 4057 03:03:18,400 --> 03:03:22,320 WE KNOW THAT PEOPLE GET 4058 03:03:22,320 --> 03:03:23,440 COLONOSCOPIES THEY FLUSH OUT 4059 03:03:23,440 --> 03:03:25,320 EVERYTHING AND WITHIN A SHORT 4060 03:03:25,320 --> 03:03:28,560 AMOUNT OF TIME THEIR MICROBIOTA 4061 03:03:28,560 --> 03:03:29,520 RECONSTITUTES. 4062 03:03:29,520 --> 03:03:31,440 BECAUSE OF THE ORGANISMS THAT 4063 03:03:31,440 --> 03:03:33,840 HAVE BEEN GRAFTED OR ARE 4064 03:03:33,840 --> 03:03:35,640 PERSISTENT IN THE MUCUS AND ARE 4065 03:03:35,640 --> 03:03:37,000 ASSOCIATED WITH THE HUMAN HOST 4066 03:03:37,000 --> 03:03:41,440 AND THEY'VE REGENERATED. 4067 03:03:41,440 --> 03:03:43,600 THAT GIVES US THE PRINCIPLE THAT 4068 03:03:43,600 --> 03:03:45,640 THOSE ORGANISMS THAT ARE 4069 03:03:45,640 --> 03:03:47,840 ASSOCIATED WITH US MAY BE THE 4070 03:03:47,840 --> 03:03:49,240 MOST IMPORTANT WHEN WE THINK 4071 03:03:49,240 --> 03:03:51,400 ABOUT PERSISTENCE AND 4072 03:03:51,400 --> 03:03:51,840 ENGRAPHMENT. 4073 03:03:51,840 --> 03:03:53,640 ONE THING THAT WE DID NOT TALK 4074 03:03:53,640 --> 03:03:58,600 ABOUT SO FAR IS THE NOTION OF "A 4075 03:03:58,600 --> 03:04:03,440 BIOFILM." 4076 03:04:03,440 --> 03:04:07,200 ONE CAN THINK ABOUT IT AT A 4077 03:04:07,200 --> 03:04:09,680 COMPLEX COMMUNITY JUST AS IS 4078 03:04:09,680 --> 03:04:13,960 TOOTH ENAMEL OR CONSORTIUM THAT 4079 03:04:13,960 --> 03:04:15,960 EXIST WITH EACH OTHER AND THIS 4080 03:04:15,960 --> 03:04:20,440 GETS TO A LEAPING NOTION OF A 4081 03:04:20,440 --> 03:04:24,000 COMMUNITIES THAT COEXIST BECAUSE 4082 03:04:24,000 --> 03:04:36,000 OF MUTUAL INTERACTIONS. 4083 03:04:36,000 --> 03:04:37,840 >> A QUESTION BUILT ON SOMETHING 4084 03:04:37,840 --> 03:04:39,440 GARY JUST SAID BUT TO START WITH 4085 03:04:39,440 --> 03:04:43,840 ONE OF THE THINGS -- THROUGHOUT 4086 03:04:43,840 --> 03:04:46,280 THE SESSION FOCUSED OFF STRAINS 4087 03:04:46,280 --> 03:04:49,280 AND EVEN YESTERDAY TO SOME 4088 03:04:49,280 --> 03:04:52,240 EXTENT TO THINKING ABOUT STRAIN 4089 03:04:52,240 --> 03:04:56,280 PHENOTYPE AND METABOLIC OUTPUT 4090 03:04:56,280 --> 03:04:56,880 PATHWAYS. 4091 03:04:56,880 --> 03:04:58,960 THIS IDEA OF NexGen BEING 4092 03:04:58,960 --> 03:05:01,480 ASSOCIATED WITH SOME SORT OF 4093 03:05:01,480 --> 03:05:02,880 MECHANISM OF ACTION OR 4094 03:05:02,880 --> 03:05:03,760 THERAPEUTIC BENEFIT. 4095 03:05:03,760 --> 03:05:07,720 AND WE HEARD A COUPLE OF 4096 03:05:07,720 --> 03:05:11,800 EXAMPLES OF WHERE A PHENOTYPE IS 4097 03:05:11,800 --> 03:05:13,600 IDENTIFIED AND VERIFIED AND 4098 03:05:13,600 --> 03:05:15,840 MAYBE EITHER AN ANIMAL SYSTEM OR 4099 03:05:15,840 --> 03:05:18,400 OTHER WAYS AND THAT MY QUESTION 4100 03:05:18,400 --> 03:05:20,480 TO THE ENTIRE PANEL IS HOW 4101 03:05:20,480 --> 03:05:22,280 IMPORTANT IS IT TO UNDERSTAND 4102 03:05:22,280 --> 03:05:25,360 THE PHENOTYPES AND HOW 4103 03:05:25,360 --> 03:05:26,600 PHENOTYPES CHANGE DEPENDING ON 4104 03:05:26,600 --> 03:05:28,240 THE SYSTEM THEY ARE IN. 4105 03:05:28,240 --> 03:05:30,680 A PHENOTYPE FOR BUTYRATE IS 4106 03:05:30,680 --> 03:05:33,000 OUTPUT AS ONE IN ISOLATION 4107 03:05:33,000 --> 03:05:34,840 VERSUS A FECAL SLURRY. 4108 03:05:34,840 --> 03:05:37,440 THAT TYPE OF CHANGE SO I'M 4109 03:05:37,440 --> 03:05:39,520 THINKING OF SYSTEMS FOR EXAMPLE 4110 03:05:39,520 --> 03:05:41,560 JUST LOOKING AT IT IN THE 4111 03:05:41,560 --> 03:05:45,840 CONTEXT OF A COMPLEX MICROBIAL 4112 03:05:45,840 --> 03:05:48,400 ECOSYSTEM OR BIOREACT OR IN THAT 4113 03:05:48,400 --> 03:05:49,360 WAY OR ANOTHER SYSTEM THAT I 4114 03:05:49,360 --> 03:05:54,360 HEARD MENTIONED OR ORGANOIDS AND 4115 03:05:54,360 --> 03:05:57,280 THIS IDEA OF INTESTINAL 4116 03:05:57,280 --> 03:05:59,040 ORGANOIDS AND HOW THEY CAN BE 4117 03:05:59,040 --> 03:06:03,160 USED TO STUDY -- GARY MENTIONED 4118 03:06:03,160 --> 03:06:06,560 O2 AND GEOGRAPHY -- WITHIN THE 4119 03:06:06,560 --> 03:06:09,840 MUCOS A AND ALSO BIOFILMS. 4120 03:06:09,840 --> 03:06:12,040 AS WE UNPACK AND SELECT AND WE 4121 03:06:12,040 --> 03:06:14,040 THINK WE'VE LOCKED DOWN THE 4122 03:06:14,040 --> 03:06:15,720 PHENOTYPE HOW IMPORTANT IS IT 4123 03:06:15,720 --> 03:06:17,160 FOR EACH INDIVIDUAL PROGRAM AS 4124 03:06:17,160 --> 03:06:19,840 THEY ADVANCE TO TEST THE 4125 03:06:19,840 --> 03:06:21,480 DURABILITY WITHIN THE DIFFERENT 4126 03:06:21,480 --> 03:06:22,600 CONTEXT. 4127 03:06:22,600 --> 03:06:23,480 MAYBE -- 4128 03:06:23,480 --> 03:06:25,640 >> ARE YOU LOOKING FOR MODELS? 4129 03:06:25,640 --> 03:06:26,560 >> YES. 4130 03:06:26,560 --> 03:06:27,960 EXACTLY AND AGAIN IT DOESN'T 4131 03:06:27,960 --> 03:06:29,840 HAVE TO BE JUST THE GUT BUT IT 4132 03:06:29,840 --> 03:06:31,160 CAN BE OTHERWISE. 4133 03:06:31,160 --> 03:06:34,520 FOCUSING ON PHENOTYPES THAT ARE 4134 03:06:34,520 --> 03:06:36,840 IMPORTANT AND METABOLIC OUTPUT 4135 03:06:36,840 --> 03:06:38,400 AND HOW THAT MIGHT CHANGE 4136 03:06:38,400 --> 03:06:40,280 DEPENDING ON THE SYSTEM THAT 4137 03:06:40,280 --> 03:06:42,000 YOU'RE LOOKING AT. 4138 03:06:42,000 --> 03:06:48,160 AND I'LL STOP THERE. 4139 03:06:48,160 --> 03:07:02,560 >> ANY RESPONSES FROM THE PANEL? 4140 03:07:02,560 --> 03:07:03,960 >> IT WOULD MAKE PERFECT SENSE 4141 03:07:03,960 --> 03:07:06,280 THAT THE PHENOTYPE WOULD BE 4142 03:07:06,280 --> 03:07:07,400 DIFFERENT. 4143 03:07:07,400 --> 03:07:09,960 THERE IS IG AND ALL KINDS OF 4144 03:07:09,960 --> 03:07:10,720 OTHER STUFF. 4145 03:07:10,720 --> 03:07:11,200 OXYGEN. 4146 03:07:11,200 --> 03:07:12,080 PERHAPS FOOD. 4147 03:07:12,080 --> 03:07:14,560 THAT IS VERY DIFFERENT 4148 03:07:14,560 --> 03:07:16,200 ENVIRONMENT THAN EVEN THE LARGE 4149 03:07:16,200 --> 03:07:19,760 ENTRUST ON OR COLON. 4150 03:07:19,760 --> 03:07:22,040 SO YOU COULD EXPECT DIFFERENT 4151 03:07:22,040 --> 03:07:23,720 PHENOTYPES ACROSS THE GUT AND 4152 03:07:23,720 --> 03:07:24,920 IT'S IMPORTANT TO FIGURE OUT HOW 4153 03:07:24,920 --> 03:07:26,840 TO ACTUALLY PROFILE THAT. 4154 03:07:26,840 --> 03:07:30,040 CAN WE DO -- IN THESE 4155 03:07:30,040 --> 03:07:32,560 COMMUNITIES OR CAN WE JUST TO 4156 03:07:32,560 --> 03:07:35,120 UNDERSTAND THE ISSUE -- DYNAMICS 4157 03:07:35,120 --> 03:07:38,640 AND GENE EXPRESSION -- WOULD BE 4158 03:07:38,640 --> 03:07:39,800 INTERESTING AND IMPORTANT TO 4159 03:07:39,800 --> 03:07:42,760 KNOW. 4160 03:07:42,760 --> 03:07:46,600 I MEAN I'M 99.9% THEY WILL BE 4161 03:07:46,600 --> 03:07:47,440 DIFFERENT. 4162 03:07:47,440 --> 03:07:49,600 JUST DON'T KNOW WHAT KIND OF 4163 03:07:49,600 --> 03:07:50,520 DIFFERENCES THERE WOULD BE. 4164 03:07:50,520 --> 03:07:51,600 7 4165 03:07:51,600 --> 03:07:55,640 >> RYAN -- LOOKS LIKE SOMEBODY 4166 03:07:55,640 --> 03:07:57,640 ELSE RAISED THEIR HAND SO I'LL 4167 03:07:57,640 --> 03:08:01,440 WAIT. 4168 03:08:01,440 --> 03:08:01,880 >> OKAY. 4169 03:08:01,880 --> 03:08:06,720 MY QUESTION IS FOR GARY. 4170 03:08:06,720 --> 03:08:11,440 THAT IN PANKY YACHTIC CANCER WE 4171 03:08:11,440 --> 03:08:14,440 -- ARE LOOKING FOR SOME MARKERS 4172 03:08:14,440 --> 03:08:19,280 * THAT CAN DETECT PANCREATIC 4173 03:08:19,280 --> 03:08:21,400 CANCER EARLY AND WHAT ARE 4174 03:08:21,400 --> 03:08:23,280 MICROBIOMES AND THEIR -- RELATED 4175 03:08:23,280 --> 03:08:24,120 TO CANCER. 4176 03:08:24,120 --> 03:08:28,000 THE QUESTION IS DO YOU SEE WHAT 4177 03:08:28,000 --> 03:08:31,760 ARE MICR MICROBIOTA IN COLITIS OR 4178 03:08:31,760 --> 03:08:35,400 CHRON'S DISEASE. 4179 03:08:35,400 --> 03:08:36,680 HAVE YOU SEEN THAT? 4180 03:08:36,680 --> 03:08:37,440 >> YES. 4181 03:08:37,440 --> 03:08:40,080 IT'S ACTUALLY INTERESTING. 4182 03:08:40,080 --> 03:08:41,440 -- IT SEEMS TO BE ASSOCIATED 4183 03:08:41,440 --> 03:08:43,440 WITH A NUMBER OF DIFFERENT 4184 03:08:43,440 --> 03:08:47,160 DISEASES AS YOU POINTED OUT. 4185 03:08:47,160 --> 03:08:49,800 IN PANCREATIC CANCER. 4186 03:08:49,800 --> 03:08:52,880 BUT IN INFLAMMATORY BOWEL 4187 03:08:52,880 --> 03:08:58,320 DISEASE AND EVEN IN COLON CANCER 4188 03:08:58,320 --> 03:09:03,240 -- -- SO YOU CAN THINK OF IT AS 4189 03:09:03,240 --> 03:09:04,520 ONE LONG TUBE AND THE THINGS 4190 03:09:04,520 --> 03:09:07,120 THAT YOU SWALLOW IN YOUR MOUTH 4191 03:09:07,120 --> 03:09:09,360 COULD EASILY END UP THROUGHOUT 4192 03:09:09,360 --> 03:09:15,400 YOUR I INTESTINAL TRACT. 4193 03:09:15,400 --> 03:09:17,960 THERE ARE A NUMBER OF EXAMPLES 4194 03:09:17,960 --> 03:09:20,400 INCLUDING INFLAMMATORY BOWEL 4195 03:09:20,400 --> 03:09:21,240 DISEASE. 4196 03:09:21,240 --> 03:09:23,040 I'M SURE THERE ARE STUDIES THAT 4197 03:09:23,040 --> 03:09:25,360 I'M NOT AWARE OF LOOKING AT 4198 03:09:25,360 --> 03:09:27,440 STRAIN ASSOCIATIONS BETWEEN WHAT 4199 03:09:27,440 --> 03:09:29,240 IS IN THE MOUTH AND WHAT IS IN 4200 03:09:29,240 --> 03:09:30,880 THE INTESTINAL TRACT. 4201 03:09:30,880 --> 03:09:33,640 AND ASSOCIATED WITH INFLAMMATORY 4202 03:09:33,640 --> 03:09:36,000 CONTEXT LIKE THE -- TAMI MIGHT 4203 03:09:36,000 --> 03:09:37,640 HAVE A BETTER NOTION OF THAT 4204 03:09:37,640 --> 03:09:39,960 THAN ME. 4205 03:09:39,960 --> 03:09:43,440 I CAN'T PULL OUT LITERATURE ON 4206 03:09:43,440 --> 03:09:44,000 THAT. 4207 03:09:44,000 --> 03:09:46,240 BUT I DID WANT TO ACTUALLY 4208 03:09:46,240 --> 03:09:48,600 RESPOND TO RYAN'S QUESTION ABOUT 4209 03:09:48,600 --> 03:09:50,360 MODEL SYSTEMS. 4210 03:09:50,360 --> 03:09:52,880 SO WHEN I THINK ABOUT IT THESE 4211 03:09:52,880 --> 03:09:54,680 MODEL SYSTEMS ARE BASICALLY IF 4212 03:09:54,680 --> 03:09:56,720 YOUR GOAL IS TO TREAT AND 4213 03:09:56,720 --> 03:09:58,720 UNDERSTAND HUMAN PHYSIOLOGY 4214 03:09:58,720 --> 03:10:01,480 THESE MODEL SYSTEMS ARE BASED ON 4215 03:10:01,480 --> 03:10:04,240 FENO COPY WHAT WE ACTUALLY SEE 4216 03:10:04,240 --> 03:10:07,680 IN HUMAN BIOLOGY BUT WE CANNOT 4217 03:10:07,680 --> 03:10:11,080 STUDY HUMAN BIOLOGY BECAUSE IT'S 4218 03:10:11,080 --> 03:10:12,040 TOO COMPLEX. 4219 03:10:12,040 --> 03:10:15,480 TO FIGURE OUT CAUSE AND EFFECT 4220 03:10:15,480 --> 03:10:16,720 MECHANISMS BUS JUST BECAUSE WE 4221 03:10:16,720 --> 03:10:20,440 TRY TO FENO COPY WHAT WE SEE IN 4222 03:10:20,440 --> 03:10:23,120 HUMANS DOESN'T MEAN THAT THAT IS 4223 03:10:23,120 --> 03:10:24,840 ACTUALLY THE COMPLETE ANSWER TO 4224 03:10:24,840 --> 03:10:26,600 THE BIOLOGICAL MECHANISM. 4225 03:10:26,600 --> 03:10:28,440 THE WAY I WOULD THINK ABOUT IT 4226 03:10:28,440 --> 03:10:32,760 IS IF YOU CAN COME AT IT FROM 4227 03:10:32,760 --> 03:10:35,640 SEVERAL SYSTEMS AND COME UP WITH 4228 03:10:35,640 --> 03:10:37,640 A CONSISTENT ANSWER THEN YOU'RE 4229 03:10:37,640 --> 03:10:40,080 FENO COPYING HUMAN BIOLOGY 4230 03:10:40,080 --> 03:10:43,640 WHETHER YOU'RE USING ORGANOIDS 4231 03:10:43,640 --> 03:10:45,640 OR WHATEVER OR A MOUSE MODEL 4232 03:10:45,640 --> 03:10:47,960 SYSTEM IF THEY POINT IN THE SAME 4233 03:10:47,960 --> 03:10:49,640 DIRECTION IT'S LIKELY TO BE MORE 4234 03:10:49,640 --> 03:10:51,040 TRUE THAN JUST ONE PARTICULAR 4235 03:10:51,040 --> 03:10:51,800 MODEL SYSTEM. 4236 03:10:51,800 --> 03:10:52,960 7 4237 03:10:52,960 --> 03:10:55,280 >> I WAS THINKING -- FROM A 4238 03:10:55,280 --> 03:10:56,680 DEVELOPMENT STANDPOINT. 4239 03:10:56,680 --> 03:10:59,040 AS WE PULL THESE OUT OF THE LAB 4240 03:10:59,040 --> 03:11:01,240 AND START TO DEVELOP AND TRY TO 4241 03:11:01,240 --> 03:11:04,160 UNDERSTAND HOW THEY WORK MORE 4242 03:11:04,160 --> 03:11:07,840 HOW VALUABLE IS THIS TYPE OF 4243 03:11:07,840 --> 03:11:08,400 CHARACTERIZATION. 4244 03:11:08,400 --> 03:11:13,040 TO ME IT SEEMS IMPORTANT BUT NOT 4245 03:11:13,040 --> 03:11:13,440 ESSENTIAL. 4246 03:11:13,440 --> 03:11:17,040 AND GOING ALONG WITH THAT HOW -- 4247 03:11:17,040 --> 03:11:19,320 DOES ONE TAKE A MODEL SYSTEM AND 4248 03:11:19,320 --> 03:11:22,200 TRY TO UNDERSTAND FRIENDS STRAIN 4249 03:11:22,200 --> 03:11:22,640 EVOLUTION. 4250 03:11:22,640 --> 03:11:26,520 WHERE PERHAPS A STRAIN EVOLVES 4251 03:11:26,520 --> 03:11:28,240 BASED ON THE PRESSURE FROM THE 4252 03:11:28,240 --> 03:11:33,880 HOST TO ENGRAFT OR PERSIST 4253 03:11:33,880 --> 03:11:35,920 VERSUS SOMETHING WHERE J.P. WAS 4254 03:11:35,920 --> 03:11:38,240 TALKING ABOUT THAT IS NOT THE 4255 03:11:38,240 --> 03:11:40,320 GOAL AT ALL. 4256 03:11:40,320 --> 03:11:42,320 ENGRAFT MEANT MAY NOT BE THE 4257 03:11:42,320 --> 03:11:43,640 GOAL. 4258 03:11:43,640 --> 03:11:45,280 * AND THAT SYSTEM THERE IS 4259 03:11:45,280 --> 03:11:47,640 DIFFERENT THERE ARE DIFFERENT 4260 03:11:47,640 --> 03:11:49,520 REQUIREMENTS FOR 4261 03:11:49,520 --> 03:11:49,920 CHARACTERIZATION. 4262 03:11:49,920 --> 03:11:51,440 THAT IS ALL I'M THINKING. 4263 03:11:51,440 --> 03:11:53,960 THE KIND OF DICHOTOMY. 4264 03:11:53,960 --> 03:11:57,040 I DON'T KNOW IF YOU OR J.P. WANT 4265 03:11:57,040 --> 03:12:06,440 TO PINE ON THAT AT ALL. 4266 03:12:06,440 --> 03:12:07,680 >> AND I AGREE. 4267 03:12:07,680 --> 03:12:10,240 IT DEPENDS ON WHAT YOU'RE 4268 03:12:10,240 --> 03:12:12,440 STUDYING AND WHICH CONTEXT 4269 03:12:12,440 --> 03:12:14,760 YOU'RE STUDYING IT IS AND DON'T 4270 03:12:14,760 --> 03:12:17,000 GET ME WRONG I'M NOT SAYING THAT 4271 03:12:17,000 --> 03:12:18,040 COLONIZATION IS NEVER A 4272 03:12:18,040 --> 03:12:19,120 REQUIREMENT. 4273 03:12:19,120 --> 03:12:21,120 IT MAY CERTAIN BEING SITUATIONS 4274 03:12:21,120 --> 03:12:23,440 WHERE ENGRAPHMENT OF 4275 03:12:23,440 --> 03:12:28,240 COLONIZATION DOES CONTRIBUTE TO 4276 03:12:28,240 --> 03:12:33,120 THE MICROBIAL EFFECT BUT IN MY 4277 03:12:33,120 --> 03:12:34,920 HUMBLE EFFECT THAT COLONIZATION 4278 03:12:34,920 --> 03:12:37,080 IS NOT A REQUIREMENT. 4279 03:12:37,080 --> 03:12:39,080 BUT I AGREE WITH WHAT YOU WERE 4280 03:12:39,080 --> 03:12:40,520 SAYING EARLIER. 4281 03:12:40,520 --> 03:12:43,320 JUST MY TWO CENTS. 4282 03:12:43,320 --> 03:12:45,240 >> INTERESTED IN METABOLITE 4283 03:12:45,240 --> 03:12:46,880 PRODUCTION MAYBE YOU DON'T 4284 03:12:46,880 --> 03:12:49,640 NECESSARILY NEED TO HAVE THE 4285 03:12:49,640 --> 03:12:50,920 ORGANIZE I WILL ENGRAPH. 4286 03:12:50,920 --> 03:12:53,960 YOU CAN TAKE IT ON A REGULAR 4287 03:12:53,960 --> 03:12:54,480 BASES. 4288 03:12:54,480 --> 03:12:56,600 IT'S GOING TO PRODUCE THE 4289 03:12:56,600 --> 03:13:01,280 METABOLITE OF INTEREST. 4290 03:13:01,280 --> 03:13:04,040 >> I AGREE BUT IT DEPENDS ON HOW 4291 03:13:04,040 --> 03:13:06,640 MANY METABOLITES YOU WANT TO 4292 03:13:06,640 --> 03:13:07,560 PRODUCE. 4293 03:13:07,560 --> 03:13:08,680 ACTIVE TREATMENT OF DISEASE AND 4294 03:13:08,680 --> 03:13:10,040 I AGREE. 4295 03:13:10,040 --> 03:13:12,200 WE CAN PROBABLY DESIGN SOME 4296 03:13:12,200 --> 03:13:14,640 BACTERIA THAT HAS SOME 4297 03:13:14,640 --> 03:13:17,720 THERAPEUTIC EFFECT WHILE THEY 4298 03:13:17,720 --> 03:13:22,520 ARE -- PASSING THROUGH. 4299 03:13:22,520 --> 03:13:26,960 YOU WANT TO HAVE ENGRAPHMENT AND 4300 03:13:26,960 --> 03:13:32,520 ALSO FOR MAYBE I'M TOO 4301 03:13:32,520 --> 03:13:34,360 FUTURISTIC -- WHERE WE HAVE MANY 4302 03:13:34,360 --> 03:13:37,680 MICROBE THAT'S WE ADD TO OUR 4303 03:13:37,680 --> 03:13:38,800 MICROBIOMES DURING HEALTH AND 4304 03:13:38,800 --> 03:13:41,040 THE FUTURE OF MEDICINE IS ABOUT 4305 03:13:41,040 --> 03:13:42,600 PROLONGING HEALTH AND NOT JUST 4306 03:13:42,600 --> 03:13:45,600 TREATING DISEASE AND IN THAT 4307 03:13:45,600 --> 03:13:47,440 CASE I THINK ENGRAPHMENT SHOULD 4308 03:13:47,440 --> 03:13:53,160 BE A GOAL. 4309 03:13:53,160 --> 03:13:55,880 >> YOU HAVE YOUR HAND UP -- 4310 03:13:55,880 --> 03:14:00,320 >> CAN YOU HEAR ME? 4311 03:14:00,320 --> 03:14:00,800 >> GREAT. 4312 03:14:00,800 --> 03:14:06,000 I'M ON MY BIKE AND I'VE BEEN 4313 03:14:06,000 --> 03:14:07,880 LISTENING IN AND A GREAT MORNING 4314 03:14:07,880 --> 03:14:09,240 SESSION. 4315 03:14:09,240 --> 03:14:12,080 JUST -- TO ADD A BRIEF COMMENT 4316 03:14:12,080 --> 03:14:14,600 ABOUT THE CONCEPT OF ENGRAPHMENT 4317 03:14:14,600 --> 03:14:18,640 I THINK -- THE NexGen 4318 03:14:18,640 --> 03:14:20,600 PRO-BIOTICS IDEA IS SUCH A BROAD 4319 03:14:20,600 --> 03:14:21,160 ONE. 4320 03:14:21,160 --> 03:14:24,440 AND WE'RE BUILDING OFF OF THIS 4321 03:14:24,440 --> 03:14:27,080 WELL SEND DEFINITION OF 4322 03:14:27,080 --> 03:14:28,160 PRO-BIOTICS BUT WE'RE TALKING 4323 03:14:28,160 --> 03:14:32,040 ABOUT A HUGE RANGE OF POTENTIAL 4324 03:14:32,040 --> 03:14:33,480 APPLICATIONS, PRODUCTS, 4325 03:14:33,480 --> 03:14:35,840 INDICATIONS AND I THINK WE DON'T 4326 03:14:35,840 --> 03:14:40,040 WANT TO BE TOO ENCUMBERED BY THE 4327 03:14:40,040 --> 03:14:46,760 TRADITIONAL ARE DIGS -- CONCEPT 4328 03:14:46,760 --> 03:14:47,640 *. 4329 03:14:47,640 --> 03:14:49,480 MAKING SURE WE FRAME THE 4330 03:14:49,480 --> 03:14:51,640 CONVERSATION AROUND NOTHING 4331 03:14:51,640 --> 03:14:52,680 BEING MUTUALLY EXCLUSIVE. 4332 03:14:52,680 --> 03:14:55,040 THERE ARE SO MANY POSSIBILITIES 4333 03:14:55,040 --> 03:14:58,560 THAT ENGRAPHMENT MAYBE PARTIAL 4334 03:14:58,560 --> 03:14:59,320 ENGRAPH MEANT. 4335 03:14:59,320 --> 03:15:00,400 MAYBE TEMPORARY. 4336 03:15:00,400 --> 03:15:02,560 ALL OF THESE THINGS ARE SUPER 4337 03:15:02,560 --> 03:15:04,440 EXCITING SO I JUST WANTED TO ADD 4338 03:15:04,440 --> 03:15:04,640 THAT. 4339 03:15:04,640 --> 03:15:05,480 THANK YOU. 4340 03:15:05,480 --> 03:15:10,320 >> THANK YOU. 4341 03:15:10,320 --> 03:15:15,720 >> I HAVE ANOTHER QUESTION -- -- 4342 03:15:15,720 --> 03:15:18,840 REPORTED MANY TIMES WITH MANY 4343 03:15:18,840 --> 03:15:20,280 MICROORGANISMS AND WE KNOW THAT 4344 03:15:20,280 --> 03:15:29,400 THIS IS -- -- ---SO HOW MUCH -- 4345 03:15:29,400 --> 03:15:30,280 REGENERATION DO YOU HAVE -- AND 4346 03:15:30,280 --> 03:15:35,560 ALSO IN COLON ESPECIALLY LEFT 4347 03:15:35,560 --> 03:15:38,560 AND RIGHT COLON THEY HAVE -- -- 4348 03:15:38,560 --> 03:15:49,880 THAT -- PHENOTYPE -- AND -- --- 4349 03:15:49,880 --> 03:16:01,280 ---SO HOW MUCH EPPI -- EPIGENETICS -- 4350 03:16:01,280 --> 03:16:23,760 >> ANYBODY? 4351 03:16:23,760 --> 03:16:26,080 >> BUTYRATE IS AN INHIBITOR -- 4352 03:16:26,080 --> 03:16:31,400 SO IT REALLY IS A VERY, VERY 4353 03:16:31,400 --> 03:16:33,240 BROAD LANDSCAPER OF THE 4354 03:16:33,240 --> 03:16:33,680 EPIGENOME. 4355 03:16:33,680 --> 03:16:35,240 AND I THINK THERE IS A LITTLE 4356 03:16:35,240 --> 03:16:37,400 BIT OF EVIDENCE THAT MAYBE IT 4357 03:16:37,400 --> 03:16:39,440 PLAYS A ROLE. 4358 03:16:39,440 --> 03:16:41,120 HOW MUCH EVIDENCE ACTUALLY IS 4359 03:16:41,120 --> 03:16:43,000 THAT IT WOULD SIGNIFICANTLY 4360 03:16:43,000 --> 03:16:48,680 ALTER THE EPIGENOME -- 4361 03:16:48,680 --> 03:16:51,240 INHIBITION THE WAY THAT WE WOULD 4362 03:16:51,240 --> 03:16:58,920 SEE IT IN CELL CULTURE IS -- -- 4363 03:16:58,920 --> 03:17:01,120 NORMALLY CELLS WOULD ACTUALLY 4364 03:17:01,120 --> 03:17:03,120 OXIDIZE QUICKLY AND MAY OR MAY 4365 03:17:03,120 --> 03:17:06,000 NOT ALLOW BUTYRATE TO REACH 4366 03:17:06,000 --> 03:17:08,000 CONCENTRATION THAT'S WOULD IN 4367 03:17:08,000 --> 03:17:11,840 HIP STATE THE ACTIVITY AND * AND 4368 03:17:11,840 --> 03:17:17,360 CHANGE THE NUCLEUS. 4369 03:17:17,360 --> 03:17:19,480 CELLS THAT ARE NOT -- MAY BE 4370 03:17:19,480 --> 03:17:22,800 MORE AVAILABLE TO LANDSCAPE THE 4371 03:17:22,800 --> 03:17:25,440 EPIGENOME THAT WOULD THEN 4372 03:17:25,440 --> 03:17:26,640 INHIBIT PROLIFERATION. 4373 03:17:26,640 --> 03:17:30,080 SO IT DEPENDS ON THE METABOLIC 4374 03:17:30,080 --> 03:17:31,520 CAPABILITIES OF THE CELL WHEN 4375 03:17:31,520 --> 03:17:33,120 YOU'RE JUST TALKING ABOUT 4376 03:17:33,120 --> 03:17:33,560 BUTYRATE. 4377 03:17:33,560 --> 03:17:35,600 THERE IS A BODY OF LITERATURE 4378 03:17:35,600 --> 03:17:38,640 THAT THE MICROBIOTA IS 4379 03:17:38,640 --> 03:17:40,760 ASSOCIATED WITH THE EPIGENOME. 4380 03:17:40,760 --> 03:17:42,720 HOW MUCH IS BIOLOGICALLY 4381 03:17:42,720 --> 03:17:45,520 RELEVANT IN HUMANS WE DON'T KNOW 4382 03:17:45,520 --> 03:17:45,960 THAT. 4383 03:17:45,960 --> 03:17:51,840 UNLESS I'M NOT -- I'M NOT AWARE 4384 03:17:51,840 --> 03:17:53,360 OF THE MOST RELEVANT LITERATURE 4385 03:17:53,360 --> 03:17:57,000 RIGHT NOW. 4386 03:17:57,000 --> 03:18:00,440 >> -- AND THE APPROVED -- IN 4387 03:18:00,440 --> 03:18:03,760 COMBINATION -- -- ---THEY WORK 4388 03:18:03,760 --> 03:18:05,880 VERY WELL. 4389 03:18:05,880 --> 03:18:09,120 8 4390 03:18:09,120 --> 03:18:13,760 >> SO GARY, YOU HAVE A QUESTION. 4391 03:18:13,760 --> 03:18:16,440 >> I THINK YOU DID ANSWER THE 4392 03:18:16,440 --> 03:18:19,160 QUESTION BUT THEY APPRECIATE IF 4393 03:18:19,160 --> 03:18:21,160 YOU CAN ANSWER ON THE ZOOM 4394 03:18:21,160 --> 03:18:21,640 CALLS. 4395 03:18:21,640 --> 03:18:27,280 SO HER QUESTION IS HOW JUST -- 4396 03:18:27,280 --> 03:18:32,840 LIFESTYLE INTERVENTION AND 4397 03:18:32,840 --> 03:18:36,040 STRESS MANAGEMENT CAN BE HELPFUL 4398 03:18:36,040 --> 03:18:42,040 -- COMBINE LIFESTYLE AND MICRO 4399 03:18:42,040 --> 03:18:44,840 BIOME INTERACTIONS -- THAT IS 4400 03:18:44,840 --> 03:18:46,280 THE QUESTION. 4401 03:18:46,280 --> 03:18:46,920 >> YEAH. 4402 03:18:46,920 --> 03:18:49,040 SO I THINK THAT IS A VERY 4403 03:18:49,040 --> 03:18:50,800 FORWARD THINKING QUESTION. 4404 03:18:50,800 --> 03:18:53,880 THERE IS A LOT MORE INTEREST NOW 4405 03:18:53,880 --> 03:18:57,920 ABOUT STRESS AND INFLAMMATORY 4406 03:18:57,920 --> 03:18:59,960 DISEASES AND INFLAMMATORY BOWEL 4407 03:18:59,960 --> 03:19:02,240 DISEASE IS ONE OF THE PARADIGMS. 4408 03:19:02,240 --> 03:19:05,920 THERE IS A LOT OF THOUGHT -- BUT 4409 03:19:05,920 --> 03:19:09,440 IT IS REFLECTED IN INFLAMMATORY 4410 03:19:09,440 --> 03:19:11,080 BOWEL DISEASE. 4411 03:19:11,080 --> 03:19:14,840 HOW MUCH IS ACTUALLY AN EFFECT 4412 03:19:14,840 --> 03:19:17,280 TO DISEASE MANAGEMENT WE DON'T 4413 03:19:17,280 --> 03:19:19,320 HAVE EXACT NOTION OF THAT IN 4414 03:19:19,320 --> 03:19:20,640 HUMANS. 4415 03:19:20,640 --> 03:19:22,440 CERTAINLY ANIMAL MODELS STRESS 4416 03:19:22,440 --> 03:19:24,960 IS IMPORTANT IN REGULATING THE 4417 03:19:24,960 --> 03:19:25,680 IMMUNE RESPONSE BUT THINKING 4418 03:19:25,680 --> 03:19:29,440 FORWARD IT MAY ACTUALLY BE MORE 4419 03:19:29,440 --> 03:19:31,240 IN A MAINTENANCE PHASE OF 4420 03:19:31,240 --> 03:19:32,960 TREATMENT. 4421 03:19:32,960 --> 03:19:34,400 IN OTHER WORDS MAYBE IT'S GOING 4422 03:19:34,400 --> 03:19:36,520 TO BE VERY DIFFICULT IN TERMS OF 4423 03:19:36,520 --> 03:19:39,720 JUST LIFESTYLE MODIFICATIONS OR 4424 03:19:39,720 --> 03:19:41,960 EVEN THE NEXT GENERATION OF 4425 03:19:41,960 --> 03:19:43,520 PRO-BIOTICS TO TREAT ACTIVE 4426 03:19:43,520 --> 03:19:45,720 DISEASE FOR MANY REASONS THAT WE 4427 03:19:45,720 --> 03:19:47,040 HIGHLIGHTED THIS MORNING. 4428 03:19:47,040 --> 03:19:49,440 HOWEVER ONCE YOU INDUCE 4429 03:19:49,440 --> 03:19:51,440 REMISSION THE OPPORTUNITY THEN 4430 03:19:51,440 --> 03:19:52,480 IS CAN YOU CHANGE THE 4431 03:19:52,480 --> 03:19:52,880 ENVIRONMENT? 4432 03:19:52,880 --> 03:19:55,440 AND THAT WOULD BE YOUR LIFESTYLE 4433 03:19:55,440 --> 03:19:56,800 TOO. 4434 03:19:56,800 --> 03:19:58,280 LIFESTYLE, REDUCE STRESS. 4435 03:19:58,280 --> 03:20:00,320 EAT A HEALTHIER DIET. 4436 03:20:00,320 --> 03:20:02,960 TAKE THE RIGHT PRO-BIOTIC. 4437 03:20:02,960 --> 03:20:04,520 AND CHANGE THE ENVIRONMENT SO 4438 03:20:04,520 --> 03:20:08,480 YOU CAN REDUCE IMMUNO 4439 03:20:08,480 --> 03:20:10,120 SUPPRESSION. 4440 03:20:10,120 --> 03:20:13,240 THERE IS A NOTION THAT AND THIS 4441 03:20:13,240 --> 03:20:17,720 IS EVEN GOES TO THE TRANSPLANT 4442 03:20:17,720 --> 03:20:19,000 PHYSIOLOGY THAT YOU MIGHT BE 4443 03:20:19,000 --> 03:20:22,920 ABLE TO REDUCE OR ELIMINATE IT 4444 03:20:22,920 --> 03:20:25,040 BUT YOU MIGHT NEED TO CHANGE THE 4445 03:20:25,040 --> 03:20:25,480 ENVIRONMENT. 4446 03:20:25,480 --> 03:20:29,040 THAT IS WHERE COMPANION 4447 03:20:29,040 --> 03:20:31,000 DIAGNOSTIC WOULD BE IMPORTANT. 4448 03:20:31,000 --> 03:20:32,800 YOU DON'T WANT TO HAVE 4449 03:20:32,800 --> 03:20:34,040 SOMEBODY'S DISEASE GO 4450 03:20:34,040 --> 03:20:34,440 UNCONTROLLED. 4451 03:20:34,440 --> 03:20:36,800 YOU WANT TO IDENTIFY IN ADVANCE 4452 03:20:36,800 --> 03:20:39,320 WHO YOU MIGHT BE ABLE TO SAFELY 4453 03:20:39,320 --> 03:20:40,760 REDUCE IMMUNO SUPPRESSION. 4454 03:20:40,760 --> 03:20:42,440 SO IT'S A VERY FORWARD THINKING 4455 03:20:42,440 --> 03:20:44,320 AND IT WOULD BE THE ULTIMATE 4456 03:20:44,320 --> 03:20:45,200 GOAL. 4457 03:20:45,200 --> 03:20:47,160 >> THANK YOU. 4458 03:20:47,160 --> 03:20:49,480 ANYTHING TO ADD TO THAT? 4459 03:20:49,480 --> 03:20:52,160 >> I WAS GOING TO ECHO WHAT -- 4460 03:20:52,160 --> 03:20:53,440 GARY SAID. 4461 03:20:53,440 --> 03:20:56,440 I THINK STRESS IS A COMPLICATED 4462 03:20:56,440 --> 03:20:57,080 FEATURE. 4463 03:20:57,080 --> 03:21:00,840 STRESS MAY BE INVOLVED IN THE 4464 03:21:00,840 --> 03:21:03,720 EARLY PATHOGENESIS OR 4465 03:21:03,720 --> 03:21:04,600 COMORBIDITY. 4466 03:21:04,600 --> 03:21:07,320 BUT IN IBD IT MAY COME AFTER THE 4467 03:21:07,320 --> 03:21:11,640 ONSET OF DISEASE AS BEING MORE 4468 03:21:11,640 --> 03:21:15,800 ANNEX AGE RATING FACTOR -- *. 4469 03:21:15,800 --> 03:21:18,640 WHEN IT SHOULD BE ADDRESSED AND 4470 03:21:18,640 --> 03:21:20,480 HOW WOULD DEPEND ON DIFFERENT 4471 03:21:20,480 --> 03:21:22,480 DISEASES BECAUSE IT PLAYS A PART 4472 03:21:22,480 --> 03:21:25,800 IN MOST DISEASES. 4473 03:21:25,800 --> 03:21:32,520 THEY CAN ALTER THE MUCOS A BY 4474 03:21:32,520 --> 03:21:34,600 ALTERING THE GUT. 4475 03:21:34,600 --> 03:21:37,120 THERE ARE DIFFERENCES BETWEEN 4476 03:21:37,120 --> 03:21:42,480 ACUTE AN -- AND CHRONIC STRESS. 4477 03:21:42,480 --> 03:21:45,360 IT'S RELEVANT TO MOST OF THESE 4478 03:21:45,360 --> 03:21:51,120 CHRONIC DISEASES. 4479 03:21:51,120 --> 03:21:52,480 >> MAYBE CAN I ADD A COMMENT TO 4480 03:21:52,480 --> 03:21:53,240 THIS. 4481 03:21:53,240 --> 03:21:54,440 I APPRECIATE THESE COMMENTS. 4482 03:21:54,440 --> 03:21:56,880 78 IT'S VERY IMPORTANT -- THAT 4483 03:21:56,880 --> 03:21:59,840 WE'RE INTERESTED IN WHAT WE CALL 4484 03:21:59,840 --> 03:22:01,440 MULTI-MODEL INTERVENTIONS THAT 4485 03:22:01,440 --> 03:22:03,240 ACT ON MULTIPLE ASPECTS. 4486 03:22:03,240 --> 03:22:04,560 SO THIS IS AN INTERESTING 4487 03:22:04,560 --> 03:22:05,040 THOUGHT. 4488 03:22:05,040 --> 03:22:07,680 THAT YOU COULD HAVE AND 4489 03:22:07,680 --> 03:22:08,680 MULTI-COMPONENT INTERVENTION 4490 03:22:08,680 --> 03:22:10,480 THAT COULD ADDRESS MANY FACTORS 4491 03:22:10,480 --> 03:22:11,800 INCLUDING THE DIET. 4492 03:22:11,800 --> 03:22:14,440 INCLUDING THE MICROBIOME AND 4493 03:22:14,440 --> 03:22:15,320 LIFESTYLE. 4494 03:22:15,320 --> 03:22:19,000 AND IT WOULD BRING TOGETHER A 4495 03:22:19,000 --> 03:22:23,160 LOT OF THE AREAS THAT THEY ARE 4496 03:22:23,160 --> 03:22:24,480 INTERESTED IN INCLUDING MIND AND 4497 03:22:24,480 --> 03:22:27,040 BODY THERAPIES THAT WE HAVE 4498 03:22:27,040 --> 03:22:29,000 ROBUST INTERVENTIONS NOW AND WE 4499 03:22:29,000 --> 03:22:31,400 CAN REDUCE NOT ONLY 4500 03:22:31,400 --> 03:22:33,280 PSYCHOLOGICAL STRESS BUT THE 4501 03:22:33,280 --> 03:22:40,080 INDEXES THAT INDUCE STRESS. 4502 03:22:40,080 --> 03:22:41,440 THIS MIGHT BE SOMETHING THAT 4503 03:22:41,440 --> 03:22:43,760 WOULD REALLY FIT WELL INTO THIS 4504 03:22:43,760 --> 03:22:44,240 FIELD OF WORK. 4505 03:22:44,240 --> 03:22:45,520 7 4506 03:22:45,520 --> 03:22:49,240 >> THANK YOU. 4507 03:22:49,240 --> 03:22:51,840 7 4508 03:22:51,840 --> 03:22:52,600 >> JUST TO ADD. 4509 03:22:52,600 --> 03:22:56,640 I THINK ALSO THAT LIFESTYLE AND 4510 03:22:56,640 --> 03:23:03,240 ALSO THAT IS IMPORTANT ALSO. 4511 03:23:03,240 --> 03:23:03,840 FOR HEALTH. 4512 03:23:03,840 --> 03:23:10,640 7 YOU CAN SIMPLY -- BY 4513 03:23:10,640 --> 03:23:12,040 INTRODUCING -- THE STRAIN 4514 03:23:12,040 --> 03:23:13,320 WITHOUT CHANGING ANYTHING ELSE 4515 03:23:13,320 --> 03:23:17,040 THAT IS PROBABLY NOT THE HOLY 4516 03:23:17,040 --> 03:23:17,800 GRAIL. 4517 03:23:17,800 --> 03:23:19,480 YOU ALSO NEED TO FOR EXAMPLE 4518 03:23:19,480 --> 03:23:23,000 FROM A MICROBIAL POINT OF VIEW 4519 03:23:23,000 --> 03:23:25,440 YOU CAN PRODUCE BUTYRATE -- THAT 4520 03:23:25,440 --> 03:23:27,120 YOU MIGHT BE MISSING BUT THEY 4521 03:23:27,120 --> 03:23:29,560 ALSO NEED TO PROVIDE THE SOURCE 4522 03:23:29,560 --> 03:23:32,280 FOR WHICH IT CAN PRODUCE 4523 03:23:32,280 --> 03:23:34,760 BUTYRATE BECAUSE MANY OF THE 4524 03:23:34,760 --> 03:23:39,440 MICROBES THAT ARE REVERSIBLE. 4525 03:23:39,440 --> 03:23:43,760 THE BUTYRATE PRODUCER MIGHT 4526 03:23:43,760 --> 03:23:47,840 PRODUCE -- BUTYRATE THAT IS 4527 03:23:47,840 --> 03:23:49,880 DEGRADING THE FIBERS. 4528 03:23:49,880 --> 03:23:51,880 SO I THINK THIS APPROACH THAT 4529 03:23:51,880 --> 03:23:54,640 YOU NEED ALSO PROBABLY LIFESTYLE 4530 03:23:54,640 --> 03:23:55,320 MODIFICATIONS. 4531 03:23:55,320 --> 03:23:58,760 I THINK THAT'S AN IMPORTANT ONE. 4532 03:23:58,760 --> 03:24:01,240 >> GARY. 4533 03:24:01,240 --> 03:24:05,400 >> I JUST WANTED TO ADD THAT THE 4534 03:24:05,400 --> 03:24:07,440 MULTI-MODALITY TREATMENT AND 4535 03:24:07,440 --> 03:24:09,560 LIFESTYLE ALTERATIONS IF THAT 4536 03:24:09,560 --> 03:24:11,560 INCLUDES QUALITY OF LIFE THAT'S 4537 03:24:11,560 --> 03:24:15,520 AN IMPORTANT END POINT FOR 4538 03:24:15,520 --> 03:24:15,840 PATIENCES. 4539 03:24:15,840 --> 03:24:17,520 QUALITY OF LIFE IS JUST AS 4540 03:24:17,520 --> 03:24:19,040 IMPORTANT AND WE HAVE DIFFERENT 4541 03:24:19,040 --> 03:24:24,400 TYPES OF MATRIXES AND WAYS TO 4542 03:24:24,400 --> 03:24:25,600 EVALUATE THAT. 4543 03:24:25,600 --> 03:24:28,680 THAT IS A VERY RELEVANT END 4544 03:24:28,680 --> 03:24:31,080 POINT FOR TREATMENT OF PATIENTS. 4545 03:24:31,080 --> 03:24:32,840 >> THANK YOU. 4546 03:24:32,840 --> 03:24:35,280 SO WE JUST HAVE A COUPLE OF 4547 03:24:35,280 --> 03:24:37,440 MINUTES TO GO BACK TO THE 4548 03:24:37,440 --> 03:24:38,760 GENERAL QUESTIONS THAT OUR 4549 03:24:38,760 --> 03:24:41,480 ORGANIZERS HAVE POSED TO US. 4550 03:24:41,480 --> 03:24:44,240 IF YOU HAVE ANY FINAL COMMENTS 4551 03:24:44,240 --> 03:24:46,040 ON THESE TWO QUESTIONS. 4552 03:24:46,040 --> 03:24:48,440 WHAT ARE CRITICAL GAPS IN OUR 4553 03:24:48,440 --> 03:24:51,000 KNOWLEDGE AND METHODOLOGIES FOR 4554 03:24:51,000 --> 03:24:53,120 THE RESEARCH AREAS PRESENTED? 4555 03:24:53,120 --> 03:24:56,280 AND WHAT NEW RESOURCES OR 4556 03:24:56,280 --> 03:24:59,400 METHODS -- ARE NEEDED TO FILL 4557 03:24:59,400 --> 03:25:01,120 THE GAPS IN THE SHORT-TERM OR IN 4558 03:25:01,120 --> 03:25:02,240 THE LONG-TERM? 4559 03:25:02,240 --> 03:25:04,640 IF YOU HAVE ANY FINAL CONTINUES 4560 03:25:04,640 --> 03:25:06,760 ON THESE TWO QUESTIONS WE'LL 4561 03:25:06,760 --> 03:25:09,080 SPEND A COUPLE OF MINUTES TO GO 4562 03:25:09,080 --> 03:25:10,200 OVER THEM. 4563 03:25:10,200 --> 03:25:16,440 WHO WANTS TO GO FIRST? 4564 03:25:16,440 --> 03:25:17,320 JULIE. 4565 03:25:17,320 --> 03:25:19,320 >> MY FAVORITE NEW TECHNOLOGY IS 4566 03:25:19,320 --> 03:25:23,480 THE NC2 TRANSCRIPT OMICS BECAUSE 4567 03:25:23,480 --> 03:25:25,640 WE NEED TO UNDERSTAND WHERE THE 4568 03:25:25,640 --> 03:25:28,640 MICROBES ARE WITH RESPECT TO THE 4569 03:25:28,640 --> 03:25:30,160 RELEVANT HOST CELLS. 4570 03:25:30,160 --> 03:25:32,920 BECAUSE IT LOOKS LIKE THEY ARE 4571 03:25:32,920 --> 03:25:35,120 SPECIFIC POPULATIONS. 4572 03:25:35,120 --> 03:25:43,120 THAT ARE RESPONDING TO MICROBIAL 4573 03:25:43,120 --> 03:25:44,880 COLONIZATION. 4574 03:25:44,880 --> 03:25:50,040 AND OUR -- THAT DON'T CAPTURE 4575 03:25:50,040 --> 03:25:51,480 THAT NUISANCE. 4576 03:25:51,480 --> 03:25:56,080 RIGHT NOW -- I DON'T THINK THE 4577 03:25:56,080 --> 03:25:59,400 -- HAS BEEN REALLY SOLVED FOR 4578 03:25:59,400 --> 03:26:02,480 MICROBES GIVEN HOW DIFFICULT THE 4579 03:26:02,480 --> 03:26:03,640 TECHNOLOGY IS. 4580 03:26:03,640 --> 03:26:06,040 7 BUT THERE ARE A LOT OF 4581 03:26:06,040 --> 03:26:10,600 PROMISING WORK IN THE MAMMALIAN 4582 03:26:10,600 --> 03:26:12,880 FIELD THAT I THINK WILL AT LEAST 4583 03:26:12,880 --> 03:26:15,760 BE RELATIVELY AND IMMEDIATELY 4584 03:26:15,760 --> 03:26:17,960 APPLICABLE TO LOOKING AT THESE 4585 03:26:17,960 --> 03:26:18,240 INTERACTIONS 4586 03:26:18,240 --> 03:26:18,640 >> THANK YOU. 4587 03:26:18,640 --> 03:26:21,360 8 4588 03:26:21,360 --> 03:26:23,880 >> I ALSO THINK -- ONE OF THE 4589 03:26:23,880 --> 03:26:27,520 GAPS IS -- AND THAT HAS BEEN 4590 03:26:27,520 --> 03:26:29,440 DISCUSSED THAT IS WE NEED TO 4591 03:26:29,440 --> 03:26:35,840 KNOW THE STRAIN VARIATION AND -- 4592 03:26:35,840 --> 03:26:37,400 KNOWING WHAT THEY ARE DOING. 4593 03:26:37,400 --> 03:26:41,040 BECAUSE WE ALSO LOOK AT THE NAME 4594 03:26:41,040 --> 03:26:47,840 AND -- ---THE SMALL INTESTINE -- 4595 03:26:47,840 --> 03:26:51,120 THAT DIDN'T LIKE TO SEE. 4596 03:26:51,120 --> 03:26:53,680 AND THERE IS ALSO THE IDEA THAT 4597 03:26:53,680 --> 03:27:01,840 WE SAY THAT -- -- -- AND STAPH 4598 03:27:01,840 --> 03:27:03,320 IS ALSO ASSOCIATED WITH 4599 03:27:03,320 --> 03:27:05,280 SOMETHING THAT IS NOT SO HEALTHY 4600 03:27:05,280 --> 03:27:09,480 BUT ON THE OTHER HAND -- IT'S 4601 03:27:09,480 --> 03:27:11,240 ALSO IN THE YOGURT THAT WE 4602 03:27:11,240 --> 03:27:12,240 CONSUME DAILY. 4603 03:27:12,240 --> 03:27:14,720 WE NEED TO GO INTO A NOT BASED 4604 03:27:14,720 --> 03:27:17,480 ON THE NAME JUST ASSUME THAT 4605 03:27:17,480 --> 03:27:21,040 THEY ARE IN -- OR THE OTHER AND 4606 03:27:21,040 --> 03:27:23,720 TO TAKE E. COLI AS AN EXAMPLE. 4607 03:27:23,720 --> 03:27:28,720 IT CAN BE A NASTY PATHOGEN THAT 4608 03:27:28,720 --> 03:27:30,160 CILICES YOU BUT IN ANOTHER 4609 03:27:30,160 --> 03:27:38,040 STRAIN IT CAN HELP YOU. 4610 03:27:38,040 --> 03:27:48,320 >> THANK YOU. 4611 03:27:48,320 --> 03:27:50,760 >> WE NEED TO GO BEYOND NAMES 4612 03:27:50,760 --> 03:27:52,720 AND GET TO GENOMES AND 4613 03:27:52,720 --> 03:27:53,000 FUNCTIONS. 4614 03:27:53,000 --> 03:27:54,840 AND I'M THE FIRST TO ARGUE FOR 4615 03:27:54,840 --> 03:27:58,200 THREE OTHER COMPONENTS. 4616 03:27:58,200 --> 03:27:59,640 UNDERSTANDING THINGS 4617 03:27:59,640 --> 03:28:03,040 QUANTITATIVELY IS REALLY 4618 03:28:03,040 --> 03:28:04,840 IMPORTANT BECAUSE THE RANGE OF 4619 03:28:04,840 --> 03:28:06,520 POSSIBILITY IS SO HUGE THAT IT'S 4620 03:28:06,520 --> 03:28:08,520 NOT ABOUT PERCENT ANY MORE. 4621 03:28:08,520 --> 03:28:10,040 IT'S ABOUT ABSOLUTELY 4622 03:28:10,040 --> 03:28:11,640 QUANTITIES. 4623 03:28:11,640 --> 03:28:13,880 AND ALSO SPATIAL INTERACTIONS -- 4624 03:28:13,880 --> 03:28:18,280 AND NUMBER OF PEOPLE -- -- 4625 03:28:18,280 --> 03:28:20,640 ABSOLUTELY CRITICAL IN 4626 03:28:20,640 --> 03:28:21,960 UNDERSTANDING -- THAT WOULD BE 4627 03:28:21,960 --> 03:28:24,200 REALLY IMPORTANT AND THE THIRD 4628 03:28:24,200 --> 03:28:26,480 POINT IS WE REALLY SHOULD FIND A 4629 03:28:26,480 --> 03:28:30,440 WAY TO DO THIS GREAT HUMAN AND 4630 03:28:30,440 --> 03:28:32,240 NOT MODEL SYMPTOMS. 4631 03:28:32,240 --> 03:28:33,680 IF YOU THINK BY THE WE DON'T 4632 03:28:33,680 --> 03:28:36,440 KNOW WHAT WE'RE TRYING TO MODEL. 