1 00:00:05,400 --> 00:00:08,400 >>I'M FROM 2 00:00:08,400 --> 00:00:13,480 THE MALIGNANCY BRANCH AND I HAVE 3 00:00:13,480 --> 00:00:18,080 THE HONOR AND PRIVILEGE TO 4 00:00:18,080 --> 00:00:20,240 INTRODUCE TODAY'S SPEAKER. 5 00:00:20,240 --> 00:00:24,360 AND THE REASON IS THAT I HAVE 6 00:00:24,360 --> 00:00:25,560 KNOWN AMIRAN DZUTSEV FOR QUITE 7 00:00:25,560 --> 00:00:27,640 SOME TIME BECAUSE WE'VE BEEN 8 00:00:27,640 --> 00:00:28,160 DISCUSSING ALF SCIENCE AND 9 00:00:28,160 --> 00:00:29,360 DIFFERENT RESEARCH PROJECTS AND 10 00:00:29,360 --> 00:00:35,360 WE WERE KIND OF IN SIMILAR YEARS 11 00:00:35,360 --> 00:00:37,000 SO I'M HAPPY TO INTRODUCE HIM. 12 00:00:37,000 --> 00:00:38,480 AMIRAN DZUTSEV GOT HIS TRAINING 13 00:00:38,480 --> 00:00:43,560 AS AN MD AT THE NORTH STATE 14 00:00:43,560 --> 00:00:45,080 MEDICAL ACADEMIA IN RUSSIA 15 00:00:45,080 --> 00:00:49,040 RUSSIA AND HAD A PH.D IN RUSSIA 16 00:00:49,040 --> 00:00:51,240 AND HE CAME TO THE NCI, I 17 00:00:51,240 --> 00:00:57,400 BELIEVE IN 2003 AS A POSTDOC. 18 00:00:57,400 --> 00:01:00,360 HE SPENT A COUPLE OF YEARS WITH 19 00:01:00,360 --> 00:01:03,000 2009 WHERE HE WAS WORKING ON 20 00:01:03,000 --> 00:01:05,880 QUESTIONS IN MUCOSAL IMMUNOLOGY 21 00:01:05,880 --> 00:01:09,040 AND THEN HE MOVED ON AND WENT TO 22 00:01:09,040 --> 00:01:11,840 THE GROUP OF GEORGIA THAT 23 00:01:11,840 --> 00:01:13,640 CHANGED THE NAME SEVERAL TIMES 24 00:01:13,640 --> 00:01:15,840 AND I ALWAYS FORGET THE NAME 25 00:01:15,840 --> 00:01:16,840 THAT IT'S RIGHT NOW. 26 00:01:16,840 --> 00:01:21,480 IN THE END, HE REALLY LED SOME 27 00:01:21,480 --> 00:01:25,000 PIVOTAL STUDIES AND INVOLVED 28 00:01:25,000 --> 00:01:26,800 STUDYING THE GUT MICROBIOME AND 29 00:01:26,800 --> 00:01:28,360 HOW THE GUT MICROBIOME MAY 30 00:01:28,360 --> 00:01:33,480 AFFECT OUTCOME OF CHEMOTHERAPY, 31 00:01:33,480 --> 00:01:35,440 IMMUNOTHERAPY, AND NOT ONLY IN 32 00:01:35,440 --> 00:01:38,160 ANIMAL STUDIES BUT ALSO IN 33 00:01:38,160 --> 00:01:39,040 CLINICAL TRIALS. 34 00:01:39,040 --> 00:01:41,680 PART OF THEM BEING CONDUCTED 35 00:01:41,680 --> 00:01:44,080 HERE AND THEN A LOT OF THEM ALSO 36 00:01:44,080 --> 00:01:47,400 IN COLLABORATION WITH OUTSIDE 37 00:01:47,400 --> 00:01:50,440 INVESTIGATORS IN THE CONTEXT OF 38 00:01:50,440 --> 00:01:54,320 MAINLY MELANOMA AND IMMUNE 39 00:01:54,320 --> 00:01:55,800 CHECKPOINT INHIBITOR THEORY. 40 00:01:55,800 --> 00:01:59,400 HE HAS A GREAT EXPERTISE IN THIS 41 00:01:59,400 --> 00:02:04,920 CHILD FIELD. 42 00:02:04,920 --> 00:02:07,720 HE IS ONE OF THE PRIVILEGED 43 00:02:07,720 --> 00:02:09,440 INDIVIDUALS WHO DO NOT ONLY KNOW 44 00:02:09,440 --> 00:02:12,000 THE MEDICINE BUT BASED ON HIS 45 00:02:12,000 --> 00:02:13,480 TRAINING AND IMMUNOLOGY BUT 46 00:02:13,480 --> 00:02:15,200 TOWARDS A VERY GOOD IN 47 00:02:15,200 --> 00:02:17,480 MATHEMATICS AND BIO INFORMATICS 48 00:02:17,480 --> 00:02:21,240 WHICH IS OBVIOUSLY KEY WHEN YOU 49 00:02:21,240 --> 00:02:22,640 WORK WITH ALL THAT DATA. 50 00:02:22,640 --> 00:02:25,320 I DON'T WANT TO TAKE MORE OF HIS 51 00:02:25,320 --> 00:02:26,000 TIME. 52 00:02:26,000 --> 00:02:28,400 WITHOUT FURTHER ADIEU, AMIRAN 53 00:02:28,400 --> 00:02:32,480 DZUTSEV WE'RE LOOKING FORWARD TO 54 00:02:32,480 --> 00:02:35,840 YOUR TALK. 55 00:02:35,840 --> 00:02:36,640 >>Dr. Dzutsev: THANK YOU VERY 56 00:02:36,640 --> 00:02:36,840 MUCH. 57 00:02:36,840 --> 00:02:39,000 IT'S A VERY KIND INTRODUCTION 58 00:02:39,000 --> 00:02:41,120 AND THANK YOU TO OUR DIRECTORS, 59 00:02:41,120 --> 00:02:43,200 THOMAS, FOR GIVING ME THE 60 00:02:43,200 --> 00:02:43,840 OPPORTUNITY TO PRESENT OUR WORK 61 00:02:43,840 --> 00:02:45,480 IN FRONT OF YOU. 62 00:02:45,480 --> 00:02:50,600 THAT IS A PRIVILEGE. 63 00:02:50,600 --> 00:02:51,920 SO I STILL ALREADY I'M GOING TO 64 00:02:51,920 --> 00:02:57,560 BE TALKING ABOUT THE MICROBIOME. 65 00:02:57,560 --> 00:02:58,240 SO WHAT IS MICROBIOME IN 66 00:02:58,240 --> 00:03:00,000 GENERAL? 67 00:03:00,000 --> 00:03:04,600 SO MICROBIOME IS A COLLECTION OF 68 00:03:04,600 --> 00:03:05,760 DIFFERENT MICROBES THAT OCCUPY 69 00:03:05,760 --> 00:03:07,440 THE SAME NICHE IN THE ORGANISM. 70 00:03:07,440 --> 00:03:10,720 THIS MICROS BUILDING TO MULTIPLE 71 00:03:10,720 --> 00:03:11,960 DIFFERENT MEMBERS OF THE TREE OF 72 00:03:11,960 --> 00:03:12,560 LIFE. 73 00:03:12,560 --> 00:03:17,200 SO THEY CAN COME FROM BACTERIA 74 00:03:17,200 --> 00:03:19,400 SPECIES, FROM FUNGI, BACTERIA, 75 00:03:19,400 --> 00:03:26,320 FROM THE VIRUSES, PROTOZOA AND 76 00:03:26,320 --> 00:03:28,240 OF COURSE THE MOST ABUNDANT OF 77 00:03:28,240 --> 00:03:31,760 THEM ALL IS BACTERIA AND HOW 78 00:03:31,760 --> 00:03:34,520 DIVERSE HUMAN BACTERIA 79 00:03:34,520 --> 00:03:35,720 MICROBIOME AND EXTREMELY 80 00:03:35,720 --> 00:03:36,480 DIVERSE. 81 00:03:36,480 --> 00:03:40,480 THERE ARE THOUSANDS OF SPECIES 82 00:03:40,480 --> 00:03:42,520 OF DIFFERENT -- HUNDREDS OF 83 00:03:42,520 --> 00:03:43,320 THOUSANDS OF STRAINS THAT 84 00:03:43,320 --> 00:03:44,760 CONTAINS HUNDREDS OF THOUSANDS 85 00:03:44,760 --> 00:03:46,960 OF DIFFERENT GENES THAT HAVE 86 00:03:46,960 --> 00:03:49,200 VARIETY OF DIFFERENT FUNCTIONS 87 00:03:49,200 --> 00:03:52,600 THAT OCCUPY OUR BODIES AND THE 88 00:03:52,600 --> 00:03:55,240 SIDE THAT IS THE MOST IN THIS 89 00:03:55,240 --> 00:03:56,760 BACTERIA IN TERMS OF THE SPECIES 90 00:03:56,760 --> 00:04:02,280 AND THE DIVERSITIES AND THE 91 00:04:02,280 --> 00:04:04,000 NUMBERS, IS THE G.I. TRACT. 92 00:04:04,000 --> 00:04:09,280 AS YOU CAN SEE HERE, THE STOOL 93 00:04:09,280 --> 00:04:10,400 MICROBIOME IS REPRESENTED THE 94 00:04:10,400 --> 00:04:10,720 MOST. 95 00:04:10,720 --> 00:04:14,040 SO WHAT IS THE EFFECT OF 96 00:04:14,040 --> 00:04:14,920 SPECIFICALLY GUT MICROBIOME ON 97 00:04:14,920 --> 00:04:16,200 HUMAN HEALING AND DISEASE AND 98 00:04:16,200 --> 00:04:21,840 IT'S EXTREMELY DEPENDENT ON THE 99 00:04:21,840 --> 00:04:26,200 HEALTH OF THE G.I. TRACT 100 00:04:26,200 --> 00:04:26,800 MICROBIOTA. 101 00:04:26,800 --> 00:04:29,040 WE KNOW ALREADY THAT MICROBIOME 102 00:04:29,040 --> 00:04:31,240 EFFECTS MANY ASPECTS OF THE 103 00:04:31,240 --> 00:04:33,600 SYSTEMIC DISEASES. 104 00:04:33,600 --> 00:04:38,400 IT EFFECTS DEVELOPMENT OF THE 105 00:04:38,400 --> 00:04:38,680 COLITIS. 106 00:04:38,680 --> 00:04:41,880 IT EFFECTS EVEN THE BRAIN 107 00:04:41,880 --> 00:04:45,800 DISORDERS SUCH AS ATTENTION 108 00:04:45,800 --> 00:04:47,200 DEFICITS, THE ALZHEIMER'S, 109 00:04:47,200 --> 00:04:49,680 PARKINSON'S DISEASE, 110 00:04:49,680 --> 00:04:51,840 DEPRESSIONS, ALSO IT HAS AN 111 00:04:51,840 --> 00:04:53,600 EFFECT ON CARDIOVASCULAR 112 00:04:53,600 --> 00:04:54,240 DISEASES. 