1 00:00:05,320 --> 00:00:08,040 I'M PATRICK STILL. 2 00:00:08,040 --> 00:00:11,760 DIRECTOR IN THE BRANCH AT 3 00:00:11,760 --> 00:00:13,520 THE NATIONAL CENTER FOR 4 00:00:13,520 --> 00:00:14,120 COMPLEMENTARY AND INTEGRATIVE 5 00:00:14,120 --> 00:00:18,680 HEALTH, OR NCCIH AT THE NATIONAL 6 00:00:18,680 --> 00:00:20,200 INSTITUTES OF HEALTH. 7 00:00:20,200 --> 00:00:23,760 THANK YOU FOR JOINING US FOR 8 00:00:23,760 --> 00:00:24,280 EXPANDING TRANSLATIONALLY 9 00:00:24,280 --> 00:00:25,440 RELEVANT CHEMICAL SPACE, 10 00:00:25,440 --> 00:00:26,040 INSIGHTS INTO NATURAL PRODUCT 11 00:00:26,040 --> 00:00:26,640 RESOURCES, TECHNOLOGIES, AND 12 00:00:26,640 --> 00:00:26,960 MECHANISMS. 13 00:00:26,960 --> 00:00:31,000 THE SECOND PART OF A TWO-PART 14 00:00:31,000 --> 00:00:31,720 WEBINAR SERIES. 15 00:00:31,720 --> 00:00:34,080 FIRST I WOULD LIKE TO TAKE A FEW 16 00:00:34,080 --> 00:00:35,440 MOMENTS TO ACKNOWLEDGE THE MANY 17 00:00:35,440 --> 00:00:37,160 PEOPLE THAT BROUGHT THIS WEBINAR 18 00:00:37,160 --> 00:00:39,560 TO FRUITION, INCLUDING DR. 19 00:00:39,560 --> 00:00:42,520 EMMELINE EDWARDS, DIRECTOR OF 20 00:00:42,520 --> 00:00:43,760 OUR DIVISION OF EXTRAMURAL 21 00:00:43,760 --> 00:00:46,520 RESEARCH, WHO REALLY CHAMPIONED 22 00:00:46,520 --> 00:00:48,160 THIS WEBINAR. 23 00:00:48,160 --> 00:00:52,520 DR. CRAIG HOPP, DIRECTOR OF OUR 24 00:00:52,520 --> 00:00:54,520 EXTRAMURAL RESEARCH BRANCH AND 25 00:00:54,520 --> 00:00:58,720 DR. WEN CHEN, CHIEF OF 26 00:00:58,720 --> 00:00:59,440 MECHANICISTIC AND RESEARCH 27 00:00:59,440 --> 00:01:01,120 BRANCH AS WELL AS THE MANY 28 00:01:01,120 --> 00:01:03,320 COLLEAGUES WHO PLANNED LOGISTICS 29 00:01:03,320 --> 00:01:07,080 AND PROMOTIONS OF THIS EVENT, 30 00:01:07,080 --> 00:01:12,000 CATHERINE LAW, IRENE LOU, MS. 31 00:01:12,000 --> 00:01:13,920 WILLIAMS, MS. EILEEN AMADOR AND 32 00:01:13,920 --> 00:01:17,280 MANY OTHERS WHO WORKED BEHIND 33 00:01:17,280 --> 00:01:22,920 THE SCENES. 34 00:01:22,920 --> 00:01:30,480 BEFORE WE BEGIN TODAY, A FEW 35 00:01:30,480 --> 00:01:31,280 LOGISTICS. 36 00:01:31,280 --> 00:01:36,000 FOR NIH VIDEO CAST VIEWERS, YOU 37 00:01:36,000 --> 00:01:40,200 CAN PROVIDE FEEDBACK IN THE FORM 38 00:01:40,200 --> 00:01:41,320 BELOW YOUR SCREEN FOR VIEWING 39 00:01:41,320 --> 00:01:42,120 THE LIVE STREAM. 40 00:01:42,120 --> 00:01:44,760 WE WILL TRY TO GET TO AS MANY 41 00:01:44,760 --> 00:01:46,320 QUESTIONS AS POSSIBLE DURING THE 42 00:01:46,320 --> 00:01:47,440 QUESTION AND ANSWER PERIODS, BUT 43 00:01:47,440 --> 00:01:50,520 WE ARE UNLIKELY TO GET TO EVERY 44 00:01:50,520 --> 00:01:50,920 QUESTION. 45 00:01:50,920 --> 00:01:53,200 HOWEVER, ALL QUESTIONS SUBMITTED 46 00:01:53,200 --> 00:01:55,480 WILL BE COLLECTED AND SHARED 47 00:01:55,480 --> 00:01:56,840 WITH THE PLANNING TEAM. 48 00:01:56,840 --> 00:01:58,840 FINALLY, THIS EVENT IS BEING 49 00:01:58,840 --> 00:02:02,200 RECORDED AND WILL BE ARCHIVED ON 50 00:02:02,200 --> 00:02:04,360 THE NIH VIDEO CAST WEBSITE FOR 51 00:02:04,360 --> 00:02:07,680 FUTURE VIEWING. 52 00:02:07,680 --> 00:02:07,880 OKAY. 53 00:02:07,880 --> 00:02:10,480 SO WITH THOSE REMINDERS COVERED, 54 00:02:10,480 --> 00:02:13,240 I'M NOW PLEASED TO INTRODUCE DR. 55 00:02:13,240 --> 00:02:17,480 EMMELINE EDWARDS, DIRECTOR OF 56 00:02:17,480 --> 00:02:21,480 THE NCCIH DIVISION OF EXTRAMURAL 57 00:02:21,480 --> 00:02:23,480 RESEARCH WHO WILL SHARE WORDS OF 58 00:02:23,480 --> 00:02:26,120 WELCOME BEFORE WE DIVE INTO OUR 59 00:02:26,120 --> 00:02:26,480 PRESENTATIONS. 60 00:02:26,480 --> 00:02:27,320 DR. EDWARDS. 61 00:02:27,320 --> 00:02:28,720 >>THANK YOU, PATRICK. 62 00:02:28,720 --> 00:02:29,720 WELCOME, EVERYONE. 63 00:02:29,720 --> 00:02:32,160 IT IS REALLY A PLEASURE TO 64 00:02:32,160 --> 00:02:35,920 REALIZE THE INTEREST THAT THOSE 65 00:02:35,920 --> 00:02:37,320 WEBINARS HAVE ENCOUNTERED. 66 00:02:37,320 --> 00:02:39,000 AND I'M REALLY PLEASED TO TELL 67 00:02:39,000 --> 00:02:43,440 YOU A LITTLE BIT ABOUT THE 68 00:02:43,440 --> 00:02:45,640 IMPORTANCE OF NATURAL PRODUCT AS 69 00:02:45,640 --> 00:02:47,640 ESSENTIAL PORTION OF OUR 70 00:02:47,640 --> 00:02:49,680 PORTFOLIO AT NCCIH. 71 00:02:49,680 --> 00:02:52,600 WE SUPPORT RESEARCH ACROSS THE 72 00:02:52,600 --> 00:02:53,040 RESEARCH CONTINUUM. 73 00:02:53,040 --> 00:02:59,120 WE SUPPORT IN VITRO, IN VIVO AS 74 00:02:59,120 --> 00:03:01,320 WELL AS CLINICAL TRIALS. 75 00:03:01,320 --> 00:03:04,200 THE LAST COUPLE OF YEARS WE HAVE 76 00:03:04,200 --> 00:03:08,760 FOCUSED IMPACT ON THE 77 00:03:08,760 --> 00:03:10,200 CANNABINOID ON THERAPEUTIC 78 00:03:10,200 --> 00:03:11,680 POTENTIAL, NATURAL PRODUCTS IN 79 00:03:11,680 --> 00:03:13,680 GENERAL IN PAIN AND NUTRITION 80 00:03:13,680 --> 00:03:15,120 FOR PRECISION HEALTH. 81 00:03:15,120 --> 00:03:17,200 ALL OF THIS FALL VERY NICELY 82 00:03:17,200 --> 00:03:21,840 WITH OUR VISION OF WHOLE-PERSON 83 00:03:21,840 --> 00:03:24,480 HEALTH PERSON HEALTH AND 84 00:03:24,480 --> 00:03:27,880 INTEGRATION OF NATURAL PRODUCT 85 00:03:27,880 --> 00:03:32,160 INTO, YOU KNOW, PHYSIOLOGY, 86 00:03:32,160 --> 00:03:32,640 IMPACTING PHYSIOLOGY. 87 00:03:32,640 --> 00:03:34,800 WE'VE ALSO HAD A LONG STANDING 88 00:03:34,800 --> 00:03:37,240 INTEREST IN IMPROVING THE 89 00:03:37,240 --> 00:03:38,840 TECHNOLOGY THAT WOULD ADVANCE 90 00:03:38,840 --> 00:03:42,400 THE FIELD OF NATURAL PRODUCTS. 91 00:03:42,400 --> 00:03:43,960 AND, IN FACT, FOR THE PAST 92 00:03:43,960 --> 00:03:46,200 COUPLE OF YEARS WE HAVE HAD 93 00:03:46,200 --> 00:03:48,560 FUNDING OPPORTUNITY THAT 94 00:03:48,560 --> 00:03:50,480 ACTUALLY ENCOURAGED NEW 95 00:03:50,480 --> 00:03:52,560 METHODOLOGY AND TECHNOLOGY IN 96 00:03:52,560 --> 00:03:53,160 THAT FIELD. 97 00:03:53,160 --> 00:03:57,840 NOW WITH THE ADVANCE OF MACHINE 98 00:03:57,840 --> 00:03:58,280 LEARNING, ARTIFICIAL 99 00:03:58,280 --> 00:04:01,480 INTELLIGENCE, OMIX, WE WANT TO 100 00:04:01,480 --> 00:04:02,880 ENCOURAGE INVESTIGATORS TO 101 00:04:02,880 --> 00:04:05,520 EMPLOYEE THOSE SOPHISTICATED 102 00:04:05,520 --> 00:04:06,920 TECHNOLOGY TO MOVE THEIR 103 00:04:06,920 --> 00:04:07,840 RESEARCH FORWARD. 104 00:04:07,840 --> 00:04:10,520 SO THE SPEAKERS AT THIS PART TWO 105 00:04:10,520 --> 00:04:14,960 OF THIS WEBINAR SERIES REALLY 106 00:04:14,960 --> 00:04:16,520 WILL HIGHLIGHT SOME TECHNOLOGIES 107 00:04:16,520 --> 00:04:19,680 THAT ARE SPECIFIC TO STRUCTURE 108 00:04:19,680 --> 00:04:21,200 ELUCIDATION AND APPLICATION OF 109 00:04:21,200 --> 00:04:22,960 THOSE TECHNOLOGY SO THAT THEY 110 00:04:22,960 --> 00:04:24,480 BECOME MORE AVAILABLE TO THE 111 00:04:24,480 --> 00:04:27,320 BROADER NATURAL PART OF RESEARCH 112 00:04:27,320 --> 00:04:27,600 COMMUNITY. 113 00:04:27,600 --> 00:04:29,840 SO WE ARE PLEASED TO TURN THIS 114 00:04:29,840 --> 00:04:31,840 OVER TO PATRICK WHO WILL NOW 115 00:04:31,840 --> 00:04:33,840 INTRODUCE THE SPEAKERS. 116 00:04:33,840 --> 00:04:36,360 THANK YOU VERY MUCH AND HOPE YOU 117 00:04:36,360 --> 00:04:38,800 ENJOY THOSE PRESENTATIONS. 118 00:04:38,800 --> 00:04:40,880 >>THANK YOU VERY MUCH, DR. 119 00:04:40,880 --> 00:04:41,120 EDWARDS. 120 00:04:41,120 --> 00:04:45,520 AND AS I MENTIONED, DIRECTOR AT 121 00:04:45,520 --> 00:04:47,720 NCCIH IN OUR BASIC AND 122 00:04:47,720 --> 00:04:49,000 MECHANISTIC RESEARCH BRANCH AND 123 00:04:49,000 --> 00:04:52,440 I MANAGE A PORTFOLIO THAT SPANS 124 00:04:52,440 --> 00:04:55,480 NCCIH'S PRIORITIES IN 125 00:04:55,480 --> 00:04:57,800 TRANSLATIONAL AND CLINICAL 126 00:04:57,800 --> 00:04:59,840 APPLICATIONS OF NATURAL 127 00:04:59,840 --> 00:05:00,200 PRODUCTS. 128 00:05:00,200 --> 00:05:03,080 AS DR. EDWARDS MENTIONED OUR 129 00:05:03,080 --> 00:05:05,160 FIRST WEBINAR FOCUSED ON 130 00:05:05,160 --> 00:05:06,720 FOUNDATIONAL RESOURCES AND 131 00:05:06,720 --> 00:05:08,080 TECHNOLOGIES THAT ENAVAILABLE 132 00:05:08,080 --> 00:05:09,520 DISCOVERY OF NATURAL PRODUCTS 133 00:05:09,520 --> 00:05:11,560 AND IN PART TWO WE ARE PICKING 134 00:05:11,560 --> 00:05:14,120 UP WITH ADDITIONAL TECHNOLOGY 135 00:05:14,120 --> 00:05:16,720 SPECIFIC TO UNAMBIGUOUS 136 00:05:16,720 --> 00:05:17,560 STRUCTURE ELUCIDATION AND 137 00:05:17,560 --> 00:05:19,320 APPLICATION OF THOSE 138 00:05:19,320 --> 00:05:22,000 TECHNOLOGIES IN PROTEIN 139 00:05:22,000 --> 00:05:24,200 STRUCTURAL BIOLOGY FOR EXAMPLE, 140 00:05:24,200 --> 00:05:26,240 BUT WE WILL TOUCH GUT MICROBE 141 00:05:26,240 --> 00:05:27,600 AND HOST RESPONSES. 142 00:05:27,600 --> 00:05:30,640 TODAY WE ARE JOINED BY OUR 143 00:05:30,640 --> 00:05:31,600 EXCELLENT SPEAKERS AS WELL AS 144 00:05:31,600 --> 00:05:34,440 NIH PARTNERS WHO WILL SHARE 145 00:05:34,440 --> 00:05:38,600 THEIR PERSPECTIVES ON WEBINAR 146 00:05:38,600 --> 00:05:40,440 THEMES AND NATURAL PRODUCT 147 00:05:40,440 --> 00:05:41,640 CONTEXT IN THEIR INSTITUTE AND 148 00:05:41,640 --> 00:05:45,720 CENTER PRIORITIES. 149 00:05:45,720 --> 00:05:48,440 AND IN INTRODUCING OUR SPEAKERS, 150 00:05:48,440 --> 00:05:49,960 I WOULD FIRST LIKE TO INTRODUCE 151 00:05:49,960 --> 00:05:51,880 YOU TO DR. HOSEA NELSON, 152 00:05:51,880 --> 00:05:53,320 PROFESSOR OF CHEMISTRY IN THE 153 00:05:53,320 --> 00:05:54,520 DIVISION OF CHEMISTRY AND 154 00:05:54,520 --> 00:05:58,800 CHEMICAL ENGINEERING AT CALTECH, 155 00:05:58,800 --> 00:06:04,120 WHO WILL DISCUSS ELECTRON 156 00:06:04,120 --> 00:06:04,760 MICROSCOPY TECHNIQUES TO ENABLE 157 00:06:04,760 --> 00:06:05,320 CHARACTERIZATION OF COMPLEX 158 00:06:05,320 --> 00:06:05,720 NATURAL PRODUCTS. 159 00:06:05,720 --> 00:06:07,640 FOLLOWING DR. NELSON'S TALK, WE 160 00:06:07,640 --> 00:06:09,440 WILL HEAR FROM DR. MELINDA 161 00:06:09,440 --> 00:06:12,000 DIVER, ASSISTANT MEMBER OF THE 162 00:06:12,000 --> 00:06:12,880 STRUCTURAL BIOLOGY PROGRAM AT 163 00:06:12,880 --> 00:06:15,040 THE SLOAN KETERRING INSTITUTE 164 00:06:15,040 --> 00:06:20,520 WHO WILL PRESENT ON STRUCTURAL 165 00:06:20,520 --> 00:06:21,840 INSIGHTS ON I ONCHANNEL 166 00:06:21,840 --> 00:06:22,920 DETECTION OF PHYSICAL AND 167 00:06:22,920 --> 00:06:32,000 CHEMICAL STIMULI. 168 00:06:32,000 --> 00:06:38,960 OUR THIRD SPEAKER IS CHELSI 169 00:06:38,960 --> 00:06:41,760 CASSILLY, POST DOCTORAL FELLOW 170 00:06:41,760 --> 00:06:43,440 AT CLARDY LABORATORY DEPARTMENT 171 00:06:43,440 --> 00:06:47,640 OF BIOLOGICAL KEM TRI AND 172 00:06:47,640 --> 00:06:51,080 MOLECULAR FARM LOLG AT HARVARD 173 00:06:51,080 --> 00:06:53,000 MEDICAL SCHOOL WHO WILL TALK 174 00:06:53,000 --> 00:06:53,560 ABOUT CHEMICAL CORRELATIONS 175 00:06:53,560 --> 00:06:54,160 BETWEEN GUT MICROBES AND HOST 176 00:06:54,160 --> 00:06:54,680 RESPONSES. 177 00:06:54,680 --> 00:06:56,440 I WOULD LIKE TO TURN THINGS OVER 178 00:06:56,440 --> 00:06:59,160 TO OUR FIRST SPEAKER, DR. HOSEA 179 00:06:59,160 --> 00:07:00,640 NELSON TO BEGIN OUR 180 00:07:00,640 --> 00:07:00,960 PRESENTATIONS. 181 00:07:00,960 --> 00:07:02,960 DR. NELSON, PLEASE FEEL FREE TO 182 00:07:02,960 --> 00:07:03,920 SHARE YOUR SLIDES. 183 00:07:03,920 --> 00:07:07,280 >>YEAH. 184 00:07:07,280 --> 00:07:08,520 THANK YOU FOR THAT KIND 185 00:07:08,520 --> 00:07:09,000 INTRODUCTION. 186 00:07:09,000 --> 00:07:11,080 IT IS AN ABSOLUTE HONOR TO BE 187 00:07:11,080 --> 00:07:13,120 HERE TODAY TALKING ABOUT SOME OF 188 00:07:13,120 --> 00:07:16,960 THE RESEARCH FOCUSED ON 189 00:07:16,960 --> 00:07:17,960 UNAMBIGUOUSLY DETERMINING THE 190 00:07:17,960 --> 00:07:19,920 STRUCTURES OF NATURAL PRODUCTS. 191 00:07:19,920 --> 00:07:21,760 BEFORE I GET INTO THAT, I WOULD 192 00:07:21,760 --> 00:07:24,000 LIKE TO FIRST ACKNOWLEDGE ALL OF 193 00:07:24,000 --> 00:07:25,560 THE INDIVIDUALS WHO DID THE 194 00:07:25,560 --> 00:07:25,880 RESEARCH. 195 00:07:25,880 --> 00:07:30,320 I DON'T DO THAT MUCH PHYSICALLY. 196 00:07:30,320 --> 00:07:33,680 THESE GRADUATE STUDENTS AND 197 00:07:33,680 --> 00:07:35,880 UNDERGRADUATES AND POSTDOCTORAL 198 00:07:35,880 --> 00:07:37,880 FELLOWS ARE REALLY THE FUEL 199 00:07:37,880 --> 00:07:40,800 BEHIND ALL OF THE COOL THINGS I 200 00:07:40,800 --> 00:07:42,400 WILL SHOW YOU TODAY. 201 00:07:42,400 --> 00:07:46,040 THEY ARE AN INCREDIBLY 202 00:07:46,040 --> 00:07:49,000 PASSIONATE AND BRILLIANT GROUP 203 00:07:49,000 --> 00:07:52,760 OF YOUNG RESEARCHERS. 204 00:07:52,760 --> 00:07:54,560 MOST OF ALL THE WORK I WILL TELL 205 00:07:54,560 --> 00:07:56,840 YOU WAS FUNDED BY NCCIH, AS MANY 206 00:07:56,840 --> 00:08:00,200 OF YOU KNOW IN TODAY'S 207 00:08:00,200 --> 00:08:03,440 SOCIOECONOMIC CLIMATE, IT TAKES 208 00:08:03,440 --> 00:08:08,320 A VILLAGE TO FUND A PROGRAM LIKE 209 00:08:08,320 --> 00:08:10,760 I AM SHOWING YOU TODAY. 210 00:08:10,760 --> 00:08:16,800 I'M A SYNTHETIC ORGANIC CHEMIST. 211 00:08:16,800 --> 00:08:17,520 NATURAL PRODUCTS STARTS IN A 212 00:08:17,520 --> 00:08:18,600 DIFFERENT AREA. 213 00:08:18,600 --> 00:08:21,000 MY GROUP FOCUSES ON REACTION 214 00:08:21,000 --> 00:08:21,680 DISCOVERY. 215 00:08:21,680 --> 00:08:23,360 WE WANT TO DEVELOP NEW METHODS 216 00:08:23,360 --> 00:08:25,280 THAT WILL ALLOW THE CONSTRUCTION 217 00:08:25,280 --> 00:08:27,880 OF COMPLEX BIOACTIVE COMPOUNDS 218 00:08:27,880 --> 00:08:30,760 IN THE PHARMACEUTICAL INDUSTRY 219 00:08:30,760 --> 00:08:33,360 AND ACADEMICS FOR CHEMICAL 220 00:08:33,360 --> 00:08:33,640 BIOLOGY. 221 00:08:33,640 --> 00:08:35,920 WHAT WE DO IS TRY TO THINK ABOUT 222 00:08:35,920 --> 00:08:39,360 MAKING BONDS WAYS THAT ARE 223 00:08:39,360 --> 00:08:39,760 NONTRADITIONAL. 224 00:08:39,760 --> 00:08:41,800 WAY BACK WHEN IN 2017 WHEN MY 225 00:08:41,800 --> 00:08:45,640 GROUP FIRST STARTED WE 226 00:08:45,640 --> 00:08:47,800 DISCOVERED THESE INTERESTING 227 00:08:47,800 --> 00:08:49,000 INTERACTIONS WHERE YOU COULD 228 00:08:49,000 --> 00:08:53,240 TAKE THESE CHEMICALS TO FORM 229 00:08:53,240 --> 00:08:56,520 CARBON/CARBON BONDS AND BUILD A 230 00:08:56,520 --> 00:08:57,000 MOLECULAR COMPLEXITY. 231 00:08:57,000 --> 00:08:58,440 WE WANTED TO UNDERSTAND THE 232 00:08:58,440 --> 00:09:00,280 MECHANISM AND WE SINGLED OUT 233 00:09:00,280 --> 00:09:02,840 THESE TWO SPECIES I'M SHOWING 234 00:09:02,840 --> 00:09:13,360 HERE CALLED PHENYL CATIONS THAT 235 00:09:13,600 --> 00:09:14,000 WERE NOT STRUCTURED. 236 00:09:14,000 --> 00:09:17,000 WE DID CALCULATIONS OF HOW THEY 237 00:09:17,000 --> 00:09:17,240 BEHAVE. 238 00:09:17,240 --> 00:09:19,040 THIS IS A COMPUTATIONAL SLIDE 239 00:09:19,040 --> 00:09:21,520 THAT YOU SHOULDN'T WORRY ABOUT 240 00:09:21,520 --> 00:09:22,640 EXPECT THE STRUCTURE ON THE 241 00:09:22,640 --> 00:09:22,840 LEFT. 242 00:09:22,840 --> 00:09:25,000 THIS IS ONE OF THE INTERMEDIATES 243 00:09:25,000 --> 00:09:26,840 WE LEVERAGED I JUST DESCRIBED 244 00:09:26,840 --> 00:09:28,360 AND HAVE UNUSUAL BONDING. 245 00:09:28,360 --> 00:09:30,160 I DIDN'T BELIEVE OUR THEORISTS 246 00:09:30,160 --> 00:09:31,840 AND OUR GROUP THIS WAS THE 247 00:09:31,840 --> 00:09:32,120 STRUCTURE. 248 00:09:32,120 --> 00:09:36,240 WE DECIDED TO GET AN X-RAY 249 00:09:36,240 --> 00:09:38,440 CRYSTAL STRUCTURE IN THE 250 00:09:38,440 --> 00:09:38,680 SPECIES. 251 00:09:38,680 --> 00:09:42,520 WE COULD ONLY GET MICROCHRIS CAL 252 00:09:42,520 --> 00:09:43,920 COMPOUNDS OF THIS COMPOUND. 253 00:09:43,920 --> 00:09:47,200 I WAS DRINKING BEER AND HAVING 254 00:09:47,200 --> 00:09:49,040 LUNCH WITH COLLEAGUES OF MINE 255 00:09:49,040 --> 00:09:51,440 AND THEY SUGGESTED THAT WE TRY 256 00:09:51,440 --> 00:09:53,640 TO USE TRANSMISSIONAL ELECTRON 257 00:09:53,640 --> 00:09:56,600 MICROSCOPY TO SOLVE THE 258 00:09:56,600 --> 00:09:56,880 STRUCTURE. 259 00:09:56,880 --> 00:09:58,600 THEY HAD A LOT OF SUCCESSES 260 00:09:58,600 --> 00:10:02,640 WORKING WITH MICROCRYSTALINE 261 00:10:02,640 --> 00:10:05,520 POUDERS FROM PROTEIN AND 262 00:10:05,520 --> 00:10:08,920 POLYPEPTIDES. 263 00:10:08,920 --> 00:10:11,800 I DON'T THINK ANYONE ORGANIC KEM 264 00:10:11,800 --> 00:10:16,680 CYST KNEW THIS TECHNIQUE, 265 00:10:16,680 --> 00:10:17,600 MICROCRYSTAL ELECTRON 266 00:10:17,600 --> 00:10:17,920 TRANSMISSION. 267 00:10:17,920 --> 00:10:21,600 YOU PUT THEM IN ELECTRON 268 00:10:21,600 --> 00:10:24,560 MICROSCOPES AND GET THESE NANO 269 00:10:24,560 --> 00:10:26,200 METER TYPE CRYSTALS. 270 00:10:26,200 --> 00:10:29,760 IF YOU SWITCH YOUR MICROSCOPE 271 00:10:29,760 --> 00:10:37,640 AND SELECT THIS AP PATURE. 272 00:10:37,640 --> 00:10:41,080 YOU COULD GET DATA IF IF YOU 273 00:10:41,080 --> 00:10:41,320 ROTATE. 274 00:10:41,320 --> 00:10:44,600 THE DATA SO MUCH SO YOU COULD 275 00:10:44,600 --> 00:10:46,400 USE X-RAY SOFTWARE TO SOLVE 276 00:10:46,400 --> 00:10:47,560 THREE DIMENSIONAL STRUCTURES OF 277 00:10:47,560 --> 00:10:50,120 THE MOLECULES THAT MADE UP THOSE 278 00:10:50,120 --> 00:10:50,400 CRYSTALS. 279 00:10:50,400 --> 00:10:52,400 THE WAY THIS WORKS IN THIS VIDEO 280 00:10:52,400 --> 00:10:54,520 YOU HAVE SUSPENSION OF 281 00:10:54,520 --> 00:10:55,680 MICROCRYSTALS WHICH LOOK LIKE 282 00:10:55,680 --> 00:10:58,160 POWDER AND YOU PUT THEM ON TO A 283 00:10:58,160 --> 00:11:01,680 TEM GRID AND BASICALLY YOU WILL 284 00:11:01,680 --> 00:11:03,480 INSERT THIS INTO AN ELECTRON 285 00:11:03,480 --> 00:11:03,800 MICROSCOPE. 286 00:11:03,800 --> 00:11:06,720 THIS IS A VIDEO DETAILING HOW WE 287 00:11:06,720 --> 00:11:09,840 WOULD USE THE STANDARD 288 00:11:09,840 --> 00:11:10,840 MICROSCOPE FOR DOING STRUCTURAL 289 00:11:10,840 --> 00:11:12,800 BIOLOGY, SAME TOOL, YOU SHOOT 290 00:11:12,800 --> 00:11:15,320 YOUR ELECTRON BEAM AND WHILE IN 291 00:11:15,320 --> 00:11:16,200 ROLLING SHUTTER MODE COLLECT THE 292 00:11:16,200 --> 00:11:18,320 FRACTION IMAGES AND THE IMAGES 293 00:11:18,320 --> 00:11:20,720 CAN BE PIECED TOGETHER INTO A 294 00:11:20,720 --> 00:11:22,520 DEFRACTION MOVIE AND YOU CAN PUT 295 00:11:22,520 --> 00:11:25,760 IT INTO XDX AND SHELL X AND ALL 296 00:11:25,760 --> 00:11:27,840 THESE SUCCESSFUL AND GET A THREE 297 00:11:27,840 --> 00:11:28,600 DIMENSIONAL STRUCTURE. 298 00:11:28,600 --> 00:11:30,960 WE PUBLISHED OUR FIRST PAPER 299 00:11:30,960 --> 00:11:33,800 DESCRIBING. 300 00:11:33,800 --> 00:11:34,160 THIS. 301 00:11:34,160 --> 00:11:35,680 I THINK THE WORLD WAS SURPRISED 302 00:11:35,680 --> 00:11:38,360 YOU COULD DO THIS. 303 00:11:38,360 --> 00:11:40,560 WHAT BLEW MY MIND IS YOU COULD 304 00:11:40,560 --> 00:11:42,720 HAVE MIXTURES OF NATURAL 305 00:11:42,720 --> 00:11:44,640 PRODUCTS OR NATURAL PRODUCT LIKE 306 00:11:44,640 --> 00:11:47,160 MOLECULES AND SINGLE STRUCTURE 307 00:11:47,160 --> 00:11:48,920 TO OSOLVE. 308 00:11:48,920 --> 00:11:51,560 EEP OF THESE PARTICLES OR NANO 309 00:11:51,560 --> 00:11:55,720 CHRIS CALS ARE SUB MICRON SIZE. 310 00:11:55,720 --> 00:12:02,040 BIOTIN IS A PHENTOGRAM MATERIAL. 311 00:12:02,040 --> 00:12:03,800 WE GET A THREE DIMENSIONAL 312 00:12:03,800 --> 00:12:05,000 STRUCTURE AND THIS BLEW MY MIND. 313 00:12:05,000 --> 00:12:06,520 THE AMOUNT OF MATERIAL WE NEEDED 314 00:12:06,520 --> 00:12:07,680 TO GET STRUCTURES WAS REMARK 315 00:12:07,680 --> 00:12:10,720 BLG. 316 00:12:10,720 --> 00:12:12,080 -- REMARKABLE. 317 00:12:12,080 --> 00:12:15,040 SO MY GROUP FOUND YOU CAN TAKE 318 00:12:15,040 --> 00:12:19,880 AH COMPLEX NATURAL PRODUCT AND 319 00:12:19,880 --> 00:12:21,640 ACQUIRE DATA SUFFICIENT TO SOLVE 320 00:12:21,640 --> 00:12:22,200 STRUCTURE. 321 00:12:22,200 --> 00:12:23,680 AT THAT POINT WE STARTED 322 00:12:23,680 --> 00:12:25,600 THINKING THE COMPLEX MOLECULES 323 00:12:25,600 --> 00:12:27,320 LIKE NATURAL PRODUCTS ARE IN 324 00:12:27,320 --> 00:12:28,480 SMALL AMOUNTS. 325 00:12:28,480 --> 00:12:30,040 PERHAPS WE COULD LEVERAGE THIS 326 00:12:30,040 --> 00:12:32,000 TECHNIQUE AND INTRODUCE A 327 00:12:32,000 --> 00:12:33,800 GAME-CHANGING METHOD INTO THE 328 00:12:33,800 --> 00:12:35,080 NATURAL PRODUCT STRUCTURE 329 00:12:35,080 --> 00:12:35,360 ELUCIDATION. 330 00:12:35,360 --> 00:12:38,080 WE STARTED REACHING OUT TO 331 00:12:38,080 --> 00:12:39,280 COLLABORATETORS ALL OVER THE 332 00:12:39,280 --> 00:12:41,280 WORLD IN THE NATURAL PRODUCT 333 00:12:41,280 --> 00:12:42,000 SPACE. 334 00:12:42,000 --> 00:12:44,600 ONE OF THE FIRST WAS WITH THE 335 00:12:44,600 --> 00:12:49,240 SCHROEDER LAB AT CORNELL. 336 00:12:49,240 --> 00:12:52,920 THEY WERE HAVING DIFFICULTY 337 00:12:52,920 --> 00:12:56,480 DESCRIBING THIS. 338 00:12:56,480 --> 00:13:00,520 THERE WAS A QUESTION OF THE 339 00:13:00,520 --> 00:13:01,000 CHEMICALS. 340 00:13:01,000 --> 00:13:02,200 WE WERE QUICKLY ABLE TO 341 00:13:02,200 --> 00:13:06,400 DETERMINE THE STRUCTURE WAS IN 342 00:13:06,400 --> 00:13:07,720 9, USING MIKE KRO CHRIS CAL 343 00:13:07,720 --> 00:13:08,440 ELECTRON DETRACTION. 344 00:13:08,440 --> 00:13:10,800 ONE OF THE OTHER EXAMPLES THAT 345 00:13:10,800 --> 00:13:12,800 IS PRETTY COOL IS THERE A 346 00:13:12,800 --> 00:13:19,160 MOLECULE HERE, A MEMBER OF THE 347 00:13:19,160 --> 00:13:20,120 LOMAVIDICIN FAMILY. 348 00:13:20,120 --> 00:13:24,400 IT IS $10 MILLION OF FEDERAL 349 00:13:24,400 --> 00:13:28,160 GRANTS TO STUDY ITS SYNTHESIS 350 00:13:28,160 --> 00:13:30,000 AND BIOLOGY AND BIOACTIVITY. 