4633 03:28:36,440 --> 03:28:37,640 AND IF YOU DON'T KNOW WHAT 4634 03:28:37,640 --> 03:28:40,440 YOU'RE TRYING TO MODEL YOU'RE 4635 03:28:40,440 --> 03:28:45,600 JUST TOE -- TRYING TO STUDY WHATEVER 4636 03:28:45,600 --> 03:28:46,600 IS IN THE DISH. 4637 03:28:46,600 --> 03:28:49,320 WE CAN BE MUCH MORE DELIBERATE 4638 03:28:49,320 --> 03:28:51,560 ABOUT BUILDING THE MODELS THAT 4639 03:28:51,560 --> 03:28:59,640 REFLECT THE HUMAN MODEL. 4640 03:28:59,640 --> 03:29:03,120 SO TO ME GETTING HUMAN DATA EVEN 4641 03:29:03,120 --> 03:29:04,800 THOUGH IT'S GOING TO BE HARD AND 4642 03:29:04,800 --> 03:29:07,040 IT'S NOT GOING TO BE POSSIBLE TO 4643 03:29:07,040 --> 03:29:09,240 DO IT IN HUGE NUMBERS BUT 4644 03:29:09,240 --> 03:29:13,080 GETTING HUMAN DATA SO WE CAN 4645 03:29:13,080 --> 03:29:15,240 ANCHOR THE OTHER WORK IS SO 4646 03:29:15,240 --> 03:29:16,880 CRITICAL THAT WE CANNOT WAIT TO 4647 03:29:16,880 --> 03:29:17,120 DO THAT. 4648 03:29:17,120 --> 03:29:19,400 THANK YOU. 4649 03:29:19,400 --> 03:29:21,120 >> GARY. 4650 03:29:21,120 --> 03:29:24,840 >> SO I WOULD SAY AN 4651 03:29:24,840 --> 03:29:26,320 ASPIRATIONAL GOALS WE BEGIN TO 4652 03:29:26,320 --> 03:29:28,520 DO MORE AND MORE HUMAN SUBJECT 4653 03:29:28,520 --> 03:29:29,640 STUDIES. 4654 03:29:29,640 --> 03:29:30,960 HUMAN INTERVENTION STUDIES. 4655 03:29:30,960 --> 03:29:33,240 IT WOULD BE GREAT AND I KNOW 4656 03:29:33,240 --> 03:29:35,400 PEOPLE HAVE TAKEN APPROACHES TO 4657 03:29:35,400 --> 03:29:38,560 THIS BUT IT COULD BE DONE 4658 03:29:38,560 --> 03:29:38,800 BETTER. 4659 03:29:38,800 --> 03:29:41,040 ACTUALLY TO SHARE DATA AND SHARE 4660 03:29:41,040 --> 03:29:41,600 INFORMATION. 4661 03:29:41,600 --> 03:29:44,480 SHARE BIOSPECIMENS BECAUSE HUMAN 4662 03:29:44,480 --> 03:29:46,400 SUBJECT STUDIES ARE EXPENSIVE 4663 03:29:46,400 --> 03:29:48,360 AND TAKE A LONG TIME TO DO AND 4664 03:29:48,360 --> 03:29:49,640 THERE IS A GREAT OPPORTUNITY TO 4665 03:29:49,640 --> 03:29:50,640 LEARN FROM EACH OTHER. 4666 03:29:50,640 --> 03:29:54,280 I KNOW THAT IN CERTAIN 4667 03:29:54,280 --> 03:29:56,560 CIRCUMSTANCES THAT MIGHT BE 4668 03:29:56,560 --> 03:29:58,840 NAIVE BUT THE MORE THAT WE DO 4669 03:29:58,840 --> 03:30:00,520 THIS WITH ALL OF THE DIFFERENT 4670 03:30:00,520 --> 03:30:03,040 TYPES OF EXPERTISE WE CAN LEARN 4671 03:30:03,040 --> 03:30:04,240 A A LOT. 4672 03:30:04,240 --> 03:30:06,200 EVEN WHEN THE END POINTS NOT MET 4673 03:30:06,200 --> 03:30:08,160 WE CAN STILL LEARN A LOT BY 4674 03:30:08,160 --> 03:30:08,680 SHARING THE INFORMATION 4675 03:30:08,680 --> 03:30:10,840 TOGETHER. 4676 03:30:10,840 --> 03:30:11,840 >> THANK YOU. 4677 03:30:11,840 --> 03:30:16,280 TAMI. 4678 03:30:16,280 --> 03:30:20,600 >> I -- IT WAS LARGELY SAID. 4679 03:30:20,600 --> 03:30:22,840 AS GARY WAS JUST TALKING I WAS 4680 03:30:22,840 --> 03:30:24,240 TRYING TO THINK ABOUT WHAT ARE 4681 03:30:24,240 --> 03:30:26,040 WAYS THAT WE COULD REALLY 4682 03:30:26,040 --> 03:30:31,440 LEVERAGE THESE TRIALS. 4683 03:30:31,440 --> 03:30:34,800 IN A MORE POWERFUL WAY AND TO 4684 03:30:34,800 --> 03:30:36,600 HAVE OPEN CALLS FOR 4685 03:30:36,600 --> 03:30:38,240 COLLABORATION WHEN YOU DO A BIG 4686 03:30:38,240 --> 03:30:41,640 TRIAL. 4687 03:30:41,640 --> 03:30:44,280 A WAY OF INVITING LARGER 4688 03:30:44,280 --> 03:30:45,520 COMMUNITIES TO HELP. 4689 03:30:45,520 --> 03:30:49,400 AND REALLY THINKING ABOUT THAT 4690 03:30:49,400 --> 03:30:52,840 AT THE GET-GO IN TERMS OF SAMPLE 4691 03:30:52,840 --> 03:30:53,360 COLLECTION. 4692 03:30:53,360 --> 03:30:57,160 WHEN SAMPLES ARE COLLECTED A LOT 4693 03:30:57,160 --> 03:30:59,640 OF THE TRIALS THEY ARE COLLECTED 4694 03:30:59,640 --> 03:31:04,560 IN WAYS IN -- A BUT THEY ARE 4695 03:31:04,560 --> 03:31:06,520 PRESERVES IT BUT MAKES IT 4696 03:31:06,520 --> 03:31:08,840 IMPOSSIBLE TO CULTURE THE 4697 03:31:08,840 --> 03:31:09,840 ORGANISMS FROM. 4698 03:31:09,840 --> 03:31:11,840 MAKING SURE THAT WE'RE 4699 03:31:11,840 --> 03:31:13,880 COLLECTING SAMPLES IN A WAY THAT 4700 03:31:13,880 --> 03:31:16,040 WE CAN ANALYZE. 4701 03:31:16,040 --> 03:31:18,040 CULTURALLING ORGANISMS IS SO 4702 03:31:18,040 --> 03:31:18,280 IMPORTANT 4703 03:31:18,280 --> 03:31:19,320 >> THANK YOU SO UP IN. 4704 03:31:19,320 --> 03:31:20,680 WE'RE COMING TO THE END OF THE 4705 03:31:20,680 --> 03:31:20,880 HOUR. 4706 03:31:20,880 --> 03:31:23,680 WE HAVE TO STOP AT THIS POINT. 4707 03:31:23,680 --> 03:31:25,960 FIRST OF ALL I THANK YOU ALL FOR 4708 03:31:25,960 --> 03:31:27,080 YOUR EXCELLENT TALKS AND ALSO 4709 03:31:27,080 --> 03:31:31,640 YOUR INSIGHTFUL COMMENTS AND 4710 03:31:31,640 --> 03:31:32,760 KNOWLEDGE AND ANSWERS TO THE 4711 03:31:32,760 --> 03:31:34,600 QUESTIONS POSED. 4712 03:31:34,600 --> 03:31:38,320 AND AT THIS POINT I JOIN MY 4713 03:31:38,320 --> 03:31:42,120 COLLEAGUE -- IN THANKING YOU ALL 4714 03:31:42,120 --> 03:31:44,760 AND HANDING IT OVER TO DIANE. 4715 03:31:44,760 --> 03:31:49,440 DO YOU HAVE ANY FINAL CONTINUES? 4716 03:31:49,440 --> 03:31:52,040 >> I DON'T SEE -- RYAN. 4717 03:31:52,040 --> 03:31:53,240 YOU'RE ON MUTE 4718 03:31:53,240 --> 03:31:54,320 >> SORRY. 4719 03:31:54,320 --> 03:31:55,560 I DON'T. 4720 03:31:55,560 --> 03:31:56,280 APPRECIATE IT. 4721 03:31:56,280 --> 03:32:00,280 HANDS IT OVER TO KATHERINE. 4722 03:32:00,280 --> 03:32:00,920 >> THANK YOU. 4723 03:32:00,920 --> 03:32:03,480 THAT WAS A GREAT SESSION AND 4724 03:32:03,480 --> 03:32:04,400 WONDERFUL DISCUSSION AND THANK 4725 03:32:04,400 --> 03:32:07,520 YOU TO OUR SPEAKERS FOR PUTTING 4726 03:32:07,520 --> 03:32:09,600 FORWARD SOME FASCINATING TALKS. 4727 03:32:09,600 --> 03:32:13,160 NOW I'M GOING TO TAKE US TO 4728 03:32:13,160 --> 03:32:14,040 LUNCH. 4729 03:32:14,040 --> 03:32:16,680 WELCOME BACK FROM LUNCH, IT IS 4730 03:32:16,680 --> 03:32:18,080 2:00 P.M. AND TIME TO START 4731 03:32:18,080 --> 03:32:20,200 SESSION 4 FOR THE PROBIOTICS 4732 03:32:20,200 --> 03:32:21,600 ME WANTING. 4733 03:32:21,600 --> 03:32:31,640 THIS SESSION WILL BE MONITORED 4734 03:32:31,640 --> 03:32:37,240 BY MUKESH VERMA AND Dr. 4735 03:32:37,240 --> 03:32:39,040 DONAHUE FROM NIDDK. 4736 03:32:39,040 --> 03:32:42,480 THIS SESSION WILL BE EMERGING 4737 03:32:42,480 --> 03:32:44,000 TECHNOLOGIES FOR PRECISION 4738 03:32:44,000 --> 03:32:46,880 PROBIOTICS AND Dr. VERMA 4739 03:32:46,880 --> 03:32:49,400 WILL BE PRODUCING THE SESSION 4740 03:32:49,400 --> 03:32:49,800 SPEAKERS. 4741 03:32:49,800 --> 03:32:52,040 AND SO WITH THAT SAID, I WILL 4742 03:32:52,040 --> 03:32:55,400 TURN IT OVER TO Dr. VERMA TO 4743 03:32:55,400 --> 03:32:59,160 TAKE IT AWAY TO INTRODUCE OUR 4744 03:32:59,160 --> 03:33:01,480 FIRST SPEAKER. 4745 03:33:01,480 --> 03:33:06,120 >> THANKS, WELCOME, EARN, TO 4746 03:33:06,120 --> 03:33:08,520 ANOTHER EXCITING SESSION OF 4747 03:33:08,520 --> 03:33:11,080 PROBIOTICS AND WITH THAT, I 4748 03:33:11,080 --> 03:33:19,240 WOULD LIKE TO INVITE Dr. KIM 4749 03:33:19,240 --> 03:33:25,840 TO DISCUSS AND HE IS FROM THE 4750 03:33:25,840 --> 03:33:28,240 UNIVERSITY OF TEXAS AUSTIN. 4751 03:33:28,240 --> 03:33:33,080 >> THANK YOU FOR YOUR 4752 03:33:33,080 --> 03:33:33,760 ATTENTION. 4753 03:33:33,760 --> 03:33:36,040 I AM IN PRESENTATION MODE, CAN 4754 03:33:36,040 --> 03:33:43,000 YOU SEE THE SLIDES? 4755 03:33:43,000 --> 03:33:45,640 >> WE CAN SEE THE SLIDES, 4756 03:33:45,640 --> 03:33:45,920 YEAH. 4757 03:33:45,920 --> 03:33:53,120 >> LET ME RESCALE THAT. 4758 03:33:53,120 --> 03:33:54,280 >> HERE YOU GO. 4759 03:33:54,280 --> 03:33:55,280 >> DID THAT WORK? 4760 03:33:55,280 --> 03:33:58,640 >> IT IS NOT CONVERTING OVER 4761 03:33:58,640 --> 03:34:00,920 TO PRESENTATION MODE. 4762 03:34:00,920 --> 03:34:01,880 >> HMM. 4763 03:34:01,880 --> 03:34:04,000 >> DAN OR DIANE, DOES EITHER 4764 03:34:04,000 --> 03:34:09,400 OF YOU HAVE Dr -- YES, HERE 4765 03:34:09,400 --> 03:34:10,880 WE GO, DAN HAS THAT UP FOR 4766 03:34:10,880 --> 03:34:11,720 YOU. 4767 03:34:11,720 --> 03:34:12,280 THANK YOU, DAN. 4768 03:34:12,280 --> 03:34:15,320 >> THANK YOU SO MUCH AND I 4769 03:34:15,320 --> 03:34:17,840 REALLY APPRECIATE FOR THIS 4770 03:34:17,840 --> 03:34:21,440 OPPORTUNITY. 4771 03:34:21,440 --> 03:34:22,000 NEXT SLIDE, PLEASE. 4772 03:34:22,000 --> 03:34:28,240 SO I AM GOING TO GIVE YOU SOME 4773 03:34:28,240 --> 03:34:32,840 IDEA ON HOW THE CHIP ALLOWS 4774 03:34:32,840 --> 03:34:35,840 YOU TO GET THE MICROBIOME 4775 03:34:35,840 --> 03:34:38,840 ENVIRONMENT AND MAKE IT 4776 03:34:38,840 --> 03:34:40,840 POSSIBLE FOR CROSSOVER SITE. 4777 03:34:40,840 --> 03:34:42,760 IN ANY EVENT, YOU WANT TO 4778 03:34:42,760 --> 03:34:48,160 BUILD UP THE PATIENT'S SLOWLY. 4779 03:34:48,160 --> 03:34:49,160 NEXT SLIDE, PLEASE. 4780 03:34:49,160 --> 03:34:53,520 I AM SORRY, WOULD YOU GO BACK? 4781 03:34:53,520 --> 03:34:54,840 THANK YOU. 4782 03:34:54,840 --> 03:34:56,440 SO WHAT WE ARE TRYING TO MAKE 4783 03:34:56,440 --> 03:34:58,840 HERE IS A TISSUE INTERFACE OF 4784 03:34:58,840 --> 03:35:11,760 OUR TEST SO HAVING THE CORE 4785 03:35:11,760 --> 03:35:16,240 MEMBRANE AND THEN EVENTUALLY 4786 03:35:16,240 --> 03:35:22,000 ONCE THESE ARE PATHEN S, YOU 4787 03:35:22,000 --> 03:35:24,280 CAN DETERMINE THE PATHO CELLS 4788 03:35:24,280 --> 03:35:34,640 AND EVENTUALLY YOU ARE JUST 4789 03:35:34,640 --> 03:35:35,600 MAKING THEMICROBIOME THAT 4790 03:35:35,600 --> 03:35:39,040 ALLOWS THEM TO INTERACT. 4791 03:35:39,040 --> 03:35:40,040 NEXT SLIDE, PLEASE. 4792 03:35:40,040 --> 03:35:44,240 SO WE ARE USING SILICON 4793 03:35:44,240 --> 03:35:45,720 POLYMER TO MAKE THE CHIP AND 4794 03:35:45,720 --> 03:35:47,880 ONCE WE HAVE THE PATTERN ON 4795 03:35:47,880 --> 03:35:51,440 THE SURFACE WITH PUNCHING, 4796 03:35:51,440 --> 03:35:53,880 CUTTING AND ALIGNING, THEN WE 4797 03:35:53,880 --> 03:35:55,280 CAN ALSO INTRODUCE SOME CHIPS 4798 03:35:55,280 --> 03:35:56,520 THAT CONTAIN THE CELLS AND 4799 03:35:56,520 --> 03:36:00,520 THEN YOU ARE GROWING THE CELLS 4800 03:36:00,520 --> 03:36:02,520 IN THE DATA AND THEN YOU CAN 4801 03:36:02,520 --> 03:36:06,240 TAKE IT OUT AND COLLECT THE 4802 03:36:06,240 --> 03:36:11,120 SAMPLE FROM THE DERMA SITE AND 4803 03:36:11,120 --> 03:36:19,120 YOU CAN LAUNCH ANY ASSAYS OR 4804 03:36:19,120 --> 03:36:22,480 EXTINGUISH OR AFFIX THE CELLS 4805 03:36:22,480 --> 03:36:25,800 FOR STAINING AND MICROSCOPY. 4806 03:36:25,800 --> 03:36:26,320 NEXT SLIDE, PLEASE. 4807 03:36:26,320 --> 03:36:31,280 SO YOU ARE LOOKING AT THE 4808 03:36:31,280 --> 03:36:34,200 CHIP, THE SILICON POLYMER IS 4809 03:36:34,200 --> 03:36:37,640 CRYSTAL CLEAR AND YOU HAVE A 4810 03:36:37,640 --> 03:36:38,680 MICROCHANNEL AS MENTIONED 4811 03:36:38,680 --> 03:36:39,800 INSIDE THAT AND HOPEFULLY YOU 4812 03:36:39,800 --> 03:36:42,840 CAN SEE THERE IS A VACUUM 4813 03:36:42,840 --> 03:36:46,880 CHAMBER CONNECTED TO THE 4814 03:36:46,880 --> 03:36:50,960 VACUUM CONTROLLER ESSENTIALLY 4815 03:36:50,960 --> 03:36:51,640 MAKING THE FUNCTION SITE HAVE 4816 03:36:51,640 --> 03:36:52,160 NEGATIVE PRESSURE. 4817 03:36:52,160 --> 03:36:54,000 NEXT SLIDE, PLEASE. 4818 03:36:54,000 --> 03:37:01,680 SO HERE YOU SEE EVERYTHING 4819 03:37:01,680 --> 03:37:06,440 HERE WITH THE TKPWEUZ LOGICAL 4820 03:37:06,440 --> 03:37:08,840 FLOW IN FUNCTION AND NEXT 4821 03:37:08,840 --> 03:37:09,440 SLIDE, PLEASE. 4822 03:37:09,440 --> 03:37:15,040 AND THIS IS A DIFFERENT TYPE 4823 03:37:15,040 --> 03:37:21,040 IT HAVE EPITHELIAL CELLS HERE. 4824 03:37:21,040 --> 03:37:25,440 YOU CAN USE SEVERAL MODELS AND 4825 03:37:25,440 --> 03:37:27,400 HERE USING THIS 4826 03:37:27,400 --> 03:37:33,880 MICROARCHITECTURE IN VITRO, 4827 03:37:33,880 --> 03:37:38,640 YOU CAN USE THIS AND 4828 03:37:38,640 --> 03:37:41,480 REPRODUCIBLY FILL THIS MODEL 4829 03:37:41,480 --> 03:37:44,040 WITH DIFFERENT TYPES OF FILM. 4830 03:37:44,040 --> 03:37:44,720 NEXT SLIDE, PLEASE. 4831 03:37:44,720 --> 03:37:56,400 SO HERE YOU CAN SEE WE CAN USE 4832 03:37:56,400 --> 03:37:57,440 THE MO RPHODENISIS, STARTING 4833 03:37:57,440 --> 03:38:01,200 WITH THE BOTTOM LAYER. 4834 03:38:01,200 --> 03:38:01,840 NEXT SLIDE. 4835 03:38:01,840 --> 03:38:05,000 AND THAT WAY YOU ARE NOT ONLY 4836 03:38:05,000 --> 03:38:07,040 MAKING THIS MIMICRY OF THE 4837 03:38:07,040 --> 03:38:10,440 CULTURE, YOU CAN ALSO 4838 03:38:10,440 --> 03:38:11,480 DEMONSTRATE THE ACTUAL 4839 03:38:11,480 --> 03:38:13,880 BEHAVIOR OF THE PROLIFIC CELLS 4840 03:38:13,880 --> 03:38:19,400 HIGHLIGHTED IN RED, THEY ARE 4841 03:38:19,400 --> 03:38:26,480 MIGRATING AND ALSO YESTERDAY, 4842 03:38:26,480 --> 03:38:28,280 ANOTHER SPEAKER MENTIONED THE 4843 03:38:28,280 --> 03:38:30,600 HOST CELL IS IMPORTANT FOR THE 4844 03:38:30,600 --> 03:38:35,880 MICROBIOME SIDE BUT WE CAN USE 4845 03:38:35,880 --> 03:38:40,120 THE CELLS FOR THE LAYER. 4846 03:38:40,120 --> 03:38:40,640 NEXT SLIDE, PLEASE. 4847 03:38:40,640 --> 03:38:46,440 AND THERE ARE A COUPLE OF BASE 4848 03:38:46,440 --> 03:38:50,720 THAT USE INVIVO OR INVITRO 4849 03:38:50,720 --> 03:38:53,920 MODELS AND AS WE DISCUSSED A 4850 03:38:53,920 --> 03:38:56,560 COUPLE OF TIMES, THE HUMAN 4851 03:38:56,560 --> 03:38:59,560 MICROBIOME IS NOT NECESSARILY 4852 03:38:59,560 --> 03:39:02,160 REFLECTING THE ANIMAL 4853 03:39:02,160 --> 03:39:02,960 MICROBIOME. 4854 03:39:02,960 --> 03:39:07,080 AND ALSO WHEN YOU THINK ABOUT 4855 03:39:07,080 --> 03:39:08,720 THE IN VITRO MODELS, IT IS 4856 03:39:08,720 --> 03:39:10,440 VERY DIFFICULT TO REGULATE THE 4857 03:39:10,440 --> 03:39:13,640 OVERGROWTH OF THE BACTERIA AND 4858 03:39:13,640 --> 03:39:16,080 SOMETIMES PEOPLE ARE JUST 4859 03:39:16,080 --> 03:39:17,840 TRYING TO USE PART OF IT BUT 4860 03:39:17,840 --> 03:39:20,840 YOU NEED TO PUNCTURE IT TO 4861 03:39:20,840 --> 03:39:22,640 INTRODUCE THE LIVING CELLS 4862 03:39:22,640 --> 03:39:24,440 INTO THE BACTERIA SLIDE. 4863 03:39:24,440 --> 03:39:25,640 NEXT SLIDE, PLEASE. 4864 03:39:25,640 --> 03:39:28,040 SO THESE ARE LIMITATIONS THAT 4865 03:39:28,040 --> 03:39:29,240 WE ACTUALLY HAVE OVERCOME WHEN 4866 03:39:29,240 --> 03:39:33,200 YOU CONSIDER FOR THE NEXT 4867 03:39:33,200 --> 03:39:37,280 GENERATION MODELS OF TESTING. 4868 03:39:37,280 --> 03:39:38,000 NEXT SLIDE, PLEASE. 4869 03:39:38,000 --> 03:39:40,120 SO THE COURSE YOU ARE TAKING 4870 03:39:40,120 --> 03:39:42,240 HERE IS ONCE WE HAVE ONE 4871 03:39:42,240 --> 03:39:47,200 LAYER, WE CAN STRUCTURE THE 4872 03:39:47,200 --> 03:39:48,240 EPITHELIAL CELLS, LOOKING AT 4873 03:39:48,240 --> 03:39:50,240 THE LEFT BOTTOM, THE 4874 03:39:50,240 --> 03:39:52,800 SCHEMATIC, WE PICTURE THE 4875 03:39:52,800 --> 03:39:54,520 CELLS AND ACTUALLY YOU CAN 4876 03:39:54,520 --> 03:40:00,440 STOP THE FLOW, ALLOW THEM TO 4877 03:40:00,440 --> 03:40:04,840 BE CIRCUITUOUS AND THEN RESUME 4878 03:40:04,840 --> 03:40:07,240 THE INFUSION USING FRESH 4879 03:40:07,240 --> 03:40:11,960 MEDIUM AND SUPPLY OXYGEN. 4880 03:40:11,960 --> 03:40:13,720 ALSO WE ARE MOVING ALL THE 4881 03:40:13,720 --> 03:40:18,440 WEIGHT AND EVENTUALLY YOU CAN 4882 03:40:18,440 --> 03:40:21,560 CHIP OFF THE MICROCELLS TO BE 4883 03:40:21,560 --> 03:40:23,440 HAPPY SO YOU ARE LOOKING AT 4884 03:40:23,440 --> 03:40:32,680 THE LIVE IMAGES OF THE 4885 03:40:32,680 --> 03:40:36,440 PROBIOTICS CHAIN, OR YOU CAN 4886 03:40:36,440 --> 03:40:39,960 LOOK AT THE COLI, NEXT SLIDE, 4887 03:40:39,960 --> 03:40:40,560 PLEASE. 4888 03:40:40,560 --> 03:40:46,400 AND AT THE BOTTOM, YOU CAN SEE 4889 03:40:46,400 --> 03:40:53,200 IT WILL SPREAD AND CAN BE 4890 03:40:53,200 --> 03:40:54,640 STUDIED OUTANY COMPROMISE TO 4891 03:40:54,640 --> 03:40:56,000 THE BARRIER. 4892 03:40:56,000 --> 03:40:57,240 NEXT SLIDE, PLEASE. 4893 03:40:57,240 --> 03:41:00,840 THE NEXT CHALLENGE, WE REALLY 4894 03:41:00,840 --> 03:41:05,640 NEED TO OVERCOME SOME AEROBIC 4895 03:41:05,640 --> 03:41:07,400 BACTERIA, SOME OF THEM ARE 4896 03:41:07,400 --> 03:41:10,040 LIVING IN THE CULTURE BUT WE 4897 03:41:10,040 --> 03:41:12,800 HAVE TO PUNCTURE THE CELLS. 4898 03:41:12,800 --> 03:41:14,520 NEXT SLIDE. 4899 03:41:14,520 --> 03:41:20,760 FOR THIS, WE INTRODUCE THE 4900 03:41:20,760 --> 03:41:26,160 MULTICULTURE MEDIUM ON THE 4901 03:41:26,160 --> 03:41:26,440 CHIP. 4902 03:41:26,440 --> 03:41:28,840 SO THERE IS A SHARP RADIUS ON 4903 03:41:28,840 --> 03:41:32,640 THE SIDE AND ON THE RIGHTHAND 4904 03:41:32,640 --> 03:41:38,840 SIDE, CO-CULTURE IT 4905 03:41:38,840 --> 03:41:42,200 WITHINTERIM BAGUETTE TEAR YUM, 4906 03:41:42,200 --> 03:41:47,000 THEY COMMUNICATE TO EACH OTHER 4907 03:41:47,000 --> 03:41:49,080 VITRALLY SO WE CAN 4908 03:41:49,080 --> 03:41:50,240 SUCCESSFULLY CULTURE THEM FOR 4909 03:41:50,240 --> 03:41:53,000 UP TO A WEEK WITHOUT ANY 4910 03:41:53,000 --> 03:41:56,280 COMPROMISE OF THE BACTERIA. 4911 03:41:56,280 --> 03:41:57,760 NEXT SLIDE. 4912 03:41:57,760 --> 03:41:59,160 SO BY LEVERAGING THIS 4913 03:41:59,160 --> 03:42:01,960 APPROACH, WE ARE ALSO TAKING 4914 03:42:01,960 --> 03:42:03,600 FECAL SAMPLES AND PROCESS THEM 4915 03:42:03,600 --> 03:42:04,840 AND INTRODUCE THEM ON A CHIP 4916 03:42:04,840 --> 03:42:09,000 AND YOU CAN LOOK AT ON THE 4917 03:42:09,000 --> 03:42:12,880 LEFTHAND SIDE, THIS IS THE 4918 03:42:12,880 --> 03:42:14,920 LIVE CULTURE AND YOU CAN 4919 03:42:14,920 --> 03:42:18,240 COMPARE BEFORE AND AFTER THE 4920 03:42:18,240 --> 03:42:19,480 INOCULATION AND ON THE BOTTOM 4921 03:42:19,480 --> 03:42:26,200 LEFT YOU CAN SEE THE PATH OF 4922 03:42:26,200 --> 03:42:26,560 MIGRATION. 4923 03:42:26,560 --> 03:42:27,040 NETWORKS SLIDE. 4924 03:42:27,040 --> 03:42:32,480 AND ALSO YOU CAN SEE IN THIS 4925 03:42:32,480 --> 03:42:36,480 CASE LIKE FOR CHIP 1 THROUGH 4926 03:42:36,480 --> 03:42:44,120 3, THEY JUST REPLICATE THE 4927 03:42:44,120 --> 03:42:48,160 CHIP WITH FECAL MICROBIOTA AND 4928 03:42:48,160 --> 03:42:51,680 IN THE LABORATORY, YOU CAN SEE 4929 03:42:51,680 --> 03:42:52,840 THE FECAL SAMPLE, THE SEQUENCE 4930 03:42:52,840 --> 03:42:57,600 RESULTS OF THE BUILDUP IN THE 4931 03:42:57,600 --> 03:43:01,880 CHIP ALLOWS YOU TO MAKE THE 4932 03:43:01,880 --> 03:43:04,960 BEST OF THE CHIP CULTURALLY. 4933 03:43:04,960 --> 03:43:14,120 HOWEVER IN THE LIQUID CULTURE, 4934 03:43:14,120 --> 03:43:16,640 YOU ONLY SEE ONE IN VITRO 4935 03:43:16,640 --> 03:43:21,040 WHICH YOU CAN SEE HERE. 4936 03:43:21,040 --> 03:43:26,040 SO WE CAN LOOK AT THE MICROBE 4937 03:43:26,040 --> 03:43:28,440 DIVERSITY AND ALSO THE BIOME 4938 03:43:28,440 --> 03:43:30,440 FROM THE FECAL SAMPLE. 4939 03:43:30,440 --> 03:43:30,920 NEXT SLIDE. 4940 03:43:30,920 --> 03:43:33,120 SO WE ARE TRYING TO LEVERAGE 4941 03:43:33,120 --> 03:43:36,840 OUR SYSTEM TO UNDERSTAND THE 4942 03:43:36,840 --> 03:43:40,040 MECHANISTIC BACKGROUND HOW AND 4943 03:43:40,040 --> 03:43:42,240 WHICH COMPLEX FACTORS CAN 4944 03:43:42,240 --> 03:43:44,880 ACTUALLY BE USED IN THE ONSET 4945 03:43:44,880 --> 03:43:46,560 OF INFLAMMATION. 4946 03:43:46,560 --> 03:43:49,400 NEXT SLIDE. 4947 03:43:49,400 --> 03:43:54,640 WE STARTED TO USE DSF -- DSS 4948 03:43:54,640 --> 03:43:57,520 AND YOU HAVE TO USE A LOT OF 4949 03:43:57,520 --> 03:44:04,600 TIME FOR THE CULT CHOW AND 4950 03:44:04,600 --> 03:44:07,040 WITH THE INFLAMMATION IN 4951 03:44:07,040 --> 03:44:11,840 ANIMAL MODELS, WE CAN 4952 03:44:11,840 --> 03:44:13,440 INTRODUCE THE BARRIER CENTER 4953 03:44:13,440 --> 03:44:16,760 AND YOU CAN SEE WE DON'T SEE 4954 03:44:16,760 --> 03:44:17,760 ANY BUILDUP HERE. 4955 03:44:17,760 --> 03:44:20,440 SO WE THOUGHT THIS WAS A GREAT 4956 03:44:20,440 --> 03:44:21,800 OPPORTUNITY TO MANIPULATE 4957 03:44:21,800 --> 03:44:23,520 PHYSICALLY TOWARDS THE BARRIER 4958 03:44:23,520 --> 03:44:24,880 FUNCTION. 4959 03:44:24,880 --> 03:44:26,840 NEXT SLIDE, PLEASE. 4960 03:44:26,840 --> 03:44:32,000 SO WE CAN UNCOUPLE OF 4961 03:44:32,000 --> 03:44:33,640 CONSTRUCT OF FACTORS IN THIS 4962 03:44:33,640 --> 03:44:35,680 AND RECOUPLE THEM ONE AT A 4963 03:44:35,680 --> 03:44:38,200 TIME TO UNDERSTAND WHICH 4964 03:44:38,200 --> 03:44:40,680 FACTOR ACTUALLY INDUCED THE 4965 03:44:40,680 --> 03:44:41,400 INFLAMMATION. 4966 03:44:41,400 --> 03:44:48,560 SO WE STARTED BY USING THE 4967 03:44:48,560 --> 03:44:49,960 VITREOUS ONLY COUPLED WITH 4968 03:44:49,960 --> 03:44:50,640 IMMUNE CELLS. 4969 03:44:50,640 --> 03:44:55,640 SO WE STARTED THAT ON THE LEFT 4970 03:44:55,640 --> 03:44:59,240 AND YOU CAN SEE WITH THE 4971 03:44:59,240 --> 03:45:01,880 CELLS, IT INCREASED BUT WE 4972 03:45:01,880 --> 03:45:06,440 DON'T SEE ANY FUNCTION TO 4973 03:45:06,440 --> 03:45:08,200 INFLAME SO THAT MEANS WE DON'T 4974 03:45:08,200 --> 03:45:09,520 HAVE IT YET. 4975 03:45:09,520 --> 03:45:11,400 SO NEXT SLIDE, PLEASE. 4976 03:45:11,400 --> 03:45:21,240 SO HERE YOU CAN SEE THE 4977 03:45:21,240 --> 03:45:29,120 VITREOUS AND THE LEVEL HAS 4978 03:45:29,120 --> 03:45:30,880 BEEN AMPLIFIED. 4979 03:45:30,880 --> 03:45:32,320 NEXT SLIDE, PLEASE. 4980 03:45:32,320 --> 03:45:37,480 AND THE BARRIER FUNCTION IS 4981 03:45:37,480 --> 03:45:38,280 VERY IMPORTANT. 4982 03:45:38,280 --> 03:45:45,400 WE ALREADY HAVE THE MICROBIAL 4983 03:45:45,400 --> 03:45:47,360 CELLS AND BACTERIA WITH THE 4984 03:45:47,360 --> 03:45:48,840 PREMISE OF THE CELLS 4985 03:45:48,840 --> 03:45:51,240 THEMSELVES BUT DON'T 4986 03:45:51,240 --> 03:45:52,240 NECESSARILY HAVE INFLAMMATION 4987 03:45:52,240 --> 03:45:55,320 AND MAINLY BECAUSE WE 4988 03:45:55,320 --> 03:46:00,920 DEMONSTRATE THE FUNCTION 4989 03:46:00,920 --> 03:46:04,600 LITERALLY MAINTAINS THE 4990 03:46:04,600 --> 03:46:06,720 EPITHILEAL FUNCTION. 4991 03:46:06,720 --> 03:46:07,400 NEXT SLIDE, PLEASE. 4992 03:46:07,400 --> 03:46:09,080 SO SOMETIMES IT WORKS, 4993 03:46:09,080 --> 03:46:10,560 SOMETIMES IT DOES NOT AND THAT 4994 03:46:10,560 --> 03:46:12,640 IS ONE OF THE KEY ISSUES WE 4995 03:46:12,640 --> 03:46:16,960 WANT TO SHOW HERE. 4996 03:46:16,960 --> 03:46:25,640 SO HERE WE TESTED WITH THE 4997 03:46:25,640 --> 03:46:29,280 EPITHILEAL BARRIER AND 4998 03:46:29,280 --> 03:46:30,320 THEN-PROVING THE BARRIER 4999 03:46:30,320 --> 03:46:30,840 FUNCTION. 5000 03:46:30,840 --> 03:46:33,360 >> YOU HAVE THREE MINUTES. 5001 03:46:33,360 --> 03:46:35,520 >> SO WE DEMONSTRATE IF WE 5002 03:46:35,520 --> 03:46:38,560 JUST INTRODUCE THE PROBIOTIC 5003 03:46:38,560 --> 03:46:41,400 STRAIN BEFORE WE DISRUPT THE 5004 03:46:41,400 --> 03:46:43,760 BARRIER, THEN WE CAN ACHIEVE 5005 03:46:43,760 --> 03:46:44,680 THE BARRIERS. 5006 03:46:44,680 --> 03:46:49,280 BUT IF THE BARRIER IS ALREADY 5007 03:46:49,280 --> 03:46:50,040 COMPROMISED, THE PROBIOTIC 5008 03:46:50,040 --> 03:46:52,000 STRAIN DOES NOT WORK. 5009 03:46:52,000 --> 03:46:53,040 NEXT SLIDE, PLEASE. 5010 03:46:53,040 --> 03:46:55,200 AND ALSO WE USE SIMILAR 5011 03:46:55,200 --> 03:46:57,240 APPROACHES FOR INTRODUCING THE 5012 03:46:57,240 --> 03:46:58,800 BARRIER OPTIONS, ONE MORE 5013 03:46:58,800 --> 03:47:00,720 SLIDE, PLEASE. 5014 03:47:00,720 --> 03:47:03,640 AND DEMONSTRATE THAT WITH THE 5015 03:47:03,640 --> 03:47:11,800 CO-CULTURE WHICH YOU SEE HERE. 5016 03:47:11,800 --> 03:47:18,920 ALSO THE DISORGANIZED 5017 03:47:18,920 --> 03:47:19,880 BARRIERS. 5018 03:47:19,880 --> 03:47:20,760 NEXT SLIDE PLEASE. 5019 03:47:20,760 --> 03:47:22,400 SO THE NEXT THREE MINUTES I 5020 03:47:22,400 --> 03:47:25,000 WILL GIVE YOU SOME APPROACHES 5021 03:47:25,000 --> 03:47:29,200 FOR CREATING A PATIENT AVATAR 5022 03:47:29,200 --> 03:47:31,640 TO VALIDATE THE SAMPLE. 5023 03:47:31,640 --> 03:47:32,400 NEXT SLIDE, PLEASE. 5024 03:47:32,400 --> 03:47:36,040 SO WE CAN WAIT A MINUTE FOR 5025 03:47:36,040 --> 03:47:40,040 THE APPROACH TO BUILD THE 5026 03:47:40,040 --> 03:47:41,480 INDIVIDUAL SITUATION WITH THE 5027 03:47:41,480 --> 03:47:42,320 PATIENT, NEXT SLIDE, PLEASE. 5028 03:47:42,320 --> 03:47:47,000 SO YOU CAN SEE HERE WE CAN 5029 03:47:47,000 --> 03:47:49,600 RECREATE THE CELLS AND ON 5030 03:47:49,600 --> 03:47:56,440 CHIPS, WE CAN ALSO DEMONSTRATE 5031 03:47:56,440 --> 03:47:57,640 THE MUTANT SESSIONS. 5032 03:47:57,640 --> 03:47:58,200 NEXT SLIDE, PLEASE. 5033 03:47:58,200 --> 03:48:04,640 SO WE HAVE A LOT OF APPROACHES 5034 03:48:04,640 --> 03:48:09,640 WITH OUR CLIPIANS FOR SHOWING 5035 03:48:09,640 --> 03:48:11,280 CANCER ON THE CHIPS AND ONE OF 5036 03:48:11,280 --> 03:48:13,680 THE THINGS WE'RE FOCUSING ON 5037 03:48:13,680 --> 03:48:21,240 HERE IS THE MICROBIOME 5038 03:48:21,240 --> 03:48:25,840 CONTROLS ON IMMUNOTHERAPY, 5039 03:48:25,840 --> 03:48:27,120 METASTASIS AND METABOLISM. 5040 03:48:27,120 --> 03:48:38,280 SO HERE WE TAKE THE PATIENT'S 5041 03:48:38,280 --> 03:48:42,000 MATERIAL AND PUT IT ON A CHIP 5042 03:48:42,000 --> 03:48:44,200 ON A BAGUETTE TERM BASIS AND 5043 03:48:44,200 --> 03:48:48,160 FOCUSING ON HOW IT CAN MOT 5044 03:48:48,160 --> 03:48:50,480 LAID WITH EXPRESS TUMOR CELLS. 5045 03:48:50,480 --> 03:48:51,600 NEXT SLIDE, PLEASE. 5046 03:48:51,600 --> 03:48:57,040 SO HERE WE FOCUS ON PD1 AND 5047 03:48:57,040 --> 03:49:13,720 YOU CAN SEE HERE THE POTENTIAL 5048 03:49:13,720 --> 03:49:14,360 EXPRESSION IS PARTICULARLY 5049 03:49:14,360 --> 03:49:15,040 HIGH BUT WHEN YOU CULTURE WITH 5050 03:49:15,040 --> 03:49:16,720 LIVING BACTERIA CELLS, YOU 5051 03:49:16,720 --> 03:49:19,080 DON'T REALLY SEE THAT. 5052 03:49:19,080 --> 03:49:19,640 NEXT SLIDE, PLEASE. 5053 03:49:19,640 --> 03:49:25,640 SO HERE WE TESTED WITH THE 5054 03:49:25,640 --> 03:49:28,040 BACTERIA ALONE OR THE LIVE 5055 03:49:28,040 --> 03:49:30,040 BACTERIA ALONE AND YOU CAN SEE 5056 03:49:30,040 --> 03:49:34,000 HERE WITH THE T CELLS, THEY DO 5057 03:49:34,000 --> 03:49:36,840 INDUCE A POTENTIAL IMMUNE 5058 03:49:36,840 --> 03:49:39,040 RESPONSE ON THE TUMOR HERE. 5059 03:49:39,040 --> 03:49:40,400 NEXT SLIDE, PLEASE. 5060 03:49:40,400 --> 03:49:43,120 SO WRAPPING UP HERE THEN, IT 5061 03:49:43,120 --> 03:49:47,200 IS TRYING TO PAINT VARIOUS 5062 03:49:47,200 --> 03:49:54,840 PATIENT SAMPLES THAT HAVE 5063 03:49:54,840 --> 03:49:59,360 CHANGES, BIOCHANGES OR RACE OR 5064 03:49:59,360 --> 03:50:00,800 ETHNICITY GROUP AND YOU CAN 5065 03:50:00,800 --> 03:50:08,680 TAKE DIFFERENT TYPES OF 5066 03:50:08,680 --> 03:50:10,520 PROBIOTICS OR SMT AND 5067 03:50:10,520 --> 03:50:11,560 UNDERSTAND THE COMBINATION OF 5068 03:50:11,560 --> 03:50:19,760 THE FACTORS FOR INDUCING AND 5069 03:50:19,760 --> 03:50:22,040 PRODUCING OUTCOMES IN HUMAN 5070 03:50:22,040 --> 03:50:26,880 MICROBIOME. 5071 03:50:26,880 --> 03:50:31,840 NEXT SLIDE, PLEASE. 5072 03:50:31,840 --> 03:50:36,520 SO I WANT TO THANK ALL THE 5073 03:50:36,520 --> 03:50:38,120 COLLABORATORS, THANK YOU VERY 5074 03:50:38,120 --> 03:50:38,440 MUCH. 5075 03:50:38,440 --> 03:50:55,240 >> THANK YOU AND WE INTRODUCE 5076 03:50:55,240 --> 03:50:59,040 THE NEXT SPEAKER. 5077 03:50:59,040 --> 03:50:59,440 THANK YOU. 5078 03:50:59,440 --> 03:51:02,400 >> OKAY, I THANK THE NIH FOR 5079 03:51:02,400 --> 03:52:06,680 ALLOWING ME TO GIVE MY TALK SO 5080 03:52:06,680 --> 03:52:10,840 HERE WE SHOW THE SRT LEVELS 5081 03:52:10,840 --> 03:52:13,800 IMPORTANT FOR MICROBIOME 5082 03:52:13,800 --> 03:52:16,360 HEALTH. 5083 03:52:16,360 --> 03:52:17,840 THESE PROPOSALS SHOW THE 5084 03:52:17,840 --> 03:52:20,360 PROPOSAL TO SHIFT TO A 5085 03:52:20,360 --> 03:52:21,680 STRATEGY FOR RESPONDERS AND 5086 03:52:21,680 --> 03:52:23,120 NONRESPONDERS AND THAT IS 5087 03:52:23,120 --> 03:52:27,840 BASED ON HUMAN GENOMIC 5088 03:52:27,840 --> 03:52:32,920 MATERIAL FOR EXAMPLE AND ALSO 5089 03:52:32,920 --> 03:52:34,040 MICROBIAL INFORMATION FOR 5090 03:52:34,040 --> 03:52:36,240 STRATIFIED PATIENTS AND MAKE A 5091 03:52:36,240 --> 03:52:39,000 PREDICTION BASED ON THEIR 5092 03:52:39,000 --> 03:52:40,920 RESPONDER STATUS AND THEN 5093 03:52:40,920 --> 03:52:43,800 SPECIFICALLY TAILORED THERAPY 5094 03:52:43,800 --> 03:52:51,840 OF THE INDIVIDUAL. 5095 03:52:51,840 --> 03:52:54,120 AND THAT IS DONE ON NOT ONLY A 5096 03:52:54,120 --> 03:52:55,440 GROUP LEVEL BUT INDIVIDUALLY. 5097 03:52:55,440 --> 03:52:59,480 SO THIS IS THE MECHANIC CAN 5098 03:52:59,480 --> 03:53:02,520 FIFTHIC APPROACH AND BASED ON 5099 03:53:02,520 --> 03:53:06,960 A NUMBER OF HUMAN STUDIES AND 5100 03:53:06,960 --> 03:53:08,120 ANIMAL MODELS. 5101 03:53:08,120 --> 03:53:10,640 THE TRANSLATION FOR HUMAN 5102 03:53:10,640 --> 03:53:12,880 CONDITIONS IS NOT ALWAYS TRUE, 5103 03:53:12,880 --> 03:53:17,040 IT CERTAINLY HOLDS TRUE FOR 5104 03:53:17,040 --> 03:53:18,240 PRECISION PROBIOTICS AND IS 5105 03:53:18,240 --> 03:53:21,520 ALSO DRIVEN BY THE ORGANISM 5106 03:53:21,520 --> 03:53:21,840 ITSELF. 5107 03:53:21,840 --> 03:53:25,080 SO HERE IN VITRO TECHNOLOGIES 5108 03:53:25,080 --> 03:53:28,920 ARE COMING, LOOKING AROUND THE 5109 03:53:28,920 --> 03:53:31,480 CORNER, MULTIPLE STAGES OF THE 5110 03:53:31,480 --> 03:53:33,800 ENVIRONMENT OF MUCOSA OR 5111 03:53:33,800 --> 03:53:34,880 INTEGRATION OF THE HOST FROM 5112 03:53:34,880 --> 03:53:37,040 THE SWITCH WE JUST HEARD ABOUT 5113 03:53:37,040 --> 03:53:38,560 IN THE TALK FROM Dr. KIM. 5114 03:53:38,560 --> 03:53:41,560 SO IT IS IMPORTANT TO 5115 03:53:41,560 --> 03:53:43,080 APPRECIATE WHAT THE IN VITRO 5116 03:53:43,080 --> 03:53:43,760 MODELS CAN OFFER. 5117 03:53:43,760 --> 03:53:53,520 SO DUE TO THE FACT THERE IS A 5118 03:53:53,520 --> 03:53:56,360 MULTILEVEL CONTROL YOU CAN 5119 03:53:56,360 --> 03:53:58,440 PROVIDE IMPORTANT INFORMATION 5120 03:53:58,440 --> 03:54:20,160 FOR EXPLAINING THESE 5121 03:54:20,160 --> 03:54:20,600 OBSERVATIONS. 5122 03:54:20,600 --> 03:54:24,280 SO THIS TAKES INTO ACCOUNT 5123 03:54:24,280 --> 03:54:26,720 THERE ARE LONGITUDINAL 5124 03:54:26,720 --> 03:54:27,560 GRADIENTS, SECTIONAL GRADIENTS 5125 03:54:27,560 --> 03:54:30,440 AND TAKE INTO CONSIDERATION 5126 03:54:30,440 --> 03:54:31,960 THE ENVIRONMENT AND THEN WE 5127 03:54:31,960 --> 03:54:33,680 ALSO NEED TO BETTER LOOK AT 5128 03:54:33,680 --> 03:54:36,520 THE INTEGRATION FROM THE DATA 5129 03:54:36,520 --> 03:54:38,640 SETS, LOOKING FOR EXAMPLE, AT 5130 03:54:38,640 --> 03:54:44,200 TIMELY ANALYSIS TO TRACK 5131 03:54:44,200 --> 03:54:44,920 MICROPRECISIONS AND ENDPOINTS. 5132 03:54:44,920 --> 03:54:47,480 I THINK IT IS CLEAR TO 5133 03:54:47,480 --> 03:54:48,480 APPROACH -- AS MENTIONED IN 5134 03:54:48,480 --> 03:54:50,040 ONE OF THE PREVIOUS TALKS -- 5135 03:54:50,040 --> 03:54:58,200 TO APPROACH IT IN A MICROBIAL 5136 03:54:58,200 --> 03:54:58,520 MANNER. 5137 03:54:58,520 --> 03:55:03,640 SO WHAT WE ARE WORKING WITH IS 5138 03:55:03,640 --> 03:55:07,160 CALLED SHINE IN THE HUMAN IN 5139 03:55:07,160 --> 03:55:10,240 VITRO SYSTEM AND JUST LIKE 5140 03:55:10,240 --> 03:55:11,960 OTHER SAMPLES WORLDWIDE, IT 5141 03:55:11,960 --> 03:55:13,360 CAN BE INOCULATED WITH DONOR 5142 03:55:13,360 --> 03:55:14,600 MATERIALS FROM AN INDIVIDUAL 5143 03:55:14,600 --> 03:55:17,240 AND THEN THE MODEL MIMICS THE 5144 03:55:17,240 --> 03:55:18,720 AVERAGE HUMAN BEING SO IN THAT 5145 03:55:18,720 --> 03:55:21,800 SENSE, MANY OF THE PARAMETERS 5146 03:55:21,800 --> 03:55:23,160 ARE ACTUALLY STANDARDIZED. 5147 03:55:23,160 --> 03:55:25,840 HOWEVER, IF WE REALLY WANT TO 5148 03:55:25,840 --> 03:55:29,840 UNDERSTAND THE VALUE OF 5149 03:55:29,840 --> 03:55:31,440 PERSONAL EVALUATION, WE 5150 03:55:31,440 --> 03:55:35,080 CONTINUE TO MOVE TOWARDS 5151 03:55:35,080 --> 03:55:35,640 PERSONALIZATION CELL. 5152 03:55:35,640 --> 03:55:46,560 I WOULD LIKE TO POINT OUT ONE 5153 03:55:46,560 --> 03:55:50,320 EXTREMELY IMPORTANT MICROBE 5154 03:55:50,320 --> 03:55:51,440 ACQUIRED. 5155 03:55:51,440 --> 03:55:59,080 THE DATA OBTAINED AND COMPARED 5156 03:55:59,080 --> 03:56:02,760 WITH DATA AND THIS IS KNOWN TO 5157 03:56:02,760 --> 03:56:05,480 BE VALUABLE IN SEVERAL HEALTH 5158 03:56:05,480 --> 03:56:07,040 EFFECTS. 5159 03:56:07,040 --> 03:56:10,320 FOR EXAMPLE, THE MICROBE 5160 03:56:10,320 --> 03:56:14,440 QUANTITY IN EXTREME OF SLIDE 1 5161 03:56:14,440 --> 03:56:24,120 OR 2 LANDSCAPE, SHOWN TO HIGH 5162 03:56:24,120 --> 03:56:25,800 LIFE OR THE QUANTITYIZATION 5163 03:56:25,800 --> 03:56:33,720 AND MAY IMPACT THE SUCCESS OF 5164 03:56:33,720 --> 03:56:35,320 PRECISION BIOTICS AND 5165 03:56:35,320 --> 03:56:36,240 PATHOGENS. 5166 03:56:36,240 --> 03:56:42,240 SO MANY FACTORS UNDER LIE THE 5167 03:56:42,240 --> 03:56:43,640 MICROBIAL DATA BUT MOST 5168 03:56:43,640 --> 03:56:46,160 IMPORTANTLY, IT APPEARS TO BE 5169 03:56:46,160 --> 03:56:53,840 A VERY DOMINANT FORM SHAPING 5170 03:56:53,840 --> 03:56:55,560 BOTH THE COEFFICIENTS AND 5171 03:56:55,560 --> 03:56:55,920 QUANTITY. 5172 03:56:55,920 --> 03:56:58,560 SO AN EXAMPLE OF WHAT WE TOOK 5173 03:56:58,560 --> 03:56:59,600 IN OUR CONTROLLED MODEL 5174 03:56:59,600 --> 03:57:00,960 SYSTEM, WE STARTED OFF WITH 5175 03:57:00,960 --> 03:57:02,040 INDIVIDUALS WITH EITHER A 5176 03:57:02,040 --> 03:57:06,920 SHORT, LONG OR MEDIUM TRANSIT 5177 03:57:06,920 --> 03:57:09,320 TIME, LUCKILY GO INTO THE 5178 03:57:09,320 --> 03:57:11,400 SYSTEM, STABILIZE THE SYSTEM 5179 03:57:11,400 --> 03:57:17,880 INTO A MODEL AND THEN INDUCE 5180 03:57:17,880 --> 03:57:19,400 THREE DIFFERENT TRANSIT TIMES. 5181 03:57:19,400 --> 03:57:24,440 THE FULL SCALE IS RELATED WITH 5182 03:57:24,440 --> 03:57:25,440 THE TRANSIT TIME. 5183 03:57:25,440 --> 03:57:27,920 SHORT TRAFFIC TIMES, THEY 5184 03:57:27,920 --> 03:57:31,040 CORRESPOND WITH LOWER 5185 03:57:31,040 --> 03:57:32,920 MICROBIAL QUANTITIES. 5186 03:57:32,920 --> 03:57:34,760 AND ON THE LEFT PART OF THE 5187 03:57:34,760 --> 03:57:35,840 SLIDE, YOU CAN SEE WE WERE 5188 03:57:35,840 --> 03:57:38,120 ABLE TO CAP PIT LATE THE 5189 03:57:38,120 --> 03:57:40,280 EFFECT AND FOUND TRANSIT TIME 5190 03:57:40,280 --> 03:57:44,320 TO DETERMINE THE DIFFERENCES 5191 03:57:44,320 --> 03:57:44,960 IN MICROBIAL COMPOSITION. 5192 03:57:44,960 --> 03:57:53,520 SO I WOULD LIKE TO ZOOM IN ON 5193 03:57:53,520 --> 03:57:55,360 TWO OF THESE AND THE 5194 03:57:55,360 --> 03:57:56,560 DIFFERENCES IN TRANSIT TIME WE 5195 03:57:56,560 --> 03:57:58,360 HAVE TALKED ABOUT IN THIS 5196 03:57:58,360 --> 03:58:01,120 WORKSHOP HAVE A HUGE 5197 03:58:01,120 --> 03:58:03,840 DIFFERENCE ON THE MICROBIAL 5198 03:58:03,840 --> 03:58:07,360 SUCCESS AND ON THE LEFT SIDE 5199 03:58:07,360 --> 03:58:13,440 YOU CAN SEE IT PREFERS THE 5200 03:58:13,440 --> 03:58:16,360 RESIDENT COLON BUT ALSO OCCURS 5201 03:58:16,360 --> 03:58:17,360 LONGER TRANSITION TIMES. 5202 03:58:17,360 --> 03:58:19,080 THEN ON THE RIGHT YOU HAVE 5203 03:58:19,080 --> 03:58:21,960 OTHER STREAMS WITH A SHORTER 5204 03:58:21,960 --> 03:58:24,840 TIME SO MAYBE THIS IS FOR 5205 03:58:24,840 --> 03:58:26,760 SPECIFIC PROGRAM APPLICATIONS. 5206 03:58:26,760 --> 03:58:28,240 PERMIZATION ALSO PLAYS AT THE 5207 03:58:28,240 --> 03:58:31,520 LEVEL OF A SPECIFIC METABOLIC 5208 03:58:31,520 --> 03:58:32,280 CONVERSION. 5209 03:58:32,280 --> 03:58:35,040 SO THIS IS AN EXAMPLE FROM THE 5210 03:58:35,040 --> 03:58:38,440 FIELD AND I CONVERTED IT WITH 5211 03:58:38,440 --> 03:58:41,200 HUMAN MICROBES THAT MIGHT BE 5212 03:58:41,200 --> 03:58:43,080 IMPORTANT FOR INDIVIDUALS WITH 5213 03:58:43,080 --> 03:58:48,160 SUDDEN CHANGES IN HORMONE 5214 03:58:48,160 --> 03:58:48,520 LEVEL. 5215 03:58:48,520 --> 03:58:59,840 SO WE'RE DOING FECAL 5216 03:58:59,840 --> 03:59:00,560 VACCINATIONS SAMPLES FROM THE 5217 03:59:00,560 --> 03:59:01,720 INDIVIDUAL AND YOU CAN SEE IT 5218 03:59:01,720 --> 03:59:04,240 IS GOING FROM ZERO TO 5219 03:59:04,240 --> 03:59:04,640 100 PERCENT. 