113 00:04:54,240 --> 00:04:55,680 BUT THE THINGS THAT IT EFFECTS 114 00:04:55,680 --> 00:05:00,840 THE MOST IS THE IMMUNE SYSTEM. 115 00:05:00,840 --> 00:05:02,720 AND MICROBIOME HAS EFFECTS ON 116 00:05:02,720 --> 00:05:05,480 BOTH LOCAL LEON IMMUNE SYSTEMS 117 00:05:05,480 --> 00:05:07,440 AND GLOBALLY. 118 00:05:07,440 --> 00:05:08,400 LOCALLY, IT'S MORE OBVIOUS THING 119 00:05:08,400 --> 00:05:10,080 TO EXPECT FROM MICROBIOME AFTER 120 00:05:10,080 --> 00:05:14,640 ALL IT'S A BACTERIA THAT IS A 121 00:05:14,640 --> 00:05:16,800 FOREIGN BODY TO OURSELVES AND 122 00:05:16,800 --> 00:05:19,720 THE FACT THAT WE'RE OBSERVED 123 00:05:19,720 --> 00:05:22,320 GLOBALLY CONCERNS NOT ONLY IN 124 00:05:22,320 --> 00:05:24,000 THE LIMP NODES THAT DRAIN ALL 125 00:05:24,000 --> 00:05:26,880 THESE PERIPHERAL SITES SUCH AS 126 00:05:26,880 --> 00:05:28,800 RESPIRATORY SYSTEM G.I., TRACT, 127 00:05:28,800 --> 00:05:31,520 ET CETERA BUT ALSO THINGS LIKE 128 00:05:31,520 --> 00:05:35,680 BONE MARROW AND INTERNAL ORGANS 129 00:05:35,680 --> 00:05:37,520 INCLUDING ALSO THE TUMOR THAT IS 130 00:05:37,520 --> 00:05:39,720 A FOREIGN BODY BUT NEVERTHELESS 131 00:05:39,720 --> 00:05:45,240 ORIGINATES FROM INTERNAL ORGANS. 132 00:05:45,240 --> 00:05:48,080 SO FOCUSING ON THE LARGEST SIDE 133 00:05:48,080 --> 00:05:53,680 OF THE INTERACTION OF MICROBIOTA 134 00:05:53,680 --> 00:05:55,720 WITH THE HOST THE G.I. TRACT, 135 00:05:55,720 --> 00:05:57,920 THE G.I. TRACT BOTH SMALL 136 00:05:57,920 --> 00:05:59,760 INTESTINE AND THE LARGE 137 00:05:59,760 --> 00:06:01,440 INTESTINE HAVE A LARGE NUMBER OF 138 00:06:01,440 --> 00:06:03,800 MICK ROW ORGANISMS THAT INHABIT 139 00:06:03,800 --> 00:06:05,880 IT AND THEY EFFECT IMMUNE 140 00:06:05,880 --> 00:06:07,400 SYSTEMS, NOT JUST BY SOMETHING 141 00:06:07,400 --> 00:06:11,000 THAT WE WOULD EXPECT WHICH IS 142 00:06:11,000 --> 00:06:12,640 BACTERIAL PRODUCTS, AND THINGS 143 00:06:12,640 --> 00:06:15,200 LIKE THAT BUT ALSO BY THE 144 00:06:15,200 --> 00:06:18,200 METABOLITES WHICH WE VERY WELL 145 00:06:18,200 --> 00:06:21,040 KNOW ALREADY HAVE AN EFFECT, 146 00:06:21,040 --> 00:06:24,360 SUCH AS SHORT CHAIN FATTY ACIDS 147 00:06:24,360 --> 00:06:26,320 AND DIFFERENT TYPES OF 148 00:06:26,320 --> 00:06:28,240 METABOLITES AND IT EFFECTS THE 149 00:06:28,240 --> 00:06:29,280 SYSTEM IN MULTIPLE DIFFERENT 150 00:06:29,280 --> 00:06:29,640 WAYS. 151 00:06:29,640 --> 00:06:32,000 I'M GOING TO ACTUALLY START 152 00:06:32,000 --> 00:06:35,240 TALKING ABOUT THE INTERACTION OF 153 00:06:35,240 --> 00:06:39,400 THE MICROBIOTA WITH THE HOST, 154 00:06:39,400 --> 00:06:41,680 SPEAKING ABOUT THE COLON. 155 00:06:41,680 --> 00:06:43,920 COLON HAS, AS I JUST MENTIONED, 156 00:06:43,920 --> 00:06:46,240 THE LARGEST NUMBER OF BACTERIAL 157 00:06:46,240 --> 00:06:48,680 SPECIES IN THE BODY. 158 00:06:48,680 --> 00:06:52,080 IT HAS ABOUT 1,000 TIMES MORE 159 00:06:52,080 --> 00:06:53,160 MICROBES THAN SMALL INTESTINE 160 00:06:53,160 --> 00:06:57,000 AND YET SURPRISINGLY, THE VAST 161 00:06:57,000 --> 00:06:58,480 MAJORITY OF THE G.I. TRUTH 162 00:06:58,480 --> 00:07:00,400 IMMUNE SYSTEM IS IN THE SMALL AT 163 00:07:00,400 --> 00:07:00,800 THE SCENE TIN. 164 00:07:00,800 --> 00:07:03,880 COLON ON THE OTHER HAND, HAS 165 00:07:03,880 --> 00:07:06,600 VERY VIEW FORWARD STRUCTURES 166 00:07:06,600 --> 00:07:09,720 THAT ARE RANDOMLY DISBURSED THAT 167 00:07:09,720 --> 00:07:11,440 ARE CALLED COLON I CAN PATCH. 168 00:07:11,440 --> 00:07:14,480 THEY LOOK LIKE AND THE FUNCTION 169 00:07:14,480 --> 00:07:18,600 LOOK LIKE VERY SMALL NODULES HE 170 00:07:18,600 --> 00:07:20,800 EMBEDDED IN THE TISSUE OF THE 171 00:07:20,800 --> 00:07:21,080 G.I. TRACT. 172 00:07:21,080 --> 00:07:24,280 AND THEY DO HAVE ALL THE 173 00:07:24,280 --> 00:07:29,280 FEATURES OF THE LYMPH NODES. 174 00:07:29,280 --> 00:07:32,520 THEY HAVE B. CELLS, SPECIALIZED 175 00:07:32,520 --> 00:07:35,320 TYPE OF STROM OWE CELLS AND IN 176 00:07:35,320 --> 00:07:38,520 THE COLON, THIS ORGAN, THIS 177 00:07:38,520 --> 00:07:41,680 PATCH IS SEPARATED FROM THE WITH 178 00:07:41,680 --> 00:07:52,440 A THIN LAYER OF ONE OVER THE OVP 179 00:07:52,440 --> 00:07:53,200 A THEELY YUM. 180 00:07:53,200 --> 00:07:55,840 IF THEY LOOK FLAT IN THE COLON 181 00:07:55,840 --> 00:07:56,320 IT'S CALLED DOME. 182 00:07:56,320 --> 00:08:01,360 THIS IS THE SINGLE EPITHELIAL. 183 00:08:01,360 --> 00:08:07,120 IT'S SURROUNDED BY CRYPTS. 184 00:08:07,120 --> 00:08:09,680 IN CONTRAST, DOME DOESN'T HAVE 185 00:08:09,680 --> 00:08:11,880 THE MUCUS SO IT ACTUALLY IS MORE 186 00:08:11,880 --> 00:08:13,680 EXPOSED TO THE CONTENT COMPARED 187 00:08:13,680 --> 00:08:17,960 TO THE OTHER PLACES IN THE G.I. 188 00:08:17,960 --> 00:08:18,160 TRACT. 189 00:08:18,160 --> 00:08:22,800 SO WE WANTED TO STUDY THE 190 00:08:22,800 --> 00:08:23,400 INTERACTION OF THE MICROBIOME 191 00:08:23,400 --> 00:08:26,080 HOST IN THE COLON AND AS A MODEL 192 00:08:26,080 --> 00:08:29,520 WE CHOSE TO REPLACE MICROBIOTA 193 00:08:29,520 --> 00:08:32,480 WITH DIFFERENT SIZES OF 194 00:08:32,480 --> 00:08:34,280 NANOPARTICLES. 195 00:08:34,280 --> 00:08:36,360 THESE WERE VERY DENSE SIZE FROM 196 00:08:36,360 --> 00:08:41,120 20 TO 1,000 NANOMETERS. 197 00:08:41,120 --> 00:08:43,120 FOR REFERENCE, THE SIZE OF THE 198 00:08:43,120 --> 00:08:45,440 BACTERIA IS TYPICALLY LARGER 199 00:08:45,440 --> 00:08:48,040 THAN 200 NANOMETERS SO THESE ARE 200 00:08:48,040 --> 00:08:50,360 MUCH SMALLER IN THE SIZE OF THE 201 00:08:50,360 --> 00:08:51,040 VIRUSES. 202 00:08:51,040 --> 00:08:54,520 BUT WHEN WE LOOKED AT THE COLON 203 00:08:54,520 --> 00:09:03,320 I COLICWE SAW THE BEADS WHICH WS 204 00:09:03,320 --> 00:09:06,520 THAN NANOMETERS OF SIZE, THE 205 00:09:06,520 --> 00:09:10,080 SMALLER END OF OUR TESTED SAMPLE 206 00:09:10,080 --> 00:09:11,960 SIZES OF THE BEATS WERE ABLE TO 207 00:09:11,960 --> 00:09:15,600 TRUST INTO THE COLON I CAN PATCH 208 00:09:15,600 --> 00:09:15,880 TISSUE. 209 00:09:15,880 --> 00:09:18,000 IT WAS THE ONLY PLACE WHERE WE 210 00:09:18,000 --> 00:09:19,280 FOUND THE BEATS. 211 00:09:19,280 --> 00:09:22,440 NOWHERE ELSE WERE THESE TRANCE 212 00:09:22,440 --> 00:09:23,000 LOCATED INSIDE. 213 00:09:23,000 --> 00:09:30,440 IF YOU LOOK CAREFULLY ON THIS 214 00:09:30,440 --> 00:09:36,200 IMAGE, RIGHT UNDER, THERE ARE 215 00:09:36,200 --> 00:09:40,080 DEN DRY DICK CELLS IN RED AND 216 00:09:40,080 --> 00:09:41,200 THE BEATS ARE IN GREEN. 