351 00:13:30,000 --> 00:13:32,240 WE LOOKED AT THE DIFFICULTY OF 352 00:13:32,240 --> 00:13:34,320 MAKING THIS COMPOUND. 353 00:13:34,320 --> 00:13:37,120 WITH SETH HERZON QUESTIONED IF 354 00:13:37,120 --> 00:13:39,080 WE WERE WORKING WITH THE RIGHT 355 00:13:39,080 --> 00:13:39,320 STRUCTURE. 356 00:13:39,320 --> 00:13:43,960 THE HERZON LAB AT YALE AND OUR 357 00:13:43,960 --> 00:13:46,360 LAB AT UCLA COLLABORATED AND 358 00:13:46,360 --> 00:13:48,800 FROM A VERY SMALL SAMPLE OF 359 00:13:48,800 --> 00:13:53,080 MICROGRAM AMOUNT, DETERMINED OR 360 00:13:53,080 --> 00:13:54,040 REASSIGNED THE STRUCTURE. 361 00:13:54,040 --> 00:13:56,960 AND I THINK THAT IS ONE OF THE 362 00:13:56,960 --> 00:13:58,440 MOST IMPORTANT INITIATE EXAMPLES 363 00:13:58,440 --> 00:14:04,640 OF A REAL WORLD APPLICATION OF 364 00:14:04,640 --> 00:14:06,240 USING MIKE ED TO SOLVE 365 00:14:06,240 --> 00:14:06,560 STRUCTURES. 366 00:14:06,560 --> 00:14:10,040 THIS WILL ENABLE THE CHEMICAL 367 00:14:10,040 --> 00:14:11,040 SYNTHESIS AND GREATER 368 00:14:11,040 --> 00:14:13,760 UNDERSTANDING OF BIOACTIVITY. 369 00:14:13,760 --> 00:14:15,760 WE HAVE A MAJOR COLLABORATION 370 00:14:15,760 --> 00:14:20,560 UNDER OUR NCCIH FUNDING WITH THE 371 00:14:20,560 --> 00:14:24,040 TONG LAB AT UCLA AND DEVELOPING 372 00:14:24,040 --> 00:14:26,240 METHODS TO DISCOVER NEW NATURAL 373 00:14:26,240 --> 00:14:27,120 PRODUCTS. 374 00:14:27,120 --> 00:14:32,520 THIS IS ONE OF TP NEW METHOD, 375 00:14:32,520 --> 00:14:34,240 THIS IS AN INTERESTING EXAMPLE 376 00:14:34,240 --> 00:14:35,800 WHERE WE WERE ABLE TO TAKE A 377 00:14:35,800 --> 00:14:36,920 SMALL SAMPLE FROM MATERIAL FROM 378 00:14:36,920 --> 00:14:40,360 THE TONL LAB AT UCLA AND IN A 379 00:14:40,360 --> 00:14:43,920 FEW HOURS SIGN THE STRUCTURE OF 380 00:14:43,920 --> 00:14:47,840 THIS NONPEPTIDYL NEW NATURAL 381 00:14:47,840 --> 00:14:48,080 PRODUCT. 382 00:14:48,080 --> 00:14:51,160 OUR WORK IN THE METHOD EXTENDS 383 00:14:51,160 --> 00:14:52,520 BEYOND NATURAL PRODUCT 384 00:14:52,520 --> 00:14:52,760 DISCOVERY. 385 00:14:52,760 --> 00:14:54,160 THIS IS A COOL EXAMPLE THAT 386 00:14:54,160 --> 00:14:55,800 HASN'T BEEN PUBLISHED. 387 00:14:55,800 --> 00:14:57,680 IT WAS NOT PUBLISHABLE FOR OTHER 388 00:14:57,680 --> 00:14:58,800 REASONS FOR MANY YEARS. 389 00:14:58,800 --> 00:15:01,600 THIS WAS IN A THESIS FROM MY 390 00:15:01,600 --> 00:15:04,240 GROUP, GILEAD REACHED OUT TO US 391 00:15:04,240 --> 00:15:05,880 TO HELP THEM SOLVE THE STRUCTURE 392 00:15:05,880 --> 00:15:08,200 OF A COMPOUND THEY WERE WORKING 393 00:15:08,200 --> 00:15:08,480 ON. 394 00:15:08,480 --> 00:15:10,160 THERE WAS -- THEY WERE NOT ABLE 395 00:15:10,160 --> 00:15:17,640 TO UNAMBIGUOUSLY ASSIGN THE 396 00:15:17,640 --> 00:15:19,680 ISOMER OR WANTED FURTHER 397 00:15:19,680 --> 00:15:20,000 CONFIRMATION. 398 00:15:20,000 --> 00:15:22,240 THEY HAD REALLY SMALL CRYSTALS 399 00:15:22,240 --> 00:15:28,200 AND WE WERE ABLE TO ASSIGN THE 400 00:15:28,200 --> 00:15:32,600 ISOMER OF THIS MOLECULE. 401 00:15:32,600 --> 00:15:33,840 DR. JESSICA BIRCH IN MY LAB. 402 00:15:33,840 --> 00:15:35,960 SO WE HAD SOME SUCCESSES 403 00:15:35,960 --> 00:15:37,680 ASSIGNING STRUCTURES OF NATURAL 404 00:15:37,680 --> 00:15:38,680 PRODUCTS IN ONE OFF CASES. 405 00:15:38,680 --> 00:15:40,880 TO BE HONEST, BY THE TIME THESE 406 00:15:40,880 --> 00:15:42,880 SAMPLES GOT TO US, THEY WERE 407 00:15:42,880 --> 00:15:44,920 VERY DIFFICULT SAMPLES COMING 408 00:15:44,920 --> 00:15:46,920 FROM REALLY GOOD RESEARCH GROUPS 409 00:15:46,920 --> 00:15:49,800 COMING FROM STRUCTURAL 410 00:15:49,800 --> 00:15:50,520 ELUCIDA 411 00:15:50,520 --> 00:15:50,800 ELUCIDATION. 412 00:15:50,800 --> 00:15:52,760 OUR HIT RATE IS PROBABLY AROUND 413 00:15:52,760 --> 00:15:53,120 10%. 414 00:15:53,120 --> 00:15:54,920 I'M AN ORGANIC SYNTHETIC CHEMIST 415 00:15:54,920 --> 00:15:57,360 AND WE LIKE TO DO STUFF IN BULK. 416 00:15:57,360 --> 00:15:59,400 I WANTED TO THINK ABOUT WAYS OF 417 00:15:59,400 --> 00:16:01,720 HOW TO GET MORE NATURAL PRODUCT 418 00:16:01,720 --> 00:16:02,000 STRUCTURES. 419 00:16:02,000 --> 00:16:04,880 ONE OF THE IDEAS WE HAD IF WE 420 00:16:04,880 --> 00:16:11,280 CAN DEVELOP A HIGH-THREWPUT 421 00:16:11,280 --> 00:16:13,760 STRUCTURE, WE COULD LOOK AT A 422 00:16:13,760 --> 00:16:15,800 MILLION SAMPLES AND SOLVE 423 00:16:15,800 --> 00:16:16,640 100,000 NATURAL PRODUCT 424 00:16:16,640 --> 00:16:18,120 STRUCTURES THAT WOULD BE AN 425 00:16:18,120 --> 00:16:19,120 EXCITING DEVELOPMENT IN THE 426 00:16:19,120 --> 00:16:19,680 COMMUNITY. 427 00:16:19,680 --> 00:16:21,680 WE STARTED CLAP RATING WITH A 428 00:16:21,680 --> 00:16:25,720 FEW PEOPLE, IN PARTICULAR CASSIE 429 00:16:25,720 --> 00:16:27,960 CLAVE AND WE DECIDED TO COME 430 00:16:27,960 --> 00:16:29,360 TOGETHER AND PUT TOGETHER A 431 00:16:29,360 --> 00:16:31,080 LIBRARY OF NATURAL PRODUCTS SO 432 00:16:31,080 --> 00:16:33,200 FAR AROUND 13,000 EXTRACTS AND 433 00:16:33,200 --> 00:16:35,760 SEE IF WE COULD DEVELOP A HIGH 434 00:16:35,760 --> 00:16:37,280 THROUGHPUT PLATFORM FOR NATURAL 435 00:16:37,280 --> 00:16:38,240 PRODUCT DISCOVERY. 436 00:16:38,240 --> 00:16:40,440 THE EXTRACTS CAME FROM ALL OVER, 437 00:16:40,440 --> 00:16:44,960 SPONGES, PLANTS, FUNGI AND 438 00:16:44,960 --> 00:16:45,280 BACTERIA. 439 00:16:45,280 --> 00:16:48,720 TO REFRESH YOUR MEMORY, I HAD 440 00:16:48,720 --> 00:16:50,000 SHOWN YOU WE CAN SOLVE 441 00:16:50,000 --> 00:16:51,520 STRUCTURES OF NATURAL PRODUCTS 442 00:16:51,520 --> 00:16:53,280 FROM COMPLEX MIXTURES, KIND OF. 443 00:16:53,280 --> 00:16:55,600 THIS IS A RIGGED SYSTEM WHERE WE 444 00:16:55,600 --> 00:16:56,880 HAVE PURE NATURAL PRODUCT 445 00:16:56,880 --> 00:16:58,520 POUDERS AND MIX THEM TOGETHER 446 00:16:58,520 --> 00:17:00,960 AND SOLVE STRUCTURES OF 447 00:17:00,960 --> 00:17:03,080 INDIVIDUAL KRYSTALITES. 448 00:17:03,080 --> 00:17:05,200 YOU KNOW THAT IS UNREALISTIC. 449 00:17:05,200 --> 00:17:08,080 IF YOU HAVE A NATURAL PRODUCT 450 00:17:08,080 --> 00:17:11,640 EXTRACT, YOU PIT' IT ON AN HBLC 451 00:17:11,640 --> 00:17:12,880 AND GET SOMETHING WHAT I'M 452 00:17:12,880 --> 00:17:13,520 SHOWING HERE. 453 00:17:13,520 --> 00:17:16,200 NOT A MIXTURE OF PURIFIED 454 00:17:16,200 --> 00:17:17,640 POUDERS, BUT A MIXTURE OF 455 00:17:17,640 --> 00:17:18,800 COMPOUNDS AND SOLUTION YOU HAVE 456 00:17:18,800 --> 00:17:21,760 TO FIGURE OUT HOW TO SEPARATE 457 00:17:21,760 --> 00:17:22,760 AND STRUCK CHURLGLY 458 00:17:22,760 --> 00:17:23,080 CHARACTERIZE. 459 00:17:23,080 --> 00:17:26,040 WHAT WE WANTED TO DO WAS GO 460 00:17:26,040 --> 00:17:28,320 THROUGH AND GRAB EVERY PEAK AND 461 00:17:28,320 --> 00:17:29,400 GET DEFRACTION DATA. 462 00:17:29,400 --> 00:17:31,560 AND SO THAT TURNS OUT THAT IS 463 00:17:31,560 --> 00:17:32,320 REALLY DIFFICULT. 464 00:17:32,320 --> 00:17:34,400 IT TAKES OFTENTIMES AN HOUR TO 465 00:17:34,400 --> 00:17:37,120 PUT ONE SAMPLE IN AN 466 00:17:37,120 --> 00:17:38,840 ELECTROMICROSCOPE. 467 00:17:38,840 --> 00:17:41,480 IF WE HAVE 13,000 EXTRACTS, WE 468 00:17:41,480 --> 00:17:43,400 ARE TALKING ABOUT TENS OF 469 00:17:43,400 --> 00:17:44,080 THOUSANDS OF DATA COLLECTION ON 470 00:17:44,080 --> 00:17:47,000 A TEM, WHICH IS A LITTLE 471 00:17:47,000 --> 00:17:48,160 EXPENSIVE. 472 00:17:48,160 --> 00:17:50,480 WE HAD TO MINIATURIZE THE 473 00:17:50,480 --> 00:17:50,840 SAMPLES. 474 00:17:50,840 --> 00:17:55,280 SO WE DECIDED TO TAKE HPLC 475 00:17:55,280 --> 00:17:57,120 FRACTION NATION AND DO TIME 476 00:17:57,120 --> 00:17:59,040 BASED FRACTIONATION AND COLLECT 477 00:17:59,040 --> 00:18:02,120 IN WELL PLATES AND USE A DNA 478 00:18:02,120 --> 00:18:05,920 MICRO ARRAYER AND TAKE SAMPLES 479 00:18:05,920 --> 00:18:08,760 AND DEPOSIT THEM ON TEM GRIDS TO 480 00:18:08,760 --> 00:18:11,520 ADD HUNDREDS OF FRACTIONS OR 481 00:18:11,520 --> 00:18:12,640 HUNDREDS OF POTENTIAL NATURAL 482 00:18:12,640 --> 00:18:14,360 PRODUCT FRACTIONS DIRECTLY INTO 483 00:18:14,360 --> 00:18:17,440 A TEM GRID IN ONE OPERATION. 484 00:18:17,440 --> 00:18:21,000 SHOWN HERE IS A CRUDE EXTRACT, 485 00:18:21,000 --> 00:18:25,040 115 MILLIGRAMS OF CRUDE EXTRACT 486 00:18:25,040 --> 00:18:29,800 PROVIDED BY THE QUAVE LAB. 487 00:18:29,800 --> 00:18:32,840 WE SEPARATED AND THAT AND 488 00:18:32,840 --> 00:18:34,920 DEPOSITED IT ON A TEM GRID. 489 00:18:34,920 --> 00:18:38,120 WE WERE EXCITED TO COLLECT 490 00:18:38,120 --> 00:18:39,480 ELECTRON DEFRACTION DATA. 491 00:18:39,480 --> 00:18:42,320 I SHOULD NOTE ONLY IN SOME CASES 492 00:18:42,320 --> 00:18:44,160 WERE WE ABLE TO SOLVE STRUCTURES 493 00:18:44,160 --> 00:18:47,400 FROM THE DROPLETS. 494 00:18:47,400 --> 00:18:49,720 WE HAVE ENGINEERING STRUCTURES 495 00:18:49,720 --> 00:18:51,440 TO DO THAT MORE OFTEN. 496 00:18:51,440 --> 00:18:55,040 WE CAN IDENTIFY CRYSTALINE 497 00:18:55,040 --> 00:18:55,440 PRODUCTS. 498 00:18:55,440 --> 00:19:00,560 I SHOULD MENTION THIS TERPINE 499 00:19:00,560 --> 00:19:03,160 WAS SOLVED FROM THIS ARRAY ED 500 00:19:03,160 --> 00:19:03,360 GRID. 501 00:19:03,360 --> 00:19:05,880 THE OTHER COMPOUNDS, THE THREE 502 00:19:05,880 --> 00:19:07,720 WE ISOLATED FROM THIS EXTRACT 503 00:19:07,720 --> 00:19:10,040 TOOK A LITTLE BIT MORE WORK. 504 00:19:10,040 --> 00:19:11,440 THIS METHOD IS SOMEWHAT GENERAL. 505 00:19:11,440 --> 00:19:12,920 WE LOOKED AT MORE EXTRACTS. 506 00:19:12,920 --> 00:19:15,760 THIS IS ONE OF THE OTHER 507 00:19:15,760 --> 00:19:20,360 EXTRACTS, FROM A FUNGAL EXTRACT 508 00:19:20,360 --> 00:19:22,520 AND WE ARE ABLE TO SOLVE FOR 509 00:19:22,520 --> 00:19:23,560 NATURAL PRODUCTS. 510 00:19:23,560 --> 00:19:25,000 I SHOULD NOTE SOME OF THESE 511 00:19:25,000 --> 00:19:27,160 COMPOUNDS WOULDN'T HAVE BEEN SO 512 00:19:27,160 --> 00:19:28,920 APPARENT USING STANDARD LCMS 513 00:19:28,920 --> 00:19:29,720 WORK FLOW. 514 00:19:29,720 --> 00:19:31,480 FOR EXAMPLE, THIS IS MAYBE NOT 515 00:19:31,480 --> 00:19:34,200 THE MOST EXCITING NATURAL 516 00:19:34,200 --> 00:19:37,120 PRODUCT, IT IS CALCIUM OXOLATE. 517 00:19:37,120 --> 00:19:39,000 YOU WOULDN'T NECESSARILY SEE 518 00:19:39,000 --> 00:19:42,880 COMING UP IN UV TRACE OR MASS 519 00:19:42,880 --> 00:19:44,160 SPEC TRACE. 520 00:19:44,160 --> 00:19:48,000 THIS RELATIVELY SMALL DIF RIF 521 00:19:48,000 --> 00:19:50,640 SHOWN DELOW WOULD ALSO BE A 522 00:19:50,640 --> 00:19:53,160 SITUATION WHERE THAT MIGHT FALL 523 00:19:53,160 --> 00:19:56,920 BELOW THE LOWER LIMIT OF M/Z FOR 524 00:19:56,920 --> 00:19:59,440 MASS SPEC AND COLLECT FRACTION 525 00:19:59,440 --> 00:20:02,320 DATA AND ASSIGN STRUCTURE 526 00:20:02,320 --> 00:20:03,160 WITHOUT ANY OTHER INFORMATION. 527 00:20:03,160 --> 00:20:04,680 SO WE ARE STILL IN THE FIRST 528 00:20:04,680 --> 00:20:07,880 YEAR OF THE NCCIH-FUNDED 529 00:20:07,880 --> 00:20:08,120 PROJECT. 530 00:20:08,120 --> 00:20:09,880 WE ARE STILL WORKING ON 531 00:20:09,880 --> 00:20:12,720 AUTOMATION AND AUTOMATED DATA 532 00:20:12,720 --> 00:20:14,720 ANALYSIS USING MACHINE LEARNING 533 00:20:14,720 --> 00:20:17,000 ANALYSIS AND ADVANCED DATA 534 00:20:17,000 --> 00:20:17,320 TECHNIQUES. 535 00:20:17,320 --> 00:20:19,520 IN OUR FIRST RUN THROUGH OF 20 536 00:20:19,520 --> 00:20:23,840 EXTRAKTS -- EXTRACTS WE HAVE 537 00:20:23,840 --> 00:20:26,600 BEEN ABLE TO STRUCTURALLY 538 00:20:26,600 --> 00:20:28,480 CHARACTERIZE MORE THAN 15 539 00:20:28,480 --> 00:20:30,200 NATURAL PRODUCTS AND MORE THAN 540 00:20:30,200 --> 00:20:32,520 10 ARE BRAND NEW CRYSTAL 541 00:20:32,520 --> 00:20:32,800 STRUCTURES. 542 00:20:32,800 --> 00:20:35,200 WE THINK THAT IS AN EXCITING 543 00:20:35,200 --> 00:20:36,680 ADVANCE FOR THE FIELD. 544 00:20:36,680 --> 00:20:38,640 WE DISCOVERED WEIRD THINGS. 545 00:20:38,640 --> 00:20:42,080 HERE IS AN EXAMPLE OF ONE OF 546 00:20:42,080 --> 00:20:42,280 THEM. 547 00:20:42,280 --> 00:20:44,080 HERE IS A TRACE, THE DOTTED 548 00:20:44,080 --> 00:20:46,200 LINES ARE EVERYWHERE WE TOOK A 549 00:20:46,200 --> 00:20:46,480 FRACTION. 550 00:20:46,480 --> 00:20:48,440 THIS BIG PEAK AT 15 MINUTES WAS 551 00:20:48,440 --> 00:20:50,040 SPLIT INTO THREE FRACTIONS. 552 00:20:50,040 --> 00:20:51,720 WHEN WE STARTED COLLECTING DATA 553 00:20:51,720 --> 00:20:53,960 ON THESE FRACTIONS WE WERE 554 00:20:53,960 --> 00:20:57,000 INTERESTED TO FIND FRACTION E7 555 00:20:57,000 --> 00:21:01,920 WAS THIS NATURAL PRODUCT 556 00:21:01,920 --> 00:21:02,920 PACHYBACIN. 557 00:21:02,920 --> 00:21:07,840 FRACTION EN WAS CHRYSOPHANOL, 558 00:21:07,840 --> 00:21:10,240 THIS FRACTION E8 WAS A 559 00:21:10,240 --> 00:21:11,880 CO-CRYSTAL OF THE TWO NATURAL 560 00:21:11,880 --> 00:21:12,160 PRODUCTS. 561 00:21:12,160 --> 00:21:15,000 WE ARE NOT QUITE SURE HOW THAT 562 00:21:15,000 --> 00:21:17,440 WILL BECOME RELEVANT IN THE 563 00:21:17,440 --> 00:21:19,080 METHOD. 564 00:21:19,080 --> 00:21:21,520 IT EXEMPLIFIES OF THE DIFFERENT 565 00:21:21,520 --> 00:21:26,800 FRACTIONATION ALLOWS US TO FIND 566 00:21:26,800 --> 00:21:27,600 DIFFERENT INFORMATION. 567 00:21:27,600 --> 00:21:29,760 IN THIS FIRST ROUND OF 20 568 00:21:29,760 --> 00:21:33,280 EXTRACT SEARCH WERE ABLE, USING 569 00:21:33,280 --> 00:21:35,200 MNR AND MASS SPEC IN COMBINATION 570 00:21:35,200 --> 00:21:38,040 WITH MICROED TO SOLVE THE 571 00:21:38,040 --> 00:21:43,080 STRUCTURES OF THESE PRODUCTS. 572 00:21:43,080 --> 00:21:45,240 WE THOUGHT THESE WOULDN'T BE A 573 00:21:45,240 --> 00:21:45,880 CRYSTALINE. 574 00:21:45,880 --> 00:21:47,560 SO ONE OF THE MOST SURPRISING 575 00:21:47,560 --> 00:21:49,240 THINGS AND I GUESS I'M ALMOST 576 00:21:49,240 --> 00:21:51,600 OUT OF TIME HERE, ONE OF THE 577 00:21:51,600 --> 00:21:53,480 MOST SURPRISING THINGS WE FOUND 578 00:21:53,480 --> 00:21:54,760 IS REALLY ENCOURAGING. 579 00:21:54,760 --> 00:21:57,320 WHEN WE STARTED THIS PROJECT, I 580 00:21:57,320 --> 00:21:59,840 ANTICIPATED WE WOULD HAVE 5% OF 581 00:21:59,840 --> 00:22:03,040 THE COMPOUNDS OR FRACTIONS WE 582 00:22:03,040 --> 00:22:07,560 OBSERVED WOULD BE CRYSTALINI. 583 00:22:07,560 --> 00:22:10,320 20% OF THE FRACTIONS ARE 584 00:22:10,320 --> 00:22:10,600 CRYSTALINE. 585 00:22:10,600 --> 00:22:12,920 WE ARE NOT GETTING ALL THE 586 00:22:12,920 --> 00:22:13,840 STRUCTURES, NOT YET ANYWAY. 587 00:22:13,840 --> 00:22:16,120 THAT IS ENCOURAGING AND 588 00:22:16,120 --> 00:22:21,880 HIGHLIGHTS THE POTENTIAL USING 589 00:22:21,880 --> 00:22:23,560 DEFRACTION WITH LICK KWID -- 590 00:22:23,560 --> 00:22:26,000 ARRAY ED TO ELUCIDATE THE 591 00:22:26,000 --> 00:22:28,320 STRUCTURES THAT ARE KRAS TALINE 592 00:22:28,320 --> 00:22:29,440 AND LEND THEMSELVES TO THAT TYPE 593 00:22:29,440 --> 00:22:30,760 OF ANALYSIS. 594 00:22:30,760 --> 00:22:32,400 I'M GOING TO CUT IT THERE 595 00:22:32,400 --> 00:22:34,160 BECAUSE I AM OUT OF TIME. 596 00:22:34,160 --> 00:22:37,280 I WANT TO THANK YOU ALL FOR YOUR 597 00:22:37,280 --> 00:22:37,560 ATTENTION. 598 00:22:37,560 --> 00:22:38,960 MY AWESOME RESEARCH LAB, THEY 599 00:22:38,960 --> 00:22:40,520 DID ALL OF THIS WORK AND HAD 600 00:22:40,520 --> 00:22:45,640 MOST OF THESE GD -- IDEAS. 601 00:22:45,640 --> 00:22:47,640 GENEROUS FUNDING FROM THE NIH 602 00:22:47,640 --> 00:22:51,480 ESPECIALLY NCCIH AND ALL THOSE 603 00:22:51,480 --> 00:22:53,520 WHO HAVE WORKS WITH US ON THIS 604 00:22:53,520 --> 00:22:55,280 OVER THE YEARS SO THANK YOU VERY 605 00:22:55,280 --> 00:22:55,480 MUCH. 606 00:22:55,480 --> 00:22:57,680 >>THANK YOU DR. NELSON. 607 00:22:57,680 --> 00:23:00,320 AND AS A REMINDER WE WILL HOLD 608 00:23:00,320 --> 00:23:01,840 QUESTIONS TO THE END OF THE 609 00:23:01,840 --> 00:23:04,800 THREE SPEAKERS AND WITH THAT, I 610 00:23:04,800 --> 00:23:06,960 WOULD LIKE TO NOW MOVE TO DR. 611 00:23:06,960 --> 00:23:08,600 DIVER FOR HER TALK. 612 00:23:08,600 --> 00:23:09,600 PLEASE FEEL FREE TO SHARE YOUR 613 00:23:09,600 --> 00:23:16,400 SLIDES. 614 00:23:16,400 --> 00:23:17,080 >>HELLO. 615 00:23:17,080 --> 00:23:19,360 IT IS WONDERFUL TO BE HERE. 616 00:23:19,360 --> 00:23:22,160 IN THE DIVER LAB AT SLOAN 617 00:23:22,160 --> 00:23:23,480 KETERRING INSTITUTE WE ARE 618 00:23:23,480 --> 00:23:26,000 INTERESTED IN UNDERSTANDING AT A 619 00:23:26,000 --> 00:23:27,320 MOLECULAR LEVEL HOW WE SENSE THE 620 00:23:27,320 --> 00:23:29,440 WORLD AROUND US. 621 00:23:29,440 --> 00:23:31,600 TODAY I'M GOING TO TALK ABOUT 622 00:23:31,600 --> 00:23:34,280 TRIP M8, OUR PRIMARY COLD SENSOR 623 00:23:34,280 --> 00:23:37,120 IN THE BODY AND WHAT HELPS US 624 00:23:37,120 --> 00:23:38,360 SENSE NATURAL PRODUCT COOLING 625 00:23:38,360 --> 00:23:48,600 AGENTS LIKE MINT OR MENTHOL AND 626 00:23:48,600 --> 00:23:50,080 EUCALYPTUS. 627 00:23:50,080 --> 00:23:53,640 I'M GOING TO SHARE WHAT WE 628 00:23:53,640 --> 00:23:53,960 OBTAINED. 629 00:23:53,960 --> 00:23:55,680 HOW DO WE INTERFACE WITH OUR 630 00:23:55,680 --> 00:23:56,960 ENVIRONMENT. 631 00:23:56,960 --> 00:23:58,120 SIGNALS IN OUR ENVIRONMENT 632 00:23:58,120 --> 00:24:00,040 NONPAIN CAUSING AND INNOCUOUS 633 00:24:00,040 --> 00:24:02,240 AND THOSE THAT ARE PAIN CAUSING 634 00:24:02,240 --> 00:24:09,880 ARE DETECTED BY NEURONS, CALL 635 00:24:09,880 --> 00:24:10,160 NOCESEPTORS. 636 00:24:10,160 --> 00:24:12,280 THEY ARE IN OUR SKIN, OUR LUNGS 637 00:24:12,280 --> 00:24:13,000 AND OUR GUT. 638 00:24:13,000 --> 00:24:17,360 IT IS A VARIETY OF ION CHANNELS 639 00:24:17,360 --> 00:24:20,640 THAT HELP US DETECT LIKE ITCH, 640 00:24:20,640 --> 00:24:22,120 TEMPERATURE, LIKE MECHANICAL 641 00:24:22,120 --> 00:24:22,440 PAIN. 642 00:24:22,440 --> 00:24:24,920 BUT ALSO CHEMICAL AND CHEMICAL 643 00:24:24,920 --> 00:24:25,200 IRRITANTS. 644 00:24:25,200 --> 00:24:28,360 AND THESE CAN INCLUDE A WIDE 645 00:24:28,360 --> 00:24:31,040 VAST VARIETY OF NATURAL PRODUCT. 646 00:24:31,040 --> 00:24:34,400 THINGS FROM PLANTS LIKE TRIP M8 647 00:24:34,400 --> 00:24:35,880 BUT ALSO THINGS THAT COME FROM 648 00:24:35,880 --> 00:24:38,200 VENOMOUS ANIMALS LIKE THIS 649 00:24:38,200 --> 00:24:41,880 SCORPION SHOWN HERE THAT MAKES 650 00:24:41,880 --> 00:24:44,520 THIS PEPTIDE TOXIN. 651 00:24:44,520 --> 00:24:46,560 SO MANY OF THE ION CHANNELS THAT 652 00:24:46,560 --> 00:24:48,960 DO THIS DETECTION ARE PART OF 653 00:24:48,960 --> 00:24:51,160 THE LARGER TRIP ION CHANNEL 654 00:24:51,160 --> 00:24:51,360 FAMILY. 655 00:24:51,360 --> 00:24:53,720 TRIP CHANNELS ARE A VERY, VERY 656 00:24:53,720 --> 00:24:55,840 LARGE FAMILY OF ION CHANNELS. 657 00:24:55,840 --> 00:24:57,840 THERE ARE ALMOST 30 MEMBERS IN 658 00:24:57,840 --> 00:24:58,560 MAMMALS. 659 00:24:58,560 --> 00:25:01,440 IT IS SECOND ONLY TO POTASSIUM 660 00:25:01,440 --> 00:25:01,680 CHANNELS. 661 00:25:01,680 --> 00:25:04,600 AND THEY HAVE VERY DIVERSE 662 00:25:04,600 --> 00:25:06,760 FUNCTIONS IN TERMS OF PHYSIOLOGY 663 00:25:06,760 --> 00:25:07,480 AND BIOLOGY. 664 00:25:07,480 --> 00:25:11,240 THE ONES WE UNDERSTAND WELL WE 665 00:25:11,240 --> 00:25:12,040 BASICALLY UNDERSTAND BECAUSE OF 666 00:25:12,040 --> 00:25:12,800 NATURAL PRODUCTS. 667 00:25:12,800 --> 00:25:14,960 I'M HIGHLIGHTING THREE OF THE 668 00:25:14,960 --> 00:25:17,320 MOST BEST STUDIED AND BEST 669 00:25:17,320 --> 00:25:18,640 UNDERSTOOD ION CHANNELS WE KNOW 670 00:25:18,640 --> 00:25:20,160 HERE AND ALSO THE NATURAL 671 00:25:20,160 --> 00:25:21,800 PRODUCTS IT HELPED US TO 672 00:25:21,800 --> 00:25:22,920 IDENTIFY THEM. 673 00:25:22,920 --> 00:25:25,760 SO WE HAVE TRIP V1. 674 00:25:25,760 --> 00:25:28,960 TRIP V1 IS OUR PRIMARY HEAT 675 00:25:28,960 --> 00:25:30,880 SENSOR, BUT IT IS SENSITIVE TO 676 00:25:30,880 --> 00:25:38,000 THE NATURAL PRODUCT CAP SASIN IN 677 00:25:38,000 --> 00:25:42,520 PEPPERS. 678 00:25:42,520 --> 00:25:46,080 WE HAVE TRM8 MENT OL. 679 00:25:46,080 --> 00:25:49,760 AT THE BOTTOM TRPA1 IS A GENERAL 680 00:25:49,760 --> 00:25:51,480 IRRITANT SENSOR. 681 00:25:51,480 --> 00:25:52,880 SOME THINGS IT SENSES ARE 682 00:25:52,880 --> 00:25:56,360 NATURAL PRODUCTS LIKE CHEMICAL 683 00:25:56,360 --> 00:26:00,480 COMPOUNDS IN GARLIC, ONION, AND 684 00:26:00,480 --> 00:26:00,720 WASABI. 685 00:26:00,720 --> 00:26:02,600 IN TERMS OF WHAT WE UNDERSTAND 686 00:26:02,600 --> 00:26:06,840 ABOUT THE MOLECULAR MECHANISMS 687 00:26:06,840 --> 00:26:09,320 OF TRPM8, WE UNDERSTAND THERE 688 00:26:09,320 --> 00:26:12,000 ARE THREE STATES OF THIS ION 689 00:26:12,000 --> 00:26:12,240 CHANNEL. 690 00:26:12,240 --> 00:26:13,840 THE ION CHANNEL CAN BE CLOSED. 691 00:26:13,840 --> 00:26:15,280 IT CAN ALSO BE OPENED. 692 00:26:15,280 --> 00:26:18,280 THIS IS WHEN ACTUAL IONS ARE 693 00:26:18,280 --> 00:26:19,080 ALLOW TO FLOW THROUGH. 694 00:26:19,080 --> 00:26:21,680 THESE ARE POSITIVELY CHARGED 695 00:26:21,680 --> 00:26:23,120 IONS, LIKE CALCIUM AND SODIUM. 696 00:26:23,120 --> 00:26:25,520 THERE IS A VERY UNIQUE STATE 697 00:26:25,520 --> 00:26:28,520 CALLED THE DESENSITIZED STATE. 698 00:26:28,520 --> 00:26:29,960 DESENSITIZED BASICALLY MEANS 699 00:26:29,960 --> 00:26:32,760 THERE IS SOME TYPE OF STIMULUS 700 00:26:32,760 --> 00:26:35,520 AROUND LIKE MENTHOL, BUT IT IS 701 00:26:35,520 --> 00:26:37,400 NOT ALLOWING IONS TO FLOW 702 00:26:37,400 --> 00:26:37,600 THROUGH. 