5220 03:59:04,640 --> 03:59:08,320 SO WHAT WE DID WAS SELECT A 5221 03:59:08,320 --> 03:59:13,640 LOW TO MODERATE AND HIGH 5222 03:59:13,640 --> 03:59:15,440 MICROBIAL SAMPLE FROM 5223 03:59:15,440 --> 03:59:17,600 INDIVIDUALS AND SO WE HAVE 5224 03:59:17,600 --> 03:59:21,600 STUDIES WHERE WE SEE 5225 03:59:21,600 --> 03:59:22,360 INDIVIDUALS INGESTING THE 5226 03:59:22,360 --> 03:59:25,280 SAMPLE, YOU CAN SEE THE 5227 03:59:25,280 --> 03:59:27,400 EXCRETION PROFILES ARE 5228 03:59:27,400 --> 03:59:30,480 REFLECTED OF THEIR HIGH, 5229 03:59:30,480 --> 03:59:35,600 MODERATE OR LOW SE CRETER 5230 03:59:35,600 --> 03:59:39,000 STATUS AND ALSO THIS IS 5231 03:59:39,000 --> 03:59:39,920 SIMULATED WHERE THE SAME 5232 03:59:39,920 --> 03:59:41,200 MATERIAL FROM THE INDIVIDUALS 5233 03:59:41,200 --> 03:59:45,440 IS ABLE TO CONSERVE THAT 5234 03:59:45,440 --> 03:59:48,320 STATUS AND SHOW IT IN 5235 03:59:48,320 --> 03:59:48,920 PROFILES. 5236 03:59:48,920 --> 03:59:51,360 THE PERSONALIZATION IS NOT 5237 03:59:51,360 --> 03:59:52,760 ONLY ABOUT THESE GENOTYPES BUT 5238 03:59:52,760 --> 03:59:54,280 SOMETIMES WE NEED TO ALSO LOOK 5239 03:59:54,280 --> 03:59:55,440 INTO THE PATIENT SHALL 5240 03:59:55,440 --> 03:59:56,720 ORGANIZATION AND THIS IS A 5241 03:59:56,720 --> 03:59:58,720 SLIDE I OFTEN USE IN MY 5242 03:59:58,720 --> 03:59:59,920 PRESENTATION BUT I THINK YOU 5243 03:59:59,920 --> 04:00:03,320 WOULD ALL AGREE WITH ME THERE 5244 04:00:03,320 --> 04:00:09,560 IS NO SUCH THING AS A TRAINING 5245 04:00:09,560 --> 04:00:13,640 MICROBIAL LEVEL WITH ALL THESE 5246 04:00:13,640 --> 04:00:14,600 ENVIRONMENTS BUT A PLATFORM 5247 04:00:14,600 --> 04:00:16,400 IMPORTANT TO CONSIDER AND IN 5248 04:00:16,400 --> 04:00:20,840 THE LAB, WE HAVE SEVEN 5249 04:00:20,840 --> 04:00:25,040 DIFFERENT ONES FOR THESE 5250 04:00:25,040 --> 04:00:25,440 MICROBIOMES. 5251 04:00:25,440 --> 04:00:29,840 SO HERE WE ARE LOOKING AT THE 5252 04:00:29,840 --> 04:00:31,320 FIBER, WHEAT BRAND FOR EXAMPLE 5253 04:00:31,320 --> 04:00:35,160 ENRICHED WITH A VERY COMPLEX 5254 04:00:35,160 --> 04:00:37,560 STRUGGLE SURE WHICH CAN BE 5255 04:00:37,560 --> 04:00:39,240 TAKEN FROM ONE VESSEL TO 5256 04:00:39,240 --> 04:00:40,520 ANOTHER IN THE SHINE SYSTEMS 5257 04:00:40,520 --> 04:00:42,160 AND JUST LET THE SYSTEM 5258 04:00:42,160 --> 04:00:46,640 STABILIZE AND WE LOOK AT THE 5259 04:00:46,640 --> 04:00:48,640 GRAPH EFFECT ON THESE WHEAT 5260 04:00:48,640 --> 04:00:50,000 BRAND PARTICLES AND WHAT YOU 5261 04:00:50,000 --> 04:01:02,360 SEE IS WHEAT BRAND IS ALSO A 5262 04:01:02,360 --> 04:01:03,200 DRIVER OF COMPLICATION, YOU 5263 04:01:03,200 --> 04:01:07,120 SEE THERE IS A NICE FIXATION 5264 04:01:07,120 --> 04:01:14,640 BETWEEN THE BRAN ASSOCIATED 5265 04:01:14,640 --> 04:01:18,320 WITH ENRICHED WITH BIOIC 5266 04:01:18,320 --> 04:01:19,240 INDUCING ABILITIES. 5267 04:01:19,240 --> 04:01:21,960 SO YOU CAN TAKE THESE TAILS 5268 04:01:21,960 --> 04:01:24,920 FOR A VERY TIMED RESULT, 5269 04:01:24,920 --> 04:01:25,960 SEVERAL MINUTES OR OVER 5270 04:01:25,960 --> 04:01:27,800 SEVERAL HOURS AND LOOK HOW IT 5271 04:01:27,800 --> 04:01:30,520 TAKES PLACE AND AGAIN WE CAN 5272 04:01:30,520 --> 04:01:32,120 SEE HERE FOR THE INDIVIDUALS 5273 04:01:32,120 --> 04:01:34,440 HERE, THEY HAVE NIGHT DYNAMICS 5274 04:01:34,440 --> 04:01:36,840 OF THIS PROCESS, EVENTUALLY 5275 04:01:36,840 --> 04:01:38,640 ENDING UP WITH THE EXECUTION 5276 04:01:38,640 --> 04:01:47,880 AND FUNCTION BEING SUPPORTED 5277 04:01:47,880 --> 04:01:48,640 BY THESE PARTICLES. 5278 04:01:48,640 --> 04:01:53,960 SO WE HAVE THE FUNCTIONAL 5279 04:01:53,960 --> 04:01:56,280 NICHE AND SHOW IN VITRO IT 5280 04:01:56,280 --> 04:01:59,680 INCREASED IN PRODUCTION AND 5281 04:01:59,680 --> 04:02:01,520 ALSO ENHANCED THE INTEGRITY 5282 04:02:01,520 --> 04:02:05,280 AND THEN IN THOSE GROUPS, LIKE 5283 04:02:05,280 --> 04:02:06,760 TO DEMONSTRATE SEVERAL OF 5284 04:02:06,760 --> 04:02:21,680 THESE ARE ABLE TO INDUCE 5285 04:02:21,680 --> 04:02:24,480 REGULATORY T-CELLS. 5286 04:02:24,480 --> 04:02:26,240 SO THIS DEMONSTRATES VARIOUS 5287 04:02:26,240 --> 04:02:29,240 INDIVIDUALS, IN THIS CASE, 5288 04:02:29,240 --> 04:02:32,600 CONE'S DISEASE IN TERMS OF 5289 04:02:32,600 --> 04:02:34,600 HEALTH STATUS AND IN TERMS OF 5290 04:02:34,600 --> 04:02:36,920 THE DISEASE AND YOU SEE THIS 5291 04:02:36,920 --> 04:02:38,720 IS CORRESPONDING IN 5292 04:02:38,720 --> 04:02:41,160 FUNCTIONALITY, 35 PERCENT, IN 5293 04:02:41,160 --> 04:02:42,320 THIS CASE, ACTIVE CROHN'S 5294 04:02:42,320 --> 04:02:43,840 DISEASE COMPARED TO PATIENTS 5295 04:02:43,840 --> 04:02:45,560 IN REMISSION AND HERE YOU SEE 5296 04:02:45,560 --> 04:02:58,040 THIS IS ALL CORRESPONDED WITH 5297 04:02:58,040 --> 04:02:58,400 ABILITIES. 5298 04:02:58,400 --> 04:03:01,840 A LOT OF DOWN REGULATED 5299 04:03:01,840 --> 04:03:06,600 MATERIAL HERE FOR CROHN'S 5300 04:03:06,600 --> 04:03:07,560 DISEASE AND DIVERTICULITIS, 5301 04:03:07,560 --> 04:03:10,480 YOU SEE IT IS SLIGHTLY 5302 04:03:10,480 --> 04:03:12,800 OXYGENIZING AND WE CAN STUDY 5303 04:03:12,800 --> 04:03:15,800 THAT OVER THIS MEMBRANE AND 5304 04:03:15,800 --> 04:03:17,840 DEMONSTRATE IT IS ABLE TO DO 5305 04:03:17,840 --> 04:03:23,200 SO TO COPE WITH THIS OXIDATIVE 5306 04:03:23,200 --> 04:03:23,520 STRESS. 5307 04:03:23,520 --> 04:03:24,920 >> YOU HAVE THREE MINUTES. 5308 04:03:24,920 --> 04:03:25,560 >> THAT'S GREAT. 5309 04:03:25,560 --> 04:03:27,760 SO TO FINISH OFF, I WOULD LIKE 5310 04:03:27,760 --> 04:03:30,040 TO HAVE A COUPLE SLIDES MORE 5311 04:03:30,040 --> 04:03:33,600 ON THE UNRAFFLING OF HOW WE 5312 04:03:33,600 --> 04:03:36,400 CAN USE THIS IN VITRO 5313 04:03:36,400 --> 04:03:38,160 TECHNOLOGY TO UNRAFFLE THE 5314 04:03:38,160 --> 04:03:44,240 INTEGRATION OF THE PROBIOTICS 5315 04:03:44,240 --> 04:03:46,200 SHOWN ON THE PROMINENT SIDE. 5316 04:03:46,200 --> 04:03:49,360 SO WE HAVE CAPTURED THE 5317 04:03:49,360 --> 04:03:56,560 BACTERIA BUT ALSO SOMETIMES 5318 04:03:56,560 --> 04:04:00,760 THE STRESSORS. 5319 04:04:00,760 --> 04:04:10,400 THERE IS A CERTAIN COLIZATION 5320 04:04:10,400 --> 04:04:13,160 THAT IS PRESENT IN INDIVIDUALS 5321 04:04:13,160 --> 04:04:16,600 AND THIS MAY COMPROMISE THE 5322 04:04:16,600 --> 04:04:17,520 GRAPHIC SUCCESS. 5323 04:04:17,520 --> 04:04:20,160 THERE IS ANOTHER PROCESS 5324 04:04:20,160 --> 04:04:23,720 TAKING PLACE AND THAT IS 5325 04:04:23,720 --> 04:04:27,440 LINOLEIC ACID. 5326 04:04:27,440 --> 04:04:29,840 BASICALLY YOU ARE SEPARATING 5327 04:04:29,840 --> 04:04:31,760 THIS ACID AND ALLEVIATING 5328 04:04:31,760 --> 04:04:32,120 TOXICITY. 5329 04:04:32,120 --> 04:04:46,840 AND THIS IS SOMETHING THAT IS 5330 04:04:46,840 --> 04:04:49,040 DONE THIS IS TAKING PLACE IN 5331 04:04:49,040 --> 04:04:51,240 THE MICROBIOME SO WHEN YOU 5332 04:04:51,240 --> 04:04:53,200 COMPARE THE FATTY ACID 5333 04:04:53,200 --> 04:04:54,240 PROFILES BETWEEN THE AREAS, 5334 04:04:54,240 --> 04:05:00,280 YOU SEE THERE IS AN ENRICHMENT 5335 04:05:00,280 --> 04:05:01,440 OF THE MUCOSAL AREAS. 5336 04:05:01,440 --> 04:05:03,440 SO WHEN WE DO FURTHER STUDIES 5337 04:05:03,440 --> 04:05:05,200 WITH THE SHINE SYSTEM AND LOOK 5338 04:05:05,200 --> 04:05:07,320 AT THE SEQUENCING DATA AND 5339 04:05:07,320 --> 04:05:09,240 THEN DRAFT THESE CORE CURRENT 5340 04:05:09,240 --> 04:05:11,560 NETWORKS, IT IS INTERESTING TO 5341 04:05:11,560 --> 04:05:16,160 SEE THE CORE CURRENT NETWORKS 5342 04:05:16,160 --> 04:05:20,120 ARE MADE AUTOMATICALLY BY THE 5343 04:05:20,120 --> 04:05:26,520 PATIENT, FOR EXAMPLE, BASED ON 5344 04:05:26,520 --> 04:05:29,240 MUCOSAL BUT BROADER LINOLEIC 5345 04:05:29,240 --> 04:05:29,600 DUCTS. 5346 04:05:29,600 --> 04:05:33,480 AND THE MOMENT WE ADD LINOLEIC 5347 04:05:33,480 --> 04:05:40,080 ACID, SOMETHING ELSE HAPPENS. 5348 04:05:40,080 --> 04:05:42,800 YOU CAN SEE HERE THE EFFECT 5349 04:05:42,800 --> 04:05:48,120 AND THIS TELLS US MAYBE THESE 5350 04:05:48,120 --> 04:05:50,640 ARE AN IMPORTANT STABILIZING 5351 04:05:50,640 --> 04:05:52,920 EFFECT FOR THE SYSTEM AND THEN 5352 04:05:52,920 --> 04:06:01,120 THE QUESTION IS CAN EACH 5353 04:06:01,120 --> 04:06:04,200 SPECIES CONTROL THE STRESS. 5354 04:06:04,200 --> 04:06:08,840 SO WE CAN SEE IN THE CASES OF 5355 04:06:08,840 --> 04:06:11,640 LINOLEIC ACID, THERE IS 5356 04:06:11,640 --> 04:06:13,680 TOXICITY FOR BOTH BACTERIA AND 5357 04:06:13,680 --> 04:06:19,960 WE HAD A COMPLETE LOSS OF 5358 04:06:19,960 --> 04:06:20,920 BUTRATE PRODUCING 5359 04:06:20,920 --> 04:06:21,760 FUNCTIONALITY. 5360 04:06:21,760 --> 04:06:25,240 BUT IN THE PRESENCE OF IT, YOU 5361 04:06:25,240 --> 04:06:28,480 CAN SEE THE WE HAVE PROTECTION 5362 04:06:28,480 --> 04:06:30,600 OF THE LEVELS AND PROTECTION 5363 04:06:30,600 --> 04:06:32,160 OF PRODUCING FUNCTION. 5364 04:06:32,160 --> 04:06:33,560 SO THIS COULD RESULT 5365 04:06:33,560 --> 04:06:35,360 EVENTUALLY IN INFORMATION ON 5366 04:06:35,360 --> 04:06:40,040 HOW TO GUIDE US TOWARDS 5367 04:06:40,040 --> 04:06:44,320 PRECISION BIOTICS, MAKING 5368 04:06:44,320 --> 04:06:49,640 COCKTAILS FROM LINOLEIC ACID, 5369 04:06:49,640 --> 04:06:51,160 HYDROGEN PRODUCING CELLS -- 5370 04:06:51,160 --> 04:06:51,840 [INDISCERNIBLE] 5371 04:06:51,840 --> 04:06:53,240 SO TO END, I WOULD LIKE TO 5372 04:06:53,240 --> 04:06:55,880 JUST GIVE A COUPLE OF 5373 04:06:55,880 --> 04:06:58,920 OPPORTUNITIES AND CHALLENGES. 5374 04:06:58,920 --> 04:07:01,120 SO IN VITRO TECHNOLOGY, I HOPE 5375 04:07:01,120 --> 04:07:03,880 YOU AGREE WITH ME THAT 5376 04:07:03,880 --> 04:07:04,920 PERSONALIZATION IS ACHIEVABLE 5377 04:07:04,920 --> 04:07:06,440 AND VALIDATION IS CRUCIAL. 5378 04:07:06,440 --> 04:07:07,480 I THINK AN IMPORTANT CHALLENGE 5379 04:07:07,480 --> 04:07:22,000 IS WE NEED TO EXPAND THIS TO 5380 04:07:22,000 --> 04:07:25,840 THE SITE OF ACTION AND THE 5381 04:07:25,840 --> 04:07:33,040 INTRODUCTION OF MEDIUM SUCH AS 5382 04:07:33,040 --> 04:07:33,440 LINOLEICS. 5383 04:07:33,440 --> 04:07:34,640 AND EVENTUALLY PROVIDE MORE 5384 04:07:34,640 --> 04:07:42,240 INSIGHT ON THE PRECISION 5385 04:07:42,240 --> 04:07:43,120 MICROBIOTICS IMPORTANCE AND 5386 04:07:43,120 --> 04:07:44,360 THEN COMBINATION OF THE 5387 04:07:44,360 --> 04:07:47,200 STUDIES IS VERY VALUABLE BUT I 5388 04:07:47,200 --> 04:07:49,840 WOULD GO ALSO FROM AVERAGE 5389 04:07:49,840 --> 04:07:54,800 DATA TO INDIVIDUAL DATA SO WE 5390 04:07:54,800 --> 04:07:56,520 UNDERSTAND IT ON A PERSONAL 5391 04:07:56,520 --> 04:07:59,280 LEVEL AND WITH THAT I WOULD 5392 04:07:59,280 --> 04:08:02,840 LIKE TO THANK YOU FOR YOUR 5393 04:08:02,840 --> 04:08:03,280 ATTENTION. 5394 04:08:03,280 --> 04:08:06,560 >> THANKS A LOT, DOCTOR AND 5395 04:08:06,560 --> 04:08:10,200 NOW WE MOVE ON TO 5396 04:08:10,200 --> 04:08:36,080 MICROBIOACTIVITY 5397 04:08:36,080 --> 04:08:37,680 >> OKAY, SO I AM SURE EVERYONE 5398 04:08:37,680 --> 04:08:39,640 WOULD AGREE WITH THE STATEMENT 5399 04:08:39,640 --> 04:08:41,480 THAT EVEN THOUGH WE HAVE MADE 5400 04:08:41,480 --> 04:08:42,640 HUGE AMOUNT OF PROGRESS IN THE 5401 04:08:42,640 --> 04:08:50,440 FIELD OVER THE PAST FEW YEARS, 5402 04:08:50,440 --> 04:08:52,760 IDENTIFYING CAUSAL OR 5403 04:08:52,760 --> 04:08:54,560 MECHANISTIC THINGS IN THE 5404 04:08:54,560 --> 04:08:55,600 MICROBIOME IS STILL A 5405 04:08:55,600 --> 04:08:58,440 CHALLENGE AND THIS IS AFTER WE 5406 04:08:58,440 --> 04:09:01,040 HAVE BEEN ABLE TO PRODUCE 5407 04:09:01,040 --> 04:09:03,880 CATALOGS OF GENES AND THE 5408 04:09:03,880 --> 04:09:05,320 MICROBES THEY PRODUCE AND THAT 5409 04:09:05,320 --> 04:09:09,440 IS TO MY POINT TODAY THAT EVEN 5410 04:09:09,440 --> 04:09:16,200 THOUGH WE HAVE THESE, THE 5411 04:09:16,200 --> 04:09:19,920 ANALOGIES ARE POOR AT 5412 04:09:19,920 --> 04:09:22,560 ANALYZING THE GENES AND STILL 5413 04:09:22,560 --> 04:09:23,320 LACK FUNCTIONAL IMPLEMENTATION 5414 04:09:23,320 --> 04:09:24,960 SO I THINK THIS IS REALLY ONE 5415 04:09:24,960 --> 04:09:29,560 OF THE KEY BARRIERS WE HAVE. 5416 04:09:29,560 --> 04:09:31,560 SO ONE OF THE QUESTIONS THAT 5417 04:09:31,560 --> 04:09:52,160 HALF OF MY LAB WORKS ON IS 5418 04:09:52,160 --> 04:09:55,560 ESSENTIALLY THE TIERS AND 5419 04:09:55,560 --> 04:09:56,720 FUNCTION PARTICULARLY IN THIS 5420 04:09:56,720 --> 04:09:58,200 RELEVANT NOISE. 5421 04:09:58,200 --> 04:09:59,240 SO OUR SOMEWHAT UNIQUE 5422 04:09:59,240 --> 04:10:00,360 APPROACH OR FOCUS TO 5423 04:10:00,360 --> 04:10:02,800 APPROACHING THIS PROBLEM IS TO 5424 04:10:02,800 --> 04:10:04,160 DEVELOP NEW TECHNOLOGIES THAT 5425 04:10:04,160 --> 04:10:06,400 WE REFER TO AS FUNCTIONAL 5426 04:10:06,400 --> 04:10:08,760 APPROACHES TO DISTINGUISH THEM 5427 04:10:08,760 --> 04:10:09,800 FROM BIOGENETIC APPROACHES AND 5428 04:10:09,800 --> 04:10:11,960 THEY ARE ALL BASED AROUND THE 5429 04:10:11,960 --> 04:10:13,000 SAME FUNDAMENTAL PRINCIPLE 5430 04:10:13,000 --> 04:10:15,440 WHEN WE SOMETIMES 5431 04:10:15,440 --> 04:10:16,600 CONCEPTUALIZE AS USING THE 5432 04:10:16,600 --> 04:10:19,160 HOST AS A LENS TO ILLUMINATE 5433 04:10:19,160 --> 04:10:20,760 THE MICRO BIOTICS THAT SHAPE 5434 04:10:20,760 --> 04:10:26,440 OUR OWN BIOLOGY AS WELL AS THE 5435 04:10:26,440 --> 04:10:27,040 MACROBIOTIC ACTION. 5436 04:10:27,040 --> 04:10:29,000 AND THIS IS AROUND THE IDEA 5437 04:10:29,000 --> 04:10:30,480 THAT THE MICROBES THAT ARE 5438 04:10:30,480 --> 04:10:31,640 LIKELY TO DO INTERESTING 5439 04:10:31,640 --> 04:10:33,360 THINGS WITH US ARE THOSE 5440 04:10:33,360 --> 04:10:34,840 PRODUCTS THAT CAN INTERACT 5441 04:10:34,840 --> 04:10:37,200 WITH OUR OWN BIOLOGY IN SOME 5442 04:10:37,200 --> 04:10:39,840 SPECIFIC WAY AT A MOLECULAR 5443 04:10:39,840 --> 04:10:40,400 LEVEL. 5444 04:10:40,400 --> 04:10:43,120 SO IF WE PRODUCE TOOLS LIKE 5445 04:10:43,120 --> 04:10:47,240 FISHING HOOKS THAT FISH OUT 5446 04:10:47,240 --> 04:10:47,920 MICROBES DIRECTLY INTERACTING 5447 04:10:47,920 --> 04:10:51,520 WITH THE HOST OR BETTER YET, 5448 04:10:51,520 --> 04:10:52,800 TO PROFILE POTENTIAL 5449 04:10:52,800 --> 04:10:54,280 INTERACTIONS BETWEEN MICROBES 5450 04:10:54,280 --> 04:10:57,480 AND VARIOUS HOST PROTEINS THAT 5451 04:10:57,480 --> 04:11:04,720 MAY BE SENSING THOSE MICROBES, 5452 04:11:04,720 --> 04:11:06,960 THAT MAY SHOW WHAT IS 5453 04:11:06,960 --> 04:11:07,720 AFFECTING THEIR SUCCESS. 5454 04:11:07,720 --> 04:11:10,000 SO WE HAVE SCHOOL DISTRICT 5455 04:11:10,000 --> 04:11:12,640 SOME SUCCESS IN THE PAST WITH 5456 04:11:12,640 --> 04:11:13,880 MICROBES AND THINGS YOU HAVE 5457 04:11:13,880 --> 04:11:15,520 HEARD ABOUT ALREADY CALLED IGA 5458 04:11:15,520 --> 04:11:22,760 AS WELL AS RECENTLY STUDIED 5459 04:11:22,760 --> 04:11:28,280 PUBLISHED STUDIES STILL IN 5460 04:11:28,280 --> 04:11:32,440 REVIEW THROUGH ULTRA HIGH 5461 04:11:32,440 --> 04:11:34,160 INPUT BIOASSAYS AND SO WE CAN 5462 04:11:34,160 --> 04:11:36,160 ENGAGE THIS IMPORTANT FAMILY 5463 04:11:36,160 --> 04:11:36,760 OF HOST RECEPTORS. 5464 04:11:36,760 --> 04:11:40,240 BUT TODAY I WANT TO FOCUS ON A 5465 04:11:40,240 --> 04:11:42,160 THIRD AREA OF INTEREST WHICH 5466 04:11:42,160 --> 04:11:43,240 IS COMPLETELY UNPICK 5467 04:11:43,240 --> 04:11:45,320 ACCOMPLISHED BASED ON THE IDEA 5468 04:11:45,320 --> 04:11:47,480 OF PROFILING DIRECT PHYSICAL 5469 04:11:47,480 --> 04:11:49,080 INTERACTION BETWEEN IMPACT 5470 04:11:49,080 --> 04:11:50,640 MICROBES AND EXTRA CELLULAR 5471 04:11:50,640 --> 04:11:51,080 PROTEIN. 5472 04:11:51,080 --> 04:11:53,360 SO THIS STORY I WILL TELL YOU 5473 04:11:53,360 --> 04:11:54,640 VERY BRIEFLY TODAY STARTED 5474 04:11:54,640 --> 04:11:56,880 ALMOST SEVEN YEARS AGO, 5475 04:11:56,880 --> 04:11:58,960 ACTUALLY, WITH A CONVERSATION 5476 04:11:58,960 --> 04:12:00,760 WITH MY COLLEAGUE ERIN RING AS 5477 04:12:00,760 --> 04:12:09,080 WELL AS BOTH OF OUR FIRST 5478 04:12:09,080 --> 04:12:11,120 GRADUATE STUDENTS WHO, ONE OF 5479 04:12:11,120 --> 04:12:13,440 WHOM HAS TAKEN OVER IN MY LAB 5480 04:12:13,440 --> 04:12:14,480 AND ANOTHER WHO WILL COME 5481 04:12:14,480 --> 04:12:15,440 LATER TO UNDERSTAND THE 5482 04:12:15,440 --> 04:12:17,280 STRUCTURE AND FUNCTION OF THIS 5483 04:12:17,280 --> 04:12:18,480 DATA. 5484 04:12:18,480 --> 04:12:21,400 BUT THE BASIC IDEA AS I 5485 04:12:21,400 --> 04:12:24,120 ELABORATED THAT BACTERIAL 5486 04:12:24,120 --> 04:12:30,080 INTERACTION WITH DEXO PROTEINS 5487 04:12:30,080 --> 04:12:33,600 MAY REVEAL THE MICROBIOTA AND 5488 04:12:33,600 --> 04:12:35,000 THEIR INTERACTIONS. 5489 04:12:35,000 --> 04:12:37,600 ANYONE WHO STUDIES THESE WOULD 5490 04:12:37,600 --> 04:12:38,760 KNOW WHY THEY ARE INTERESTING 5491 04:12:38,760 --> 04:12:40,960 BUT NOT ONLY ARE THERE 5492 04:12:40,960 --> 04:12:43,320 INTERESTING OPPORTUNITIES FOR 5493 04:12:43,320 --> 04:12:46,880 MICROBES TO INTERACT WITH POST 5494 04:12:46,880 --> 04:12:48,280 BARRIER SERVICES BUT SINCE WE 5495 04:12:48,280 --> 04:12:49,760 STARTED THIS PROJECT SEVEN 5496 04:12:49,760 --> 04:12:51,840 YEARS AGO, A HUGE AMOUNT OF 5497 04:12:51,840 --> 04:12:53,680 EMERGING EVIDENCE TO SUGGEST 5498 04:12:53,680 --> 04:12:54,960 THAT MICROBES MAY ACTUALLY 5499 04:12:54,960 --> 04:12:56,080 HAVE THE OPPORTUNITY TO 5500 04:12:56,080 --> 04:12:59,040 INTERACT WITH DIVERSE CELL 5501 04:12:59,040 --> 04:13:02,280 TYPES AND THEREFORE THERE ARE 5502 04:13:02,280 --> 04:13:04,600 EXTRA CELLULAR AND SEEK CRETED 5503 04:13:04,600 --> 04:13:06,200 PROTEINS EVEN IN AREAS WE 5504 04:13:06,200 --> 04:13:07,840 PREVIOUSLY THOUGHT WERE 5505 04:13:07,840 --> 04:13:08,400 STERILE. 5506 04:13:08,400 --> 04:13:09,880 SO DESPITE THE POTENTIAL 5507 04:13:09,880 --> 04:13:10,800 IMPORTANCE OF THESE 5508 04:13:10,800 --> 04:13:12,440 INTERACTIONS, IF YOU GO TO THE 5509 04:13:12,440 --> 04:13:13,480 LITERATURE, YOU WILL FIND 5510 04:13:13,480 --> 04:13:17,800 ACTUALLY THIS INTERACTION WITH 5511 04:13:17,800 --> 04:13:19,720 THE MICROBIOTA IS ALMOST 5512 04:13:19,720 --> 04:13:20,680 COMPLETELY UNMATCHED. 5513 04:13:20,680 --> 04:13:28,480 SO ASIDE FROM A FEW REALLY 5514 04:13:28,480 --> 04:13:29,520 NOTABLE EXAMPLES, ONE 5515 04:13:29,520 --> 04:13:31,680 DESCRIBED BY WENDY HERE AND 5516 04:13:31,680 --> 04:13:33,280 OTHER POST SERVICE RECEPTORS, 5517 04:13:33,280 --> 04:13:37,400 PARTICULARLY IN THE CONTEXT OF 5518 04:13:37,400 --> 04:13:38,800 MODULATION IN COLORECTAL 5519 04:13:38,800 --> 04:13:40,880 CANCER, ASIDE FROM A FEW 5520 04:13:40,880 --> 04:13:42,360 ANTIDOTES, THESE ARE 5521 04:13:42,360 --> 04:13:43,680 COMPLETELY UNMATCHED. 5522 04:13:43,680 --> 04:13:46,280 SO WHAT WE SET OUT TO DO IS 5523 04:13:46,280 --> 04:13:47,840 DEVELOP A TECHNOLOGY THAT 5524 04:13:47,840 --> 04:13:49,000 WOULD SYSTEMATICALLY ALLOW US 5525 04:13:49,000 --> 04:13:50,160 TO EXPLORE THIS SPACE AND 5526 04:13:50,160 --> 04:13:51,400 SPECIFIC AREAS OF INTERACTION. 5527 04:13:51,400 --> 04:13:55,280 SO THE DREAM WAS IN A WAY TO 5528 04:13:55,280 --> 04:13:58,440 DEVELOP WHAT YOU CAN KIND OF 5529 04:13:58,440 --> 04:14:00,680 CONCEPTUALIZE IN THE MOLECULAR 5530 04:14:00,680 --> 04:14:06,080 SEARCH ENGINE THAT WOULD ALLOW 5531 04:14:06,080 --> 04:14:07,440 US TO SPONTANEOUSLY OCCUR 5532 04:14:07,440 --> 04:14:09,280 ACTIONS BETWEEN THE MICROBES 5533 04:14:09,280 --> 04:14:11,240 AND THE BINDING PARTNER. 5534 04:14:11,240 --> 04:14:13,760 SO THESE WOULD ALL BE THE 5535 04:14:13,760 --> 04:14:15,840 PROTEINS OR WHAT MY COLLEAGUE 5536 04:14:15,840 --> 04:14:23,040 REFERS TO AS THE XEXOPROTEUM, 5537 04:14:23,040 --> 04:14:25,280 IN A SINGLE TUBE. 5538 04:14:25,280 --> 04:14:30,600 AND WITHIN THE INTERACTUM 5539 04:14:30,600 --> 04:14:32,040 WOULD BE INTEREST THAT WOULD 5540 04:14:32,040 --> 04:14:34,280 ALLOW US TO ASSIGN WHAT WE 5541 04:14:34,280 --> 04:14:38,440 THINK OF AS POST DENDRIC 5542 04:14:38,440 --> 04:14:40,480 MICROBE FUNCTION AND USE THE 5543 04:14:40,480 --> 04:14:43,600 RECEPTORS OF THE MICROBES 5544 04:14:43,600 --> 04:14:44,760 ENGAGING, AGAIN TO REITERATE 5545 04:14:44,760 --> 04:14:49,760 THE IDEA OF USING A HOST AS A 5546 04:14:49,760 --> 04:14:54,640 LENS, USING THE DEEPOLOGY OF 5547 04:14:54,640 --> 04:14:57,000 BIOLOGY RECEPTORS TO EXPLORE 5548 04:14:57,000 --> 04:14:58,960 THE HYPOTHESIS OF WHAT 5549 04:14:58,960 --> 04:15:02,520 RECEPTORS ARE BINDING AND THE 5550 04:15:02,520 --> 04:15:04,280 PHYSICIAN LODGIC OUTCOMES THAT 5551 04:15:04,280 --> 04:15:05,640 MAY RESULT FROM THOSE 5552 04:15:05,640 --> 04:15:06,080 INTERACTIONS. 5553 04:15:06,080 --> 04:15:09,400 SO THIS IS A CLASSIC SLIDE, 5554 04:15:09,400 --> 04:15:12,880 TECHNOLOGY SLIDE THAT SUMS UP 5555 04:15:12,880 --> 04:15:15,320 FIVE OR SIX YEARS OF WORK IN A 5556 04:15:15,320 --> 04:15:17,440 SINGLE CARTOON AND I WILL GO 5557 04:15:17,440 --> 04:15:19,640 OVER IT QUICKLY BECAUSE OF 5558 04:15:19,640 --> 04:15:21,520 TIME. 5559 04:15:21,520 --> 04:15:24,600 SO IN ESSENCE, WHAT WE MANAGED 5560 04:15:24,600 --> 04:15:26,440 TO DO WAS TO DEVELOP THIS 5561 04:15:26,440 --> 04:15:31,680 YEAST SYSTEM IN ERIN'S LAB TO 5562 04:15:31,680 --> 04:15:35,200 DEVELOP A LIBRARY OF BAR CODED 5563 04:15:35,200 --> 04:15:39,680 YEAST AND HE DID THIS BY 5564 04:15:39,680 --> 04:15:41,720 CURATING AND CLONING THESE 5565 04:15:41,720 --> 04:15:44,720 INDIVIDUALLY INTO YEAST 5566 04:15:44,720 --> 04:15:47,560 SECTORS AND TRANSFORMING THESE 5567 04:15:47,560 --> 04:15:49,160 INTO YEAST CLONES SUCH THAT 5568 04:15:49,160 --> 04:15:51,120 YOU HAVE A DISPLAY OF PRETTY 5569 04:15:51,120 --> 04:15:52,960 TEENS LINKED TO THIS BAR CODE. 5570 04:15:52,960 --> 04:15:56,280 THEN WE CAN TAKE THAT LIBRARY 5571 04:15:56,280 --> 04:15:58,360 OF YEAST CLONES, MIX IT WITH A 5572 04:15:58,360 --> 04:16:00,600 BACTERIA THAT IS LABELED, FISH 5573 04:16:00,600 --> 04:16:02,760 OUT THE YEAST AND BECAUSE 5574 04:16:02,760 --> 04:16:06,840 THESE ARE BAR CODED YEAST, YOU 5575 04:16:06,840 --> 04:16:10,920 CAN THEN USE SIMPLE SEQUENCING 5576 04:16:10,920 --> 04:16:13,560 TO DECONVOLUTE THE ENRICHMENT 5577 04:16:13,560 --> 04:16:38,320 INTO THE HOST MICROBIOTA 5578 04:16:38,320 --> 04:16:38,720 INTERACTOME. 5579 04:16:38,720 --> 04:16:41,080 SO WHAT WE HAVE IS THE 5580 04:16:41,080 --> 04:16:42,920 INTERACTION AND I ALLUDED TO 5581 04:16:42,920 --> 04:16:47,480 WE DIDN'T WANT TO DO THAT JUST 5582 04:16:47,480 --> 04:16:49,680 FOR ONE BIOME BUT LOOK ACROSS 5583 04:16:49,680 --> 04:16:50,960 MULTIPLE BIOMES TO LOOK FOR 5584 04:16:50,960 --> 04:16:54,800 PATTERNS AND UNDERSTAND THE 5585 04:16:54,800 --> 04:16:55,520 EXTENSIVE PATTERN INTERACTION 5586 04:16:55,520 --> 04:16:58,120 AND WHETHER WE CAN MAKE ANY 5587 04:16:58,120 --> 04:16:58,960 PREDICTIONS OF BIOLOGY BASED 5588 04:16:58,960 --> 04:16:59,720 ON THAT. 5589 04:16:59,720 --> 04:17:13,400 SO WHAT WE DID WAS HAVE OUR 5590 04:17:13,400 --> 04:17:15,480 FIRST FORUM ON WHETHER WE CAN 5591 04:17:15,480 --> 04:17:21,560 USE THIS FOR INTERACTOMES 5592 04:17:21,560 --> 04:17:26,280 ACROSS DIVERSE PH YLOGENIES 5593 04:17:26,280 --> 04:17:28,280 AND TISSUE OF ORIGINAL. 5594 04:17:28,280 --> 04:17:32,800 SO THIS IS WHAT WE FOUND WHICH 5595 04:17:32,800 --> 04:17:35,960 WAS REALLY REMARKABLE. 5596 04:17:35,960 --> 04:17:37,360 WE LOOKED ACROSS 519 STRAINS, 5597 04:17:37,360 --> 04:17:45,040 MORE THAN OF 0 PERCENT OF ALL 5598 04:17:45,040 --> 04:17:47,480 HUMAN EX EXOPROTEINS, 5599 04:17:47,480 --> 04:17:48,560 IDENTIFIED THOUSANDS OF 5600 04:17:48,560 --> 04:17:49,280 INTERACTIONS INVOLVING 5601 04:17:49,280 --> 04:17:54,560 HUNDREDS OF STRAINS AND 5602 04:17:54,560 --> 04:17:54,920 PROTEINS. 5603 04:17:54,920 --> 04:17:56,440 AND THIS STAIN IS OF TISSUES 5604 04:17:56,440 --> 04:17:58,080 AS WELL AS PATTERNS OF 5605 04:17:58,080 --> 04:17:58,520 INTERACTIONS. 5606 04:17:58,520 --> 04:18:01,640 AND WE WERE ABLE TO VALIDATE 5607 04:18:01,640 --> 04:18:05,160 THE INTERACTION WITH OUR 5608 04:18:05,160 --> 04:18:06,080 APPROACHES WITH PROTEINS IN 5609 04:18:06,080 --> 04:18:09,160 THE CELLS SO THIS IS OUR YEAST 5610 04:18:09,160 --> 04:18:12,400 DISPLAY AND THEY ACTUALLY SHOW 5611 04:18:12,400 --> 04:18:14,560 OVER ARCHING BINDING PATTERNS 5612 04:18:14,560 --> 04:18:16,440 WITH A BIOLOGICAL LOGIC, VERY 5613 04:18:16,440 --> 04:18:19,240 INTERESTING TO US BECAUSE KIND 5614 04:18:19,240 --> 04:18:21,560 OF A GUT CHECK ON WHETHER THIS 5615 04:18:21,560 --> 04:18:24,480 IS WORKING OR NOT. 5616 04:18:24,480 --> 04:18:26,040 SO I CAN'T HAVE TIME TO GO 5617 04:18:26,040 --> 04:18:28,200 THROUGH ALL OF THIS HERE BUT 5618 04:18:28,200 --> 04:18:33,200 ONE OF THE THINGS WE LOOKED AT 5619 04:18:33,200 --> 04:18:35,600 IS STRAINS FROM SIMILAR GENRE 5620 04:18:35,600 --> 04:18:36,600 ACTUALLY INTERACT WITH 5621 04:18:36,600 --> 04:18:42,480 PROTEINS THAT ARE PART OF THE 5622 04:18:42,480 --> 04:18:59,280 SAME PATHWAY. 5623 04:18:59,280 --> 04:18:59,840 YOU SEE TISSUE EXPRESS 5624 04:18:59,840 --> 04:19:00,520 PROTEINS IN SKIN AND MICROBES 5625 04:19:00,520 --> 04:19:01,240 IN OTHER SITES DO NOT INTERACT 5626 04:19:01,240 --> 04:19:01,760 WITH THOSE PROTEINS. 5627 04:19:01,760 --> 04:19:02,400 NOT SURPRISINGLY, A SHARED 5628 04:19:02,400 --> 04:19:03,080 INTERACTION AND ESPECIALLY AS 5629 04:19:03,080 --> 04:19:03,800 A SPECIES IN GENUS LEVEL, AT 5630 04:19:03,800 --> 04:19:04,480 LEAST PARTIALLY EXPLAINED BY 5631 04:19:04,480 --> 04:19:06,200 GENE TRANSFERS AND INTERACTION 5632 04:19:06,200 --> 04:19:07,360 IN HAVING AN INDIVIDUAL NIB 5633 04:19:07,360 --> 04:19:09,200 BUT ALSO ON THE FLIP SIDE AS 5634 04:19:09,200 --> 04:19:11,000 YOU HAVE HEARD A LOT ABOUT, WE 5635 04:19:11,000 --> 04:19:14,560 HAVE SEEN A LOT OF VARIATION 5636 04:19:14,560 --> 04:19:19,120 BETWEEN STRAINS WHICH IMPLIES 5637 04:19:19,120 --> 04:19:19,800 FUNCTIONAL RELATION. 5638 04:19:19,800 --> 04:19:22,640 WE HAVE ALSO SEEN A MYRIAD OF 5639 04:19:22,640 --> 04:19:26,120 INTERACTIONS WHICH WE THINK 5640 04:19:26,120 --> 04:19:27,760 APPLY CRITICAL ROLES IN 5641 04:19:27,760 --> 04:19:30,280 BACTERIAL LIFE IN THE COMPLEX 5642 04:19:30,280 --> 04:19:35,760 OF A HOST INCLUDING NICHE 5643 04:19:35,760 --> 04:19:37,480 COLONIZATION, TISSUE 5644 04:19:37,480 --> 04:19:38,000 REMODELING AND 5645 04:19:38,000 --> 04:19:38,480 IMMUNOMODULATION. 5646 04:19:38,480 --> 04:19:39,880 AND I WILL TELL YOU IN THE 5647 04:19:39,880 --> 04:19:42,440 LAST COUPLE OF MINUTES A 5648 04:19:42,440 --> 04:19:48,280 REALLY FASCINATING ONE WE 5649 04:19:48,280 --> 04:19:52,400 THINK EXISTS AND USING THE T 5650 04:19:52,400 --> 04:19:55,280 CELL PRODUCED IN MAMALIAN 5651 04:19:55,280 --> 04:19:55,760 CELLS. 5652 04:19:55,760 --> 04:19:57,960 THIS WAS REALLY FASCINATING TO 5653 04:19:57,960 --> 04:20:00,880 US BECAUSE CD7 IS HIGHLY 5654 04:20:00,880 --> 04:20:05,680 EXPRESSED IN THE EPITHELIAL 5655 04:20:05,680 --> 04:20:08,520 LIMPOCYTES IN THE INTESTINE 5656 04:20:08,520 --> 04:20:11,280 AND THE SPECIES DIRECTLY 5657 04:20:11,280 --> 04:20:13,000 ENGAGING THESE CELLS DON'T 5658 04:20:13,000 --> 04:20:18,280 REQUIRE T CELL SIMULATION FOR 5659 04:20:18,280 --> 04:20:22,960 ACTIVATION AND THERE BY 5660 04:20:22,960 --> 04:20:24,880 RELIEVING THE PHENOTYPES IN 5661 04:20:24,880 --> 04:20:25,800 CROHN'S. 5662 04:20:25,800 --> 04:20:28,240 SO WE WERE INTERESTED IN 5663 04:20:28,240 --> 04:20:31,680 KNOWING WHETHER THIS WAS HOST 5664 04:20:31,680 --> 04:20:34,280 SPECIES SPECIFIC AND FOR BOTH 5665 04:20:34,280 --> 04:20:35,640 REVOLUTIONARY AND PRACTICAL 5666 04:20:35,640 --> 04:20:38,440 REASONS, WE WERE INTERESTED IN 5667 04:20:38,440 --> 04:20:39,360 UNDERSTANDING WHETHER THIS 5668 04:20:39,360 --> 04:20:40,880 INTERACTION WAS SPECIFIC TO 5669 04:20:40,880 --> 04:20:42,480 HUMAN HOSTS OR WHETHER IT 5670 04:20:42,480 --> 04:20:44,480 COULD BE FOUND IN OTHER HOSTS. 5671 04:20:44,480 --> 04:20:46,400 AND WE FOUND IN THIS CASE IT 5672 04:20:46,400 --> 04:20:49,840 COULD ONLY BIND TO HUMAN CD7 5673 04:20:49,840 --> 04:20:52,400 AND COMPLETELY FAILED TO BIND 5674 04:20:52,400 --> 04:20:52,960 TO MOUSE CD7. 5675 04:20:52,960 --> 04:20:55,080 >> YOU HAVE THREE MINUTES. 5676 04:20:55,080 --> 04:20:55,480 >> PARDON? 5677 04:20:55,480 --> 04:20:56,080 >> THREE MINUTES. 5678 04:20:56,080 --> 04:20:57,400 >> PERFECT, I AM ALMOST DONE. 5679 04:20:57,400 --> 04:21:00,320 SO JUST TO SUM UP, WE THINK 5680 04:21:00,320 --> 04:21:02,080 THAT TECHNOLOGY REALLY OFFERS 5681 04:21:02,080 --> 04:21:10,760 THE FIRST EVER GLIMPSE OF A 5682 04:21:10,760 --> 04:21:14,320 COMPREHENSIVE POST MICROBIOTIC 5683 04:21:14,320 --> 04:21:20,960 INTERACTOME, IT ALLOWS US TO 5684 04:21:20,960 --> 04:21:24,160 GET A GLIMPSE OF COMPREHENSIVE 5685 04:21:24,160 --> 04:21:30,240 HOST MARC CROWBEEN IOTA 5686 04:21:30,240 --> 04:21:34,440 INTERACTOME, USING A HOST AS A 5687 04:21:34,440 --> 04:21:37,280 LENS TO DECONVOLUTE THE 5688 04:21:37,280 --> 04:21:41,680 COMPLEXITY OF THE HUMAN 5689 04:21:41,680 --> 04:21:43,680 MICROBIOTA AND ALSO TO GAIN 5690 04:21:43,680 --> 04:21:45,680 ANS UNDERSTANDING HOW 5691 04:21:45,680 --> 04:21:48,440 APPROPRIATE MOUSE MODELS ARE 5692 04:21:48,440 --> 04:21:50,360 IN STUDYING EFFECTS OF HUMAN 5693 04:21:50,360 --> 04:21:50,680 DISEASE. 5694 04:21:50,680 --> 04:21:54,960 SO JUST KIND OF LAST SIDE, 5695 04:21:54,960 --> 04:21:56,440 FUTURE OUTLOOK, HOPEFULLY I 5696 04:21:56,440 --> 04:21:58,280 HAVE INTRODUCED THIS TO YOU IN 5697 04:21:58,280 --> 04:22:01,080 AN INTERESTING WAY ON THE 5698 04:22:01,080 --> 04:22:06,520 FUNCTIONAL PROFILING OF THE 5699 04:22:06,520 --> 04:22:10,600 MICROBEEN IOME. 5700 04:22:10,600 --> 04:22:17,640 AND WHILE I DISPARAGED THESE 5701 04:22:17,640 --> 04:22:24,600 IDEAS IN THE BEGINNING, THIS 5702 04:22:24,600 --> 04:22:27,280 IS REALLY INTERESTING WHEN WE 5703 04:22:27,280 --> 04:22:28,760 COMBINE THE EXPERIMENTAL 5704 04:22:28,760 --> 04:22:34,880 PLATFORMS WITH THE DATA, WE 5705 04:22:34,880 --> 04:22:36,920 GET THE RESULT FROM THE GBC 5706 04:22:36,920 --> 04:22:38,680 WORK I DIDN'T HAVE TIME TO 5707 04:22:38,680 --> 04:22:40,840 TELL YOU ABOUT. 5708 04:22:40,840 --> 04:22:42,320 WE ALSO FIND THAT THERE ARE 5709 04:22:42,320 --> 04:22:51,320 PATIENT SUBSETS THAT HAVE A 5710 04:22:51,320 --> 04:22:55,680 SHARED MICROBIAL PICTURE OF 5711 04:22:55,680 --> 04:22:56,880 THE DISEASE AND THIS WOULD 5712 04:22:56,880 --> 04:22:59,760 ACTUALLY MOVE AWAY FROM 5713 04:22:59,760 --> 04:23:02,600 TARGETING MERE MICROBES AND 5714 04:23:02,600 --> 04:23:04,440 TOWARDS POTENTIAL HOST TARGET 5715 04:23:04,440 --> 04:23:08,840 ZONES COMPUTED WITH PATHOGENIC 5716 04:23:08,840 --> 04:23:09,640 MICROBES. 5717 04:23:09,640 --> 04:23:11,000 SO WITH THAT, WE WILL THANK 5718 04:23:11,000 --> 04:23:12,400 EVERYONE WHO DID THE WORK AS 5719 04:23:12,400 --> 04:23:14,920 WELL AS THE NOTABLE FUNDING 5720 04:23:14,920 --> 04:23:16,920 FROM NIH AND THANK EVERYONE 5721 04:23:16,920 --> 04:23:18,240 FOR THEIR ATTENTION. 5722 04:23:18,240 --> 04:23:24,280 >> THANK YOU, THIS WAS REALLY 5723 04:23:24,280 --> 04:23:24,640 EXCITING. 5724 04:23:24,640 --> 04:23:37,080 SO NOW WE MOVE ON TO THE NEXT 5725 04:23:37,080 --> 04:23:37,680 SPEAKER FROM HARVARD 5726 04:23:37,680 --> 04:23:40,160 UNIVERSITY WHO WILL TALK ON 5727 04:23:40,160 --> 04:23:40,880 MICROBIOME CHEMISTRY. 5728 04:23:40,880 --> 04:23:43,320 >> ALL RIGHT, I WOULD LIKE TO 5729 04:23:43,320 --> 04:23:44,400 THANK THE ORGANIZERS FOR 5730 04:23:44,400 --> 04:23:46,120 INVITING ME TO BE A PART OF 5731 04:23:46,120 --> 04:23:47,520 THIS VERY INTERESTING 5732 04:23:47,520 --> 04:23:47,880 WORKSHOP. 5733 04:23:47,880 --> 04:23:49,720 MY TRAINING IS ORIGINALLY IN 5734 04:23:49,720 --> 04:23:53,000 CHEMISTRY AND WHAT INITIALLY 5735 04:23:53,000 --> 04:23:58,520 IN MY LABS, MICROBES WAS THE 5736 04:23:58,520 --> 04:24:04,240 AMAZING METABOLISM PRODUCED 5737 04:24:04,240 --> 04:24:04,800 WITH THESE ORGANISMS. 5738 04:24:04,800 --> 04:24:08,000 SO THIS HAS PROVIDED RICH 5739 04:24:08,000 --> 04:24:09,680 OPPORTUNITIES TO DISCOVER 5740 04:24:09,680 --> 04:24:11,880 ENZYME AND ANA BOLIC 5741 04:24:11,880 --> 04:24:13,480 ACTIVITIES BUT I HAVE ALSO 5742 04:24:13,480 --> 04:24:15,560 BECOME REALLY PASS IT NEIGHED 5743 04:24:15,560 --> 04:24:19,480 BY THE ROLES THESE METABOLITES 5744 04:24:19,480 --> 04:24:23,800 PLAY IN COMMUNITIES LIKE 5745 04:24:23,800 --> 04:24:24,560 MICROBIOMES. 5746 04:24:24,560 --> 04:24:26,960 IT EXPANDS THE TISSUE BODY AND 5747 04:24:26,960 --> 04:24:27,600 IMMEDIATE UNITED STATES 5748 04:24:27,600 --> 04:24:29,080 REPORTED INTERACTIONS WITH THE 5749 04:24:29,080 --> 04:24:29,360 HOST. 5750 04:24:29,360 --> 04:24:30,680 WE HAVE SEEN ACTUALLY MANY 5751 04:24:30,680 --> 04:24:35,880 EXAMPLES OF THIS THROUGHOUT 5752 04:24:35,880 --> 04:24:40,120 THE WORKSHOP, THAT MICROBIAL 5753 04:24:40,120 --> 04:24:42,080 METABOLISM CAN BE STRONGLY 5754 04:24:42,080 --> 04:24:43,280 CORRELATED WITH HEALTH 5755 04:24:43,280 --> 04:24:43,920 OUTCOMES. 5756 04:24:43,920 --> 04:24:46,000 HOWEVER OUR UNDERSTANDING OF 5757 04:24:46,000 --> 04:24:47,720 THE BIOLOGICAL CONSEQUENCES IS 5758 04:24:47,720 --> 04:24:48,960 STILL QUITE LIMITED. 5759 04:24:48,960 --> 04:24:51,600 WAS A WAS HIGHLIGHTED IN THE 5760 04:24:51,600 --> 04:24:52,880 LAST TALK, MOST ACTIVITIES 5761 04:24:52,880 --> 04:24:55,320 HAVE IN THE BEEN LINKED TO 5762 04:24:55,320 --> 04:24:57,880 REGIMES OR INSCIENCE AND A 5763 04:24:57,880 --> 04:25:00,240 HUGE FRACTION OF THESE GENES 5764 04:25:00,240 --> 04:25:02,320 OR MOLECULES ASSOCIATED WITH 5765 04:25:02,320 --> 04:25:04,720 THIS COMMUNITY ARE STILL 5766 04:25:04,720 --> 04:25:11,320 UNRACQUET RISED AND -- 5767 04:25:11,320 --> 04:25:11,800 UNCHARACTERIZED. 5768 04:25:11,800 --> 04:25:22,880 SO THESE ARE THE TYPES OF 5769 04:25:22,880 --> 04:25:28,440 QUESTIONS. 5770 04:25:28,440 --> 04:25:33,840 WE USE THESE STUDIES TO GAIN A 5771 04:25:33,840 --> 04:25:36,000 MOLECULAR UNDERSTANDING OF 5772 04:25:36,000 --> 04:25:37,280 METABOLISM WILL REVEAL NEW 5773 04:25:37,280 --> 04:25:38,080 FUNDAMENTAL INSIGHTS INTO THE 5774 04:25:38,080 --> 04:25:40,840 BIOLOGY OF THIS COMMUNITY BUT 5775 04:25:40,840 --> 04:25:43,360 ALSO PERHAPS ENABLE 5776 04:25:43,360 --> 04:25:44,000 THERAPEUTIC INTERVENTIONS 5777 04:25:44,000 --> 04:25:46,120 INCLUDING THE SELECTION AND 5778 04:25:46,120 --> 04:25:47,080 ENGINEERING OF PROBIOTIC 5779 04:25:47,080 --> 04:25:48,160 THERAPIES. 5780 04:25:48,160 --> 04:25:50,480 SO FOR TODAY'S PRESENTATION, I 5781 04:25:50,480 --> 04:25:54,520 WANTED TO PROVIDE ON WHAT IS 5782 04:25:54,520 --> 04:25:56,080 HOPEFULLY A FORWARD-LOOKING 5783 04:25:56,080 --> 04:25:58,520 UNDERSTANDING OF THE GUT 5784 04:25:58,520 --> 04:25:59,800 BACTERIAL FUNCTION AND THE 5785 04:25:59,800 --> 04:26:02,000 ROLE I SEE CHEMISTRY PLAYING 5786 04:26:02,000 --> 04:26:03,680 NOW AND IN THE FUTURE. 5787 04:26:03,680 --> 04:26:08,680 SO THERE ARE EXAMPLES OF 5788 04:26:08,680 --> 04:26:09,480 ENZYME METABOLITE DISCOVERIES 5789 04:26:09,480 --> 04:26:13,600 FROM MY LAB BUT I WANT TO 5790 04:26:13,600 --> 04:26:14,560 BEGIN BY REEMPHASIZING THIS 5791 04:26:14,560 --> 04:26:15,240 PROBLEM. 5792 04:26:15,240 --> 04:26:20,000 WE HAVE AN EXTREMELY POOR 5793 04:26:20,000 --> 04:26:21,480 UNDERSTANDING OF MICROBIOMES 5794 04:26:21,480 --> 04:26:22,680 FROM A FUNCTIONAL PERSPECTIVE. 