217 00:09:41,200 --> 00:09:45,160 WHAT IS INTERESTED IS THESE ARE 218 00:09:45,160 --> 00:09:46,720 LOCALIZED AS A STRAINS THAT 219 00:09:46,720 --> 00:09:49,920 FOLLOWS SOME INVISIBLE PATH. 220 00:09:49,920 --> 00:09:53,160 IF YOU LOOK CLOSER UNDER THIS 221 00:09:53,160 --> 00:09:54,760 IMAGE, IT HAS MULTIPLE ELEMENTS 222 00:09:54,760 --> 00:09:57,280 HERE THAT I WANT TO CONVEY. 223 00:09:57,280 --> 00:10:03,080 YOU WILL SEE THAT SOME OF THESE 224 00:10:03,080 --> 00:10:09,360 CONTINUE WITH A RED COLOR OF THE 225 00:10:09,360 --> 00:10:12,320 CDC WHICH IS A DAN CRADDOCK CELL 226 00:10:12,320 --> 00:10:14,280 AND SOMETIMES YOU HAVE THE 227 00:10:14,280 --> 00:10:18,120 ENTIRETY OF THE CHAIN BEING 228 00:10:18,120 --> 00:10:21,720 TRANSMITTED ALL THE WAY THROUGH 229 00:10:21,720 --> 00:10:23,560 INSIDE AND TO NOTE THAT THE 230 00:10:23,560 --> 00:10:27,920 RESULTS ARE VERY STRONG VERY 231 00:10:27,920 --> 00:10:31,200 THAT IS BASED ON MEMBRANE THAT 232 00:10:31,200 --> 00:10:38,040 LIES ON THE THESE DEN DIRECT 233 00:10:38,040 --> 00:10:39,760 CELLS PENETRATE FOR THESE SMALL 234 00:10:39,760 --> 00:10:41,160 PARTICLES TO GO THROUGH AND ON 235 00:10:41,160 --> 00:10:42,920 THIS IMAGE, FOR EXAMPLE, YOU SEE 236 00:10:42,920 --> 00:10:45,320 THAT THESE TINY CHANNELS 237 00:10:45,320 --> 00:10:48,040 ACTUALLY MADE BY DENDRITES FROM 238 00:10:48,040 --> 00:10:50,000 THE CELL AND I'M NOT SHOWING IT 239 00:10:50,000 --> 00:10:51,480 HERE BECAUSE OF THE LACK OF THE 240 00:10:51,480 --> 00:10:55,000 TIME, BUT WE DID DEMONSTRATE 241 00:10:55,000 --> 00:11:00,840 THAT THIS PROCESS IS DEPENDENT 242 00:11:00,840 --> 00:11:04,320 AND WHILE WE DEPLETE THE CELLS 243 00:11:04,320 --> 00:11:06,000 THESE CHANNELS STAY OPEN FOR 244 00:11:06,000 --> 00:11:10,640 ALMOST TWO HOURS. 245 00:11:10,640 --> 00:11:13,800 AND AGAIN THIS PROCESS IS THAT 246 00:11:13,800 --> 00:11:17,600 EXTENDED BASED ON MEMBRANE INTO 247 00:11:17,600 --> 00:11:20,880 THE SPACE AND ONLY FOUND 248 00:11:20,880 --> 00:11:23,200 ASSOCIATED WITH THE DOME OF THE 249 00:11:23,200 --> 00:11:26,560 COLONIC PATCH, AS YOU CAN SEE, 250 00:11:26,560 --> 00:11:29,080 GREEN CELLS AND THEY PENETRATE 251 00:11:29,080 --> 00:11:35,640 THE MEMBRANE TOWARDS THE LIEU 252 00:11:35,640 --> 00:11:36,320 MIN WHICH IS RIGHT HERE. 253 00:11:36,320 --> 00:11:38,000 THIS IS A SIMPLIFIED VERSION. 254 00:11:38,000 --> 00:11:39,680 WHAT WE SEE ON THE LEFT, YOU 255 00:11:39,680 --> 00:11:43,680 HAVE PROCESSES THAT PENETRATE TO 256 00:11:43,680 --> 00:11:46,160 FORM THIS PORES AND THE SMALL 257 00:11:46,160 --> 00:11:49,840 PARTICLES IS 20 NANOMETERS IN 258 00:11:49,840 --> 00:11:50,880 SIZE, PENETRATE INTO THE COLONIC 259 00:11:50,880 --> 00:11:51,320 PATCH. 260 00:11:51,320 --> 00:11:54,280 SO HOW QUICKLY THIS PARTICLE CAN 261 00:11:54,280 --> 00:11:56,080 ACTUALLY REACH THE AREAS, 262 00:11:56,080 --> 00:11:57,880 DIFFERENT AREAS OF THE COLONIC 263 00:11:57,880 --> 00:12:00,440 PATCH THAT ACTUALLY MATTER FOR 264 00:12:00,440 --> 00:12:02,480 THE RESPONSE AND IT'S ABOUT FOUR 265 00:12:02,480 --> 00:12:03,720 HOURS. 266 00:12:03,720 --> 00:12:06,080 THESE PARTICLES ALREADY FOUND 267 00:12:06,080 --> 00:12:09,520 DEEP WITHIN THIS PATCH AND BEING 268 00:12:09,520 --> 00:12:16,080 PRESENTED TO THE B-CELL BY THESE 269 00:12:16,080 --> 00:12:18,160 DENDRIC CELLS THAT YOU CAN SEE 270 00:12:18,160 --> 00:12:19,720 IN GREEN. 271 00:12:19,720 --> 00:12:21,000 INTERESTINGLY, THE TRANSPORT OF 272 00:12:21,000 --> 00:12:27,360 THESE PARTICLES WAS INDEPENDENT 273 00:12:27,360 --> 00:12:30,640 OF DENDRIDIC CELLS. 274 00:12:30,640 --> 00:12:33,560 YOU CAN SEE ON THIS GRAPH AND 275 00:12:33,560 --> 00:12:38,080 THIS IS THE INTENSITY OF THE Y 276 00:12:38,080 --> 00:12:40,240 AXIS AND IS ABOUT HALF OF THESE 277 00:12:40,240 --> 00:12:43,680 PARTICLES ACTUALLY DO NOT GET 278 00:12:43,680 --> 00:12:45,160 ASSOCIATED WITH THE CELLS AND 279 00:12:45,160 --> 00:12:46,960 THEY'VE BEEN TRANSPORTED TO SOME 280 00:12:46,960 --> 00:12:48,800 OTHER WAY PROBABLY IN THE 281 00:12:48,800 --> 00:12:52,400 PASSIVE MANNER. 282 00:12:52,400 --> 00:12:54,240 SO, WE ALSO LOOKED AT THE OTHER 283 00:12:54,240 --> 00:12:56,720 TYPES OF THE ANTIGEN SAMPLEING 284 00:12:56,720 --> 00:12:59,400 AND THIS IS DIFFERENT TYPES OF 285 00:12:59,400 --> 00:13:01,280 CELL THAT HAS A DIFFERENT 286 00:13:01,280 --> 00:13:02,080 PHENOTYPE. 287 00:13:02,080 --> 00:13:06,520 THIS WAS POSITIVE DENDRITIC 288 00:13:06,520 --> 00:13:08,080 CELLS AND THEY HAVE A VERY 289 00:13:08,080 --> 00:13:09,480 DIFFERENT BEHAVIOR FROM THE ONES 290 00:13:09,480 --> 00:13:11,640 THAT I JUST SHOWED A SECOND AGO. 291 00:13:11,640 --> 00:13:14,760 THEY DO NOT EXTEND DENDRITES. 292 00:13:14,760 --> 00:13:16,120 INSTEAD THEY EXHIBIT ACTIVE 293 00:13:16,120 --> 00:13:17,840 PATROL AND BEHAVIOR AND ON THE 294 00:13:17,840 --> 00:13:22,560 LEFT SIDE, YOU HAVE THE LAYER 295 00:13:22,560 --> 00:13:24,320 AND THE LINE IN THE MIDDLE IS 296 00:13:24,320 --> 00:13:26,560 ACTUALLY A LUME IN FROM THE 297 00:13:26,560 --> 00:13:30,120 COLLAPSED SIDE OF THE INTESTINE 298 00:13:30,120 --> 00:13:34,880 AND YOU SEE THIS C POSITIVE CELL 299 00:13:34,880 --> 00:13:35,680 PENETRATES BASED ON MEMBRANE, 300 00:13:35,680 --> 00:13:38,480 GOES UP TO THE LUMEN AND SAMPLES 301 00:13:38,480 --> 00:13:38,840 IT. 302 00:13:38,840 --> 00:13:44,200 THE SAME CAN BE SAID ABOUT THE 303 00:13:44,200 --> 00:13:45,200 CRYPT ON THE RIGHT. 304 00:13:45,200 --> 00:13:49,160 THE CRYPTS NEXT TO THE ARE 305 00:13:49,160 --> 00:13:51,480 PATROL BY DENDRITIC CELLS AND 306 00:13:51,480 --> 00:13:53,440 CAN THESE CELLS TAKE UP THE 307 00:13:53,440 --> 00:13:54,120 BACTERIA. 308 00:13:54,120 --> 00:13:55,280 YES, THEY CAN. 309 00:13:55,280 --> 00:13:59,240 AND THIS IS A RED FLUORESCENT 310 00:13:59,240 --> 00:14:02,000 SALMONELLA THAT HAS TAKEN OUT BY 311 00:14:02,000 --> 00:14:06,480 THIS HIGHLY DENDRITIC CELL AND 312 00:14:06,480 --> 00:14:10,520 TAKES IT TO PRESENT TO IMMUNE 313 00:14:10,520 --> 00:14:13,840 CELLS AND THESE CELLS LOCALIZE 314 00:14:13,840 --> 00:14:16,720 MOSTLY IN THE T-CELL AREAS 315 00:14:16,720 --> 00:14:18,920 PROBABLY MEANING THE MOST IMPACT 316 00:14:18,920 --> 00:14:21,320 THESE ANTIGENS WOULD HAVE ON THE 317 00:14:21,320 --> 00:14:22,960 T-CELL IS CLOSEST. 318 00:14:22,960 --> 00:14:27,680 WE WOULD REALLY WONDER HOW THIS 319 00:14:27,680 --> 00:14:29,200 INTERACTIONS BETWEEN THE CELLS. 