703 00:26:37,600 --> 00:26:39,200 THIS IS AN INTERESTING STATE TO 704 00:26:39,200 --> 00:26:42,000 ME AND TO STUDY AND HOW THIS 705 00:26:42,000 --> 00:26:43,560 RECEPTOR WORKS IN RESPONSE TO 706 00:26:43,560 --> 00:26:46,040 THINGS BECAUSE IT HAS LARGE 707 00:26:46,040 --> 00:26:47,720 IMPLICATIONS IN HOW WE AS HUMANS 708 00:26:47,720 --> 00:26:51,560 ADAPT TO COLD TEMPERATURES. 709 00:26:51,560 --> 00:26:54,080 SO FROM A MORE THERAPEUTIC POINT 710 00:26:54,080 --> 00:26:59,120 OF VIEW, IT HAS BEEN LONG KNOWN 711 00:26:59,120 --> 00:27:04,800 TARGETING TRYPM8 HAS AN 712 00:27:04,800 --> 00:27:06,320 ANALGESIC EFFECT. 713 00:27:06,320 --> 00:27:08,120 REMEMBER WHEN YOU WERE A SMALL 714 00:27:08,120 --> 00:27:11,200 CHILD YOU HAD A SPRAIN ANKLE AND 715 00:27:11,200 --> 00:27:12,560 YOU PUT ICE. 716 00:27:12,560 --> 00:27:15,040 YOU FEEL A COLD AND A BIT OF 717 00:27:15,040 --> 00:27:17,840 COUGH AND YOU GO TO THE 718 00:27:17,840 --> 00:27:23,000 DRUGSTORE AND PURCHASE VICKS 719 00:27:23,000 --> 00:27:24,680 VAPORUB OR YOU HAVE RUN A 720 00:27:24,680 --> 00:27:27,640 MARATHON AND YOU GET ICY COOLING 721 00:27:27,640 --> 00:27:30,040 GELS OR PATCHES. 722 00:27:30,040 --> 00:27:32,360 THEY ARE ACTIVE INGREDIENTS OR 723 00:27:32,360 --> 00:27:37,280 NATURAL PRODUCTS THAT ACT ON 724 00:27:37,280 --> 00:27:45,080 TRPM8, MENTHOL AND EUCOLLYPTOL 725 00:27:45,080 --> 00:27:47,040 AND CAMPHOR. 726 00:27:47,040 --> 00:27:49,280 IF WE CAN UNDERSTAND THESE 727 00:27:49,280 --> 00:27:51,080 NATURAL PRODUCT DRUGS WE COULD 728 00:27:51,080 --> 00:27:52,960 EXTEND THEM TO SYNTHETIC SPACE 729 00:27:52,960 --> 00:27:56,040 AND EXPAND USAGE FROM A LIMITED 730 00:27:56,040 --> 00:27:59,080 PAIN, ACUTE PAIN FROM SPORTS 731 00:27:59,080 --> 00:28:02,800 INJURIES OR MINOR COLDS TO SOME 732 00:28:02,800 --> 00:28:03,440 LARGER CONCEPT FOR PAIN 733 00:28:03,440 --> 00:28:07,760 TREATMENT. 734 00:28:07,760 --> 00:28:12,120 SO MY WORK PRIMARILY UTILIZES 735 00:28:12,120 --> 00:28:16,040 SINGLE PARTICLE CROEEM TO 736 00:28:16,040 --> 00:28:17,480 CAPTURE HIGH RESOLUTION 737 00:28:17,480 --> 00:28:19,040 SNAPSHOTS OF ION CHANNELS AND 738 00:28:19,040 --> 00:28:21,640 HOPEFULLY BOUND TO THINGS LIKE 739 00:28:21,640 --> 00:28:23,680 NATURAL PRODUCT ACTIVATORS TO 740 00:28:23,680 --> 00:28:25,000 UNDERSTAND WHERE THEY BIND AND 741 00:28:25,000 --> 00:28:26,800 HOW THEY WORK AND ACT ON THE 742 00:28:26,800 --> 00:28:27,400 CHANNEL. 743 00:28:27,400 --> 00:28:29,720 WE HAD A BIT OF AN INTRODUCTION 744 00:28:29,720 --> 00:28:32,400 JUST BEFORE THIS TO MICROED AND 745 00:28:32,400 --> 00:28:35,040 OTHER THINGS YOU CAN DO IN THE 746 00:28:35,040 --> 00:28:36,040 CHEMICAL SPACE. 747 00:28:36,040 --> 00:28:41,440 IN SING HL-PARTICLE CRYO-EM, WE 748 00:28:41,440 --> 00:28:43,040 PURIFY THE PROTEIN, TAKE THEM 749 00:28:43,040 --> 00:28:45,560 OUT OF THE PLASMA MEMBRANE TO DO 750 00:28:45,560 --> 00:28:47,800 THIS AND REPLACE THE MEMBRANE 751 00:28:47,800 --> 00:28:50,200 WITH DETERGENTS. 752 00:28:50,200 --> 00:28:53,520 THESE ARE DIFFERENT MEMBRANE 753 00:28:53,520 --> 00:28:55,640 MEMBETICS TO KEEP OUR PROTEIN 754 00:28:55,640 --> 00:28:58,240 HAPPY IN SOLUTION OUT OF THE 755 00:28:58,240 --> 00:29:08,360 PROTEIN. 756 00:29:46,760 --> 00:29:48,880 -- VERY RELEVANT TO DRUG 757 00:29:48,880 --> 00:29:49,600 DISCOVERY AND UNDERSTANDING HOW 758 00:29:49,600 --> 00:29:51,240 NATURAL PRODUCTS WORK. 759 00:29:51,240 --> 00:29:53,920 ONE OF THE MOST EXCITING THING 760 00:29:53,920 --> 00:29:57,240 ABOUT SINGLE-PARTICLE CRYO-EM, 761 00:29:57,240 --> 00:29:59,600 NOT ONLY CAN WE CAPTURE A 762 00:29:59,600 --> 00:30:00,800 STRUCTURE, EVERYTHING IS IN 763 00:30:00,800 --> 00:30:02,480 SOLUTION, FROZEN SOLUTION, BUT 764 00:30:02,480 --> 00:30:02,760 SOLUTION. 765 00:30:02,760 --> 00:30:04,240 WE DON'T JUST CAPTURE ONE STATE. 766 00:30:04,240 --> 00:30:06,400 WE CAN CAPTURE MANY, MANY RANGES 767 00:30:06,400 --> 00:30:08,600 OF STATES AND EVEN DEFINE 768 00:30:08,600 --> 00:30:10,040 MOVEMENTS BETWEEN THESE STATES. 769 00:30:10,040 --> 00:30:12,760 SO IN ONE SAMPLE IT COULD BE 770 00:30:12,760 --> 00:30:15,040 POSSIBLE TO SEE CLOSED OR OPENED 771 00:30:15,040 --> 00:30:17,320 OR TRANSITIONS OR HOW WE GO FROM 772 00:30:17,320 --> 00:30:19,800 THESE DIFFERENT STATES. 773 00:30:19,800 --> 00:30:22,880 SO I SET OUT TO USE THIS 774 00:30:22,880 --> 00:30:33,200 TECHNIQUE ON TRYPM8. 775 00:30:37,040 --> 00:30:37,480 THIS IS THE FIRST HIGH 776 00:30:37,480 --> 00:30:37,880 RESOLUTION WE GOT. 777 00:30:37,880 --> 00:30:38,480 LIKE OTHER TRYP CHANNELS THAT 778 00:30:38,480 --> 00:30:39,160 SHARE A SIMILAR TYPOLOGY, IT IS 779 00:30:39,160 --> 00:30:39,760 A TETROMER. 780 00:30:39,760 --> 00:30:41,880 IT HAS A REGION THAT FITS WITHIN 781 00:30:41,880 --> 00:30:45,320 THE PLASMA MEMBRANE AND A VERY, 782 00:30:45,320 --> 00:30:48,080 VERY LARGE REGION THAT SITS OUT 783 00:30:48,080 --> 00:30:49,560 OF THE REGION. 784 00:30:49,560 --> 00:30:51,520 THIS REGION IS POORLY UNDERSTOOD 785 00:30:51,520 --> 00:30:53,680 WHAT IT DOES. 786 00:30:53,680 --> 00:30:56,600 YOU ARE GOING TO NOTICE AS I 787 00:30:56,600 --> 00:30:59,560 FOCUS ON IT AND TELL YOU WHAT I 788 00:30:59,560 --> 00:31:01,840 LEARNED, I'M FOCUSING ON THE 789 00:31:01,840 --> 00:31:03,840 TRANSMEMBRANE DOMAIN. 790 00:31:03,840 --> 00:31:06,600 HOPEFULLY FURTHER STUDIES WILL 791 00:31:06,600 --> 00:31:08,800 ELUCIDATE WHY, THERE ARE ALL 792 00:31:08,800 --> 00:31:10,880 THESE PROTEINS WE CAN'T 793 00:31:10,880 --> 00:31:12,200 ATTRIBUTE A FUNCTION TO YET. 794 00:31:12,200 --> 00:31:15,320 SO THAT WE ARE ABLE TO ORIENT 795 00:31:15,320 --> 00:31:16,720 OURSELVES AND TALK ABOUT DRUG 796 00:31:16,720 --> 00:31:18,680 BINDING TO TALK ABOUT WHERE 797 00:31:18,680 --> 00:31:20,080 THESE NATURAL PRODUCTS SIT, I 798 00:31:20,080 --> 00:31:23,200 WANT TO GIVE YOU IDEA ABOUT THE 799 00:31:23,200 --> 00:31:25,120 TOPOLOGY OF THIS ION CHANNEL. 800 00:31:25,120 --> 00:31:28,360 WITHIN THE MEMBRANE THERE ARE 801 00:31:28,360 --> 00:31:33,800 SIX TRANSMEMBRANE HELOCES. 802 00:31:33,800 --> 00:31:34,080 S1-S4. 803 00:31:34,080 --> 00:31:36,520 ANYONE WHO THINKS ABOUT BOLTED 804 00:31:36,520 --> 00:31:39,400 GATED CHANNELS, THIS IS 805 00:31:39,400 --> 00:31:43,040 SYNONYMOUS TO THE BOLDED SENSOR 806 00:31:43,040 --> 00:31:43,680 IN THOSE. 807 00:31:43,680 --> 00:31:47,720 IN THE MIDDLE HERE WE HAVE OUR 808 00:31:47,720 --> 00:31:51,840 PORE HELIXES, S5 AND S6. 809 00:31:51,840 --> 00:31:53,440 THEY LINE THE SPACE WHERE THE 810 00:31:53,440 --> 00:31:55,200 IONS ARE GOING TO GO THROUGH AND 811 00:31:55,200 --> 00:31:57,400 MOVE AND REARRANGE IN ORDER TO 812 00:31:57,400 --> 00:32:02,880 LET THOSE IONS THROUGH OR NOT. 813 00:32:02,880 --> 00:32:05,880 SO IF I WANT TO UNDERSTAND 814 00:32:05,880 --> 00:32:07,120 SOMETHING ABOUT THE, YOU KNOW, 815 00:32:07,120 --> 00:32:14,320 CAPTURING, REALLY, OF A STIMULI, 816 00:32:14,320 --> 00:32:15,800 THE UNDERSTANDING OF PHYSICAL 817 00:32:15,800 --> 00:32:17,440 AND CHEMICAL STIMULI AND HOW 818 00:32:17,440 --> 00:32:20,360 THEY WORK ON THE ION CHANNEL, I 819 00:32:20,360 --> 00:32:22,520 NEED TO BIAS MY BIOCHEMICAL 820 00:32:22,520 --> 00:32:22,880 SYSTEM. 821 00:32:22,880 --> 00:32:25,080 YOU CAN IMAGINE DOING THESE 822 00:32:25,080 --> 00:32:26,520 EXPERIMENTS WITH NO STIMULUS 823 00:32:26,520 --> 00:32:28,800 AROUND TO SEE HOW IT IS BEHAVING 824 00:32:28,800 --> 00:32:30,720 IN SOLUTION. 825 00:32:30,720 --> 00:32:33,480 YOU CAN SHIFT THE EQUILIBRIUM TO 826 00:32:33,480 --> 00:32:35,200 SEE HOW IT WOULD RESPOND IN OUR 827 00:32:35,200 --> 00:32:35,400 BODY. 828 00:32:35,400 --> 00:32:39,680 SUCH AS IN THE CASE OF TRYPM8 ON 829 00:32:39,680 --> 00:32:41,920 COLD OR MAYBE ADDING SOME OF 830 00:32:41,920 --> 00:32:49,200 THESE NATURAL PRODUCTING INGAGO. 831 00:32:49,200 --> 00:32:51,400 OR A LOT OF SYNTHETIC DRUGS THAT 832 00:32:51,400 --> 00:32:57,720 ARE ANTAGONISTS AND AGONISTS 833 00:32:57,720 --> 00:33:00,560 COMMERCIALLY AVAILABLE AT ONE'S 834 00:33:00,560 --> 00:33:01,160 DISPOSAL. 835 00:33:01,160 --> 00:33:02,840 WORKING WITH TWO DIFFERENT 836 00:33:02,840 --> 00:33:04,960 SYNTHETIC ANTAGONISTS, I WAS 837 00:33:04,960 --> 00:33:08,840 ABLE TO IDENTIFY DRUGS BIND TO 838 00:33:08,840 --> 00:33:11,160 TRYPM8 THROUGH THE S-1 THROUGH 839 00:33:11,160 --> 00:33:11,760 S-4 POCKET. 840 00:33:11,760 --> 00:33:15,640 IT WAS REALLY UNCLEAR WHAT THIS 841 00:33:15,640 --> 00:33:17,680 ENTIRE REGION OF TRYP CHANNELS 842 00:33:17,680 --> 00:33:18,200 WERE DOING. 843 00:33:18,200 --> 00:33:21,240 IT IS CONSERVED IN ALL CHANNELS, 844 00:33:21,240 --> 00:33:22,400 BUT NOT VOLTAGE SENSING. 845 00:33:22,400 --> 00:33:24,240 THIS IS ONE OF THE FIRST CASES 846 00:33:24,240 --> 00:33:27,400 WE WERE ABLE TO ATTRIBUTE WHY DO 847 00:33:27,400 --> 00:33:28,960 THEY HAVE THESE CHANNELS AND 848 00:33:28,960 --> 00:33:30,600 WHAT CAN IT DO. 849 00:33:30,600 --> 00:33:32,960 BY BEING ABLE TO CAPTURE 850 00:33:32,960 --> 00:33:34,760 CHEMICAL -- IN THIS POCKET, WE 851 00:33:34,760 --> 00:33:36,920 WERE ABLE TO SEE THAT IT IS 852 00:33:36,920 --> 00:33:38,680 BASICALLY THE SHAPE OF THE 853 00:33:38,680 --> 00:33:40,320 POCKET, NOT SO MUCH THE 854 00:33:40,320 --> 00:33:41,960 CHEMISTRY OR THE SPECIFIC SIDE 855 00:33:41,960 --> 00:33:42,720 CHAINS OF IT. 856 00:33:42,720 --> 00:33:44,560 THAT ALLOW FOR MOLECULES TO SIT 857 00:33:44,560 --> 00:33:45,400 IN IT. 858 00:33:45,400 --> 00:33:48,160 IT IS INCREDIBLY ADAPTABLE. 859 00:33:48,160 --> 00:33:49,440 SO BASICALLY YOU PUT SOMETHING 860 00:33:49,440 --> 00:33:51,520 DIFFERENT IN, IT SITS GENERALLY 861 00:33:51,520 --> 00:33:53,680 IN A DIFFERENT CONFIRMATION. 862 00:33:53,680 --> 00:33:55,120 THE SIDE CHAINS ALMOST MOVE 863 00:33:55,120 --> 00:33:56,960 AROUND IT TO MATCH THE 864 00:33:56,960 --> 00:33:57,480 CHEMICALS. 865 00:33:57,480 --> 00:33:58,880 THIS IS REALLY EXPLAINS WHY 866 00:33:58,880 --> 00:34:01,040 THERE IS SUCH A DIVERSE CHEMICAL 867 00:34:01,040 --> 00:34:05,160 SPACE FOR SOMETHING LIKE THE ION 868 00:34:05,160 --> 00:34:08,000 CHANNEL TRYPM8. 869 00:34:08,000 --> 00:34:10,440 NOT ONLY ANTAGONISTS FIND THIS 870 00:34:10,440 --> 00:34:13,600 AREA, BUT AGONISTS FIND THIS 871 00:34:13,600 --> 00:34:14,120 AREA, TOO. 872 00:34:14,120 --> 00:34:17,880 YOU CAN SEE THE DENSITY FOR A 873 00:34:17,880 --> 00:34:20,800 SYNTHETIC COOLING AGENT CALLED 874 00:34:20,800 --> 00:34:21,160 ICILIN. 875 00:34:21,160 --> 00:34:22,320 WE HAVEN'T SEEN THIS 876 00:34:22,320 --> 00:34:23,800 STRUCTURALLY, IT IS CONCLUSIVE 877 00:34:23,800 --> 00:34:25,080 FROM STRUCTURE FUNCTION ANALYSIS 878 00:34:25,080 --> 00:34:27,600 THIS IS THE BINDING SITE FOR 879 00:34:27,600 --> 00:34:27,840 MENTHOL. 880 00:34:27,840 --> 00:34:29,240 SO NOW YOU HAVE A SITUATION 881 00:34:29,240 --> 00:34:31,880 WHERE YOU HAVE A VERY ADAPTABLE 882 00:34:31,880 --> 00:34:33,480 BINDING POCKET, THINGS THAT 883 00:34:33,480 --> 00:34:35,280 COMBINE THERE THAT CAN CLOSE THE 884 00:34:35,280 --> 00:34:36,280 GATE AND THINGS THAT COMBINE 885 00:34:36,280 --> 00:34:37,440 THAT CAN OPEN THE GATE. 886 00:34:37,440 --> 00:34:39,360 IT IS REALLY INTERESTING TO 887 00:34:39,360 --> 00:34:41,920 THINK ABOUT HOW THIS ALL COMES 888 00:34:41,920 --> 00:34:43,760 TOGETHER AND HOW YOU COULD 889 00:34:43,760 --> 00:34:46,720 FURTHER THIS CHEMICAL SPACE. 890 00:34:46,720 --> 00:34:49,120 SO TO MAKE THE SITUATION MORE 891 00:34:49,120 --> 00:34:50,320 EXCITING AND INTERESTING, I 892 00:34:50,320 --> 00:34:52,440 WOULD SAY, IT TURNS OUT IT IS 893 00:34:52,440 --> 00:34:54,200 NOT ONLY CHEMICALS THAT COMBINE 894 00:34:54,200 --> 00:34:56,240 IN THIS SPACE, BUT IT IS 895 00:34:56,240 --> 00:34:58,000 ACTUALLY LIPIDS, TOO. 896 00:34:58,000 --> 00:35:00,000 THIS COULD HAVE INTERESTING 897 00:35:00,000 --> 00:35:01,640 IMPLICATIONS FOR THE REGULATION 898 00:35:01,640 --> 00:35:03,400 OF HOW THESE NATURAL PRODUCTS 899 00:35:03,400 --> 00:35:03,680 WORK. 900 00:35:03,680 --> 00:35:05,560 SO WHEN I SOLVE MY STRUCTURES I 901 00:35:05,560 --> 00:35:07,240 CAN SEE PROBABLY NOT 902 00:35:07,240 --> 00:35:08,360 SURPRISINGLY SO THERE WERE A 903 00:35:08,360 --> 00:35:10,680 BUNCH OF LIPIDS THAT SAT BETWEEN 904 00:35:10,680 --> 00:35:14,200 THE TETROMERS. 905 00:35:14,200 --> 00:35:15,400 THIS IS EMPTY SPACE. 906 00:35:15,400 --> 00:35:16,920 YOU CAN IMAGINE THEY HAVE TO BE 907 00:35:16,920 --> 00:35:20,040 THERE STRUCTURALLY SO AS THE 908 00:35:20,040 --> 00:35:21,520 MEMBRANE AND PROTEIN UNITE AND 909 00:35:21,520 --> 00:35:22,000 ARE ONE. 910 00:35:22,000 --> 00:35:24,520 IT TURNS OUT THE TAIL OF ONE OF 911 00:35:24,520 --> 00:35:27,320 THESE LIPIDS ACTUALLY STRETCHES 912 00:35:27,320 --> 00:35:30,880 RIGHT UP INTO THE LIGAND BINDING 913 00:35:30,880 --> 00:35:32,280 POCKET WHEN NO CHEMICALS HAVE 914 00:35:32,280 --> 00:35:34,360 BEEN ADDED TO THE PROTEIN --. 915 00:35:34,360 --> 00:35:37,520 IT SEEMS LIKE IF WE DON'T HAVE 916 00:35:37,520 --> 00:35:40,440 AN ACTIVATOR OR AGONTIST AROUND 917 00:35:40,440 --> 00:35:42,520 A LIPID TAIL LIKES TO SIT IN 918 00:35:42,520 --> 00:35:43,480 THERE. 919 00:35:43,480 --> 00:35:44,880 OBVIOUSLY, MAYBE NOT OBVIOUSLY, 920 00:35:44,880 --> 00:35:46,280 BUT OBVIOUSLY FROM THE 921 00:35:46,280 --> 00:35:48,000 STRUCTURES I HAVE LOOKED AT, YOU 922 00:35:48,000 --> 00:35:50,320 NEED TO REMOVE THE LIPID TAIL TO 923 00:35:50,320 --> 00:35:52,520 HAVE MENTHOL SIT IN THAT BINDING 924 00:35:52,520 --> 00:35:52,840 POCKET. 925 00:35:52,840 --> 00:35:54,000 THE SPACE IS COMPLETELY 926 00:35:54,000 --> 00:35:57,000 OVERLAPPING. 927 00:35:57,000 --> 00:35:59,320 SO SOMETHING THAT IS EVEN MORE 928 00:35:59,320 --> 00:36:00,560 INTERESTING TO THINK ABOUT IS 929 00:36:00,560 --> 00:36:02,840 WHAT COULD THIS LIPID BE AND IS 930 00:36:02,840 --> 00:36:04,440 IT AN IMPORTANT SIGNALLING 931 00:36:04,440 --> 00:36:04,840 LIPID? 932 00:36:04,840 --> 00:36:06,880 ONE OF THE MOST IMPORTANT 933 00:36:06,880 --> 00:36:08,440 SIGNALLING LIPIDS IN OUR BODY, 934 00:36:08,440 --> 00:36:10,800 KNOWN TO NEGATIVELY AND 935 00:36:10,800 --> 00:36:14,520 POSITIVELY REGULATE THEM IS 936 00:36:14,520 --> 00:36:14,720 PIP2. 937 00:36:14,720 --> 00:36:17,560 IT IS OF LOW ABUNDANCE AND 938 00:36:17,560 --> 00:36:19,520 SYNTHESIS IS HEAVILY CONTROLLED. 939 00:36:19,520 --> 00:36:23,360 WE KNOW TRYPM8 IS POSITIVELY 940 00:36:23,360 --> 00:36:25,800 REGULATED BY PIP2. 941 00:36:25,800 --> 00:36:28,560 IT LEADS TO FURTHER ACTIVATION 942 00:36:28,560 --> 00:36:31,200 OF THE CHANNEL. 943 00:36:31,200 --> 00:36:33,760 WE KNOW ITS HEAD GROUPS SITS IN 944 00:36:33,760 --> 00:36:36,640 THIS VICINITY AND IN TERMS OF 945 00:36:36,640 --> 00:36:41,280 SPACE IT WOULD MAKE SENSE IF 946 00:36:41,280 --> 00:36:45,640 THIS WAS A LIPID TAIL. 947 00:36:45,640 --> 00:36:48,080 HOW PIP 2 IS IN THE BINDING IS A 948 00:36:48,080 --> 00:36:49,480 CONTINUING AIR UH YEAH OF 949 00:36:49,480 --> 00:36:51,960 RESEARCH. 950 00:36:51,960 --> 00:36:55,880 SO THIS WORK ON TRYPM8 AND OTHER 951 00:36:55,880 --> 00:36:58,280 WORK THAT HAS COME ALONG SIDE 952 00:36:58,280 --> 00:36:59,920 HAVE REALLY ALLOWED US TO COME 953 00:36:59,920 --> 00:37:02,160 UP WITH WHAT I WOULD CALL GATING 954 00:37:02,160 --> 00:37:04,160 MODELS OR IDEAS HOW THESE 955 00:37:04,160 --> 00:37:05,760 DIFFERENT NATURAL PRODUCT 956 00:37:05,760 --> 00:37:06,160 RECEPTORS WORK. 957 00:37:06,160 --> 00:37:08,720 SO WHAT YOU SEE ON THE LEFT-HAND 958 00:37:08,720 --> 00:37:13,200 SIDE IS TRPV1, THE HEAT SENSORS, 959 00:37:13,200 --> 00:37:16,240 RESPONSIVE TO CAPSASIN. 960 00:37:16,240 --> 00:37:19,720 AND ON THE RIGHT TRPM8, THE COLD 961 00:37:19,720 --> 00:37:21,640 WE HAVE BEEN TALKING ABOUT. 962 00:37:21,640 --> 00:37:24,800 FOR TRPV1 YOU SEE VERY, VERY 963 00:37:24,800 --> 00:37:26,480 LIMITS MOTION. 964 00:37:26,480 --> 00:37:28,760 PERHAPS YOU SHALL SQUINT AT YOUR 965 00:37:28,760 --> 00:37:29,040 SCREEN. 966 00:37:29,040 --> 00:37:30,320 ON THE RIGHT-HAND SIDE YOU SEE 967 00:37:30,320 --> 00:37:35,640 THOSE MOTIONS IN TRPM8 AND YOU 968 00:37:35,640 --> 00:37:37,960 SEE HOW MUCH THEY ARE INVOLVING 969 00:37:37,960 --> 00:37:39,280 THAT DOMAIN WE UNDERSTAND SO 970 00:37:39,280 --> 00:37:42,360 LITTLE ABOUT. 971 00:37:42,360 --> 00:37:46,680 SO THIS HAS LED US TO PROPOSE 972 00:37:46,680 --> 00:37:47,680 THE FOLLOWING. 973 00:37:47,680 --> 00:37:49,720 THE IMPORTANCE OF WHERE THESE 974 00:37:49,720 --> 00:37:51,640 NATURAL PRODUCT DRUGS BIND LEAD 975 00:37:51,640 --> 00:37:53,800 TO THE GATING MECHANISMS FOR 976 00:37:53,800 --> 00:37:54,480 THESE CHANNELS. 977 00:37:54,480 --> 00:38:02,120 IN THE CASE OF TRPV1 CAB SAICIN 978 00:38:02,120 --> 00:38:03,720 BINDS RIGHT NEAR THE PORE. 979 00:38:03,720 --> 00:38:06,000 IT CAUSES A REARRANGEMENT OF A 980 00:38:06,000 --> 00:38:07,720 COUPLE OF RESIDUES IN THE PORE 981 00:38:07,720 --> 00:38:10,640 AND IT IS OPEN AND IONS CAN FLY 982 00:38:10,640 --> 00:38:10,880 THROUGH. 983 00:38:10,880 --> 00:38:12,520 WE DISCOVERED THE BINDING POCKET 984 00:38:12,520 --> 00:38:14,840 FOR MENTHOL IS PRETTY FAR FROM 985 00:38:14,840 --> 00:38:15,920 THE GATE HERE. 986 00:38:15,920 --> 00:38:18,920 SO WHAT ACTUALLY HAPPENS IN THIS 987 00:38:18,920 --> 00:38:20,680 CASE IS LARGE CONFIRMATIONAL 988 00:38:20,680 --> 00:38:23,600 MOVEMENTS FROM S-1 THROUGH S-4 989 00:38:23,600 --> 00:38:25,040 DOMAIN ARE NEEDED IN ORDER TO 990 00:38:25,040 --> 00:38:29,120 MAKE LARGE MOVEMENTS OF THE TRP 991 00:38:29,120 --> 00:38:31,080 DOMAIN THAT BASICALLY SPANS THE 992 00:38:31,080 --> 00:38:33,600 SPACE BETWEEN THE PORE AND WHERE 993 00:38:33,600 --> 00:38:35,120 THE CHEMICAL BINDS. 994 00:38:35,120 --> 00:38:37,320 AND THIS WAS ALSO VERY 995 00:38:37,320 --> 00:38:38,560 INTERESTING TO SEE BECAUSE IT 996 00:38:38,560 --> 00:38:39,840 WASN'T KNOWN FOR A VERY LONG 997 00:38:39,840 --> 00:38:42,640 TIME WHAT THE ROLE OF THE TRP 998 00:38:42,640 --> 00:38:44,360 DOMAIN WAS. 999 00:38:44,360 --> 00:38:45,800 OBVIOUSLY, PEOPLE THOUGHT IT WAS 1000 00:38:45,800 --> 00:38:47,800 IMPORTANT AS IT WAS NAMED AFTER 1001 00:38:47,800 --> 00:38:50,240 THE ENTIRE FAMILY. 1002 00:38:50,240 --> 00:38:53,400 SO THAT WAS QUITE NEAT TO SEE. 1003 00:38:53,400 --> 00:38:58,800 SINGLE PARTICLE CRO-EM IS 1004 00:38:58,800 --> 00:39:00,440 IMPORTANT FOR STUDYING. 1005 00:39:00,440 --> 00:39:03,280 WE HAVE CLOSED STRUCTURES, OPEN 1006 00:39:03,280 --> 00:39:05,280 STRUCTURES AND DESENSITIZED 1007 00:39:05,280 --> 00:39:05,840 STRUCTURES NOW. 1008 00:39:05,840 --> 00:39:07,160 WHAT WE ARE STILL WORKINGEN ON 1009 00:39:07,160 --> 00:39:09,640 IS DETECTION OF TEMPERATURE. 1010 00:39:09,640 --> 00:39:11,720 IT IS A VERY ACTIVE AREA IN THE 1011 00:39:11,720 --> 00:39:11,920 FIELD. 1012 00:39:11,920 --> 00:39:14,360 EVERYONE IS EXCITED AND WE ARE 1013 00:39:14,360 --> 00:39:15,680 SCRATCHING OUR HEADS THINKING 1014 00:39:15,680 --> 00:39:19,680 HOW CAN WE DO THIS, HOW CAN WE 1015 00:39:19,680 --> 00:39:20,480 CAPTURE THESE THINGS? 1016 00:39:20,480 --> 00:39:22,240 MORE IMPORTANTLY, HOW DO WE KNOW 1017 00:39:22,240 --> 00:39:24,000 THE CHANGE WE SEE, WHERE IT 1018 00:39:24,000 --> 00:39:25,720 STARTED FROM AND HOW IT 1019 00:39:25,720 --> 00:39:36,200 PROPAGATED AND PROBABLY IT 1020 00:40:13,960 --> 00:40:19,960 >>NOW WE WITH RIGHT AT OUR LAST 1021 00:40:19,960 --> 00:40:21,320 SPEAKER WHO WILL SHARE HER 1022 00:40:21,320 --> 00:40:25,320 SLIDES, DR. CHELSI CASSILLY. 1023 00:40:25,320 --> 00:40:28,880 THANK YOU SO MUCH FOR THE 1024 00:40:28,880 --> 00:40:30,360 INVITATION TO JOIN AND TO SPEAK 1025 00:40:30,360 --> 00:40:32,920 AT THIS SEMINAR. 1026 00:40:32,920 --> 00:40:34,920 SO THIS IS AS PATRICK SAID, WHEN 1027 00:40:34,920 --> 00:40:37,680 HE WAS INTRODUCING, I HAVE NOT 1028 00:40:37,680 --> 00:40:39,600 BEEN IN THE CLARDY LAB FOR ABOUT 1029 00:40:39,600 --> 00:40:41,360 TWO YEARS NOW, SO THE WORK I'M 1030 00:40:41,360 --> 00:40:42,840 GOING TO BE PRESENTING IS VERY 1031 00:40:42,840 --> 00:40:45,360 FOND TO MY HEART, BUT I HAVEN'T 1032 00:40:45,360 --> 00:40:47,120 REALLY BEEN DOING IT IN PERSON 1033 00:40:47,120 --> 00:40:47,800 IN A WHILE. 1034 00:40:47,800 --> 00:40:51,000 SO IT WAS REALLY FUN FOR ME TO 1035 00:40:51,000 --> 00:40:53,720 LOOK BACK ON THIS RESEARCH AND 1036 00:40:53,720 --> 00:40:54,360 REFAMILIARIZE MYSELF WITH 1037 00:40:54,360 --> 00:40:56,440 SOMETHING I REALLY ENJOYED QUITE 1038 00:40:56,440 --> 00:40:57,120 A BIT. 1039 00:40:57,120 --> 00:40:58,640 TODAY I'M GOING TO BE TALKING 1040 00:40:58,640 --> 00:41:01,360 ABOUT THE CHEMICAL CORRELATIONS 1041 00:41:01,360 --> 00:41:03,080 BETWEEN GUT MICROBES AND THEIR 1042 00:41:03,080 --> 00:41:04,320 HOST RESPONSES. 