5795 04:26:22,680 --> 04:26:28,120 SO HERE I AM SHOWING YOU DATA 5796 04:26:28,120 --> 04:26:31,240 FROM A PERSPECTIVE, THIS DATA 5797 04:26:31,240 --> 04:26:33,160 FROM THE HUMAN MICROBIOME 5798 04:26:33,160 --> 04:26:36,480 PROJECT AND REALLY SHOWS HOW 5799 04:26:36,480 --> 04:26:39,240 ANNOTATIONS OF GENES IN GUT 5800 04:26:39,240 --> 04:26:41,080 MICROBIOME SAMPLES IS 5801 04:26:41,080 --> 04:26:41,640 PROBLEMATIC. 5802 04:26:41,640 --> 04:26:46,280 THERE IS A HUGE GAP IN OUR 5803 04:26:46,280 --> 04:26:50,520 ABILITY TO LINK THESE GENES TO 5804 04:26:50,520 --> 04:26:51,120 FUNCTIONS CONFIDENTLY. 5805 04:26:51,120 --> 04:26:54,240 AND THIS IS OF COURSE A 5806 04:26:54,240 --> 04:26:58,720 PROBLEM THAT EXISTS FOR OTHER 5807 04:26:58,720 --> 04:26:59,880 MICROBIAL COMMUNES, OTHER BODY 5808 04:26:59,880 --> 04:27:00,160 SITES. 5809 04:27:00,160 --> 04:27:04,880 SO IF WE WANT TO UNDERSTAND 5810 04:27:04,880 --> 04:27:06,400 WHAT THE HUMAN MICROBIOME IS 5811 04:27:06,400 --> 04:27:07,480 DOING, WE NEED TO CONNECT 5812 04:27:07,480 --> 04:27:09,280 THESE REGIMES TO FUNCTION AND 5813 04:27:09,280 --> 04:27:11,800 MY LAB IN PARTICULAR HAS BEEN 5814 04:27:11,800 --> 04:27:13,960 TRYING TO MATCH METABOLIC 5815 04:27:13,960 --> 04:27:15,360 ACTIVITIES WITH GENES AND 5816 04:27:15,360 --> 04:27:17,880 ENZYMES SO AGAIN WE REALLY 5817 04:27:17,880 --> 04:27:19,280 THINK UNDERSTANDING BACTERIAL 5818 04:27:19,280 --> 04:27:21,880 ENZYMES WILL BE CRITICAL FOR 5819 04:27:21,880 --> 04:27:23,960 THE UNDERSTANDING OF 5820 04:27:23,960 --> 04:27:26,080 MICROBIOMES, DISCOVERING AND 5821 04:27:26,080 --> 04:27:28,360 STUDYING ENZYMES APPROVES OUR 5822 04:27:28,360 --> 04:27:30,400 ABILITY TO ANALYZE MICROBIAL 5823 04:27:30,400 --> 04:27:33,920 AGAIN HOME IN AND MICROBIOME 5824 04:27:33,920 --> 04:27:38,000 SEQUENCING DATA AND MAKE MORE 5825 04:27:38,000 --> 04:27:40,600 ACCURATE PREDICTIONS ABOUT THE 5826 04:27:40,600 --> 04:27:41,200 CAPABILITIES. 5827 04:27:41,200 --> 04:27:44,480 AND ENZYMES THEMSELVES CAN 5828 04:27:44,480 --> 04:27:46,240 PROVIDE KEY INSIGHTS IN 5829 04:27:46,240 --> 04:27:48,880 ENVIRONMENTAL FACTORS SUCH AS 5830 04:27:48,880 --> 04:27:49,520 PH. 5831 04:27:49,520 --> 04:27:51,920 FINALLY UNDERSTANDING ENZYMES 5832 04:27:51,920 --> 04:27:54,200 CAN HELP US MANIPULATE 5833 04:27:54,200 --> 04:27:56,360 MICROBIAL FUNCTION EITHER 5834 04:27:56,360 --> 04:27:57,880 THROUGH DEVELOPING SMALL 5835 04:27:57,880 --> 04:28:00,200 INHIBITORS OF ENZYME ACTIVITY 5836 04:28:00,200 --> 04:28:03,600 OR HELPING US ENGINEER A 5837 04:28:03,600 --> 04:28:06,080 PROBIOTIC STRAIN WITH SPECIFIC 5838 04:28:06,080 --> 04:28:06,680 FUNCTIONAL CAPABILITIES. 5839 04:28:06,680 --> 04:28:08,000 THESE SOMETIMES OF STRATEGIES 5840 04:28:08,000 --> 04:28:11,200 CAN BE USEFUL TOOLS TO APPLY 5841 04:28:11,200 --> 04:28:13,120 TO ACTUALLY STUDY THE 5842 04:28:13,120 --> 04:28:15,640 FUNDAMENTAL ROLES OF METABOLIC 5843 04:28:15,640 --> 04:28:16,320 ACTIVITY IN COMPLEX 5844 04:28:16,320 --> 04:28:18,080 COMMUNITIES BUT OF COURSE CAN 5845 04:28:18,080 --> 04:28:21,960 ALSO BE THE POTENTIAL FOR 5846 04:28:21,960 --> 04:28:23,120 THERAPEUTIC INTERVENTION. 5847 04:28:23,120 --> 04:28:25,560 SO MUCH OF MY LAB'S WORK IN 5848 04:28:25,560 --> 04:28:28,400 THIS SPACE HAS INVOLVED 5849 04:28:28,400 --> 04:28:32,600 LINKING KNOWN GUT METABOLIC 5850 04:28:32,600 --> 04:28:34,280 ACTIVITIES TO SPECIFIC MIKE 5851 04:28:34,280 --> 04:28:35,680 MICROBIAL GENES AND PROJECTS. 5852 04:28:35,680 --> 04:28:38,360 AND ONE OF MY FIRST PROJECTS 5853 04:28:38,360 --> 04:28:40,640 ILLUSTRATED HOW A CHEMICAL 5854 04:28:40,640 --> 04:28:43,120 UNDERSTANDING OF ENZYMES AND 5855 04:28:43,120 --> 04:28:45,520 METABOLISM CAN BE VERY 5856 04:28:45,520 --> 04:28:46,800 POWERFUL IN THIS COMPLEX 5857 04:28:46,800 --> 04:28:48,760 PROBLEM SO THIS ACTIVITY WAS 5858 04:28:48,760 --> 04:28:52,160 OF INTEREST TO US BECAUSE IT 5859 04:28:52,160 --> 04:28:54,120 GENERATES THIS MOLECULE, TMA 5860 04:28:54,120 --> 04:28:56,800 WHICH IS A PRECURSOR TO TMAO 5861 04:28:56,800 --> 04:28:59,800 WHICH HAS BEEN LINKED TO 5862 04:28:59,800 --> 04:29:01,400 CARDIO METABOLIC DISEASE. 5863 04:29:01,400 --> 04:29:04,040 WHEN WE BEGAN OUR STUDIES, THE 5864 04:29:04,040 --> 04:29:05,880 GENE THAT ENZYMES ARE 5865 04:29:05,880 --> 04:29:10,720 RESPONSIBLE FOR THE CHOL INE 5866 04:29:10,720 --> 04:29:12,880 METABOLISM WERE NOT KNOWN. 5867 04:29:12,880 --> 04:29:15,640 WE BEGAN OUR STUDY BY THINKING 5868 04:29:15,640 --> 04:29:18,120 ABOUT THE ENZYME IN THE 5869 04:29:18,120 --> 04:29:20,120 PATHWAY WHICH INVOLVES A VERY 5870 04:29:20,120 --> 04:29:21,000 COMPLEX CLEAVE LADIES AND 5871 04:29:21,000 --> 04:29:24,760 GENTLEMEN REACTION AND THIS 5872 04:29:24,760 --> 04:29:25,800 BIOCHEMICAL LOGIC REMINDED US 5873 04:29:25,800 --> 04:29:32,880 OF A BETTER CHARACTERIZED 5874 04:29:32,880 --> 04:29:33,360 PATHWAY. 5875 04:29:33,360 --> 04:29:35,320 THIS HELPS US ASSIGN THE TWO 5876 04:29:35,320 --> 04:29:40,480 ENZYMES IN THE PATHWAY THAT 5877 04:29:40,480 --> 04:29:44,640 WERE SHARED TO RESEARCH THE CH 5878 04:29:44,640 --> 04:29:45,960 OL INE GENE CLUSTER. 5879 04:29:45,960 --> 04:29:49,320 THIS ALSO LED US TO IDENTIFY 5880 04:29:49,320 --> 04:29:52,280 EVEN IN THAT CLUSTER, THE GENE 5881 04:29:52,280 --> 04:29:58,920 INCLUDING THE KEY ENZYME 5882 04:29:58,920 --> 04:30:01,120 RESPONSIBLE FOR METHYLENE 5883 04:30:01,120 --> 04:30:01,520 PRODUCTION. 5884 04:30:01,520 --> 04:30:04,080 THIS TURNS AUDIT TO BE A 5885 04:30:04,080 --> 04:30:07,200 ENZYME IN A MUCH LARGER FAMILY 5886 04:30:07,200 --> 04:30:10,400 AND WE COULD GO ON TO 5887 04:30:10,400 --> 04:30:12,520 CHARACTERIZE THE ENZYME AND 5888 04:30:12,520 --> 04:30:14,440 GAIN A DEEPER UNDERSTANDING OF 5889 04:30:14,440 --> 04:30:15,920 HOW IT WORKS AND HOW IT IS 5890 04:30:15,920 --> 04:30:18,560 DIFFERENT FROM THE LARGER 5891 04:30:18,560 --> 04:30:19,480 ENZYME FAMILY AND THAT 5892 04:30:19,480 --> 04:30:20,680 KNOWLEDGE IS CRITICAL FOR 5893 04:30:20,680 --> 04:30:22,080 ALLOWING US AND OTHERS TO 5894 04:30:22,080 --> 04:30:23,680 BETTER UNDERSTAND THIS 5895 04:30:23,680 --> 04:30:26,440 ACTIVITY IN GUT MICROBIOMES. 5896 04:30:26,440 --> 04:30:30,320 SO WE COULD MORE ACTIVELY 5897 04:30:30,320 --> 04:30:34,080 IDENTIFY THE CHOL INE BACTERIA 5898 04:30:34,080 --> 04:30:36,800 AND IDENTIFY THIS GENE IN 5899 04:30:36,800 --> 04:30:37,840 SEQUENCING DATA. 5900 04:30:37,840 --> 04:30:43,720 WE WERE ABLE TO GENETICALLY 5901 04:30:43,720 --> 04:30:44,520 MANIPULATE THE CHOLINE 5902 04:30:44,520 --> 04:30:46,560 BACTERIA AND USE THESE IN 5903 04:30:46,560 --> 04:30:49,680 ANIMAL MODELS TO STUDY THE 5904 04:30:49,680 --> 04:30:52,360 EFFECTS ON VARIOUS PHENOTYPES. 5905 04:30:52,360 --> 04:30:53,800 AND WE ALSO WERE ABLE TO 5906 04:30:53,800 --> 04:30:56,640 LEVERAGE THE UNDERSTANDING TO 5907 04:30:56,640 --> 04:30:59,240 START DEVELOPING SMALL 5908 04:30:59,240 --> 04:31:01,320 MOLECULE INHIBITORS WHICH MAY 5909 04:31:01,320 --> 04:31:03,080 BE CANDIDATES FOR 5910 04:31:03,080 --> 04:31:03,880 THERAPEUTICS. 5911 04:31:03,880 --> 04:31:05,040 SO THIS EARLY WORK I THINK 5912 04:31:05,040 --> 04:31:07,840 ILLUSTRATES THE VALUE OF BEING 5913 04:31:07,840 --> 04:31:10,440 ABLE TO LINK METABOLISM TO 5914 04:31:10,440 --> 04:31:12,920 GENES BUT IT ALSO TOOK US IN 5915 04:31:12,920 --> 04:31:14,880 AN OPPOSITE DIRECTION, 5916 04:31:14,880 --> 04:31:17,280 STARTING OFF BY CONTRACTIZING 5917 04:31:17,280 --> 04:31:19,840 A GENE TO A HOST PHENOTYPE AND 5918 04:31:19,840 --> 04:31:21,040 TRYING TO UNDERSTAND THEIR 5919 04:31:21,040 --> 04:31:21,400 FUNCTIONS. 5920 04:31:21,400 --> 04:31:23,400 A LOT OF OUR WORK IN THIS 5921 04:31:23,400 --> 04:31:30,800 SPACE HAS INVOLVED A GUT 5922 04:31:30,800 --> 04:31:34,440 BACTERIAL GINO TOXIN AND THESE 5923 04:31:34,440 --> 04:31:36,360 GENES WERE IDENTIFIED IN E. 5924 04:31:36,360 --> 04:31:37,440 COLI STRAINS. 5925 04:31:37,440 --> 04:31:39,400 THEY ALSO TURN OUT TO BE 5926 04:31:39,400 --> 04:31:42,280 PREVALENT IN A PROBIOTIC 5927 04:31:42,280 --> 04:31:42,760 STRAIN. 5928 04:31:42,760 --> 04:31:44,800 THESE GENES WERE INITIALLY 5929 04:31:44,800 --> 04:31:47,160 IDENTIFIED BECAUSE THEY CAUSED 5930 04:31:47,160 --> 04:31:49,920 THE BACTERIA CARRYING THEM TO 5931 04:31:49,920 --> 04:31:51,680 BE GINO TOPIC TOWARDS HUMAN 5932 04:31:51,680 --> 04:31:54,160 CELL LINES AND OVER THE YEARS, 5933 04:31:54,160 --> 04:31:55,520 BACTERIA CARRYING THESE GENES 5934 04:31:55,520 --> 04:31:57,360 HAVE BEEN STRONGLY CORRELATED 5935 04:31:57,360 --> 04:32:00,920 TO THE DEVELOPMENT OF 5936 04:32:00,920 --> 04:32:02,760 COLORECTAL CANCER. 5937 04:32:02,760 --> 04:32:05,040 THE ENZYMES INVOLVED IN MAKING 5938 04:32:05,040 --> 04:32:07,800 A NATURAL PRODUCT, THE ACTUAL 5939 04:32:07,800 --> 04:32:09,720 MOLECULE PRODUCED BY THE GENE 5940 04:32:09,720 --> 04:32:12,160 WAS HARD TO ISOLATE AND 5941 04:32:12,160 --> 04:32:14,800 CHARACTERIZE EVEN USING 5942 04:32:14,800 --> 04:32:15,360 TRADITIONAL METHODS. 5943 04:32:15,360 --> 04:32:20,800 SO I DECIDED TO TAKE A 5944 04:32:20,800 --> 04:32:21,840 CONVENTIONAL APPROACH TO LEARN 5945 04:32:21,840 --> 04:32:23,480 MORE ABOUT THIS MOLECULE. 5946 04:32:23,480 --> 04:32:28,560 USING THIS STRATEGY AS WELL AS 5947 04:32:28,560 --> 04:32:29,680 ISOLATING METABOL ITES FROM 5948 04:32:29,680 --> 04:32:32,280 THE STAIN, WE WERE ABLE TO 5949 04:32:32,280 --> 04:32:34,280 COMPOSE A FINAL STRUCTURE OF 5950 04:32:34,280 --> 04:32:35,280 THIS GINO TOXIN. 5951 04:32:35,280 --> 04:32:39,640 THIS IS A COMPLEX MOLECULE BUT 5952 04:32:39,640 --> 04:32:43,760 I WOULD LIKE TO EMPHASIZE ONE 5953 04:32:43,760 --> 04:32:45,560 IMPORTANT AND UNEXPECTANT 5954 04:32:45,560 --> 04:32:48,680 FEATURE, THESE TWO STRAINS 5955 04:32:48,680 --> 04:32:56,640 HAVE A POTENTIALLY REACTIVE 5956 04:32:56,640 --> 04:32:58,240 DISPLAY AND THIS UNDERSTANDING 5957 04:32:58,240 --> 04:33:00,120 OF THE CHEMICAL STRUCTURE AND 5958 04:33:00,120 --> 04:33:02,200 ACTIVITY HAS BEEN NOW REALLY 5959 04:33:02,200 --> 04:33:05,480 CRITICAL IN EFFORTS TO BETTER 5960 04:33:05,480 --> 04:33:06,440 UNDERSTAND CANCER DEVELOPMENT 5961 04:33:06,440 --> 04:33:10,680 AND THE RISK IT MAY POSE NOT 5962 04:33:10,680 --> 04:33:11,480 AGENT. 5963 04:33:11,480 --> 04:33:14,720 SO THESE ARE EXAMPLES OF 5964 04:33:14,720 --> 04:33:15,680 DETRIMENTAL ACTIVITIES THAT 5965 04:33:15,680 --> 04:33:18,280 ONE MAY NOT WANT IN A 5966 04:33:18,280 --> 04:33:21,080 POTENTIAL BIOTIC BUT WHAT 5967 04:33:21,080 --> 04:33:21,840 ABOUT BENEFICIAL ACTIVITIES? 5968 04:33:21,840 --> 04:33:24,040 WELL, WE HAVE BEEN RECENT LOO 5969 04:33:24,040 --> 04:33:31,000 HE INVESTIGATING ONE SUCH 5970 04:33:31,000 --> 04:33:35,400 ACTIVITY AND THIS IS 5971 04:33:35,400 --> 04:33:36,960 CHOLESTEROL METABOLISM. 5972 04:33:36,960 --> 04:33:41,240 CHOLESTEROL HAS BEEN LONG 5973 04:33:41,240 --> 04:33:43,360 HYPOTHESIZED IT IS SPECIFIC TO 5974 04:33:43,360 --> 04:33:47,120 THE HOST BUT AGAIN IT IS 5975 04:33:47,120 --> 04:33:49,720 DIFFICULT TO CORRELATE BECAUSE 5976 04:33:49,720 --> 04:33:57,320 IT IS POORLY UNDERSTOOD. 5977 04:33:57,320 --> 04:34:00,280 SO WE USE THIS INFORMATION TO 5978 04:34:00,280 --> 04:34:04,560 SEARCH FOR POTENTIAL KLESKO 5979 04:34:04,560 --> 04:34:07,200 TROT METABOLIZING ENZYMES IN 5980 04:34:07,200 --> 04:34:08,360 GUT MICROBIOMES AND WHAT IS 5981 04:34:08,360 --> 04:34:09,480 PARTICULARLY NEAT ABOUT THE 5982 04:34:09,480 --> 04:34:16,600 SEARCH WE DID WAS WE WERE ABLE 5983 04:34:16,600 --> 04:34:18,480 TO LEVERAGE DATA AND MATCHED 5984 04:34:18,480 --> 04:34:18,920 STOOL ENZYMES. 5985 04:34:18,920 --> 04:34:22,000 SO WE WERE ABLE TO LOOK FOR 5986 04:34:22,000 --> 04:34:24,600 CANDIDATE ENZYMES THAT 5987 04:34:24,600 --> 04:34:31,920 CORRELATED WITH THE PRESENCE 5988 04:34:31,920 --> 04:34:34,480 OF THIS AND THE TWO STEPS IN 5989 04:34:34,480 --> 04:34:35,720 THIS PATHWAY. 5990 04:34:35,720 --> 04:34:38,240 SO THE ENZYME IS ACTUALLY 5991 04:34:38,240 --> 04:34:40,800 FOUND IN UNCULTURED GUT 5992 04:34:40,800 --> 04:34:42,640 BACTERIA, HIGHLIGHTING THOSE 5993 04:34:42,640 --> 04:34:44,080 ORGANISMS HAVE AN IMPORTANCE 5994 04:34:44,080 --> 04:34:47,080 AND AN UNDER EXPLORED SOURCE 5995 04:34:47,080 --> 04:34:48,120 OF METABOLISM. 5996 04:34:48,120 --> 04:34:50,760 FINALLY WE ALSO OBSERVED A 5997 04:34:50,760 --> 04:34:54,040 CORRELATION BETWEEN HAVING 5998 04:34:54,040 --> 04:34:55,880 CHOLESTEROL METABOLIZING 5999 04:34:55,880 --> 04:34:58,520 BACTERIA IN ONE'S MICROBIOME 6000 04:34:58,520 --> 04:35:01,040 AND HAVING LOWER SERUN 6001 04:35:01,040 --> 04:35:03,560 CHOLESTEROL LEVELS SO THAT 6002 04:35:03,560 --> 04:35:04,840 CORRELATION IS SUBJECTIVE THIS 6003 04:35:04,840 --> 04:35:06,320 ACTIVITY MAY BE BENEFICIAL FOR 6004 04:35:06,320 --> 04:35:08,960 THE HOST AND PLAY A ROLE IN 6005 04:35:08,960 --> 04:35:09,600 LOWERING CHOLESTEROL. 6006 04:35:09,600 --> 04:35:11,200 SO WITH THE IDENTIFICATION OF 6007 04:35:11,200 --> 04:35:12,840 REGIMES INVOLVED IN THIS 6008 04:35:12,840 --> 04:35:14,800 PATHWAY, THIS HIGHLIGHTS THE 6009 04:35:14,800 --> 04:35:16,680 POSSIBILITY OF PERHAPS 6010 04:35:16,680 --> 04:35:17,680 ENGINEERING PROBIOTICS TO BE 6011 04:35:17,680 --> 04:35:24,880 ABLE TO PERFORM THIS 6012 04:35:24,880 --> 04:35:25,360 METABOLISM. 6013 04:35:25,360 --> 04:35:29,560 SO I HOPE THE POWER OF 6014 04:35:29,560 --> 04:35:33,480 CHEMICAL KNOWLEDGE CAN BE USED 6015 04:35:33,480 --> 04:35:34,800 TO GUIDE METABOLISM BUT I WANT 6016 04:35:34,800 --> 04:35:37,720 TO TALK ABOUT HOW TO 6017 04:35:37,720 --> 04:35:40,000 ACCELERATE THESE AS WELL. 6018 04:35:40,000 --> 04:35:42,280 LIKE THE REASON REVOLUTION IN 6019 04:35:42,280 --> 04:35:43,880 DNA SEQUENCING, I WOULD ARGUE 6020 04:35:43,880 --> 04:35:46,840 WE HAVEN'T YET HAD AFFECTED 6021 04:35:46,840 --> 04:35:56,920 OUR ABILITY TO PERFORM 6022 04:35:56,920 --> 04:36:00,600 FUNCTIONAL CONTRACT FUNCTION 6023 04:36:00,600 --> 04:36:03,080 AND SO WE HAVE THIS -- 6024 04:36:03,080 --> 04:36:04,840 >> YOU ARE JUST OVER THREE 6025 04:36:04,840 --> 04:36:05,160 MINUTES. 6026 04:36:05,160 --> 04:36:07,120 >> OKAY, I THINK IT IS 6027 04:36:07,120 --> 04:36:08,840 CRITICAL TO PRIORITIZE 6028 04:36:08,840 --> 04:36:10,320 FUNCTIONS AND GENES FOR 6029 04:36:10,320 --> 04:36:11,920 INTEREST FOR FURTHER STUDY AND 6030 04:36:11,920 --> 04:36:14,480 ONE WAY THIS CAN BE DONE IS 6031 04:36:14,480 --> 04:36:16,080 FOCUS ON UNCHARACTERIZED 6032 04:36:16,080 --> 04:36:17,720 MEMBERS OF LARGE PROTEIN SUPER 6033 04:36:17,720 --> 04:36:22,480 FAMILIES AND HERE IS A 6034 04:36:22,480 --> 04:36:23,400 SEQUENCE NETWORK BEING 6035 04:36:23,400 --> 04:36:27,360 SELECTED, SO WE CLUSTER 6036 04:36:27,360 --> 04:36:29,720 PROTEINS BASED ON THEIR 6037 04:36:29,720 --> 04:36:32,080 SHARED, POTENTIAL SHARED 6038 04:36:32,080 --> 04:36:34,080 FUNCTIONS AND YOU ACTUALLY SEE 6039 04:36:34,080 --> 04:36:36,240 WITHIN THIS NETWORK, THERE ARE 6040 04:36:36,240 --> 04:36:40,680 MANY CLUSTERS OF ENZYMES WHICH 6041 04:36:40,680 --> 04:36:42,280 ARE NOT PROPOSED INACTIVITY. 6042 04:36:42,280 --> 04:36:46,480 BECAUSE WE KNOW ABOUT HOW THIS 6043 04:36:46,480 --> 04:36:49,280 BROADER ENZYME FAMILY DOES 6044 04:36:49,280 --> 04:36:51,120 CATALYSIS, WE MIGHT HAVE A 6045 04:36:51,120 --> 04:36:53,320 BETTER STARTING PLACE TO 6046 04:36:53,320 --> 04:36:55,640 CHARACTERIZE NEW ENZYME FAMILY 6047 04:36:55,640 --> 04:36:56,080 MEMBERS. 6048 04:36:56,080 --> 04:36:57,600 ANOTHER STRATEGY MY LAB HAS 6049 04:36:57,600 --> 04:37:01,760 BEEN USING IS REALLY ASSESS 6050 04:37:01,760 --> 04:37:05,200 THE ABUNDANCE AND DISTRIBUTION 6051 04:37:05,200 --> 04:37:13,840 OF PROTEIN FAMILY MICROBIOMES. 6052 04:37:13,840 --> 04:37:16,080 SO HERE IS DATA AND USING THIS 6053 04:37:16,080 --> 04:37:18,680 WE CAN ACTUALLY IDENTIFY 6054 04:37:18,680 --> 04:37:21,080 ENZYME FUNCTION THAT ARE 6055 04:37:21,080 --> 04:37:21,880 PARTICULARLY PROMINENT IN 6056 04:37:21,880 --> 04:37:23,520 ENVIRONMENTS LIKE THE GUT 6057 04:37:23,520 --> 04:37:24,080 MICROBIOME. 6058 04:37:24,080 --> 04:37:26,160 SO FOR EXAMPLE, WE ACTUALLY 6059 04:37:26,160 --> 04:37:30,120 FOUND THE MOST ABUNDANT PLACE 6060 04:37:30,120 --> 04:37:31,920 FOR THE ENZYME WAS 6061 04:37:31,920 --> 04:37:34,040 UNCHARACTERIZED AND WE WERE 6062 04:37:34,040 --> 04:37:35,520 ABLE TO ACTUALLY CHARACTERIZE 6063 04:37:35,520 --> 04:37:38,160 THE FUNCTION OF THIS ENZYME 6064 04:37:38,160 --> 04:37:42,560 AND DISCOVER THAT IT IS 6065 04:37:42,560 --> 04:37:46,600 INVOLVED IN METABOLIZING THE 6066 04:37:46,600 --> 04:37:51,800 HOST AND DIETARY ABUNDANCE OF 6067 04:37:51,800 --> 04:37:52,480 OBJECTION SEEPROLINE. 6068 04:37:52,480 --> 04:37:54,760 SO WE ARE NOW USING THIS 6069 04:37:54,760 --> 04:37:56,160 APPROACH TO ANALYZE OTHER 6070 04:37:56,160 --> 04:37:58,000 TYPES OF DATA SETS AND WE 6071 04:37:58,000 --> 04:37:59,920 THINK BY APPLYING IT IN A 6072 04:37:59,920 --> 04:38:02,800 COMPARATIVE MANNER TO BE 6073 04:38:02,800 --> 04:38:04,080 PARTICULARLY HELPFUL IN 6074 04:38:04,080 --> 04:38:06,880 ALLOWING US TO FIND UNKNOWN 6075 04:38:06,880 --> 04:38:08,880 ENZYMES THAT MAY BE CONNECTED 6076 04:38:08,880 --> 04:38:12,600 TO THE DISEASE. 6077 04:38:12,600 --> 04:38:16,880 SO FINALLY WE ALSO THINK THERE 6078 04:38:16,880 --> 04:38:21,000 ARE OPPORTUNITIES TO 6079 04:38:21,000 --> 04:38:22,600 CHARACTERIZE MEMBERS OF LARGE 6080 04:38:22,600 --> 04:38:24,080 ENZYME FAMILIES IN PARALLEL 6081 04:38:24,080 --> 04:38:28,720 AND WE STARTED DOING THIS 6082 04:38:28,720 --> 04:38:29,440 THROUGH CATAPULTING ENZYMES 6083 04:38:29,440 --> 04:38:32,840 AND THE FAMILY OF 6084 04:38:32,840 --> 04:38:35,240 UNDERSTANDING THE NEURAL 6085 04:38:35,240 --> 04:38:36,120 TRANSMITTER DOPAMINE. 6086 04:38:36,120 --> 04:38:38,080 BECAUSE THIS TYPE OF ACTIVITY 6087 04:38:38,080 --> 04:38:41,800 IS INDUCED BY THE SUBSTRATE, 6088 04:38:41,800 --> 04:38:45,080 WE RECOGNIZED WE COULD USE RNA 6089 04:38:45,080 --> 04:38:53,080 SEQUENCING TO RAPIDLY CONNECT 6090 04:38:53,080 --> 04:38:54,320 OTHER DEHYDROXYLATION EVENTS 6091 04:38:54,320 --> 04:38:55,720 RESPONSIBLE FOR THAT 6092 04:38:55,720 --> 04:38:56,080 CHEMISTRY. 6093 04:38:56,080 --> 04:39:00,360 WE CAN UNDERSTAND THE 6094 04:39:00,360 --> 04:39:01,480 CORRELATION BETWEEN GENE 6095 04:39:01,480 --> 04:39:03,040 PARENT AND ARE METABOLISM AND 6096 04:39:03,040 --> 04:39:06,000 THAT WORKFLOW IS EX SAINTING 6097 04:39:06,000 --> 04:39:08,480 AND A WAY TO SCALE THE 6098 04:39:08,480 --> 04:39:10,560 FUNCTION TO MANY ENZYMES 6099 04:39:10,560 --> 04:39:11,040 SIMULTANEOUSLY. 6100 04:39:11,040 --> 04:39:14,480 SO I WOULD LIKE TO NOW END BY 6101 04:39:14,480 --> 04:39:17,440 HIGHLIGHTING I THINK THERE HAS 6102 04:39:17,440 --> 04:39:19,080 BEEN VERY ENCOURAGING PROGRESS 6103 04:39:19,080 --> 04:39:23,120 IN THE LAST TEN YEARS AND IN 6104 04:39:23,120 --> 04:39:24,280 CHARACTERIZING FUNCTION OF 6105 04:39:24,280 --> 04:39:30,640 MICROBIOMES BUT WE NEED TO DO 6106 04:39:30,640 --> 04:39:38,040 MORE, TRULY ANALYZING THE 6107 04:39:38,040 --> 04:39:43,200 FUNCTIONAL REVOLUTION NEEDS TO 6108 04:39:43,200 --> 04:39:45,040 BE DONE BUT WE KNOW THEY PLAY 6109 04:39:45,040 --> 04:39:47,240 A ROLE SO I WOULD LIKE TO END 6110 04:39:47,240 --> 04:39:48,760 BY THANKING MY COLLABORATORS, 6111 04:39:48,760 --> 04:39:50,280 SOURCES OF FUNDING AND YOU ALL 6112 04:39:50,280 --> 04:39:51,480 AGAIN FOR THE OPPORTUNITY TO 6113 04:39:51,480 --> 04:39:54,760 PARTICIPATE IN THE WORKSHOP. 6114 04:39:54,760 --> 04:40:05,480 >> VERY EXCITING, VERY NICE 6115 04:40:05,480 --> 04:40:05,760 TALK.. 6116 04:40:05,760 --> 04:40:06,280 VERY INTERESTING. 6117 04:40:06,280 --> 04:40:10,000 NOW WE WILL MOVE ON TO OUR 6118 04:40:10,000 --> 04:40:14,720 NEXT SPEAKER TALKING ABOUT 6119 04:40:14,720 --> 04:40:21,080 PROBIOTICS IN HUMAN 6120 04:40:21,080 --> 04:40:21,760 MICROBIOME. 6121 04:40:21,760 --> 04:40:24,320 >> OKAY, GREAT, THANKS SO MUCH 6122 04:40:24,320 --> 04:40:25,240 EVERYONE. 6123 04:40:25,240 --> 04:40:26,440 THIS IS REALLY A DELIGHT TO 6124 04:40:26,440 --> 04:40:27,480 WATCH AND PARTICIPATE IN THE 6125 04:40:27,480 --> 04:40:28,960 WORKSHOP THE PAST COUPLE OF 6126 04:40:28,960 --> 04:40:29,280 DAYS. 6127 04:40:29,280 --> 04:40:31,960 I WANT TO START BY EMPHASIZING 6128 04:40:31,960 --> 04:40:35,160 A POINT ABOUT THE WORKSHOP 6129 04:40:35,160 --> 04:40:36,720 THAT GARY ALLUDED TO THIS 6130 04:40:36,720 --> 04:40:37,680 MORNING, THAT I THINK 6131 04:40:37,680 --> 04:40:39,440 SOMETHING THAT REALLY MAKES IT 6132 04:40:39,440 --> 04:40:41,840 STRONG IS THE DIVERSITY OF 6133 04:40:41,840 --> 04:40:42,800 DEFINITIONS OF PROBIOTICS THAT 6134 04:40:42,800 --> 04:40:43,600 WE HAVE ESPECIALLY COUNTERED 6135 04:40:43,600 --> 04:40:45,560 IN THE PAST COUPLE OF DAYS 6136 04:40:45,560 --> 04:40:47,400 WHERE WE ALL KIND OF AGREE 6137 04:40:47,400 --> 04:40:51,760 THAT IT HAS SOMETHING TO DO 6138 04:40:51,760 --> 04:40:54,560 WITH INFLUENCING MICROBIAL 6139 04:40:54,560 --> 04:40:57,200 COMMUNITY BY ADDING LIVE 6140 04:40:57,200 --> 04:40:59,400 MICROBES, BUT WE HAVE HEARD 6141 04:40:59,400 --> 04:41:04,000 ABOUT PROBIOTICS FROM THE 6142 04:41:04,000 --> 04:41:10,840 PERSPECTIVE OF DIET DERIVED, 6143 04:41:10,840 --> 04:41:12,280 WE HAVE HEARD ABOUT PRODUCTS 6144 04:41:12,280 --> 04:41:14,760 THAT CAN BE ORALLY DELIVERED 6145 04:41:14,760 --> 04:41:18,240 OR OTHERWISE AND I RECOGNIZE 6146 04:41:18,240 --> 04:41:21,200 AFTER JULIA'S TALK USING SKIN 6147 04:41:21,200 --> 04:41:24,760 BIOTICS AS A EXAMINER. 6148 04:41:24,760 --> 04:41:27,080 WE HAVE HEARD ABOUT PROBIOTICS 6149 04:41:27,080 --> 04:41:31,040 THAT CAN BE LITERALLY THE 6150 04:41:31,040 --> 04:41:36,280 ADDITION OF WHOLE LIVE 6151 04:41:36,280 --> 04:41:38,360 MICROBAL CELLS OR THOSE THAT 6152 04:41:38,360 --> 04:41:41,000 ARE TRANSIENT OR HAVE A 6153 04:41:41,000 --> 04:41:42,120 BENEFICIAL EFFECT ON THE 6154 04:41:42,120 --> 04:41:43,080 COMMUNITY BASED ON THE 6155 04:41:43,080 --> 04:41:44,680 PRODUCTS THEY MAKE SO I THINK 6156 04:41:44,680 --> 04:41:48,440 IT IS IMPORTANT TO REMEMBER IN 6157 04:41:48,440 --> 04:41:54,280 CONTEXT OF THE SCIENCE WITH 6158 04:41:54,280 --> 04:41:56,040 REGARD TO WHICH PROJECT, PART 6159 04:41:56,040 --> 04:41:58,200 OF WHAT HAS MADE THE WORKSHOP 6160 04:41:58,200 --> 04:42:02,360 SO GREAT IS THE SCIENCE AROUND 6161 04:42:02,360 --> 04:42:04,360 THE PROBIOTICS CAN BE USED TO 6162 04:42:04,360 --> 04:42:06,080 HELP EACH OTHER, TO GET AN 6163 04:42:06,080 --> 04:42:07,480 UNDERSTANDING OF WHY THEY WORK 6164 04:42:07,480 --> 04:42:09,240 AND HOW TO MAKE THEM WORK 6165 04:42:09,240 --> 04:42:09,560 BETTER. 6166 04:42:09,560 --> 04:42:11,080 SO WITH THAT IN MIND, I WANT 6167 04:42:11,080 --> 04:42:13,080 TO SPEND SOME TIME TODAY ON 6168 04:42:13,080 --> 04:42:19,040 RESULTS WE HAVE FROM THE HUMAN 6169 04:42:19,040 --> 04:42:33,240 MICROBIOME BIOACTIVE RESOURCE 6170 04:42:33,240 --> 04:42:37,400 OR HMBR AND TO POTENTIALLY 6171 04:42:37,400 --> 04:42:40,640 IDENTIFY AND CHARACTERIZE AS A 6172 04:42:40,640 --> 04:42:43,840 FOLKS ON THE GUT MICROBIOME. 6173 04:42:43,840 --> 04:42:47,040 AND HERE WE HAVE WHOLE 6174 04:42:47,040 --> 04:42:50,280 MICROBIAL CELLS THAT CAN BE 6175 04:42:50,280 --> 04:42:53,760 BENEFICIAL OR PRO INFLAMMATORY 6176 04:42:53,760 --> 04:42:56,000 IN THE GUT. 6177 04:42:56,000 --> 04:42:59,760 ALSO BIOACTIVE IN THE SENSE OF 6178 04:42:59,760 --> 04:43:01,680 MICROBIAL PROTEINS PRODUCTS OR 6179 04:43:01,680 --> 04:43:03,280 SMALL MOLECULE MODIFICATIONS 6180 04:43:03,280 --> 04:43:04,880 THAT INDUCE SOME PHENOTYPE ON 6181 04:43:04,880 --> 04:43:07,000 THE HOST. 6182 04:43:07,000 --> 04:43:10,280 AGAIN IN HMBR, WE ARE FOCUSING 6183 04:43:10,280 --> 04:43:12,240 ON INFLAMMATORY BOWEL DISEASE 6184 04:43:12,240 --> 04:43:14,000 AND GUT INFLAMMATION BUT A LOT 6185 04:43:14,000 --> 04:43:15,600 OF THE RESOURCES THAT COME OUT 6186 04:43:15,600 --> 04:43:23,760 OF THIS ARE GENERALIZED TO 6187 04:43:23,760 --> 04:43:25,680 OTHER SETTINGS OF 6188 04:43:25,680 --> 04:43:26,120 MICROBIOTICS. 6189 04:43:26,120 --> 04:43:28,120 SO THERE IS A WHOLE LOT OF 6190 04:43:28,120 --> 04:43:30,080 INFORMATION I WON'T HAVE TIME 6191 04:43:30,080 --> 04:43:34,680 TO TALK ABOUT TODAY BUT HMBR 6192 04:43:34,680 --> 04:43:39,440 DOES EVERYTHING FROM SCALING, 6193 04:43:39,440 --> 04:43:40,920 FINDING, MICROBIOME 6194 04:43:40,920 --> 04:43:43,200 COMPUTATIONAL METHODS, DATA 6195 04:43:43,200 --> 04:43:44,840 RESOURCES SPECIFICALLY FOR 6196 04:43:44,840 --> 04:43:46,680 IBP, METHODS I WILL FOCUS ON 6197 04:43:46,680 --> 04:43:48,480 TODAY FOR ACTUALLY WHAT EMILY 6198 04:43:48,480 --> 04:43:50,480 WAS ALLUDING TO AT THE END OF 6199 04:43:50,480 --> 04:43:52,840 HER TALK, PRIORITIZATION OF 6200 04:43:52,840 --> 04:43:56,800 THE MOST INTERESTING POTENTIAL 6201 04:43:56,800 --> 04:44:01,040 BIOACTIVE DEVELOPMENTS, BE 6202 04:44:01,040 --> 04:44:02,280 THEY WHOLE SPECIES OR OTHER 6203 04:44:02,280 --> 04:44:03,880 PRODUCTS AND I WILL TALK A 6204 04:44:03,880 --> 04:44:05,280 LITTLE ABOUT THIS TODAY. 6205 04:44:05,280 --> 04:44:12,720 IT WILL BLEED A LITTLE INTO IN 6206 04:44:12,720 --> 04:44:15,320 VITRO AND SCREENING METHODS 6207 04:44:15,320 --> 04:44:16,880 AND KUDOS TO THE TEAM FOR 6208 04:44:16,880 --> 04:44:19,240 PUTTING ALL OF THIS ONLINE 6209 04:44:19,240 --> 04:44:20,640 THROUGH THE PORTAL THAT YOU 6210 04:44:20,640 --> 04:44:22,280 ARE WELCOME TO TAKE A LOOK AT 6211 04:44:22,280 --> 04:44:23,080 FOR MORE INFORMATION. 6212 04:44:23,080 --> 04:44:24,880 SO MANY OF THE EXAMPLES I WILL 6213 04:44:24,880 --> 04:44:26,960 FOCUS ON TODAY COME FROM THE 6214 04:44:26,960 --> 04:44:29,240 DATA RESOURCES THAT HMBR 6215 04:44:29,240 --> 04:44:32,680 PROVIDES WHICH IS A UNIFORMLY 6216 04:44:32,680 --> 04:44:42,440 PROCESSED SET OF JUST OVER 6217 04:44:42,440 --> 04:44:45,200 7500IBD MICROBIOME PROFILES. 6218 04:44:45,200 --> 04:44:47,000 AND THESE THEN HARMONIZE WITH 6219 04:44:47,000 --> 04:44:49,760 EACH OTHER FOR ABOUT 15 TOTAL 6220 04:44:49,760 --> 04:44:52,600 STUDIES USING A PACKAGE THAT 6221 04:44:52,600 --> 04:44:59,120 IS NOW GENERALLY AVAILABLE 6222 04:44:59,120 --> 04:45:01,840 WITH METADATA SO THE SCORES 6223 04:45:01,840 --> 04:45:02,800 AND MEDICATION USAGE MEAN 6224 04:45:02,800 --> 04:45:04,280 ROUGHLY THE SAME THING FROM 6225 04:45:04,280 --> 04:45:05,600 DATA SET TO DATA SET. 6226 04:45:05,600 --> 04:45:08,600 SO IN THE DATA HERE, WE 6227 04:45:08,600 --> 04:45:11,440 UNIFORMLY PROCESS THESE DATA 6228 04:45:11,440 --> 04:45:11,720 SETS. 6229 04:45:11,720 --> 04:45:20,640 MUFFIN PROVIDES A BATCHED 6230 04:45:20,640 --> 04:45:24,720 CORRECT ADJUSTMENT AND WE CAN 6231 04:45:24,720 --> 04:45:26,880 IDENTIFY WHICH MICROBES OR 6232 04:45:26,880 --> 04:45:31,960 PRODUCTS ARE ASSOCIATED WITH 6233 04:45:31,960 --> 04:45:33,560 THE GINO TYPE TOPICS AND 6234 04:45:33,560 --> 04:45:38,640 WHETHER THERE ARE MULTIPLE 6235 04:45:38,640 --> 04:45:40,560 MICROBIAL SUBTYPES FOR BOWEL 6236 04:45:40,560 --> 04:45:41,840 DISEASE FOR EXAMPLE, OR 6237 04:45:41,840 --> 04:45:44,560 WHETHER THERE ARE CONSISTENT 6238 04:45:44,560 --> 04:45:45,720 PATTERNS FOR MICROBIOME 6239 04:45:45,720 --> 04:45:46,800 PROFILES WITHIN THE 6240 04:45:46,800 --> 04:45:47,200 POPULATION. 6241 04:45:47,200 --> 04:45:55,520 SO THIS RESULTS IN JUST OVER 6242 04:45:55,520 --> 04:45:57,840 516 SAMPLES FROM SEVERAL DATA 6243 04:45:57,840 --> 04:46:00,680 SETS WHICH ARE LONGITUDINAL 6244 04:46:00,680 --> 04:46:04,920 AND YOU CAN SEE FROM THE QUICK 6245 04:46:04,920 --> 04:46:07,760 BREAK DOWN HERE, A FOURTH WITH 6246 04:46:07,760 --> 04:46:09,240 CROHN'S DISEASE, A QUARTER 6247 04:46:09,240 --> 04:46:13,240 FROM A VARIETY OF DIFFERENT 6248 04:46:13,240 --> 04:46:14,280 POPULATIONS, BACKGROUNDS, 6249 04:46:14,280 --> 04:46:14,920 SAMPLING METHODOLOGIES, ET 6250 04:46:14,920 --> 04:46:16,120 CETERA, ET CETERA. 6251 04:46:16,120 --> 04:46:17,760 A QUICK ASIDE ABOUT ANOTHER 6252 04:46:17,760 --> 04:46:18,720 PLATFORM THAT HAS REALLY 6253 04:46:18,720 --> 04:46:20,080 HELPED IN THE UNIFORM 6254 04:46:20,080 --> 04:46:21,480 PROCESSING OF THESE DATA IS 6255 04:46:21,480 --> 04:46:25,360 THAT WE JUST RECENTLY UPDATED 6256 04:46:25,360 --> 04:46:31,040 THE BIOBAKERY WHICH IS OUR 6257 04:46:31,040 --> 04:46:35,000 SUITE OF MOSELEY SHOTGUN 6258 04:46:35,000 --> 04:46:36,160 COLLABORATIVE METHODS AND NICK 6259 04:46:36,160 --> 04:46:41,680 IS WORKING HARD ON A FOURTH 6260 04:46:41,680 --> 04:46:43,520 VERSION THAT INCORPORATES 6261 04:46:43,520 --> 04:46:45,680 INFORMATION FROM SHOTGUN 6262 04:46:45,680 --> 04:46:49,320 METADATA ASSEMBLIES SO KEEP AN 6263 04:46:49,320 --> 04:46:51,040 EYE OUT FOR ANOTHER VERSION IN 6264 04:46:51,040 --> 04:46:52,800 THE NEXT FEW WEEKS THAT 6265 04:46:52,800 --> 04:46:56,240 PROVIDE A UNIFORM WAY TO 6266 04:46:56,240 --> 04:46:57,240 PROCESS SHOTGUN METAGENOMES 6267 04:46:57,240 --> 04:47:00,880 WHILE TAKING INTO ACCOUNT FROM 6268 04:47:00,880 --> 04:47:01,680 RECENT METAGENOMIC ASSEMBLIES 6269 04:47:01,680 --> 04:47:03,440 AND THIS LETS US DO THINGS 6270 04:47:03,440 --> 04:47:05,840 LIKE PROFILE MORE DIFFICULT, 6271 04:47:05,840 --> 04:47:06,760 MORE CHALLENGING ENVIRONMENTS 6272 04:47:06,760 --> 04:47:08,280 A LITTLE BETTER AND I ALSO 6273 04:47:08,280 --> 04:47:13,920 WANTED TO CALL OUTLY VIE'S 6274 04:47:13,920 --> 04:47:17,160 GROUP ON THE METADATA PACKAGE 6275 04:47:17,160 --> 04:47:19,080 THAT REPRESENTS TENS OF 6276 04:47:19,080 --> 04:47:21,520 THOUSANDS METAGENOMES IN A 6277 04:47:21,520 --> 04:47:25,960 SIMILARLY PROCESSED MANNER FOR 6278 04:47:25,960 --> 04:47:29,240 IBE AND OTHERWISE. 6279 04:47:29,240 --> 04:47:33,120 SO THEN ONE THING THE HMBR 6280 04:47:33,120 --> 04:47:36,520 MAKES VERY EASY IS TO QUICKLY 6281 04:47:36,520 --> 04:47:39,280 COMPARE FOR A SIMPLE MICROBIAL 6282 04:47:39,280 --> 04:47:41,680 PROFILE ASSOCIATED WITH IBD 6283 04:47:41,680 --> 04:47:42,840 INFLAMMATION ACROSS THE 6284 04:47:42,840 --> 04:47:45,440 DIFFERENT STUDIES AND FIND 6285 04:47:45,440 --> 04:47:46,480 CONSISTENCY THAT MATCHED VERY 6286 04:47:46,480 --> 04:47:48,120 CLOSELY WHAT HAS BEEN 6287 04:47:48,120 --> 04:47:48,920 PUBLISHED BEFORE. 6288 04:47:48,920 --> 04:47:51,360 SO GARY MENTIONED THIS EARLIER 6289 04:47:51,360 --> 04:47:54,520 THIS MORNING WHERE THERE IS 6290 04:47:54,520 --> 04:47:57,920 THIS WELL APPROACHED AND 6291 04:47:57,920 --> 04:48:00,160 ESTABLISHED PRO INFLAMMATORY 6292 04:48:00,160 --> 04:48:05,680 MICROBES IN CD/UC, DEPLETED IN 6293 04:48:05,680 --> 04:48:07,680 ERRANT ORGANIZATIONS AND ARE 6294 04:48:07,680 --> 04:48:10,640 MANY TYPICAL MICROBES THAT 6295 04:48:10,640 --> 04:48:13,040 LIKE IN COLORECTAL CANCER TEND 6296 04:48:13,040 --> 04:48:15,120 TO BE ENRICHED IN IBD. 6297 04:48:15,120 --> 04:48:19,000 MANY OF THESE HAVE BEEN SEEN 6298 04:48:19,000 --> 04:48:21,280 IN STUDIES WITH DATA SETS AND 6299 04:48:21,280 --> 04:48:24,800 DIFFERENTIATE WHICH ONES ARE 6300 04:48:24,800 --> 04:48:27,400 SPECIFICALLY ASSOCIATED WITH 6301 04:48:27,400 --> 04:48:30,040 INFLAMMATION VERSUS USED IN 6302 04:48:30,040 --> 04:48:32,520 MEDICATIONS, STEROIDS AND 6303 04:48:32,520 --> 04:48:32,920 SUCH. 6304 04:48:32,920 --> 04:48:35,080 WHAT GETS MORE INTERESTING IS 6305 04:48:35,080 --> 04:48:37,600 DIGGING INTO THE HOW AND WHY 6306 04:48:37,600 --> 04:48:39,320 OF THIS AND WE CAN EXPLAIN 6307 04:48:39,320 --> 04:48:42,400 SOME OF THESE IN TERMS OF THE 6308 04:48:42,400 --> 04:48:58,800 FUNCTIONAL DATA THAT COMES 6309 04:48:58,800 --> 04:48:59,280 ALONG WITH THEM. 6310 04:48:59,280 --> 04:48:59,920 SO THE SETS THAT ARE UNIQUE 6311 04:48:59,920 --> 04:49:00,640 SNEAK TO FUNCTIONALLY ENRICHED 6312 04:49:00,640 --> 04:49:01,280 IN THE SHOTGUN METAGENOMES, 6313 04:49:01,280 --> 04:49:02,000 THINGS LIKE IRON SEQUESTRATION 6314 04:49:02,000 --> 04:49:02,720 WHICH TENDS TO BE A UNIQUE 6315 04:49:02,720 --> 04:49:04,920 TIPPING POINT OR RESOURCE 6316 04:49:04,920 --> 04:49:07,120 DURING INFLAMMATION AND THEN 6317 04:49:07,120 --> 04:49:14,680 LOST IN INFLAMMATION MORE 6318 04:49:14,680 --> 04:49:17,080 BROADLY ASSOCIATED 6319 04:49:17,080 --> 04:49:19,080 POLYSACCHARIDE MEMORIMENTATION 6320 04:49:19,080 --> 04:49:20,560 THAT ARE LOST. 6321 04:49:20,560 --> 04:49:21,880 AND REALLY THERE WAS JUST ONE 6322 04:49:21,880 --> 04:49:24,400 PATTERN OF THIS ANALYSIS OR 6323 04:49:24,400 --> 04:49:25,920 ONE SET OF MICROBIAL CHANGES 6324 04:49:25,920 --> 04:49:28,080 THAT GOT MORE AND MORE EXTREME 6325 04:49:28,080 --> 04:49:30,080 IN CONJUNCTION WITH GREATER 6326 04:49:30,080 --> 04:49:30,480 INFLAMMATION. 6327 04:49:30,480 --> 04:49:32,840 EVEN WHEN WE LOOKED FOR 6328 04:49:32,840 --> 04:49:35,480 MULTIPLE DIFFERENT TYPES OF 6329 04:49:35,480 --> 04:49:36,600 MICROBIAL CONFIGURATIONS OR 6330 04:49:36,600 --> 04:49:38,280 MULTIPLE DIFFERENT WAYS IN 6331 04:49:38,280 --> 04:49:40,080 WHICH INFORMATION MIGHT 6332 04:49:40,080 --> 04:49:40,800 DISRUPT THE MICROBIOME. 6333 04:49:40,800 --> 04:49:42,120 THERE WAS REALLY JUST ONE 6334 04:49:42,120 --> 04:49:44,400 DIRECTION OF CHANGE HERE WE 6335 04:49:44,400 --> 04:49:47,840 COULD SEE VERY CLEARLY WITH 6336 04:49:47,840 --> 04:49:49,680 THE INFLAMMATION INGREDIENT IN 6337 04:49:49,680 --> 04:49:52,080 A CROHN'S DISEASE POPULATION. 6338 04:49:52,080 --> 04:49:56,720 THIS SAME GRADIENT EXISTED IN 6339 04:49:56,720 --> 04:49:58,000 OUR NONIBD ROLES WHICH ALLOWS 6340 04:49:58,000 --> 04:50:01,760 TO US PICK OUT THE NONIBD BUT 6341 04:50:01,760 --> 04:50:02,800 NOT TRULY HEALTHY INDIVIDUALS 6342 04:50:02,800 --> 04:50:06,320 AND THEN THE ONE EXTREME THAT 6343 04:50:06,320 --> 04:50:08,280 IS GENERALLY PREVALENT IN OUR 6344 04:50:08,280 --> 04:50:09,680 HEALTHY CONTROLS. 6345 04:50:09,680 --> 04:50:12,080 SO WE EXPECTED THERE WOULD BE 6346 04:50:12,080 --> 04:50:13,920 THESE MORE EXTREME TYPES OF 6347 04:50:13,920 --> 04:50:16,880 IBD BUT WHAT WE FOUND IS THERE 6348 04:50:16,880 --> 04:50:19,520 IS A GRADIENT OF CHANGE THAT 6349 04:50:19,520 --> 04:50:21,000 OCCURS ACROSS THE POPULATION 6350 04:50:21,000 --> 04:50:21,840 OF SUBJECTS. 6351 04:50:21,840 --> 04:50:24,880 AS ANOTHER QUICK ASSIGNMENT ON 6352 04:50:24,880 --> 04:50:25,760 THE METHODOLOGY, ONE OF THE 6353 04:50:25,760 --> 04:50:27,200 THINGS THAT WE HAVE BEEN 6354 04:50:27,200 --> 04:50:31,400 INTERESTING IN BREAKING OUT A 6355 04:50:31,400 --> 04:50:34,240 LITTLE MORE IN MICROBES 6356 04:50:34,240 --> 04:50:36,520 ASSOCIATED WITH ACTIVITIES 6357 04:50:36,520 --> 04:50:39,600 HERE AND WITH COLORECTAL 6358 04:50:39,600 --> 04:50:42,280 CANCER, WHAT THE STRAINS OF 6359 04:50:42,280 --> 04:50:46,080 THESE ARE OR WHAT CASSETTES OR 6360 04:50:46,080 --> 04:50:47,880 ENRICHMENT MIGHT BE IN A 6361 04:50:47,880 --> 04:50:50,440 SPECIFIC SPECIES IN 6362 04:50:50,440 --> 04:50:52,960 ASSOCIATION WITH IBD OR OTHER 6363 04:50:52,960 --> 04:50:54,200 PHENOTYPES. 6364 04:50:54,200 --> 04:50:57,160 SO A VERY EARLY PACKAGE WE'RE 6365 04:50:57,160 --> 04:51:02,280 WORKING ON THAT ESSENTIALLY 6366 04:51:02,280 --> 04:51:04,240 LOOKS AT FOUR STREAMS. 