320 00:14:29,200 --> 00:14:31,720 HOW DO THEY MANAGE TO MANIPULATE 321 00:14:31,720 --> 00:14:34,360 THE CELLS TO EXHIBIT SUCH A 322 00:14:34,360 --> 00:14:35,400 STRANGE BEHAVIOR AND ONE WAVE 323 00:14:35,400 --> 00:14:37,240 DOING IT IS SO DO THE SINGLE 324 00:14:37,240 --> 00:14:39,880 CELL SEQUENCES AND LOOK FOR THE 325 00:14:39,880 --> 00:14:43,160 CELLS OF THE CHEMOKINES AND 326 00:14:43,160 --> 00:14:45,240 CHEMOKINES RECEPTORS SO HERE WE 327 00:14:45,240 --> 00:14:48,800 LOOK AT THE CHEMOKINES AND THE 328 00:14:48,800 --> 00:14:50,520 RECEPTORS ON THE CELLS THAT WE 329 00:14:50,520 --> 00:14:53,400 RECOGNIZE IN THOSE CHEMOKINES 330 00:14:53,400 --> 00:14:57,480 AND WE FOUND CCL20, CCL6 AS A 331 00:14:57,480 --> 00:15:03,160 PAIR AND WE FOUND CCL6 AND CCL1. 332 00:15:03,160 --> 00:15:05,480 I'M GOING TO FOCUS ON CCL20 FOR 333 00:15:05,480 --> 00:15:08,520 A BIT. 334 00:15:08,520 --> 00:15:10,160 SO THE COLONIC PATCH WITH THE 335 00:15:10,160 --> 00:15:14,880 GREEN CCL20 AND RED CD11 CELLS 336 00:15:14,880 --> 00:15:17,160 YIELDS US THE INFORMATION THAT 337 00:15:17,160 --> 00:15:20,760 SHOWS THAT THESE CELLS ARE 338 00:15:20,760 --> 00:15:21,720 COLOCALIZED QUITE WELL. 339 00:15:21,720 --> 00:15:26,760 IN THIS CASE, FOUR LOCALIZE 340 00:15:26,760 --> 00:15:29,200 AROUND THE CRYPT SURROUNDING THE 341 00:15:29,200 --> 00:15:30,240 COLONIC PATCH AND THIS IS TRUE 342 00:15:30,240 --> 00:15:31,600 FOR BOTH OF THEM. 343 00:15:31,600 --> 00:15:33,000 ANOTHER INTERESTING FEATURE OF 344 00:15:33,000 --> 00:15:35,080 THIS CHEMOKINES THAT WHEN WE USE 345 00:15:35,080 --> 00:15:39,040 THE SPECIALIZED TYPE OF FIX TIVE 346 00:15:39,040 --> 00:15:41,640 THAT PRESERVES THE MUCUS TO LOOK 347 00:15:41,640 --> 00:15:44,240 AT INTERACTION OF THE MUCUS WE 348 00:15:44,240 --> 00:15:46,680 SAW IN THIS IMAGE, SEEN VERY 349 00:15:46,680 --> 00:15:52,240 WELL, THAT THE KEEP CHEMOKINES 350 00:15:52,240 --> 00:15:55,960 IS BEING SECRETED INTO THE LUMEN 351 00:15:55,960 --> 00:15:59,680 BECAUSE YOU HAVE A CELL THAT 352 00:15:59,680 --> 00:16:02,800 SAMPLES NOT ONLY THE CONTENT BUT 353 00:16:02,800 --> 00:16:07,680 THE LUMEN THAT CONTAINS AND AND 354 00:16:07,680 --> 00:16:10,400 ANOTHER FEATURE OF THESE TYPE OF 355 00:16:10,400 --> 00:16:14,080 CELLS ARE VERY SPECIFICALLY WERE 356 00:16:14,080 --> 00:16:18,400 PRODUCING CCL20s ONLY WHEN IN 357 00:16:18,400 --> 00:16:20,120 THE CLOSE CONTACT WITH THE 358 00:16:20,120 --> 00:16:20,920 COLONIC PATCHES. 359 00:16:20,920 --> 00:16:23,120 YOU CAN SEE THESE SEMI CIRCLES 360 00:16:23,120 --> 00:16:26,760 OF THE GREEN SURROUNDING THE 361 00:16:26,760 --> 00:16:30,040 COLONIC PATCH ON THE RIGHT. 362 00:16:30,040 --> 00:16:32,440 SO THIS IS OUR VERY SIMPLIFIED 363 00:16:32,440 --> 00:16:33,000 MODEL. 364 00:16:33,000 --> 00:16:36,360 YOU HAVE EPITHELIUM THAT 365 00:16:36,360 --> 00:16:39,320 SEPARATES BACTERIA FROM THE 366 00:16:39,320 --> 00:16:40,120 COLONIC PATCH AND YOU HAVE CELLS 367 00:16:40,120 --> 00:16:43,760 THAT CREATE THIS NANO PORES THAT 368 00:16:43,760 --> 00:16:49,440 WILL ACTUALLY FIRST IDENTIFIED 369 00:16:49,440 --> 00:16:52,960 AND THIS THEY ALLOW PASSIVE 370 00:16:52,960 --> 00:16:54,920 SMALL FRAGMENTS OF THE 371 00:16:54,920 --> 00:16:57,440 MICROBIOTA AND THIS PROBABLY 372 00:16:57,440 --> 00:16:58,960 PIECES OF THE DEAD BACTERIA AND 373 00:16:58,960 --> 00:17:05,720 MIGHT BE SOME FAGES AND VIRUSES 374 00:17:05,720 --> 00:17:06,960 AND DIFFERENT TYPE OF 375 00:17:06,960 --> 00:17:08,400 METABOLITES AND WE HAVE TO 376 00:17:08,400 --> 00:17:09,400 RECOGNIZE THERE'S NO MECHANISM 377 00:17:09,400 --> 00:17:13,000 IN THE COLON TO TRANSPORT ANY 378 00:17:13,000 --> 00:17:15,360 TYPE OF METABOLITES INSIDE THE 379 00:17:15,360 --> 00:17:17,840 BODY EXCEPT FOR THIS TYPE OF 380 00:17:17,840 --> 00:17:18,400 MECHANISM. 381 00:17:18,400 --> 00:17:26,200 BECAUSE MOST OF THE COLON CELLS 382 00:17:26,200 --> 00:17:29,120 ABSORB WATER AND SALTS. 383 00:17:29,120 --> 00:17:31,280 AND OF COURSE, WE HAVE ANOTHER 384 00:17:31,280 --> 00:17:33,920 TYPE OF CELL THAT SAMPLES THE 385 00:17:33,920 --> 00:17:36,680 LUMEN CONTENT AND TAKES UP 386 00:17:36,680 --> 00:17:39,000 ANTIGEN INSIDE OF THE COLONIC 387 00:17:39,000 --> 00:17:39,600 PATCH TO PRESENT THIS TO THE 388 00:17:39,600 --> 00:17:40,360 CELLS. 389 00:17:40,360 --> 00:17:43,080 THE FIRST MECHANISM MOSTLILY 390 00:17:43,080 --> 00:17:46,760 EFFECTS THE B CELLS FROM THE T 391 00:17:46,760 --> 00:17:49,280 CELLS AS WELL AND THE DENDRITIC 392 00:17:49,280 --> 00:17:51,400 CELLS THAT PATROL MOST LIKELY 393 00:17:51,400 --> 00:17:53,560 PRESENT ANTIGEN TO THE T-CELLS 394 00:17:53,560 --> 00:17:58,400 AND OF COURSE, THIS IS BY THE 395 00:17:58,400 --> 00:18:00,880 CHEMOKINES AND PRESUMABLY THIS 396 00:18:00,880 --> 00:18:03,560 WOULD BE A GOOD POTENTIAL FOR A 397 00:18:03,560 --> 00:18:06,400 TARGET FOR VARIETY OF DISEASES 398 00:18:06,400 --> 00:18:10,560 THAT ACTUALLY USES THIS 399 00:18:10,560 --> 00:18:16,520 MECHANISM TO SAMPLE MICROBES. 400 00:18:16,520 --> 00:18:20,000 NOW HOW DOES THIS WHOLE 401 00:18:20,000 --> 00:18:22,400 INTERACTION OF THE MICROBIOTA 402 00:18:22,400 --> 00:18:25,560 WITH THE HOST EFFECT THE 403 00:18:25,560 --> 00:18:27,240 RESPONSES TO THE CANCER, FOR 404 00:18:27,240 --> 00:18:27,840 EXAMPLE? 405 00:18:27,840 --> 00:18:30,360 IT'S AN EXAMPLE OF INTERACTION 406 00:18:30,360 --> 00:18:37,360 OF THE MIC MICROBIOME AND THE PT 407 00:18:37,360 --> 00:18:39,040 SEVERAL YEARS IT'S BEEN PROVEN 408 00:18:39,040 --> 00:18:41,400 QUITE WELL THAT THERE IS VERY 409 00:18:41,400 --> 00:18:43,040 STRONG CONNECTIONS BETWEEN THE 410 00:18:43,040 --> 00:18:45,760 COMPOSITION OF MICROBIOTA AND 411 00:18:45,760 --> 00:18:49,720 THE DEVELOPMENT OF CANCER. 412 00:18:49,720 --> 00:18:52,480 THE INITIATION OF THE CANCER. 413 00:18:52,480 --> 00:18:54,000 AND OBVIOUSLY THE RESPONSE TO 414 00:18:54,000 --> 00:18:57,360 THE THERAPY. 415 00:18:57,360 --> 00:19:00,720 AND I ACTUALLY THINK THAT IN 416 00:19:00,720 --> 00:19:03,360 PART THIS IS NOT BECAUSE OF THE 417 00:19:03,360 --> 00:19:09,840 WORK THAT WE DID ALONG WITH WORK 418 00:19:09,840 --> 00:19:11,920 THAT THAT WAS DONE AND PARALLEL 419 00:19:11,920 --> 00:19:13,320 AND PUBLISHED WITH US 420 00:19:13,320 --> 00:19:14,520 BACK-TO-BACK. 421 00:19:14,520 --> 00:19:16,600 SO WHAT WE'RE OBSERVING QUITE A 422 00:19:16,600 --> 00:19:18,360 WHILE AGO, ALMOST 10 YEARS AGO 423 00:19:18,360 --> 00:19:20,360 AND THE REASON I'M SHOWING THIS 424 00:19:20,360 --> 00:19:22,360 OLD DATA BECAUSE IT WILL FEED 425 00:19:22,360 --> 00:19:24,160 INTO THE NEXT THING THAT I'M 426 00:19:24,160 --> 00:19:26,760 GOING TO TALK ABOUT SPECIFICALLY 427 00:19:26,760 --> 00:19:30,160 ABOUT PATIENT STUDIES. 428 00:19:30,160 --> 00:19:33,840 SO, MICE WERE TREATED WITH 429 00:19:33,840 --> 00:19:36,840 ANTIBODY COCKTAILS THAT WAS 430 00:19:36,840 --> 00:19:38,320 DEPLETING THE BUT THE MICROBIOTA 431 00:19:38,320 --> 00:19:39,240 TWO WEEKS. 