1043 00:41:04,320 --> 00:41:08,920 I JUST WANT TO POINT OUT THIS IS 1044 00:41:08,920 --> 00:41:11,320 WORK THAT WAS DONE WHEN I WAS A 1045 00:41:11,320 --> 00:41:13,560 POSTDOCTORAL FELLOW AT THE 1046 00:41:13,560 --> 00:41:17,200 CLARDY LAB AT THE HARVARD MIDDLE 1047 00:41:17,200 --> 00:41:19,600 SCHOOL AND WORKED WITH 1048 00:41:19,600 --> 00:41:20,800 INDIVIDUALS AT THE BROAD 1049 00:41:20,800 --> 00:41:21,440 INSTITUTE AS WELL. 1050 00:41:21,440 --> 00:41:25,680 THE ORGANISM I'M TALKING ABOUT 1051 00:41:25,680 --> 00:41:27,640 TODAY IS AN ORGANISM YOU HAVE 1052 00:41:27,640 --> 00:41:29,480 HEARD OF BECAUSE OF HOW POPULAR 1053 00:41:29,480 --> 00:41:31,360 AND INTERESTING THIS ORGANISM 1054 00:41:31,360 --> 00:41:31,840 IS. 1055 00:41:31,840 --> 00:41:35,320 IT IS CONSIDERED UNIQUE IN TERMS 1056 00:41:35,320 --> 00:41:37,800 OF THE GUT MICROBE BIOTA. 1057 00:41:37,800 --> 00:41:42,280 IT IS AT THIS POINT THE ONLY 1058 00:41:42,280 --> 00:41:45,280 SPECIES WITHIN THE GENE US IN 1059 00:41:45,280 --> 00:41:46,440 AKKERMANSIA WE KNOW OF IN THE 1060 00:41:46,440 --> 00:41:47,080 GUT. 1061 00:41:47,080 --> 00:41:49,520 IT MAKES UP ON AVERAGE 3% OF THE 1062 00:41:49,520 --> 00:41:52,480 HEALTHY HUMAN GUT. 1063 00:41:52,480 --> 00:41:55,600 NOW, 3% MAY NOT SOUND LIKE VERY 1064 00:41:55,600 --> 00:41:57,040 MUCH, BUT WHEN WE ARE TALKING 1065 00:41:57,040 --> 00:41:59,640 ABOUT THE INSANE COMPLEXITY OF 1066 00:41:59,640 --> 00:42:02,720 THE HUMAN GUT MICROBIOME, 3% IS 1067 00:42:02,720 --> 00:42:06,760 AN AMAZING AMOUNT OF REAL ESTATE 1068 00:42:06,760 --> 00:42:08,240 FOR THIS ONE ORGANISM TO TAKE 1069 00:42:08,240 --> 00:42:18,320 UP. 1070 00:42:19,960 --> 00:42:20,560 THIS ORGANISM IS DOING SOMETHING 1071 00:42:20,560 --> 00:42:21,160 THAT IS CLEARLY IMPORTANT TO 1072 00:42:21,160 --> 00:42:21,760 HAVE THAT MUCH SPACE WITHIN THE 1073 00:42:21,760 --> 00:42:32,000 GUT. 1074 00:42:32,000 --> 00:42:32,560 THERE ARE LINKS THAT HAVE BEEN 1075 00:42:32,560 --> 00:42:33,200 DESCRIBED THAT POINT OUT THAT 1076 00:42:33,200 --> 00:42:33,880 WHEN AKKERMANSIA IS PRESENT 1077 00:42:33,880 --> 00:42:36,880 WITHIN A HOST, A HUMAN, IT SEEMS 1078 00:42:36,880 --> 00:42:41,400 TO LOWER THE RISK OF OBESITY OR 1079 00:42:41,400 --> 00:42:44,000 CERTAIN TYPES OF DIABETES. 1080 00:42:44,000 --> 00:42:47,720 AND FURTHERMORE, THAT WHENEVER 1081 00:42:47,720 --> 00:42:49,400 PATIENTS WOULD DRINK HEAT 1082 00:42:49,400 --> 00:42:51,720 INACTIVATED AKKERMANSIA 1083 00:42:51,720 --> 00:42:54,160 MUCINIPHILA THEY SAW ALLEVIATION 1084 00:42:54,160 --> 00:42:56,960 OF METABOLIC SYNDROME IN 1085 00:42:56,960 --> 00:42:59,120 OVERWEIGHT OR OBESE PATIENTS. 1086 00:42:59,120 --> 00:43:00,920 THIS AS WELL AS MANY OTHER TYPES 1087 00:43:00,920 --> 00:43:04,240 OF PUBLICATIONS OUT THERE POINT 1088 00:43:04,240 --> 00:43:06,160 OUT AKKERMANSIA WHEN PRESENT 1089 00:43:06,160 --> 00:43:07,960 WITHIN A HUMAN DOES SEEM TO HAVE 1090 00:43:07,960 --> 00:43:10,560 THIS RELATIONSHIP IT IS HELPING 1091 00:43:10,560 --> 00:43:12,240 TO PREVENT INFLAMMATORY DISEASES 1092 00:43:12,240 --> 00:43:13,600 OR INFLAMMATORY STATES WITHIN 1093 00:43:13,600 --> 00:43:15,960 ITS HOST. 1094 00:43:15,960 --> 00:43:17,680 HOWEVER, IT IS NOT COMPLETELY 1095 00:43:17,680 --> 00:43:19,120 KNOCKING OUT INFLAMMATION. 1096 00:43:19,120 --> 00:43:22,000 BECAUSE WE DO SEE THAT IT HAS A 1097 00:43:22,000 --> 00:43:25,040 POSITIVE CORRELATION WITH A 1098 00:43:25,040 --> 00:43:31,840 POSITIVE RESPONSE TO IMMUNO 1099 00:43:31,840 --> 00:43:32,120 THERAPIES. 1100 00:43:32,120 --> 00:43:33,880 WHEN IT IS PRESENT THERE IS A 1101 00:43:33,880 --> 00:43:39,440 BETTER RESPONSE TO PD1 BLOCKADE 1102 00:43:39,440 --> 00:43:41,320 CANCER IMMUNO THERAPY. 1103 00:43:41,320 --> 00:43:51,920 THERE SEEMS TO BE A CONTROL OR 1104 00:43:51,920 --> 00:43:52,520 HOME YO STATIC RESPONSE, WHEN 1105 00:43:52,520 --> 00:43:53,120 AKKERMANSIA IS PRESENT, SOMEONE 1106 00:43:53,120 --> 00:43:53,760 IS ABLE TO PREVENT OR HOPEFULLY 1107 00:43:53,760 --> 00:43:54,280 NOT SEE THE SYMPTOMS OF 1108 00:43:54,280 --> 00:43:54,760 INFLAMMATORY DISEASES. 1109 00:43:54,760 --> 00:43:56,120 HOWEVER, THEY ARE ALSO ABLE TO 1110 00:43:56,120 --> 00:43:57,200 MOUNT AN APPROPRIATE IMMUNE 1111 00:43:57,200 --> 00:44:00,600 RESPONSE IN RELATION TO IMMUNO 1112 00:44:00,600 --> 00:44:00,880 THERAPIES. 1113 00:44:00,880 --> 00:44:02,360 THE PAPER I'M PRESENTING TODAY 1114 00:44:02,360 --> 00:44:04,280 DESCRIBES THIS NATURE A LITTLE 1115 00:44:04,280 --> 00:44:07,560 MORE, BUT WE ALSO WROTE A LITTLE 1116 00:44:07,560 --> 00:44:08,960 BLOG POST IN SMALL THINGS 1117 00:44:08,960 --> 00:44:11,240 CONSIDERED AND WE KIND OF 1118 00:44:11,240 --> 00:44:14,760 RELATED THIS ORGANISM TO 1119 00:44:14,760 --> 00:44:16,240 GOLDILOCKS AND SAID THIS 1120 00:44:16,240 --> 00:44:17,720 ORGANISM HELPS TO MAINTAIN 1121 00:44:17,720 --> 00:44:19,280 SOMEWHERE RIGHT IN THE MIDDLE 1122 00:44:19,280 --> 00:44:21,600 WHEN WE TALK ABOUT INFLAMMATION. 1123 00:44:21,600 --> 00:44:24,000 NOT TOO MUCH, NOT TOO LITTLE. 1124 00:44:24,000 --> 00:44:25,600 AKKERMANSIA IS TRYING TO KEEP IT 1125 00:44:25,600 --> 00:44:27,080 RIGHT THERE IN THE MIDDLE. 1126 00:44:27,080 --> 00:44:29,280 SO WITH THIS IN MIND, THE LAB 1127 00:44:29,280 --> 00:44:32,160 WAS VERY INTERESTED IN 1128 00:44:32,160 --> 00:44:33,720 UNDERSTANDING WHAT THE ORGANISM 1129 00:44:33,720 --> 00:44:35,280 WAS DOING SPECIFICALLY IN TERMS 1130 00:44:35,280 --> 00:44:36,400 OF MOLECULES. 1131 00:44:36,400 --> 00:44:43,520 SO HOW IS IT CONTROLLING THIS 1132 00:44:43,520 --> 00:44:44,680 HOMEO STATIC STATE WHEN 1133 00:44:44,680 --> 00:44:45,800 AKKERMANSIA IS PRESENT. 1134 00:44:45,800 --> 00:44:47,520 IN ORDER TO ASSESS WHAT 1135 00:44:47,520 --> 00:44:49,160 MOLECULES MIGHT BE HELPING OR 1136 00:44:49,160 --> 00:44:51,680 CONTRIBUTES TO THIS INTERESTING 1137 00:44:51,680 --> 00:44:54,640 RESPONSE, WE RELIED UPON AN 1138 00:44:54,640 --> 00:44:56,760 ASSAY THAT WAS ALREADY VERY WELL 1139 00:44:56,760 --> 00:44:58,240 DESCRIBED AND DEVELOPED WITHIN 1140 00:44:58,240 --> 00:45:00,160 OUR LAB AND THE BROAD LAB WE 1141 00:45:00,160 --> 00:45:02,920 WERE COLLABORATING WITH. 1142 00:45:02,920 --> 00:45:07,240 AND SO THIS ASSAY IS PREVIOUSLY 1143 00:45:07,240 --> 00:45:09,600 DESCRIBED IN OTHER PUBLICATIONS. 1144 00:45:09,600 --> 00:45:10,880 ESSENTIALLY WE WERE LOOKING FOR 1145 00:45:10,880 --> 00:45:16,480 A RELEASE OF A CYTOKINE, AN 1146 00:45:16,480 --> 00:45:19,640 INFLAMMATORY PROTEIN AND USING 1147 00:45:19,640 --> 00:45:23,040 BONE-MARROW-DERIVED DENDRITIC 1148 00:45:23,040 --> 00:45:23,240 CELLS. 1149 00:45:23,240 --> 00:45:26,200 WE COLLECT FEMURS AND TIBIAS, 1150 00:45:26,200 --> 00:45:28,080 CHOP OFF THE ENDS OF THE BONE 1151 00:45:28,080 --> 00:45:31,120 AND PUSH THE BONE MARROW THROW. 1152 00:45:31,120 --> 00:45:35,000 WE MATURE THAT INTO DENDRITIC 1153 00:45:35,000 --> 00:45:36,800 CELLS IN SEVEN DAYS. 1154 00:45:36,800 --> 00:45:39,080 THEN YOU CAN TREAT THEM WITH A 1155 00:45:39,080 --> 00:45:40,640 VARIETY OF NATURAL PRODUCTS OR 1156 00:45:40,640 --> 00:45:41,520 BACTERIAL FRACTIONS. 1157 00:45:41,520 --> 00:45:43,760 THAT IS WHAT WE DID WITH 1158 00:45:43,760 --> 00:45:45,560 AKKERMANSIA MUCINIPHILA. 1159 00:45:45,560 --> 00:45:48,800 WE FRACTIONATED IT AND TREATED 1160 00:45:48,800 --> 00:45:52,520 THE DENDRITIC CELLS AND LOOKED 1161 00:45:52,520 --> 00:45:55,640 FOR CYTOKINE RELEASE. 1162 00:45:55,640 --> 00:46:00,160 I'M FOCUSING ON TUMOR NECROSIS 1163 00:46:00,160 --> 00:46:02,200 ALPHA, BUT WE DID LOOK AT A 1164 00:46:02,200 --> 00:46:07,000 VARIETY OF CYTOKINES. 1165 00:46:07,000 --> 00:46:08,840 THIS IS AN ASSAY YOU CAN CHANGE 1166 00:46:08,840 --> 00:46:10,680 MANY POINTS TO ANSWER DIFFERENT 1167 00:46:10,680 --> 00:46:20,360 QUESTIONS. 1168 00:46:20,360 --> 00:46:20,920 AS I MENTIONED WE DID THIS 1169 00:46:20,920 --> 00:46:21,440 PROCESS WITH AKKERMANSIA. 1170 00:46:21,440 --> 00:46:22,080 AND I WANT TO POINT OUT A LOT OF 1171 00:46:22,080 --> 00:46:22,760 THIS INITIAL WORK WITH GROWING 1172 00:46:22,760 --> 00:46:25,760 ORGANISM AND STARTING TO 1173 00:46:25,760 --> 00:46:31,560 FRACTIONATE WAS DONE BY MY 1174 00:46:31,560 --> 00:46:34,280 CO-FIRST AUTHOR DR. BAE. 1175 00:46:34,280 --> 00:46:35,960 HE GREW COPIOUS AMOUNTS OF 1176 00:46:35,960 --> 00:46:36,280 AKKERMANSIA. 1177 00:46:36,280 --> 00:46:38,520 YOU CAN SEE FROM THIS SLIDE, THE 1178 00:46:38,520 --> 00:46:43,240 SECTION ON THE LEFT HERE, THAT 1179 00:46:43,240 --> 00:46:46,760 HE GREW THE ORGANISM, STARTED 1180 00:46:46,760 --> 00:46:48,360 SEPARATING OUT MATERIALS IN 1181 00:46:48,360 --> 00:46:50,120 VARIOUS WAYS. 1182 00:46:50,120 --> 00:46:51,440 PHYSICAL SEPARATION AND CHEMICAL 1183 00:46:51,440 --> 00:46:51,760 SEPARATION. 1184 00:46:51,760 --> 00:46:54,640 AT VARIOUS POINTS WITHIN HIS 1185 00:46:54,640 --> 00:46:56,840 PROCESS HE WOULD GIVE ME THE 1186 00:46:56,840 --> 00:46:58,520 FRACTIONS AND I WOULD DO THE 1187 00:46:58,520 --> 00:46:59,000 ASSAYS. 1188 00:46:59,000 --> 00:47:00,520 I'M MORE OF A BIOLOGIST SO I 1189 00:47:00,520 --> 00:47:02,440 WOULD HELP DO THE ASSAYS. 1190 00:47:02,440 --> 00:47:04,080 I WOULD TELL HIM IN WHICH 1191 00:47:04,080 --> 00:47:06,400 FRACTIONS THE ACTIVITY OR 1192 00:47:06,400 --> 00:47:07,680 INFLAMMATORY ACTIVITY WOULD LIE. 1193 00:47:07,680 --> 00:47:12,600 HE WOULD GO BACK AND DO MORE 1194 00:47:12,600 --> 00:47:13,600 FRACTIONATION UNTIL WE 1195 00:47:13,600 --> 00:47:14,680 EVENTUALLY FOUND, FOLLOWING THE 1196 00:47:14,680 --> 00:47:17,840 RED NUMBERS, THAT WAS WHERE THE 1197 00:47:17,840 --> 00:47:20,160 ACTIVITY WAS FOUND AND WE ENDED 1198 00:47:20,160 --> 00:47:23,480 UP WITH AKKERMANSIA 1199 00:47:23,480 --> 00:47:25,800 MUCINIPHILA -- OR AMPE. 1200 00:47:25,800 --> 00:47:32,640 THAT WAS A GENERAL FRACTION THAT 1201 00:47:32,640 --> 00:47:37,000 HAD SEVERAL ACETYL. 1202 00:47:37,000 --> 00:47:40,680 WE HAVE RELIEF ON THE Y AXIS AND 1203 00:47:40,680 --> 00:47:41,600 TREATMENTS ON THE X. 1204 00:47:41,600 --> 00:47:48,560 IF YOU LOOK AT THE AMPE THERE IS 1205 00:47:48,560 --> 00:47:51,440 RELEASE F DMSO IS OUR NEGATIVE 1206 00:47:51,440 --> 00:47:51,680 CONTROL. 1207 00:47:51,680 --> 00:47:56,680 TWO POSITIVES ARE INFLAMMATORY 1208 00:47:56,680 --> 00:48:01,880 LIGINS, LPS AND PAM3CSK. 1209 00:48:01,880 --> 00:48:05,040 HE FURTHER PURIFIED OUT A SINGLE 1210 00:48:05,040 --> 00:48:06,880 MOLECULE RESPONSIBLE FOR THIS 1211 00:48:06,880 --> 00:48:07,160 ACTIVITY. 1212 00:48:07,160 --> 00:48:07,840 AND THAT MOLECULE LOOKS LIKE 1213 00:48:07,840 --> 00:48:09,360 THIS. 1214 00:48:09,360 --> 00:48:18,600 SO LIKE I SAID, IT WAS A 1215 00:48:18,600 --> 00:48:19,800 PHOSPHATAL STRUCTURE. 1216 00:48:19,800 --> 00:48:21,480 THE ONLY REAL DIFFERENCE HERE IS 1217 00:48:21,480 --> 00:48:28,640 IT HAS SOME BRANCHES ON THE 1218 00:48:28,640 --> 00:48:30,400 PHOSPH LIPID TAILS. 1219 00:48:30,400 --> 00:48:33,520 ON ONE CHAIN IT HAS AN ISOBRANCH 1220 00:48:33,520 --> 00:48:37,240 AND THE OTHER CHAIN HAS AN 1221 00:48:37,240 --> 00:48:37,640 ANTI-ISOBRANCH. 1222 00:48:37,640 --> 00:48:39,280 AT THIS POINT I DON'T SAY WE 1223 00:48:39,280 --> 00:48:41,240 WERE BUMMED WITH THE STRUCTURE, 1224 00:48:41,240 --> 00:48:43,960 BUT THIS IS A TYPICAL MOLECULE, 1225 00:48:43,960 --> 00:48:46,280 NOT SUPER EXCITING, BUT WHAT WAS 1226 00:48:46,280 --> 00:48:47,800 INTERESTING IS THAT THIS WAS 1227 00:48:47,800 --> 00:48:50,680 RESPONSIBLE FOR THE ACTIVITY WE 1228 00:48:50,680 --> 00:48:51,480 WERE SEEING. 1229 00:48:51,480 --> 00:48:53,600 WE DECIDED TO CONFIRM THAT 1230 00:48:53,600 --> 00:48:56,320 WITHOUT A DOUBT BY PERFORMING A 1231 00:48:56,320 --> 00:48:59,760 SYNTHETIC REACTION WITH OUR 1232 00:48:59,760 --> 00:49:05,240 COLLABORATORS IN THE DANA FASHER 1233 00:49:05,240 --> 00:49:05,520 INSTITUTE. 1234 00:49:05,520 --> 00:49:10,240 -- DANA FARBER INSTITUTE. 1235 00:49:10,240 --> 00:49:12,440 WE WERE CALLING A15 AND I15 IN 1236 00:49:12,440 --> 00:49:14,280 THE LAP BECAUSE OF THE VERY LONG 1237 00:49:14,280 --> 00:49:15,040 NAME. 1238 00:49:15,040 --> 00:49:19,320 HE SYNTHESIZED THE EXACT 1239 00:49:19,320 --> 00:49:23,280 REPLICATED PRODUCT IN THE BLUE 1240 00:49:23,280 --> 00:49:23,560 TRIANGLES. 1241 00:49:23,560 --> 00:49:25,760 AND THEN HE ALSO SWITCHED THE 1242 00:49:25,760 --> 00:49:27,880 BRANCHED CHAINS TO THE OPPOSITE 1243 00:49:27,880 --> 00:49:28,120 LOCATIONS. 1244 00:49:28,120 --> 00:49:29,320 HE SWAPPED WHERE THE BRANCHES 1245 00:49:29,320 --> 00:49:32,560 WERE AND THAT WAS IN THE GREEN 1246 00:49:32,560 --> 00:49:32,840 DIAMONDS. 1247 00:49:32,840 --> 00:49:34,840 AND SO YOU CAN SEE THAT THEY 1248 00:49:34,840 --> 00:49:36,880 WERE ABLE TO REPLICATE THE 1249 00:49:36,880 --> 00:49:38,280 ACTIVITY OF THE NATURAL PRODUCT 1250 00:49:38,280 --> 00:49:39,800 VERY WELL AND SO THIS INDICATED 1251 00:49:39,800 --> 00:49:41,440 THAT WHAT WE WERE SEEING WAS 1252 00:49:41,440 --> 00:49:44,920 REALLY ACTIVITY BASED ON THIS 1253 00:49:44,920 --> 00:49:55,280 ALMOST PRETTY COMMON 1254 00:49:59,000 --> 00:50:00,240 PHOSPHATAL --. 1255 00:50:00,240 --> 00:50:01,680 WE WERE INTERESTED IN 1256 00:50:01,680 --> 00:50:02,480 UNDERSTANDING WHAT WAS HAPPENING 1257 00:50:02,480 --> 00:50:03,920 TO TRIGGER THIS RESPONSE. 1258 00:50:03,920 --> 00:50:05,760 IT WAS PROBABLY A TOLL LIKE 1259 00:50:05,760 --> 00:50:08,240 RECEPTOR BINDS TO THIS NATURAL 1260 00:50:08,240 --> 00:50:08,480 PRODUCT. 1261 00:50:08,480 --> 00:50:10,960 AND WE DECIDED TO LOOK AND SEE 1262 00:50:10,960 --> 00:50:13,440 IF IT WAS TLR2 SPECIFIC. 1263 00:50:13,440 --> 00:50:14,960 WE THOUGHT SO BECAUSE IT WAS -- 1264 00:50:14,960 --> 00:50:17,080 IT IS A LIPID. 1265 00:50:17,080 --> 00:50:19,240 TLR2 IS KNOWN TO BIND TO LIPIDS. 1266 00:50:19,240 --> 00:50:21,120 AND SO WHAT WE DID WAS WE TOOK 1267 00:50:21,120 --> 00:50:23,360 THE SAME ASSAY I HAVE DESCRIBED 1268 00:50:23,360 --> 00:50:24,320 TO YOU PREVIOUSLY. 1269 00:50:24,320 --> 00:50:26,960 WE USED MICE THAT DIDN'T HAVE 1270 00:50:26,960 --> 00:50:27,160 TLR2. 1271 00:50:27,160 --> 00:50:30,080 THEY WERE MUTANTS OR DIDN'T HAVE 1272 00:50:30,080 --> 00:50:31,720 TLR1 OR TLR6. 1273 00:50:31,720 --> 00:50:34,320 SO WE WENT THROUGH THE BATTERY 1274 00:50:34,320 --> 00:50:36,720 OF THOSE, TREATED THOSE CELLS 1275 00:50:36,720 --> 00:50:38,560 WITH THE MOLECULE AND FOUND WHEN 1276 00:50:38,560 --> 00:50:40,800 MICE OR WHEN THE CELLS WERE 1277 00:50:40,800 --> 00:50:46,560 MISSING TLR2 OR TLR1 WE SAW NO 1278 00:50:46,560 --> 00:50:46,840 ACTIVITIES. 1279 00:50:46,840 --> 00:50:48,800 I'M NOT SHOWING THAT DATA. 1280 00:50:48,800 --> 00:50:51,520 WE SAW LOSS OF ACTIVITY WHEN 1281 00:50:51,520 --> 00:50:54,120 THOSE TWO TLRs WERE MISSING. 1282 00:50:54,120 --> 00:50:58,080 THIS MOLECULE IS BINDING TO TLR1 1283 00:50:58,080 --> 00:51:00,480 AND TLR2 DIMER. 1284 00:51:00,480 --> 00:51:03,600 WE DECIDED TO LOOK AT A MODELING 1285 00:51:03,600 --> 00:51:03,880 APPROACH. 1286 00:51:03,880 --> 00:51:07,200 THIS WAS DONE WITH A STUDENT AT 1287 00:51:07,200 --> 00:51:10,200 THE UNIVERSITY OF ATAGO IN NEW 1288 00:51:10,200 --> 00:51:10,440 ZEALAND. 1289 00:51:10,440 --> 00:51:13,200 HE MODELLED HOW THIS MOLECULE 1290 00:51:13,200 --> 00:51:15,120 MIGHT BE BINDING TO THE DIMER. 1291 00:51:15,120 --> 00:51:17,600 YOU CAN SEE FROM THE RIGHT IMAGE 1292 00:51:17,600 --> 00:51:19,800 THE MOLECULE REALLY DIGS DEEP 1293 00:51:19,800 --> 00:51:21,000 INTO THE BINDING POCKET. 1294 00:51:21,000 --> 00:51:22,920 IT IS PRETTY HIDDEN. 1295 00:51:22,920 --> 00:51:25,080 THIS WAS REALLY INTERESTING TO 1296 00:51:25,080 --> 00:51:27,000 US BECAUSE WE THOUGHT MAYBE THE 1297 00:51:27,000 --> 00:51:28,680 BRANCH CHAINS MIGHT PREVENT IT 1298 00:51:28,680 --> 00:51:30,480 FROM GOING FAR INTO THE BINDING 1299 00:51:30,480 --> 00:51:30,680 POCKET. 1300 00:51:30,680 --> 00:51:31,880 MAYBE THAT WAS CAUSING THIS 1301 00:51:31,880 --> 00:51:33,640 RESPONSE WE WERE SEEING. 1302 00:51:33,640 --> 00:51:35,120 IT IS GENERALLY THOUGHT THAT 1303 00:51:35,120 --> 00:51:38,480 HEAD GROUPS ARE PRETTY IMPORTANT 1304 00:51:38,480 --> 00:51:40,520 TO TRIGGER THE IMMUNE RESPONSE. 1305 00:51:40,520 --> 00:51:42,720 THIS HEAD GROUP SEEMS TO BE 1306 00:51:42,720 --> 00:51:44,960 BURIED WITHIN THE MODEL WE ARE 1307 00:51:44,960 --> 00:51:45,480 LOOKING AT. 1308 00:51:45,480 --> 00:51:48,040 NOT ONLY THAT, BUT WE SAW AN 1309 00:51:48,040 --> 00:51:49,760 INTERESTING SPLIT OF THE TAIL. 1310 00:51:49,760 --> 00:51:52,640 ONE TAIL LOOKING ON THE LEFT, 1311 00:51:52,640 --> 00:51:54,880 ONE TAIL IS GOING INTO THE LR2 1312 00:51:54,880 --> 00:51:58,880 AND ONE IS FITTING INTO TLR1. 1313 00:51:58,880 --> 00:52:00,720 AGAIN, WE WEREN'T SURE EXACTLY 1314 00:52:00,720 --> 00:52:02,480 HOW THAT WAS GOING TO HAPPEN. 1315 00:52:02,480 --> 00:52:04,920 THIS DIMER TYPICALLY BINDS TO 1316 00:52:04,920 --> 00:52:06,080 LIPIDS WITH THREE TAILS. 1317 00:52:06,080 --> 00:52:07,880 AND SO WE WERE JUST VERY 1318 00:52:07,880 --> 00:52:09,200 INTERESTED AND THIS WAS A LITTLE 1319 00:52:09,200 --> 00:52:10,960 BIT OF A SURPRISING RESULT IT 1320 00:52:10,960 --> 00:52:13,560 WAS RELYING AND BINDING THROUGH 1321 00:52:13,560 --> 00:52:14,720 TLR1 AND TLR2. 1322 00:52:14,720 --> 00:52:16,560 AND FINALLY, THE LAST EXPERIMENT 1323 00:52:16,560 --> 00:52:19,080 THAT I WANT TO SHOW IS A LITTLE 1324 00:52:19,080 --> 00:52:20,480 BIT MORE CHALLENGING TO EXPLAIN 1325 00:52:20,480 --> 00:52:22,040 SO I'M GOING TO MOVE A LITTLE 1326 00:52:22,040 --> 00:52:22,800 SLOWER THROUGH THIS. 1327 00:52:22,800 --> 00:52:24,400 THIS WAS PROBABLY ONE OF THE 1328 00:52:24,400 --> 00:52:25,840 MOST INTERESTING RESPONSES THAT 1329 00:52:25,840 --> 00:52:27,520 WE SAW WITH THIS LIPID. 1330 00:52:27,520 --> 00:52:29,280 SO THIS WAS DONE IN HUMAN CELLS. 1331 00:52:29,280 --> 00:52:32,320 SO I WANT TO POINT OUT WE WERE 1332 00:52:32,320 --> 00:52:34,240 ABLE TO REPRODUCE OUR RESULTS IN 1333 00:52:34,240 --> 00:52:35,320 HUMAN CELLS AS WELL. 1334 00:52:35,320 --> 00:52:37,040 WHAT WE DID IS TOOK THE HUMAN 1335 00:52:37,040 --> 00:52:38,480 CELLS AND WE EITHER TREATED THEM 1336 00:52:38,480 --> 00:52:40,280 WITH NOTHING, SO THAT IS WHAT IS 1337 00:52:40,280 --> 00:52:41,280 SHOWN IN RED. 1338 00:52:41,280 --> 00:52:44,120 OR WE TREATED IT WITH VARIOUS 1339 00:52:44,120 --> 00:52:45,760 CONCENTRATIONS OF THE NATURAL 1340 00:52:45,760 --> 00:52:46,040 PRODUCT. 1341 00:52:46,040 --> 00:52:50,400 SO .1, 1, OR 10 MICROGRAM PER 1342 00:52:50,400 --> 00:52:54,520 MIL OF THE A15I15 NATURAL 1343 00:52:54,520 --> 00:52:54,760 PRODUCT. 1344 00:52:54,760 --> 00:52:56,480 WE DID THAT FOR 18 HOURS. 1345 00:52:56,480 --> 00:52:58,880 THEY WERE TREATED FOR 18 HOURS. 1346 00:52:58,880 --> 00:53:00,360 AFTER THAT 18-HOUR PRETREATMENT, 1347 00:53:00,360 --> 00:53:02,200 WE DECIDED TO LEAVE THEM ALONE 1348 00:53:02,200 --> 00:53:03,840 AND LOOK AT THE IMMUNE RESPONSE 1349 00:53:03,840 --> 00:53:04,440 FOR THAT. 1350 00:53:04,440 --> 00:53:06,240 THAT IS WHAT IS IN THE CONTROL. 1351 00:53:06,240 --> 00:53:10,560 OR WE THEN TREATED THEM WITH THE 1352 00:53:10,560 --> 00:53:15,160 TWO KNOWN LIGANDS, PAM 3CYS OR 1353 00:53:15,160 --> 00:53:16,040 THE LPS. 1354 00:53:16,040 --> 00:53:18,200 WE WANTED TO SEE IF WE HAD A 1355 00:53:18,200 --> 00:53:19,560 PRETREATMENT WITH THE NATURAL 1356 00:53:19,560 --> 00:53:20,800 PRODUCT AND A KNOWN STIMULANT. 1357 00:53:20,800 --> 00:53:22,760 WHEN WE DID THAT WE SAW VERY 1358 00:53:22,760 --> 00:53:23,760 INTERESTING RESULTS. 1359 00:53:23,760 --> 00:53:26,200 SO I'M LOOKING HERE AT THE 1360 00:53:26,200 --> 00:53:28,240 MIDDLE SECTION WHERE THE NORMAL 1361 00:53:28,240 --> 00:53:33,960 RESPONSE TO PAM 3CYSK IS SHOWN 1362 00:53:33,960 --> 00:53:34,400 IN RED. 1363 00:53:34,400 --> 00:53:36,920 WHEN WE HAD A PRETREATMENT WITH 1364 00:53:36,920 --> 00:53:39,080 A NATURAL PRODUCT WE SAW A 1365 00:53:39,080 --> 00:53:41,520 DEPRESSION OR REDUCTION IN 1366 00:53:41,520 --> 00:53:43,760 RESPONSE TO PAM 3CSK. 1367 00:53:43,760 --> 00:53:45,960 IT DOESN'T SEEM TO BE AS ROBUST 1368 00:53:45,960 --> 00:53:47,480 WITH THE HIGHER CONCENTRATIONS 1369 00:53:47,480 --> 00:53:49,160 OF THE NATURAL PRODUCT. 1370 00:53:49,160 --> 00:53:51,320 WHEN WE LOOK AT LPS, WE SEE THE 1371 00:53:51,320 --> 00:53:54,240 PRODUCT ALONE IN RED SHOWS VERY 1372 00:53:54,240 --> 00:53:56,040 SHY IMMUNE RESPONSE. 1373 00:53:56,040 --> 00:53:57,200 HOWEVER, WHEN PRETREATED WITH 1374 00:53:57,200 --> 00:53:58,480 THE NATURAL PRODUCT, WE SEE, 1375 00:53:58,480 --> 00:54:00,560 AGAIN, A DEPRESSION OF THAT 1376 00:54:00,560 --> 00:54:01,080 RESPONSE. 1377 00:54:01,080 --> 00:54:03,160 AND WHAT WE THINK IS THAT THIS 1378 00:54:03,160 --> 00:54:04,760 IS SOMEHOW DOING SORT OF A RESET 1379 00:54:04,760 --> 00:54:06,360 OF THE IMMUNE SYSTEM. 1380 00:54:06,360 --> 00:54:09,360 SO THIS MOLECULE IS ABLE TO 1381 00:54:09,360 --> 00:54:11,840 CHANGE THE THRESHOLD OF WHAT IS 1382 00:54:11,840 --> 00:54:14,560 NEEDED FOR AN IMMUNE RESPONSE. 1383 00:54:14,560 --> 00:54:16,840 SO WE THINK THIS BEHAVIOR MAY BE 1384 00:54:16,840 --> 00:54:18,400 RESPONSIBLE FOR SOME OF THAT 1385 00:54:18,400 --> 00:54:24,840 HOME YO -- HOMEO STATIC 1386 00:54:24,840 --> 00:54:25,120 RESPONSE. 