6367 04:51:04,240 --> 04:51:06,080 AS WAS MENTIONED EARLIER, IT 6368 04:51:06,080 --> 04:51:09,920 WILL BE VERY DIFFICULT WITH 6369 04:51:09,920 --> 04:51:12,880 SHOTGUN GENOMES BUT IT SAYS 6370 04:51:12,880 --> 04:51:14,520 OKAY HERE ARE THE SAMPLES 6371 04:51:14,520 --> 04:51:17,200 WHERE I DON'T JUST DETECT THE 6372 04:51:17,200 --> 04:51:19,560 ORGANISM BUT I CAN TELL WHICH 6373 04:51:19,560 --> 04:51:22,720 STRAIN IT IS IN THE SAMPLE, 6374 04:51:22,720 --> 04:51:23,880 WHETHER THEY ARE STRAINS OF 6375 04:51:23,880 --> 04:51:25,520 THE SAME SPECIES IN AND 6376 04:51:25,520 --> 04:51:29,160 OUTSIDE OF A PHENOTYPE SO THIS 6377 04:51:29,160 --> 04:51:31,560 IS A COLORECTAL CANCER EXAMPLE 6378 04:51:31,560 --> 04:51:35,200 RATHER THAN A IBD EXAMPLE. 6379 04:51:35,200 --> 04:51:38,120 OR ENRICHMENT SO MAYBE THERE 6380 04:51:38,120 --> 04:51:39,520 IS NOT SOMETHING THAT 6381 04:51:39,520 --> 04:51:41,320 IDENTIFIES A PARTICULAR STRAIN 6382 04:51:41,320 --> 04:51:45,560 BUT SUBSETS OF THOSE STRAINS 6383 04:51:45,560 --> 04:51:47,400 ENRICHED IN A PHENOTYPE. 6384 04:51:47,400 --> 04:51:49,240 SO THIS IS A VERY EARLY STAGE 6385 04:51:49,240 --> 04:51:51,480 BUT FEEL FREE TO LOOK AT THIS 6386 04:51:51,480 --> 04:51:53,440 AS A UPCOMING METHOD OF 6387 04:51:53,440 --> 04:51:54,160 DEVELOPMENT. 6388 04:51:54,160 --> 04:51:55,280 FINISHING UP THOUGH, JUMPING 6389 04:51:55,280 --> 04:51:58,320 BACK TO OUR IBD SAMPLES AGAIN, 6390 04:51:58,320 --> 04:51:59,400 UP WITH OF THE THINGS WE 6391 04:51:59,400 --> 04:52:01,400 WANTED TO USE THE DATA 6392 04:52:01,400 --> 04:52:03,400 RESOURCES OF THE HB MR FOR IS 6393 04:52:03,400 --> 04:52:05,840 HAVE A BETTER UNDERSTANDING 6394 04:52:05,840 --> 04:52:08,400 WHY PRO AND ANTIINFLAMMATORY 6395 04:52:08,400 --> 04:52:09,960 MICROBES MIGHT DO THE THINGS 6396 04:52:09,960 --> 04:52:12,280 THEY DO, ESPECIALLY IN THE 6397 04:52:12,280 --> 04:52:14,680 CONTEXT OF POTENTIAL 6398 04:52:14,680 --> 04:52:15,080 PROBIOTICS. 6399 04:52:15,080 --> 04:52:16,600 SO ERIC AND OTHERS IN THE 6400 04:52:16,600 --> 04:52:18,320 GROUP PUT TOGETHER A SYSTEM 6401 04:52:18,320 --> 04:52:20,680 FOR TAKING THIS GIANT MASS, AS 6402 04:52:20,680 --> 04:52:22,680 EMILY MENTIONED IN THE 6403 04:52:22,680 --> 04:52:25,520 PREVIOUS SLIDE, DISEASE 6404 04:52:25,520 --> 04:52:26,680 ASSOCIATED BUT UNCHARACTERIZED 6405 04:52:26,680 --> 04:52:28,200 MICROBIAL PRODUCTS AND TRYING 6406 04:52:28,200 --> 04:52:29,800 TO PRIORITIZE AND AN NOTATE 6407 04:52:29,800 --> 04:52:33,000 THOSE BASED ON INTEGRATION OF 6408 04:52:33,000 --> 04:52:35,720 DIFFERENT INFORMATION ACROSS 6409 04:52:35,720 --> 04:52:37,000 MICROBIOME POPULATIONS. 6410 04:52:37,000 --> 04:52:38,480 SO THE SYSTEM OF METADATA 6411 04:52:38,480 --> 04:52:43,120 STARTS WITH A COLLECTION OF 6412 04:52:43,120 --> 04:52:44,080 METAGENOMES, IDENTIFIES THE 6413 04:52:44,080 --> 04:52:46,240 GENE FAMILIES AND TAXOMIC 6414 04:52:46,240 --> 04:52:47,840 ASSOCIATION AND THEN 6415 04:52:47,840 --> 04:52:51,440 INTEGRATES A SET OF 6416 04:52:51,440 --> 04:52:55,080 INFORMATION FROM METAGENOMIC 6417 04:52:55,080 --> 04:52:56,960 SEQUENCES, THEIR HOMOLOGY TO 6418 04:52:56,960 --> 04:53:01,480 KNOWN ISOLATES AND THEN 6419 04:53:01,480 --> 04:53:05,320 NONHOMOLOGY INFORMATION FROM 6420 04:53:05,320 --> 04:53:08,680 THINGS LIKE THEIR CARRIAGE OR 6421 04:53:08,680 --> 04:53:10,440 ECOLOGICAL DISTRIBUTION TO 6422 04:53:10,440 --> 04:53:11,080 THEN PRIORITIZE -- 6423 04:53:11,080 --> 04:53:12,680 >> YOU HAVE THREE MINUTES. 6424 04:53:12,680 --> 04:53:14,840 >> TIME WARNING, GREAT, THANK 6425 04:53:14,840 --> 04:53:15,200 YOU. 6426 04:53:15,200 --> 04:53:18,360 TO THEN PRIORITIZE BASED ON 6427 04:53:18,360 --> 04:53:19,760 ECOLOGICAL PHENOTYPIC AND 6428 04:53:19,760 --> 04:53:20,520 SEQUENCE BASED INFORMATION 6429 04:53:20,520 --> 04:53:24,040 WHICH OUT OF THE MANY MILLIONS 6430 04:53:24,040 --> 04:53:24,680 OF UNCHARACTERIZED PROTEINS 6431 04:53:24,680 --> 04:53:28,040 MIGHT BE THE ONES THAT BEST 6432 04:53:28,040 --> 04:53:30,720 EXPLAIN HEALTH OR DISEASE 6433 04:53:30,720 --> 04:53:32,040 ASSOCIATED MICROBES AND THESE 6434 04:53:32,040 --> 04:53:35,360 WE WILL REFER TO AGAIN AS KIND 6435 04:53:35,360 --> 04:53:36,520 OF SHORTHANDED BIOGENE 6436 04:53:36,520 --> 04:53:37,040 PRODUCTS. 6437 04:53:37,040 --> 04:53:39,280 SO USING A SUBSET OF THE DATA 6438 04:53:39,280 --> 04:53:45,720 FOCUSING ON THE HUMAN 6439 04:53:45,720 --> 04:53:48,280 MICROBIOME PROJECT IBG SHOTGUN 6440 04:53:48,280 --> 04:53:52,560 GENOMES, THE DATA WAS ABLE TO 6441 04:53:52,560 --> 04:53:57,120 CLUSTER GENES RESULTING IN A 6442 04:53:57,120 --> 04:53:59,760 BIT UNDER 45 MILLION 6443 04:53:59,760 --> 04:54:01,400 INDIVIDUAL MICROBIAL READING 6444 04:54:01,400 --> 04:54:02,760 STRAINS, CLUSTERING DOWN TO 6445 04:54:02,760 --> 04:54:07,600 JUST OVER TWO MILLION UNIQUE 6446 04:54:07,600 --> 04:54:08,960 NUCLEOTIDES AND A MILLION AND 6447 04:54:08,960 --> 04:54:11,000 A HALF PROTEIN FAMILIES THAT 6448 04:54:11,000 --> 04:54:13,800 ARE MORE GENEROUS WITH AMINO 6449 04:54:13,800 --> 04:54:14,920 ACID IDENTITY. 6450 04:54:14,920 --> 04:54:16,280 SO THESE CORRESPOND ROUGHLY 6451 04:54:16,280 --> 04:54:18,120 WHERE YOU WOULD EXPECT A 6452 04:54:18,120 --> 04:54:20,880 SEQUENCE TO HAVE A UNIQUE 6453 04:54:20,880 --> 04:54:22,280 BIOCHEMICAL FUNCTION AND AS 6454 04:54:22,280 --> 04:54:23,480 EMILY ALSO MENTIONED IN THE 6455 04:54:23,480 --> 04:54:26,520 TALK, ONLY A THIRD OR A 6456 04:54:26,520 --> 04:54:30,680 QUARTER OF THEM HAVE 6457 04:54:30,680 --> 04:54:32,080 REASONABLE CHARACTERIZATION. 6458 04:54:32,080 --> 04:54:35,600 EITHER THEY ARE TOO DIVERTED 6459 04:54:35,600 --> 04:54:40,800 TO BE CONFIDENT ABOUT 6460 04:54:40,800 --> 04:54:43,000 TRANSFERRING BIOHOMOLOGY IN 6461 04:54:43,000 --> 04:54:44,480 THE REMAINING OR 6462 04:54:44,480 --> 04:54:44,960 UNCHARACTERIZED. 6463 04:54:44,960 --> 04:54:47,320 SO I WAS ABLE TO CATALOG THESE 6464 04:54:47,320 --> 04:54:49,040 SEVERAL MILLION BREATHE TEEN 6465 04:54:49,040 --> 04:54:52,480 FAMILIES FROM THE MMV2 AND 6466 04:54:52,480 --> 04:54:55,080 PRIORITIZE THEM AND FOR THE 6467 04:54:55,080 --> 04:54:56,280 SAKE OF TIME, I WILL SKIP OVER 6468 04:54:56,280 --> 04:54:58,240 THE PROCESS OF THAT 6469 04:54:58,240 --> 04:54:58,640 METHODOLOGY. 6470 04:54:58,640 --> 04:55:00,600 A COUPLE OF EXAMPLES THAT END 6471 04:55:00,600 --> 04:55:02,440 UP GETTING SNIPPED OFF THE TOP 6472 04:55:02,440 --> 04:55:06,200 ARE A COUPLE THOUSAND PROTEINS 6473 04:55:06,200 --> 04:55:08,480 THAT ARE PRIORITIZED MOST IBD 6474 04:55:08,480 --> 04:55:11,480 RELEVANT OVER THE POTENTIAL 6475 04:55:11,480 --> 04:55:12,280 MILLION PROTEINS, A FEW WE 6476 04:55:12,280 --> 04:55:16,040 HAVE BEEN ABLE TO VALIDATE. 6477 04:55:16,040 --> 04:55:23,040 ONE IS A COLLECTION OF PILL 6478 04:55:23,040 --> 04:55:24,080 VARIANTS ENRICHED WHERE 6479 04:55:24,080 --> 04:55:26,320 SURPRISINGLY EVEN THOUGH WE 6480 04:55:26,320 --> 04:55:30,960 DIDN'T LOOK AT TRANSCRIPT 6481 04:55:30,960 --> 04:55:32,440 GENOMIC INFORMATION, ALMOST 6482 04:55:32,440 --> 04:55:37,680 ALL THE ENTIRE SET OF THE 6483 04:55:37,680 --> 04:55:41,280 VARIANTS WERE OVEREXPRESSED IN 6484 04:55:41,280 --> 04:55:42,480 ACCOMPANYING METATRANSCRIPT 6485 04:55:42,480 --> 04:55:43,480 INFORMATION DURING 6486 04:55:43,480 --> 04:55:45,680 INFLAMMATION AND THESE TURNED 6487 04:55:45,680 --> 04:55:49,720 OUT TO BE IMMUNOGENIC WHEN 6488 04:55:49,720 --> 04:55:51,000 TESTED IN CELL LINES 6489 04:55:51,000 --> 04:55:52,400 AFTERWARDS AND AGAIN FOR THE 6490 04:55:52,400 --> 04:55:54,040 SAKE OF TIME, I WON'T GET INTO 6491 04:55:54,040 --> 04:55:59,280 IT BUT THE SAME WAS TRUE FOR A 6492 04:55:59,280 --> 04:56:12,000 HIGHLY PRIORITIZED FAMILY OF 6493 04:56:12,000 --> 04:56:16,120 OTHER SAMPLES SPECIFICALLY 6494 04:56:16,120 --> 04:56:17,480 WITH MUCOUS. 6495 04:56:17,480 --> 04:57:00,360 AND WAS UNABLE TO FORM PROPER 6496 04:57:00,360 --> 04:57:00,720 BIOFILMS. 6497 04:57:00,720 --> 04:57:02,960 AND SO I WILL THANK THOSE IN 6498 04:57:02,960 --> 04:57:08,800 MY LAB AND THE FUNDERS AND 6499 04:57:08,800 --> 04:57:13,040 THANK YOU FOR THE OPPORTUNITY. 6500 04:57:13,040 --> 04:57:22,240 >> OKAY, NEXT WE HAVE THE NEXT 6501 04:57:22,240 --> 04:57:32,360 SPEAKER TALKING ABOUT 6502 04:57:32,360 --> 04:57:33,280 MICROBIOT A PATHOGENS. 6503 04:57:33,280 --> 04:57:37,360 IT IS NOW ESTABLISHED THAT ALL 6504 04:57:37,360 --> 04:57:40,800 MATTER OF ORGANISMS AND 6505 04:57:40,800 --> 04:57:43,520 MICROBIOTA THAT LIVE ON US AND 6506 04:57:43,520 --> 04:57:50,960 IN US AND INVOLVED IN OUR BODY 6507 04:57:50,960 --> 04:57:53,120 SIN SIS MAY BE DIFFERENT IN 6508 04:57:53,120 --> 04:57:57,600 THE MICE AND REGIONS WE STUDY 6509 04:57:57,600 --> 04:58:00,160 BUT POTENTIALLY SERVE SIMILAR 6510 04:58:00,160 --> 04:58:03,080 FUNCTIONS, CONTRIBUTE TO ALL 6511 04:58:03,080 --> 04:58:05,280 HEALTH AND THE SEVERITY OF 6512 04:58:05,280 --> 04:58:07,360 OUTCOME OF DISEASES WE 6513 04:58:07,360 --> 04:58:08,360 ENCOUNTER DURING LIFE. 6514 04:58:08,360 --> 04:58:13,040 SO IF WE LOOK AT ANIMALS, 6515 04:58:13,040 --> 04:58:15,520 HOWEVER, THE SITUATION IS 6516 04:58:15,520 --> 04:58:15,880 DIFFERENT. 6517 04:58:15,880 --> 04:58:18,800 IN LABORATORY MICE WHICH WE 6518 04:58:18,800 --> 04:58:26,520 HAVE NOT BEEN ABLE TO KNOW THE 6519 04:58:26,520 --> 04:58:29,520 PATHOGENICS OF DISEASES, 6520 04:58:29,520 --> 04:58:31,240 POPULATED WITH MICROBIOTA 6521 04:58:31,240 --> 04:58:32,720 WHICH IS NOT VERY SIMILAR TO 6522 04:58:32,720 --> 04:58:34,560 WHAT THEY HAVE IN THE WILD. 6523 04:58:34,560 --> 04:58:39,040 AND TO PROVE THAT MICROBIOTA 6524 04:58:39,040 --> 04:58:41,200 CONTRIBUTES TO SPECIFIC 6525 04:58:41,200 --> 04:58:51,840 DISEASE PATHWAYS, THESE MICE 6526 04:58:51,840 --> 04:58:56,280 HAVE BEEN PREPARED FOR 6527 04:58:56,280 --> 04:58:56,680 MICROBIOMES. 6528 04:58:56,680 --> 04:59:03,280 SO THIS IS AN ASPECT OF THE 6529 04:59:03,280 --> 04:59:04,120 STUDY THEN THAT MODELS WHAT IS 6530 04:59:04,120 --> 04:59:05,640 FOUND IN THE NATURAL WORLD. 6531 04:59:05,640 --> 04:59:08,080 AND THE QUESTION IS WHAT CAN 6532 04:59:08,080 --> 04:59:13,400 WE LEARN FROM THE MICROBIOME 6533 04:59:13,400 --> 04:59:14,320 ABOUT INFLAMMATION IMMUNE 6534 04:59:14,320 --> 04:59:16,400 RESPONSES. 6535 04:59:16,400 --> 04:59:19,280 SO THIS STUDY STARTED WHEN 6536 04:59:19,280 --> 04:59:22,840 STEFAN JOINED THE LABORATORY 6537 04:59:22,840 --> 04:59:23,480 SEVERAL YEARS AGO. 6538 04:59:23,480 --> 04:59:25,840 HE IS NOW AN INDEPENDENT 6539 04:59:25,840 --> 04:59:26,920 INVESTIGATOR IN GERMANY. 6540 04:59:26,920 --> 04:59:31,120 HE ESSENTIALLY WENT OUT AND 6541 04:59:31,120 --> 04:59:34,200 TRAPPED WHITE MICE, EUTHANIZED 6542 04:59:34,200 --> 04:59:40,080 THEM AND STUDIES THEIR 6543 04:59:40,080 --> 04:59:41,440 MICROBIOME. 6544 04:59:41,440 --> 04:59:47,760 IN THE ANALYSIS, THE WHITE 6545 04:59:47,760 --> 04:59:52,120 MOUSE BIOME WAS VERY MUCH LIKE 6546 04:59:52,120 --> 04:59:54,080 THE MOUSE READINGS -- 6547 04:59:54,080 --> 04:59:55,560 [INDISCERNIBLE] 6548 04:59:55,560 --> 05:00:18,280 SO WHAT CAN WE DO TO. 6549 05:00:18,280 --> 05:00:20,440 SO WE LOOK AT CLEAN LABORATORY 6550 05:00:20,440 --> 05:00:22,280 MICE AND THIS IS DONE 6551 05:00:22,280 --> 05:00:23,560 BASICALLY EVERY TEN 6552 05:00:23,560 --> 05:00:24,240 GENERATIONS. 6553 05:00:24,240 --> 05:00:30,840 SO IN CONTRAST HERE, WE TOOK 6554 05:00:30,840 --> 05:00:33,000 CRYO PRESERVED EMBRYOS AND 6555 05:00:33,000 --> 05:00:34,840 TRANSFERRED THEM INTO LIVE 6556 05:00:34,840 --> 05:00:35,280 MICE. 6557 05:00:35,280 --> 05:00:40,080 THE OFFSPRING THEN HAD THE 6558 05:00:40,080 --> 05:00:45,120 GENETICS OF THE INFLAMMATORY 6559 05:00:45,120 --> 05:00:51,320 MOUSE STRAIN BUT ALSO THE 6560 05:00:51,320 --> 05:00:51,840 WHITE MICROBIOME. 6561 05:00:51,840 --> 05:00:54,680 AND THIS WILL NOT MAKE THEM AN 6562 05:00:54,680 --> 05:00:56,160 IDEAL MODEL BUT AT LEAST 6563 05:00:56,160 --> 05:00:57,800 POINTING IN THE RIGHT 6564 05:00:57,800 --> 05:00:58,840 DIRECTION AS REPRESENTED BY 6565 05:00:58,840 --> 05:01:05,440 THIS ARROW AND MAY INCREASE 6566 05:01:05,440 --> 05:01:08,160 THE PRESENTATION OF BIOME 6567 05:01:08,160 --> 05:01:10,480 INFORMATION WITH THESE MOUSE 6568 05:01:10,480 --> 05:01:10,840 MODELS. 6569 05:01:10,840 --> 05:01:12,760 THE HUMAN MICROBIOME IN THE 6570 05:01:12,760 --> 05:01:17,360 GUT, NOT IDENTICAL IN THESE 6571 05:01:17,360 --> 05:01:20,120 MICE, NOW DOWN TO GENERATION 6572 05:01:20,120 --> 05:01:23,240 6, 7 OF THESE MICE AND WITH 6573 05:01:23,240 --> 05:01:24,440 EACH GENERATION, THE 6574 05:01:24,440 --> 05:01:25,400 MICROBIOME IS TRANSPOLICE 6575 05:01:25,400 --> 05:01:28,480 DEPARTMENT TO THE OFFSPRING. 6576 05:01:28,480 --> 05:01:30,760 SO IN THE GUT, THE INSTANCE IS 6577 05:01:30,760 --> 05:01:42,440 NOT EXACTLY THE SAME AS THE 6578 05:01:42,440 --> 05:01:45,520 WHITE MICE BUT ALSO INCLUDED 6579 05:01:45,520 --> 05:01:48,440 THE OTHER DATA SETS FROM THE 6580 05:01:48,440 --> 05:01:49,120 WHITE MICE. 6581 05:01:49,120 --> 05:01:58,920 SO YOU LOOK AT THE COLONY, YOU 6582 05:01:58,920 --> 05:02:05,200 HAVE ALSO MORE VIRAL AND 6583 05:02:05,200 --> 05:02:11,360 SPATIAL BIOME IN THESE MICE. 6584 05:02:11,360 --> 05:02:14,800 SO WE LOOK AT IMMUNE WITH THE 6585 05:02:14,800 --> 05:02:28,000 GENES AND BLOOD TO SEE THE 6586 05:02:28,000 --> 05:02:32,440 WHITE MOUSE TRANSCRIPTOME. 6587 05:02:32,440 --> 05:02:35,760 SO HOW DOES THIS TRANSLATE TO 6588 05:02:35,760 --> 05:02:36,280 IMMUNE RESPONSES? 6589 05:02:36,280 --> 05:02:41,040 SO TO BE ABLE TO TEST THIS, WE 6590 05:02:41,040 --> 05:02:46,800 ENGAGED THIS STUDY TO LOOK AT 6591 05:02:46,800 --> 05:02:50,840 THE BASICALLY WE FIND TWO 6592 05:02:50,840 --> 05:03:05,240 MODELS THAT WERE DOCUMENTED 6593 05:03:05,240 --> 05:03:10,680 AND ONE OF THEM I WILL SHOW 6594 05:03:10,680 --> 05:03:14,400 FROM THIS STUDY, THE 6595 05:03:14,400 --> 05:03:24,200 LABORATORY MICE ININJECTION OF 6596 05:03:24,200 --> 05:03:25,680 THIS AND WHAT WAS SUPPOSED TO 6597 05:03:25,680 --> 05:04:34,360 BE DEVELOPED IN THE TREATMENT 6598 05:04:34,360 --> 05:04:38,080 FOR ANY DISEASE SO WITH THE 6599 05:04:38,080 --> 05:04:43,120 INDUCTION OF INFORDHAM TORE 6600 05:04:43,120 --> 05:04:44,200 CCYTOKINES WITH THESE MICE, 6601 05:04:44,200 --> 05:04:49,120 YOU SEE THE HIGHER CYTOKINES 6602 05:04:49,120 --> 05:04:54,560 IN THE LAB MICE THAN THE 6603 05:04:54,560 --> 05:04:55,720 WILDLING MICE. 6604 05:04:55,720 --> 05:05:02,680 THE ONE EXCEPTION WAS I10 WHEN 6605 05:05:02,680 --> 05:05:03,720 ANTIINFLAMMATORY OCCURS IN 6606 05:05:03,720 --> 05:05:07,280 GREATER LEVELS IN THE LAB MICE 6607 05:05:07,280 --> 05:05:21,040 THAN THE WILDLING MICE. 6608 05:05:21,040 --> 05:05:25,120 SO THE IN LOOKING AT THE 6609 05:05:25,120 --> 05:05:36,120 METABOLISM, THIS STUDY SHOWS 6610 05:05:36,120 --> 05:05:39,280 THE MICROBIOME HAS TWO 6611 05:05:39,280 --> 05:05:40,240 EFFECTS. 6612 05:05:40,240 --> 05:05:49,000 IN THE LAB MICE, AND THE 6613 05:05:49,000 --> 05:05:51,640 WILD-TYPE, IT PROTECTED THEM 6614 05:05:51,640 --> 05:05:56,040 FROM THE HIGH FAT DIET. 6615 05:05:56,040 --> 05:06:03,280 SO IF YOU LOOK AT THE CONTENT 6616 05:06:03,280 --> 05:06:10,280 TO SEE THE LAB MICE LIVER 6617 05:06:10,280 --> 05:06:12,560 ENZYMES ARE MUCH HIGHER IN THE 6618 05:06:12,560 --> 05:06:19,840 LAB MICE THAN IN THE WILDLING 6619 05:06:19,840 --> 05:06:20,160 MICE. 6620 05:06:20,160 --> 05:06:24,200 THIS WAS DUE TO THE HIGH FAT 6621 05:06:24,200 --> 05:06:26,120 DIET BECAUSE INITIALLY WE WERE 6622 05:06:26,120 --> 05:06:28,680 INTERESTED IN OBSERVING THAT 6623 05:06:28,680 --> 05:06:33,520 BUT THE WILDLING MICE NEVER 6624 05:06:33,520 --> 05:06:36,000 DEVELOPED ANY SIGNIFICANT 6625 05:06:36,000 --> 05:06:36,320 OBESITY. 6626 05:06:36,320 --> 05:06:39,560 WE TRIED TO TREAT THE OBESE 6627 05:06:39,560 --> 05:06:43,080 MICE BUT UNFORTUNATELY THIS 6628 05:06:43,080 --> 05:06:45,680 DID NOT WORK. 6629 05:06:45,680 --> 05:06:49,480 THE LAB MICE DIET AND THE 6630 05:06:49,480 --> 05:06:52,480 WILDLING MICE AND TRANSFER THE 6631 05:06:52,480 --> 05:06:56,080 MICROBIOME, THE LAB MICE DO 6632 05:06:56,080 --> 05:06:59,200 NOT BECOME PROTECTED FROM HIGH 6633 05:06:59,200 --> 05:07:01,960 FAT DIET AND OBESITY. 6634 05:07:01,960 --> 05:07:05,600 AND AT THE SAME TIME WHEN WE 6635 05:07:05,600 --> 05:07:12,400 TRIED TO ELIMINATE THE 6636 05:07:12,400 --> 05:07:15,680 WILDLING MICROBIOME AND THESE 6637 05:07:15,680 --> 05:07:18,680 ACCUMULATE IN THE WILDLING 6638 05:07:18,680 --> 05:07:21,840 MICE, THEY DO NOT HAVE THE 6639 05:07:21,840 --> 05:07:30,480 SAME NET EFFECT. 6640 05:07:30,480 --> 05:07:33,480 THE EXPERIMENT ITSELF, YOU SEE 6641 05:07:33,480 --> 05:07:35,160 HERE THE MICROBIOME OF THE LAB 6642 05:07:35,160 --> 05:07:40,720 MICE IS MOVED TO THE LEFT ON 6643 05:07:40,720 --> 05:07:42,120 AXIS1 AND DID NOT MATCH THAT 6644 05:07:42,120 --> 05:07:47,120 CLOSELY TO THE WILDLING MICE 6645 05:07:47,120 --> 05:07:48,200 AND THEN TREATED WITH 6646 05:07:48,200 --> 05:07:51,600 ANTIBIOTICS, YOU SEE THE SAME 6647 05:07:51,600 --> 05:07:55,120 SHIFT FOR BOTH THE LAB MICE 6648 05:07:55,120 --> 05:07:59,120 MICROBIOME AND THE WILDLING 6649 05:07:59,120 --> 05:07:59,680 MICROBIOME. 6650 05:07:59,680 --> 05:08:04,520 SO BOTH WERE AFFECTED BUT THE 6651 05:08:04,520 --> 05:08:08,240 EFFECT ON THE WILDLING MICE 6652 05:08:08,240 --> 05:08:09,880 WAS NOT REPLICATED. 6653 05:08:09,880 --> 05:08:15,680 SO WHEN YOU TAKE LAB MICE AND 6654 05:08:15,680 --> 05:08:18,080 FOSTER THEM, THEN YOU CAN 6655 05:08:18,080 --> 05:08:20,080 TRANSFER THE PROTECTIVE 6656 05:08:20,080 --> 05:08:24,440 EFFECTS OF THE WILD MICE 6657 05:08:24,440 --> 05:08:28,680 MICROBIOME TO THE LAB MICE IN 6658 05:08:28,680 --> 05:08:34,880 RESPONSE TO HIGH FAT DIET. 6659 05:08:34,880 --> 05:08:38,200 THE WEIGHT GAIN IN THE COHORT 6660 05:08:38,200 --> 05:08:41,600 MICE WAS NOT FOUND IN THE WILD 6661 05:08:41,600 --> 05:08:42,040 MICE. 6662 05:08:42,040 --> 05:08:42,880 AND THIS IS INTERESTING 6663 05:08:42,880 --> 05:08:48,840 BECAUSE THEY USE THE SAME 6664 05:08:48,840 --> 05:08:51,720 AMOUNT OF ENERGY SO WHAT WE 6665 05:08:51,720 --> 05:08:53,240 LOOKED AT WAS THE ENERGY 6666 05:08:53,240 --> 05:08:53,640 EXPENDITURE. 6667 05:08:53,640 --> 05:08:55,640 THERE WAS A HIGHER BODY 6668 05:08:55,640 --> 05:08:58,720 TEMPERATURE IN THE WILDLING 6669 05:08:58,720 --> 05:09:04,360 MICE COMPARED TO THE LAB MICE 6670 05:09:04,360 --> 05:09:09,080 AND YOU SEE THAT IT IS GREATER 6671 05:09:09,080 --> 05:09:10,440 IN WILDLING MICE, THE 6672 05:09:10,440 --> 05:09:13,080 TEMPERATURE AND THE SAME FOR 6673 05:09:13,080 --> 05:09:14,480 MALES AND FEMALES ON ANY OF 6674 05:09:14,480 --> 05:09:16,720 THE DATA I SHOWED. 6675 05:09:16,720 --> 05:09:18,680 THIS IS INTERESTING THAT THE 6676 05:09:18,680 --> 05:09:21,000 WILDLING MICE HAVE A HIGHER 6677 05:09:21,000 --> 05:09:22,160 BODY TEMPERATURE THAN LAB 6678 05:09:22,160 --> 05:09:22,480 MICE. 6679 05:09:22,480 --> 05:09:24,920 WHAT DOES THIS TELL US ABOUT 6680 05:09:24,920 --> 05:09:25,280 HUMANS? 6681 05:09:25,280 --> 05:09:27,000 WE KNOW WITH HUMANS, THE 6682 05:09:27,000 --> 05:09:29,960 NORMAL BODY TEMPERATURE IS SET 6683 05:09:29,960 --> 05:09:35,160 TO 37 DEGREES CELSIUS AND THIS 6684 05:09:35,160 --> 05:09:41,280 WAS ESTABLISHED BY A GERMAN 6685 05:09:41,280 --> 05:09:44,120 PHYSICIANS IN LEIPZIG IN 1851 6686 05:09:44,120 --> 05:09:51,280 AND HE MEASURED THE 6687 05:09:51,280 --> 05:09:55,800 TEMPERATURE IN 25,000 PATIENTS 6688 05:09:55,800 --> 05:09:58,960 THAT PROVIDED IN TEMPERATURE 6689 05:09:58,960 --> 05:10:04,160 BEING SET TO CERTAIN -- OR 6690 05:10:04,160 --> 05:10:05,360 98.6 DEGREES FAHRENHEIT. 6691 05:10:05,360 --> 05:10:07,000 AT THAT TIME THE STANDARD LIFE 6692 05:10:07,000 --> 05:10:09,280 EXPECT TAPS SEE WAS ONLY 38 6693 05:10:09,280 --> 05:10:12,800 YEARS AND IT IS BECAUSE THERE 6694 05:10:12,800 --> 05:10:13,920 WERE MANY INFECTIONS THAT 6695 05:10:13,920 --> 05:10:15,160 BASICALLY KILLED PEOPLE EARLY 6696 05:10:15,160 --> 05:10:15,520 IN LIFE. 6697 05:10:15,520 --> 05:10:17,920 SO WHAT HAPPENED AFTER THIS? 6698 05:10:17,920 --> 05:10:19,000 VERY INTERESTING TO SEE WHAT 6699 05:10:19,000 --> 05:10:19,440 HAPPENED. 6700 05:10:19,440 --> 05:10:24,680 THERE WAS A RECENT PAPER 6701 05:10:24,680 --> 05:10:26,560 PUBLISHED THAT BASICALLY USED 6702 05:10:26,560 --> 05:10:47,920 TEMPERATURE MEASUREMENT AS A 6703 05:10:47,920 --> 05:10:49,320 PUBLISHED IN HUMANS, AND WAS 6704 05:10:49,320 --> 05:10:51,200 USED TO SEE ABOUT TEMPERATURE 6705 05:10:51,200 --> 05:10:52,080 CHANGE OVER TIME. 6706 05:10:52,080 --> 05:10:55,080 WHAT YOU CAN SEE IS THERE IS A 6707 05:10:55,080 --> 05:10:58,680 SIGNIFICANT DECREASE IN BODY 6708 05:10:58,680 --> 05:11:02,800 TEMPERATURE FROM THE 19TH 6709 05:11:02,800 --> 05:11:05,680 CENTURY TO TODAY. 6710 05:11:05,680 --> 05:11:07,320 AND 1.6 PERCENT IN BODY 6711 05:11:07,320 --> 05:11:11,520 TEMPERATURE OVER THIS PERIOD 6712 05:11:11,520 --> 05:11:17,080 OF TIME AND AND DECREASE IN 6713 05:11:17,080 --> 05:11:18,280 MEN AND FEMALES. 6714 05:11:18,280 --> 05:11:20,480 SO THIS MEANS WE MAY HAVE LOST 6715 05:11:20,480 --> 05:11:29,640 SOME OF THE PROTECTION EFFECTS 6716 05:11:29,640 --> 05:11:34,080 THAT THE WILD MICE MICROBIOTA 6717 05:11:34,080 --> 05:11:38,560 HAS GIVEN US WITH EXPANDED 6718 05:11:38,560 --> 05:11:41,280 LIFE THAT MAY HAVE ROBBED US 6719 05:11:41,280 --> 05:11:42,080 OF POTENTIAL MICROBES. 6720 05:11:42,080 --> 05:11:48,600 SO THIS IS WHAT I SHOWED. 6721 05:11:48,600 --> 05:11:55,040 THE PROTECTION AGAINST 6722 05:11:55,040 --> 05:11:59,160 DIET-INDUCED OBESITY 6723 05:11:59,160 --> 05:12:01,200 THROUGHOUT ADULT LIFE AND 6724 05:12:01,200 --> 05:12:04,240 ANIMAL MODELS WITH NATURAL 6725 05:12:04,240 --> 05:12:06,760 MICROBIOTA MAY INCREASE THE 6726 05:12:06,760 --> 05:12:08,120 USEFULNESS OF LABORATORY MICE 6727 05:12:08,120 --> 05:12:11,040 AS MODELS FOR HUMAN IMMUNE 6728 05:12:11,040 --> 05:12:13,160 RESPONSES IN PRECLINICAL 6729 05:12:13,160 --> 05:12:16,480 STUDIES AND ALLOW 6730 05:12:16,480 --> 05:12:17,760 MECHANISTICALLY, RESEARCH ON 6731 05:12:17,760 --> 05:12:22,920 THE ROLE OF ALL KINGDOMS OF 6732 05:12:22,920 --> 05:12:24,120 COMPLEX MICROBIOTA IN HEALTH 6733 05:12:24,120 --> 05:12:24,560 AND DISEASE. 6734 05:12:24,560 --> 05:12:26,280 SO I WOULD LIKE TO THANK THOSE 6735 05:12:26,280 --> 05:12:41,840 WHO HELPED ME IN THIS WORK, MY 6736 05:12:41,840 --> 05:12:44,400 LAB AND COLLABORATORS, ALL 6737 05:12:44,400 --> 05:12:46,000 INTRAMURALLY AND EXTRAMURALLY 6738 05:12:46,000 --> 05:12:58,760 AND LIKE TO MENTION THESE -- 6739 05:12:58,760 --> 05:13:04,200 [INDISCERNIBLE] 6740 05:13:04,200 --> 05:13:05,240 THANK YOU. 6741 05:13:05,240 --> 05:13:05,600 THANK YOU. 6742 05:13:05,600 --> 05:13:08,640 I WILL TURN IT OVER TO THE 6743 05:13:08,640 --> 05:13:09,960 NEXT SPEAKER. 6744 05:13:09,960 --> 05:13:19,360 >> THANK YOU VERY MUCH BARBARA 6745 05:13:19,360 --> 05:13:19,960 REHEMANN. 6746 05:13:19,960 --> 05:13:28,240 OUR NEXT TALK IS SAMEER 6747 05:13:28,240 --> 05:13:28,720 SONKUSALE. 6748 05:13:28,720 --> 05:13:31,840 >> CAN YOU SEE MY SCREEN? 6749 05:13:31,840 --> 05:13:35,040 >> YES BUT NOT -- OKAY NOW IT 6750 05:13:35,040 --> 05:13:36,080 IS RIGHT. 6751 05:13:36,080 --> 05:13:38,280 >> OKAY, SO FIRST I WILL THANK 6752 05:13:38,280 --> 05:13:41,840 THE ORGANIZERS FOR INVITING ME 6753 05:13:41,840 --> 05:13:42,520 TO PRESENT HERE. 6754 05:13:42,520 --> 05:13:44,280 I BRING A DIFFERENT 6755 05:13:44,280 --> 05:13:45,240 PERSPECTIVE TO THIS 6756 05:13:45,240 --> 05:13:45,880 CONVERSATION. 6757 05:13:45,880 --> 05:13:48,480 I REALLY ENJOY LISTENING AND 6758 05:13:48,480 --> 05:13:51,800 LEARNING FROM ALL OF YOU IN 6759 05:13:51,800 --> 05:13:57,480 THE LAST TWO DAYS AND I BRING 6760 05:13:57,480 --> 05:13:59,920 A PERSPECTIVE AS I AM TRAINED 6761 05:13:59,920 --> 05:14:07,560 AS A ELECTRICAL AND 6762 05:14:07,560 --> 05:14:10,680 BIOENGINEER AND AM TRAINED IN 6763 05:14:10,680 --> 05:14:11,600 SOME OF THE CHALLENGES THAT 6764 05:14:11,600 --> 05:14:14,320 YOU ALL ARE LOOKING AT AND 6765 05:14:14,320 --> 05:14:16,280 MADE SOME PROGRESS TO SHOW WE 6766 05:14:16,280 --> 05:14:21,880 CAN DO SPATIAL MAPPING OF THE 6767 05:14:21,880 --> 05:14:22,960 MICROBIOME USING ENGINEERING 6768 05:14:22,960 --> 05:14:25,120 INNOVATIONS SO THIS IS MORE OF 6769 05:14:25,120 --> 05:14:27,080 AN ENGINEERING TALK RATHER 6770 05:14:27,080 --> 05:14:28,560 THAN A MICROBIOME DISCUSSION. 6771 05:14:28,560 --> 05:14:31,040 LET'S SEE IF I CAN ADVANCE MY 6772 05:14:31,040 --> 05:14:31,360 SLIDES. 6773 05:14:31,360 --> 05:14:43,480 SO I HAVE SOME CON FLICKS. 6774 05:14:43,480 --> 05:14:45,320 ONE OF THE KEY MESSAGES THAT 6775 05:14:45,320 --> 05:14:46,920 CAME THROUGH DURING THE TWO 6776 05:14:46,920 --> 05:14:52,400 DAYS OF DISCUSSIONS IS THAT 6777 05:14:52,400 --> 05:14:53,720 THE MICROBIAL 6778 05:14:53,720 --> 05:14:54,760 BIOEMPLOYEOGRAPHY OF THE GUT 6779 05:14:54,760 --> 05:14:55,680 IS REALLY IMPORTANT AND THIS 6780 05:14:55,680 --> 05:14:57,200 IS A PICTURE I BORROWED FROM 6781 05:14:57,200 --> 05:15:00,360 ONE OF THE REVIEW ARTICLES AND 6782 05:15:00,360 --> 05:15:02,640 IT SHOWS THAT DIFFERENT ORGANS 6783 05:15:02,640 --> 05:15:06,840 IN DIFFERENT AREAS OF OUR GI 6784 05:15:06,840 --> 05:15:08,560 TRACT HARBOR DIFFERENT 6785 05:15:08,560 --> 05:15:11,200 MICROBIAL SPECIES. 6786 05:15:11,200 --> 05:15:12,640 SO UNDERSTANDING WHERE AND HOW 6787 05:15:12,640 --> 05:15:15,920 THEY INTERACT WITH THE HOST IS 6788 05:15:15,920 --> 05:15:17,000 REALLY IMPORTANT. 6789 05:15:17,000 --> 05:15:20,440 SO I ACTUALLY TRIED TO COME UP 6790 05:15:20,440 --> 05:15:23,400 WITH AN ANALOGY TRYING TO 6791 05:15:23,400 --> 05:15:25,040 UNDERSTAND, AND I DON'T HAVE A 6792 05:15:25,040 --> 05:15:26,880 SLIDE FOR THAT BUT THESE ARE 6793 05:15:26,880 --> 05:15:28,320 THE KEY OBSERVATIONS OF ALL 6794 05:15:28,320 --> 05:15:32,320 THE TALKS I HEARD OVER THE 6795 05:15:32,320 --> 05:15:37,480 LAST TWO DAYS AND IT WAS 6796 05:15:37,480 --> 05:15:39,280 MENTIONED THE MICROBIIOTA IN 6797 05:15:39,280 --> 05:15:41,240 SMALL INTESTINE IS QUITE 6798 05:15:41,240 --> 05:15:43,200 DISTINCT FROM THE MICROBIOTA 6799 05:15:43,200 --> 05:15:45,760 IN THE STOOL AND REALLY DOES 6800 05:15:45,760 --> 05:15:49,000 NOT CAPTURE THE DIVERSITY OR 6801 05:15:49,000 --> 05:15:51,280 CON SHORTIUM SEEN IN THE SMALL 6802 05:15:51,280 --> 05:15:51,680 INTESTINE. 6803 05:15:51,680 --> 05:15:56,360 ALSO AS I JUST ALLUDED TO 6804 05:15:56,360 --> 05:15:59,680 EARLIER, THE MICROBIOME 6805 05:15:59,680 --> 05:16:00,520 VARIOUS LONGITUDINALLY ACROSS 6806 05:16:00,520 --> 05:16:03,480 THE GI TRACT FROM THE STOMACH 6807 05:16:03,480 --> 05:16:12,600 TO THE COLON AND ACTUALLY THE 6808 05:16:12,600 --> 05:16:15,040 MUCOSAAL MICROBIOTA IS QUITE 6809 05:16:15,040 --> 05:16:18,560 DISTINCT FROM THE LUMINAL 6810 05:16:18,560 --> 05:16:20,080 MICROBIOTA SO THE SPATIAL 6811 05:16:20,080 --> 05:16:20,840 MAPPING IS REALLY IMPORTANT 6812 05:16:20,840 --> 05:16:24,400 WHERE YOU ARE TRYING TO 6813 05:16:24,400 --> 05:16:27,520 UNDERSTAND THE MICROBIOME HOST 6814 05:16:27,520 --> 05:16:29,640 CONDITION FOR UNDERSTANDING A 6815 05:16:29,640 --> 05:16:30,000 CONDITION. 6816 05:16:30,000 --> 05:16:33,160 FINALLY, WE RECOGNIZE IT IS A 6817 05:16:33,160 --> 05:16:35,320 LIVING, DYNAMIC ECOSYSTEM AND 6818 05:16:35,320 --> 05:16:38,440 WE HEARD CIRCADIAN RHYTHM 6819 05:16:38,440 --> 05:16:39,480 INFLUENCES THE MICROBIAL 6820 05:16:39,480 --> 05:16:41,880 COMPOSITION SO IN SOME WAY 6821 05:16:41,880 --> 05:16:57,320 ANALYZING A STOOL SAMPLE DOES 6822 05:16:57,320 --> 05:17:00,440 NOT WIDELY REPRESENT THE 6823 05:17:00,440 --> 05:17:01,160 SPATIAL AND TEMPORAL 6824 05:17:01,160 --> 05:17:01,600 DISTRIBUTION. 6825 05:17:01,600 --> 05:17:08,400 WHEN YOU ARE TRYING TO CAPTURE 6826 05:17:08,400 --> 05:17:11,880 THE MICROBIOTA FROM THE STOOL, 6827 05:17:11,880 --> 05:17:16,280 IT IS EX EXTREMELY HARD TO I 6828 05:17:16,280 --> 05:17:17,280 HAVE AN UNDERSTANDING THE 6829 05:17:17,280 --> 05:17:20,600 COMMUNITY IS FACING AND 6830 05:17:20,600 --> 05:17:23,600 ESSENTIALLY THE FECAL MATTER 6831 05:17:23,600 --> 05:17:24,240 ANALYSIS IS INADEQUATE. 6832 05:17:24,240 --> 05:17:26,800 SO I FAIL TO RECALL WHO 6833 05:17:26,800 --> 05:17:30,760 INTRODUCED ME TO THIS BUT THIS 6834 05:17:30,760 --> 05:17:33,640 POINT THAT IT IS A VERY 6835 05:17:33,640 --> 05:17:34,880 COMPLEX ECOSYSTEM, YOU HAVE 6836 05:17:34,880 --> 05:17:37,320 LOTS OF DIFFERENT ORGANISMS IN 6837 05:17:37,320 --> 05:17:40,320 DIFFERENT AREAS, THERE ARE 6838 05:17:40,320 --> 05:17:40,920 MICROCLIMATES AND 6839 05:17:40,920 --> 05:17:42,160 MICROENVIRONMENTS THAT ARE 6840 05:17:42,160 --> 05:17:43,560 VERY IMPORTANT, SUPPORTING 6841 05:17:43,560 --> 05:17:44,640 DIFFERENT ORGANISMS ALL THE 6842 05:17:44,640 --> 05:17:47,160 WAY TO SMALL INSECTS, 6843 05:17:47,160 --> 05:17:48,880 BUTTERFLIES, TO LARGE ANIMALS 6844 05:17:48,880 --> 05:17:49,960 AND ANIMALS THAT LIVE AT THE 6845 05:17:49,960 --> 05:17:51,160 BOTTOM IN THE SO I WILL AND 6846 05:17:51,160 --> 05:17:53,080 THEN THERE ARE SOME SPECIES 6847 05:17:53,080 --> 05:17:57,360 THAT LIVE ON THE CANOPY ON THE 6848 05:17:57,360 --> 05:17:59,720 ROOFTOP AND THESE SPECIES, YOU 6849 05:17:59,720 --> 05:18:01,800 KNOW, EVEN DURING THE DAY, YOU 6850 05:18:01,800 --> 05:18:03,480 HAVE DIFFERENT SPECIES 6851 05:18:03,480 --> 05:18:07,120 POPULATING THAT ARE COMING OUT 6852 05:18:07,120 --> 05:18:09,200 AND THE LIFETIME OF DIFFERENT 6853 05:18:09,200 --> 05:18:10,040 SPECIES THAT ACTUALLY SPENT 6854 05:18:10,040 --> 05:18:11,400 TIME IN THE FOREST. 6855 05:18:11,400 --> 05:18:13,520 AND THE WAY WE ARE TRYING TO 6856 05:18:13,520 --> 05:18:14,680 UNDERSTAND THE RAIN FOREST OR 6857 05:18:14,680 --> 05:18:18,280 THE WAY I SEE IT, THE ANALOGY 6858 05:18:18,280 --> 05:18:19,360 HERE, ESSENTIALLY ALL YOU ARE 6859 05:18:19,360 --> 05:18:20,640 DOING IS BLENDING ALL THE 6860 05:18:20,640 --> 05:18:23,080 INFORMATION IN A BLENDER AND 6861 05:18:23,080 --> 05:18:25,120 THEN ANALYZING THE STOOL 6862 05:18:25,120 --> 05:18:28,880 SAMPLE AND HOSTING THE STOOL 6863 05:18:28,880 --> 05:18:30,280 SAMPLE SOMEHOW PRESENTS OR 6864 05:18:30,280 --> 05:18:32,280 WILL CAPTURE THE EXTREME 6865 05:18:32,280 --> 05:18:36,360 SPATIAL AND TEMPORAL DIVERSITY 6866 05:18:36,360 --> 05:18:38,080 THAT THE RAIN FOREST HAVE. 6867 05:18:38,080 --> 05:18:43,040 SO I BELIEVE THE FIRST PROBLEM 6868 05:18:43,040 --> 05:19:02,840 TO SOLVE HERE IS LOOK AT WAYS 6869 05:19:02,840 --> 05:19:03,480 THAT GEOGRAPHY MAPPING CAN 6870 05:19:03,480 --> 05:19:04,040 HELP TO REPRODUCE THE 6871 05:19:04,040 --> 05:19:05,000 DIVERSITY OF THE MICROBIOME 6872 05:19:05,000 --> 05:19:13,880 THAT WILL GIVE US MORE 6873 05:19:13,880 --> 05:19:15,520 SOLUTION SO ESSENTIALLY THIS 6874 05:19:15,520 --> 05:19:17,720 IDEA IS USED TO LOOK AT THE 6875 05:19:17,720 --> 05:19:20,560 BACTERIA AND OBJECTIVES AS 6876 05:19:20,560 --> 05:19:21,120 WELL. 6877 05:19:21,120 --> 05:19:23,520 SO I WAS RECRUITED WHEN I WAS 6878 05:19:23,520 --> 05:19:28,960 LOOKING TO WORK ON DEVELOPING 6879 05:19:28,960 --> 05:19:30,240 DIAGNOSTIC PLATFORMS, THE 6880 05:19:30,240 --> 05:19:34,880 PROGRAM MANAGER APPROACHED ME 6881 05:19:34,880 --> 05:19:38,640 AND SAID CAN YOU DEVELOP TOOLS 6882 05:19:38,640 --> 05:19:40,080 OR DEVICES TO SOLVE THIS 6883 05:19:40,080 --> 05:19:43,960 PROBLEM AND AN ENGINEER LIKES 6884 05:19:43,960 --> 05:19:44,800 RESOLVING CHALLENGES AND 6885 05:19:44,800 --> 05:19:46,080 CHALLENGES SO IT WAS AN 6886 05:19:46,080 --> 05:19:46,960 INTERESTING PROJECT OVER THE 6887 05:19:46,960 --> 05:19:49,040 LAST FIVE OR SIX YEARS AND I 6888 05:19:49,040 --> 05:19:50,520 WILL SHOW YOU SOME PLATFORMS 6889 05:19:50,520 --> 05:19:51,680 DEVELOPED OVER TIME THAT WILL 6890 05:19:51,680 --> 05:19:58,480 TAKE US IN THAT DIRECTION. 6891 05:19:58,480 --> 05:20:01,720 SO THIS IS THE FIRST BUILD, IT 6892 05:20:01,720 --> 05:20:07,000 IS CALLED AN OSMOTIC PILL THAT 6893 05:20:07,000 --> 05:20:11,480 ALLOWS YOU TO TAKE A SPATIALLY 6894 05:20:11,480 --> 05:20:14,480 SAMPLING FROM THE GI TRACT. 6895 05:20:14,480 --> 05:20:16,440 IT IS EXTREMELY SAFE. 6896 05:20:16,440 --> 05:20:19,480 THERE IS NO ELECTRONICS IN 6897 05:20:19,480 --> 05:20:20,280 THIS PILL. 6898 05:20:20,280 --> 05:20:28,840 IT IS A FACETED PILL, HAS FOUR 6899 05:20:28,840 --> 05:20:32,040 HELICAL CHANNELS DRIVEN BY A 6900 05:20:32,040 --> 05:20:34,920 MICROPUMP AND THE MICROPUMP 6901 05:20:34,920 --> 05:20:36,240 USES THE PRINCIPLE OF 6902 05:20:36,240 --> 05:20:39,080 RESPONSES ON ONE SIDE AND THEN 6903 05:20:39,080 --> 05:20:41,120 BASICALLY PULLS THE FLUID 6904 05:20:41,120 --> 05:20:42,160 THROUGH THE ECOCHANNELS WHERE 6905 05:20:42,160 --> 05:20:44,120 YOU ESSENTIALLY HAVE A 6906 05:20:44,120 --> 05:20:45,480 MICROPUMP PULLING A EXAMINER 6907 05:20:45,480 --> 05:20:47,080 IN. 6908 05:20:47,080 --> 05:20:56,160 THERE IS A MAGNET INSIDE AND I 6909 05:20:56,160 --> 05:20:57,760 WILL EXPLAIN THE PURPOSE OF 6910 05:20:57,760 --> 05:21:01,480 THE MAGNET AND THEN BASICALLY 6911 05:21:01,480 --> 05:21:07,360 SOME DYE FOR EASY SPOTTING. 6912 05:21:07,360 --> 05:21:11,120 SO THE DESIGN OF ALL THE 6913 05:21:11,120 --> 05:21:13,000 INLETS AND EXIT NOZZLE IS VERY 6914 05:21:13,000 --> 05:21:14,880 WELL CONTROLLED SO YOU HAVE 6915 05:21:14,880 --> 05:21:18,600 THE BEST POSSIBLE SAMPLING 6916 05:21:18,600 --> 05:21:18,960 SCENARIO. 6917 05:21:18,960 --> 05:21:22,640 SO THIS IS HOW THE PILL LOOKS, 6918 05:21:22,640 --> 05:21:24,320 THIS PICTURE HERE JUST A 6919 05:21:24,320 --> 05:21:25,840 COLLECTION OF DIFFERENT PILLS. 6920 05:21:25,840 --> 05:21:28,080 THE GOOD NEWS HERE IS THE PILL 6921 05:21:28,080 --> 05:21:31,640 DESIGN IS VERY SIMPLE, IT CAN 6922 05:21:31,640 --> 05:21:34,160 BE TREATED, IT NOT EXPENSIVE 6923 05:21:34,160 --> 05:21:35,560 SO THIS BOWEDS WELL FOR THE 6924 05:21:35,560 --> 05:21:35,920 COMMUNITY. 6925 05:21:35,920 --> 05:21:39,000 IF YOU ARE TRYING TO USE THE 6926 05:21:39,000 --> 05:21:44,200 PILL FOR LARGE STUDIES, THESE 6927 05:21:44,200 --> 05:21:45,040 PILLS ARE STRAIGHTFORWARD FOR 6928 05:21:45,040 --> 05:21:47,320 US TO MAKE AND HAPPY TO SHARE 6929 05:21:47,320 --> 05:21:49,720 THESE WITH YOU FOR YOUR OWN 6930 05:21:49,720 --> 05:21:50,160 INVESTIGATION. 6931 05:21:50,160 --> 05:21:52,600 THIS PICTURE SHOWS YOU THE 6932 05:21:52,600 --> 05:22:04,480 DESIGN OF THE SEMI PERMEA -- 6933 05:22:04,480 --> 05:22:05,720 SEMIPERMEABLE ACTION AND THE 6934 05:22:05,720 --> 05:22:08,080 WAY IT WORKS, YOU INGEST THE 6935 05:22:08,080 --> 05:22:12,480 PILL WITH AN ENTERIC COATING, 6936 05:22:12,480 --> 05:22:14,240 PH DEPEND ENT AND PROTECTS THE 6937 05:22:14,240 --> 05:22:16,800 PILL IN IT THE ACIDIC 6938 05:22:16,800 --> 05:22:18,520 ENVIRONMENT OF THE STOMACH. 6939 05:22:18,520 --> 05:22:23,440 AFTER IT REACHES THE SMALL 6940 05:22:23,440 --> 05:22:25,360 INTESTINE, THE ENTERIC COATING 6941 05:22:25,360 --> 05:22:27,080 WILL BE DISSOLVED AND WILL 6942 05:22:27,080 --> 05:22:28,920 START THE SAMPLING PROCESS. 6943 05:22:28,920 --> 05:22:30,520 YOU CAN CONTROL THE SAMPLING 6944 05:22:30,520 --> 05:22:32,720 PROCESS BY CONTROLLING THE PH 6945 05:22:32,720 --> 05:22:34,960 OF THE SOLUTION SO YOU CAN 6946 05:22:34,960 --> 05:22:36,560 EITHER START SOONER OR LATER 6947 05:22:36,560 --> 05:22:39,680 BASED ON HOW YOU FORM THIS 6948 05:22:39,680 --> 05:22:40,080 COMPOSITION. 