432 00:19:39,240 --> 00:19:40,880 TUMORS WERE IMPLANTED INTO THE 433 00:19:40,880 --> 00:19:45,280 MICE AND WE HAD TWO TYPES OF 434 00:19:45,280 --> 00:19:46,440 THERAPIES THAT WERE GIVEN TO THE 435 00:19:46,440 --> 00:19:47,520 MICE. 436 00:19:47,520 --> 00:19:49,000 IMMUNOTHERAPY AND THE 437 00:19:49,000 --> 00:19:49,680 CHEMOTHERAPY. 438 00:19:49,680 --> 00:19:54,840 AS YOU CAN SEE, AND THESE TWO 439 00:19:54,840 --> 00:20:05,400 PANELS, ABSENCE OF THE THIS WAS 440 00:20:17,080 --> 00:20:18,720 REPEATED BY MANY OTHER GROUPS 441 00:20:18,720 --> 00:20:22,000 AND THIS IS VERY PRODUCING 442 00:20:22,000 --> 00:20:24,120 PHENOMENON BECAUSE NOW, IT'S 443 00:20:24,120 --> 00:20:26,760 ESTABLISHED VERY WELL AND THEN 444 00:20:26,760 --> 00:20:31,800 IF YOU DO THE SAME TRICK, BUT 445 00:20:31,800 --> 00:20:33,280 WITH THE CHEMOTHERAPY YOU WILL 446 00:20:33,280 --> 00:20:37,960 SEE EXACTLY THE SAME FEE ONLY 447 00:20:37,960 --> 00:20:42,960 ON. 448 00:20:42,960 --> 00:20:47,600 THE MICE STILL RESPONDING TO 449 00:20:47,600 --> 00:20:48,080 THE. 450 00:20:48,080 --> 00:20:49,720 THE DIFFERENCE HERE IS STARK FOR 451 00:20:49,720 --> 00:20:54,560 SURVIVAL AS YOU CAN SEE. 452 00:20:54,560 --> 00:20:56,520 SO WE ACTUALLY TRIED TO ANSWER 453 00:20:56,520 --> 00:21:00,800 THE QUESTION EXACTLY HOW THIS IS 454 00:21:00,800 --> 00:21:03,320 HAPPENING AND WE DID CRIP TOM I 455 00:21:03,320 --> 00:21:04,800 CAN STUDIES AND FULL STUDIES AND 456 00:21:04,800 --> 00:21:06,760 THE CONCLUSION THAT WE CAME UP 457 00:21:06,760 --> 00:21:09,160 WITH IS THAT THE ANTIBODY OF 458 00:21:09,160 --> 00:21:13,800 TREATMENT OR JUST THE DEPRESSION 459 00:21:13,800 --> 00:21:18,240 WITH LIKE JOHN FREEMA RESULTS IN 460 00:21:18,240 --> 00:21:20,320 REDUCTION OF BOTH NUMBERS OF 461 00:21:20,320 --> 00:21:22,600 IMMUNE CELLS AND ACTIVITY. 462 00:21:22,600 --> 00:21:24,680 AS YOU CAN SEE HERE ON THE LEFT 463 00:21:24,680 --> 00:21:26,960 PANEL THAT SHOWS THE DIFFERENT 464 00:21:26,960 --> 00:21:31,920 PATHWAYS, YOU HAVE REDUCTION IN 465 00:21:31,920 --> 00:21:33,560 TOXICITY, YOU HAVE INCUBATION OF 466 00:21:33,560 --> 00:21:35,320 THE PROLIFERATION OF DIFFERENT 467 00:21:35,320 --> 00:21:37,160 CELL TYPES AND THIS IS MIRRORED 468 00:21:37,160 --> 00:21:40,880 BY THE FLOW SEM TOM TREE DATA SO 469 00:21:40,880 --> 00:21:44,080 IN GENERAL, BACTERIA IS CRITICAL 470 00:21:44,080 --> 00:21:47,960 FOR MAINTAINING PROPER IMMUNE 471 00:21:47,960 --> 00:21:50,680 CELL HOMEOSTASIS IN THE TUMOR 472 00:21:50,680 --> 00:21:51,720 FOR SUCCESSFUL TREATMENT OVER 473 00:21:51,720 --> 00:21:54,960 THESE CANCERS. 474 00:21:54,960 --> 00:21:56,560 FOLLOWING OUR AND OTHER SIMILAR 475 00:21:56,560 --> 00:22:00,720 TYPE OF PAPERS, MAINLY 476 00:22:00,720 --> 00:22:02,400 INVESTIGATORS RUSHED INTO 477 00:22:02,400 --> 00:22:07,160 LOOKING AT THE FACTS OF THE GUT 478 00:22:07,160 --> 00:22:09,320 MICROBIOTA INSIDE THE PATIENTS 479 00:22:09,320 --> 00:22:14,760 AND IN THIS PARTICULAR STUDY ALF 480 00:22:14,760 --> 00:22:17,400 THEM DID IMMUNOTHERAPY WITH 481 00:22:17,400 --> 00:22:20,000 CONTACT PD1 AND THEY LOOPED THE 482 00:22:20,000 --> 00:22:24,040 EFFECTS OF TREATMENT IN 483 00:22:24,040 --> 00:22:25,040 PATIENTS. 484 00:22:25,040 --> 00:22:30,800 THE PROBLEM AROSE WHEN, AS WE 485 00:22:30,800 --> 00:22:31,840 SPEAK, DUST SETTLED AND WE 486 00:22:31,840 --> 00:22:33,800 STARTED LOOKING SPECIFICALLY AT 487 00:22:33,800 --> 00:22:37,880 THE TYPE OF MICROBES THAT WERE 488 00:22:37,880 --> 00:22:39,360 SPECIFIC FOR EACH ONE OF THESE 489 00:22:39,360 --> 00:22:42,640 STUDIES AND UNFORTUNATELY, WHAT 490 00:22:42,640 --> 00:22:44,160 EVERYBODY REALIZED VERY QUICKLY 491 00:22:44,160 --> 00:22:46,080 THAT THE RESULTS WERE VERY 492 00:22:46,080 --> 00:22:48,000 DIFFERENT BETWEEN THE DIFFERENT 493 00:22:48,000 --> 00:22:51,200 STUDIES AND THAT PRESENTED A 494 00:22:51,200 --> 00:22:53,640 HUGE PROBLEM BECAUSE HOW CAN WE 495 00:22:53,640 --> 00:22:57,920 TRUST THIS TYPE OF DATA? 496 00:22:57,920 --> 00:22:59,440 OBVIOUSLY IN ANY KIND OF 497 00:22:59,440 --> 00:23:02,680 CLINICAL STUDY, IF YOU ANSWER 498 00:23:02,680 --> 00:23:04,720 THE QUESTION TO THIS 499 00:23:04,720 --> 00:23:06,480 CONTROVERSIAL DATA, WITH TWO 500 00:23:06,480 --> 00:23:06,920 THINGS. 501 00:23:06,920 --> 00:23:08,920 ONE IS OBVIOUSLY THE META 502 00:23:08,920 --> 00:23:09,960 ANALYSIS BUT THE OTHER THING IS 503 00:23:09,960 --> 00:23:12,680 GOING WITH THE MUCH LARGER 504 00:23:12,680 --> 00:23:13,040 SAMPLE SIZE. 505 00:23:13,040 --> 00:23:15,360 THIS IS WHAT OUR CLINICAL 506 00:23:15,360 --> 00:23:19,000 COLLABORATORS IN PITTSBURG, 507 00:23:19,000 --> 00:23:23,520 HASSAN AND DIWAKAR DID, THEY 508 00:23:23,520 --> 00:23:25,600 DECIDED, TOGETHER WITH US, A 509 00:23:25,600 --> 00:23:26,480 LARGER CLINICAL STUDY. 510 00:23:26,480 --> 00:23:27,760 AT THE TIME IT WAS THE LARGEST 511 00:23:27,760 --> 00:23:31,360 ONE THAT WERE TREATING MELANOMA 512 00:23:31,360 --> 00:23:35,000 PATIENTS WITH ANTI PD1 THERAPY 513 00:23:35,000 --> 00:23:37,280 AND FOLLOWED THE RADIO GRAPHIC 514 00:23:37,280 --> 00:23:42,000 RESPONSES TO THE TREATMENT FOR 515 00:23:42,000 --> 00:23:42,480 SOME TIME. 516 00:23:42,480 --> 00:23:46,800 THIS IS THE FIRST R THE FIRST RE 517 00:23:46,800 --> 00:23:47,600 RESULTS WE GOT. 518 00:23:47,600 --> 00:23:49,560 ON THE LEFT SIDE, THIS IS A MAP 519 00:23:49,560 --> 00:23:52,800 AND BLUE AND RESPONDERS AND RED 520 00:23:52,800 --> 00:23:55,320 NOTE RESPONDERS AND YOU CAN SEE 521 00:23:55,320 --> 00:23:57,800 THAT THE CENTRAL SEPARATION IS 522 00:23:57,800 --> 00:23:59,440 QUITE SIGNIFICANT AND THIS IS 523 00:23:59,440 --> 00:24:04,360 REFLECTED IN THE VERY GOOD P 524 00:24:04,360 --> 00:24:06,520 VALUE AND ALSO WE GOT VERY GOOD 525 00:24:06,520 --> 00:24:08,560 LIST OF THE TOXONEME THAT WERE 526 00:24:08,560 --> 00:24:09,800 DIFFERENT BETWEEN THE RESPONDERS 527 00:24:09,800 --> 00:24:12,800 AND NOTE RESPONDERS ACTUALLY. 528 00:24:12,800 --> 00:24:23,320 THERE WAS MUCH LARGER LIST THE 529 00:24:30,360 --> 00:24:31,800 ANSWER WAS IN THE META ANALYSIS. 530 00:24:31,800 --> 00:24:33,600 SO WE DOWNLOADED THE DATA FROM 531 00:24:33,600 --> 00:24:35,200 THESE DIFFERENT STUDIES AND WE 532 00:24:35,200 --> 00:24:40,000 PUT THEM TOGETHER AND FOR 533 00:24:40,000 --> 00:24:42,960 PIPELINE AND IN ORDER TO SEE 534 00:24:42,960 --> 00:24:53,520 RESPONDERS AND VERY QUICKLY AND 535 00:24:55,080 --> 00:24:56,160 IT'S ALL THE DIFFERENT STUDIES 536 00:24:56,160 --> 00:24:58,000 IN DIFFERENT COLORS AND DID NOT 537 00:24:58,000 --> 00:24:59,560 LINEUP WITH EACH OTHER SO THEY 538 00:24:59,560 --> 00:25:01,320 WERE VERY QUITE DIFFERENT. 