1387 00:54:25,120 --> 00:54:28,160 I'M GETTING CLOSE TO THE END SO 1388 00:54:28,160 --> 00:54:31,960 I'M GOING TO WRAP UP AND JUST 1389 00:54:31,960 --> 00:54:33,600 SAY THAT, SO MEMBRANE LIPIDS ARE 1390 00:54:33,600 --> 00:54:34,080 TYPICALLY OVERLOOKED. 1391 00:54:34,080 --> 00:54:36,120 A LOT OF TIMES THEY ARE THOUGHT 1392 00:54:36,120 --> 00:54:38,200 TO BE UBIQUITOUS THAT PEOPLE 1393 00:54:38,200 --> 00:54:39,240 TEND TO IGNORE THEM. 1394 00:54:39,240 --> 00:54:41,000 WE WANTED TO POINT OUT THAT IS 1395 00:54:41,000 --> 00:54:42,760 WHAT WE THOUGHT, TOO, BUT THEY 1396 00:54:42,760 --> 00:54:45,040 CAN BE IMMUNE SIGNALS AND THEY 1397 00:54:45,040 --> 00:54:46,600 SHOULDN'T BE IGNORED. 1398 00:54:46,600 --> 00:54:48,600 THEY CAN REALLY BE DOING SOME 1399 00:54:48,600 --> 00:54:49,160 INTERESTING THINGS. 1400 00:54:49,160 --> 00:54:51,680 I WANT TO POINT OUT, I KNOW MY 1401 00:54:51,680 --> 00:54:52,760 PRESENTATION WASN'T NECESSARILY 1402 00:54:52,760 --> 00:54:54,480 ABOUT NEWER METHODS OF LOOKING 1403 00:54:54,480 --> 00:54:59,240 FOR MOLECULES, BUT THIS BIOASSAY 1404 00:54:59,240 --> 00:55:02,480 GUIDED FRACTIONATION MAY BE OLD 1405 00:55:02,480 --> 00:55:05,040 FASHIONED OR CLASSICAL, IS STILL 1406 00:55:05,040 --> 00:55:05,320 RELEVANT. 1407 00:55:05,320 --> 00:55:07,040 IT DOESN'T HAVE TO BE ONE OR THE 1408 00:55:07,040 --> 00:55:07,240 OTHER. 1409 00:55:07,240 --> 00:55:09,600 WE CAN DO HAND IN HAND APPROACH 1410 00:55:09,600 --> 00:55:11,880 WHERE WE USE NEW METHODS AND OLD 1411 00:55:11,880 --> 00:55:14,040 AND FIND EVEN MORE MOLECULES. 1412 00:55:14,040 --> 00:55:16,520 I WANTED TO POINT OUT AGAIN THE 1413 00:55:16,520 --> 00:55:18,120 AKKERMANSIA MAY BE BALANCING 1414 00:55:18,120 --> 00:55:21,560 INFLAMMATORY RESPONSES IN THE 1415 00:55:21,560 --> 00:55:29,400 GUT RESULTING IN META IMMUNE 1416 00:55:29,400 --> 00:55:31,200 HOMEOSTASIS AND CONTROL IN 1417 00:55:31,200 --> 00:55:34,720 DISEASES OR CANCER IMMUNO 1418 00:55:34,720 --> 00:55:35,920 THERAPY RESPONSES. 1419 00:55:35,920 --> 00:55:38,400 WE ARE INTERESTED IN DOING 1420 00:55:38,400 --> 00:55:42,160 FURTHER RESEARCH LOOKING AT IN 1421 00:55:42,160 --> 00:55:44,600 VIVO RESPONSING WITH NATURAL AND 1422 00:55:44,600 --> 00:55:45,600 SYNTHESIZED COMPOUNDS. 1423 00:55:45,600 --> 00:55:47,480 FINALLY, I WANT TO SAY THANK YOU 1424 00:55:47,480 --> 00:55:49,880 TO THE PEOPLE WHO HAVE HELPED 1425 00:55:49,880 --> 00:55:50,960 THE MOST. 1426 00:55:50,960 --> 00:55:54,040 MY PROFESSOR, MY ADVISOR JOHN 1427 00:55:54,040 --> 00:55:57,200 CLARDY WAS AMAZING. 1428 00:55:57,200 --> 00:56:00,280 MY CO-FIRST ON THIS PAPER, WE 1429 00:56:00,280 --> 00:56:03,160 HAD A KUN ON V OF PEOPLE 1430 00:56:03,160 --> 00:56:03,720 HELPING. 1431 00:56:03,720 --> 00:56:05,800 IT WAS ON AN F32 DURING THIS 1432 00:56:05,800 --> 00:56:07,920 WORK SO I WANT TO ACKNOWLEDGE 1433 00:56:07,920 --> 00:56:08,440 THAT AS WELL. 1434 00:56:08,440 --> 00:56:09,760 WITH THAT I'M DONE AND THANK YOU 1435 00:56:09,760 --> 00:56:11,760 SO MUCH FOR YOUR ATTENTION. 1436 00:56:11,760 --> 00:56:14,000 >>WELL, THIS IS CRAIG HOPP. 1437 00:56:14,000 --> 00:56:17,080 THANK YOU SO MUCH TO ALL OF OUR 1438 00:56:17,080 --> 00:56:17,360 SPEAKERS. 1439 00:56:17,360 --> 00:56:24,000 DOCTORS NELSON, DIVER, AND 1440 00:56:24,000 --> 00:56:24,240 CASSILLY. 1441 00:56:24,240 --> 00:56:25,680 I APPRECIATE THE INTERESTING 1442 00:56:25,680 --> 00:56:26,040 TALKS. 1443 00:56:26,040 --> 00:56:27,720 I ENCOURAGE VIDEOCAST AUDIENCE 1444 00:56:27,720 --> 00:56:30,320 TO PUT IN QUESTIONS YOU MIGHT 1445 00:56:30,320 --> 00:56:32,280 HAVE THROUGH THE FEEDBACK FORM 1446 00:56:32,280 --> 00:56:33,720 ON THE VIDEOCAST LINK. 1447 00:56:33,720 --> 00:56:35,160 SO FOR NOW WE ARE GOING TO MOVE 1448 00:56:35,160 --> 00:56:36,840 INTO SOME QUESTIONS. 1449 00:56:36,840 --> 00:56:38,120 WE HAVE TIME FOR SEVERAL. 1450 00:56:38,120 --> 00:56:41,400 MY FIRST IS, I GUESS, FOR BOTH 1451 00:56:41,400 --> 00:56:48,080 DR. NELSON AND DR. DIVER. 1452 00:56:48,080 --> 00:56:54,880 AT THE MOMENT CRYO EM, IT STARTS 1453 00:56:54,880 --> 00:56:58,400 OFF BEING EXPENSIVE. 1454 00:56:58,400 --> 00:57:00,440 HOPE YOU HAVE ASPECTS A DECADE 1455 00:57:00,440 --> 00:57:00,920 LATER. 1456 00:57:00,920 --> 00:57:03,360 WHEN DO YOU THINK OR WHAT WILL 1457 00:57:03,360 --> 00:57:04,720 IT TAKE DO YOU THINK FOR THIS 1458 00:57:04,720 --> 00:57:06,520 SORT OF TECHNOLOGY TO BE MORE 1459 00:57:06,520 --> 00:57:07,440 WIDELY AVAILABLE TO MORE PEOPLE, 1460 00:57:07,440 --> 00:57:10,680 BASICALLY? 1461 00:57:10,680 --> 00:57:12,560 >>I CAN START OFF. 1462 00:57:12,560 --> 00:57:14,920 I THINK A COUPLE OF THINGS. 1463 00:57:14,920 --> 00:57:19,560 I THINK THAT THE TECHNOLOGICAL 1464 00:57:19,560 --> 00:57:21,600 REQUIREMENTS FOR DOING ELECTRON 1465 00:57:21,600 --> 00:57:24,000 DEFRACTION AND MICROED ARE 1466 00:57:24,000 --> 00:57:25,960 SMALLER FOR LARGER 1467 00:57:25,960 --> 00:57:26,920 MACROMOLECULAR SYSTEMS. 1468 00:57:26,920 --> 00:57:29,640 I THINK THERE IS AN OPPORTUNITY 1469 00:57:29,640 --> 00:57:32,240 FOR MICROSCOPE VENDORS TO 1470 00:57:32,240 --> 00:57:34,640 LEVERAGE THAT AND MAKING LOWER 1471 00:57:34,640 --> 00:57:37,000 COST INSTRUMENTS LESS THAN $1 1472 00:57:37,000 --> 00:57:37,400 MILLION. 1473 00:57:37,400 --> 00:57:40,760 BECAUSE OF THE CRYO-EM 1474 00:57:40,760 --> 00:57:41,680 REVOLUTION, MOST UNIVERSITIES 1475 00:57:41,680 --> 00:57:42,840 HAVE THESE TOOLS. 1476 00:57:42,840 --> 00:57:44,520 SO WHAT IT REALLY BOILS DOWN 1477 00:57:44,520 --> 00:57:46,960 FROM MY PERSPECTIVE IS HAVING 1478 00:57:46,960 --> 00:57:49,720 THE RIGHT SOFTWARE AND WORK 1479 00:57:49,720 --> 00:57:50,840 FLOWS AVAILABLE TO THE COMMUNITY 1480 00:57:50,840 --> 00:57:52,440 WHERE FOLKS CAN WALK UP AND DO 1481 00:57:52,440 --> 00:57:53,480 THESE TYPES OF EXPERIMENTS. 1482 00:57:53,480 --> 00:57:54,880 THAT IS PART OF IT. 1483 00:57:54,880 --> 00:57:56,560 THE OTHER PART IS WE ARE STILL 1484 00:57:56,560 --> 00:57:57,320 IN RESEARCH MODE. 1485 00:57:57,320 --> 00:57:59,800 IT IS NOT -- SOMETIMES IT WORKS 1486 00:57:59,800 --> 00:58:00,320 INCREDIBLY WELL. 1487 00:58:00,320 --> 00:58:02,400 WE HAVE SOLVED MANY, MANY 1488 00:58:02,400 --> 00:58:05,080 STRUCTURES IN A SINGLE DAY, BUT 1489 00:58:05,080 --> 00:58:06,360 SOMETIMES WE SPEND SIX MONTHS 1490 00:58:06,360 --> 00:58:07,440 WORKING ON A STRUCTURE. 1491 00:58:07,440 --> 00:58:09,280 AT LEAST GETTING A WORK FLOW OUT 1492 00:58:09,280 --> 00:58:11,720 THERE THAT ALLOWS PEOPLE TO DO 1493 00:58:11,720 --> 00:58:14,360 THE QUOTE-UNQUOTE EASY STUFF 1494 00:58:14,360 --> 00:58:17,480 WOULD BE A POWERFUL ADVANCE ON 1495 00:58:17,480 --> 00:58:20,400 THE ELECTRON DEFRACTION SIDE. 1496 00:58:20,400 --> 00:58:22,720 >>I COMPLETELY AGREE WITH ALL 1497 00:58:22,720 --> 00:58:24,360 THAT AND WILL ADD ONE THING. 1498 00:58:24,360 --> 00:58:26,360 IN ADDITION TO MANY, MANY PLACES 1499 00:58:26,360 --> 00:58:29,320 HAVING ACTIVE CENTERS, THERE ARE 1500 00:58:29,320 --> 00:58:30,800 ALSO NATIONAL CENTERS SPONSORED 1501 00:58:30,800 --> 00:58:32,880 BY THE NIH THAT ARE FABULOUS. 1502 00:58:32,880 --> 00:58:33,880 AND PEOPLE SHOULD USE THEM. 1503 00:58:33,880 --> 00:58:35,400 THERE IS ONE IN OREGON. 1504 00:58:35,400 --> 00:58:37,600 THERE IS STUFF GOING ON IN 1505 00:58:37,600 --> 00:58:38,040 COLORADO. 1506 00:58:38,040 --> 00:58:40,520 THERE IS A GIANT CENTER IN NEW 1507 00:58:40,520 --> 00:58:43,800 YORK AND IT IS NOT, YOU HAVE 1508 00:58:43,800 --> 00:58:44,200 TRAINING THERE. 1509 00:58:44,200 --> 00:58:47,520 YOU HAVE TONS OF INFRASTRUCTURE, 1510 00:58:47,520 --> 00:58:49,240 IT IS ALL AVAILABLE AT YOUR 1511 00:58:49,240 --> 00:58:50,280 FINGERTIPS AND THEY ARE AN 1512 00:58:50,280 --> 00:58:51,520 AMAZING TEAM. 1513 00:58:51,520 --> 00:58:52,960 IF YOU ARE SOMEWHERE WITHOUT IT, 1514 00:58:52,960 --> 00:58:53,880 CONTACT THEM AND THEY WILL HELP 1515 00:58:53,880 --> 00:58:57,320 YOU. 1516 00:58:57,320 --> 00:58:58,040 >>GREAT. 1517 00:58:58,040 --> 00:59:01,680 I SEE SOME OF MY NIH COLLEAGUES 1518 00:59:01,680 --> 00:59:08,520 ON THE TEAM HERE HAVE SOME 1519 00:59:08,520 --> 00:59:08,800 QUESTIONS. 1520 00:59:08,800 --> 00:59:13,040 SO NIDES, ASK YOUR QUESTION. 1521 00:59:13,040 --> 00:59:14,680 >>CAN YOU HEAR ME? 1522 00:59:14,680 --> 00:59:16,400 >>YES. 1523 00:59:16,400 --> 00:59:17,680 >>THANKS, CRAIG. 1524 00:59:17,680 --> 00:59:20,880 I HAVE A QUESTION ON THE 1525 00:59:20,880 --> 00:59:23,400 STRUCTURAL INSIGHT ON TRYP 1526 00:59:23,400 --> 00:59:23,760 CHANNELS. 1527 00:59:23,760 --> 00:59:27,280 ANY THOUGHTS ON HOW YOU CAN 1528 00:59:27,280 --> 00:59:29,720 LEVERAGE ON THE INFORMATION, 1529 00:59:29,720 --> 00:59:31,800 STRUCTURAL INFORMATION IN A 1530 00:59:31,800 --> 00:59:36,560 MULTIPLE TRYP CHANNEL AND THEN 1531 00:59:36,560 --> 00:59:38,800 REALLY, AGGREGATE THOSE IN A 1532 00:59:38,800 --> 00:59:39,320 THERAPEUTIC SITE. 1533 00:59:39,320 --> 00:59:41,960 ANY THOUGHTS ON THAT? 1534 00:59:41,960 --> 00:59:43,240 >>IT IS A VERY, VERY 1535 00:59:43,240 --> 00:59:45,680 INTERESTING QUESTION. 1536 00:59:45,680 --> 00:59:49,440 SO WHAT I THINK THE SINGLE 1537 00:59:49,440 --> 00:59:51,880 PARTICLE CO EM RESOLUTION HAS 1538 00:59:51,880 --> 00:59:53,280 COME TO BASICALLY ILLUMINATE. 1539 00:59:53,280 --> 00:59:55,920 WE HAVE MANY TRYP CHANNEL 1540 00:59:55,920 --> 00:59:56,400 STRUCTURES NOW. 1541 00:59:56,400 --> 00:59:58,680 SOME WE KNOW A LOT ABOUT THEIR 1542 00:59:58,680 --> 01:00:01,760 BIOLOGY AND ARE INTERESTING DRUG 1543 01:00:01,760 --> 01:00:03,640 TARGETS AND PAIN DRUG TARGETS. 1544 01:00:03,640 --> 01:00:04,880 AND SOME WE DON'T KNOW MUCH. 1545 01:00:04,880 --> 01:00:05,920 THEY ARE UNIQUE. 1546 01:00:05,920 --> 01:00:07,520 THE BINDING SITES WHERE THEY 1547 01:00:07,520 --> 01:00:13,000 BIND DRUGS ARE YUNIQUE, AND THEE 1548 01:00:13,000 --> 01:00:14,880 ISN'T USUALLY ONE SITE. 1549 01:00:14,880 --> 01:00:18,000 YOU CAN FIND LIPID MODULATORS, 1550 01:00:18,000 --> 01:00:22,040 CHEMICAL MODULATORS. 1551 01:00:22,040 --> 01:00:23,640 IT IS PUSHING THE RESOLUTION AND 1552 01:00:23,640 --> 01:00:24,960 TRYING TO OVERCOME SOME OF THE 1553 01:00:24,960 --> 01:00:26,480 PROBLEMS WE HAVE HAD IN THE 1554 01:00:26,480 --> 01:00:26,680 CLINIC. 1555 01:00:26,680 --> 01:00:28,280 I DIDN'T TALK ABOUT THAT HERE, 1556 01:00:28,280 --> 01:00:30,080 BUT THERE HAS BEEN A BIG EFFORT 1557 01:00:30,080 --> 01:00:33,080 TO DEVELOP DRUGS TO TARGET OUR 1558 01:00:33,080 --> 01:00:36,000 HEAT AND PAIN RECEPTOR TRYPV1 1559 01:00:36,000 --> 01:00:37,360 FOR 20 YEARS. 1560 01:00:37,360 --> 01:00:39,160 WE HAVE TO OVERCOME THE PRODUCTS 1561 01:00:39,160 --> 01:00:40,680 WHEN YOU DRUG THESE TEMPERATURE 1562 01:00:40,680 --> 01:00:43,560 SENSORS IN OUR BODY, THERM 1563 01:00:43,560 --> 01:00:47,080 OREGULATION GOES QUITE AWRY. 1564 01:00:47,080 --> 01:00:49,200 WE FINALLY HAVE THE STRUCTURAL 1565 01:00:49,200 --> 01:00:50,320 TOOLS AND THE KNOWLEDGE AND IT 1566 01:00:50,320 --> 01:00:52,040 IS ALL POURING IN, BUT WE HAVE 1567 01:00:52,040 --> 01:00:53,440 SOME THINGS TO FIGURE OUT 1568 01:00:53,440 --> 01:00:56,440 PROBABLY IN THE CLINIC, TOO. 1569 01:00:56,440 --> 01:00:57,680 >>ABSOLUTELY. 1570 01:00:57,680 --> 01:00:58,480 WELL SAID. 1571 01:00:58,480 --> 01:01:03,160 AND THAT IS THE CORE OF 1572 01:01:03,160 --> 01:01:03,680 QUESTION. 1573 01:01:03,680 --> 01:01:06,520 HOW TO REALLY LEVERAGE ON THIS 1574 01:01:06,520 --> 01:01:10,680 INHERENT PROPERTIES OF THE 1575 01:01:10,680 --> 01:01:12,960 CHANNELS AND HOW TO ALLOCATE 1576 01:01:12,960 --> 01:01:15,840 THOSE STRUCTURAL ASPECTS SO YOU 1577 01:01:15,840 --> 01:01:18,400 CAN TARGET THESE CHANNELS 1578 01:01:18,400 --> 01:01:20,080 WITHOUT INFLUENCING THE 1579 01:01:20,080 --> 01:01:22,400 TEMPERATURE SENSORS OF THE BODY, 1580 01:01:22,400 --> 01:01:25,640 OTHER THAN JUST FOCUSING ON THE 1581 01:01:25,640 --> 01:01:28,640 PAIN TRANSDUCTION MECHANISM, NOT 1582 01:01:28,640 --> 01:01:29,720 MUCH ON THE CORE TEMPERATURE. 1583 01:01:29,720 --> 01:01:31,160 >>IT IS VERY INTERESTING TO 1584 01:01:31,160 --> 01:01:32,360 THINK ABOUT. 1585 01:01:32,360 --> 01:01:35,680 I THINK YOU ARE NAILING INTO THE 1586 01:01:35,680 --> 01:01:37,320 PERFECT FACT. 1587 01:01:37,320 --> 01:01:38,680 IF WE COULD UNDERSTAND -- 1588 01:01:38,680 --> 01:01:40,160 BASICALLY AT THIS POINT WE DON'T 1589 01:01:40,160 --> 01:01:42,560 KNOW IF THERE ARE DIFFERENCES OF 1590 01:01:42,560 --> 01:01:46,080 HOW THESE CHANNELS RESPOND TO 1591 01:01:46,080 --> 01:01:48,200 PHYSICAL AND CHEMICAL STIMULI. 1592 01:01:48,200 --> 01:01:51,800 IF WE COULD JUST START WITH ONE 1593 01:01:51,800 --> 01:01:56,360 RESPOND TO TEMPERATURE WE COULD 1594 01:01:56,360 --> 01:01:58,240 TARGET ONE OVER THE OTHER. 1595 01:01:58,240 --> 01:02:00,280 THAT IS GOING TO BE ESSENTIAL. 1596 01:02:00,280 --> 01:02:02,240 WE HAVE BEEN LIMITED BY 1597 01:02:02,240 --> 01:02:03,640 TECHNOLOGY, BUT I THINK THINGS 1598 01:02:03,640 --> 01:02:05,760 IN THE BENCH AND COMPUTATIONALLY 1599 01:02:05,760 --> 01:02:07,080 THAT WILL PUSH THAT FORWARD I 1600 01:02:07,080 --> 01:02:10,800 HOPE WITHIN THE NEXT FIVE YEARS. 1601 01:02:10,800 --> 01:02:17,080 >>SO WE HAVE A QUESTION FOR DR. 1602 01:02:17,080 --> 01:02:17,360 CASSILLY. 1603 01:02:17,360 --> 01:02:23,120 >>HI CHELSEA, THIS IS RYAN FROM 1604 01:02:23,120 --> 01:02:23,360 NIAND. 1605 01:02:23,360 --> 01:02:26,320 YOU MENTIONED YOUR APPROACH, YOU 1606 01:02:26,320 --> 01:02:30,480 SAID OLD FASHIONED IN TERMS OF 1607 01:02:30,480 --> 01:02:32,280 FRACTIONATING EXTRACTS FROM 1608 01:02:32,280 --> 01:02:32,600 AKKERMANSIA. 1609 01:02:32,600 --> 01:02:35,360 WHAT I WAS WONDERING DO YOU 1610 01:02:35,360 --> 01:02:37,480 THINK -- HAVE YOU EVER TRIED OR 1611 01:02:37,480 --> 01:02:39,280 THOUGHT ABOUT A WHOLESALE 1612 01:02:39,280 --> 01:02:40,080 APPROACH? 1613 01:02:40,080 --> 01:02:41,480 USING THE BUG ITSELF, OF COURSE, 1614 01:02:41,480 --> 01:02:43,520 IN THOSE ASSAYS? 1615 01:02:43,520 --> 01:02:45,520 AND I'M THINKING MY THOUGHTS ARE 1616 01:02:45,520 --> 01:02:47,480 THAT YOU MIGHT NOT HAVE ACTUALLY 1617 01:02:47,480 --> 01:02:49,320 DETECTED THAT ACTIVITY. 1618 01:02:49,320 --> 01:02:56,000 THAT MOLECULE THERE IN TERMS OF 1619 01:02:56,000 --> 01:02:58,560 ITS EXPRESSION AND INTERACTION 1620 01:02:58,560 --> 01:03:00,560 AND THE BIOLOGY, I WONDERED IF 1621 01:03:00,560 --> 01:03:02,240 YOU HAD THOUGHT ABOUT THAT? 1622 01:03:02,240 --> 01:03:12,840 I THINK I THINK THAT IS A REALL 1623 01:04:09,640 --> 01:04:10,400 POWERFUL THING. 1624 01:04:10,400 --> 01:04:11,640 SO, YES, VERY INTERESTING. 1625 01:04:11,640 --> 01:04:16,360 I THINK THERE WERE TIMES THAT WE 1626 01:04:16,360 --> 01:04:18,560 DID EARLY IN THE LAB INTERESTED 1627 01:04:18,560 --> 01:04:21,080 IN DOING WHOLE SALE TYPES OF 1628 01:04:21,080 --> 01:04:22,200 DOING THAT WITH THAT ASSAY. 1629 01:04:22,200 --> 01:04:24,280 BUT I THINK THAT ANSWERS A BIT 1630 01:04:24,280 --> 01:04:25,120 OF A DIFFERENT QUESTION THAN 1631 01:04:25,120 --> 01:04:27,000 WHAT WE WERE LOOKING AT. 1632 01:04:27,000 --> 01:04:28,760 AND I DON'T REALLY REMEMBER IF 1633 01:04:28,760 --> 01:04:31,760 WE DID IT WITH AKKERMANSIA 1634 01:04:31,760 --> 01:04:36,000 BECAUSE OF THE AN AEROBIC NATURE 1635 01:04:36,000 --> 01:04:37,360 OF THE ORGANISM. 1636 01:04:37,360 --> 01:04:38,800 >>I APPRECIATE THAT. 1637 01:04:38,800 --> 01:04:42,800 I WAS THINKING HOW PEOPLE ARE 1638 01:04:42,800 --> 01:04:45,440 FRACTIONATING THE MICROBIOME 1639 01:04:45,440 --> 01:04:49,440 LOOKING FOR CONSORTIA THAT HAVE 1640 01:04:49,440 --> 01:04:51,120 THAT ACTIVITY. 1641 01:04:51,120 --> 01:04:52,280 I HAVE A SECOND QUESTION AND IT 1642 01:04:52,280 --> 01:04:54,600 MAY BE UNFAIR AND YOU CAN 1643 01:04:54,600 --> 01:04:55,040 TOTALLY PASS. 1644 01:04:55,040 --> 01:04:57,080 IT IS A QUESTION ABOUT HOW DOES 1645 01:04:57,080 --> 01:05:00,080 THAT ACTIVITY RELATE TO THE 1646 01:05:00,080 --> 01:05:02,760 BIOLOGY OF OBESITY AND DIABETES. 1647 01:05:02,760 --> 01:05:06,720 I WONDER IF YOU CAN EXTEND THAT 1648 01:05:06,720 --> 01:05:16,960 AND IF IT IS 1649 01:06:11,080 --> 01:06:15,400 MAYBE WE CAN STOP THE WHOLE 1650 01:06:15,400 --> 01:06:25,920 HUMAN GETTING TO A FULL BLOWN 1651 01:06:31,240 --> 01:06:31,440 DISEASE. 1652 01:06:31,440 --> 01:06:32,080 I KNOW THAT WAS PROBABLY A BIT 1653 01:06:32,080 --> 01:06:32,320 CONFUSING. 1654 01:06:32,320 --> 01:06:32,960 I THINK THAT IDEA OF RESETTING 1655 01:06:32,960 --> 01:06:33,480 WHAT IT TAKES TO GET TO A 1656 01:06:33,480 --> 01:06:34,080 DISEASE STATE MAY HELP THIS 1657 01:06:34,080 --> 01:06:34,680 ORGANISM CONTROL THAT BETTER. 1658 01:06:34,680 --> 01:06:34,880 SCHL 1659 01:06:34,880 --> 01:06:37,040 >>I THINK THAT MAKES PERFECT 1660 01:06:37,040 --> 01:06:37,360 SENSE. 1661 01:06:37,360 --> 01:06:39,920 SOME OF THE TERMINOLOGY IS -- 1662 01:06:39,920 --> 01:06:44,120 WHERE YOU ARE REALLY REDUCING 1663 01:06:44,120 --> 01:06:45,640 THE EXTREME SPOBSS. 1664 01:06:45,640 --> 01:06:47,760 THAT IS VERY INTERESTING. 1665 01:06:47,760 --> 01:06:48,440 >>THANK YOU. 1666 01:06:48,440 --> 01:06:49,560 >>I WILL CHIME IN. 1667 01:06:49,560 --> 01:06:53,000 ONE OF THE BUZZ WORDS. 1668 01:06:53,000 --> 01:06:54,840 NCCIH IS INTERESTED IN, ACROSS 1669 01:06:54,840 --> 01:06:57,320 NICHE IS THE TERM RESILIENCE. 1670 01:06:57,320 --> 01:06:58,560 SO MAYBE THERE IS SOMETHING 1671 01:06:58,560 --> 01:07:00,040 ABOUT AKKERMANSIA THAT HELPS 1672 01:07:00,040 --> 01:07:02,200 MAKE THE HOST MORE RESILIENT TO 1673 01:07:02,200 --> 01:07:04,040 SOME OF THESE INFLAMMATORY 1674 01:07:04,040 --> 01:07:06,480 INSULTS, IF YOU WILL, THAT MIGHT 1675 01:07:06,480 --> 01:07:07,520 OTHERWISE RESULT IN MORE 1676 01:07:07,520 --> 01:07:09,200 DRAMATIC REACTIONS. 1677 01:07:09,200 --> 01:07:11,680 >>OR NO TURNING BACK TYPE 1678 01:07:11,680 --> 01:07:12,440 POINT. 1679 01:07:12,440 --> 01:07:13,320 YEAH. 1680 01:07:13,320 --> 01:07:13,600 ABSOLUTELY. 1681 01:07:13,600 --> 01:07:15,320 >>THE OTHER QUESTION FOR YOU 1682 01:07:15,320 --> 01:07:19,040 DR. CASSILLY FROM THE AUDIENCE, 1683 01:07:19,040 --> 01:07:22,040 YOU SHOWED THE STRUCTURE OF THIS 1684 01:07:22,040 --> 01:07:23,840 COMPOUND, SYNTHETIC, OR THE 1685 01:07:23,840 --> 01:07:28,440 NATURAL, OR THE TAILS, THEY ARE 1686 01:07:28,440 --> 01:07:29,360 EQUI POTENT. 1687 01:07:29,360 --> 01:07:30,960 THE QUESTIONER IS ASKING THIS 1688 01:07:30,960 --> 01:07:33,040 SEEMS LIKE A PARADOX GIVEN THE 1689 01:07:33,040 --> 01:07:34,640 SPECIFICITY OF THE RECEPTOR. 1690 01:07:34,640 --> 01:07:37,800 CAN YOU COMMENT ON WHY SWAPPING 1691 01:07:37,800 --> 01:07:39,560 THOSE TAILS SEEMS TO HAVE NO 1692 01:07:39,560 --> 01:07:40,880 IMPACT ON THE ACTIVITY? 1693 01:07:40,880 --> 01:07:41,040 IS 1694 01:07:41,040 --> 01:07:42,600 >>SO I WANT TO POINT OUT THERE 1695 01:07:42,600 --> 01:07:44,920 WAS A LITTLE BIT OF ACTIVITY. 1696 01:07:44,920 --> 01:07:47,560 THE ONE WHERE WE SWAPPED THE 1697 01:07:47,560 --> 01:07:50,400 CHAINS, WE DID SEE MAYBE A 1698 01:07:50,400 --> 01:07:52,480 LITTLE BIT OF A DECREASE IN 1699 01:07:52,480 --> 01:07:52,760 ACTIVITY. 1700 01:07:52,760 --> 01:07:54,360 I THINK THE POINT WAS AND I 1701 01:07:54,360 --> 01:07:55,280 DIDN'T MENTION THIS, IT IS IN 1702 01:07:55,280 --> 01:07:57,280 THE PAPER. 1703 01:07:57,280 --> 01:08:00,800 WE DID SYNTHESIZE MANY OTHER 1704 01:08:00,800 --> 01:08:02,600 VERSIONS WHERE WE SHORTENED THE 1705 01:08:02,600 --> 01:08:05,480 CHAINS OR WE CHANGED WHERE THE 1706 01:08:05,480 --> 01:08:06,760 BRANCHES WERE EVEN FURTHER OR WE 1707 01:08:06,760 --> 01:08:08,880 JUST REMOVED THE BRANCHES ALL 1708 01:08:08,880 --> 01:08:10,520 TOGETHER AND WE SAW NO ACTIVITY 1709 01:08:10,520 --> 01:08:11,120 WITH THAT. 1710 01:08:11,120 --> 01:08:12,680 WITH ANY OF THOSE. 1711 01:08:12,680 --> 01:08:14,480 SO IT REALLY DOES SAY THAT THERE 1712 01:08:14,480 --> 01:08:16,600 IS SOMETHING INTERESTING ABOUT 1713 01:08:16,600 --> 01:08:19,120 THE WAY THAT THOSE BRANCHES ARE. 1714 01:08:19,120 --> 01:08:23,080 MAYBE THE CHAIN ON WHICH THE 1715 01:08:23,080 --> 01:08:25,160 ANTI-VERSUS ISO, MAYBE THAT IS 1716 01:08:25,160 --> 01:08:26,080 NOT SO IMPORTANT. 1717 01:08:26,080 --> 01:08:27,920 IF YOU CHANGE THEM AT ALL OR 1718 01:08:27,920 --> 01:08:32,360 EVEN IF YOU PUT BOTH OF THEM 1719 01:08:32,360 --> 01:08:35,760 ANTI-ISO OR ISO, WE DID NOT SEE 1720 01:08:35,760 --> 01:08:37,400 ACTIVITY IN THOSE CASES. 1721 01:08:37,400 --> 01:08:39,440 THERE IS SOMETHING SPECIFIC AND 1722 01:08:39,440 --> 01:08:41,040 INTERESTING AND BUT IT IS 1723 01:08:41,040 --> 01:08:41,560 DEFINITELY AND IMPORTANT 1724 01:08:41,560 --> 01:08:44,000 QUESTION OF LOOKING AT THE 1725 01:08:44,000 --> 01:08:45,160 STRUCTURE RELATED TO THE 1726 01:08:45,160 --> 01:08:45,480 FUNCTION. 1727 01:08:45,480 --> 01:08:47,240 THERE IS MORE TO ASK AS WELL. 1728 01:08:47,240 --> 01:08:48,240 >>GREAT. 1729 01:08:48,240 --> 01:08:48,800 THANK YOU. 1730 01:08:48,800 --> 01:08:52,040 SO QUESTION FOR DR. NELSON. 