6949 05:22:40,080 --> 05:22:41,440 IMAGINE IT HAS A VERY 6950 05:22:41,440 --> 05:22:42,880 IMPORTANT ROLE. 6951 05:22:42,880 --> 05:22:49,040 THE PILL MOVES ON ITS OWN DUE 6952 05:22:49,040 --> 05:22:50,280 TO NATURAL PERISTALTIC 6953 05:22:50,280 --> 05:22:52,360 FUNCTION SO YOU HOLD THE 6954 05:22:52,360 --> 05:22:54,720 MAGNET CLOSE TO THE LOCATION 6955 05:22:54,720 --> 05:22:57,840 YOU WANT AND THIS ESSENTIALLY 6956 05:22:57,840 --> 05:22:59,720 CAPTURED MORE SAMPLING FROM 6957 05:22:59,720 --> 05:23:00,360 THAT AREA. 6958 05:23:00,360 --> 05:23:03,880 SO THE PILL IS ESSENTIALLY A 6959 05:23:03,880 --> 05:23:07,840 PROPORTIONAL SAMPLING PILL AND 6960 05:23:07,840 --> 05:23:09,080 KEEPS SAMPLING UNTILL ALL THE 6961 05:23:09,080 --> 05:23:10,360 CHANNELS IN THE PILL ARE FULL 6962 05:23:10,360 --> 05:23:12,600 AND THEN WHEN IT EXITS ON THE 6963 05:23:12,600 --> 05:23:15,120 OTHER SIDE, YOU CAN ANALYZE 6964 05:23:15,120 --> 05:23:18,120 THE CONTENTS OF THE PILL, DO 6965 05:23:18,120 --> 05:23:20,440 ALL YOUR OMIC STUDIES ON THE 6966 05:23:20,440 --> 05:23:20,760 CONTENT. 6967 05:23:20,760 --> 05:23:23,880 SO IT IS NOT JUST SAMPLING THE 6968 05:23:23,880 --> 05:23:27,280 MICROBIOME BUT THE BILUMEN AND 6969 05:23:27,280 --> 05:23:28,280 ESSENTIALLY ALL THE OTHER 6970 05:23:28,280 --> 05:23:31,640 CONTENTS IN THE AREA OF THE GI 6971 05:23:31,640 --> 05:23:32,400 TRACT. 6972 05:23:32,400 --> 05:23:35,520 SO WE MAKE VERY DIFFERENT 6973 05:23:35,520 --> 05:23:37,480 VERSIONS OF OSMOTIC PILLS. 6974 05:23:37,480 --> 05:23:39,000 THE ONES INJECTED IN ANIMALS 6975 05:23:39,000 --> 05:23:41,280 ARE THE ONES ON THE LEFT BUT 6976 05:23:41,280 --> 05:23:43,040 WE ALSO MAKE A PILL THAT CAN 6977 05:23:43,040 --> 05:23:45,680 BE TESTED WITH LARGE AND SMALL 6978 05:23:45,680 --> 05:23:48,480 ANIMAL USE, SHOWING YOU 6979 05:23:48,480 --> 05:23:50,440 DIFFERENT SAMPLING CAPACITY 6980 05:23:50,440 --> 05:23:52,640 FOR DIFFERENT PILLS THAT WE 6981 05:23:52,640 --> 05:23:53,680 MADE WITH DIFFERENT FUNCTIONS. 6982 05:23:53,680 --> 05:24:04,080 SO YOU CAN TEST ALL THE WAY 6983 05:24:04,080 --> 05:24:09,080 FROM MICE TO LARGE ANIMALS. 6984 05:24:09,080 --> 05:24:11,080 SO THE PUMPING ACTION IN THE 6985 05:24:11,080 --> 05:24:13,600 PILL IS USING PRINCIPLE0s 6986 05:24:13,600 --> 05:24:19,440 MOST SIS, LOOKING AT THE 6987 05:24:19,440 --> 05:24:21,920 PERMEABLE MEMBRANE ON ONE SIDE 6988 05:24:21,920 --> 05:24:24,800 AND OVER TIME, CREATES0s MOT 6989 05:24:24,800 --> 05:24:26,840 TICK PRESSURE DIFFERENCE AND 6990 05:24:26,840 --> 05:24:28,200 THAT IS BASICALLY WHAT IS 6991 05:24:28,200 --> 05:24:28,880 DRIVING. 6992 05:24:28,880 --> 05:24:33,200 WHAT IS SHOWING HERE IS IT 6993 05:24:33,200 --> 05:24:40,840 CONTINUES TO OPERATE UP TO 48 6994 05:24:40,840 --> 05:24:42,760 HOURS SO SAMPLING FOR A VERY 6995 05:24:42,760 --> 05:24:45,920 LONG TIME IN THE PILL. 6996 05:24:45,920 --> 05:24:48,880 SO THIS IS POTENTIALLY A VERY 6997 05:24:48,880 --> 05:24:55,720 SIMPLE WAY OF GETTING THE 6998 05:24:55,720 --> 05:24:56,680 AQUEOUS SAMPLE FROM THE 6999 05:24:56,680 --> 05:24:57,080 ENVIRONMENT. 7000 05:24:57,080 --> 05:24:58,520 SO THE FIRST TIME I WAS TRYING 7001 05:24:58,520 --> 05:25:00,920 TO WORK ON THIS, WE HAD COULD 7002 05:25:00,920 --> 05:25:04,280 COME UP WITH OUR OWN CUSTOM 7003 05:25:04,280 --> 05:25:06,760 SETUP FOR THE FUNCTION OF THE 7004 05:25:06,760 --> 05:25:08,480 PILL, JUST MAKING SURE THE 7005 05:25:08,480 --> 05:25:14,600 PILL WORKS AS WE INTENDED. 7006 05:25:14,600 --> 05:25:17,880 SO HOW THE PILL IS INSERTED, 7007 05:25:17,880 --> 05:25:22,240 IS THERE ANY LEAKAGE AND ONCE 7008 05:25:22,240 --> 05:25:24,520 YOU SAMPLE THE CONTENT, DOES 7009 05:25:24,520 --> 05:25:27,280 ANY OF IT LEAK OUT DOWNSTREAM 7010 05:25:27,280 --> 05:25:28,880 OF THE COLON AND THEN YOU HAVE 7011 05:25:28,880 --> 05:25:32,520 TO MAKE SURE THE ACTIVATION 7012 05:25:32,520 --> 05:25:34,120 PORTION IS WORKING, WHEN YOU 7013 05:25:34,120 --> 05:25:36,280 BRING THE MAGNET TO THE PILL, 7014 05:25:36,280 --> 05:25:37,880 DOES IT EXAMINER MORE IN THE 7015 05:25:37,880 --> 05:25:39,760 AREA YOU WANT AS OPPOSED TO 7016 05:25:39,760 --> 05:25:40,560 ANOTHER. 7017 05:25:40,560 --> 05:25:46,480 SO WE BASICALLY MADE A SET OF 7018 05:25:46,480 --> 05:25:53,160 EX VIVO GI TRACT AND 7019 05:25:53,160 --> 05:25:57,960 ESSENTIALLY MONITOR THE 7020 05:25:57,960 --> 05:25:59,120 PERISTALTIC MOTION WITH THE 7021 05:25:59,120 --> 05:26:01,280 PUMP AND TRYING TO UNDERSTAND 7022 05:26:01,280 --> 05:26:02,640 HOW THE GI TRACT MOVES. 7023 05:26:02,640 --> 05:26:04,360 TO COME UP WITH A CLEAR 7024 05:26:04,360 --> 05:26:05,640 UNDERSTANDING OF THE ASPECTS 7025 05:26:05,640 --> 05:26:08,680 OF THE PILL THAT CONTRIBUTE TO 7026 05:26:08,680 --> 05:26:10,880 THE SAMPLING PROCESS MORE THAN 7027 05:26:10,880 --> 05:26:12,080 ANYTHING. 7028 05:26:12,080 --> 05:26:15,280 SO WE REALIZED THE PILL DID 7029 05:26:15,280 --> 05:26:17,280 WORK WELL, THE CONTENTS OF THE 7030 05:26:17,280 --> 05:26:20,720 PILL AND THE SAMPLING ACTION 7031 05:26:20,720 --> 05:26:21,480 IS QUITE RELIABLE. 7032 05:26:21,480 --> 05:26:23,040 >> YOU ARE JUST UNDER THREE 7033 05:26:23,040 --> 05:26:23,520 MINUTES. 7034 05:26:23,520 --> 05:26:24,440 >> OKAY, THANK YOU. 7035 05:26:24,440 --> 05:26:28,760 SO WE DID A LOT OF LEAKAGE AND 7036 05:26:28,760 --> 05:26:29,800 CONTAMINATION STUDIES AND IN 7037 05:26:29,800 --> 05:26:31,200 THE INTEREST OF TIME, I WILL 7038 05:26:31,200 --> 05:26:35,080 NOT GO OVER THE DETAILS OF 7039 05:26:35,080 --> 05:26:37,280 THIS BUT BASICALLY A SETUP 7040 05:26:37,280 --> 05:26:39,000 THAT EXPOSES THE PILL TO 7041 05:26:39,000 --> 05:26:41,160 CERTAIN CONTENTS AND MAKE SURE 7042 05:26:41,160 --> 05:26:44,040 THE SAMPLE YOU ACQUIRED IS 7043 05:26:44,040 --> 05:26:45,880 POTENTIALLY THE SAMPLE YOU 7044 05:26:45,880 --> 05:26:47,800 INTENDED TO THIS SHOWS HERE IT 7045 05:26:47,800 --> 05:26:50,680 IS CAPABLE OF SAMPLING THREE 7046 05:26:50,680 --> 05:26:52,800 DIFFERENT DYES WITHOUT ANY 7047 05:26:52,800 --> 05:26:53,640 LEAKAGE OR CONTAMINATION. 7048 05:26:53,640 --> 05:26:56,280 SO THE PILLS ARE TESTED IN 7049 05:26:56,280 --> 05:26:57,880 VIVO, IN THE ANIMAL. 7050 05:26:57,880 --> 05:27:06,480 SO THIS IS THE PCO A PLOT OF 7051 05:27:06,480 --> 05:27:10,480 WHAT WE FIND IN THE PILL 7052 05:27:10,480 --> 05:27:11,640 THROUGH THE DIFFERENT FEATURES 7053 05:27:11,640 --> 05:27:12,680 OF THE GI TRACT. 7054 05:27:12,680 --> 05:27:17,280 THIS IS JUST A VERY SMALL 7055 05:27:17,280 --> 05:27:19,720 STUDY ON A PIG AND THEN THERE 7056 05:27:19,720 --> 05:27:23,720 ARE TWO IN VIVO STUDIES WITH A 7057 05:27:23,720 --> 05:27:25,920 MOUSE AND CAT AND THE STUDIES 7058 05:27:25,920 --> 05:27:27,680 HERE SHOW WE ARE CAPABLE OF 7059 05:27:27,680 --> 05:27:30,480 SAMPLING FROM THE REGION OF 7060 05:27:30,480 --> 05:27:34,680 THE GI TRACT WHERE WE 7061 05:27:34,680 --> 05:27:35,160 INTENDED. 7062 05:27:35,160 --> 05:27:39,040 SO WE ALSO DID ANOTHER STUDY 7063 05:27:39,040 --> 05:27:41,280 IN MONKEYS WHERE WE ALSO -- SO 7064 05:27:41,280 --> 05:27:43,600 THIS STUDY WAS NOT TO DO 7065 05:27:43,600 --> 05:27:50,480 TARGETED SAMPLING BUT TO FIND 7066 05:27:50,480 --> 05:27:52,080 OUT WHETHER IT IS DIFFERENT 7067 05:27:52,080 --> 05:27:53,880 THAN OTHER SPECIES AND WE 7068 05:27:53,880 --> 05:27:55,840 FOUND THAT YES WHAT WE SEE IN 7069 05:27:55,840 --> 05:27:57,600 THE PILL IS A PRESENTATION OF 7070 05:27:57,600 --> 05:27:59,440 THE ENTIRE GI TRACT, NOT JUST 7071 05:27:59,440 --> 05:28:01,360 WHAT YOU FIND IN THE FECES. 7072 05:28:01,360 --> 05:28:03,720 SO THERE ARE SOME CHALLENGES 7073 05:28:03,720 --> 05:28:08,840 WITH THE0s MOT TICK PILL. 7074 05:28:08,840 --> 05:28:10,080 WE ARE WORKING ON NEW VERSIONS 7075 05:28:10,080 --> 05:28:12,080 OF THE PILL AND ONE OF THE 7076 05:28:12,080 --> 05:28:13,880 THINGS WE OBSERVED IS THERE IS 7077 05:28:13,880 --> 05:28:15,760 SOME CONTAMINATION OF THE PILL 7078 05:28:15,760 --> 05:28:16,400 CONTENT DOWNSTREAM AND YOU 7079 05:28:16,400 --> 05:28:23,480 HAVE TO BE ABLE TO SAMPLE 7080 05:28:23,480 --> 05:28:24,840 HIGHLY VISCOUS GI CONTENT. 7081 05:28:24,840 --> 05:28:30,080 SO WE MADE SOME NEW PILLS AS I 7082 05:28:30,080 --> 05:28:31,960 DISCUSSED, AND THESE ARE PILLS 7083 05:28:31,960 --> 05:28:37,200 THAT ACTUALLY WORK BY SAMPLING 7084 05:28:37,200 --> 05:28:39,680 FROM THE LIPS ON THE SIDE AND 7085 05:28:39,680 --> 05:28:42,480 WITH THE ACTION OF THE GI 7086 05:28:42,480 --> 05:28:43,560 TRACT WILL ACTUALLY PUSH THE 7087 05:28:43,560 --> 05:28:45,160 SAMPLE INTO THE PILL. 7088 05:28:45,160 --> 05:28:47,680 AS IT GET IN THE PILL, THERE 7089 05:28:47,680 --> 05:28:50,960 ARE THESE TINY BEADS, WATER 7090 05:28:50,960 --> 05:28:52,080 ABSORBING BEADS AND OVER TIME 7091 05:28:52,080 --> 05:28:54,560 ONCE IT IS FULL, THEY LOCK. 7092 05:28:54,560 --> 05:28:57,080 SO BECAUSE OF THIS CLOSING 7093 05:28:57,080 --> 05:29:06,160 MECHANISM, YOU HAVE ALMOST NO 7094 05:29:06,160 --> 05:29:10,640 LEAKAGE OR CONTAMINATION AND 7095 05:29:10,640 --> 05:29:14,280 ARRIVED AT THE SAME CONCLUSION 7096 05:29:14,280 --> 05:29:25,640 THAT THE PILL HAS LITTLE 7097 05:29:25,640 --> 05:29:26,400 LEAKAGE OR CONTAMINATION. 7098 05:29:26,400 --> 05:29:28,000 WE HAVE A VERSION 3 OF THE 7099 05:29:28,000 --> 05:29:30,400 PILL CALLED THE ARCHIMEDES 7100 05:29:30,400 --> 05:29:30,680 SCREW. 7101 05:29:30,680 --> 05:29:34,920 IT IS A TINY BIOPSY DEVICE, 7102 05:29:34,920 --> 05:29:36,960 VERY GENTLE AND ESSENTIALLY 7103 05:29:36,960 --> 05:29:39,920 ALLOWS SAMPLING OF THE MUCOSA. 7104 05:29:39,920 --> 05:29:43,240 SO I WILL SHOW YOU THIS IS HOW 7105 05:29:43,240 --> 05:29:47,880 IT WORKS, HAS TINY MOTOR AND 7106 05:29:47,880 --> 05:29:51,520 WITH AN ON/OFF CONTROL, 7107 05:29:51,520 --> 05:29:53,040 TRIGGERS THE PILL TO TURN ON 7108 05:29:53,040 --> 05:29:55,920 AND OFF BASED ON WHERE YOU 7109 05:29:55,920 --> 05:29:57,040 WANT THE SAMPLE. 7110 05:29:57,040 --> 05:29:58,680 SO ONCE YOU KNOW WHERE THE 7111 05:29:58,680 --> 05:30:04,160 PILL IS, YOU CAN ACTIVATE IT 7112 05:30:04,160 --> 05:30:06,280 USING A MAGNET WITH THE MOTOR 7113 05:30:06,280 --> 05:30:08,200 INSIDE THAT WILL POTENTIALLY 7114 05:30:08,200 --> 05:30:10,960 ALLOW YOU TO SAMPLE THE 7115 05:30:10,960 --> 05:30:11,800 CONTENT. 7116 05:30:11,800 --> 05:30:13,600 SO DESIGNED CAREFULLY, THIS 7117 05:30:13,600 --> 05:30:18,280 WILL ALSO ALLOW YOU TO SAMPLE 7118 05:30:18,280 --> 05:30:19,240 THE MUCOSAL MICROBIOME. 7119 05:30:19,240 --> 05:30:21,760 SO THIS IS SHOWING THE VIDEO 7120 05:30:21,760 --> 05:30:25,040 FROM THE TOP VIEW AND SOME 7121 05:30:25,040 --> 05:30:25,840 EXPERIMENTAL STUDIES, NEXT 7122 05:30:25,840 --> 05:30:27,200 SHIED, WE WILL MOVE FORWARD 7123 05:30:27,200 --> 05:30:32,760 AND THIS IS THE SAME SET SHOWN 7124 05:30:32,760 --> 05:30:34,440 EARLIER FOR CHARACTERIZING THE 7125 05:30:34,440 --> 05:30:34,880 FUNCTIONALITY. 7126 05:30:34,880 --> 05:30:36,640 BEFORE I END, I JUST WANT TO 7127 05:30:36,640 --> 05:30:38,040 GIVE YOU AN OVERVIEW, THERE IS 7128 05:30:38,040 --> 05:30:40,480 A LOT OF OPPORTUNITIES FOR 7129 05:30:40,480 --> 05:30:44,960 ENGINEERS TO CONTRIBUTE TO 7130 05:30:44,960 --> 05:30:47,480 THIS AREA OF PROBIOTICS. 7131 05:30:47,480 --> 05:30:48,960 OVER THE YEARS, WE HAVE 7132 05:30:48,960 --> 05:30:50,120 DEVELOPED A LOT OF DEVICES AND 7133 05:30:50,120 --> 05:30:53,240 THIS IS JUST SHOWING YOU A 7134 05:30:53,240 --> 05:30:56,000 LANDSCAPE OF WHAT HAS HAPPENED 7135 05:30:56,000 --> 05:30:56,680 SO FAR. 7136 05:30:56,680 --> 05:31:00,280 A PIN CAM IS VERY WELL-KNOWN 7137 05:31:00,280 --> 05:31:02,480 FOR ENDOSCOPY AND I SHOWED YOU 7138 05:31:02,480 --> 05:31:06,360 A PILL THAT CAN DO NONINVASIVE 7139 05:31:06,360 --> 05:31:08,080 BIOPSY, THERE ARE DEVICES THAT 7140 05:31:08,080 --> 05:31:09,840 CAN TRACK WHERE THE PILL IS 7141 05:31:09,840 --> 05:31:11,200 INSIDE THE GI TRACT. 7142 05:31:11,200 --> 05:31:12,960 THERE WAS RECENT WORK ON 7143 05:31:12,960 --> 05:31:14,320 TRACKING, YOU KNOW, ALL THE 7144 05:31:14,320 --> 05:31:20,880 GASSES IN THE SMALL INTESTINE 7145 05:31:20,880 --> 05:31:23,160 SO THIS ALLOWS US TO CAPTURE 7146 05:31:23,160 --> 05:31:26,480 THE FATTY ACIDS IN THE SMALL 7147 05:31:26,480 --> 05:31:27,320 INTESTINE. 7148 05:31:27,320 --> 05:31:28,240 JUST VERY EXCITING WORK 7149 05:31:28,240 --> 05:31:30,400 HAPPENING IN THE AREA OF 7150 05:31:30,400 --> 05:31:31,520 INGESTIBLE DEVICES AND I THINK 7151 05:31:31,520 --> 05:31:33,200 THE COMMUNITY WILL BE VERY 7152 05:31:33,200 --> 05:31:34,960 INTERESTED IN CONTRIBUTING AND 7153 05:31:34,960 --> 05:31:37,480 WITH THAT, I WILL STOP, THANK 7154 05:31:37,480 --> 05:31:38,000 YOU. 7155 05:31:38,000 --> 05:31:43,120 >> OKAY, THANK YOU, OKAY, 7156 05:31:43,120 --> 05:31:43,440 GREAT. 7157 05:31:43,440 --> 05:31:45,680 Dr. VERMA? 7158 05:31:45,680 --> 05:31:49,320 >> OUR NEXT DISCUSSION WILL BE 7159 05:31:49,320 --> 05:31:52,120 HELD BY MY COMODERATOR BUT 7160 05:31:52,120 --> 05:31:52,920 FIRST AN ANNOUNCEMENT? 7161 05:31:52,920 --> 05:31:54,520 >> YES, I KNOW WE ARE A LITTLE 7162 05:31:54,520 --> 05:31:55,840 OVER FOLKS BY TEN MINUTES BUT 7163 05:31:55,840 --> 05:31:57,560 I STILL WANT TO GIVE EVERYBODY 7164 05:31:57,560 --> 05:31:59,280 A FIVE MINUTE BREAK 7165 05:31:59,280 --> 05:32:03,640 >>> AND WELCOME BACK, 7166 05:32:03,640 --> 05:32:07,840 EVERYBODY, AFTER A SHORT BREAK 7167 05:32:07,840 --> 05:32:10,240 BEFORE WE BEGIN OUR QUESTION 7168 05:32:10,240 --> 05:32:19,520 AND ANSWERS SO TAKE IT AWAY. 7169 05:32:19,520 --> 05:32:22,040 >> THIS IS A GREAT WAY TO END 7170 05:32:22,040 --> 05:32:23,080 THE WORKSHOP. 7171 05:32:23,080 --> 05:32:27,080 I FELT THESE TALKS EMPHASIZED 7172 05:32:27,080 --> 05:32:31,280 THE NEED FOR MECHANISTIC DATA 7173 05:32:31,280 --> 05:32:33,680 AND CURRENT CONVENTIONALITY OF 7174 05:32:33,680 --> 05:32:36,000 THE MICROBIOME HOST AND HOW IT 7175 05:32:36,000 --> 05:32:37,400 RELATES TO DISEASE AND I GUESS 7176 05:32:37,400 --> 05:32:39,680 I WOULD START BY SAYING HOW 7177 05:32:39,680 --> 05:32:42,520 CAN WE LEVERAGE THESE 7178 05:32:42,520 --> 05:32:44,040 TECHNOLOGIES, KIND OF MODEL 7179 05:32:44,040 --> 05:32:54,400 THIS FOR THE DYNAMIC NATURE OF 7180 05:32:54,400 --> 05:32:55,080 THE THESE INTERACTIONS? 7181 05:32:55,080 --> 05:32:57,280 OR CAN YOU DO IT, OR IS IT 7182 05:32:57,280 --> 05:32:59,840 JUST ONE MORE DIFFICULTY IN A 7183 05:32:59,840 --> 05:33:04,680 VERY COMPLEX MODELING SYSTEM? 7184 05:33:04,680 --> 05:33:07,160 >> MAYBE I CAN START 7185 05:33:07,160 --> 05:33:07,600 ANSWERING. 7186 05:33:07,600 --> 05:33:11,320 WITH RESPECT TO THE 7187 05:33:11,320 --> 05:33:16,720 LONGITUDINAL MODEL, YES, OF 7188 05:33:16,720 --> 05:33:20,080 COURSE BUT WITH REGARD TO THE 7189 05:33:20,080 --> 05:33:24,200 INTRUSIONS IN THE MOUSE MODELS 7190 05:33:24,200 --> 05:33:36,440 COULD IMPAIR THE FUNCTIONING 7191 05:33:36,440 --> 05:33:38,040 MICROBIAL CONDITION. 7192 05:33:38,040 --> 05:33:40,880 >> OKAY, WHAT ABOUT IN TERMS 7193 05:33:40,880 --> 05:33:44,480 OF THIS, YOU KNOW, THIS TALK 7194 05:33:44,480 --> 05:33:47,600 HAS BEEN A LOT ON THE 7195 05:33:47,600 --> 05:33:49,920 MICROBIOME BUT REALLY 7196 05:33:49,920 --> 05:33:51,040 INVOLVING PROBIOTICS. 7197 05:33:51,040 --> 05:33:53,760 SO WHERE DOES PRECISION 7198 05:33:53,760 --> 05:33:54,480 PROBIOTICS FIT INTO YOUR 7199 05:33:54,480 --> 05:33:56,200 SYSTEM IN TERMS OF HOW THEY 7200 05:33:56,200 --> 05:34:01,080 MIGHT BE USED TO DEVELOP THE 7201 05:34:01,080 --> 05:34:01,960 PRECISION PROBIOTICS? 7202 05:34:01,960 --> 05:34:05,800 >> WELL, IF I LOOK AT OUR 7203 05:34:05,800 --> 05:34:09,880 SITUATION, I WOULD SAY WE 7204 05:34:09,880 --> 05:34:16,240 STARTED FROM IN VIVO WITH THE 7205 05:34:16,240 --> 05:34:18,560 PATIENT, SEE IN THE COMMUNITY 7206 05:34:18,560 --> 05:34:20,120 OTHER FUNCTIONALITIES AND 7207 05:34:20,120 --> 05:34:21,720 TRYING TO CHASE WHAT IS GOING 7208 05:34:21,720 --> 05:34:23,800 ON IN THE ENVIRONMENTS AND 7209 05:34:23,800 --> 05:34:26,320 THAT IS ACTUALLY LEADING US TO 7210 05:34:26,320 --> 05:34:27,880 IDENTIFICATION OF CERTAIN BUGS 7211 05:34:27,880 --> 05:34:28,960 OR CERTAIN FUNCTIONS THAT SEEM 7212 05:34:28,960 --> 05:34:31,720 TO BE MISSING AND WE CAN 7213 05:34:31,720 --> 05:34:34,080 ALLOCATE THESE TO THE SPECIFIC 7214 05:34:34,080 --> 05:34:34,840 SITES OF INFECTION. 7215 05:34:34,840 --> 05:34:38,320 AND I THINK WITH MY TALK, I 7216 05:34:38,320 --> 05:34:41,480 TRIED TO INDICATE HOW WE COULD 7217 05:34:41,480 --> 05:34:43,680 ACTUALLY COMBINE THIS 7218 05:34:43,680 --> 05:34:45,040 INFORMATION TO SEE, OKAY, WHAT 7219 05:34:45,040 --> 05:34:47,480 MIGHT FIT WITH ONE ANOTHER, 7220 05:34:47,480 --> 05:34:49,160 WHAT ARE FUNCTIONAL 7221 05:34:49,160 --> 05:34:50,600 COMPLIMENTARY TO EACH OTHER 7222 05:34:50,600 --> 05:34:52,880 AND THEN TO START COMPOSING 7223 05:34:52,880 --> 05:34:53,360 THESE COCKTAILS. 7224 05:34:53,360 --> 05:34:58,440 SO THAT IS ONE OF THE WAYS 7225 05:34:58,440 --> 05:35:01,720 THAT ARE BEING DEVELOPED AND 7226 05:35:01,720 --> 05:35:07,960 THAT ARE DONE IN VERY SIMPLE 7227 05:35:07,960 --> 05:35:08,640 STRAIGHTFORWARD SYSTEMS BUT 7228 05:35:08,640 --> 05:35:11,560 NEED TO BE DONE IN QUICK 7229 05:35:11,560 --> 05:35:14,120 CLINICAL IN VIVO STUDIES 7230 05:35:14,120 --> 05:35:14,800 BEFORE MEDICAL TRIALS. 7231 05:35:14,800 --> 05:35:17,680 >> AND YOU ALL HAVE QUESTIONS 7232 05:35:17,680 --> 05:35:18,120 FOR EACH OTHER. 7233 05:35:18,120 --> 05:35:23,480 I SEE KURT HAS HIS HAND 7234 05:35:23,480 --> 05:35:23,800 RAISED. 7235 05:35:23,800 --> 05:35:31,960 >> GEMMA IS BEFORE ME. 7236 05:35:31,960 --> 05:35:33,200 >> OKAY, GO AHEAD. 7237 05:35:33,200 --> 05:35:39,520 >> RIGHT, SO AS THE 7238 05:35:39,520 --> 05:35:46,800 PERSPECTIVE OF ENGINEERING I 7239 05:35:46,800 --> 05:35:58,200 SHARED WITH YOU, JUNG, WITH 7240 05:35:58,200 --> 05:36:02,360 PROBIOTICS, WE CAN UNDERSTAND 7241 05:36:02,360 --> 05:36:07,240 HOW THEY TRAIN IN RELATION TO 7242 05:36:07,240 --> 05:36:08,800 THE EPITHELIAL SAMPLES AND 7243 05:36:08,800 --> 05:36:09,840 TRACING THOSE FROM DIFFERENT 7244 05:36:09,840 --> 05:36:11,880 LOCATIONS OF THE PATIENT, 7245 05:36:11,880 --> 05:36:16,880 EITHER SMALL OR LARGE 7246 05:36:16,880 --> 05:36:19,600 INTESTINE AND ALSO YOU CAN 7247 05:36:19,600 --> 05:36:22,440 MATCH THE DIFFERENT TYPE OF 7248 05:36:22,440 --> 05:36:23,280 MICROORGANISMS AS WELL. 7249 05:36:23,280 --> 05:36:26,920 SO THAT IS ONE POSSIBLE 7250 05:36:26,920 --> 05:36:31,960 APPROACH THAT OUR SYSTEM CAN 7251 05:36:31,960 --> 05:36:33,600 CONTRIBUTE FROM IN STUDY AS IT 7252 05:36:33,600 --> 05:36:38,080 IS NOW. 7253 05:36:38,080 --> 05:36:38,960 >> THANK YOU, CURTIS? 7254 05:36:38,960 --> 05:36:40,880 >> SOMETHING TOM SAID 7255 05:36:40,880 --> 05:36:43,000 RESONATED WITH ME IN RESPONSE 7256 05:36:43,000 --> 05:36:50,440 TO BOTH OF QUESTIONS IN 7257 05:36:50,440 --> 05:36:52,240 THAT FROM A BIOPERSPECTIVE, 7258 05:36:52,240 --> 05:36:53,880 SOMETHING WE FOUND HELPFUL AND 7259 05:36:53,880 --> 05:36:55,280 MANY OF US HIGHLIGHTED THIS 7260 05:36:55,280 --> 05:36:56,600 AFTERNOON, THE IMPORTANCE OF 7261 05:36:56,600 --> 05:37:02,320 SLIDING BACK AND FORTH ALONG 7262 05:37:02,320 --> 05:37:04,840 THAT SCALE BETWEEN BIG 7263 05:37:04,840 --> 05:37:08,880 POPULATION STUDIES AND THEN 7264 05:37:08,880 --> 05:37:09,480 IMMUNOLOGICAL BIOLOGICAL 7265 05:37:09,480 --> 05:37:10,640 MECHANISTIC STUDIES AND IT IS 7266 05:37:10,640 --> 05:37:12,120 EASY FOR ONE PROJECT TO GET 7267 05:37:12,120 --> 05:37:14,080 STUCK AT ONE END OF THAT 7268 05:37:14,080 --> 05:37:16,600 STRICT TRUM BUT IN ORDER TO 7269 05:37:16,600 --> 05:37:19,160 FIND AND TRANSLATE PROBIOTICS 7270 05:37:19,160 --> 05:37:20,880 DEFINED BROADLY, BEING ABLE TO 7271 05:37:20,880 --> 05:37:22,160 MOVE FROM ONE INTO THE OTHER 7272 05:37:22,160 --> 05:37:26,600 AND BACK IS PARTICULARLY 7273 05:37:26,600 --> 05:37:27,440 HELPFUL. 7274 05:37:27,440 --> 05:37:28,080 >> ONE. QUESTIONS WE HAD 7275 05:37:28,080 --> 05:37:29,920 COMING IN JUST DURING THE 7276 05:37:29,920 --> 05:37:33,000 CHAT, I THINK IT WAS TO TOM 7277 05:37:33,000 --> 05:37:34,920 AND ABOUT THE CHEMICAL 7278 05:37:34,920 --> 05:37:37,760 COMPOSITION OF THE MEDIUM SO I 7279 05:37:37,760 --> 05:37:38,880 THINK YOU MAY HAVE SAID 7280 05:37:38,880 --> 05:37:42,880 SOMETHING IN THE CHAT BUT OUR 7281 05:37:42,880 --> 05:37:44,840 AUDIENCE AT LARGE MAY BE 7282 05:37:44,840 --> 05:37:47,360 INTERESTED SO WHAT IS THE 7283 05:37:47,360 --> 05:37:50,680 EXPECTED LOOMAL FACTORS ON ALL 7284 05:37:50,680 --> 05:37:51,880 YOUR OUTCOMES? 7285 05:37:51,880 --> 05:37:56,040 >> WELL, IT IS HUGE. 7286 05:37:56,040 --> 05:38:01,600 WE WORK IN A CONVENTIONAL 7287 05:38:01,600 --> 05:38:07,120 BASIS BUT IF YOU ARE TRYING TO 7288 05:38:07,120 --> 05:38:08,600 TAKE FECAL SAMPLES FROM 7289 05:38:08,600 --> 05:38:11,080 DONORS, OF COURSE YOU HAVE TO 7290 05:38:11,080 --> 05:38:12,920 CONSIDER THE FIBER INTAKE 7291 05:38:12,920 --> 05:38:14,760 OTHER OTHER THINGS THAT MIGHT 7292 05:38:14,760 --> 05:38:19,600 HAVE AN IMPACT ON NOT ONLY 7293 05:38:19,600 --> 05:38:22,640 UPPER DIGESTION BUT ALSO 7294 05:38:22,640 --> 05:38:23,000 MICROBIAL. 7295 05:38:23,000 --> 05:38:27,520 AND IT HAS A TREMENDOUS 7296 05:38:27,520 --> 05:38:33,280 DIFFERENCE AND YOU CAN SEE 7297 05:38:33,280 --> 05:38:36,560 FROM THE BIOGRAPH CALL GROWTH 7298 05:38:36,560 --> 05:38:42,040 ON ONE HAND AND THEN ON THE 7299 05:38:42,040 --> 05:38:43,560 OTHER HAND, TOTALLY DIFFERENT 7300 05:38:43,560 --> 05:38:44,680 SO YES, THAT IS ONE THING YOU 7301 05:38:44,680 --> 05:38:47,880 HAVE TO TAKE INTO THE 7302 05:38:47,880 --> 05:38:48,280 EQUATION. 7303 05:38:48,280 --> 05:38:49,480 >> ANOTHER QUESTION COMING IN 7304 05:38:49,480 --> 05:38:52,640 THROUGH THE CHAT WAS ABOUT THE 7305 05:38:52,640 --> 05:38:54,320 WILDLING MICE IN TERMS OF HOW 7306 05:38:54,320 --> 05:38:56,400 LONG, HOW MANY GENERATIONS 7307 05:38:56,400 --> 05:39:02,160 THEY RETAIN THEIR MICROBIOME 7308 05:39:02,160 --> 05:39:03,000 AS WILDLING MICE? 7309 05:39:03,000 --> 05:39:05,200 >> YEAH, WE DON'T KNOW. 7310 05:39:05,200 --> 05:39:07,480 I ASSUME EVENTUALLY SOMETHING 7311 05:39:07,480 --> 05:39:08,160 WILL GET LOST. 7312 05:39:08,160 --> 05:39:12,040 WE ARE CURRENTLY AT GENERATION 7313 05:39:12,040 --> 05:39:18,080 6-7 AND IT IS THE SAME 7314 05:39:18,080 --> 05:39:24,400 PHENOTYPE AND WE HAVE KNOCKOUT 7315 05:39:24,400 --> 05:39:29,560 WILD MICE AND WE ASSUME THAT 7316 05:39:29,560 --> 05:39:33,440 THE PATHOGENS MAY ALSO NOT BE 7317 05:39:33,440 --> 05:39:35,920 THAT COMMON SO I THINK 7318 05:39:35,920 --> 05:39:37,560 EVENTUALLY WE WILL HAVE TO 7319 05:39:37,560 --> 05:39:38,960 EXPOSE THEM AGAIN BUT SO FAR 7320 05:39:38,960 --> 05:39:42,360 IT HAS BEEN STABLE. 7321 05:39:42,360 --> 05:39:44,200 >> OKAY, A QUESTION COMING IN 7322 05:39:44,200 --> 05:39:48,680 FROM THE AUDIENCE AT LARGE AND 7323 05:39:48,680 --> 05:39:52,120 THAT IS TO Dr. VALKAS WHICH 7324 05:39:52,120 --> 05:39:56,240 IS THE E. COLI USED TO TREAT 7325 05:39:56,240 --> 05:39:57,880 PATIENTS, BENEFICIAL PATIENTS 7326 05:39:57,880 --> 05:40:02,120 WITH IBD, YOU SAID IT WAS 7327 05:40:02,120 --> 05:40:05,200 PHENO TOXIC AND SO THE 7328 05:40:05,200 --> 05:40:07,760 QUESTION IS, IS THAT INVENTED 7329 05:40:07,760 --> 05:40:10,960 OR DOES THIS STRAIN HAVE 7330 05:40:10,960 --> 05:40:12,160 PREVENTIVE OR LOW-LYING 7331 05:40:12,160 --> 05:40:13,360 PROTECTION AS WELL? 7332 05:40:13,360 --> 05:40:15,520 >> YEAH, KIND OF THE DEBATE 7333 05:40:15,520 --> 05:40:18,480 ABOUT WHAT THESE GENES ARE 7334 05:40:18,480 --> 05:40:23,640 DOING IN THE MUCOSAL HAS BEEN 7335 05:40:23,640 --> 05:40:27,920 GOING BACK AND FORTH NOW WITH 7336 05:40:27,920 --> 05:40:29,480 TWO GROUPS REPORTING DIFFERENT 7337 05:40:29,480 --> 05:40:32,120 GENOTYPES AND THERE IS ALSO 7338 05:40:32,120 --> 05:40:33,720 INTERESTINGLY SOME CROSS TALK 7339 05:40:33,720 --> 05:40:41,320 WITH PROTEINS INVOLVED AND 7340 05:40:41,320 --> 05:40:42,760 MAKING THIS UNITOXIN AND 7341 05:40:42,760 --> 05:40:44,520 TRANSPORT SOME OF THE PRODUCTS 7342 05:40:44,520 --> 05:40:46,080 THAT ARE SUPPOSED TO BE 7343 05:40:46,080 --> 05:40:48,520 INVOLVED IN THE BENEFICIAL 7344 05:40:48,520 --> 05:40:50,680 EFFECTS OF THE MUCOSAL. 7345 05:40:50,680 --> 05:40:55,280 SO THERE IS KIND OF, YEAH, BIG 7346 05:40:55,280 --> 05:40:56,680 QUESTIONS REGARDING YOU CAN -- 7347 05:40:56,680 --> 05:40:59,000 IF THIS STRAIN HAS BEEN USED 7348 05:40:59,000 --> 05:41:01,400 FOR SO LONG, YOU KNOW, IS THAT 7349 05:41:01,400 --> 05:41:03,040 MAYBE AN INDICATION THAT, YOU 7350 05:41:03,040 --> 05:41:05,080 KNOW, IT IS NOT LIKELY TO 7351 05:41:05,080 --> 05:41:07,600 REALLY BE INVOLVED IN CANCER 7352 05:41:07,600 --> 05:41:07,960 IN HUMANS? 7353 05:41:07,960 --> 05:41:11,440 THERE IS STILL A LOT OF 7354 05:41:11,440 --> 05:41:13,040 QUESTIONS ABOUT WHETHER THE 7355 05:41:13,040 --> 05:41:14,400 ACTIVITY IS ACTUALLY OCCURRING 7356 05:41:14,400 --> 05:41:17,280 IN PATIENTS WHO ARE TAKING 7357 05:41:17,280 --> 05:41:17,680 THIS STRAIN. 7358 05:41:17,680 --> 05:41:19,680 CERTAINLY I THINK IT MAY 7359 05:41:19,680 --> 05:41:21,280 DEPEND ON WHERE THE STRAIN IS 7360 05:41:21,280 --> 05:41:23,120 IN THE GUT AND PARTICULARLY 7361 05:41:23,120 --> 05:41:28,880 WHETHER IT CAN CONTACT THE GUT 7362 05:41:28,880 --> 05:41:31,720 EPITHELIUM BECAUSE THE RESULT 7363 05:41:31,720 --> 05:41:34,080 FROM EXPOSURE IS CONTACT 7364 05:41:34,080 --> 05:41:37,480 DEPENDENT SO IF THE ORGANS ARE 7365 05:41:37,480 --> 05:41:39,080 NOT CONTACTING THE FECAL 7366 05:41:39,080 --> 05:41:47,040 CELLS, THERE SHOULDN'T BE 7367 05:41:47,040 --> 05:41:48,400 GINO -- GENOTOXICITY SO A LOT 7368 05:41:48,400 --> 05:41:50,760 OF QUESTIONS STILL COMING. 7369 05:41:50,760 --> 05:41:52,880 >> SO WE WOULD ALL LOVE TO 7370 05:41:52,880 --> 05:41:54,360 HEAR YOUR THOUGHTS ON WHAT ARE 7371 05:41:54,360 --> 05:41:55,600 THE CRITICAL THOUGHTS IN OUR 7372 05:41:55,600 --> 05:41:57,440 KNOWLEDGE, SOME OF THE 7373 05:41:57,440 --> 05:41:59,880 METHODOLOGY, GAPS IN THE 7374 05:41:59,880 --> 05:42:01,640 METHODOLOGY FOR THE RESEARCH 7375 05:42:01,640 --> 05:42:03,600 AREAS OR, YOU KNOW, WHAT NEW 7376 05:42:03,600 --> 05:42:05,080 RESOURCES OR METHODS ARE 7377 05:42:05,080 --> 05:42:06,560 NEEDED TO FILL THESE GAPS IN 7378 05:42:06,560 --> 05:42:11,000 EITHER THE SHORT OR LONG-TERM. 7379 05:42:11,000 --> 05:42:12,600 SO WE WOULD LOVE TO HAVE A 7380 05:42:12,600 --> 05:42:15,120 LITTLE BIT OF YOUR INSIGHTS 7381 05:42:15,120 --> 05:42:15,880 INTO THESE AREAS. 7382 05:42:15,880 --> 05:42:32,440 THESE ARE THE QUESTIONS FROM 7383 05:42:32,440 --> 05:42:32,880 EACH SESSION. 7384 05:42:32,880 --> 05:42:35,240 >> YOU WANT TO GO FIRST? 7385 05:42:35,240 --> 05:42:37,280 >> YES, WHAT CONFUSES ME IS 7386 05:42:37,280 --> 05:42:41,120 THIS SINGLE CELL SORTING SO 7387 05:42:41,120 --> 05:42:44,760 BASED ON THE SORTER, YOU CAN 7388 05:42:44,760 --> 05:42:48,840 ACTUALLY LOOK AT FUNCTIONAL 7389 05:42:48,840 --> 05:42:51,680 MICROBES AND ALSO SPECIFIC 7390 05:42:51,680 --> 05:42:52,440 LABELING OF THESE. 7391 05:42:52,440 --> 05:43:01,640 ONE CAN ALSO LOOK AT SPECIFIC 7392 05:43:01,640 --> 05:43:03,400 METABOLIC INTERACTIONS SUCH AS 7393 05:43:03,400 --> 05:43:06,560 METABOLISM AND SEE TO WHAT 7394 05:43:06,560 --> 05:43:12,040 EXTENT THE MICROBES ARE 7395 05:43:12,040 --> 05:43:13,800 DIRECTED IN METABOLISM. 7396 05:43:13,800 --> 05:43:16,480 AND I THINK NEXT STEP WOULD 7397 05:43:16,480 --> 05:43:18,880 BE, OKAY, HOW CAN WE FURTHER 7398 05:43:18,880 --> 05:43:19,560 ADVANCE THAT INSIGHT. 7399 05:43:19,560 --> 05:43:21,200 SO IF YOU CAN SEPARATE THEM, 7400 05:43:21,200 --> 05:43:24,360 CAN YOU ALSO STUDY THEM IN 7401 05:43:24,360 --> 05:43:33,680 MORE DETAIL JUST FROM AN ANA 7402 05:43:33,680 --> 05:43:35,680 TOMIC PERSPECTIVE AND AN 7403 05:43:35,680 --> 05:43:36,600 INTERESTING QUESTION FOR 7404 05:43:36,600 --> 05:43:39,320 ISOLATION PURPOSES SO THAT IS 7405 05:43:39,320 --> 05:43:42,640 SOMETHING I AM VERY 7406 05:43:42,640 --> 05:43:43,440 INTERESTED. 7407 05:43:43,440 --> 05:43:43,680 IN. 7408 05:43:43,680 --> 05:43:46,880 >> OKAY, YOU ALSO HAD YOUR 7409 05:43:46,880 --> 05:43:47,680 HAND UP? 7410 05:43:47,680 --> 05:43:49,680 >> YES FROM, A SIMILAR 7411 05:43:49,680 --> 05:43:50,880 PERSPECTIVE WITH MY PREVIOUS 7412 05:43:50,880 --> 05:44:07,400 COMMENTS THAT THE GLASS HALF 7413 05:44:07,400 --> 05:44:08,040 EMPTY ANSWER MIGHT BE THAT 7414 05:44:08,040 --> 05:44:08,680 THERE IS OF COURSE NO SILVER 7415 05:44:08,680 --> 05:44:09,400 BULLET BUT THE GLASS HALF FULL 7416 05:44:09,400 --> 05:44:10,080 ANSWER FROM SOMEBODY WHO WORKS 7417 05:44:10,080 --> 05:44:10,720 IN THE ENVIRONMENT THAT IS 7418 05:44:10,720 --> 05:44:11,440 ENRICHED FOR HUMAN POPULATION 7419 05:44:11,440 --> 05:44:12,080 GENETICISTS FOR EXAMPLE AND 7420 05:44:12,080 --> 05:44:15,200 OTHER TYPES OF MOLECULAR 7421 05:44:15,200 --> 05:44:16,880 ETIOLOGY, HUMAN SEQUENCING 7422 05:44:16,880 --> 05:44:17,680 DIDN'T SOLVE EVERYTHING 20 7423 05:44:17,680 --> 05:44:18,720 YEARS AGO AND EVERYTHING BUILT 7424 05:44:18,720 --> 05:44:20,320 ON THAT TO ADDRESS THESE 7425 05:44:20,320 --> 05:44:22,280 QUESTIONS IN HUMAN GENETICS 7426 05:44:22,280 --> 05:44:24,920 HAVE BEEN BETTER IN THE THODZ 7427 05:44:24,920 --> 05:44:26,760 FOR POPULATION STUDIES, BETTER 7428 05:44:26,760 --> 05:44:27,800 TECHNOLOGIES AND ANALYTIC 7429 05:44:27,800 --> 05:44:33,200 METHODS FOR WIN KNOWING OUT 7430 05:44:33,200 --> 05:44:35,120 SIGNAL VERSUS NOISE, 7431 05:44:35,120 --> 05:44:36,640 COLLECTING FROM MORE DIVERSE 7432 05:44:36,640 --> 05:44:38,480 POPULATIONS AND THEN JUST 7433 05:44:38,480 --> 05:44:40,640 ELBOW GREASE ON FOLLOWING UP 7434 05:44:40,640 --> 05:44:43,960 ON THE ESPECIALLY TEAM LOGICAL 7435 05:44:43,960 --> 05:44:44,600 PART IN DETAIL. 7436 05:44:44,600 --> 05:44:46,560 SO WE HAVE SEEN THAT PLAY OUT 7437 05:44:46,560 --> 05:44:50,560 IN TERMS OF HUMAN GENETICS THE 7438 05:44:50,560 --> 05:44:52,200 LAST FEW YEARS. 7439 05:44:52,200 --> 05:44:55,320 AND I FORGOT TO SHOW THE CURVE 7440 05:44:55,320 --> 05:44:56,960 IN THE PRESENTATION EARLIER 7441 05:44:56,960 --> 05:44:57,800 BUT WE'RE STILL AT THE 7442 05:44:57,800 --> 05:45:01,680 BEGINNING OF THAT PROCESS FOR 7443 05:45:01,680 --> 05:45:02,960 MICROBIOTIC DEVELOPMENT. 7444 05:45:02,960 --> 05:45:05,320 WE NEED BIGGER, MORE DIVERSE 7445 05:45:05,320 --> 05:45:07,680 POPULATIONS WITH MORE CAREFUL 7446 05:45:07,680 --> 05:45:08,840 METHODOLOGIES AND THEN JUST 7447 05:45:08,840 --> 05:45:11,160 PLAIN FOLLOWING UP ON WHAT THE 7448 05:45:11,160 --> 05:45:11,960 MECHANISMS AND PROMISING HITS 7449 05:45:11,960 --> 05:45:13,920 OF THE BEST COUPLE OF THOUSAND 7450 05:45:13,920 --> 05:45:15,520 OUT OF THE TOTAL POSSIBLE 7451 05:45:15,520 --> 05:45:21,280 MILLIONS OF HITS WE GET FROM 7452 05:45:21,280 --> 05:45:21,600 THOSE. 7453 05:45:21,600 --> 05:45:25,840 >> ANY OTHER TAKERS ON THIS 7454 05:45:25,840 --> 05:45:26,320 QUESTION? 7455 05:45:26,320 --> 05:45:30,120 ONE OF THE THINGS -- 7456 05:45:30,120 --> 05:45:32,280 >> I GUESS I WILL JUST FILL 7457 05:45:32,280 --> 05:45:33,880 OUT WHAT TOM SAID. 7458 05:45:33,880 --> 05:45:40,960 ALSO I THINK GENERALLY INSIGHT 7459 05:45:40,960 --> 05:45:43,680 TO TRANSFER, GOING TO BE VERY 7460 05:45:43,680 --> 05:45:44,880 BORING, VERY TECHNICAL ANSWER 7461 05:45:44,880 --> 05:45:46,280 BUT WE STILL DON'T HAVE A GOOD 7462 05:45:46,280 --> 05:45:48,440 WAY TO LOOK AT WHAT MICROBES 7463 05:45:48,440 --> 05:45:49,840 ARE DOING WHERE THEY ARE DOING 7464 05:45:49,840 --> 05:45:51,800 IT IN AN UNBIASED, BROADER 7465 05:45:51,800 --> 05:45:52,160 WAY. 7466 05:45:52,160 --> 05:45:54,680 AND WE CAN DO THIS MAYBE A 7467 05:45:54,680 --> 05:45:56,720 LITTLE BIT ONE GENE AT A TIME 7468 05:45:56,720 --> 05:45:59,040 BUT I THINK IT WOULD BE -- 7469 05:45:59,040 --> 05:46:01,280 YEAH, IT WOULD BE PRETTY 7470 05:46:01,280 --> 05:46:03,000 REVOLUTIONARY TO BE ABLE TO DO 7471 05:46:03,000 --> 05:46:05,160 THAT ON A GENOME SCALE AND 7472 05:46:05,160 --> 05:46:08,080 RIGHT NOW I GUESS MAYBE CURTIS 7473 05:46:08,080 --> 05:46:11,720 OR OTHERS COULD COMMENT BUT I 7474 05:46:11,720 --> 05:46:14,160 THINK JUST MICROBIAL 7475 05:46:14,160 --> 05:46:15,960 TRANSCRIPTOMICS GENERALLY IS 7476 05:46:15,960 --> 05:46:17,240 STILL RELATIVELY UNDER 7477 05:46:17,240 --> 05:46:18,600 UTILIZED AND I DON'T KNOW IF 7478 05:46:18,600 --> 05:46:21,040 THAT IS BECAUSE EVERYONE HAS 7479 05:46:21,040 --> 05:46:22,200 CONVERGED ON THE IDEA IN A IF 7480 05:46:22,200 --> 05:46:24,080 YOU ARE GETTING RNA FROM 7481 05:46:24,080 --> 05:46:25,800 STOOL, IT IS NOT MEANINGFUL 7482 05:46:25,800 --> 05:46:28,680 ANY WAY BECAUSE THAT IS NOT 7483 05:46:28,680 --> 05:46:29,720 WHERE THE MEANINGFUL THING IS 7484 05:46:29,720 --> 05:46:31,920 HAPPENING OR IF THERE ARE 7485 05:46:31,920 --> 05:46:33,200 OTHER TECHNICAL REASONS THAT 7486 05:46:33,200 --> 05:46:35,880 THIS IS STILL -- YEAH, FEW AND 7487 05:46:35,880 --> 05:46:37,640 FAR BETWEEN, THESE KINDS OF 7488 05:46:37,640 --> 05:46:38,080 STUDIES. 7489 05:46:38,080 --> 05:46:40,400 >> IN OUR HANDS, THERE ARE 7490 05:46:40,400 --> 05:46:41,280 DEFINITELY TECHNICAL HURDLES 7491 05:46:41,280 --> 05:46:43,360 STILL, WHERE IT IS JUST PLAIN 7492 05:46:43,360 --> 05:46:46,520 HARD TO GET GOOD UNBIASED 7493 05:46:46,520 --> 05:46:55,680 OSAMA RNA FROM THE STOOL SO 7494 05:46:55,680 --> 05:47:00,680 THE COMBINATION OF EXTRACTION 7495 05:47:00,680 --> 05:47:02,680 AND DEPLETION OF RNA AND 7496 05:47:02,680 --> 05:47:03,640 SEQUENCING OF A SUFFICIENT 7497 05:47:03,640 --> 05:47:05,400 AMOUNT OF MATERIAL FROM THE 7498 05:47:05,400 --> 05:47:06,600 RESULTING EXTRACT, IT IS JUST 7499 05:47:06,600 --> 05:47:08,520 PLAIN TOUGH TO PUT ALL THOSE 7500 05:47:08,520 --> 05:47:09,080 STEPS TOGETHER. 7501 05:47:09,080 --> 05:47:12,000 SO I HAVE LEAN IS BE REALLY A 7502 05:47:12,000 --> 05:47:12,680 TECHNICAL CHALLENGE. 7503 05:47:12,680 --> 05:47:14,920 IN THE FEW CASES WHERE WE HAVE 7504 05:47:14,920 --> 05:47:18,200 BEEN ABLE TO GET MICROBIAL 7505 05:47:18,200 --> 05:47:21,520 TRANSCRIPTO ME DATA, IT IS NOT 7506 05:47:21,520 --> 05:47:23,960 THE END YOU WILL BE ALL, YOU 7507 05:47:23,960 --> 05:47:25,280 HAVE TO GET IT IN THE RIGHT 7508 05:47:25,280 --> 05:47:27,720 PLACE AT THE RIGHT TIME BUT 7509 05:47:27,720 --> 05:47:28,720 DEFINITELY INFORMATIVE WHEN 7510 05:47:28,720 --> 05:47:30,840 YOU CAN GET IT. 7511 05:47:30,840 --> 05:47:31,320 [LAUGHTER] 7512 05:47:31,320 --> 05:47:31,680 >> GREAT. 7513 05:47:31,680 --> 05:47:33,480 I WAS GOING TO SAY ONE OF THE 7514 05:47:33,480 --> 05:47:36,680 THINGS TO KIND OF ANNOUNCE TO 7515 05:47:36,680 --> 05:47:40,880 EVERYBODY WHO MAY NOT ALREADY 7516 05:47:40,880 --> 05:47:41,440 KNOW IT, THERE IS AN 7517 05:47:41,440 --> 05:47:45,480 ANNOUNCEMENT OF FUNDING, 7518 05:47:45,480 --> 05:47:47,480 OPPORTUNITY ANNOUNCEMENT 7519 05:47:47,480 --> 05:47:53,720 IDENTIFYING MICROBIAL 7520 05:47:53,720 --> 05:47:58,720 M ETABOLITES AND THE NUMBER IS 7521 05:47:58,720 --> 05:48:00,120 PAR-21-253 AND YOU CAN E-MAIL 7522 05:48:00,120 --> 05:48:03,440 ANY OF US TO GET IT. 7523 05:48:03,440 --> 05:48:19,280 THE INSTITUTE HAS A NUMBER OF 7524 05:48:19,280 --> 05:48:20,480 THEM. 7525 05:48:20,480 --> 05:48:20,960 [INDISCERNIBLE] 7526 05:48:20,960 --> 05:48:24,280 SO PLEASE LOOK AT THAT FOR A 7527 05:48:24,280 --> 05:48:24,880 FUNDING OPPORTUNITY. 