539 00:25:01,320 --> 00:25:03,040 OF COURSE, THERE ARE STATISTICAL 540 00:25:03,040 --> 00:25:09,440 TOOLS TO DEAL WITH THIS AND YOU 541 00:25:09,440 --> 00:25:12,320 CAN ALSO DO IT AS WELL META 542 00:25:12,320 --> 00:25:16,080 ANALYSIS WITH MULTIPLE DIFFERENT 543 00:25:16,080 --> 00:25:19,320 TECHNIQUES AND GET YOUR TAXONOMY 544 00:25:19,320 --> 00:25:20,120 LIST. 545 00:25:20,120 --> 00:25:22,720 THE CORRECTED DATA YIELDED US 546 00:25:22,720 --> 00:25:24,920 ACTUALLY IMPROVED P VALUE STUDY 547 00:25:24,920 --> 00:25:32,040 AND IT WAS INSTEAD OF .006, 548 00:25:32,040 --> 00:25:33,120 ..002 WHICH WAS GOOD. 549 00:25:33,120 --> 00:25:35,520 WE WERE CONFIDENT THAT WE SHOULD 550 00:25:35,520 --> 00:25:40,120 BE NOW LOOKING AT THE DATA AND 551 00:25:40,120 --> 00:25:44,240 THIS IS WHAT IT LOOKS LIKE. 552 00:25:44,240 --> 00:25:49,720 THIS IS A CLY DRO GRAM. 553 00:25:49,720 --> 00:25:51,400 IT'S A SIMPLIFIED WAY. 554 00:25:51,400 --> 00:25:56,520 IT'S CIRCLIZED TREE OF LIFE. 555 00:25:56,520 --> 00:26:01,240 IN THE CIRCLES, ARE HIGHER 556 00:26:01,240 --> 00:26:03,680 LEVELS SUCH AS CLASS AND PHYLUM 557 00:26:03,680 --> 00:26:07,360 AND THE OUTER SURGERIES, 558 00:26:07,360 --> 00:26:09,360 SPECIES, GENUS, ET CETERA. 559 00:26:09,360 --> 00:26:12,760 ONE OF THE REASONS WHY THIS IS 560 00:26:12,760 --> 00:26:14,360 ACTUALLY USEFUL WAY OF LOOKING 561 00:26:14,360 --> 00:26:16,640 AT IT BECAUSE IT LOOKS AT HIGHER 562 00:26:16,640 --> 00:26:20,400 LEVEL TOXIC AND IT'S EFFECTED. 563 00:26:20,400 --> 00:26:21,920 FROM ANALYZING MULTIPLE 564 00:26:21,920 --> 00:26:23,080 DIFFERENT DAY SETS THIS WAY I 565 00:26:23,080 --> 00:26:29,040 CAN TELL YOU THAT THIS IS A VERY 566 00:26:29,040 --> 00:26:30,960 RARE TYPE OF VISUALIZATION OF 567 00:26:30,960 --> 00:26:31,920 THE ANALYSIS. 568 00:26:31,920 --> 00:26:35,000 WHAT I MEAN IS, TYPICALLY WE 569 00:26:35,000 --> 00:26:40,120 DON'T SEE THE TIGHTLY CLUSTERED 570 00:26:40,120 --> 00:26:42,760 BACTERIA THAT SIGNIFIES THE 571 00:26:42,760 --> 00:26:47,440 WHOLE TREE EFFECTED IN YOUR 572 00:26:47,440 --> 00:26:51,000 COMPARISON. 573 00:26:51,000 --> 00:27:01,520 SO BLUE HERE, AND TALKING ABOUT 574 00:27:03,280 --> 00:27:07,800 HERE AND NO RESPONDERS WILL 575 00:27:07,800 --> 00:27:13,560 MOSTLY RELATED TO BACTERIA AND 576 00:27:13,560 --> 00:27:15,920 THAT WAS MOSTLY COMPRISED OF 577 00:27:15,920 --> 00:27:23,440 DIFFERENT SPECIES THAT GO ON TO. 578 00:27:23,440 --> 00:27:25,800 AND MOST AND SEVERAL TRAINS 579 00:27:25,800 --> 00:27:27,240 BACTERIA AND SOME STUDIES 580 00:27:27,240 --> 00:27:31,800 REPORTED EARLIER. 581 00:27:31,800 --> 00:27:34,920 SO, OF COURSE THE PROBLEM WAS 582 00:27:34,920 --> 00:27:37,920 MAY WERE NOT HAPPY ABOUT BAN 583 00:27:37,920 --> 00:27:41,000 MUCH CORRECTION BECAUSE WHAT IF 584 00:27:41,000 --> 00:27:42,600 IT CONTAINED INFORMATION WE'RE 585 00:27:42,600 --> 00:27:43,400 MISSING. 586 00:27:43,400 --> 00:27:45,600 ONE WAY IS TO GET MORE DATA. 587 00:27:45,600 --> 00:27:47,360 HOW DO WE GET MORE DATA? 588 00:27:47,360 --> 00:27:51,720 IT DOESN'T EXIST ANYMORE. 589 00:27:51,720 --> 00:27:54,400 WE TRY THE TECHNIQUES AND IF YOU 590 00:27:54,400 --> 00:27:57,400 MANAGED TO ALIGN YOUR DATA WITH 591 00:27:57,400 --> 00:28:01,640 A LARGER DATA, YOU CAN IMPUTE 592 00:28:01,640 --> 00:28:02,800 YOUR LARGER DATA WITH 593 00:28:02,800 --> 00:28:04,080 INFORMATION THAT CONTAINS THE 594 00:28:04,080 --> 00:28:04,560 SMALLER DATA. 595 00:28:04,560 --> 00:28:06,640 IT HAS A LOT OF LIMITATIONS AND 596 00:28:06,640 --> 00:28:08,160 THIS OBVIOUSLY IT'S NOT A 597 00:28:08,160 --> 00:28:09,080 REPLACEMENT FOR THE REAL THING 598 00:28:09,080 --> 00:28:11,840 OF THE LARGER ANALYSIS. 599 00:28:11,840 --> 00:28:14,160 FOR THE TIME BEING, FOR CURIOUS 600 00:28:14,160 --> 00:28:16,640 MICE, WHICH WERE AT THE MOMENT, 601 00:28:16,640 --> 00:28:20,760 IT WAS A GOOD THING TO DO. 602 00:28:20,760 --> 00:28:23,400 FORTUNATELY FOR US IT WAS A 603 00:28:23,400 --> 00:28:24,280 PROJECT THAT AMERICAN GUT 604 00:28:24,280 --> 00:28:26,960 PROJECT THAT MANAGED TO COLLECT 605 00:28:26,960 --> 00:28:27,880 ABOUT 10,000 STOOL SAMPLES AT A 606 00:28:27,880 --> 00:28:35,960 TIME OF ANALYSIS AND FORTUNATELY 607 00:28:35,960 --> 00:28:37,920 THIS DATASET WAS DONE WITH THE 608 00:28:37,920 --> 00:28:40,640 SAME TECHNIQUES AS WAS DONE WITH 609 00:28:40,640 --> 00:28:43,360 THIS DATASETS THAT WE HAD IN OUR 610 00:28:43,360 --> 00:28:43,920 HANDS. 611 00:28:43,920 --> 00:28:48,280 SO WE ANALYZED IT WITH OUR OWN 612 00:28:48,280 --> 00:28:49,560 TOOLS PRIOR TO VENTURING OFF AND 613 00:28:49,560 --> 00:28:52,320 TRYING TO ALIGN OUR DATA AND 614 00:28:52,320 --> 00:28:55,680 IMPUTE IT AND SO ON. 615 00:28:55,680 --> 00:28:58,760 WHAT WE SAW FROM THIS DATA 616 00:28:58,760 --> 00:28:59,800 ANALYSIS WAS DIFFERENT FROM WHAT 617 00:28:59,800 --> 00:29:01,960 WAS REPORTED BEFORE BECAUSE WE 618 00:29:01,960 --> 00:29:04,000 USED OUR OWN TOOLS THAT WERE 619 00:29:04,000 --> 00:29:06,080 QUITE IMPROVED COMPUTATIONAL 620 00:29:06,080 --> 00:29:07,480 TOOLS WERE IMPROVED SINCE THE 621 00:29:07,480 --> 00:29:10,000 TIME OF THE PUBLICATIONS OF THIS 622 00:29:10,000 --> 00:29:10,480 DATASETS. 623 00:29:10,480 --> 00:29:13,200 BECAUSE OF THE SINGLE CELL 624 00:29:13,200 --> 00:29:15,480 SEQUENCE AND TECHNOLOGY THERE 625 00:29:15,480 --> 00:29:16,920 WERE MANY TOOLS DEVELOPED FOR 626 00:29:16,920 --> 00:29:20,440 THESE TYPE OF DATA. 627 00:29:20,440 --> 00:29:22,400 SO WHAT YOU CAN SEE HERE ON THE 628 00:29:22,400 --> 00:29:28,400 LEFT SIDE IS THE UMAP AND EVERY 629 00:29:28,400 --> 00:29:30,640 DOT IS A STOOL SAMPLE. 630 00:29:30,640 --> 00:29:32,960 WHAT YOU CAN SEE IS IN COLOR A 631 00:29:32,960 --> 00:29:39,640 DIFFERENT CLUSTER THAT WE USE 632 00:29:39,640 --> 00:29:40,920 SOFTWARE AND TO PREDICT WHAT 633 00:29:40,920 --> 00:29:43,360 TYPE OF CLUSTERS IT CONTAINS AND 634 00:29:43,360 --> 00:29:47,200 THEN WE LOOKED AT THE TOX 635 00:29:47,200 --> 00:29:49,080 SPECIFIC FOR THESE CLUSTERS ON 636 00:29:49,080 --> 00:29:50,320 THE RIGHT X WHAT WE SAW IS THAT 637 00:29:50,320 --> 00:29:51,520 EVERY SINGLE CLUSTER THAT YOU 638 00:29:51,520 --> 00:29:55,160 CAN SEE ON THE LEFT, HAD ITS OWN 639 00:29:55,160 --> 00:29:58,320 SIGNATURE THAT WAS BUILT OUT OF 640 00:29:58,320 --> 00:29:59,360 DIFFERENT UNITS. 641 00:29:59,360 --> 00:30:01,800 ALL THESE CLUSTERS WERE 642 00:30:01,800 --> 00:30:02,800 DIFFERENT. 