1731 01:08:52,040 --> 01:08:54,240 SO ONE OF THE AUDIENCE MEMBERS 1732 01:08:54,240 --> 01:08:56,680 ASKS, HOW DOES ONE DETERMINE IF 1733 01:08:56,680 --> 01:08:58,720 ONE'S FAVORITE OILY NATURAL 1734 01:08:58,720 --> 01:09:01,760 PRODUCT CAN MAKE MICROCRYSTALS 1735 01:09:01,760 --> 01:09:02,760 FOR ED? 1736 01:09:02,760 --> 01:09:06,120 IS THERE A BIAS FOR CRYSTALINE 1737 01:09:06,120 --> 01:09:07,520 COMPOUNDS AND THE OILS ARE 1738 01:09:07,520 --> 01:09:08,320 PASSED BY? 1739 01:09:08,320 --> 01:09:13,840 >>THAT IS A GREAT QUESTION. 1740 01:09:13,840 --> 01:09:18,360 WE NEED CRYSTALINE COMPOUNDS. 1741 01:09:18,360 --> 01:09:20,680 WE HAVE GOTTEN CRYSTAL 1742 01:09:20,680 --> 01:09:24,680 STRUCTURES AT THE MSO, OPERATING 1743 01:09:24,680 --> 01:09:28,360 MINUS 170 COLLECTING DATA, WE 1744 01:09:28,360 --> 01:09:30,240 HAVE COLLECTED FATTY ACIDS. 1745 01:09:30,240 --> 01:09:33,120 IT IS TRUE WE WILL ONLY SOLVE 1746 01:09:33,120 --> 01:09:36,280 STRUCTURES OF CRYSTALINE 1747 01:09:36,280 --> 01:09:36,560 COMPOUNDS. 1748 01:09:36,560 --> 01:09:38,800 IF YOU LOOK AT THE PERCENTAGE OF 1749 01:09:38,800 --> 01:09:41,920 COMPOUNDS THAT ARE KNOWN VERSUS 1750 01:09:41,920 --> 01:09:43,480 UNKNOWN, EVEN IF WE COULD SOLVE 1751 01:09:43,480 --> 01:09:45,560 THE STRUCTURES OF 1% OF THAT 1752 01:09:45,560 --> 01:09:47,040 SPACE, IT WOULD BE DRAMATIC. 1753 01:09:47,040 --> 01:09:49,440 I THINK THE QUESTION IS DEAD ON. 1754 01:09:49,440 --> 01:09:51,920 WE CAN ONLY GET CRYSTALS OR 1755 01:09:51,920 --> 01:09:55,480 STRUCTURES THAT ARE THINGS ARE 1756 01:09:55,480 --> 01:09:57,120 CRYSTALINE IN ORDER, BUT ONE HAS 1757 01:09:57,120 --> 01:09:58,840 TO RECOGNIZE FROM CHEMICAL SPACE 1758 01:09:58,840 --> 01:10:01,680 THAT IS A SIGNIFICANT NUMBER OF 1759 01:10:01,680 --> 01:10:02,040 COMPOUNDS. 1760 01:10:02,040 --> 01:10:04,760 MOREOVER, THE TYPES OF 1761 01:10:04,760 --> 01:10:07,080 CONDITIONS IN A MICROSCOPE ARE 1762 01:10:07,080 --> 01:10:10,480 CONDUCIVE TO CRYSTALLIZATION. 1763 01:10:10,480 --> 01:10:13,760 WITHOUT THINKING OF OTHER THINGS 1764 01:10:13,760 --> 01:10:15,720 CRYSTAL FORMING A CHEMICAL 1765 01:10:15,720 --> 01:10:15,960 SPECIES. 1766 01:10:15,960 --> 01:10:17,840 >>ANOTHER RELATED QUESTION FOR 1767 01:10:17,840 --> 01:10:19,040 YOU DR. NELSON. 1768 01:10:19,040 --> 01:10:21,120 YOU WERE EXPECTING ONLY 5%, BUT 1769 01:10:21,120 --> 01:10:24,160 YOU GOT 20%. 1770 01:10:24,160 --> 01:10:27,560 WHAT WAS WRONG WITH THE OTHER 1771 01:10:27,560 --> 01:10:27,760 80%? 1772 01:10:27,760 --> 01:10:29,640 WHY DON'T THEY CRYSTALLIZE? 1773 01:10:29,640 --> 01:10:31,560 >>I WAS CAREFUL IN MY WORDS, 1774 01:10:31,560 --> 01:10:32,280 BUT VAGUE. 1775 01:10:32,280 --> 01:10:34,760 20% OF THE FRACTIONS WE LOOK AT 1776 01:10:34,760 --> 01:10:40,160 DISPLAY CRYSTAL INITIY THAT 1777 01:10:40,160 --> 01:10:42,440 SOLVENT WERE LOST. 1778 01:10:42,440 --> 01:10:42,920 WHEN WE. 1779 01:10:42,920 --> 01:10:46,320 >>FRACTIONING THEM, OUT OF 100 1780 01:10:46,320 --> 01:10:49,200 FRACTIONS, 20 WILL BE CRYSTALINE 1781 01:10:49,200 --> 01:10:49,600 OR DEFRACTURE. 1782 01:10:49,600 --> 01:10:53,040 PROBABLY A LOT OF OTHEM ARE 1783 01:10:53,040 --> 01:10:55,760 EMPTY WELLS THAT DON'T HAVE 1784 01:10:55,760 --> 01:10:56,040 COMPOUNDS. 1785 01:10:56,040 --> 01:11:05,520 ANOTHER SUBSET WOULD CRYSTAL LIE 1786 01:11:05,520 --> 01:11:05,800 ISOPROPINOL. 1787 01:11:05,800 --> 01:11:08,720 IF WE TO FIGURE OUT THE FRACTION 1788 01:11:08,720 --> 01:11:11,320 ARE CRYSTALINE, I DON'T HAVE AN 1789 01:11:11,320 --> 01:11:11,680 ANSWER. 1790 01:11:11,680 --> 01:11:13,440 I DON'T HAVE AN IDEA. 1791 01:11:13,440 --> 01:11:17,200 WHEN WE FRACTIONATED THIS 1792 01:11:17,200 --> 01:11:19,080 COMPOUNDS ON AVERAGE WE GET 20 1793 01:11:19,080 --> 01:11:20,800 THINGS THAT DEFRACTURE THAT ARE 1794 01:11:20,800 --> 01:11:21,200 UNIQUE. 1795 01:11:21,200 --> 01:11:22,680 SO I DON'T HAVE AN ANSWER FOR 1796 01:11:22,680 --> 01:11:26,440 THAT QUESTION, BUT I THINK IN 1797 01:11:26,440 --> 01:11:30,560 REALITY THE NUMBER OF THINGS AT 1798 01:11:30,560 --> 01:11:32,040 THAT TEMPERATURE THAT ARE 1799 01:11:32,040 --> 01:11:34,400 CRYSTAL IS GREATER THAN 20%. 1800 01:11:34,400 --> 01:11:44,680 MY SBU TIGS OF A 1801 01:12:20,680 --> 01:12:22,360 THE SLIDES ARE KNOWN, I DON'T 1802 01:12:22,360 --> 01:12:24,440 KNOW IF THAT IS ENTIRELY TRUE, 1803 01:12:24,440 --> 01:12:26,480 THOSE BIOLOGICAL ACTIVITIES CAN 1804 01:12:26,480 --> 01:12:27,680 BE PRODETECTIVABLE. 1805 01:12:27,680 --> 01:12:30,480 I'M THINKING HOW THESE TECH LINK 1806 01:12:30,480 --> 01:12:34,160 TO DISCOVERY THAT ARE NOT CYTO 1807 01:12:34,160 --> 01:12:35,240 STATIC MOLECULES. 1808 01:12:35,240 --> 01:12:36,960 ANYBODY FEEL LIKE THEY ARE ABLE 1809 01:12:36,960 --> 01:12:39,920 TO ANSWER THAT? 1810 01:12:39,920 --> 01:12:43,040 >>I DON'T UNDERSTAND THE 1811 01:12:43,040 --> 01:12:45,480 BIOLOGY, BUT ONLY ONE WAS IN 1812 01:12:45,480 --> 01:12:47,200 KNOWN SOLID STATE STRUCTURE AND 1813 01:12:47,200 --> 01:12:48,920 WE SHOWED YOU A LOT OF 1814 01:12:48,920 --> 01:12:49,200 STRUCTURES. 1815 01:12:49,200 --> 01:12:51,560 >>I THINK, TOO, EVEN IF WE 1816 01:12:51,560 --> 01:12:55,240 KNEW, LET'S SAY FOR TRPM8 WE 1817 01:12:55,240 --> 01:12:56,720 KNOW ITS BIOLOGY, IT IS 1818 01:12:56,720 --> 01:12:58,280 IMPORTANT, WE HAD SOME 1819 01:12:58,280 --> 01:12:59,400 CHEMICALS, WE DIDN'T UNDERSTAND 1820 01:12:59,400 --> 01:13:00,800 WHY THERE WERE SO MANY CHEMICALS 1821 01:13:00,800 --> 01:13:03,560 THAT BIND TO IT AND WHY THEY 1822 01:13:03,560 --> 01:13:06,360 BIND SO POORLY AND SUCH TERRIBLE 1823 01:13:06,360 --> 01:13:06,880 DRUGS. 1824 01:13:06,880 --> 01:13:12,080 THEY ARE HYDROPHOBIC, POOR 1825 01:13:12,080 --> 01:13:12,360 EFFICACY. 1826 01:13:12,360 --> 01:13:14,360 AND NOW YOU SEE THE POCKET, IT 1827 01:13:14,360 --> 01:13:15,720 CAN ADAPT AND CHANGE TO THE 1828 01:13:15,720 --> 01:13:17,480 DIFFERENT MOLECULES, IT GIVES 1829 01:13:17,480 --> 01:13:19,360 YOU SPACE TO SYNTHESIZE AND THIN 1830 01:13:19,360 --> 01:13:21,400 OF SOMETHING THAT COULD BE MORE 1831 01:13:21,400 --> 01:13:26,000 SPECIFIC AND MORE DRUG LIKE. 1832 01:13:26,000 --> 01:13:28,720 >>I GUESS ONE MORE GENERIC 1833 01:13:28,720 --> 01:13:30,640 QUESTION, FOR MYSELF MORE THAN 1834 01:13:30,640 --> 01:13:34,560 PATIK, WHAT IS THE NCCIH 1835 01:13:34,560 --> 01:13:39,040 INTEREST IN PHENOTYPIC. 1836 01:13:39,040 --> 01:13:46,200 NOT DIRECTLY TO THE TALKS WE 1837 01:13:46,200 --> 01:13:46,600 HEARD. 1838 01:13:46,600 --> 01:13:49,880 NCCIH IS VERY INTERESTED. 1839 01:13:49,880 --> 01:13:53,600 WE ARE IN THE IGNITE PROGRAM 1840 01:13:53,600 --> 01:14:04,120 ACTIVELY SEEKING ASSAYS, FEEN 1841 01:14:06,040 --> 01:14:09,760 TYPE ASSAY S. 1842 01:14:09,760 --> 01:14:11,480 WE ARE FUNDING THAT AREA. 1843 01:14:11,480 --> 01:14:12,960 THERE IS ONE MORE GENERAL 1844 01:14:12,960 --> 01:14:14,640 QUESTION I WILL SCROLL BACK TO. 1845 01:14:14,640 --> 01:14:16,640 IT IS NOT FOR ANYBODY, PER SE 1846 01:14:16,640 --> 01:14:18,120 DIRECTLY ADDRESSING THE TALKS. 1847 01:14:18,120 --> 01:14:19,880 I WILL ASK IT ANY WAY. 1848 01:14:19,880 --> 01:14:21,640 SO THE QUESTION IS MANY OF THE 1849 01:14:21,640 --> 01:14:23,680 MEASUREMENTS WE USE IN NATURAL 1850 01:14:23,680 --> 01:14:25,160 PRODUCTS RESEARCH ARE THE MASS 1851 01:14:25,160 --> 01:14:27,320 SPEC ESPECIALLY ARE DESTRUCTIVE. 1852 01:14:27,320 --> 01:14:30,000 WITH PROHIBITS OTHER DOWNSTREAM 1853 01:14:30,000 --> 01:14:33,160 ASSAYS FROM USING THOSE SAME 1854 01:14:33,160 --> 01:14:33,560 PRODUCTS. 1855 01:14:33,560 --> 01:14:35,960 WHAT ROLE DO YOU FEEL 1856 01:14:35,960 --> 01:14:37,640 NONDESTRUCTIVE, NONINVASIVE 1857 01:14:37,640 --> 01:14:41,960 CHEMICAL ASSAYS, FTIR, RAMN, 1858 01:14:41,960 --> 01:14:44,520 WHICH IS THEIR ROLE IN 1859 01:14:44,520 --> 01:14:45,840 DETERMINING CHEMICAL COMPOSITION 1860 01:14:45,840 --> 01:14:49,240 AND HOW IMPORTANT IT IS TO HAVE 1861 01:14:49,240 --> 01:14:51,480 NONDESTRUCTIVENESS TO DEVELOP 1862 01:14:51,480 --> 01:14:55,200 CELL LINES WITH PHENOTYPE. 1863 01:14:55,200 --> 01:14:58,520 THE LAST PART WAS NON SEQUITUR 1864 01:14:58,520 --> 01:14:59,520 OF THE FIRST PART. 1865 01:14:59,520 --> 01:15:02,120 WHAT ARE YOUR THOUGHTS ON 1866 01:15:02,120 --> 01:15:02,920 NONDESTRUCTIVE METHODS? 1867 01:15:02,920 --> 01:15:04,920 >>IT IS POINT ON. 1868 01:15:04,920 --> 01:15:06,120 NONDESTRUCTIVE METHODS ARE 1869 01:15:06,120 --> 01:15:06,960 REALLY IMPORTANT. 1870 01:15:06,960 --> 01:15:09,160 WHAT WE DO IS DESTRUCTIVE IN 1871 01:15:09,160 --> 01:15:10,680 PRACTICAL SENSES, BUT THE AMOUNT 1872 01:15:10,680 --> 01:15:12,880 OF STUFF WE ARE LOOKING AT IS SO 1873 01:15:12,880 --> 01:15:19,240 SMALL EVEN IF YOU HAVE A 1874 01:15:19,240 --> 01:15:23,440 NANOGRAM MATERIAL, IT IS OKAY TO 1875 01:15:23,440 --> 01:15:29,200 DRAW OFF A PICO GRAM PART OF THE 1876 01:15:29,200 --> 01:15:30,280 SOLUTION. 1877 01:15:30,280 --> 01:15:34,000 FROM MY PERSPECTIVE AS A 1878 01:15:34,000 --> 01:15:36,120 CHEMIST, MULTIPLEXING OF METHODS 1879 01:15:36,120 --> 01:15:38,680 WILL PROVIDE THE MOST THOROUGH 1880 01:15:38,680 --> 01:15:42,120 PICTURE TR FROM A CHEMICAL AND 1881 01:15:42,120 --> 01:15:44,160 BIOLOGICAL STANDPOINT SO IT IS 1882 01:15:44,160 --> 01:15:46,560 REALLY IMPORTANT TO DEVELOP 1883 01:15:46,560 --> 01:15:47,560 NONDESTRUCTIVE METHODS. 1884 01:15:47,560 --> 01:15:49,600 >>TWO MORE QUESTIONS AND WE 1885 01:15:49,600 --> 01:15:51,120 HAVE TO MOVE ON. 1886 01:15:51,120 --> 01:15:53,240 LOOKS LIKE BOTH ARE FOR YOU DR. 1887 01:15:53,240 --> 01:15:53,800 NELSON. 1888 01:15:53,800 --> 01:15:56,640 DO YOU SEE FOOD SCIENCE OR FOOD 1889 01:15:56,640 --> 01:15:58,080 PRODUCT DEVELOPMENT RESEARCH 1890 01:15:58,080 --> 01:15:59,360 BEYOND NEW DRUG DEVELOPMENT 1891 01:15:59,360 --> 01:15:59,680 APPLICATIONS. 1892 01:15:59,680 --> 01:16:03,880 THE QUESTIONER IS THINKING ABOUT 1893 01:16:03,880 --> 01:16:09,760 NANO IMMULSIONS OR OTHER FOOD 1894 01:16:09,760 --> 01:16:10,120 OPPORTUNITIES. 1895 01:16:10,120 --> 01:16:12,080 >>I THINK ANYWHERE THERE IS 1896 01:16:12,080 --> 01:16:13,720 MOLECULAR ORDER THERE IS AN 1897 01:16:13,720 --> 01:16:14,440 APPLICATION POTENTIALLY. 1898 01:16:14,440 --> 01:16:16,000 ONE OF THE THINGS WE LOOK AT 1899 01:16:16,000 --> 01:16:18,680 THAT MIGHT BE RELATED IN THE 1900 01:16:18,680 --> 01:16:20,160 PHARMACEUTICAL INDUSTRY IS FROM 1901 01:16:20,160 --> 01:16:21,400 A FORMULATION STANDPOINT. 1902 01:16:21,400 --> 01:16:23,400 IF YOU FORMULATE AN API WITH A 1903 01:16:23,400 --> 01:16:27,720 BINDER OR LOOKING AT HOW THE 1904 01:16:27,720 --> 01:16:29,360 CRYSTAL MOR FOLG CHANGES AS A 1905 01:16:29,360 --> 01:16:31,000 FUNCTION OF FORMATION IS 1906 01:16:31,000 --> 01:16:33,040 IMPORTANT FOR BIOAVAILABILITY. 1907 01:16:33,040 --> 01:16:35,200 YOU CAN THINK OF THOSE SAME 1908 01:16:35,200 --> 01:16:37,760 TIMES OF THINGS IN THE FOOD 1909 01:16:37,760 --> 01:16:38,280 MEDICINE INDUSTRY. 1910 01:16:38,280 --> 01:16:41,560 IN GENERAL, WE ARE CERTAINLY 1911 01:16:41,560 --> 01:16:42,720 OPEN TO THOSE THINGS. 1912 01:16:42,720 --> 01:16:44,080 WE HAVEN'T THOUGHT ABOUT IT. 1913 01:16:44,080 --> 01:16:45,920 ANYWHERE THERE IS ORDER, WE ARE 1914 01:16:45,920 --> 01:16:48,360 EXCITED ABOUT LOOKING. 1915 01:16:48,360 --> 01:16:51,520 >>ONE MORE CRYO EM QUESTION FOR 1916 01:16:51,520 --> 01:16:52,680 DR. DIVER, DR. NELSON. 1917 01:16:52,680 --> 01:16:54,960 WHAT TYPES OF NATURAL PRODUCTS 1918 01:16:54,960 --> 01:16:57,400 OR PROTEINS ARE PARTICULARLY 1919 01:16:57,400 --> 01:17:00,440 WELL SUITED FOR CRYO-EM AND THIS 1920 01:17:00,440 --> 01:17:05,680 ONES PRAPS ARE NOT? 1921 01:17:05,680 --> 01:17:06,600 PERHAPS ARE NOT? 1922 01:17:06,600 --> 01:17:08,120 >>I'M HAPPY TO COMMENT ON THAT. 1923 01:17:08,120 --> 01:17:11,120 WHEN I FIRST STARTED OUT, 1924 01:17:11,120 --> 01:17:17,560 WORKING ON SINGLE PARTICLE CRYO, 1925 01:17:17,560 --> 01:17:18,560 TRPM8 IS PERFECT. 1926 01:17:18,560 --> 01:17:19,760 IT IS BIG. 1927 01:17:19,760 --> 01:17:20,000 DYNAMIC. 1928 01:17:20,000 --> 01:17:23,840 IT WAS NOT ABLE TO BE 1929 01:17:23,840 --> 01:17:24,160 CRYSTALLIZED. 1930 01:17:24,160 --> 01:17:27,600 MANY TRIES FOR TRYP CHANNELS FOR 1931 01:17:27,600 --> 01:17:28,920 DECADES AND DECADES. 1932 01:17:28,920 --> 01:17:32,440 THE ANSWER NOW IS EVERYTHING IS 1933 01:17:32,440 --> 01:17:34,960 A GOOD TARGET. 1934 01:17:34,960 --> 01:17:38,240 IT IS AMAZING FOR RECEPTORS AND 1935 01:17:38,240 --> 01:17:40,240 COMPLEXES AND THE THINGS THAT 1936 01:17:40,240 --> 01:17:42,240 USED TO BOG US DOWN, SMALLER 1937 01:17:42,240 --> 01:17:44,640 SIZE, NOT MUCH OUT OF THE 1938 01:17:44,640 --> 01:17:45,920 MEMBRANE, WHICH DOESN'T GIVE THE 1939 01:17:45,920 --> 01:17:48,120 PROGRAMS A LOT TO ALIGN THE 1940 01:17:48,120 --> 01:17:48,880 PARTICLES TO. 1941 01:17:48,880 --> 01:17:50,520 ALL OF THOSE THINGS HAVE 1942 01:17:50,520 --> 01:17:52,760 SOLUTIONS AND ALL OF IT IS 1943 01:17:52,760 --> 01:17:54,160 FIXABLE AND PRACTICALLY THEY ALL 1944 01:17:54,160 --> 01:17:54,400 WORK. 1945 01:17:54,400 --> 01:17:57,160 WE ARE BASICALLY AT A NO LIMIT. 1946 01:17:57,160 --> 01:17:59,680 >>THAT IS EXCITING. 1947 01:17:59,680 --> 01:18:02,400 ANYTHING ELSE TO ADD DR. NELSON? 1948 01:18:02,400 --> 01:18:04,200 >>YEAH. 1949 01:18:04,200 --> 01:18:07,560 SURE WE HAVEN'T FIGURED THAT OUT 1950 01:18:07,560 --> 01:18:08,040 YET. 1951 01:18:08,040 --> 01:18:10,840 WE HAVEN'T SOLVED ENOUGH 1952 01:18:10,840 --> 01:18:11,160 STRUCTURES. 1953 01:18:11,160 --> 01:18:13,280 THINGS THAT SHOULDN'T BE 1954 01:18:13,280 --> 01:18:15,080 CRYSTALINE, BUT DARN IT, THEY 1955 01:18:15,080 --> 01:18:15,560 ARE. 1956 01:18:15,560 --> 01:18:19,400 I HAD TO TRUNCATE A FATTY ACID 1957 01:18:19,400 --> 01:18:22,040 CHAIN THAT HAS 20 PLUS CARBON 1958 01:18:22,040 --> 01:18:26,560 CHAINS FLOPPING IT AND WE HAVE A 1959 01:18:26,560 --> 01:18:27,320 CRYSTAL STRUCTURE. 1960 01:18:27,320 --> 01:18:29,480 IT IS WILD IF YOU LOOK AT THE 1961 01:18:29,480 --> 01:18:33,320 PACKING, IT LOOKS LIKE AN 1962 01:18:33,320 --> 01:18:34,680 INVERSE LIPID BILAYER. 1963 01:18:34,680 --> 01:18:36,360 IT IS A REMARKABLE STRUCTURE. 1964 01:18:36,360 --> 01:18:38,160 THE MORE STRUCTURES WE SOLVE, WE 1965 01:18:38,160 --> 01:18:39,720 MIGHT BE ABLE TO GET SOME IDEAS 1966 01:18:39,720 --> 01:18:41,440 OF WHAT ARE THE CHEMICAL 1967 01:18:41,440 --> 01:18:43,360 FEATURES THAT LEND THEMSELVES TO 1968 01:18:43,360 --> 01:18:45,680 ORDER BEYOND WHAT WE KNOW NOW, 1969 01:18:45,680 --> 01:18:48,760 BUT AT THIS POINT IT IS A WILD 1970 01:18:48,760 --> 01:18:49,280 WEST. 1971 01:18:49,280 --> 01:18:49,720 >>YEAH. 1972 01:18:49,720 --> 01:18:53,040 STILL EARLY DAYS FOR THE SMALL 1973 01:18:53,040 --> 01:18:53,560 MOLECULE SIDE. 1974 01:18:53,560 --> 01:18:55,160 THANK YOU EVERYONE WHO POSED 1975 01:18:55,160 --> 01:18:55,920 THOSE QUESTIONS. 1976 01:18:55,920 --> 01:18:57,520 WE ARE GOING TO SHIFT OVER TO 1977 01:18:57,520 --> 01:18:59,240 THE NEXT PHASE OF THE WEBINAR 1978 01:18:59,240 --> 01:19:07,400 NOW WHERE WE ARE HEARING FROM 1979 01:19:07,400 --> 01:19:16,120 OUR NIH COLLEAGUES, DR. MOHA' 1980 01:19:16,120 --> 01:19:20,600 ATRA AND DR. MICHELLE BOND, WHO 1981 01:19:20,600 --> 01:19:22,880 IS WITH NIGMS. 1982 01:19:22,880 --> 01:19:24,800 WE WANT TO ASK THESE FOLKS SOME 1983 01:19:24,800 --> 01:19:26,280 GENERAL QUESTIONS ABOUT HOW THE 1984 01:19:26,280 --> 01:19:30,960 SCIENCE WE TACKED ABOUT TODAY 1985 01:19:30,960 --> 01:19:32,320 RELATED TO THEIR DIFFERENT 1986 01:19:32,320 --> 01:19:33,760 INTERESTS WITHIN THEIR IC. 1987 01:19:33,760 --> 01:19:35,360 SO THE FIRST -- SO I HAVE A 1988 01:19:35,360 --> 01:19:36,760 SERIES OF QUESTIONS I'M 1989 01:19:36,760 --> 01:19:39,040 INTERESTED IN MANY ASKING. 1990 01:19:39,040 --> 01:19:42,920 THE FIRST ONE IS, I GUESS WE'LL 1991 01:19:42,920 --> 01:19:45,440 ASK MICHELLE FIRST, DR. BOND. 1992 01:19:45,440 --> 01:19:48,120 HOW HAS YOUR IC'S INTEREST IN 1993 01:19:48,120 --> 01:19:50,840 NATURAL PRODUCT TECHNOLOGY 1994 01:19:50,840 --> 01:19:51,880 EVOLVED OVER TIME. 1995 01:19:51,880 --> 01:19:54,760 AFTER SHE ANSWERS WE CAN ASK 1996 01:19:54,760 --> 01:19:57,560 OTHERS TO FILL IN THE BLANKS. 1997 01:19:57,560 --> 01:20:08,120 DR. BOND, WHICH IS NIGS'S IDEA. 1998 01:20:09,160 --> 01:20:11,600 >>HOPEFULLY YOU CAN SEE ME AND 1999 01:20:11,600 --> 01:20:12,680 HEAR ME. 2000 01:20:12,680 --> 01:20:14,280 WE ARE HAVING WEATHER HERE. 2001 01:20:14,280 --> 01:20:16,800 I WILL MENTION I AM AT THE 2002 01:20:16,800 --> 01:20:19,240 NATIONAL INSTITUTE OF GENERAL 2003 01:20:19,240 --> 01:20:19,640 MEDICAL SCIENCES. 2004 01:20:19,640 --> 01:20:22,080 THE APPLICATIONS AND AWARDS I 2005 01:20:22,080 --> 01:20:23,880 OVERSEE ARE TYPICALLY IN THE 2006 01:20:23,880 --> 01:20:26,240 NATURAL PRODUCTS AND GLYCO 2007 01:20:26,240 --> 01:20:27,280 SCIENCE AREA. 2008 01:20:27,280 --> 01:20:29,960 WHAT I WILL MENTION IS THAT WE 2009 01:20:29,960 --> 01:20:32,240 ARE INTERESTED IN SUPPORTING 2010 01:20:32,240 --> 01:20:33,200 CUTTING-EDGE RESOURCE. 2011 01:20:33,200 --> 01:20:35,080 THAT IS WITHIN OUR MISSION AND 2012 01:20:35,080 --> 01:20:36,520 TO SUPPORT SEARCH THAT INCREASES 2013 01:20:36,520 --> 01:20:38,880 OUR UNDERSTANDING OF BIOLOGICAL 2014 01:20:38,880 --> 01:20:41,760 PROCESSES AND LAYS A FOUNDATION 2015 01:20:41,760 --> 01:20:43,480 FOR DISEASE DIAGNOSIS, 2016 01:20:43,480 --> 01:20:44,880 TREATMENT, AND PREVENTION. 2017 01:20:44,880 --> 01:20:48,800 AND NIGMS IS INTERESTED IN 2018 01:20:48,800 --> 01:20:50,360 INVESTIGATOR-INITIATED EFFORTS. 2019 01:20:50,360 --> 01:20:52,320 SO OFTEN THE PARTICULAR AREAS OF 2020 01:20:52,320 --> 01:20:54,400 SCIENCE WE SUPPORT REFLECT THE 2021 01:20:54,400 --> 01:20:57,840 INTEREST AND IMPORTANCE OF THE 2022 01:20:57,840 --> 01:20:58,720 SCIENTIFIC COMMUNITY PLACES ON 2023 01:20:58,720 --> 01:21:02,120 PARTICULAR AREAS OF 2024 01:21:02,120 --> 01:21:02,520 INVESTIGATION. 2025 01:21:02,520 --> 01:21:04,000 THAT BEING SAID, WE ARE 2026 01:21:04,000 --> 01:21:05,640 INTERESTED IN TECHNOLOGIES THAT 2027 01:21:05,640 --> 01:21:07,520 ARE THE AT THE VERY BEGINNING 2028 01:21:07,520 --> 01:21:09,480 STAGE OF TECHNOLOGY DEVELOPMENT. 2029 01:21:09,480 --> 01:21:10,720 SO THE CONCEPTUAL STAGE. 2030 01:21:10,720 --> 01:21:13,760 THERE IS NO FEASIBILITY THAT HAS 2031 01:21:13,760 --> 01:21:15,880 BEEN PROVEN TO TECHNOLOGIES THAT 2032 01:21:15,880 --> 01:21:18,880 ARE READY FOR DISSEMINATION 2033 01:21:18,880 --> 01:21:19,200 COMMERCIALLY. 2034 01:21:19,200 --> 01:21:21,440 OUR EMPHASIS ON SUPPORTING 2035 01:21:21,440 --> 01:21:22,440 EFFORTS IN THIS WIDE RANGE HAS 2036 01:21:22,440 --> 01:21:24,680 BECOME A KEY FOCUS AS WE 2037 01:21:24,680 --> 01:21:27,840 RECOGNIZE THERE IS AN ITERATIVE 2038 01:21:27,840 --> 01:21:30,840 AND CYCLICAL NATURE OF 2039 01:21:30,840 --> 01:21:31,920 TECHNOLOGY DEVELOPMENT AND 2040 01:21:31,920 --> 01:21:33,280 ASKING BIOMEDICAL RELATED 2041 01:21:33,280 --> 01:21:35,840 RESEARCH QUESTIONS WITH THAT 2042 01:21:35,840 --> 01:21:36,880 TECHNOLOGY AND GOING BACK AND 2043 01:21:36,880 --> 01:21:38,080 FORTH IN THAT WAY. 2044 01:21:38,080 --> 01:21:40,320 SO I THINK, CRAIG, YOU HAVE A 2045 01:21:40,320 --> 01:21:43,240 COUPLE OF OTHER QUESTIONS AND I 2046 01:21:43,240 --> 01:21:44,760 WILL LEAVE IT THERE FOR NOW. 2047 01:21:44,760 --> 01:21:47,760 I WILL GO INTO MORE DEPTH AS WE 2048 01:21:47,760 --> 01:21:52,400 GET FARTHER ALONG. 2049 01:21:52,400 --> 01:21:56,680 >>I WAS MUTED. 2050 01:21:56,680 --> 01:22:04,240 SO DOCTOR MOHAPATRA OR DR. 2051 01:22:04,240 --> 01:22:05,280 RANALLO, ANYTHING TO ADD? 2052 01:22:05,280 --> 01:22:06,600 >>DEFINITELY. 2053 01:22:06,600 --> 01:22:08,440 AS YOU KNOW -- CAN YOU HEAR ME 2054 01:22:08,440 --> 01:22:10,720 BY THE WAY? 2055 01:22:10,720 --> 01:22:11,760 >>YES. 2056 01:22:11,760 --> 01:22:16,120 >>NINDS MAINLY SUPPORTS 2057 01:22:16,120 --> 01:22:17,440 CLINICAL RESEARCH ON THE BRAIN 2058 01:22:17,440 --> 01:22:27,960 AND UTILIZED THAT KNOWLEDGE 2059 01:22:28,520 --> 01:22:34,200 TO -- WE ARE INTERESTED IN THE 2060 01:22:34,200 --> 01:22:37,280 RESEARCH WITH THE TRYP CHANNELS. 2061 01:22:37,280 --> 01:22:39,040 ALL THOSE RESEARCH CAME THROUGH 2062 01:22:39,040 --> 01:22:40,400 THE NATURAL, UTILIZATION OF 2063 01:22:40,400 --> 01:22:42,360 NATURAL PRODUCT. 2064 01:22:42,360 --> 01:22:45,920 THAT IS HOW LIFTED THE DISCOVERY 2065 01:22:45,920 --> 01:22:50,240 AND FIELD NATURAL EXPANSION. 2066 01:22:50,240 --> 01:22:55,720 NDS HAS BEEN SUPPORTING THAT FOR 2067 01:22:55,720 --> 01:22:56,960 QUITE SOME TIME. 2068 01:22:56,960 --> 01:23:00,040 AS CRAIG MENTIONED WE HAVE A 2069 01:23:00,040 --> 01:23:02,840 PARTNERING PROGRAM ON DEVELOPING 2070 01:23:02,840 --> 01:23:04,040 SPECIFICALLY THE NATURAL 2071 01:23:04,040 --> 01:23:06,640 PRODUCTS AND DEVELOPING THOSE 2072 01:23:06,640 --> 01:23:10,960 FOR THERAPEUTICS FOR PAIN AS FOR 2073 01:23:10,960 --> 01:23:13,200 OTHER NEUROLOGICAL. 2074 01:23:13,200 --> 01:23:15,280 NINDS HAS ALSO SUMMITED A NUMBER 2075 01:23:15,280 --> 01:23:16,760 OF TECHNOLOGY DEVELOPMENT 2076 01:23:16,760 --> 01:23:22,160 THROUGH SMALL BUSINESSES, 2077 01:23:22,160 --> 01:23:23,720 RESEARCH AND NATURAL PRODUCTS. 