7528 05:48:24,880 --> 05:48:26,440 ANYTHING ELSE THAT YOU WOULD 7529 05:48:26,440 --> 05:48:35,280 LIKE TO ASK EACH OTHER? 7530 05:48:35,280 --> 05:48:35,640 SAMEER? 7531 05:48:35,640 --> 05:48:36,840 >> YES, I JUST DIDN'T GET A 7532 05:48:36,840 --> 05:48:39,520 CHANCE TO TALK ABOUT ONE OF 7533 05:48:39,520 --> 05:48:41,680 THE ASPECTS THAT WAS POSSIBLE 7534 05:48:41,680 --> 05:48:42,480 WITH THE INGESTIBLE DEVICES 7535 05:48:42,480 --> 05:48:46,120 AND I KNOW WE TALKED ABOUT 7536 05:48:46,120 --> 05:48:48,680 GRAFTING TO PROVIDE THE EXACT 7537 05:48:48,680 --> 05:48:52,600 LOCATION WHERE YOU WANT IN 7538 05:48:52,600 --> 05:48:53,080 VIVO. 7539 05:48:53,080 --> 05:48:56,320 THE PILL CAN ALSO BE USED AS A 7540 05:48:56,320 --> 05:49:02,880 TARGETED DEVICE TO DELIVER 7541 05:49:02,880 --> 05:49:04,840 PROBIOTICS FOR WHAT YOU WANT 7542 05:49:04,840 --> 05:49:07,320 FOR A TARGETED LOCATION BASED 7543 05:49:07,320 --> 05:49:08,720 ON WHERE YOU IMMOBILIZE THE 7544 05:49:08,720 --> 05:49:10,400 PILL AND RELEASE. 7545 05:49:10,400 --> 05:49:17,840 SO THIS WILL ALSO TAKE FROM 7546 05:49:17,840 --> 05:49:19,280 THE IMPOSITION FROM THE 7547 05:49:19,280 --> 05:49:21,040 APPROACH IS ALSO DELIVERY. 7548 05:49:21,040 --> 05:49:22,680 SO THERE IS A LOT OF CONTROL 7549 05:49:22,680 --> 05:49:25,680 OVER THE SPATIAL AND TEMPORAL 7550 05:49:25,680 --> 05:49:28,200 ASPECT NOT JUST FOR SAMPLING 7551 05:49:28,200 --> 05:49:31,320 BUT ALSO TO TARGET BI 7552 05:49:31,320 --> 05:49:31,720 DIRECTIONAL. 7553 05:49:31,720 --> 05:49:32,920 YOU CAN SAMPLE AND WHILE YOU 7554 05:49:32,920 --> 05:49:35,320 ARE DOING THAT, THERE IS A 7555 05:49:35,320 --> 05:49:38,560 POTENTIAL THERE TO HAVE BI 7556 05:49:38,560 --> 05:49:39,800 DIRECTIONAL CAPABILITIES THAT 7557 05:49:39,800 --> 05:49:43,280 WE HAVEN'T EVEN EXPLORED. 7558 05:49:43,280 --> 05:49:45,840 I AM SURE I AM GOING TO GET A 7559 05:49:45,840 --> 05:49:47,520 LOT OF FEEDBACK FROM ALL OF 7560 05:49:47,520 --> 05:49:49,280 YOU AND LOVE TO HEAR FROM ALL 7561 05:49:49,280 --> 05:49:51,480 OF YOU BUT THERE IS A LOT OF 7562 05:49:51,480 --> 05:49:52,280 POSSIBILITY WE HAVEN'T 7563 05:49:52,280 --> 05:49:53,200 EXPLORED FROM THE 7564 05:49:53,200 --> 05:49:53,720 TECHNOLOGICAL SIDE. 7565 05:49:53,720 --> 05:49:57,680 SO I WOULD SAY JUST BRING YOUR 7566 05:49:57,680 --> 05:49:59,200 VISION OUT, PUT IT OUT THERE 7567 05:49:59,200 --> 05:50:01,280 AND LET US FIGURE IT OUT. 7568 05:50:01,280 --> 05:50:03,200 AND YOU KNOW IT MAY BE HARD 7569 05:50:03,200 --> 05:50:04,840 BUT WE WILL START SOMEWHERE 7570 05:50:04,840 --> 05:50:07,520 AND I THINK THERE IS A BIT OF 7571 05:50:07,520 --> 05:50:10,240 FAST-FORWARD TO GETTING THERE. 7572 05:50:10,240 --> 05:50:12,680 SO JUST COUPLE OF RESPONSES 7573 05:50:12,680 --> 05:50:14,920 HERE. 7574 05:50:14,920 --> 05:50:20,800 THANKS. 7575 05:50:20,800 --> 05:50:21,480 >> THANK YOU. 7576 05:50:21,480 --> 05:50:22,960 >> I KNOW THAT IT IS KIND OF 7577 05:50:22,960 --> 05:50:24,480 TOWARDS THE END OF THE DAY, 7578 05:50:24,480 --> 05:50:27,240 THAT EVERYBODY IS QUITE TIRED 7579 05:50:27,240 --> 05:50:31,680 AS THIS HAS BEEN A WONDERFUL 7580 05:50:31,680 --> 05:50:33,920 PRODUCTIVE MEETING -- 7581 05:50:33,920 --> 05:50:36,080 >> SORRY, DID YOU SEE TOM HAS 7582 05:50:36,080 --> 05:50:36,880 HIS HAND RAISED? 7583 05:50:36,880 --> 05:50:38,880 >> NO, I DID NOT, TOM? 7584 05:50:38,880 --> 05:50:39,960 >> YEAH, THANKS FOR THAT. 7585 05:50:39,960 --> 05:50:42,880 MAYBE I HAVE A QUESTION FOR 7586 05:50:42,880 --> 05:50:52,480 Dr. KIM THAT RELATES TO THE 7587 05:50:52,480 --> 05:50:53,640 DIMENSIONS OF THE MOUSE AND 7588 05:50:53,640 --> 05:50:56,840 THE IMPORTANCE ON THE 7589 05:50:56,840 --> 05:50:57,880 MICROBIOME, JUST WONDERING 7590 05:50:57,880 --> 05:51:01,800 WHAT IS THE DIMENSION OF THE 7591 05:51:01,800 --> 05:51:03,760 MUCOSAL LAYER THAT WE CAN 7592 05:51:03,760 --> 05:51:05,480 GENERATE INTO THE TIPS YOU ARE 7593 05:51:05,480 --> 05:51:07,720 GENERATING AND DOES IT ALSO 7594 05:51:07,720 --> 05:51:09,880 COME, AS YOU DEMONSTRATED 7595 05:51:09,880 --> 05:51:11,360 THERE IS OXYGEN GRADIENT BUT 7596 05:51:11,360 --> 05:51:12,760 YOU HAVE THAT FURTHER 7597 05:51:12,760 --> 05:51:15,160 EXTENDING INTO A MUCOUS LAYER 7598 05:51:15,160 --> 05:51:18,360 IN THE SYSTEM AS WELL AND IF 7599 05:51:18,360 --> 05:51:21,440 SO, IS THERE A DIFFERENCE 7600 05:51:21,440 --> 05:51:24,520 BETWEEN LOWER AND UPPER GI 7601 05:51:24,520 --> 05:51:28,120 WITH DIFFERENT THICKNESSES OF 7602 05:51:28,120 --> 05:51:28,680 THE MUCOSAL CELLS? 7603 05:51:28,680 --> 05:51:34,840 >> SO I WILL GIVE YOU A COUPLE 7604 05:51:34,840 --> 05:51:37,720 OF DIFFERENT ANSWERS. 7605 05:51:37,720 --> 05:51:40,160 FIRST QUESTION, IN TERMS OF 7606 05:51:40,160 --> 05:51:43,920 THE LOCATIONS FOR CREATING THE 7607 05:51:43,920 --> 05:51:47,600 MUCOUS LAYER AND IT DEPENDS ON 7608 05:51:47,600 --> 05:51:49,880 HOW YOU STRUCTURE IT. 7609 05:51:49,880 --> 05:51:54,200 SO IN THIS CASE, WE ARE 7610 05:51:54,200 --> 05:51:56,680 PREPARING THE PATIENTS AHEAD 7611 05:51:56,680 --> 05:51:58,880 OF TIME, YOU CAN GIVE THEM A 7612 05:51:58,880 --> 05:52:01,280 PILL FOR GENERATING MORE 7613 05:52:01,280 --> 05:52:04,920 MUCOUS AND THEN MAYBE GREATER 7614 05:52:04,920 --> 05:52:13,520 OXYGEN, POTENTIALLY CHANGE THE 7615 05:52:13,520 --> 05:52:17,160 FILTRATION BUT WE DON'T 7616 05:52:17,160 --> 05:52:17,880 NORMALLY INCREASE MUCOUS BUT 7617 05:52:17,880 --> 05:52:20,840 THERE IS A PROCESS FOR THAT. 7618 05:52:20,840 --> 05:52:25,920 AND THEN TAKING THE CELLS AND 7619 05:52:25,920 --> 05:52:30,480 BASICALLY SAYING THAT THERE'S 7620 05:52:30,480 --> 05:52:37,800 A MANIPULATING OF THE MUCOSAL 7621 05:52:37,800 --> 05:52:38,160 ECOSYSTEM. 7622 05:52:38,160 --> 05:52:40,440 SO IT IS NOT NECESSARILY 7623 05:52:40,440 --> 05:52:43,400 COLLECTING FOR THE MICROBIOME 7624 05:52:43,400 --> 05:52:44,440 BUT BASICALLY THOSE ARE 7625 05:52:44,440 --> 05:52:46,280 SOMETHING THAT ONCE THEY HAVE 7626 05:52:46,280 --> 05:52:53,120 THE FULLY ESTABLISHED MUCOUS 7627 05:52:53,120 --> 05:52:56,080 LAYER, THE OUTR AREA, 7628 05:52:56,080 --> 05:52:59,680 DEPENDING ON OXYGEN GRADIENT 7629 05:52:59,680 --> 05:53:02,440 AND PROBABLY MAKE THEM 7630 05:53:02,440 --> 05:53:03,680 DEPENDENT WITH SOME BODIES AND 7631 05:53:03,680 --> 05:53:08,280 OTHER TYPE OF BUILD THAT CAN 7632 05:53:08,280 --> 05:53:09,640 POTENTIALLY MAKE ANTIMICROBE 7633 05:53:09,640 --> 05:53:09,920 CHIPS. 7634 05:53:09,920 --> 05:53:15,480 WE HOPE WE CAN SEE MORE 7635 05:53:15,480 --> 05:53:16,280 BIOLOGICAL BRILLIANCE, 7636 05:53:16,280 --> 05:53:20,880 MECHANICAL INSIGHT AND 7637 05:53:20,880 --> 05:53:26,880 CONTRIBUTION FOR THE MACHINE. 7638 05:53:26,880 --> 05:53:28,880 >> OKAY, SO DO YOU HAVE A SORT 7639 05:53:28,880 --> 05:53:31,800 OF A WISH LIST OF THINGS THAT 7640 05:53:31,800 --> 05:53:34,480 YOU WOULD WANT IN ORDER TO 7641 05:53:34,480 --> 05:53:36,080 MAKE, YOU KNOW, SOME KEY 7642 05:53:36,080 --> 05:53:48,320 ADVANCES IN THIS AREA? 7643 05:53:48,320 --> 05:53:48,880 AS A GROUP? 7644 05:53:48,880 --> 05:53:54,240 >> I THINK ANY OF US CAN HOP 7645 05:53:54,240 --> 05:53:56,360 IN HERE TOO. 7646 05:53:56,360 --> 05:53:59,240 >> YEAH, THIS IS JUST A PANEL 7647 05:53:59,240 --> 05:53:59,640 DISCUSSION. 7648 05:53:59,640 --> 05:54:01,800 >> ANY TIME THAT GETS ASKED IN 7649 05:54:01,800 --> 05:54:03,640 A NIH WORKSHOP, IT IS SO HARD 7650 05:54:03,640 --> 05:54:05,800 NOT TO ANSWER MORE FUNDING 7651 05:54:05,800 --> 05:54:06,520 OPPORTUNITIES. 7652 05:54:06,520 --> 05:54:07,120 [LAUGHTER] 7653 05:54:07,120 --> 05:54:08,480 >> YEAH, MORE FUNDING 7654 05:54:08,480 --> 05:54:11,240 OPPORTUNITIES BUT SOME OF IT 7655 05:54:11,240 --> 05:54:12,920 COULD BE WHAT WOULD YOU ASK 7656 05:54:12,920 --> 05:54:14,920 FOR IN TERMS OF -- IS IT 7657 05:54:14,920 --> 05:54:20,120 RESOURCES, IS IT, YOU KNOW, 7658 05:54:20,120 --> 05:54:22,400 TECHNOLOGY? 7659 05:54:22,400 --> 05:54:38,880 IS IT, YOU KNOW -- 7660 05:54:38,880 --> 05:54:49,880 >> I SEE THAT Dr. -- RUSTEM 7661 05:54:49,880 --> 05:54:50,960 HAS COME ON. 7662 05:54:50,960 --> 05:54:56,080 >> I THINK SOME OF US SAY IT 7663 05:54:56,080 --> 05:55:00,560 IS EASY TO ASK FOR HELP BUT 7664 05:55:00,560 --> 05:55:02,320 WHAT IS CHALLENGE IS GETTING 7665 05:55:02,320 --> 05:55:04,600 THE ORIGINAL DATA AND SORT -- 7666 05:55:04,600 --> 05:55:07,760 JUST HAVE ENOUGH DATA TO START 7667 05:55:07,760 --> 05:55:08,280 ASKING QUESTIONS. 7668 05:55:08,280 --> 05:55:11,520 IN OTHER WORDS WE AS A 7669 05:55:11,520 --> 05:55:13,600 COMMUNITY VALUE MECHANISTIC 7670 05:55:13,600 --> 05:55:15,360 STUDIES BUT YOU CAN'T DO THEM 7671 05:55:15,360 --> 05:55:17,440 IF YOU DON'T KNOW WHAT IS OUT 7672 05:55:17,440 --> 05:55:20,600 THERE OR KNOW WHAT QUESTIONS 7673 05:55:20,600 --> 05:55:21,680 TO ASK, ESPECIALLY WHEN YOU 7674 05:55:21,680 --> 05:55:30,800 DON'T KNOW THE SIDE AND 7675 05:55:30,800 --> 05:55:32,200 EFFECTS. 7676 05:55:32,200 --> 05:55:33,000 SO THAT IS CRITICAL AS A 7677 05:55:33,000 --> 05:55:34,080 COMMUNITY TO BE THINKING 7678 05:55:34,080 --> 05:55:38,120 ABOUT, SORT OF LIKE THE PIP 7679 05:55:38,120 --> 05:55:39,920 EFFORTS, WHAT ARE THE THINGS 7680 05:55:39,920 --> 05:55:43,480 THAT PIP CAN DO AND ALLOW A 7681 05:55:43,480 --> 05:55:45,080 LOT OF HUMAN DATA TO MOVE 7682 05:55:45,080 --> 05:55:46,680 FORWARD AND WHAT GARY 7683 05:55:46,680 --> 05:55:47,720 MENTIONED THIS MORNING, VERY 7684 05:55:47,720 --> 05:55:48,800 MUCH ALONG THESE LINES. 7685 05:55:48,800 --> 05:55:50,040 SO FIGURING THAT OUT AND HOW 7686 05:55:50,040 --> 05:55:52,520 TO GET A LOT OF HUMAN DATA AND 7687 05:55:52,520 --> 05:55:54,640 HOW TO SHARE IT IN A 7688 05:55:54,640 --> 05:55:56,680 MEANINGFUL WAY SO LOTS OF 7689 05:55:56,680 --> 05:56:00,600 PEOPLE CAN BUILD STUDIES AND 7690 05:56:00,600 --> 05:56:01,720 ASK BEAUTIFUL MECHANISTIC 7691 05:56:01,720 --> 05:56:04,520 QUESTIONS, TO ME THAT IS ONE 7692 05:56:04,520 --> 05:56:06,480 CHALLENGE NO PI COULD EVER 7693 05:56:06,480 --> 05:56:09,480 SOLVE AND KIND OF REQUIRES NIH 7694 05:56:09,480 --> 05:56:11,840 TO TACKLE IT TOP-DOWN. 7695 05:56:11,840 --> 05:56:16,280 >> CURTIS, YOU ARE NEXT. 7696 05:56:16,280 --> 05:56:20,320 >> THERE WE GO. 7697 05:56:20,320 --> 05:56:21,400 RUSTEM'S ANSWER WAS VERY 7698 05:56:21,400 --> 05:56:24,360 SIMILAR TO WHAT I WAS GOING TO 7699 05:56:24,360 --> 05:56:28,440 SAY, THERE IS NO MORE SERIOUS 7700 05:56:28,440 --> 05:56:30,840 THAN THE FUNDING MECHANISMS, 7701 05:56:30,840 --> 05:56:34,400 BECAUSE THIS IS SUCH A BROAD 7702 05:56:34,400 --> 05:56:35,560 COLLABORATIVE FIELD, 7703 05:56:35,560 --> 05:56:36,680 MECHANISMS THAT HIP BETWEEN OR 7704 05:56:36,680 --> 05:56:40,480 ON THE ONE AND BIG CONSORTIUM 7705 05:56:40,480 --> 05:56:42,480 PROJECTS LIKE HRP ARE 7706 05:56:42,480 --> 05:56:45,120 PASSENGERSLY BENEFICIAL. 7707 05:56:45,120 --> 05:56:45,960 SOMETHING HRP-1 LAUNCHED VERY 7708 05:56:45,960 --> 05:56:48,600 WELL IS SORT OF A NETWORK OF 7709 05:56:48,600 --> 05:56:49,280 COLLABORATORS, GROUPS OF 7710 05:56:49,280 --> 05:56:52,840 PEOPLE THAT ARE INTERESTED IN 7711 05:56:52,840 --> 05:56:54,040 WORKING ON MICROBIOME PROBLEMS 7712 05:56:54,040 --> 05:56:55,480 TOGETHER AND SADLY I DON'T 7713 05:56:55,480 --> 05:56:59,640 KNOW IF WE WILL EVER SEE THAT 7714 05:56:59,640 --> 05:57:02,480 BIG OF A PLATFORM AGAIN BUT 7715 05:57:02,480 --> 05:57:06,120 GROUPS THAT ARE MID-SIZED OF 7716 05:57:06,120 --> 05:57:08,280 GETTING COLLABORATORS TOGETHER 7717 05:57:08,280 --> 05:57:10,320 ON THIS PROBLEM WOULD BE VERY 7718 05:57:10,320 --> 05:57:15,520 HELPFUL, I WOULD AGREE. 7719 05:57:15,520 --> 05:57:16,600 >> CURTIS JUST ANSWERED MY 7720 05:57:16,600 --> 05:57:17,360 QUESTION. 7721 05:57:17,360 --> 05:57:20,400 BECAUSE I HAVE BEEN HEARING 7722 05:57:20,400 --> 05:57:20,840 ABOUT SO MUCH 7723 05:57:20,840 --> 05:57:22,320 INTERDISCIPLINARY RESEARCH AND 7724 05:57:22,320 --> 05:57:24,360 THE IMPORTANCE OF DIFFERENT 7725 05:57:24,360 --> 05:57:25,440 APPROACHES AND MODES OF 7726 05:57:25,440 --> 05:57:28,360 RESEARCH FROM THE MOLECULAR 7727 05:57:28,360 --> 05:57:36,280 AND CHEMICAL TO THE ECOLOGICAL 7728 05:57:36,280 --> 05:57:37,600 AND POPULATION INFORMING EACH 7729 05:57:37,600 --> 05:57:45,680 OTHER SO YOU ANSWERED MY 7730 05:57:45,680 --> 05:57:46,800 QUESTION, THANK YOU. 7731 05:57:46,800 --> 05:57:53,600 >> I HAVE QUESTIONS FOR Dr. 7732 05:57:53,600 --> 05:57:54,080 SAMEER. 7733 05:57:54,080 --> 05:57:56,320 SO THAT IS QUITE A FILE THAT 7734 05:57:56,320 --> 05:58:02,360 YOU HAVE IN THE HRP AND I KNOW 7735 05:58:02,360 --> 05:58:05,360 IT TOOK A LOT OF YEARS JUST 7736 05:58:05,360 --> 05:58:06,880 FOR THE RESEARCH TO ACQUIRE 7737 05:58:06,880 --> 05:58:10,080 BUT WHAT WOULD YOU HIGHLIGHT 7738 05:58:10,080 --> 05:58:12,040 IN A SINGLE CASE? 7739 05:58:12,040 --> 05:58:13,440 >> THAT IS A GREAT QUESTION 7740 05:58:13,440 --> 05:58:15,600 AND I THINK CORRESPONDING 7741 05:58:15,600 --> 05:58:19,360 ISSUE GET TO CLINICAL TRIALS, 7742 05:58:19,360 --> 05:58:21,080 I ACTUALLY SPECIFICALLY SHOULD 7743 05:58:21,080 --> 05:58:24,160 MENTION THAT AND IN VIVO IF IT 7744 05:58:24,160 --> 05:58:29,000 GOES WELL, WE WILL BE ON TRACK 7745 05:58:29,000 --> 05:58:32,480 TO DO SOME HUMAN TRIALS AND 7746 05:58:32,480 --> 05:58:34,200 THAT IS SOMETHING IMPENDING IN 7747 05:58:34,200 --> 05:58:35,480 THE PIPELINE. 7748 05:58:35,480 --> 05:58:39,040 SO HOW DOES THE DEVICE MEET 7749 05:58:39,040 --> 05:58:40,080 THE FDA IS THE QUESTION AND 7750 05:58:40,080 --> 05:58:41,360 THERE IS NO CLEAR ANSWER AT 7751 05:58:41,360 --> 05:58:41,800 THE MOMENT. 7752 05:58:41,800 --> 05:58:45,680 THE REASON I AM SAYING THIS IS 7753 05:58:45,680 --> 05:58:47,680 THIS STILL DOES NOT DIAGNOSE 7754 05:58:47,680 --> 05:58:49,720 OR TREAT ANYTHING SO AS A 7755 05:58:49,720 --> 05:58:50,880 MEDICAL DEVICE, IT IS 7756 05:58:50,880 --> 05:58:53,080 SOMETHING YOU ARE USING TO 7757 05:58:53,080 --> 05:58:54,200 STUDY AND UNDERSTAND WHAT IS 7758 05:58:54,200 --> 05:58:55,080 GOING ON. 7759 05:58:55,080 --> 05:58:57,680 AND AS LONG AS WE STAY SAFE 7760 05:58:57,680 --> 05:58:59,400 WITH THE MATERIALS AND THE 7761 05:58:59,400 --> 05:59:00,680 DEVICES THAT I SHOWED WHICH 7762 05:59:00,680 --> 05:59:03,680 DOES NOT HAVE ANY ELECTRONICS, 7763 05:59:03,680 --> 05:59:07,200 NO BATTERY, NOTHING TOXIC, WE 7764 05:59:07,200 --> 05:59:11,200 STAY CLOSE TO THAT. 7765 05:59:11,200 --> 05:59:21,440 WE HEARD WE EXPECT IT TO BE 7766 05:59:21,440 --> 05:59:23,000 MINIMAL TO GET. 7767 05:59:23,000 --> 05:59:27,400 SO WE SHOWED THE NEXT ONE WITH 7768 05:59:27,400 --> 05:59:28,840 THE DEVICES AND ELECTRONICS IN 7769 05:59:28,840 --> 05:59:31,560 IT AND I BELIEVE THAT WILL BE 7770 05:59:31,560 --> 05:59:33,960 DIFFICULT TO GET APPROVAL. 7771 05:59:33,960 --> 05:59:36,120 SO WE SHOWED ANOTHER VERSION 7772 05:59:36,120 --> 05:59:38,440 OF THE PILL THAT WOULD GATHER 7773 05:59:38,440 --> 05:59:40,640 A EXAMINER OF THE MICROBIOME 7774 05:59:40,640 --> 05:59:42,480 AND I THINK THAT IS SOMETHING 7775 05:59:42,480 --> 05:59:44,720 THAT CAN BE DISSEMINATED 7776 05:59:44,720 --> 05:59:46,360 BROADLY FOR HUMAN STUDIES. 7777 05:59:46,360 --> 05:59:48,760 THEY ARE VERY EASY FOR US TO 7778 05:59:48,760 --> 05:59:50,480 MAKE AND I ENVISION THE HURDLE 7779 05:59:50,480 --> 05:59:52,680 TO BE LOWER FOR THAT BUT IT IS 7780 05:59:52,680 --> 05:59:54,440 A GOOD QUESTION AND OF COURSE 7781 05:59:54,440 --> 05:59:56,720 IT STARTS WITH GETTING THE 7782 05:59:56,720 --> 05:59:57,880 REGULATORY APPROVAL FIRST AND 7783 05:59:57,880 --> 06:00:05,480 THEN SOME FUNDING TO GO THERE. 7784 06:00:05,480 --> 06:00:12,440 >> SO YOU HAVE THAT PENDING -- 7785 06:00:12,440 --> 06:00:13,080 PARDON ME. 7786 06:00:13,080 --> 06:00:16,080 >> SO HOW DOES THE SAMPLING 7787 06:00:16,080 --> 06:00:16,480 CONTRIBUTE? 7788 06:00:16,480 --> 06:00:24,880 IS IT ENOUGH QUANTITY AND 7789 06:00:24,880 --> 06:00:26,880 QUALITY FOR THE MICROBIOME 7790 06:00:26,880 --> 06:00:27,200 STUDIES? 7791 06:00:27,200 --> 06:00:30,840 >> RIGHT NOW WE ARE JUST DOING 7792 06:00:30,840 --> 06:00:34,840 THE 16S, TRYING TO LOOK AT THE 7793 06:00:34,840 --> 06:00:36,360 MICROBIAL POPULATION AND OF 7794 06:00:36,360 --> 06:00:43,680 COURSE IF YOU ARE LOOKING AT 7795 06:00:43,680 --> 06:00:54,320 POPULATIONS, TWO, 300 7796 06:00:54,320 --> 06:00:56,360 MILILITERS IS SOMETHING YOU 7797 06:00:56,360 --> 06:00:58,560 CAN DO AND OF COURSE IT IS 7798 06:00:58,560 --> 06:01:02,040 JUST A PILL BUT YOU AT LEAST 7799 06:01:02,040 --> 06:01:03,440 HAVE A STATISTICALLY USEFUL 7800 06:01:03,440 --> 06:01:04,680 DATA SET HERE WHEN YOU ARE 7801 06:01:04,680 --> 06:01:06,640 TRYING TO DO STUDIES WITH 7802 06:01:06,640 --> 06:01:08,440 HUMANS WITH MORE PILLS. 7803 06:01:08,440 --> 06:01:10,480 SO YOU GET MORE SAMPLES AND 7804 06:01:10,480 --> 06:01:13,080 THERE WILL BE MORE RIGOR IN 7805 06:01:13,080 --> 06:01:15,880 THE DATA YOU GENERATE USING 7806 06:01:15,880 --> 06:01:16,360 THESE PILLS. 7807 06:01:16,360 --> 06:01:17,880 >> SO DID YOU HAVE A QUESTION, 7808 06:01:17,880 --> 06:01:19,880 MAY NOT BE DIRECTLY RELATED TO 7809 06:01:19,880 --> 06:01:21,480 WHAT WE JUST COVERED BUT 7810 06:01:21,480 --> 06:01:32,480 SOMETHING WE TALKED ABOUT IN 7811 06:01:32,480 --> 06:01:33,360 THE SESSION, RIMA? 7812 06:01:33,360 --> 06:01:37,080 >> NO, NOT SO MUCH, I WANTED 7813 06:01:37,080 --> 06:01:38,520 TO ECHO SOME OF THE 7814 06:01:38,520 --> 06:01:42,200 SUGGESTIONS IN THE LAST 20 7815 06:01:42,200 --> 06:01:42,560 MINUTES. 7816 06:01:42,560 --> 06:01:46,760 THERE IS SO MUCH HERE, 7817 06:01:46,760 --> 06:01:47,480 MULTILINES, MULTIDEPENDENCIES 7818 06:01:47,480 --> 06:01:51,240 AND ALSO THE IMPORTANCE OF 7819 06:01:51,240 --> 06:01:52,280 CREATING PROJECTS AND OPEN 7820 06:01:52,280 --> 06:01:56,040 TIMES WHICH CAN BE USED AND 7821 06:01:56,040 --> 06:01:58,640 LEVERAGED BUT THE COMMUNITY AT 7822 06:01:58,640 --> 06:02:01,280 LARGE IS TRULY MOST IMPORTANT 7823 06:02:01,280 --> 06:02:03,520 AND ALL POWERFUL. 7824 06:02:03,520 --> 06:02:07,560 YOU ARE CREATING SOME TOOLS 7825 06:02:07,560 --> 06:02:10,440 FOR MICROBIOME METABOLITES AND 7826 06:02:10,440 --> 06:02:15,880 JUST ONE THAT CAME OUT OF A 7827 06:02:15,880 --> 06:02:17,720 POPULATION OF OVER 600 7828 06:02:17,720 --> 06:02:18,080 RESOURCES. 7829 06:02:18,080 --> 06:02:19,520 THANK YOU. 7830 06:02:19,520 --> 06:02:20,200 >> GARY? 7831 06:02:20,200 --> 06:02:25,760 >> I JUST WANTED TO TALK ON 7832 06:02:25,760 --> 06:02:26,320 THE IBF OPPORTUNITIES. 7833 06:02:26,320 --> 06:02:28,400 I THINK ONE OF THE BIG AREAS 7834 06:02:28,400 --> 06:02:30,120 THAT NIH AND OTHER PLACES 7835 06:02:30,120 --> 06:02:31,760 COULD BE PUSHING FORWARD OR 7836 06:02:31,760 --> 06:02:33,680 THINKING ABOUT GENE 7837 06:02:33,680 --> 06:02:34,400 ENVIRONMENTAL INTERACTION. 7838 06:02:34,400 --> 06:02:37,760 YOU KNOW WE HAVE DONE A LOT IN 7839 06:02:37,760 --> 06:02:39,920 HUMAN GENETICS AND GENOMICS, 7840 06:02:39,920 --> 06:02:40,960 BEGINNING TO EXPLORE THE 7841 06:02:40,960 --> 06:02:42,360 ENVIRONMENT WHICH IS VERY, 7842 06:02:42,360 --> 06:02:42,960 VERY DIFFICULT. 7843 06:02:42,960 --> 06:02:51,240 BUT I SORT OF FEEL LIKE DIET 7844 06:02:51,240 --> 06:02:52,480 AND ENVIRONMENTAL ARE TWO VERY 7845 06:02:52,480 --> 06:02:56,960 BIG FACTORS AND FROM A 7846 06:02:56,960 --> 06:02:58,560 CONCRETE STANDPOINT, THE 7847 06:02:58,560 --> 06:03:00,520 PHYSICIANS NUTRITION HOUSE IS 7848 06:03:00,520 --> 06:03:01,880 JUST BEING LAUNCHED AND THEY 7849 06:03:01,880 --> 06:03:03,680 ARE SORT OF IN THE PLANNING 7850 06:03:03,680 --> 06:03:04,440 PHASE RIGHT NOW. 7851 06:03:04,440 --> 06:03:07,920 SO I THINK THERE MAYBE IS AN 7852 06:03:07,920 --> 06:03:08,720 OPPORTUNITY FOR GETTING SOME 7853 06:03:08,720 --> 06:03:10,680 FEEDBACK FROM THE PEOPLE HERE 7854 06:03:10,680 --> 06:03:15,200 THE LAST FEW DAYS TO THE 7855 06:03:15,200 --> 06:03:16,320 NUTRITION PHYSICIANS HOUSE 7856 06:03:16,320 --> 06:03:18,160 BECAUSE THAT PROGRAM IS 7857 06:03:18,160 --> 06:03:20,680 DESIGNED TO LOOK FOR 7858 06:03:20,680 --> 06:03:22,040 BIOMARKERS TO STRAT GUY FROM 7859 06:03:22,040 --> 06:03:23,880 THE STANDPOINT OF PRECISION 7860 06:03:23,880 --> 06:03:26,080 HEALTH BUT THIS GROUP IS 7861 06:03:26,080 --> 06:03:27,480 THINKING MORE ABOUT 7862 06:03:27,480 --> 06:03:29,240 THERAPEUTICS AND MAYBE THAT IS 7863 06:03:29,240 --> 06:03:31,080 AN OPPORTUNITY TO LEVERAGE AND 7864 06:03:31,080 --> 06:03:34,080 DESIGN THE STUDY IN A WAY THAT 7865 06:03:34,080 --> 06:03:35,240 YOU COULD DUAL-PURPOSE OR 7866 06:03:35,240 --> 06:03:36,880 LEVERAGE SOMETHING OR AT LEAST 7867 06:03:36,880 --> 06:03:37,560 START THE CONVERSATION. 7868 06:03:37,560 --> 06:03:39,720 BECAUSE THERE HAS BEEN A BIG 7869 06:03:39,720 --> 06:03:41,720 INVESTMENT INTO THAT 7870 06:03:41,720 --> 06:03:43,440 PARTICULAR PROGRAM AND IT IS A 7871 06:03:43,440 --> 06:03:44,080 BIG, BIG PROJECT. 7872 06:03:44,080 --> 06:03:48,960 SO IF YOU -- YOU DON'T WANT 7873 06:03:48,960 --> 06:03:51,640 TO REALLY MISS ANY 7874 06:03:51,640 --> 06:03:52,080 OPPORTUNITIES. 7875 06:03:52,080 --> 06:03:58,000 >> AND THE MICROBIOME 7876 06:03:58,000 --> 06:03:59,520 COMPONENT, INDEED IT IS A 7877 06:03:59,520 --> 06:04:04,360 GREAT OPPORTUNITY TO CONNECT 7878 06:04:04,360 --> 06:04:04,680 WITH. 7879 06:04:04,680 --> 06:04:06,840 >> I ALSO HAVE A COUPLE OF 7880 06:04:06,840 --> 06:04:08,080 QUESTIONS COMING IN THROUGH 7881 06:04:08,080 --> 06:04:16,960 THE CHAT AND ONE IS ABOUT THE 7882 06:04:16,960 --> 06:04:21,720 WILD SITE MICE, DID YOU TRY TO 7883 06:04:21,720 --> 06:04:25,320 TRANSFER THE MICROBIOTICS AND 7884 06:04:25,320 --> 06:04:30,200 DOES IT WORK OR DO THE LAB 7885 06:04:30,200 --> 06:04:36,880 MICE GET RESISTANCE TO THE 7886 06:04:36,880 --> 06:04:37,520 WILDLING GUT MICROBIOTA? 7887 06:04:37,520 --> 06:04:41,360 >> WE FOUND THAT IN THE STUDY 7888 06:04:41,360 --> 06:04:44,800 IT DOES NOT TRANSFER ACROSS. 7889 06:04:44,800 --> 06:04:46,680 SO IN THIS NATURE, METABOLISM, 7890 06:04:46,680 --> 06:04:49,160 THERE ARE MANY MORE THINGS TO 7891 06:04:49,160 --> 06:04:49,480 STUDY. 7892 06:04:49,480 --> 06:04:53,840 >> AND THEN THIS IS A QUESTION 7893 06:04:53,840 --> 06:04:57,760 FOR NOAH, THE DISCOVERY OF THE 7894 06:04:57,760 --> 06:04:58,440 MICROBIOME INTERACTIONS, HOW 7895 06:04:58,440 --> 06:05:01,160 MANY OF THE IDENTIFIED 7896 06:05:01,160 --> 06:05:03,880 MICROBIAL PROTEINS ARE KIND OF 7897 06:05:03,880 --> 06:05:04,720 UNKNOWN PROTEINS? 7898 06:05:04,720 --> 06:05:07,680 AND THIS IS RELEVANT TO THE 7899 06:05:07,680 --> 06:05:09,440 GRAPH AND PROPORTION OF 7900 06:05:09,440 --> 06:05:13,280 MICROBIAL GENES THAT ARE 7901 06:05:13,280 --> 06:05:13,680 INDICATED? 7902 06:05:13,680 --> 06:05:15,080 >> YEAH, SO THANKS FOR THAT 7903 06:05:15,080 --> 06:05:16,360 QUESTION BECAUSE IT ALLOWS ME 7904 06:05:16,360 --> 06:05:18,200 TO MAKE A VERY IMPORTANT POINT 7905 06:05:18,200 --> 06:05:20,040 WHICH I THINK I PROBABLY 7906 06:05:20,040 --> 06:05:22,000 FAILED TO MAKE CLEARLY WHICH 7907 06:05:22,000 --> 06:05:24,240 ARE THERE ARE TWO SIDES TO 7908 06:05:24,240 --> 06:05:25,640 THIS INTERACTION EQUATION. 7909 06:05:25,640 --> 06:05:27,160 THERE IS THE MICROBIAL SIDE 7910 06:05:27,160 --> 06:05:30,040 AND HOST SIDE AND OUR 7911 06:05:30,040 --> 06:05:32,680 TECHNOLOGY, IT TELLS YOU IS 7912 06:05:32,680 --> 06:05:39,360 ACTUALLY WHICH HOST PROTEIN IS 7913 06:05:39,360 --> 06:05:40,880 BOUND BY THE BACTERIA OR WHAT 7914 06:05:40,880 --> 06:05:46,400 HOST IS TARGETED BY THE 7915 06:05:46,400 --> 06:05:46,720 PROTEIN. 7916 06:05:46,720 --> 06:05:50,960 IT DOES NOT TELL US ANYTHING 7917 06:05:50,960 --> 06:05:52,920 ABOUT THE MICROBIALS THAT THE 7918 06:05:52,920 --> 06:05:54,200 PROTEIN IS TRYING TO ADDRESS 7919 06:05:54,200 --> 06:05:56,120 AND THAT IS REALLY WHERE WE 7920 06:05:56,120 --> 06:05:57,520 WANT TO GO TO THE OTHER SIDE 7921 06:05:57,520 --> 06:05:59,480 OF THE EQUATION AND WORKING 7922 06:05:59,480 --> 06:06:00,680 WITH CURTIS TO THINK ABOUT 7923 06:06:00,680 --> 06:06:00,960 THAT. 7924 06:06:00,960 --> 06:06:03,000 AS I HAVE TRIED TO DESCRIBE, 7925 06:06:03,000 --> 06:06:08,560 WE HOPE THAT WITH THE RIGHT 7926 06:06:08,560 --> 06:06:13,160 SCALE OF INTERACTOMES PLUS 7927 06:06:13,160 --> 06:06:14,080 GENOMES, FOR EXAMPLE, WE WILL 7928 06:06:14,080 --> 06:06:15,880 BE ABLE TO MAKE THOSE 7929 06:06:15,880 --> 06:06:17,720 PREDICTIONS OF THE PROTEINS 7930 06:06:17,720 --> 06:06:19,560 INVOLVED IN THESE 7931 06:06:19,560 --> 06:06:20,000 INTERACTIONS. 7932 06:06:20,000 --> 06:06:23,080 AND MY STRONG FEELING IS, AND 7933 06:06:23,080 --> 06:06:24,920 CURTIS CAN JUMP IN AND EITHER 7934 06:06:24,920 --> 06:06:27,120 SUPPORT OR CONTRADICT ME, BUT 7935 06:06:27,120 --> 06:06:30,720 MY STRONG FEELING IS THE VAST 7936 06:06:30,720 --> 06:06:33,040 MAJORITY OF THOSE GENES WILL 7937 06:06:33,040 --> 06:06:34,520 BE UNANNOTATED BECAUSE I THINK 7938 06:06:34,520 --> 06:06:36,760 A LOT OF ANNOTATED GENES TO BE 7939 06:06:36,760 --> 06:06:38,480 HONEST AT THIS POINT ARE 7940 06:06:38,480 --> 06:06:39,480 ANNOTATED BECAUSE THEY ARE 7941 06:06:39,480 --> 06:06:42,200 CORE PARTS OF BEING A 7942 06:06:42,200 --> 06:06:46,880 BACTERIUM, CORE PARTS OF BEING 7943 06:06:46,880 --> 06:06:50,600 A BACTERIAL METABOLISM AND 7944 06:06:50,600 --> 06:06:51,520 EXIST IN ALL BACTERIA. 7945 06:06:51,520 --> 06:06:52,680 SO I THINK ONE THING WE HAVE 7946 06:06:52,680 --> 06:06:54,000 TO REMEMBER AND I AM GETTING 7947 06:06:54,000 --> 06:06:56,080 OFF ON A RANT ABOUT IT BUT ONE 7948 06:06:56,080 --> 06:06:57,800 THING WE HAVE TO REMEMBER IS 7949 06:06:57,800 --> 06:07:00,360 THE ONLY WAY TO AN NOTATE A 7950 06:07:00,360 --> 06:07:01,880 GENE THAT HAS NEVER BEEN 7951 06:07:01,880 --> 06:07:05,920 STUDIES AND NO HOMOLOGY TO THE 7952 06:07:05,920 --> 06:07:08,040 GENE THAT HAS NEVER BEEN 7953 06:07:08,040 --> 06:07:15,960 STUDIED IS TO CONDUCT A 7954 06:07:15,960 --> 06:07:16,360 EXPERIMENT. 7955 06:07:16,360 --> 06:07:21,320 A HUNDRED YEARS AGO, WE COULD 7956 06:07:21,320 --> 06:07:22,680 SEQUENTIALLY AND CHEAPLY 7957 06:07:22,680 --> 06:07:23,720 CONVENIENCE HUMAN GENOMES AND 7958 06:07:23,720 --> 06:07:26,800 THERE ARE PEOPLE SAYING IF WE 7959 06:07:26,800 --> 06:07:28,640 JUST CONVENIENCE ANOTHER 7960 06:07:28,640 --> 06:07:29,560 HUNDRED THOUSAND GENOMES, WE 7961 06:07:29,560 --> 06:07:31,080 CAN FIGURE OUT WHAT THESE 7962 06:07:31,080 --> 06:07:32,600 GENES DO AND THAT IS JUST NOT 7963 06:07:32,600 --> 06:07:35,040 HOW IT WORKS. 7964 06:07:35,040 --> 06:07:37,640 SO OBVIOUSLY I ADVOCATE WITH 7965 06:07:37,640 --> 06:07:38,920 COUPLING THESE POWERFUL 7966 06:07:38,920 --> 06:07:40,720 APPROACHES WITH THE 7967 06:07:40,720 --> 06:07:41,400 EXPERIMENTAL APPROACHES BUT 7968 06:07:41,400 --> 06:07:44,040 NOW I THINK WITH THE TOOLS WE 7969 06:07:44,040 --> 06:07:47,800 HAVE IN SYNTHETIC BIOLOGY AND 7970 06:07:47,800 --> 06:07:48,960 COMMENTORY BIOLOGY, WE CAN 7971 06:07:48,960 --> 06:07:54,000 MATCH THE SCALE OF OUR 7972 06:07:54,000 --> 06:07:54,880 EXPERIMENT POWER WITH THE 7973 06:07:54,880 --> 06:07:56,680 PROBLEM WE HAVE WITH THE 7974 06:07:56,680 --> 06:08:02,960 MICROBIOME AND THAT IS KIND OF 7975 06:08:02,960 --> 06:08:04,480 MY 2 CENTS ON THAT. 7976 06:08:04,480 --> 06:08:06,760 >> I CAN SECOND THAT. 7977 06:08:06,760 --> 06:08:08,680 I ALSO STRONGLY SUSPECT THERE 7978 06:08:08,680 --> 06:08:11,680 IS NOT JUST A MAJORITY BUT 7979 06:08:11,680 --> 06:08:14,840 ENRICHMENT FOR CHARACTERIZED 7980 06:08:14,840 --> 06:08:15,960 PROTEINS AMONG INTERACTORS 7981 06:08:15,960 --> 06:08:17,360 BECAUSE THEY ARE ENRICHED FOR 7982 06:08:17,360 --> 06:08:20,680 THINGS THAT WORK IN A DISH FOR 7983 06:08:20,680 --> 06:08:24,200 THE MOST PART. 7984 06:08:24,200 --> 06:08:28,120 EVEN HUMAN MICROBIOME 7985 06:08:28,120 --> 06:08:35,280 INTERACTORS HAVE NOT BEEN 7986 06:08:35,280 --> 06:08:38,240 STUDIED BEFORE AND IT MIGHT BE 7987 06:08:38,240 --> 06:08:40,880 ABLE TO INTEGRATE SOME KIND OF 7988 06:08:40,880 --> 06:08:42,800 SEQUENCING ACTIVITY WITH 7989 06:08:42,800 --> 06:08:43,480 FOLLOW UP. 7990 06:08:43,480 --> 06:08:45,480 AND WE DO THIS WITH YOU, WITH 7991 06:08:45,480 --> 06:08:47,320 WENDY, A LOT OF OUR PROJECTS, 7992 06:08:47,320 --> 06:08:48,680 TAKE SOMETHING THAT SHOWS UP 7993 06:08:48,680 --> 06:08:50,720 IN A MOUSE WHERE YOU SAY HUH, 7994 06:08:50,720 --> 06:08:53,280 THAT IS PRETTY COOL, GO BACK 7995 06:08:53,280 --> 06:08:55,320 TO A HUMAN DATA SET AND SEE IF 7996 06:08:55,320 --> 06:08:59,520 IT WORKS IN HUMAN POPULATIONS 7997 06:08:59,520 --> 06:09:08,080 TOO SO BOTH WORK REALLY WELL. 7998 06:09:08,080 --> 06:09:09,720 >> GARY, YOU HAVE A HAND UP, I 7999 06:09:09,720 --> 06:09:12,480 DON'T KNOW IF IT IS A NEW HAND 8000 06:09:12,480 --> 06:09:13,680 OR OLD HAND. 8001 06:09:13,680 --> 06:09:14,280 >> OH, ME? 8002 06:09:14,280 --> 06:09:18,200 IT IS AN OLD HAND, SORRY. 8003 06:09:18,200 --> 06:09:19,320 >> OKAY, SO I DON'T HAVE 8004 06:09:19,320 --> 06:09:22,880 ANYMORE QUESTIONS TO ALL THE 8005 06:09:22,880 --> 06:09:25,440 SPEAKERS. 8006 06:09:25,440 --> 06:09:28,640 I DO HAVE -- THE SESSIONS 8007 06:09:28,640 --> 06:09:31,880 WE'RE COVERING LIKE ON PILLS, 8008 06:09:31,880 --> 06:09:33,920 FUNGUS, VIRUSES, WHAT IS THE 8009 06:09:33,920 --> 06:09:36,520 PANEL'S OPINION ON USING 8010 06:09:36,520 --> 06:09:46,360 BACTERIAL SPORES AS PART OF 8011 06:09:46,360 --> 06:09:50,240 MICROBIOTA WHERE THE SPORES 8012 06:09:50,240 --> 06:09:57,760 SHOW CORRELATION, WHY NOT USE 8013 06:09:57,760 --> 06:09:59,000 THEM AS PROBES? 8014 06:09:59,000 --> 06:10:04,520 OKAY, HELP MEAN OUT HERE. 8015 06:10:04,520 --> 06:10:05,120 >> THANK YOU. 8016 06:10:05,120 --> 06:10:10,680 WELL, IT IS A DIFFERENT 8017 06:10:10,680 --> 06:10:11,200 QUESTION. 8018 06:10:11,200 --> 06:10:12,200 >> YEAH, I DON'T HAVE AN 8019 06:10:12,200 --> 06:10:13,400 ANSWER TO THAT ONE BUT IF YOU 8020 06:10:13,400 --> 06:10:15,280 HAVE AN ANSWER TO ANOTHER ONE, 8021 06:10:15,280 --> 06:10:18,080 THAT IS GREAT. 8022 06:10:18,080 --> 06:10:18,520 [LAUGHTER] 8023 06:10:18,520 --> 06:10:20,360 >> THANK YOU. 8024 06:10:20,360 --> 06:10:24,040 I HAVE A ANSWER. 8025 06:10:24,040 --> 06:10:25,520 THE META BOLITE, I WOULD LIKE 8026 06:10:25,520 --> 06:10:30,360 TO COMMENT THAT ANALYZING THE 8027 06:10:30,360 --> 06:10:31,640 META BOLITES IS VERY IMPORTANT 8028 06:10:31,640 --> 06:10:33,920 AND WE SHOULD DO THAT BUT WE 8029 06:10:33,920 --> 06:10:36,880 ALSO NEED TO KEEP IN MIND THAT 8030 06:10:36,880 --> 06:10:41,040 THE PRODUCER, THEIR PRODUCER 8031 06:10:41,040 --> 06:10:42,680 ACTUALLY EVEN MORE IMPORTANT, 8032 06:10:42,680 --> 06:10:48,280 THERE IS BECAUSE OF FUNCTIONAL 8033 06:10:48,280 --> 06:10:55,400 REDUNDANCY ON EVERY 8034 06:10:55,400 --> 06:10:57,640 BIOMETABOLITE WILL BE PRODUCED 8035 06:10:57,640 --> 06:10:59,280 BY MANY ACTIONS, NOT JUST ONE 8036 06:10:59,280 --> 06:11:00,080 EXPERIENCE. 8037 06:11:00,080 --> 06:11:01,680 AND THE HUMAN BACTERIA 8038 06:11:01,680 --> 06:11:03,280 ACTUALLY HAVE DIFFERENT IMPACT 8039 06:11:03,280 --> 06:11:04,640 ON THE HOST. 8040 06:11:04,640 --> 06:11:10,800 FOR EXAMPLE, SOME BACTERIA 8041 06:11:10,800 --> 06:11:18,840 PRODUCE PEUTRIDS WHICH IS 8042 06:11:18,840 --> 06:11:20,480 GOOD NOT ONLY FOR BACTERIA BUT 8043 06:11:20,480 --> 06:11:21,960 ALSO FOR THE HOST. 8044 06:11:21,960 --> 06:11:30,840 SO IF YOU ONLY FOCUS ON THE 8045 06:11:30,840 --> 06:11:31,960 METABOLIZE, IT WILL ACTUALLY 8046 06:11:31,960 --> 06:11:36,120 NOT HELP THE FIELD VERY MUCH. 8047 06:11:36,120 --> 06:11:38,920 SO NO MATTER WHAT WE DO, WE 8048 06:11:38,920 --> 06:11:41,120 MUST KEEP IN MIND THIS IS AN 8049 06:11:41,120 --> 06:11:45,280 ON ECOSYSTEM AND SINGLE 8050 06:11:45,280 --> 06:11:46,080 APPROACH, SINGLE METABOLITE 8051 06:11:46,080 --> 06:11:47,280 PROBABLY WILL NOT HELP. 8052 06:11:47,280 --> 06:11:57,920 THIS IS REALLY VERY, VERY 8053 06:11:57,920 --> 06:12:01,160 IMPORTANT BACK TO MORE OF THE 8054 06:12:01,160 --> 06:12:03,040 QUESTION, YOU MEAN THE 8055 06:12:03,040 --> 06:12:06,480 PERFORMANCE OF THE MICROBE 8056 06:12:06,480 --> 06:12:09,240 BACTERIA AND BECAUSE THEY ARE 8057 06:12:09,240 --> 06:12:10,480 THE DOMINANT FORM, MYSELF I 8058 06:12:10,480 --> 06:12:13,680 WOULD NOT FOCUS ON THEM, 8059 06:12:13,680 --> 06:12:17,760 UNLESS THEY ARE GERMINATING IN 8060 06:12:17,760 --> 06:12:23,160 THE GUT. 8061 06:12:23,160 --> 06:12:24,200 OTHERWISE MORE PROPERLY GO 8062 06:12:24,200 --> 06:12:25,800 PAST THE GUT AND I WOULD NOT 8063 06:12:25,800 --> 06:12:34,680 WORRY TOO MUCH ABOUT THAT. 8064 06:12:34,680 --> 06:12:36,600 >> OKAY, ANY OTHER QUESTIONS? 8065 06:12:36,600 --> 06:12:37,880 YOU CAN TAKE YOUR HAND DOWN 8066 06:12:37,880 --> 06:12:41,400 AND I WILL CALL YOU AGAIN. 8067 06:12:41,400 --> 06:12:44,120 >> AND I HAVE PUSHBACK ON WHAT 8068 06:12:44,120 --> 06:12:46,720 HE JUST SAID AND ACTUALLY 8069 06:12:46,720 --> 06:12:48,880 AGREE THAT -- I MEAN MY 8070 06:12:48,880 --> 06:12:52,080 FEELING IS THAT THERE MAY BE 8071 06:12:52,080 --> 06:12:53,600 MICROBES THAT ARE LIVING IN 8072 06:12:53,600 --> 06:12:56,680 SOME SORT OF DORMANT STATE AT 8073 06:12:56,680 --> 06:12:58,680 VERY, VERY, VERY LOW LEVELS, 8074 06:12:58,680 --> 06:13:02,200 QUITE LONG-TERM, THAT ARE 8075 06:13:02,200 --> 06:13:04,400 WAITING FOR OPPORTUNITIES TO 8076 06:13:04,400 --> 06:13:07,560 HAVE THEIR NICHE REAPPEAR. 8077 06:13:07,560 --> 06:13:08,280 I MEAN, JUSTIN, I DON'T KNOW 8078 06:13:08,280 --> 06:13:10,000 IF HE IS STILL ON THE CALL 8079 06:13:10,000 --> 06:13:12,200 HERE, I THINK HIS WORK SHOWED 8080 06:13:12,200 --> 06:13:19,880 THIS REALLY REALLY ELEGANTLY. 8081 06:13:19,880 --> 06:13:21,800 SO I WILL PUSH BACK ON THAT 8082 06:13:21,800 --> 06:13:23,520 IDEA ALTHOUGH I AGREE WITH 8083 06:13:23,520 --> 06:13:27,120 MANY OTHER THINGS THAT LIFENG 8084 06:13:27,120 --> 06:13:28,480 JUST SAID. 8085 06:13:28,480 --> 06:13:30,080 >> ANYBODY ELSE HAVE A TIE 8086 06:13:30,080 --> 06:13:31,320 BREAKER OPINION IN TERMS OF 8087 06:13:31,320 --> 06:13:33,400 WHERE THEY WANT TO GO? 8088 06:13:33,400 --> 06:13:34,120 [LAUGHTER] 8089 06:13:34,120 --> 06:13:35,240 YOU GOT THIS? 8090 06:13:35,240 --> 06:13:37,480 >> YEAH, JUST TO CHIME IN, IT 8091 06:13:37,480 --> 06:13:39,880 I AGREE WITH BOTH OF THOSE 8092 06:13:39,880 --> 06:13:40,200 POINTS. 8093 06:13:40,200 --> 06:13:42,360 I MEAN, I THINK THEY ARE 8094 06:13:42,360 --> 06:13:42,880 TOTALLY COMPATIBLE. 8095 06:13:42,880 --> 06:13:45,880 I THINK BOTH OF THOSE OPINIONS 8096 06:13:45,880 --> 06:13:48,920 ARE TOTALLY COMPATIBLE AND WE 8097 06:13:48,920 --> 06:13:50,560 KNOW THE MICROBIOME IS 8098 06:13:50,560 --> 06:14:06,720 COMPLEX, WE KNOW THAT THERE 8099 06:14:06,720 --> 06:14:07,320 ARE DEFINITELY LOW LEVEL 8100 06:14:07,320 --> 06:14:08,040 COMMUNITIES AND ORGANIZED KIND 8101 06:14:08,040 --> 06:14:08,680 OF SECLUDED SPACES THAT ARE 8102 06:14:08,680 --> 06:14:09,400 PROBABLY NOT SO METABOLICALLY 8103 06:14:09,400 --> 06:14:10,040 ACTIVE, AND MAYBE WE COULD 8104 06:14:10,040 --> 06:14:13,760 EXPAND BUT I THINK, YEAH, 8105 06:14:13,760 --> 06:14:14,480 THOSE ARE TOTALLY IN LINE WITH 8106 06:14:14,480 --> 06:14:18,920 THE WAY I THINK ABOUT THE 8107 06:14:18,920 --> 06:14:19,280 ECOSYSTEM. 