643 00:30:02,800 --> 00:30:06,400 SO YOU TRUST ME WITH THESE TYPE 644 00:30:06,400 --> 00:30:08,760 OF INFORMATION, I'M SHOWING YOU 645 00:30:08,760 --> 00:30:11,920 SOME OF THE DATA HERE. 646 00:30:11,920 --> 00:30:14,280 THIS IS THE SAME. 647 00:30:14,280 --> 00:30:16,040 L AS I JUST SHOWED BEFORE. 648 00:30:16,040 --> 00:30:20,120 THEY JUST CALL IT A BIT 649 00:30:20,120 --> 00:30:30,320 DIFFERENTLY. 650 00:30:31,520 --> 00:30:33,480 >>THIS IS VERY ANNOYING. 651 00:30:33,480 --> 00:30:39,280 I APOLOGIZE FOR THAT. 652 00:30:39,280 --> 00:30:42,240 SO, RED MEANS HIGH AND BLUE 653 00:30:42,240 --> 00:30:44,880 MEANS LOW. 654 00:30:44,880 --> 00:30:49,480 SO SOME OF THE SPECIES, IS 655 00:30:49,480 --> 00:30:50,560 ENRICHED IN ONE CLUSTER. 656 00:30:50,560 --> 00:30:57,520 THE SAME GOES FOR PEP TON FILL 657 00:30:57,520 --> 00:30:58,920 US AND THEY'RE ONE TYPE OF 658 00:30:58,920 --> 00:31:01,200 CLUSTER FOR A PERSON LIKE ME WHO 659 00:31:01,200 --> 00:31:03,000 IS DOING MICROBIOME FOR MANY 660 00:31:03,000 --> 00:31:05,480 YEARS, GOD KNOWS FOR HOW LONG, 661 00:31:05,480 --> 00:31:07,680 THIS IS A VERY STRANGE BECAUSE 662 00:31:07,680 --> 00:31:10,800 IN MY PRIMITIVE MIND I ALWAYS 663 00:31:10,800 --> 00:31:11,400 CONSIDERED MICROBIOME AS SOME 664 00:31:11,400 --> 00:31:14,840 SORT OF A CONTINUOUS SPACE THAT 665 00:31:14,840 --> 00:31:17,240 THERE ARE NO TYPES THAT WE 666 00:31:17,240 --> 00:31:18,360 CLAIMED BEFORE. 667 00:31:18,360 --> 00:31:20,080 IT JUST ONE SPACE THAT WE MAY 668 00:31:20,080 --> 00:31:21,920 HAVE HAVE AND IT MAY GO OR IT 669 00:31:21,920 --> 00:31:22,960 MAY NOT GROW. 670 00:31:22,960 --> 00:31:26,280 YES WE DID KNOW THAT THERE ARE 671 00:31:26,280 --> 00:31:28,960 SOME RELATIONSHIPS IN THE 672 00:31:28,960 --> 00:31:30,360 INTESTINE AND SOME BUGS TRY TO 673 00:31:30,360 --> 00:31:31,760 KILL ANOTHER BUG OR COMPETE FOR 674 00:31:31,760 --> 00:31:35,360 THE FOOD, ET CETERA BUT TO SEE 675 00:31:35,360 --> 00:31:36,840 THEM AS COMPRISING SOME SORT OF 676 00:31:36,840 --> 00:31:39,040 ENTITIES LIKE THIS TO BEHAVE 677 00:31:39,040 --> 00:31:41,680 LIKE A CELL TYPES IN THE HUMAN 678 00:31:41,680 --> 00:31:45,200 BODY, THAT WAS QUITE AMAZING. 679 00:31:45,200 --> 00:31:46,800 AND WE STILL DON'T UNDERSTAND 680 00:31:46,800 --> 00:31:57,280 HOW THIS SO-CALLED THERE ARE 681 00:32:26,440 --> 00:32:29,680 SOME SPOTS OF MAGENTA, GREEN, 682 00:32:29,680 --> 00:32:31,400 RED, ET CETERA AND YOU CAN 683 00:32:31,400 --> 00:32:34,200 ACTUALLY VISUALIZE THIS A BIT 684 00:32:34,200 --> 00:32:44,720 BETTER AND USING THEY OCCUPIED 685 00:32:56,360 --> 00:33:00,880 DIFFERENT PLACES AND WHY IS THIS 686 00:33:00,880 --> 00:33:03,800 IS IMPORTANT BECAUSE IT EXPLAINS 687 00:33:03,800 --> 00:33:07,600 OF THE NATURE THAT THEY'RE REAL 688 00:33:07,600 --> 00:33:09,120 AND NOT IN THE SENSE THAT 689 00:33:09,120 --> 00:33:11,840 THEY'RE TECHNICALLY PROBLEMATIC 690 00:33:11,840 --> 00:33:14,680 AND THEY'RE JUST -- THESE 691 00:33:14,680 --> 00:33:16,160 STUDIES SAMPLED THE DATASETS 692 00:33:16,160 --> 00:33:17,240 FROM DIFFERENT SPACES FROM 693 00:33:17,240 --> 00:33:19,400 DIFFERENT LOCATIONS OF THIS 694 00:33:19,400 --> 00:33:24,160 MICROBIOME HYPER SPACE. 695 00:33:24,160 --> 00:33:26,320 SO, THIS STUDY WERE COLLECTED IN 696 00:33:26,320 --> 00:33:29,440 DIFFERENT PLACES IN THE UNITED 697 00:33:29,440 --> 00:33:31,160 STATES SO NATURALLY LET'S LOOK 698 00:33:31,160 --> 00:33:35,320 IF THERE'S ANY DISTRIBUTION 699 00:33:35,320 --> 00:33:37,640 DIFFERENCES OF THE MICROBIOME 700 00:33:37,640 --> 00:33:38,560 ACROSS THE UNITED STATES. 701 00:33:38,560 --> 00:33:39,840 THIS IS WHAT WE HAVE. 702 00:33:39,840 --> 00:33:41,440 FORTUNATELY FOR US ONCE AGAIN, 703 00:33:41,440 --> 00:33:42,880 THIS DATASET IS VERY RICH. 704 00:33:42,880 --> 00:33:47,240 IT CONTAINED THE DATA OF 705 00:33:47,240 --> 00:33:48,160 GEOGRAPHICAL COR DIN AT FOR 706 00:33:48,160 --> 00:33:49,920 EVERY SINGLE SIMPLE AND WE 707 00:33:49,920 --> 00:33:54,560 STARTED FOR EVERY SINGLE MICROBE 708 00:33:54,560 --> 00:33:56,400 TYPE A MAP WHERE THEY 709 00:33:56,400 --> 00:33:57,120 DISTRIBUTED ACROSS THE UNITED 710 00:33:57,120 --> 00:33:57,600 STATES. 711 00:33:57,600 --> 00:33:59,400 IT TURNED OUT THEY DISTRIBUTED 712 00:33:59,400 --> 00:34:02,720 QUITE DIFFERENTLY FROM EACH 713 00:34:02,720 --> 00:34:03,080 OTHER. 714 00:34:03,080 --> 00:34:05,480 SOME OF THEM DISTRIBUTED EVENLY 715 00:34:05,480 --> 00:34:11,800 ACROSS THE U.S. WHERE IT'S THE 716 00:34:11,800 --> 00:34:14,920 MICRO TYPE 8 AND EAST COAST SO 717 00:34:14,920 --> 00:34:16,760 VERY DIFFERENT AND IF YOU LOOK 718 00:34:16,760 --> 00:34:19,480 AT THIS DATASETS THAT WE WERE 719 00:34:19,480 --> 00:34:20,560 DISCUSSING, THEY HAD A VERY, 720 00:34:20,560 --> 00:34:23,920 VERY DIFFERENT COMPOSITION OF 721 00:34:23,920 --> 00:34:25,560 THE MICRO BIO TYPE. 722 00:34:25,560 --> 00:34:27,440 CONTRIBUTING TO THE PROBLEMS 723 00:34:27,440 --> 00:34:30,480 THAT PEOPLE SEE BETWEEN THE 724 00:34:30,480 --> 00:34:30,760 STUDIES. 725 00:34:30,760 --> 00:34:32,240 SO GOING TO THE MORE IMPORTANT 726 00:34:32,240 --> 00:34:34,280 QUESTION HOW THIS ACTUALLY 727 00:34:34,280 --> 00:34:39,040 EFFECTS THE RESPONDERS AND NOTE 728 00:34:39,040 --> 00:34:40,560 RESPONDERS. 729 00:34:40,560 --> 00:34:42,640 WHAT DOES THIS MAP GIVE US THAT 730 00:34:42,640 --> 00:34:45,160 WE DIDN'T HAVE BEFORE IS THE 731 00:34:45,160 --> 00:34:47,120 MIKE KOBE TYPES FOR EVERY SINGLE 732 00:34:47,120 --> 00:34:50,520 CLUSTER OF MICROBE YO TYPE WE 733 00:34:50,520 --> 00:34:53,240 CALCULATE THE PREPORTION OF 734 00:34:53,240 --> 00:34:54,760 RESPONDERS AND NOT RESPONDERS 735 00:34:54,760 --> 00:34:56,160 AND MAP THIS AND THIS IS WHAT WE 736 00:34:56,160 --> 00:34:56,720 HAVE GOT. 737 00:34:56,720 --> 00:34:59,760 INSTEAD OF GETTING PATCHES OF 738 00:34:59,760 --> 00:35:02,560 BLUE AND RED, WE'RE GETTING A 739 00:35:02,560 --> 00:35:04,560 SUPER PATCH, A HUGE GROUP OF 740 00:35:04,560 --> 00:35:07,680 BLUE AND HUGE GROUP OF RED. 741 00:35:07,680 --> 00:35:11,440 SOME SORT OF A BELT OF EVILS IF 742 00:35:11,440 --> 00:35:15,240 YOU MIGHT THINK ABOUT IT BECAUSE 743 00:35:15,240 --> 00:35:17,400 THIS RED SIGNIFIES ENRICHMENT IN 744 00:35:17,400 --> 00:35:21,920 NON RESPONDERS SO NATURALLY 745 00:35:21,920 --> 00:35:24,160 THEY'RE SEPARATED INTO GOOD ONES 746 00:35:24,160 --> 00:35:27,560 AND WE SEPARATE THIS BIG BELT 747 00:35:27,560 --> 00:35:28,480 INTO TWO CLASSES AS WELL AND 748 00:35:28,480 --> 00:35:30,000 THIS IS WHAT HAPPENED. 749 00:35:30,000 --> 00:35:34,720 SO YOU HAVE THE TWO GOOD AND TWO 750 00:35:34,720 --> 00:35:36,600 BAD TYPES AND THESE ARE THE ON 751 00:35:36,600 --> 00:35:37,840 THE RIGHT SIDE THAT ARE 752 00:35:37,840 --> 00:35:38,680 SIGNIFICANT. 