2078 01:23:23,720 --> 01:23:27,600 IN ADDITION TO THAT NINDS 2079 01:23:27,600 --> 01:23:29,640 ACTIVELY PARTICIPATES AS ONE OF 2080 01:23:29,640 --> 01:23:33,880 THE NIH INSTITUTE CENTERS 2081 01:23:33,880 --> 01:23:34,880 DEVELOPING THESE MULTICENTER 2082 01:23:34,880 --> 01:23:39,680 LIKE TECHNOLOGIES, LIKE CRYO-EM. 2083 01:23:39,680 --> 01:23:43,880 THESE FACILITIES WE ACTIVELY 2084 01:23:43,880 --> 01:23:44,760 SUPPORT THOSE. 2085 01:23:44,760 --> 01:23:51,200 OUR OVERALL MISSION AND INTEREST 2086 01:23:51,200 --> 01:23:53,040 REMAINS VERY STRONG IN THE 2087 01:23:53,040 --> 01:23:54,560 DISCOVERY AND USE OF NATURAL 2088 01:23:54,560 --> 01:23:56,040 PRODUCTS AND DEVELOPING 2089 01:23:56,040 --> 01:23:56,360 THERAPEUTICS. 2090 01:23:56,360 --> 01:23:58,240 WE ARE FOCUSING ON NATURAL 2091 01:23:58,240 --> 01:23:59,800 PRODUCTS AS WELL AS UTILIZING 2092 01:23:59,800 --> 01:24:01,720 THOSE TO UNDERSTAND THE BASIC 2093 01:24:01,720 --> 01:24:07,400 BIOLOGY OF THE NERVOUS SYSTEM 2094 01:24:07,400 --> 01:24:07,920 AND 2095 01:24:07,920 --> 01:24:08,840 [INDISCERNIBLE] WE ARE COMMITTED 2096 01:24:08,840 --> 01:24:11,160 THERE SO I WILL STOP HERE AND 2097 01:24:11,160 --> 01:24:13,080 TAKE ANY QUESTIONS IN CASE 2098 01:24:13,080 --> 01:24:16,600 ANYONE HAS ANY. 2099 01:24:16,600 --> 01:24:17,560 >>THANK YOU. 2100 01:24:17,560 --> 01:24:20,880 I WILL INSERT HERE BRIEFLY, THE 2101 01:24:20,880 --> 01:24:22,040 AUDIENCE IS WELCOME TO ASK 2102 01:24:22,040 --> 01:24:23,240 QUESTIONS OF THE NIH COLLEAGUES 2103 01:24:23,240 --> 01:24:24,320 IF YOU HAVE SPECIFIC QUESTIONS 2104 01:24:24,320 --> 01:24:30,920 ABOUT AREAS OF INTEREST. 2105 01:24:30,920 --> 01:24:32,520 IF THEY ARE VERY SPECIFIC, TAKE 2106 01:24:32,520 --> 01:24:34,240 THEM OFFLINE, BUT GENERAL 2107 01:24:34,240 --> 01:24:35,240 QUESTIONS YOU CAN ASKED AT THE 2108 01:24:35,240 --> 01:24:38,840 END OF THIS SEGMENT. 2109 01:24:38,840 --> 01:24:41,640 DR. RANALLO, ANYTHING ELSE TO 2110 01:24:41,640 --> 01:24:41,800 ADD? 2111 01:24:41,800 --> 01:24:43,640 >>A LITTLE BIT. 2112 01:24:43,640 --> 01:24:46,240 AN OVERVIEW OF NIAD'S MISSION. 2113 01:24:46,240 --> 01:24:50,640 IT IS A LARGE INSTITUTE. 2114 01:24:50,640 --> 01:24:53,680 IN THE SPOTLIGHT RECENTLY AND 2115 01:24:53,680 --> 01:24:57,840 ULTIMATELY OUR MENTION IS TO 2116 01:24:57,840 --> 01:25:01,320 TREAT, PREVENT INFECTIOUS AND' 2117 01:25:01,320 --> 01:25:04,720 ALLERGIC DISEASES. 2118 01:25:04,720 --> 01:25:07,640 PRIMARILY IN THE REALM OF 2119 01:25:07,640 --> 01:25:09,640 ANTI-INFECTIVES, WE KNOW THAT. 2120 01:25:09,640 --> 01:25:12,280 WE FOCUS, AT LEAST IN MY 2121 01:25:12,280 --> 01:25:15,800 DIVISION, WE HAVE THREE LARGE 2122 01:25:15,800 --> 01:25:19,360 EXTRAMURAL DIVISIONS MINE IS THE 2123 01:25:19,360 --> 01:25:21,400 MICROBIOLOGY AND INFECTIOUS 2124 01:25:21,400 --> 01:25:21,720 DISEASES. 2125 01:25:21,720 --> 01:25:25,040 MINE IS ON THE GUT MICROBIOME 2126 01:25:25,040 --> 01:25:28,160 AND CLUSTERING. 2127 01:25:28,160 --> 01:25:31,280 AND SO THINGS THAT TRADITIONALLY 2128 01:25:31,280 --> 01:25:32,880 HAVE BEEN CONSIDERED NATURAL 2129 01:25:32,880 --> 01:25:35,120 PRODUCTS, ANTI-INFECTIVE 2130 01:25:35,120 --> 01:25:37,720 PRODUCED BY MICROBES ARE CLEARLY 2131 01:25:37,720 --> 01:25:39,760 IN OUR AREA OF INTEREST. 2132 01:25:39,760 --> 01:25:41,480 WE HAVE ADVANCING TECHNOLOGIES 2133 01:25:41,480 --> 01:25:43,560 THAT ALLOWS US TO LOOK AT THESE 2134 01:25:43,560 --> 01:25:48,800 PRODUCTS COMING FROM WHOLE 2135 01:25:48,800 --> 01:25:52,240 MICROBAL COMMUNITIES, RECENT 2136 01:25:52,240 --> 01:25:55,560 ANTIBIOTIC DISCOVERIES IN THAT 2137 01:25:55,560 --> 01:25:55,840 REALM. 2138 01:25:55,840 --> 01:25:59,840 WE HEARD FROM CHELSI. 2139 01:25:59,840 --> 01:26:03,360 WE LOOK AT THESE BUGS, BOTH AT 2140 01:26:03,360 --> 01:26:07,120 THE WHOLE, THE WHOLE BACTERIA 2141 01:26:07,120 --> 01:26:10,720 LEVEL AS WELL AS IN THE SENSE OF 2142 01:26:10,720 --> 01:26:11,560 INDIVIDUAL, YOU KNOW, ELEMENTS 2143 01:26:11,560 --> 01:26:13,080 OF THOSE MICROBES. 2144 01:26:13,080 --> 01:26:17,320 SO, AGAIN, I THINK FROM MY 2145 01:26:17,320 --> 01:26:18,000 PERSPEC 2146 01:26:18,000 --> 01:26:18,680 PERSPECTIVE, AGAIN, I WILL THINK 2147 01:26:18,680 --> 01:26:22,000 ABOUT IT IN THE CONTEXT OF LIVE 2148 01:26:22,000 --> 01:26:28,000 BACTERIA OR PROBIOTICS, FAGE, 2149 01:26:28,000 --> 01:26:30,760 THEY FALL INTO NEW PRODUCTS. 2150 01:26:30,760 --> 01:26:33,560 THERE ARE COOL NEW TECHNOLOGIES, 2151 01:26:33,560 --> 01:26:35,680 CULTURAL TECHNOLOGIES, 2152 01:26:35,680 --> 01:26:39,920 ASSOCIATED MICROBES WITH 2153 01:26:39,920 --> 01:26:41,920 MULTIDIMENSIONAL AND 2154 01:26:41,920 --> 01:26:43,560 MULTICELLULAR IN VITRO SYSTEMS. 2155 01:26:43,560 --> 01:26:46,200 RELATING TO DISCOVERY. 2156 01:26:46,200 --> 01:26:48,920 TECHNOLOGIES THAT ALLOW YOU TO 2157 01:26:48,920 --> 01:26:52,440 FRACTIONATE BUGS OR EXTRACTS IN 2158 01:26:52,440 --> 01:26:56,360 THE CONTEXT OF BACTERIA, 2159 01:26:56,360 --> 01:27:00,320 MICROBIOME TO METTA GENETIC 2160 01:27:00,320 --> 01:27:01,880 SEQUENCING TO GENOMES IN THE 2161 01:27:01,880 --> 01:27:04,040 SENSE OF IDENTIFYING DIFFERENT 2162 01:27:04,040 --> 01:27:05,240 BACTERIA WITHIN THERE. 2163 01:27:05,240 --> 01:27:08,960 I WILL STOP THERE, BUT 2164 01:27:08,960 --> 01:27:10,680 ESSENTIALLY WE DON'T HAVE ANY 2165 01:27:10,680 --> 01:27:15,720 LARGE OVERARCHING NATURAL 2166 01:27:15,720 --> 01:27:16,840 PRODUCT TECHNOLOGY INITIATIVES 2167 01:27:16,840 --> 01:27:17,360 RIGHT NOW. 2168 01:27:17,360 --> 01:27:20,080 IT IS A CONSTANT NEED AND INFLUX 2169 01:27:20,080 --> 01:27:21,760 IN OUR GRANT PORTFOLIO. 2170 01:27:21,760 --> 01:27:22,640 I'LL STOP THERE. 2171 01:27:22,640 --> 01:27:23,480 >>YEAH. 2172 01:27:23,480 --> 01:27:24,280 THANKS. 2173 01:27:24,280 --> 01:27:26,640 WE DID HAVE A FOURTH PROGRAM 2174 01:27:26,640 --> 01:27:28,680 OFFICER WHO WAS ORIGINALLY GOING 2175 01:27:28,680 --> 01:27:33,040 TO JOIN US THAT HAD A 2176 01:27:33,040 --> 01:27:35,880 LAST-SECOND CONFLICT, DR. YALI 2177 01:27:35,880 --> 01:27:38,160 FU AT NCI. 2178 01:27:38,160 --> 01:27:39,920 SHE SHARED WITH DR. STILL. 2179 01:27:39,920 --> 01:27:41,720 IF YOU HAVE ANYTHING YOU WANT TO 2180 01:27:41,720 --> 01:27:44,040 SHARE ON BEHALF OF NCI. 2181 01:27:44,040 --> 01:27:44,560 >>YES. 2182 01:27:44,560 --> 01:27:47,440 SO YALI WAS NICE ENOUGH TO SEND 2183 01:27:47,440 --> 01:27:51,480 A BRIEF OVERVIEW OF THEIR 2184 01:27:51,480 --> 01:27:53,280 INTERESTS AND SHE WANTED TO 2185 01:27:53,280 --> 01:27:56,440 CONVEY TO EVERYONE THAT THEY ARE 2186 01:27:56,440 --> 01:27:58,880 INTERESTED IN IN KNOW VATIVE 2187 01:27:58,880 --> 01:28:02,040 METHODS AND NEW TECHNOLOGIES 2188 01:28:02,040 --> 01:28:08,400 THAT ADVANCE CULTURING ACTIVE 2189 01:28:08,400 --> 01:28:11,080 NATURAL AND UNNATURAL PRODUCTS. 2190 01:28:11,080 --> 01:28:14,480 ACCORDING TO DR. FU, THEY HAVE 2191 01:28:14,480 --> 01:28:17,720 DOT HAVE A SPECIFIC QUEUE, BUT 2192 01:28:17,720 --> 01:28:19,920 THEY ENCOURAGE INNOVATIVE 2193 01:28:19,920 --> 01:28:21,440 APPROACHES ON SELECTIVE DELIVERY 2194 01:28:21,440 --> 01:28:26,560 OF NATURAL PRODUCTS VIO BUYO 2195 01:28:26,560 --> 01:28:29,480 ENGINEERING AND NANO TECHNOLOGY 2196 01:28:29,480 --> 01:28:31,400 AND NATURAL PRODUCT ANTI-CANCER 2197 01:28:31,400 --> 01:28:32,800 EFFECTS TO BRING NEW DRUGS TO 2198 01:28:32,800 --> 01:28:34,200 THE CLINIC, WHICH ARE A 2199 01:28:34,200 --> 01:28:35,000 PARTICULAR INTEREST. 2200 01:28:35,000 --> 01:28:37,120 SO WE ENCOURAGE YOU TO REACH OUT 2201 01:28:37,120 --> 01:28:38,600 TO DR. FU WITH ANY FURTHER 2202 01:28:38,600 --> 01:28:43,840 QUESTIONS RELATED TO NCI. 2203 01:28:43,840 --> 01:28:45,040 >>ALL RIGHT. 2204 01:28:45,040 --> 01:28:46,680 THANK YOU FOR THAT. 2205 01:28:46,680 --> 01:28:48,960 SO, THE NEXT QUESTION FOR THE 2206 01:28:48,960 --> 01:28:51,040 NIH FOLKS. 2207 01:28:51,040 --> 01:28:56,720 CAN YOU GIVE EXAMPLES OF NATURAL 2208 01:28:56,720 --> 01:28:59,080 PRODUCT RELEVANT, IF YOU WILL, 2209 01:28:59,080 --> 01:29:02,800 TECHNOLOGIES SUPPORTED BY YOUR, 2210 01:29:02,800 --> 01:29:03,120 IC. 2211 01:29:03,120 --> 01:29:08,040 I WILL ASK DR. RANALLO IF YOU 2212 01:29:08,040 --> 01:29:10,600 HAVE EXAMPLES THAT NIAID 2213 01:29:10,600 --> 01:29:14,040 SUPPORTED IN THE PAST OR DIRECT 2214 01:29:14,040 --> 01:29:16,040 IMPLICATIONS TO NATURAL PRODUCT 2215 01:29:16,040 --> 01:29:21,080 RESEARCH IN YOUR OPINION OF AND 2216 01:29:21,080 --> 01:29:22,520 YOUR IC. 2217 01:29:22,520 --> 01:29:24,880 >>I HAVE ONE IN THINKING HOW TO 2218 01:29:24,880 --> 01:29:25,080 RESPOND. 2219 01:29:25,080 --> 01:29:26,280 IT IS REPRESENTATIVE OF WHAT I 2220 01:29:26,280 --> 01:29:29,080 WAS SAYING BEFORE WHERE A LOT OF 2221 01:29:29,080 --> 01:29:31,600 THE NATURAL PRODUCT DISCOVERY 2222 01:29:31,600 --> 01:29:36,160 THAT IS HAPPENING IS AT THE R & 2223 01:29:36,160 --> 01:29:36,960 D LEVEL. 2224 01:29:36,960 --> 01:29:38,720 THE TECHNOLOGIES PEOPLE ARE 2225 01:29:38,720 --> 01:29:40,520 DEVELOPING OFTENTIMES WE ARE 2226 01:29:40,520 --> 01:29:42,720 TRYING TO LOOK IN THEIR NATURAL 2227 01:29:42,720 --> 01:29:43,120 ENVIRONMENT. 2228 01:29:43,120 --> 01:29:49,320 SO FOR EXAMPLE, AN ANTIBIOTIC 2229 01:29:49,320 --> 01:29:49,920 DISCOVERY. 2230 01:29:49,920 --> 01:29:53,080 TAKING HARD TO GROW BACTERIA OR 2231 01:29:53,080 --> 01:29:54,760 UNCULTURABLE AND TAKING THESE 2232 01:29:54,760 --> 01:29:56,000 BACTERIA AND LETTING THEM GROW 2233 01:29:56,000 --> 01:29:57,920 IN THE ENVIRONMENT AND USING 2234 01:29:57,920 --> 01:30:00,640 TECHNOLOGIES WHAT IS CALLED AN 2235 01:30:00,640 --> 01:30:01,920 I-CHIP TECHNOLOGY WHERE YOU ARE 2236 01:30:01,920 --> 01:30:05,560 ABLE TO EMBED THESE MICROBES IN 2237 01:30:05,560 --> 01:30:07,160 THEIR NATURAL ENVIRONMENT, ALLOW 2238 01:30:07,160 --> 01:30:09,840 THEM TO GROW TO PRODUCE 2239 01:30:09,840 --> 01:30:10,160 METABOLITES. 2240 01:30:10,160 --> 01:30:12,160 AT THE END OF THE DAY, IT IS A 2241 01:30:12,160 --> 01:30:16,400 STANDARD TECHNOLOGY TO LOOK FOR 2242 01:30:16,400 --> 01:30:17,200 ANTI-MICROBIAL ACTIVITY. 2243 01:30:17,200 --> 01:30:20,320 SO FOR US IN THE ANTI-INFECTIVE 2244 01:30:20,320 --> 01:30:23,520 SPACE, I ALSO MENTIONED A BIT OF 2245 01:30:23,520 --> 01:30:26,440 THE TECHNOLOGIES THAT WE'RE 2246 01:30:26,440 --> 01:30:31,160 SUPPORTING ON CO-CULTURE 2247 01:30:31,160 --> 01:30:33,920 SYSTEMS, WHOLE BACTERIA 2248 01:30:33,920 --> 01:30:35,960 FRACTIONATIONS AND LOOKING FOR 2249 01:30:35,960 --> 01:30:42,840 ACTIVITY IN CELLULAR-BASED 2250 01:30:42,840 --> 01:30:43,080 MODELS. 2251 01:30:43,080 --> 01:30:44,000 THESE ARE UP-AND-COMING 2252 01:30:44,000 --> 01:30:44,640 TECHNOLOGIES WE ARE ENCOURAGING 2253 01:30:44,640 --> 01:30:45,880 RATHER THAN GOING TO THE RFAs 2254 01:30:45,880 --> 01:30:47,080 THAT HAVE SUPPORTED THEM BECAUSE 2255 01:30:47,080 --> 01:30:49,400 THEY ARE NOT RELATED TO NATURAL 2256 01:30:49,400 --> 01:30:49,640 PRODUCTS. 2257 01:30:49,640 --> 01:30:51,400 BAUGH THEY ALL FEED INTO THIS 2258 01:30:51,400 --> 01:30:51,800 OVERALL EFFORT. 2259 01:30:51,800 --> 01:30:55,480 I'LL STOP THERE. 2260 01:30:55,480 --> 01:30:56,040 >>THANK YOU VERY MUCH. 2261 01:30:56,040 --> 01:30:58,000 I GUESS CONTINUING THE REVERSE 2262 01:30:58,000 --> 01:31:03,240 ORDER THEME, I WILL ASK DR. 2263 01:31:03,240 --> 01:31:05,640 MOHAPATRA IF THERE ARE NATURAL 2264 01:31:05,640 --> 01:31:08,480 PRODUCTS RELEVANT TECHNOLOGIES 2265 01:31:08,480 --> 01:31:15,640 THAT NINDS HAS SUPPORTED? 2266 01:31:15,640 --> 01:31:19,680 >>I WOULD ECHO WHAT DR. RANALLO 2267 01:31:19,680 --> 01:31:19,880 SAID. 2268 01:31:19,880 --> 01:31:22,600 WE HAVE SUPPORTED THE CRYO-EM 2269 01:31:22,600 --> 01:31:26,040 DEVELOPMENT AND EXPANSION OF THE 2270 01:31:26,040 --> 01:31:27,600 CRYO-EM FACILITIES AND 2271 01:31:27,600 --> 01:31:30,240 TECHNOLOGY STANDARDIZING AND 2272 01:31:30,240 --> 01:31:32,400 OPTIMIZING THOSE. 2273 01:31:32,400 --> 01:31:34,880 IN ADDITION NINDS HAS BEEN 2274 01:31:34,880 --> 01:31:37,280 SUPPORTING TECHNOLOGIES OF 2275 01:31:37,280 --> 01:31:40,840 CULTURES, DEVELOPING MICROFLUID 2276 01:31:40,840 --> 01:31:45,560 CO-CULTURE SYSTEMS AND DEVICES 2277 01:31:45,560 --> 01:31:49,160 TO PROBE MORE OF NEURON 2278 01:31:49,160 --> 01:31:52,600 INTERACTION WITH NEURON OTHER 2279 01:31:52,600 --> 01:31:56,080 INTERACTION, NEUROMUSCULAR 2280 01:31:56,080 --> 01:31:59,080 JUNCTIONS AND DEVELOPING THOSE 2281 01:31:59,080 --> 01:32:00,920 TECHNIQUES TO UNDERSTAND EFFECTS 2282 01:32:00,920 --> 01:32:05,200 OF TOXINS. 2283 01:32:05,200 --> 01:32:08,040 WE HAVE PARTNERED IN SUPPORTING 2284 01:32:08,040 --> 01:32:08,640 THESE TECHNOLOGY. 2285 01:32:08,640 --> 01:32:11,200 A VAST MAJORITY OF THE STUDIES 2286 01:32:11,200 --> 01:32:16,080 DEFINITELY ARE GEARED TOWARD 2287 01:32:16,080 --> 01:32:17,800 DISCOVERY OF NEUROBIOLOGICAL 2288 01:32:17,800 --> 01:32:19,360 MECHANISM, UNDERSTANDING THE 2289 01:32:19,360 --> 01:32:21,320 NEUROSCIENCE USING NATURAL 2290 01:32:21,320 --> 01:32:21,720 PRODUCTS. 2291 01:32:21,720 --> 01:32:25,680 IN TERMS OF THERAPEUTIC 2292 01:32:25,680 --> 01:32:28,480 TECHNOLOGIES, NOT REALLY THINK 2293 01:32:28,480 --> 01:32:33,520 IMMEDIATELY WHAT SPECIFIC ONES 2294 01:32:33,520 --> 01:32:35,760 WE HAVE BEEN DEVELOPING, BUT IF 2295 01:32:35,760 --> 01:32:39,640 I REMEMBER CORRECTLY, THERE ARE 2296 01:32:39,640 --> 01:32:45,720 SOME WHICH WE ARE GIVEN TO SDIA 2297 01:32:45,720 --> 01:32:47,080 MECHANISMS MAINLY FOR CELL 2298 01:32:47,080 --> 01:32:48,920 CULTURE OR SCREENING OR 2299 01:32:48,920 --> 01:32:50,240 SIMULATION DEVICES, THOSE KIND 2300 01:32:50,240 --> 01:32:52,600 OF TECHNOLOGIES TO REALLY 2301 01:32:52,600 --> 01:32:56,640 ENHANCE UNDERSTANDING THE ROLE 2302 01:32:56,640 --> 01:32:58,000 OF THIS NATURAL PRODUCT 2303 01:32:58,000 --> 01:32:59,720 SCREENING THOSE AND FINDING 2304 01:32:59,720 --> 01:33:00,200 THOSE FOR THERAPEUTIC 2305 01:33:00,200 --> 01:33:02,560 DEVELOPMENT. 2306 01:33:02,560 --> 01:33:04,440 >>AND DR. BOND, ANYTHING ELSE 2307 01:33:04,440 --> 01:33:09,680 TO ADD FROM NIGMS. 2308 01:33:09,680 --> 01:33:11,360 >>SURE. 2309 01:33:11,360 --> 01:33:13,320 WE SUPPORT BROAD AVAILABILITY 2310 01:33:13,320 --> 01:33:14,760 AND APPLICABILITY DISSEMINATION 2311 01:33:14,760 --> 01:33:17,320 OF TECHNOLOGIES SUCH AS THOSE 2312 01:33:17,320 --> 01:33:20,320 THAT REPORT RAPID DETECTION AND 2313 01:33:20,320 --> 01:33:21,760 DE -- OF NATURAL PRODUCTS. 2314 01:33:21,760 --> 01:33:23,320 SOFTWARE AND ALGORITHM 2315 01:33:23,320 --> 01:33:25,040 DEVELOPMENT FOR INTEGRATION AND 2316 01:33:25,040 --> 01:33:28,040 PROCESSING OF A VARIETY OF 2317 01:33:28,040 --> 01:33:29,560 DIFFERENT DATA TYPES. 2318 01:33:29,560 --> 01:33:31,200 PRODUCTION OF MOLECULES OF 2319 01:33:31,200 --> 01:33:33,600 INTEREST OR ANALOGS SO THAT YOU 2320 01:33:33,600 --> 01:33:35,920 HAVE A SUFFICIENT QUANTITY FOR 2321 01:33:35,920 --> 01:33:38,400 DOWNSTREAM QUERIES. 2322 01:33:38,400 --> 01:33:42,840 STRUCTURAL ANALYSIS AND HIGH 2323 01:33:42,840 --> 01:33:43,280 THROUGHPUT EFFORTS. 2324 01:33:43,280 --> 01:33:43,640 >>THANKS. 2325 01:33:43,640 --> 01:33:48,160 I GUESS I'LL JUST ADD FROM 2326 01:33:48,160 --> 01:33:50,600 NCCH'S PERSPECTIVE, WE OVERLAP A 2327 01:33:50,600 --> 01:33:52,160 FAIR AMOUNT IN THIS SPACE OF 2328 01:33:52,160 --> 01:33:52,720 TECHNOLOGY DEVELOPMENT. 2329 01:33:52,720 --> 01:33:58,000 WE HAVE SUPPORTED A FAIR AMOUNT 2330 01:33:58,000 --> 01:34:02,880 IN HETEROLOGOUS APPLICATION. 2331 01:34:02,880 --> 01:34:09,760 THERE IS A NICE PAPER FROM 2332 01:34:09,760 --> 01:34:11,600 DOCTORS CZECH AND OTHERS WHERE 2333 01:34:11,600 --> 01:34:14,120 SHE IS DEVELOPING COMPUTATIONAL 2334 01:34:14,120 --> 01:34:15,640 METHODS WHERE THEY CAN TRY TO 2335 01:34:15,640 --> 01:34:17,600 GET AT THE PRESENCE OF 2336 01:34:17,600 --> 01:34:19,080 SYNERGISTIC COMPONENTS AND 2337 01:34:19,080 --> 01:34:19,320 MIXTURES. 2338 01:34:19,320 --> 01:34:21,840 THIS IS ONE OF THE BIG -- I 2339 01:34:21,840 --> 01:34:24,120 STILL CALL IT HYPOTHESIS, HOW 2340 01:34:24,120 --> 01:34:27,960 FREQUENTLY THAT HAPPENS. 2341 01:34:27,960 --> 01:34:29,960 IT CERTAINLY HAPPENS WITH MANY 2342 01:34:29,960 --> 01:34:30,240 EXAMPLES. 2343 01:34:30,240 --> 01:34:36,960 HOW YOU FIND THOSE. 2344 01:34:36,960 --> 01:34:40,520 NCCIH IS SUPPORTING THAT AS 2345 01:34:40,520 --> 01:34:40,720 WELL. 2346 01:34:40,720 --> 01:34:43,920 EVERYONE HAS TALKED ABOUT THE 2347 01:34:43,920 --> 01:34:45,040 EXISTENCE OF FUNDING. 2348 01:34:45,040 --> 01:34:47,400 I THOUGHT I WOULD LEAVE IT OPEN 2349 01:34:47,400 --> 01:34:50,040 TO MY NIH COLLEAGUES IF THERE IS 2350 01:34:50,040 --> 01:34:52,160 ANY PARTICULAR NATURAL PRODUCT 2351 01:34:52,160 --> 01:34:55,000 OR NATURAL PRODUCTS TANGENTIAL 2352 01:34:55,000 --> 01:34:56,640 FOAs YOU WOULD LIKE TO HIGHLIGHT 2353 01:34:56,640 --> 01:34:57,960 TO THIS AUDIENCE, I WOULD 2354 01:34:57,960 --> 01:34:59,400 WELCOME YOU TO CALL THEM OUT FOR 2355 01:34:59,400 --> 01:35:01,680 THE AUDIENCE TO MAKE THEM AWARE. 2356 01:35:01,680 --> 01:35:03,800 I WILL OPEN IT UP FOR ANYONE TO, 2357 01:35:03,800 --> 01:35:06,120 IF YOU HAD ANYTHING YOU HADN'T 2358 01:35:06,120 --> 01:35:09,400 ALREADY SAID OR WANT TO RESTATE 2359 01:35:09,400 --> 01:35:11,440 CERTAIN FUNDING OPPORTUNITIES, 2360 01:35:11,440 --> 01:35:13,880 FEEL FREE TO DO SO AT THIS 2361 01:35:13,880 --> 01:35:14,080 POINT. 2362 01:35:14,080 --> 01:35:16,800 >>CRAIG, I WILL GO FIRST, IF 2363 01:35:16,800 --> 01:35:18,360 YOU DON'T MIND. 2364 01:35:18,360 --> 01:35:20,280 GM HAS A TECHNOLOGY DEVELOPMENT 2365 01:35:20,280 --> 01:35:21,480 PIPELINE I WOULD LIKE TO 2366 01:35:21,480 --> 01:35:21,840 HIGHLIGHT. 2367 01:35:21,840 --> 01:35:24,680 IT STARTS WITH A R-21 NOTICE OF 2368 01:35:24,680 --> 01:35:25,400 FUNDING OPPORTUNITY THAT 2369 01:35:25,400 --> 01:35:27,800 REQUIRES THAT THERE IS NO 2370 01:35:27,800 --> 01:35:29,760 PRELIMINARY DATA OR BIOLOGICAL 2371 01:35:29,760 --> 01:35:31,320 HYPOTHESES. 2372 01:35:31,320 --> 01:35:34,240 SO THIS IS VERY EARLY STAGES OF 2373 01:35:34,240 --> 01:35:35,880 TECHNOLOGY DEVELOPMENT. 2374 01:35:35,880 --> 01:35:38,200 A COMPANION FUNDING OPPORTUNITY 2375 01:35:38,200 --> 01:35:40,560 THAT IS AN RO1, THE OBJECTIVE IS 2376 01:35:40,560 --> 01:35:42,360 TO ALLOW FOR PROTOTYPE 2377 01:35:42,360 --> 01:35:43,360 VALIDATION WITHOUT HAVING TO 2378 01:35:43,360 --> 01:35:45,600 HAVE A BIOLOGICAL HYPOTHESES 2379 01:35:45,600 --> 01:35:46,400 ASSOCIATED WITH IT. 2380 01:35:46,400 --> 01:35:50,520 ONCE YOU DO HAVE THAT BIOLOGICAL 2381 01:35:50,520 --> 01:35:52,640 HYPOTHESIS, YOU CAN MOVE ON TO 2382 01:35:52,640 --> 01:35:58,520 THE TRADITIONAL PARENT RO1 OR 2383 01:35:58,520 --> 01:35:59,600 NIGMS MIRROR. 2384 01:35:59,600 --> 01:36:02,480 I WOULD BE HAPPY TO TALK ABOUT 2385 01:36:02,480 --> 01:36:04,320 LATER OR WITH SOMEONE OFFLINE. 2386 01:36:04,320 --> 01:36:06,000 I WOULD BE REMISS IF I DIDN'T 2387 01:36:06,000 --> 01:36:07,680 POINT OUT WE HAVE A FUNDING 2388 01:36:07,680 --> 01:36:09,400 OPPORTUNITY CALLED AN RM1. 2389 01:36:09,400 --> 01:36:14,400 THIS IS FOR, LET ME MAKE SURE I 2390 01:36:14,400 --> 01:36:18,040 GET THE ACRONYM CORRECT, 2391 01:36:18,040 --> 01:36:19,040 BIOMEDICAL TECHNOLOGY 2392 01:36:19,040 --> 01:36:21,320 OPTIMIZATION AND DISSEMINATION 2393 01:36:21,320 --> 01:36:21,560 CENTER. 2394 01:36:21,560 --> 01:36:25,760 THIS IS FOR STATE OF THE ART 2395 01:36:25,760 --> 01:36:29,920 LATE STAGE TECHNOLOGIES THAT 2396 01:36:29,920 --> 01:36:31,960 ADDRESSES BIOMEDICAL QUESTIONS 2397 01:36:31,960 --> 01:36:34,280 IN GM RELATED AREAS. 2398 01:36:34,280 --> 01:36:37,000 THE OBJECT ICH IS TO TRY AND 2399 01:36:37,000 --> 01:36:42,400 ENSURE WE CAN DISSEMINATE 2400 01:36:42,400 --> 01:36:44,760 TACTOLOGIES THAT ARE READY FOR 2401 01:36:44,760 --> 01:36:45,120 DISSEMINATION. 2402 01:36:45,120 --> 01:36:46,160 THE TECHNOLOGIES SHOULD BE AT 2403 01:36:46,160 --> 01:36:48,000 THE FOREFRONT OF THEIR FIELDS. 2404 01:36:48,000 --> 01:36:50,240 THEY ARE UNIQUE, BUT NOT WIDELY 2405 01:36:50,240 --> 01:36:51,680 AVAILABLE, DEMONSTRATED 2406 01:36:51,680 --> 01:36:54,000 FEASIBILITY OR UTILITY. 2407 01:36:54,000 --> 01:36:55,560 ONCE THEY ARE OPTIMIZED THROUGH 2408 01:36:55,560 --> 01:36:59,000 THIS PROCESS THEY CAN BE BROADLY 2409 01:36:59,000 --> 01:36:59,320 DISSEMINATED. 2410 01:36:59,320 --> 01:37:01,320 THAT IS AN RM1 THAT MIGHT BE OF 2411 01:37:01,320 --> 01:37:05,640 INTEREST TO SOME. 2412 01:37:05,640 --> 01:37:06,240 >>EXCELLENT. 2413 01:37:06,240 --> 01:37:09,440 THANK YOU SO MUCH, MICHELLE. 2414 01:37:09,440 --> 01:37:12,720 ANYTHING ELSE TO ADD FROM DR. 2415 01:37:12,720 --> 01:37:15,360 MOHAPATRA OR RANALLO? 2416 01:37:15,360 --> 01:37:18,320 >>I WILL ADD, WE DON'T HAVE ANY 2417 01:37:18,320 --> 01:37:21,840 DIRECT FOAs OR NOFOS. 2418 01:37:21,840 --> 01:37:23,400 THEY ARE MORE TANGENT. 