8108 06:14:19,280 --> 06:14:19,680 >> CURTIS? 8109 06:14:19,680 --> 06:14:20,760 >> I WAS GOING TO RELATE THIS 8110 06:14:20,760 --> 06:14:25,000 BACK TO A POINT THAT TAMMY 8111 06:14:25,000 --> 06:14:26,600 RAISED EARLIER AND I THINK WE 8112 06:14:26,600 --> 06:14:28,600 LOST TAMMY BUT I THINK THIS 8113 06:14:28,600 --> 06:14:31,480 HELPS TO EXPLAIN SOME OF THE 8114 06:14:31,480 --> 06:14:32,760 DISPARITY BETWEEN LIKE PLACES 8115 06:14:32,760 --> 06:14:36,120 LIKE THE SKIN WHERE WE SEE 8116 06:14:36,120 --> 06:14:40,040 LOTS OF LOCAL HYPERGENEITY 8117 06:14:40,040 --> 06:14:41,360 WHERE AT THE MACRO LEVEL OF 8118 06:14:41,360 --> 06:14:45,880 THE GUT, THERE IS A LOT LESS 8119 06:14:45,880 --> 06:14:46,280 HYPERGENEITY. 8120 06:14:46,280 --> 06:14:50,080 SO THE IMPORTANCE OF DORMANT 8121 06:14:50,080 --> 06:14:51,120 BUGS AND LIPIDITY OF SUITES 8122 06:14:51,120 --> 06:14:52,080 HELPS TO EXPLAIN THAT. 8123 06:14:52,080 --> 06:14:53,320 IF YOU HAVE RARE BUGS, YOU 8124 06:14:53,320 --> 06:14:55,200 WILL HAVE A LOT OF TROUBLE 8125 06:14:55,200 --> 06:15:00,960 SEEING THEM BY SEQUENCING OR 8126 06:15:00,960 --> 06:15:01,280 CULTURE. 8127 06:15:01,280 --> 06:15:03,280 BUT IF THEY ARE ABLE TO BE 8128 06:15:03,280 --> 06:15:04,440 MIXED UP IN ENVIRONMENTS LIKE 8129 06:15:04,440 --> 06:15:06,400 THE GUT AS OPPOSED TO THE 8130 06:15:06,400 --> 06:15:08,640 SKIN, IT WILL LOOK LIKE THERE 8131 06:15:08,640 --> 06:15:10,320 WILL ONLY BE ONE DOMINANT 8132 06:15:10,320 --> 06:15:11,640 STRAIN THERE. 8133 06:15:11,640 --> 06:15:14,000 SO I THINK THAT IS WHERE 8134 06:15:14,000 --> 06:15:17,080 THINGS LIKE SPORES OR LOW 8135 06:15:17,080 --> 06:15:18,560 ABUNDANT STRAINS INTERSECT 8136 06:15:18,560 --> 06:15:22,680 SOME OF THE POPULATION 8137 06:15:22,680 --> 06:15:25,520 GENOMICS THAT CAME UP IN 8138 06:15:25,520 --> 06:15:26,680 TAMMY'S TALK. 8139 06:15:26,680 --> 06:15:27,320 >> GREAT. 8140 06:15:27,320 --> 06:15:29,040 ANY OTHER COMMENTS? 8141 06:15:29,040 --> 06:15:35,680 WELL, IT LOOKS AS THOUGH THERE 8142 06:15:35,680 --> 06:15:38,760 IS A CONSENSUS IN TERMS OF A 8143 06:15:38,760 --> 06:15:41,080 GAP AND SHOULD BE MORE 8144 06:15:41,080 --> 06:15:43,680 OPPORTUNITIES FOR LARGER 8145 06:15:43,680 --> 06:15:45,600 GROUPS WORKING TOGETHER. 8146 06:15:45,600 --> 06:15:48,200 AGAIN, IT ALWAYS SEEMS LIKE 8147 06:15:48,200 --> 06:15:51,520 ONE OF THE OUTCOMES COMMONLY 8148 06:15:51,520 --> 06:15:53,120 EXPRESSED BY THE PANELS HERE 8149 06:15:53,120 --> 06:15:54,320 AND SOMETHING THAT SEEMS AS 8150 06:15:54,320 --> 06:15:55,680 THOUGH THE NATURE OF THE WORK 8151 06:15:55,680 --> 06:15:57,000 NEEDS TO HAVE SOMETHING THAT 8152 06:15:57,000 --> 06:16:04,640 IS ON A LARGER SCALE THAN 8153 06:16:04,640 --> 06:16:06,240 INDIVIDUAL OPPORTUNITIES. 8154 06:16:06,240 --> 06:16:07,880 ANY OTHER COMMENT, BARBARA? 8155 06:16:07,880 --> 06:16:09,520 >> YEAH, I THINK SPECIFICALLY 8156 06:16:09,520 --> 06:16:11,720 LARGER IN THE SENSE OF BEING 8157 06:16:11,720 --> 06:16:16,400 MORE VALUABLE, MORE CANCER, 8158 06:16:16,400 --> 06:16:16,880 MULTIDISCIPLINARY. 8159 06:16:16,880 --> 06:16:19,280 >> OKAY, SO LARGER GROUPS, 8160 06:16:19,280 --> 06:16:19,960 MORE INTERDISCIPLINARY. 8161 06:16:19,960 --> 06:16:22,320 ANYBODY ELSE WANT TO REITERATE 8162 06:16:22,320 --> 06:16:23,840 ANY OF THE MAJOR POINTS THAT 8163 06:16:23,840 --> 06:16:26,120 MIGHT HAVE BEEN MADE? 8164 06:16:26,120 --> 06:16:29,680 I FEEL LIKE I AM SUMMARIZING 8165 06:16:29,680 --> 06:16:32,480 THE GRANT REVIEW HERE. 8166 06:16:32,480 --> 06:16:32,840 [LAUGHTER] 8167 06:16:32,840 --> 06:16:34,760 >> YOU WANT ME TO BRING BACK 8168 06:16:34,760 --> 06:16:35,960 UP THE QUESTIONS? 8169 06:16:35,960 --> 06:16:37,480 >> YEAH, IF WE COULD TAKE ONE 8170 06:16:37,480 --> 06:16:38,320 LAST LOOK AT THE QUESTIONS 8171 06:16:38,320 --> 06:16:39,600 BECAUSE WE ARE GETTING CLOSE 8172 06:16:39,600 --> 06:16:41,240 TO THE END HERE AND I KNOW IT 8173 06:16:41,240 --> 06:16:45,080 HAS BEEN A VERY LONG DAY BUT I 8174 06:16:45,080 --> 06:16:48,080 THOUGHT IT WAS INCREDIBLY 8175 06:16:48,080 --> 06:16:49,440 INFORMATIVE AND INTERESTING. 8176 06:16:49,440 --> 06:16:52,080 SO AGAIN, CRITICAL GAPS IN 8177 06:16:52,080 --> 06:16:53,600 KNOWLEDGE AND METHODOLOGIES 8178 06:16:53,600 --> 06:16:55,400 FOR THE RESEARCH AREAS 8179 06:16:55,400 --> 06:16:56,200 PRESENTED. 8180 06:16:56,200 --> 06:16:58,160 ANY RESOURCES OR METHODS 8181 06:16:58,160 --> 06:17:01,680 NEEDED TO FILL THE GAB IN BOTH 8182 06:17:01,680 --> 06:17:04,400 SHORT TERM AND LONG-TERM, SO 8183 06:17:04,400 --> 06:17:05,880 THINK ABOUT THE DIFFERENCE 8184 06:17:05,880 --> 06:17:08,000 THAT MIGHT BE SHORT OR LONG. 8185 06:17:08,000 --> 06:17:15,360 THIS IS YOUR LAST CHANCE FOR 8186 06:17:15,360 --> 06:17:15,760 INTERACTION. 8187 06:17:15,760 --> 06:17:16,640 STATE YOUR CASE. 8188 06:17:16,640 --> 06:17:22,320 IF NOT, I AM GOING TO -- I SEE 8189 06:17:22,320 --> 06:17:23,680 CURTIS AND JUSTIN, IT COULD 8190 06:17:23,680 --> 06:17:27,680 HAVE BEEN A TIE SO I WILL LET 8191 06:17:27,680 --> 06:17:28,160 YOU TALK. 8192 06:17:28,160 --> 06:17:30,200 >> MINE IS VERY SHORT THIS 8193 06:17:30,200 --> 06:17:32,240 TIME AND IN TERMS OF FILLING 8194 06:17:32,240 --> 06:17:34,440 THAT LONG-TERM GAP THAT CAME 8195 06:17:34,440 --> 06:17:36,480 UP MORE YESTERDAY THAN TODAY 8196 06:17:36,480 --> 06:17:38,120 IS HOW THESE INTERSECT WITH 8197 06:17:38,120 --> 06:17:38,800 REGULATORY FRAME WORKS. 8198 06:17:38,800 --> 06:17:41,960 WE HAVE A WHOLE ADDITIONAL 8199 06:17:41,960 --> 06:17:44,760 WORKSHOP ON HOW THE DIVERSITY 8200 06:17:44,760 --> 06:17:46,600 OF PROBIOTIC RESEARCH FOR THE 8201 06:17:46,600 --> 06:17:49,320 MANY DIFFERENT POSSIBLE 8202 06:17:49,320 --> 06:17:50,480 DEFINITIONS OF PROBIOTICS 8203 06:17:50,480 --> 06:17:51,480 FALLS UNDER DIFFERENT 8204 06:17:51,480 --> 06:17:52,680 REGULATORY FRAME WORKS AND 8205 06:17:52,680 --> 06:17:54,480 WHAT IS BEING DONE FOR 8206 06:17:54,480 --> 06:17:56,880 SAMPLING PRODUCTS LIKE WE JUST 8207 06:17:56,880 --> 06:18:00,520 SAW RECENTLY VERSUS LIFE 8208 06:18:00,520 --> 06:18:02,480 THERAPEUTIC PRODUCTS VERSUS 8209 06:18:02,480 --> 06:18:04,480 DIETARY SUPPLEMENTS AND 8210 06:18:04,480 --> 06:18:05,880 ASPECTS OF PROBIOTICS THAT WE 8211 06:18:05,880 --> 06:18:07,040 HAVE HEARD ABOUT TODAY SO I 8212 06:18:07,040 --> 06:18:09,600 WILL PUT THAT OUT THERE AS A 8213 06:18:09,600 --> 06:18:11,480 LONGER-TERM NEED. 8214 06:18:11,480 --> 06:18:12,240 >> THANK YOU, JUSTIN? 8215 06:18:12,240 --> 06:18:14,480 >> YOU KNOW, I LOVE THE IDEA 8216 06:18:14,480 --> 06:18:18,240 THAT IT IS A BIG COLLABORATIVE 8217 06:18:18,240 --> 06:18:18,560 PROJECT. 8218 06:18:18,560 --> 06:18:20,080 I THINK THIS IS WHERE EXCITING 8219 06:18:20,080 --> 06:18:21,040 THINGS ARE HAPPENING IN THE 8220 06:18:21,040 --> 06:18:22,880 FIELD RIGHT NOW BUT THE OTHER 8221 06:18:22,880 --> 06:18:25,400 THING THAT STRUCK ME ABOUT THE 8222 06:18:25,400 --> 06:18:27,560 SPEAKERS HERE AND WHAT I RUN 8223 06:18:27,560 --> 06:18:28,960 INTO THE FIELD OVER AND OVER 8224 06:18:28,960 --> 06:18:30,720 AGAIN IS THE EXPANSION OF 8225 06:18:30,720 --> 06:18:32,080 YOUNG INVESTIGATORS DOING 8226 06:18:32,080 --> 06:18:33,960 REALLY EXCITING THINGS IN THE 8227 06:18:33,960 --> 06:18:35,440 FIELD AND QUITE OFTEN IT IS 8228 06:18:35,440 --> 06:18:40,280 HARD TORE FOR THEM TO FIT IN 8229 06:18:40,280 --> 06:18:43,160 TO BIG ESTABLISHED CONSORTIA 8230 06:18:43,160 --> 06:18:45,000 SO THINKING ABOUT BACK WHEN I 8231 06:18:45,000 --> 06:18:49,120 WAS STARTING MY LAB, THE NEW 8232 06:18:49,120 --> 06:18:51,280 INNOVATER WAS MASSIVE FOR 8233 06:18:51,280 --> 06:18:53,280 ALLOWING US TO DO SOME THINGS 8234 06:18:53,280 --> 06:18:55,240 BUT THE FUNDING LEVEL, I WAS 8235 06:18:55,240 --> 06:18:56,640 VERY LUCKY TO GET IT. 8236 06:18:56,640 --> 06:18:58,280 SO THINKING ABOUT OTHER 8237 06:18:58,280 --> 06:18:59,480 MECHANISMS LIKE THAT WHERE IT 8238 06:18:59,480 --> 06:19:01,480 COULD BE A SINGLE PI KIND OF 8239 06:19:01,480 --> 06:19:05,720 OUT OF THE BOX THINKING, MAYBE 8240 06:19:05,720 --> 06:19:08,080 SMALLER THAN THE INNOVATOR BUT 8241 06:19:08,080 --> 06:19:10,120 GIVING THESE NEW INNOVATIVE 8242 06:19:10,120 --> 06:19:11,760 IDEAS ROOM TO -- LIKE IF YOU 8243 06:19:11,760 --> 06:19:13,920 LOOK AT WHAT NOAH PRESENTED 8244 06:19:13,920 --> 06:19:16,920 TODAY, THIS ENTIRELY NEW 8245 06:19:16,920 --> 06:19:17,840 METHOD, TOTALLY 8246 06:19:17,840 --> 06:19:18,560 GROUNDBREAKING, MASSIVE 8247 06:19:18,560 --> 06:19:20,640 EFFORT, WOULD BE VERY HARD FOR 8248 06:19:20,640 --> 06:19:22,480 A NEW INVESTIGATOR TO DO AS 8249 06:19:22,480 --> 06:19:24,320 THEY WERE GETTING ESTABLISHED 8250 06:19:24,320 --> 06:19:25,880 BECAUSE, YOU KNOW, IT IS SUCH 8251 06:19:25,880 --> 06:19:27,680 A -- IT TAKES DEVELOPMENT, IT 8252 06:19:27,680 --> 06:19:33,000 TAKES LIKE YOU KNOW HAVING A 8253 06:19:33,000 --> 06:19:34,480 COMMITTED TEAM TO HAVE FUNDING 8254 06:19:34,480 --> 06:19:36,040 FOR A NUMBER OF YEARS. 8255 06:19:36,040 --> 06:19:38,240 TO THINKING ABOUT WAYS FOR 8256 06:19:38,240 --> 06:19:40,160 INVESTIGATORS TO EXPLORE COOL 8257 06:19:40,160 --> 06:19:41,800 NEW APPROACHES COULD BE REALLY 8258 06:19:41,800 --> 06:19:47,200 VALUABLE TOWARDS THE FIELD, 8259 06:19:47,200 --> 06:19:48,600 YEAH. 8260 06:19:48,600 --> 06:19:49,480 >> THANK YOU. 8261 06:19:49,480 --> 06:19:51,480 >> I THINK THE GAP COULD BE 8262 06:19:51,480 --> 06:19:52,440 CONVERTED TO QUESTIONS. 8263 06:19:52,440 --> 06:19:56,640 YOU KNOW, WE NEED TO ASK A FEW 8264 06:19:56,640 --> 06:19:58,880 VERY IMPORTANT QUESTIONS AND 8265 06:19:58,880 --> 06:20:00,000 THEN ANSWER THOSE QUESTIONS 8266 06:20:00,000 --> 06:20:02,680 BASED ON IS THERE A COMMON 8267 06:20:02,680 --> 06:20:04,400 BIOLOGICAL BASIS FOR HUMAN 8268 06:20:04,400 --> 06:20:04,760 BEHAVIOR. 8269 06:20:04,760 --> 06:20:08,320 AND THERE SEEMS TO BE, YOU 8270 06:20:08,320 --> 06:20:10,040 KNOW, ALL KIND OF THINGS THAT 8271 06:20:10,040 --> 06:20:15,360 SEEM TO BE CONNECTED TO 8272 06:20:15,360 --> 06:20:16,280 DIFFERENT DISEASES, LIKE OBESE 8273 06:20:16,280 --> 06:20:19,040 PATIENTS MAY HAVE HIGHER RISK 8274 06:20:19,040 --> 06:20:21,880 OF DEVELOPING MORE SEVERE FORM 8275 06:20:21,880 --> 06:20:27,080 OF COVID-19, ALL OF THESE 8276 06:20:27,080 --> 06:20:28,760 QUESTIONS BUT TALKING ABOUT 8277 06:20:28,760 --> 06:20:32,280 THE BIOLOGICAL BASIS 8278 06:20:32,280 --> 06:20:36,400 UNDERNEATH ALL THESE RISKS, IS 8279 06:20:36,400 --> 06:20:38,560 PART OF THAT COMMON BIOLOGICAL 8280 06:20:38,560 --> 06:20:38,880 BASIS. 8281 06:20:38,880 --> 06:20:52,840 AND ANOTHER YOU KNOW MORE 8282 06:20:52,840 --> 06:21:03,560 TECHNICAL ISSUE, YOU KNOW WITH 8283 06:21:03,560 --> 06:21:07,640 THE IMPACT AND MANY STUDIES 8284 06:21:07,640 --> 06:21:08,800 USE MICROBIOTICS AND PREDICT 8285 06:21:08,800 --> 06:21:15,080 RESPONSE BUT MANY OTHER 8286 06:21:15,080 --> 06:21:18,200 STUDIES SHOW THAT SOME MEMBER 8287 06:21:18,200 --> 06:21:20,560 OR EVEN NONDETECTABLE, WHEN 8288 06:21:20,560 --> 06:21:21,760 THEY BECOME DOMINANT, THEY 8289 06:21:21,760 --> 06:21:23,240 BECOME VERY IMPORTANT. 8290 06:21:23,240 --> 06:21:27,040 SO YOU CANNOT PREDICT BASED 8291 06:21:27,040 --> 06:21:28,120 JUST ON MICROBIOTICS. 8292 06:21:28,120 --> 06:21:33,800 SO MAYBE MORE LIKE THIS, THANK 8293 06:21:33,800 --> 06:21:35,520 YOU. 8294 06:21:35,520 --> 06:21:36,880 >> THANK YOU. 8295 06:21:36,880 --> 06:21:39,040 >> I WANTED TO ENTER A POINT 8296 06:21:39,040 --> 06:21:40,280 OR SEVERAL POINTS. 8297 06:21:40,280 --> 06:21:41,600 I THINK ANOTHER OPPORTUNITY 8298 06:21:41,600 --> 06:21:45,800 ALONG THIS LINE IS TO IDENTIFY 8299 06:21:45,800 --> 06:21:51,520 WHAT IS ACTUALLY NEED HE 8300 06:21:51,520 --> 06:21:55,520 NEEDED TO DO VERSUS EASY TO 8301 06:21:55,520 --> 06:21:55,800 DO. 8302 06:21:55,800 --> 06:21:58,960 SO WE CAN WORK TOGETHER TO DO 8303 06:21:58,960 --> 06:22:00,000 MEANINGFUL SITE STUDIES AND 8304 06:22:00,000 --> 06:22:01,400 THAT IS WHAT WEEK DO. 8305 06:22:01,400 --> 06:22:07,000 NOT THAT THE SMALL INTESTINE 8306 06:22:07,000 --> 06:22:08,600 IS NOT EVENTUALLY IMPORTANT, 8307 06:22:08,600 --> 06:22:10,280 IT IS JUST DIFFICULT TO DO 8308 06:22:10,280 --> 06:22:10,600 THAT. 8309 06:22:10,600 --> 06:22:12,560 SO THE POINT OF HAVING ALL 8310 06:22:12,560 --> 06:22:23,720 THESE CLEAR ROLES FOR 8311 06:22:23,720 --> 06:22:24,880 ENGINEERS, ALIGNING WITH THAT 8312 06:22:24,880 --> 06:22:27,520 AND WE WANT THESE TYPES OF 8313 06:22:27,520 --> 06:22:28,880 CAPABILITIES, JUST PAUSING AND 8314 06:22:28,880 --> 06:22:30,160 SPENDING ENOUGH TIME AND 8315 06:22:30,160 --> 06:22:32,880 RESOURCES TO MAKE THAT HAPPEN 8316 06:22:32,880 --> 06:22:34,680 BECAUSE THAT RESULTS IN 8317 06:22:34,680 --> 06:22:41,680 STUDIES THAT COULDN'T BE DONE 8318 06:22:41,680 --> 06:22:43,200 EITHER -- OTHERWISE AND MOVE 8319 06:22:43,200 --> 06:22:43,640 THAT FORWARD. 8320 06:22:43,640 --> 06:22:47,200 JUST FIGURE OUT HOW TO ASK THE 8321 06:22:47,200 --> 06:22:49,320 QUESTION AND ENGAGE THE 8322 06:22:49,320 --> 06:22:50,120 BROADER COMMUNITY. 8323 06:22:50,120 --> 06:22:55,120 THERE ARE VERY TALENTED 8324 06:22:55,120 --> 06:22:57,720 ENGINEERS OUT THERE THAT COULD 8325 06:22:57,720 --> 06:23:00,280 HELP IF WE JUST ASK THE RIGHT 8326 06:23:00,280 --> 06:23:00,960 QUESTIONS. 8327 06:23:00,960 --> 06:23:01,880 >> YES, THANK YOU, VERY 8328 06:23:01,880 --> 06:23:04,200 IMPORTANT WORK IS NEEDED. 8329 06:23:04,200 --> 06:23:05,480 ANY OTHER QUESTIONS BEFORE WE 8330 06:23:05,480 --> 06:23:08,440 PASS THIS MEETING PACK TO OUR 8331 06:23:08,440 --> 06:23:08,840 ORGANIZERS? 8332 06:23:08,840 --> 06:23:15,920 IF NOT, I WILL TAKE ONE LAST 8333 06:23:15,920 --> 06:23:16,280 LOOK HERE. 8334 06:23:16,280 --> 06:23:27,400 SO I AM GOING TO HAND IT BACK 8335 06:23:27,400 --> 06:23:27,840 OVER TO MARVA. 8336 06:23:27,840 --> 06:23:29,440 >> DO YOU HAVE ANYTHING ELSE 8337 06:23:29,440 --> 06:23:30,880 BEFORE WE MOVE ON? 8338 06:23:30,880 --> 06:23:32,880 >> NO, IT IS TIME TO GO TO 8339 06:23:32,880 --> 06:23:40,720 OUR CLOSING WITH YOU AND MARVA 8340 06:23:40,720 --> 06:23:42,920 SO HYE SOOK, I WILL TAKE IT 8341 06:23:42,920 --> 06:23:44,680 AWAY AND SHARE SOME THOUGHTS 8342 06:23:44,680 --> 06:23:45,960 IN CLOSING, LOOKING AT THE 8343 06:23:45,960 --> 06:23:49,520 HIGHLIGHTS FOR THE PAST TWO 8344 06:23:49,520 --> 06:23:52,080 DAYS, JUST FANTASTIC. 8345 06:23:52,080 --> 06:23:52,560 BARBARA? 8346 06:23:52,560 --> 06:23:57,400 >> OH, WELL, I LOOKED AT SOME 8347 06:23:57,400 --> 06:24:00,360 OF THE POINTS AND TRYING TO 8348 06:24:00,360 --> 06:24:02,640 ADDRESS REMARKS BUT FOUND IT 8349 06:24:02,640 --> 06:24:04,360 WAS ALREADY DONE IN THE 8350 06:24:04,360 --> 06:24:05,160 SESSION OF DISCUSSION. 8351 06:24:05,160 --> 06:24:12,800 SO I STRUGGLE HOW WE CAN 8352 06:24:12,800 --> 06:24:16,240 CLOSE, SO HOW ARE WE GOING TO 8353 06:24:16,240 --> 06:24:22,680 THINK ABOUT GOING THIS 8354 06:24:22,680 --> 06:24:26,280 DIRECTION BECAUSE WE HAVE THE 8355 06:24:26,280 --> 06:24:27,560 BEST CHALLENGES AND 8356 06:24:27,560 --> 06:24:30,280 OPPORTUNITIES AND KEEP TALKING 8357 06:24:30,280 --> 06:24:38,880 ABOUT IMPORTANCE OF THE 8358 06:24:38,880 --> 06:24:41,240 COLLABORATION, IMPORTANCE OF 8359 06:24:41,240 --> 06:24:43,480 THE VERIFIER, THAT IS VERY 8360 06:24:43,480 --> 06:24:45,240 IMPORTANT BUT IT CLOSE IT, WE 8361 06:24:45,240 --> 06:24:46,560 LIKE TO DISCUSS HERE AND THIS 8362 06:24:46,560 --> 06:24:52,040 IS IMPORTANT FOR THE CLINICAL 8363 06:24:52,040 --> 06:24:54,960 OUTCOME MEASUREMENTS, WORKING 8364 06:24:54,960 --> 06:24:58,840 FOR THE PROCEDURE, HOW CAN I 8365 06:24:58,840 --> 06:25:00,080 IDENTIFY THE TARGETED 8366 06:25:00,080 --> 06:25:02,280 INFORMATION THAT MOST LIKELY 8367 06:25:02,280 --> 06:25:03,720 IS MORE RESPONSIVE. 8368 06:25:03,720 --> 06:25:07,640 SO WE SCORE LONGITUDINAL 8369 06:25:07,640 --> 06:25:11,400 STUDIES ARE IMPORTANT AND ALSO 8370 06:25:11,400 --> 06:25:22,280 PROBABLY THE STRUCTURE IN THE 8371 06:25:22,280 --> 06:25:23,720 PERSPECTIVE OF TRANSCRIPTOME, 8372 06:25:23,720 --> 06:25:25,360 VERY IMPORTANT. 8373 06:25:25,360 --> 06:25:31,360 AND WE ALSO THINK ABOUT THE 8374 06:25:31,360 --> 06:25:32,960 SAMPLING AND THE METHOD TO 8375 06:25:32,960 --> 06:25:34,720 COLLECT THE DATA AND FORMAT IT 8376 06:25:34,720 --> 06:25:35,040 WELL. 8377 06:25:35,040 --> 06:25:38,480 SO NOW WE ARE TALKING ABOUT 8378 06:25:38,480 --> 06:25:40,240 SAMPLES FROM EVERYWHERE, 8379 06:25:40,240 --> 06:25:43,400 MICROBIOME SAMPLES FROM HUMANS 8380 06:25:43,400 --> 06:25:46,040 AND FROM ANIMALS SO THAT IS 8381 06:25:46,040 --> 06:25:49,480 FANTASTIC WE HAVE THAT ECODATA 8382 06:25:49,480 --> 06:25:53,800 AS WELL SO THERE MUST BE 8383 06:25:53,800 --> 06:25:56,040 SYSTEM STANDARDIZED FORMAT 8384 06:25:56,040 --> 06:26:00,040 THAT WE CAN USE FOR THIS STUDY 8385 06:26:00,040 --> 06:26:03,040 COLLABORATIVELY AS IT WOULD BE 8386 06:26:03,040 --> 06:26:04,720 EXPENSIVE WITH JUST ONE 8387 06:26:04,720 --> 06:26:05,480 PERSON. 8388 06:26:05,480 --> 06:26:13,640 SO THAT IS THE CHALLENGE AND 8389 06:26:13,640 --> 06:26:14,040 OPPORTUNITY. 8390 06:26:14,040 --> 06:26:16,480 >> YEAH, I THINK THERE IS 8391 06:26:16,480 --> 06:26:18,000 NEED FOR DEVELOPING COMMUNITY 8392 06:26:18,000 --> 06:26:20,000 CONSENSUS ABOUT WHAT MET IT 8393 06:26:20,000 --> 06:26:23,720 DATA ARE NEEDED, WHETHER IT IS 8394 06:26:23,720 --> 06:26:24,480 IN CHARACTERIZING THE 8395 06:26:24,480 --> 06:26:26,880 INTRODUCTION ITSELF, OR HOW 8396 06:26:26,880 --> 06:26:28,720 YOU ARE DOING THE STUDY, HOW 8397 06:26:28,720 --> 06:26:30,240 YOU ARE SAMPLING THE STUDY. 8398 06:26:30,240 --> 06:26:31,400 I THINK ONE OF THE ISSUES THAT 8399 06:26:31,400 --> 06:26:33,360 I WANT TO GO BACK TO THAT CAME 8400 06:26:33,360 --> 06:26:40,280 UP DURING THE WORKSHOP WAS THE 8401 06:26:40,280 --> 06:26:42,960 QUESTION. CIRCADIAN TIME AND 8402 06:26:42,960 --> 06:26:45,360 SEASONALI ITY AND WHAT A 8403 06:26:45,360 --> 06:26:46,520 DIFFERENCE THOSE MAKE AND HOW 8404 06:26:46,520 --> 06:26:49,400 WE CAN THINK ABOUT AT LEAST 8405 06:26:49,400 --> 06:26:51,000 PRESCRIBING IF NOT CONTROLLING 8406 06:26:51,000 --> 06:26:51,800 FOR THEM. 8407 06:26:51,800 --> 06:26:52,960 BEGINNING TO THINK MORE NOT 8408 06:26:52,960 --> 06:26:56,480 JUST ABOUT THE BACTERIAL 8409 06:26:56,480 --> 06:27:01,640 COMPONENT OF THE MICROBIOME, 8410 06:27:01,640 --> 06:27:03,480 MICROBIOTA BUT ALSO THE 8411 06:27:03,480 --> 06:27:04,600 ENVIRONMENT BECAUSE THOSE 8412 06:27:04,600 --> 06:27:05,520 CLEARLY HAVE IMPORTANT ROLES 8413 06:27:05,520 --> 06:27:07,880 BUT ARE MAYBE A LITTLE HARDER 8414 06:27:07,880 --> 06:27:12,640 TO STUDY THAN THE BACTERIAL 8415 06:27:12,640 --> 06:27:13,000 COMPONENT. 8416 06:27:13,000 --> 06:27:16,080 ONE OF THE THINGS THAT CAME UP 8417 06:27:16,080 --> 06:27:18,040 WAS THE IMPORTANCE OF THINKING 8418 06:27:18,040 --> 06:27:20,880 ABOUT HOW YOU CHARACTERIZE 8419 06:27:20,880 --> 06:27:21,200 NORMAL. 8420 06:27:21,200 --> 06:27:23,720 YOU KNOW, WHAT IS -- PERHAPS 8421 06:27:23,720 --> 06:27:26,280 NOT NORMAL BUT HEALTHY, WHAT 8422 06:27:26,280 --> 06:27:29,880 DOES HEALTHY LOOK LIKE, HOW 8423 06:27:29,880 --> 06:27:31,120 DOES IT VARY WITHIN AN 8424 06:27:31,120 --> 06:27:32,680 INDIVIDUAL AND FROM INDIVIDUAL 8425 06:27:32,680 --> 06:27:35,240 TO INDIVIDUAL BY THEIR, YOU 8426 06:27:35,240 --> 06:27:36,120 KNOW, DIFFERENT WAYS TO 8427 06:27:36,120 --> 06:27:36,560 DESCRIBE THAT. 8428 06:27:36,560 --> 06:27:38,840 AND I THINK THE OTHER THING WE 8429 06:27:38,840 --> 06:27:42,560 HEARD A LOT ABOUT THE 8430 06:27:42,560 --> 06:27:44,360 IMPORTANCE OF IS THE 8431 06:27:44,360 --> 06:27:45,680 IMPORTANCE OF DOING PILOT 8432 06:27:45,680 --> 06:27:48,560 CLINICAL TRIALS BEFORE YOU GO 8433 06:27:48,560 --> 06:27:51,600 TO A LARGER CLINICAL TRIAL 8434 06:27:51,600 --> 06:27:53,520 BECAUSE THE PILOT CLINICAL 8435 06:27:53,520 --> 06:27:55,120 TRIAL CAN HELP YOU FIGURE OUT 8436 06:27:55,120 --> 06:27:57,080 WHAT YOUR EFFECT SIZE IS AND 8437 06:27:57,080 --> 06:28:00,160 WHAT YOUR SAMPLE SIZE SHOULD 8438 06:28:00,160 --> 06:28:01,680 BE, WHAT OUTCOME SHOULD BE, 8439 06:28:01,680 --> 06:28:03,520 WHEN YOU LOOK AT IT, WHAT DOSE 8440 06:28:03,520 --> 06:28:05,800 IT SHOULD BE AND WHEN YOU ARE 8441 06:28:05,800 --> 06:28:07,840 EXPOSED TO IT AND FOR HOW 8442 06:28:07,840 --> 06:28:10,920 LONG, WHO SHOULD BE INCLUDED 8443 06:28:10,920 --> 06:28:13,800 IN YOUR TRIAL, WHO WILL HAVE 8444 06:28:13,800 --> 06:28:17,280 AN EFFECT, WHO CAN IT HAVE AN 8445 06:28:17,280 --> 06:28:18,720 EFFECT ON? 8446 06:28:18,720 --> 06:28:20,560 YOU KNOW ARE THERE SOME PEOPLE 8447 06:28:20,560 --> 06:28:24,920 WHO ARE ABLE TO BE COLONIZED 8448 06:28:24,920 --> 06:28:29,880 BY THE INTRODUCTION OF PEOPLE 8449 06:28:29,880 --> 06:28:31,400 FOR THE BIOME EFFECT. 8450 06:28:31,400 --> 06:28:33,360 >> YES, AND ALSO THE 8451 06:28:33,360 --> 06:28:37,600 IMPORTANCE OF COMBINING ANIMAL 8452 06:28:37,600 --> 06:28:39,720 ACTION BECAUSE WE CAN DEVELOP 8453 06:28:39,720 --> 06:28:42,120 CLEAR INTERACTION OF THE 8454 06:28:42,120 --> 06:28:44,880 MICROBIOME JUST TO KNOW WHAT 8455 06:28:44,880 --> 06:28:46,280 AND WHERE WE CAN SEE THIS 8456 06:28:46,280 --> 06:28:46,640 NATURE. 8457 06:28:46,640 --> 06:28:48,240 SO I THINK IT IS VERY 8458 06:28:48,240 --> 06:28:53,320 IMPORTANT AND VERY CHALLENGING 8459 06:28:53,320 --> 06:28:55,120 AND WHILE WE LOOK AT THIS 8460 06:28:55,120 --> 06:28:58,080 TODAY OR ANOTHER DAY, IT IS 8461 06:28:58,080 --> 06:28:59,080 ABOUT THE CHALLENGE GOING 8462 06:28:59,080 --> 06:29:04,000 FORWARD AND HOW WE CAN SEE THE 8463 06:29:04,000 --> 06:29:06,280 EFFECT OF THE MICROBIOME, THAT 8464 06:29:06,280 --> 06:29:09,160 IS THE MOST KEY PART AND VERY 8465 06:29:09,160 --> 06:29:11,880 CHALLENGING PART BUT I THINK 8466 06:29:11,880 --> 06:29:13,640 THE FEEL, I BEEN THINKING 8467 06:29:13,640 --> 06:29:17,480 ABOUT IT LONG TIME NOW, JUST 8468 06:29:17,480 --> 06:29:18,760 PUT BACK TOGETHER AND OPEN THE 8469 06:29:18,760 --> 06:29:20,720 DOOR AND WE CAN START FORMING 8470 06:29:20,720 --> 06:29:22,080 THE ROW SEARCH OF TEAMS TO 8471 06:29:22,080 --> 06:29:28,080 FIGURE OUT HOW WE CAN TACKLE 8472 06:29:28,080 --> 06:29:29,480 NEW TYPES OF ACTIVITY. 8473 06:29:29,480 --> 06:29:31,680 I THINK THAT IS IMPORTANT 8474 06:29:31,680 --> 06:29:34,960 POINT EVERYONE IS MAKING OVER 8475 06:29:34,960 --> 06:29:36,280 TWO DAYS. 8476 06:29:36,280 --> 06:29:38,640 >> AND WIDER ON THAT, Dr. 8477 06:29:38,640 --> 06:29:40,040 KIM, JUST FIGURING OUT 8478 06:29:40,040 --> 06:29:41,240 MECHANISM IS SOMETHING YOU CAN 8479 06:29:41,240 --> 06:29:43,240 GET OUT OF THE PILOT CLINICAL 8480 06:29:43,240 --> 06:29:46,200 TRIAL, ESPECIALLY IF YOU HAVE 8481 06:29:46,200 --> 06:29:53,960 THE INFRASTRUCTURE TO ARCHIVE 8482 06:29:53,960 --> 06:29:55,680 LOT SPECIMENS, WHEN DRIVES 8483 06:29:55,680 --> 06:29:57,760 THOSE SPECIMENS, A COMMUNITY 8484 06:29:57,760 --> 06:29:59,040 CONSENSUS STANDARD FOR HOW 8485 06:29:59,040 --> 06:30:00,840 THEY ARE COLLECTED AND MADE 8486 06:30:00,840 --> 06:30:01,880 AVAILABLE FOR OTHER 8487 06:30:01,880 --> 06:30:05,200 RESEARCHERS PR-PS TO ALSO 8488 06:30:05,200 --> 06:30:11,440 ACCESS AT AN APPROPRIATE TIME. 8489 06:30:11,440 --> 06:30:15,520 >> YEAH, I ACTUALLY WILL 8490 06:30:15,520 --> 06:30:19,040 MENTION SOME OF THE NIH 8491 06:30:19,040 --> 06:30:20,680 SAMPLES FOR US AND -- 8492 06:30:20,680 --> 06:30:21,480 [OVERLAPPING SPEAKERS] 8493 06:30:21,480 --> 06:30:27,240 >> YEAH, AND THEY HAD THE LAST 8494 06:30:27,240 --> 06:30:32,480 PHENO CODING AND NOT SURE THE 8495 06:30:32,480 --> 06:30:33,600 MICROBIOME BUT THEY HAVE THE 8496 06:30:33,600 --> 06:30:37,360 RECORD AS WELL AS THE METADATA 8497 06:30:37,360 --> 06:30:41,120 AND IT IS REGULARLY AVAILABLE. 8498 06:30:41,120 --> 06:30:44,880 >> I WAS CHECKING TO SEE 8499 06:30:44,880 --> 06:30:46,120 WHETHER PODMA WAS HERE SINCE 8500 06:30:46,120 --> 06:30:47,480 SHE WAS ONE OF THE PROGRAM 8501 06:30:47,480 --> 06:30:48,120 MANAGERS ON THAT. 8502 06:30:48,120 --> 06:30:54,200 THERE IS A RECENTLY MICROBIOME 8503 06:30:54,200 --> 06:30:56,560 COMPONENT BUT IT IS RECENTLY 8504 06:30:56,560 --> 06:30:57,480 PRODUCED AND IT WILL BE A 8505 06:30:57,480 --> 06:30:59,880 WHILE BEFORE IT IS AVAILABLE 8506 06:30:59,880 --> 06:31:03,960 AND I AM A PART OF THAT 8507 06:31:03,960 --> 06:31:04,880 PROJECT, PRODUCING MICROBIOME 8508 06:31:04,880 --> 06:31:05,880 SAMPLES AND PART OF THE WORK 8509 06:31:05,880 --> 06:31:09,440 THAT WILL BE AVAILABLE BUT AS 8510 06:31:09,440 --> 06:31:11,240 CURT SAID, IT WILL BE A LITTLE 8511 06:31:11,240 --> 06:31:12,920 WHILE BEFORE IT IS AVAILABLE. 8512 06:31:12,920 --> 06:31:21,200 >> AND ALSO IN TERMS OF THE 8513 06:31:21,200 --> 06:31:26,600 METADATA, WE HAVE BEEN NEEDING 8514 06:31:26,600 --> 06:31:28,800 TO STANDARDIZE SO WE CAN GET 8515 06:31:28,800 --> 06:31:32,080 ACCESS TO THE DATA AND ANALYZE 8516 06:31:32,080 --> 06:31:33,280 THE CLINICAL OUTCOME. 8517 06:31:33,280 --> 06:31:38,520 ALSO THE NIH IS ONE OF THE 8518 06:31:38,520 --> 06:31:38,960 LEAST -- 8519 06:31:38,960 --> 06:31:39,680 [INDISCERNIBLE] 8520 06:31:39,680 --> 06:31:44,280 CALLED BRIDGES FOR AI AND IT 8521 06:31:44,280 --> 06:31:47,480 IS NOT ABOUT THE DATA FOR AI 8522 06:31:47,480 --> 06:31:50,200 BUT ABOUT HOW TO GENERATE THE 8523 06:31:50,200 --> 06:31:53,840 MACHINE LEARNING AND AI DATA 8524 06:31:53,840 --> 06:31:54,160 SETS. 8525 06:31:54,160 --> 06:31:56,360 THEY ALSO HAVE SOME 8526 06:31:56,360 --> 06:31:58,520 OPPORTUNITY FOR METRO BIOME 8527 06:31:58,520 --> 06:31:59,600 GROUP TO PARTICIPATE IN THAT 8528 06:31:59,600 --> 06:32:07,800 KIND OF ACTIVITY SO THAT WE 8529 06:32:07,800 --> 06:32:10,520 CAN USE THAT TO GENERATE THE 8530 06:32:10,520 --> 06:32:14,840 ASSEMBLY OF HUMAN DATA. 8531 06:32:14,840 --> 06:32:28,520 WE HAVE A RAISED HAND? 8532 06:32:28,520 --> 06:32:33,040 >> MICROBIOME DATA IN SOURCES, 8533 06:32:33,040 --> 06:32:37,520 YOU WEIGH OUTCOME AND SO 8534 06:32:37,520 --> 06:32:40,240 BEFORE PREGNANCY AND AFTER 8535 06:32:40,240 --> 06:32:43,840 PREGNANCY, FOR SEVEN YEARS, 8536 06:32:43,840 --> 06:32:47,920 THEY ARE FOLLOWED AND APPROVE 8537 06:32:47,920 --> 06:32:51,000 ONE MONTH, SIX MONTHS, THEY 8538 06:32:51,000 --> 06:32:51,800 COLLECT MICROBIOME SPECIMEN 8539 06:32:51,800 --> 06:32:57,280 THAT WE CAN USE FOR THIS SO 8540 06:32:57,280 --> 06:33:08,760 THAT IS IMPROVED BY NIH SO 8541 06:33:08,760 --> 06:33:09,760 MICROBIOME AND OUTCOME. 8542 06:33:09,760 --> 06:33:11,240 >> OKAY, THANK YOU. 8543 06:33:11,240 --> 06:33:11,680 ANYTHING ELSE? 8544 06:33:11,680 --> 06:33:17,120 >> WELL, IF I COULD SHARE, I 8545 06:33:17,120 --> 06:33:18,720 HAD A QUICK SLIDE. 8546 06:33:18,720 --> 06:33:30,800 I WANTED TO GET TO SOME OF THE 8547 06:33:30,800 --> 06:33:38,160 CAVEATS AND CHALLENGES, YEAH, 8548 06:33:38,160 --> 06:33:39,680 JUST SOME OF THE CHALLENGES WE 8549 06:33:39,680 --> 06:33:42,680 TALKED ABOUT OVER THE COURSE 8550 06:33:42,680 --> 06:33:45,640 OF THE TWO DAYS, STRAIN 8551 06:33:45,640 --> 06:33:50,480 INSTABILITY, PART OF 8552 06:33:50,480 --> 06:33:51,760 CHARACTERIZING INTERVENTION, 8553 06:33:51,760 --> 06:33:53,840 ONE IN PARTICULAR, TALKED 8554 06:33:53,840 --> 06:33:56,200 ABOUT OUR KNOWLEDGE OF 8555 06:33:56,200 --> 06:33:57,400 BEHAVIOR OF MICROBIAL SYSTEMS. 8556 06:33:57,400 --> 06:33:59,520 THE IDEA THAT A SINGLE 8557 06:33:59,520 --> 06:34:03,680 MOLECULE MAY BE MULTIPLE 8558 06:34:03,680 --> 06:34:08,200 MECHANISMS AND MECHANISMS CAN 8559 06:34:08,200 --> 06:34:13,320 ENERGIZE OR CHEMICALLIZE AND 8560 06:34:13,320 --> 06:34:14,960 WE NEED TO KNOW ABOUT THAT 8561 06:34:14,960 --> 06:34:16,760 BECAUSE IT MAY REPRESENT AT SO 8562 06:34:16,760 --> 06:34:18,360 MANY DIFFERENT LEVELS AND THEN 8563 06:34:18,360 --> 06:34:20,080 THE IMPORTANCE OF TOGGLING 8564 06:34:20,080 --> 06:34:22,600 BACK AND FORTH BETWEEN 8565 06:34:22,600 --> 06:34:23,480 DIFFERENT SYSTEMS, BETWEEN 8566 06:34:23,480 --> 06:34:26,120 CHIPS WHERE EACH SYSTEM HAS 8567 06:34:26,120 --> 06:34:28,280 ITS OWN ADVANTAGES AND 8568 06:34:28,280 --> 06:34:29,800 DISADVANTAGES, WHETHER YOU ARE 8569 06:34:29,800 --> 06:34:32,120 DOING LARGE SCALE 8570 06:34:32,120 --> 06:34:34,120 TRANSCRIPTOME OR LOOKING AT IN 8571 06:34:34,120 --> 06:34:36,640 VIVO BUT IT IS A FIERCELY 8572 06:34:36,640 --> 06:34:38,720 COMPLEX THING TO STUDY BECAUSE 8573 06:34:38,720 --> 06:34:41,760 IT IS DYNAMIC, INTERACTIVE, 8574 06:34:41,760 --> 06:34:45,720 THE OUTCOME INTEGRATES MANY 8575 06:34:45,720 --> 06:34:46,320 DYNAMICALLY INTERACTIVE 8576 06:34:46,320 --> 06:34:46,680 INPUTS. 8577 06:34:46,680 --> 06:34:48,400 BUT I THINK WE CAME OUT OF 8578 06:34:48,400 --> 06:34:54,800 THIS MEETING WITH A LOT OF 8579 06:34:54,800 --> 06:35:04,440 EXCITING EMERGENT TOOLS, 8580 06:35:04,440 --> 06:35:12,280 WHETHER IT'S THE CURRENTLY -- 8581 06:35:12,280 --> 06:35:12,760 [INDISCERNIBLE] 8582 06:35:12,760 --> 06:35:24,320 , USING -- USING THINGS LIKE 8583 06:35:24,320 --> 06:35:25,640 SHINE, MBHR, I CAN SEE WE HAVE 8584 06:35:25,640 --> 06:35:28,040 A LOT OF NEW TOOLS TO TACKLE 8585 06:35:28,040 --> 06:35:28,840 THESE CHALLENGES AND I AM 8586 06:35:28,840 --> 06:35:33,720 HOPING WE ARE ON THE 8587 06:35:33,720 --> 06:35:36,480 ENLIGHTENMENT UPLOPE OF 8588 06:35:36,480 --> 06:35:38,120 RUSTEM'S CURVE THERE. 8589 06:35:38,120 --> 06:35:40,080 >> YEAH, AND I ALSO LIKE TO 8590 06:35:40,080 --> 06:35:42,960 COMMENT ABOUT THE CONTINUED 8591 06:35:42,960 --> 06:35:44,440 IMPORTANCE OF DIAGNOSTICS. 8592 06:35:44,440 --> 06:35:47,280 SO THE TECHNOLOGY DISCUSSED 8593 06:35:47,280 --> 06:35:49,080 TODAY IS -- COULD BE THE 8594 06:35:49,080 --> 06:35:50,680 PROTOTYPE FOR THE LONG-TERM 8595 06:35:50,680 --> 06:35:56,560 AND SOLVE THAT ISSUE IN THE 8596 06:35:56,560 --> 06:35:56,960 DIAGNOSTIC. 8597 06:35:56,960 --> 06:35:58,760 BUT I SEE THIS IS A GOOD 8598 06:35:58,760 --> 06:36:06,480 OPPORTUNITY FOR THE FIELD AS 8599 06:36:06,480 --> 06:36:06,800 WELL. 8600 06:36:06,800 --> 06:36:07,520 >> FABULOUS DISCUSSIONS. 8601 06:36:07,520 --> 06:36:14,880 I THINK MANY, MANY THINGS, MY 8602 06:36:14,880 --> 06:36:24,040 THANKS TO EVERYBODY, KUDOS TO 8603 06:36:24,040 --> 06:36:29,080 EARN EVERYONE. 8604 06:36:29,080 --> 06:36:32,160 >> AND I LIKE TO SAY 8605 06:36:32,160 --> 06:36:33,680 MICROBIOTICS, IT IS VERY NEW 8606 06:36:33,680 --> 06:36:36,280 SO I THINK WE WILL GET THERE. 8607 06:36:36,280 --> 06:36:37,800 >> AND ONE OF THE THINGS THIS 8608 06:36:37,800 --> 06:36:40,200 WAS SORT OF SAID TODAY BUT 8609 06:36:40,200 --> 06:36:42,640 PERHAPS NOT THAT EXPLICITLY IS 8610 06:36:42,640 --> 06:36:44,400 ONE OF THE LEVELS WE NEED TO 8611 06:36:44,400 --> 06:36:46,080 BE THINKING ABOUT THIS ALL IN 8612 06:36:46,080 --> 06:36:47,480 IS THE CONTEXT OF EVOLUTION, 8613 06:36:47,480 --> 06:36:49,800 WHETHER IT IS THE 8614 06:36:49,800 --> 06:36:51,720 MICROORGANISM OF EVOLUTION OUR 8615 06:36:51,720 --> 06:36:53,480 HUMAN EVOLUTION BECAUSE IF IT 8616 06:36:53,480 --> 06:36:55,680 DOESN'T MAKE SENSE IN THAT 8617 06:36:55,680 --> 06:37:00,200 CONTEXT, IT MAY NOT MAKE 8618 06:37:00,200 --> 06:37:00,480 SENSE. 8619 06:37:00,480 --> 06:37:06,320 >> MM-HMM, YES, AND I LIKE TO 8620 06:37:06,320 --> 06:37:12,640 ECHO ABOUT THE -- I LIKE THE 8621 06:37:12,640 --> 06:37:16,040 FACT THAT RESURFACING 8622 06:37:16,040 --> 06:37:17,200 MICROBIOTIC AS PREVENTIVE 8623 06:37:17,200 --> 06:37:20,240 METHOD AS WELL AS TREATMENT. 8624 06:37:20,240 --> 06:37:25,800 SO THE WHOLE QUESTION OF THE 8625 06:37:25,800 --> 06:37:28,960 RESEARCH AND I THINK IT IS 8626 06:37:28,960 --> 06:37:32,480 NEAT MICROBIOME IS APPEARING 8627 06:37:32,480 --> 06:37:40,400 IN THE PREVENTIVE METHOD. 8628 06:37:40,400 --> 06:37:41,280 ANYTHING ELSE BARBARA? 8629 06:37:41,280 --> 06:37:42,240 >> JUST A FINAL THANK YOU AND 8630 06:37:42,240 --> 06:37:49,280 I WILL LET YOU HAND IT OFF. 8631 06:37:49,280 --> 06:37:52,280 >> OH, ALL RIGHT. 8632 06:37:52,280 --> 06:37:57,200 SO ALL THE TALKS WERE VERY 8633 06:37:57,200 --> 06:37:59,120 EXCITING, VERY INFORMATIVE AND 8634 06:37:59,120 --> 06:37:59,640 ALSO -- 8635 06:37:59,640 --> 06:38:00,720 [INDISCERNIBLE] 8636 06:38:00,720 --> 06:38:05,120 AND WE MADE A LOT OF 8637 06:38:05,120 --> 06:38:06,200 CONDITIONS ON HOW THE 8638 06:38:06,200 --> 06:38:07,680 PROCEDURES OF THERAPY HAVE 8639 06:38:07,680 --> 06:38:08,680 BEEN CHALLENGING AND THE 8640 06:38:08,680 --> 06:38:10,280 DISCUSSION WAS VERY EXCITING 8641 06:38:10,280 --> 06:38:14,800 AS TO LIKE THE TALKS AND 8642 06:38:14,800 --> 06:38:16,680 STIMULATING OUR THOUGHTS ON 8643 06:38:16,680 --> 06:38:18,520 WHERE THE FIELD SHOULD MOVE 8644 06:38:18,520 --> 06:38:18,880 FORWARD. 8645 06:38:18,880 --> 06:38:21,080 SO THANK YOU ALL FOR CREATING 8646 06:38:21,080 --> 06:38:23,120 THESE OUTCOMES AND SENDING US 8647 06:38:23,120 --> 06:38:25,240 OFF IN THE DIRECTION FOR THE 8648 06:38:25,240 --> 06:38:25,600 COMMUNITY. 8649 06:38:25,600 --> 06:38:27,880 AND I LIKE TO TAKE THIS MOMENT 8650 06:38:27,880 --> 06:38:32,200 TO SAY THANK YOU ALL, OUR 8651 06:38:32,200 --> 06:38:33,800 SPEAKERS, MODERATORS AND YOU 8652 06:38:33,800 --> 06:38:36,040 WHO JOINED AS WELL. 8653 06:38:36,040 --> 06:38:47,080 AND SPECIAL THANKS TO OUR 8654 06:38:47,080 --> 06:38:48,080 COMMUNICATIONS, THE MODERATOR 8655 06:38:48,080 --> 06:38:54,840 OF THE WHOLE WORKSHOP AND WE 8656 06:38:54,840 --> 06:38:57,840 HAD THE IT TEAM WHO WORKED 8657 06:38:57,840 --> 06:38:58,680 REALLY HARD. 8658 06:38:58,680 --> 06:39:02,800 AND LAST BUT NOT LEAST I LIKE 8659 06:39:02,800 --> 06:39:06,120 TO THANK THE NIH AND ODF FOR 8660 06:39:06,120 --> 06:39:07,480 THEIR SUPPORT TO THESE 8661 06:39:07,480 --> 06:39:14,600 WORKSHOPS AS WELL AS PROPOSING 8662 06:39:14,600 --> 06:39:15,640 THE MICROBIOME TOPIC. 8663 06:39:15,640 --> 06:39:17,440 THAT IS ALL. 8664 06:39:17,440 --> 06:39:19,480 ANYTHING ELSE I NEED TO 8665 06:39:19,480 --> 06:39:20,080 DISCUSS? 8666 06:39:20,080 --> 06:39:21,880 >> NO, I THINK IT HAS BEEN A 8667 06:39:21,880 --> 06:39:23,960 LONG TWO DAYS, FABULOUS BUT 8668 06:39:23,960 --> 06:39:24,480 LONG. 8669 06:39:24,480 --> 06:39:27,480 DO WE HAND BACK TO KATHERINE? 8670 06:39:27,480 --> 06:39:27,800 >> YEP. 8671 06:39:27,800 --> 06:39:29,520 >> WELL, I JUST WANT TO SAY 8672 06:39:29,520 --> 06:39:31,480 THANK YOU EVERYBODY AND I 8673 06:39:31,480 --> 06:39:35,560 REALLY ENJOYED THAT FINAL 8674 06:39:35,560 --> 06:39:36,240 DISCUSSION SESSION. 8675 06:39:36,240 --> 06:39:38,080 I ALWAYS LIKE TO BE THE 8676 06:39:38,080 --> 06:39:39,600 CHEERLEADER FOR DISCUSSION IN 8677 06:39:39,600 --> 06:39:40,880 THE FINAL DAY BECAUSE I KNOW 8678 06:39:40,880 --> 06:39:43,080 THAT IT IS SUCH A LONG MEETING 8679 06:39:43,080 --> 06:39:45,680 AND SUCH A FASCINATING TALK 8680 06:39:45,680 --> 06:39:47,080 THAT CAN ALMOST BE 8681 06:39:47,080 --> 06:39:50,160 OVERWHELMING TO TAKE IN OVER A 8682 06:39:50,160 --> 06:39:52,080 TWO DAY PERIOD SO I THANK 8683 06:39:52,080 --> 06:39:53,200 EVERYONE FOR THEIR STICKING 8684 06:39:53,200 --> 06:39:55,320 WITH US TILL THE VERY END. 8685 06:39:55,320 --> 06:40:26,920 THANK YOU TO BARBARA AND JOE 8686 06:40:26,920 --> 06:42:02,800 AND -- THE REST