2419 01:37:23,400 --> 01:37:28,600 WE ARE PARTICIPATING IN A PAR, A 2420 01:37:28,600 --> 01:37:32,360 PROGRAM ANNOUNCEMENT. 2421 01:37:32,360 --> 01:37:37,280 21-253, IDENTIFICATION OF ACTIVE 2422 01:37:37,280 --> 01:37:38,800 METABOLITES ON MICROBE DIET AND 2423 01:37:38,800 --> 01:37:40,480 HOST INTERACTIONS. 2424 01:37:40,480 --> 01:37:42,040 IT IS MULTI-IC. 2425 01:37:42,040 --> 01:37:43,400 IT IS VERY BROAD. 2426 01:37:43,400 --> 01:37:52,480 EACH IC HAS THEIR OWN INTEREST. 2427 01:37:52,480 --> 01:37:54,800 I WILL SAY THEY ARE VERY ROBUST 2428 01:37:54,800 --> 01:37:57,400 AND IT IS REALLY THE FUNCTIONAL 2429 01:37:57,400 --> 01:37:59,880 CURRENCY OF THOSE HOST MICROBE 2430 01:37:59,880 --> 01:38:01,200 INTERACTIONS AND WE ARE TRYING 2431 01:38:01,200 --> 01:38:03,600 TO ENCOURAGE IDENTIFICATION AND 2432 01:38:03,600 --> 01:38:04,800 CHARACTERIZATION OF THOSE SO WE 2433 01:38:04,800 --> 01:38:07,000 CAN UNDERSTAND THEIR BIOLOGY AND 2434 01:38:07,000 --> 01:38:10,840 LEVERAGE THEM FOR OUR MISSION. 2435 01:38:10,840 --> 01:38:12,040 I'LL STOP THERE. 2436 01:38:12,040 --> 01:38:12,320 >>GREAT. 2437 01:38:12,320 --> 01:38:15,800 THANK YOU. 2438 01:38:15,800 --> 01:38:22,200 >>I CAN JUST ADD THE SAME WAY, 2439 01:38:22,200 --> 01:38:27,160 AT NINDS WE DON'T HAVE A FOCUS 2440 01:38:27,160 --> 01:38:28,080 FUNDING FOR NATURAL PRODUCT 2441 01:38:28,080 --> 01:38:30,840 UNFORTUNATELY AT THIS POINT. 2442 01:38:30,840 --> 01:38:34,760 BUT WE HAVE MANY DIFFERENT 2443 01:38:34,760 --> 01:38:36,880 FUNDING OPPORTUNITIES FROM 2444 01:38:36,880 --> 01:38:41,920 DISCOVERY HYPOTHESIS TO 2445 01:38:41,920 --> 01:38:42,800 THERAPEUTIC RESEARCH 2446 01:38:42,800 --> 01:38:43,600 SPECIFICALLY IGNITE LIKE 2447 01:38:43,600 --> 01:38:47,920 PROGRAMS WHERE YOU CAN COME UP 2448 01:38:47,920 --> 01:38:49,920 WITH ANY MORTAL SYSTEM 2449 01:38:49,920 --> 01:38:51,080 DEVELOPMENT OR TECHNOLOGY 2450 01:38:51,080 --> 01:38:52,920 DEVELOPMENT -- MODEL SYSTEM 2451 01:38:52,920 --> 01:38:54,520 DEVELOPMENT OR TECHNOLOGY 2452 01:38:54,520 --> 01:38:57,800 DEVELOPMENT FOR THERAPEUTIC 2453 01:38:57,800 --> 01:38:58,920 SCREEN. 2454 01:38:58,920 --> 01:39:01,160 THOSE ARE ALL SUPPORTED AND WE 2455 01:39:01,160 --> 01:39:04,560 ARE INTERESTED AND COMMITTED AT 2456 01:39:04,560 --> 01:39:07,440 THE NATURAL PRODUCT IN THE 2457 01:39:07,440 --> 01:39:07,800 [INDISCERNIBLE]. 2458 01:39:07,800 --> 01:39:08,720 >>THANKS. 2459 01:39:08,720 --> 01:39:11,560 AND I THINK JUST TO CLARIFY, 2460 01:39:11,560 --> 01:39:14,480 THERE IS SOME LINGO, WHATEVER 2461 01:39:14,480 --> 01:39:16,840 YOU HAVE IN NIH GROUP, YOU HAVE 2462 01:39:16,840 --> 01:39:17,120 ACRONYMS. 2463 01:39:17,120 --> 01:39:20,960 THE TERM NOFO WAS THROWN OUT. 2464 01:39:20,960 --> 01:39:24,680 USED TO BE CALLED FOA, FUNDING 2465 01:39:24,680 --> 01:39:25,360 OPPORTUNITY ANNOUNCEMENT. 2466 01:39:25,360 --> 01:39:27,000 JUST IN THE LAST WEEKS OR 2467 01:39:27,000 --> 01:39:31,280 MONTHS, WE HAVE BEEN TOLD THEY 2468 01:39:31,280 --> 01:39:33,360 ARE CHANGING TO CALL IT NOTICE 2469 01:39:33,360 --> 01:39:36,200 OF FUNDING OPPORTUNITY, OR NOFO. 2470 01:39:36,200 --> 01:39:39,920 THIS ALIGNS NIH WITH WHAT OTHER 2471 01:39:39,920 --> 01:39:40,800 PARTS OF THE FEDERAL GOVERNMENT 2472 01:39:40,800 --> 01:39:43,000 ARE DOING IN TERMS OF HOW THEY 2473 01:39:43,000 --> 01:39:45,080 CALL -- WHAT THEY CALL THESE 2474 01:39:45,080 --> 01:39:45,320 THINGS. 2475 01:39:45,320 --> 01:39:47,200 WHICH WILL PROBABLY CONTINUE. 2476 01:39:47,200 --> 01:39:50,880 YOU WILL PROBABLY HEAR NOFO AND 2477 01:39:50,880 --> 01:39:52,200 FOA USED INTERCHANGEABLY. 2478 01:39:52,200 --> 01:39:54,560 IF YOU HEAR A NOFO AND DON'T 2479 01:39:54,560 --> 01:39:56,160 KNOW WHAT THAT MEANS AND THINK 2480 01:39:56,160 --> 01:39:57,920 IT IS AN INSULT, IT WAS NOT. 2481 01:39:57,920 --> 01:39:59,720 THAT IS WHAT WE ARE CALLING 2482 01:39:59,720 --> 01:40:02,040 THESE THINGS THESE DAYS. 2483 01:40:02,040 --> 01:40:04,440 I THINK I WILL TURN IT OVER TO 2484 01:40:04,440 --> 01:40:07,040 MY COLLEAGUE DR. STILL AND WE 2485 01:40:07,040 --> 01:40:11,080 WILL MAYBE TAKE SOME QUESTIONS 2486 01:40:11,080 --> 01:40:14,040 FROM THE VIDEOCAST AUDIENCE FOR 2487 01:40:14,040 --> 01:40:15,560 OUR NIH COLLEAGUES. 2488 01:40:15,560 --> 01:40:16,840 THANK YOU FOR ANSWERING THE 2489 01:40:16,840 --> 01:40:17,920 QUESTIONS WE HAD SO FAR. 2490 01:40:17,920 --> 01:40:19,520 GO AHEAD, PATRICK. 2491 01:40:19,520 --> 01:40:22,720 >>OKAY. 2492 01:40:22,720 --> 01:40:25,200 WE ARE MOVING INTO THE QUESTION 2493 01:40:25,200 --> 01:40:27,680 AND ANSWER SESSION AND I DON'T 2494 01:40:27,680 --> 01:40:29,880 SEE TOO MANY QUESTIONS IN THE 2495 01:40:29,880 --> 01:40:36,960 CHAT AS OF YET IN TERMS OF FOR 2496 01:40:36,960 --> 01:40:39,120 THE NIH COLLEAGUES. 2497 01:40:39,120 --> 01:40:40,360 I DID WANT TO MENTION IN 2498 01:40:40,360 --> 01:40:44,120 ADDITION TO WHAT NCI PUT 2499 01:40:44,120 --> 01:40:46,680 FORWARD, A NOTICE THAT THEY 2500 01:40:46,680 --> 01:40:50,880 RECENTLY RELEASED ON EXPANDING 2501 01:40:50,880 --> 01:40:51,520 TRANSLATIONALLY RELEVANT SPACE 2502 01:40:51,520 --> 01:40:53,680 AND THIS IS LOOKING FOR 2503 01:40:53,680 --> 01:40:55,200 APPLICATIONS IN DRUG DISCOVERY 2504 01:40:55,200 --> 01:40:58,440 AS IT RELATES TO IMMUNE 2505 01:40:58,440 --> 01:40:59,480 COMPOUNDS. 2506 01:40:59,480 --> 01:41:01,680 AND SO SOME OF THOSE HANDLES CAN 2507 01:41:01,680 --> 01:41:02,720 BE USED TO SEARCH THAT FUNDING 2508 01:41:02,720 --> 01:41:05,880 OPPORTUNITY. 2509 01:41:05,880 --> 01:41:07,760 AND I'M NOT SURE IF CRAIG, YOU 2510 01:41:07,760 --> 01:41:10,440 HAD MENTIONED PREVIOUSLY IN 2511 01:41:10,440 --> 01:41:13,280 TERMS OF NCCIH, BUT WE DID HAVE 2512 01:41:13,280 --> 01:41:15,480 A METHODS DEVELOPMENT NOTICE 2513 01:41:15,480 --> 01:41:18,720 THAT I DID WANT TO MAKE SURE 2514 01:41:18,720 --> 01:41:21,120 EVERYONE WAS AWARE OF AND THAT 2515 01:41:21,120 --> 01:41:25,840 EXPLAINS A LOT OF NCCIH'S 2516 01:41:25,840 --> 01:41:27,360 INTEREST IN THIS SPACE. 2517 01:41:27,360 --> 01:41:30,360 WE ARE FUNDING SOME INTERESTING 2518 01:41:30,360 --> 01:41:32,720 SMALL BUSINESS INVESTIGATIONS 2519 01:41:32,720 --> 01:41:35,560 LOOKING AT ELECTROKEMLY 2520 01:41:35,560 --> 01:41:39,440 CONDUCTIVE NANO MATERIALS AND 2521 01:41:39,440 --> 01:41:40,400 IMPROVING SEPARATION PERFORMANCE 2522 01:41:40,400 --> 01:41:41,640 AT A LOWER COST. 2523 01:41:41,640 --> 01:41:44,600 THAT WOULD FALL WITHIN OUR 2524 01:41:44,600 --> 01:41:46,400 MISSION IN ADDITION TO 2525 01:41:46,400 --> 01:41:50,200 ANNOTATING COMPLEX METABOLIC 2526 01:41:50,200 --> 01:41:50,480 DATASETS. 2527 01:41:50,480 --> 01:41:54,560 AND SO, YEAH. 2528 01:41:54,560 --> 01:41:57,000 SO IF WE DON'T HAVE ANY FURTHER 2529 01:41:57,000 --> 01:41:59,600 QUESTIONS FROM THE AUDIENCE, OH, 2530 01:41:59,600 --> 01:42:07,920 ONE JUST ACTUALLY CAME IN. 2531 01:42:07,920 --> 01:42:08,920 LET'S SEE. 2532 01:42:08,920 --> 01:42:10,560 I'M NOT SURE IF WAS A COMMENTS 2533 01:42:10,560 --> 01:42:15,960 OR AN ACTUAL QUESTION, BUT IT 2534 01:42:15,960 --> 01:42:17,960 INVOLVES, YEAH, I THINK WE CAN 2535 01:42:17,960 --> 01:42:20,200 MOVE PAST THAT ONE SINCE IT WAS 2536 01:42:20,200 --> 01:42:23,760 MORE OF A COMMENT FROM A 2537 01:42:23,760 --> 01:42:24,160 PREVIOUS SECTION. 2538 01:42:24,160 --> 01:42:25,680 >>THERE WAS A QUESTION, I 2539 01:42:25,680 --> 01:42:29,240 THINK, IT WAS A SECOND HALF OF A 2540 01:42:29,240 --> 01:42:31,680 COMMENT SOMEBODY HAD ASKING 2541 01:42:31,680 --> 01:42:33,800 WHICH INSTITUTES ARE INTERESTED 2542 01:42:33,800 --> 01:42:36,600 IN DRUG DISCOVERY APPLICATIONS? 2543 01:42:36,600 --> 01:42:39,400 AND MAYBE I WILL LET MY 2544 01:42:39,400 --> 01:42:39,960 COLLEAGUES INDICATE THEIR 2545 01:42:39,960 --> 01:42:41,280 INTEREST IN THAT TOPIC, WHICH I 2546 01:42:41,280 --> 01:42:45,800 KNOW THERE IS INTEREST. 2547 01:42:45,800 --> 01:42:51,000 >>YEAH. 2548 01:42:51,000 --> 01:42:59,720 DEFINITELY NINDS IS INTERESTED 2549 01:42:59,720 --> 01:43:00,400 INCLUDING NATURAL PRODUCT. 2550 01:43:00,400 --> 01:43:05,200 >>THIS IS RYAN. 2551 01:43:05,200 --> 01:43:07,880 I WILL ADD, FOR US, ONE OF THE 2552 01:43:07,880 --> 01:43:11,400 THINGS WE SET UP IN OUR 2553 01:43:11,400 --> 01:43:15,880 DIVISION, WE ARE INTERESTED IN 2554 01:43:15,880 --> 01:43:17,720 VACCINES DIAGNOSTICS AND WE HAVE 2555 01:43:17,720 --> 01:43:19,480 SCIENCE GRANT AWARDS, BUT 2556 01:43:19,480 --> 01:43:21,400 PARALLEL TO THOSE FUNDED 2557 01:43:21,400 --> 01:43:25,520 PROJECTS, WE ALSO HAVE A SUITE 2558 01:43:25,520 --> 01:43:28,120 OF CONTRACTS THAT SERVE THE -- 2559 01:43:28,120 --> 01:43:34,200 AS A PRECLINICAL SERVICES AT 2560 01:43:34,200 --> 01:43:34,600 NIAID. 2561 01:43:34,600 --> 01:43:37,800 THESE ARE FREE TO EXTERNAL 2562 01:43:37,800 --> 01:43:38,080 REQUESTERS. 2563 01:43:38,080 --> 01:43:40,840 ONE OF THE KEY REASONS I'M 2564 01:43:40,840 --> 01:43:42,320 MENTIONING IT IS ONCE YOU HAVE A 2565 01:43:42,320 --> 01:43:43,840 NATURAL PRODUCT WITH ACTIVITY 2566 01:43:43,840 --> 01:43:46,040 THAT YOU WANT TO EXPLORE MORE, 2567 01:43:46,040 --> 01:43:48,280 IT IS POSSIBLE TO DO IT THROUGH 2568 01:43:48,280 --> 01:43:52,000 A NONGRANT BASED MECHANISM. 2569 01:43:52,000 --> 01:43:53,320 AND THE SERVICES THAT ARE 2570 01:43:53,320 --> 01:43:54,280 SUPPORTED, SOME OF THE 2571 01:43:54,280 --> 01:43:55,720 SERVICES -- THERE ARE A LOT OF 2572 01:43:55,720 --> 01:43:58,360 SERVICES THAT ARE SUPPORTED, BUT 2573 01:43:58,360 --> 01:44:01,000 SOME IN THE CONTEXT OF OUR 2574 01:44:01,000 --> 01:44:11,400 DISCUSSION ARE IN VITRO 2575 01:44:11,680 --> 01:44:12,920 ANAMICROBIAL ACTION, AGAINST A 2576 01:44:12,920 --> 01:44:17,600 WHOLE SEETHE OF BACTERIA, ANIMAL 2577 01:44:17,600 --> 01:44:24,120 TESTING, PK, PD, AND IN VIVO 2578 01:44:24,120 --> 01:44:25,960 EFFICACY TESTING DEPENDING ON 2579 01:44:25,960 --> 01:44:28,240 THE AVAILABILITY OF A MODEL. 2580 01:44:28,240 --> 01:44:31,040 WE HAVE A DEAD KALTED AND 2581 01:44:31,040 --> 01:44:32,320 SUSTAINED EFFORT TO GET YOU OUT 2582 01:44:32,320 --> 01:44:34,280 OF THE VALLEY OF THE DEATH IF 2583 01:44:34,280 --> 01:44:37,240 YOU WILL WITH A LEAD AND MORE 2584 01:44:37,240 --> 01:44:38,280 TRANSLATIONAL FOOTING. 2585 01:44:38,280 --> 01:44:40,640 I WOULD BE HAPPY TO FOLLOW UP 2586 01:44:40,640 --> 01:44:43,440 WITH ANYBODY WHO IS LISTENING ON 2587 01:44:43,440 --> 01:44:45,240 THOSE ACTIVITIES. 2588 01:44:45,240 --> 01:44:48,200 IT IS AS SIMPLE AS PROVIDES A 2589 01:44:48,200 --> 01:44:50,120 LINK TO OUR NIAD PAGE. 2590 01:44:50,120 --> 01:44:52,040 I WILL STOP THERE. 2591 01:44:52,040 --> 01:44:55,840 >>I WILL BOOKEND THIS BY SAYING 2592 01:44:55,840 --> 01:44:58,280 NIGMS, IF YOU ARE SPECIFICALLY 2593 01:44:58,280 --> 01:45:00,200 STUDYING A DRUG OR SET OF DRUGS 2594 01:45:00,200 --> 01:45:04,280 FOR A UNIQUE DISEASE OR 2595 01:45:04,280 --> 01:45:05,880 DISORDER, IT IS MORE LIKELY IT 2596 01:45:05,880 --> 01:45:10,640 WILL GO TO A CATEGORICAL 2597 01:45:10,640 --> 01:45:12,400 INSTITUTE THAN NIGMS. 2598 01:45:12,400 --> 01:45:13,480 IF YOU HAVE QUESTIONS ABOUT 2599 01:45:13,480 --> 01:45:14,480 THIS, YOU ARE WELCOME TO REACH 2600 01:45:14,480 --> 01:45:24,640 OUT TO ME. 2601 01:45:28,560 --> 01:45:31,480 >>I THINK WE DID HAVE ANOTHER 2602 01:45:31,480 --> 01:45:32,480 QUESTION FROM PRIOR WHETHER 2603 01:45:32,480 --> 01:45:36,720 NCCIH IS LOOKING AT FUNCTIONAL 2604 01:45:36,720 --> 01:45:39,200 FOODS OR MEDICINAL FOOD RESEARCH 2605 01:45:39,200 --> 01:45:40,840 AND DEVELOPMENT AND COULD THIS 2606 01:45:40,840 --> 01:45:45,680 POTENTIALLY BE A NEW AVENUE TO 2607 01:45:45,680 --> 01:45:46,160 EXPLORE. 2608 01:45:46,160 --> 01:45:49,200 SO NCCIH IS PARTICIPATING IN THE 2609 01:45:49,200 --> 01:45:51,200 NUTRITION FOR PRECISION HEALTH 2610 01:45:51,200 --> 01:45:53,080 PROGRAM, WHICH IS PART OF THE 2611 01:45:53,080 --> 01:45:54,480 NIH COMMON FUND PROGRAM. 2612 01:45:54,480 --> 01:45:56,720 AND I BELIEVE, CRAIG, YOU ARE A 2613 01:45:56,720 --> 01:45:58,400 WORKING GROUP MEMBER FOR THIS 2614 01:45:58,400 --> 01:46:02,000 AND SO WE ARE INTERESTED IN THIS 2615 01:46:02,000 --> 01:46:02,200 AREA. 2616 01:46:02,200 --> 01:46:04,640 AND IF YOU WOULD LIKE TO FILL IN 2617 01:46:04,640 --> 01:46:06,120 WHAT THAT IS ABOUT. 2618 01:46:06,120 --> 01:46:07,280 >>YEAH. 2619 01:46:07,280 --> 01:46:09,760 THAT PROGRAM IS A VERY, VERY 2620 01:46:09,760 --> 01:46:11,000 LARGE FUND PROGRAM. 2621 01:46:11,000 --> 01:46:12,520 OVER $100 MILLION. 2622 01:46:12,520 --> 01:46:14,400 AND IT IS JUST BEGINNING, SO 2623 01:46:14,400 --> 01:46:16,080 THEY ARE ONLY GETTING STARTED. 2624 01:46:16,080 --> 01:46:19,040 THEY WILL BE ENROLLING THOUSANDS 2625 01:46:19,040 --> 01:46:21,600 AND THOUSANDS OF PEOPLE AND 2626 01:46:21,600 --> 01:46:23,480 LOOKING AT HOW THEIR DIETS, HOW 2627 01:46:23,480 --> 01:46:25,120 THEY VARY IN THEIR RESPONSE TO 2628 01:46:25,120 --> 01:46:25,800 SPECIFIC DIETS. 2629 01:46:25,800 --> 01:46:29,440 IT IS VERY EXCITING, BUT EARLY 2630 01:46:29,440 --> 01:46:31,720 STAGE FOR THAT. 2631 01:46:31,720 --> 01:46:32,360 REGARDING FUNCTIONAL FOOD AND 2632 01:46:32,360 --> 01:46:35,520 MEDICAL FOOD, SOME OF THOSE ARE 2633 01:46:35,520 --> 01:46:37,280 SPECIFIC TERMINOLOGIES AND NCCIH 2634 01:46:37,280 --> 01:46:39,800 COULD BE INTERESTED. 2635 01:46:39,800 --> 01:46:42,120 OBVIOUSLY, WE HAVE A LONG 2636 01:46:42,120 --> 01:46:44,480 STANDING INTEREST IN FUNDING 2637 01:46:44,480 --> 01:46:46,040 DIETARY SUPPLEMENT RESEARCH. 2638 01:46:46,040 --> 01:46:47,480 WE FUND QUITE A BIT CURRENTLY. 2639 01:46:47,480 --> 01:46:49,720 IF YOU ARE LOOKING AT PARTICULAR 2640 01:46:49,720 --> 01:46:51,240 FUNCTIONAL FOODS OR MEDICAL 2641 01:46:51,240 --> 01:46:53,480 FOODS IT IS BEST TO REACH OUT 2642 01:46:53,480 --> 01:46:55,400 OFFLINE AND WE COULD HAVE A MORE 2643 01:46:55,400 --> 01:46:56,200 DETAILED CONVERSATION ABOUT WHAT 2644 01:46:56,200 --> 01:46:59,360 IT IS YOU WANT TO DO AND WHETHER 2645 01:46:59,360 --> 01:47:05,040 OR NOT NCCIH SHOULD BE THE BEST. 2646 01:47:05,040 --> 01:47:09,280 NIDDK, ALSO FUNDS QUITE A BIT OF 2647 01:47:09,280 --> 01:47:10,920 NUTRITION RESEARCH AT NIH. 2648 01:47:10,920 --> 01:47:12,600 DEPENDING ON WHAT YOU ARE 2649 01:47:12,600 --> 01:47:12,880 PROPOSING. 2650 01:47:12,880 --> 01:47:15,080 IT MIGHT BE APPROPRIATE FOR US 2651 01:47:15,080 --> 01:47:16,040 OR IT MIGHT BE MORE APPROPRIATE 2652 01:47:16,040 --> 01:47:26,200 FOR THEM. 2653 01:47:29,760 --> 01:47:31,520 I SEE ANOTHER COMMENT HERE TO 2654 01:47:31,520 --> 01:47:33,840 REMIND US THERE IS AN RFI, A 2655 01:47:33,840 --> 01:47:36,280 REQUEST FOR INFORMATION, ON A -- 2656 01:47:36,280 --> 01:47:40,360 THERE WAS RECENTLY A WHITE HOUSE 2657 01:47:40,360 --> 01:47:41,600 CONFERENCE ON NUTRITION AND 2658 01:47:41,600 --> 01:47:41,880 HUNGER. 2659 01:47:41,880 --> 01:47:43,600 I'M FORGETTING EXACTLY THE NAME 2660 01:47:43,600 --> 01:47:44,440 OF IT. 2661 01:47:44,440 --> 01:47:47,120 THIS CONCEPT OF FOOD AS MEDICINE 2662 01:47:47,120 --> 01:47:48,960 HAS COME OUT OF THAT. 2663 01:47:48,960 --> 01:47:53,200 AND THERE IS AN EFFORT TO GET 2664 01:47:53,200 --> 01:47:56,200 INPUT BASICALLY ON WHERE NIH AND 2665 01:47:56,200 --> 01:47:57,880 THE FEDERAL GOVERNMENT WRIT 2666 01:47:57,880 --> 01:47:59,960 LARGE, WHERE SHOULD WE BE 2667 01:47:59,960 --> 01:48:02,000 FOCUSING OUR EFFORTS WHEN IT 2668 01:48:02,000 --> 01:48:03,920 COMES TO THIS CONCEPT OF FOOD AS 2669 01:48:03,920 --> 01:48:04,200 MEDICINE. 2670 01:48:04,200 --> 01:48:06,040 THIS HAS A LOT OF THREADS TO IT. 2671 01:48:06,040 --> 01:48:09,200 SOME OF WHICH ARE RELATED TO NIH 2672 01:48:09,200 --> 01:48:11,240 SPECIFICALLY AND A LOT OF THEM 2673 01:48:11,240 --> 01:48:13,440 ARE ABOUT ACCESS TO HEALTHY 2674 01:48:13,440 --> 01:48:14,880 FOODS AND FOOD INSECURITY. 2675 01:48:14,880 --> 01:48:18,320 IT IS A VERY WIDE RANGING 2676 01:48:18,320 --> 01:48:19,640 CONCEPT. 2677 01:48:19,640 --> 01:48:21,160 CERTAINLY SOME PARTS ARE 2678 01:48:21,160 --> 01:48:24,200 RELEVANT TO NIH AND NCCIH'S 2679 01:48:24,200 --> 01:48:34,240 INTERESTS. 2680 01:48:34,240 --> 01:48:34,800 >>GREAT. 2681 01:48:34,800 --> 01:48:38,240 AND THANKS, CRAIG, FOR THAT. 2682 01:48:38,240 --> 01:48:40,600 AND I SEE THAT WE'RE A LITTLE 2683 01:48:40,600 --> 01:48:44,040 BIT AHEAD OF TIME IN TERMS OF 2684 01:48:44,040 --> 01:48:49,080 THE Q&A, WHICH IS TO WRAP UP 2685 01:48:49,080 --> 01:48:51,480 AROUND 2:50 EASTERN TIME. 2686 01:48:51,480 --> 01:48:53,720 SO NOW THAT WE ARE NOT REALLY 2687 01:48:53,720 --> 01:48:54,760 SEEING ANY ADDITIONAL QUESTIONS 2688 01:48:54,760 --> 01:48:59,200 IN THE CHAT, WE CAN MOVE TO 2689 01:48:59,200 --> 01:49:00,240 THANKING THE SPEAKERS. 2690 01:49:00,240 --> 01:49:04,600 WE COVERED QUITE A FEW TOPICS 2691 01:49:04,600 --> 01:49:06,840 TODAY FROM SINGLE PARTICLE 2692 01:49:06,840 --> 01:49:11,320 CRYO-EM TO THE STRUCTURE OF THE 2693 01:49:11,320 --> 01:49:16,240 TRYP ION CHANNEL TO LOOKING AT 2694 01:49:16,240 --> 01:49:21,600 CRYO-EM IN GENERAL AND ALSO, YOU 2695 01:49:21,600 --> 01:49:25,040 KNOW, WE DISCUSSED DIFFERENT 2696 01:49:25,040 --> 01:49:26,360 PROGRAMATIC PRIORITIES ACROSS 2697 01:49:26,360 --> 01:49:26,920 THE NIH. 2698 01:49:26,920 --> 01:49:29,160 SO WE JUST WANTED TO THANK 2699 01:49:29,160 --> 01:49:32,720 EVERYBODY FOR JOINING THE 2700 01:49:32,720 --> 01:49:34,080 WEBINAR TODAY AND I'M NOT SURE, 2701 01:49:34,080 --> 01:49:36,640 CRAIG, IF YOU HAD ANY ADDITIONAL 2702 01:49:36,640 --> 01:49:38,280 CLOSING REMARKS, THAT WOULD BE 2703 01:49:38,280 --> 01:49:38,480 GREAT? 2704 01:49:38,480 --> 01:49:39,360 >>YEAH. 2705 01:49:39,360 --> 01:49:40,080 THANKS, PAT. 2706 01:49:40,080 --> 01:49:42,520 I THINK YOU SUMMED UP NICELY. 2707 01:49:42,520 --> 01:49:44,920 IT IS A VERY EXCITING 2708 01:49:44,920 --> 01:49:47,400 TECHNOLOGIES THAT I'M LOOKING 2709 01:49:47,400 --> 01:49:51,440 FORWARD TO WHERE THEY WILL LEAD 2710 01:49:51,440 --> 01:49:52,360 US AS WE HEARD, YOU KNOW, 2711 01:49:52,360 --> 01:49:56,480 ESPECIALLY RELATED TO CRYO-EM. 2712 01:49:56,480 --> 01:50:00,280 IT SEEMS LIKE WE ARE SCRATCHING 2713 01:50:00,280 --> 01:50:01,560 THE SURFACE. 2714 01:50:01,560 --> 01:50:04,440 DR. CASSILLY POINTED OUT, YOU 2715 01:50:04,440 --> 01:50:07,760 DON'T HAVE TO HAVE THE LATEST 2716 01:50:07,760 --> 01:50:09,400 MILLION-DOLLAR INSTRUMENT TO DO 2717 01:50:09,400 --> 01:50:11,000 IMPACTFUL RESEARCH. 2718 01:50:11,000 --> 01:50:15,680 THEY DID THE OLD BIOACTIVITY 2719 01:50:15,680 --> 01:50:17,560 GUIDE FRACTIONATION. 2720 01:50:17,560 --> 01:50:19,360 YOU DON'T HAVE TO HAVE THE MOST 2721 01:50:19,360 --> 01:50:21,240 INCREDIBLE STRUCTURE TO HAVE THE 2722 01:50:21,240 --> 01:50:22,920 MOST INCREDIBLE IMPACT. 2723 01:50:22,920 --> 01:50:25,880 THE STRUCTURE SHE DISCOVERED WAS 2724 01:50:25,880 --> 01:50:28,760 AS SHE SAID A FAIRLY COMMON OR 2725 01:50:28,760 --> 01:50:30,680 NOT TERRIBLY UNIQUE STRUCTURE, 2726 01:50:30,680 --> 01:50:33,520 BUT YET THAT SEEMED TO BE VERY 2727 01:50:33,520 --> 01:50:36,040 IMPORTANT FOR MODULATING THE 2728 01:50:36,040 --> 01:50:38,040 ACTIVITY WE ASSOCIATE WITH THAT 2729 01:50:38,040 --> 01:50:40,920 PARTICULAR PRO BIOTIC COMPOUND. 2730 01:50:40,920 --> 01:50:42,520 WE ENCOURAGE ALL THOSE IN 2731 01:50:42,520 --> 01:50:45,000 ATTENDANCE TO REACH OUT TO THOSE 2732 01:50:45,000 --> 01:50:47,040 AT NIH THAT MIGHT BE MOST 2733 01:50:47,040 --> 01:50:49,040 RELEVANT TO WHAT YOU ARE DOING. 2734 01:50:49,040 --> 01:50:51,560 WE ALL ACTIVELY SUPPORT NATURAL 2735 01:50:51,560 --> 01:50:52,320 PRODUCTS RESEARCH AND WE WILL 2736 01:50:52,320 --> 01:50:53,640 CONTINUE TO DO SO. 2737 01:50:53,640 --> 01:50:55,720 WE LOOK FORWARD TO SEEING YOUR 2738 01:50:55,720 --> 01:50:58,480 APPLICATIONS AND INTERESTS AND 2739 01:50:58,480 --> 01:50:58,760 INQUIRIES. 2740 01:50:58,760 --> 01:51:00,640 AND THIS VIDEOCAST HAS BEEN 2741 01:51:00,640 --> 01:51:03,600 RECORDED AND YOU, IF YOU WERE 2742 01:51:03,600 --> 01:51:05,880 REGISTER, IF YOU ARE ON THIS, 2743 01:51:05,880 --> 01:51:10,040 YOU WILL GET AN EMAIL ALERTING 2744 01:51:10,040 --> 01:51:11,600 YOU TO WHEN THE LINK IS 2745 01:51:11,600 --> 01:51:13,440 AVAILABLE FOR THE VIDEOCAST. 2746 01:51:13,440 --> 01:51:16,040 YOU CAN REWATCH PARTS OF THIS OR 2747 01:51:16,040 --> 01:51:19,600 SHARE WITH COLLEAGUES WHO MIGHT 2748 01:51:19,600 --> 01:51:20,760 BE INTERESTED. 2749 01:51:20,760 --> 01:51:22,360 WITH THAT, WE WILL WRAP THINGS 2750 01:51:22,360 --> 01:51:23,400 UP. 2751 01:51:23,400 --> 01:51:25,200 I THANK YOU ALL OF MY NIH 2752 01:51:25,200 --> 01:51:27,000 COLLEAGUES FOR YOUR 2753 01:51:27,000 --> 01:51:28,320 PARTICIPATION AND ALL OF THOSE 2754 01:51:28,320 --> 01:51:29,480 ATTENDING AND ASKED QUESTIONS 2755 01:51:29,480 --> 01:51:32,400 AND HOPEFULLY WERE INSPIRED BY 2756 01:51:32,400 --> 01:51:34,480 SOME WAY, SHAPE OR FORM WITH 2757 01:51:34,480 --> 01:51:35,240 WHAT YOU HEARD TODAY. 2758 01:51:35,240 --> 01:51:36,080 WITH THAT, I GUESS MAYBE WE WILL 2759 01:51:36,080 --> 01:51:37,000 SIGN OFF. 2760 01:51:37,000 --> 01:51:48,000 THANK YOU, EVERYONE.