753 00:35:38,680 --> 00:35:41,160 OBVIOUSLY WE IDENTIFIED WAY MORE 754 00:35:41,160 --> 00:35:43,600 WITH THIS TYPE OF ANALYSIS 755 00:35:43,600 --> 00:35:44,320 BECAUSE THE SHEAR NUMBERS MANY 756 00:35:44,320 --> 00:35:45,680 OF IT'S THE WHOLE POINT OF 757 00:35:45,680 --> 00:35:46,840 IMPUTING THE DATA. 758 00:35:46,840 --> 00:35:49,280 WE DID IDENTIFY NEW BACTERIA, 759 00:35:49,280 --> 00:35:55,480 FOR EXAMPLE, THAT WAS NOT 760 00:35:55,480 --> 00:35:56,640 IDENTIFIED PREVIOUSLY NOW META 761 00:35:56,640 --> 00:35:58,480 ANALYSIS BUT IN THE BACK-TO-BACK 762 00:35:58,480 --> 00:36:00,600 PAPER THAT WE HAD PUBLISHED, 763 00:36:00,600 --> 00:36:03,400 WITH NICOLAS GROUP, THEY FOUND 764 00:36:03,400 --> 00:36:05,920 THAT IT'S A GOOD BACK AND THE 765 00:36:05,920 --> 00:36:10,200 SAME GOES WITH THE THINGS LIKE 766 00:36:10,200 --> 00:36:15,840 THAT. THE BAD BACTERIA WERE 767 00:36:15,840 --> 00:36:20,920 MOSTLY SIGNIFIED BY BAD AND 768 00:36:20,920 --> 00:36:22,800 MICROBIOME TYPE ONE AND TWO WAS 769 00:36:22,800 --> 00:36:25,400 MARKED BY BACTERIAS. 770 00:36:25,400 --> 00:36:28,680 AND I THINK TO MENTION FROM THIS 771 00:36:28,680 --> 00:36:33,320 SLIDE IS THAT BACTERIA THAT HAS 772 00:36:33,320 --> 00:36:36,160 BEEN A TOPIC OF MANY CLINICAL 773 00:36:36,160 --> 00:36:40,440 ACTUALLY STUDIES AND MANY 774 00:36:40,440 --> 00:36:42,200 BIOTECH STARTUPS IS A PART OF 775 00:36:42,200 --> 00:36:47,280 THE GOOD MICROBIOME TOOL. 776 00:36:47,280 --> 00:36:51,160 SO WE REALLY WANTED TO SEE IF 777 00:36:51,160 --> 00:36:53,880 THIS IS ALL TRUE AND HOW DO YOU 778 00:36:53,880 --> 00:36:55,240 GET TO THAT? 779 00:36:55,240 --> 00:37:00,840 HOW DO WE TEST THE IN SOME OTHER 780 00:37:00,840 --> 00:37:02,240 WAY AND THEY'RE NOW DATASETS 781 00:37:02,240 --> 00:37:04,040 THAT WE HAD AND THEN WE 782 00:37:04,040 --> 00:37:05,320 REMEMBERED THAT THERE WERE 783 00:37:05,320 --> 00:37:08,160 STUDIES A WHILE AGO THAT SHOWED 784 00:37:08,160 --> 00:37:10,080 THAT ANTI-BUY OT I CAN THERAPY 785 00:37:10,080 --> 00:37:14,840 PRIOR TO PD1 AND RESULTS IN THE 786 00:37:14,840 --> 00:37:17,200 LOSS OF THE EXPOS TO THE PD1 SO 787 00:37:17,200 --> 00:37:19,920 WE'RE TALKING ABOUT THE PRIOR 788 00:37:19,920 --> 00:37:22,880 ALL THE WAY TO SIX MONTHS BUT 789 00:37:22,880 --> 00:37:24,680 NOT AT THE TIME AND OF THE 790 00:37:24,680 --> 00:37:27,680 TREATMENT SO, AS YOU CAN SEE 791 00:37:27,680 --> 00:37:29,640 HERE, THE NO ANTIBIOTIC HAS 792 00:37:29,640 --> 00:37:33,120 PREVIOUS SURVIVAL WITH ANTIBODY 793 00:37:33,120 --> 00:37:35,440 BAD. 794 00:37:35,440 --> 00:37:38,120 AND AGAIN, THIS AGP PROJECT 795 00:37:38,120 --> 00:37:44,440 THANK GOD, EXISTS PROVIDED THE 796 00:37:44,440 --> 00:37:46,160 TREATMENT AND THIS IS THE RESULT 797 00:37:46,160 --> 00:37:49,600 OF THE DENSITY PLOTS THAT WE 798 00:37:49,600 --> 00:37:50,160 PROD. 799 00:37:50,160 --> 00:37:52,000 WITHOUT ANTIBIOTICS, THIS IS 800 00:37:52,000 --> 00:37:54,480 WHAT WE SEE ON THE LEFT SIDE. 801 00:37:54,480 --> 00:37:56,560 WITH ANTIBIOTIC THIS LOOKS VERY 802 00:37:56,560 --> 00:38:00,640 DIFFERENT AND IF YOU OVER LAY 803 00:38:00,640 --> 00:38:04,360 THESE TWO DENSITY PLOTS, YOU GET 804 00:38:04,360 --> 00:38:06,200 THE RED SPACES THAT SHOW WHICH 805 00:38:06,200 --> 00:38:10,280 ONE IS ACTUALLY THE MOST 806 00:38:10,280 --> 00:38:12,240 PROBLEMATIC INDUCED BY 807 00:38:12,240 --> 00:38:13,640 ANTIBIOTIC TREATMENT SO WE 808 00:38:13,640 --> 00:38:17,000 DEFINED THIS AS A MICROBE TYPE 809 00:38:17,000 --> 00:38:18,160 AND THIS IS AGAIN. 810 00:38:18,160 --> 00:38:25,320 LET'S LOOK AT OUR MAP AND THEY 811 00:38:25,320 --> 00:38:26,800 LOST THE GOOD PORTION AND GAINED 812 00:38:26,800 --> 00:38:31,840 THE WHOLE DIVERSITY OF THE BAD 813 00:38:31,840 --> 00:38:32,520 TYPE. 814 00:38:32,520 --> 00:38:33,520 APPROXIMATE VERY BRIEFLY I'M 815 00:38:33,520 --> 00:38:35,520 GOING TO TOUCH ON THE STUDY THAT 816 00:38:35,520 --> 00:38:37,400 WE WERE VERY LUCKY TO BE PART 817 00:38:37,400 --> 00:38:38,480 OF. 818 00:38:38,480 --> 00:38:44,800 WHICH IS TRANSFER OF MICROBIAL 819 00:38:44,800 --> 00:38:46,520 MATTER FROM RESPONDING PATIENTS 820 00:38:46,520 --> 00:38:49,160 TO NOT RESPONDING PATIENTS AND 821 00:38:49,160 --> 00:38:55,000 LOCKING AT THE REVERSAL OF THE 822 00:38:55,000 --> 00:38:58,160 PHENOTYPE OF LACK OF RESPONSE TO 823 00:38:58,160 --> 00:39:05,080 ANTI HD PD-1 TREATMENT. 824 00:39:05,080 --> 00:39:08,480 AGAIN TOGETHER WITH PITTSBURG, 825 00:39:08,480 --> 00:39:13,120 WE OBSERVED THAT THE RECIPIENTS 826 00:39:13,120 --> 00:39:16,080 THAT RECEIVED FECAL MICROBIAL 827 00:39:16,080 --> 00:39:19,200 TRANSPLANT ACTUALLY REVERSED THE 828 00:39:19,200 --> 00:39:20,240 NON RESPOND EGG PHENOTYPE AND 829 00:39:20,240 --> 00:39:24,280 WERE RESPONDERS TO TREATMENT 830 00:39:24,280 --> 00:39:27,160 AFTER THEY RECEIVED. 831 00:39:27,160 --> 00:39:29,600 LET'S LOOK AT THE BACTERIA THAT 832 00:39:29,600 --> 00:39:30,960 IS DIFFERENT BETWEEN RESPONDERS 833 00:39:30,960 --> 00:39:31,880 AND NOT RESPONDERS. 834 00:39:31,880 --> 00:39:33,600 THIS IS A COMPLETELY DIFFERENT 835 00:39:33,600 --> 00:39:36,560 STUDY DONE WITH DIFFERENT 836 00:39:36,560 --> 00:39:37,480 PROTOCOLS, DIFFERENT TIMES AND 837 00:39:37,480 --> 00:39:37,800 EVERYTHING. 838 00:39:37,800 --> 00:39:40,040 AND YET THE BACTERIA THAT WE SEE 839 00:39:40,040 --> 00:39:44,880 ALREADY FAMILIAR TO US, LET'S 840 00:39:44,880 --> 00:39:48,120 PUT TOGETHER THE STUDY I JUST 841 00:39:48,120 --> 00:39:51,120 SHOWED BEFORE AND WE'LL SEE, 842 00:39:51,120 --> 00:39:52,160 BECAUSE OF THE NUMBER SIZE OF 843 00:39:52,160 --> 00:39:56,120 THE PATIENTS, OF COURSE WE HAVE 844 00:39:56,120 --> 00:40:00,520 MORE IN THE META ANALYSIS 845 00:40:00,520 --> 00:40:02,480 HOWEVER, THESE TWO LOOK PRETTY 846 00:40:02,480 --> 00:40:05,440 IDENTICAL TO ME. 847 00:40:05,440 --> 00:40:07,360 SO THIS IS A VERY BRIEF 848 00:40:07,360 --> 00:40:07,680 CONCLUSION. 849 00:40:07,680 --> 00:40:09,200 SO WE HAVE ALREADY MULTIPLE 850 00:40:09,200 --> 00:40:11,040 LINES OF EVIDENCE THAT INDICATE 851 00:40:11,040 --> 00:40:16,400 THAT THE BENEFICIAL NATURE OF 852 00:40:16,400 --> 00:40:19,120 MULTIPLE SUCH AS BACTERIA AND 853 00:40:19,120 --> 00:40:23,160 WHILE HIGHLIGHTS THE ROLE 854 00:40:23,160 --> 00:40:27,680 NEGATIVE ROLE OF BACTERIAITIS 855 00:40:27,680 --> 00:40:29,040 AND THE DIFFERENCES THAT 856 00:40:29,040 --> 00:40:30,440 INITIALLY WERE KIND OF CONFUSING 857 00:40:30,440 --> 00:40:35,840 TO ALL OF US, ACTUALLY RESULT IN 858 00:40:35,840 --> 00:40:38,200 THE DIFFERENT SUB SAMPLE 859 00:40:38,200 --> 00:40:39,120 INTERESTING DIFFERENT STUDIES 860 00:40:39,120 --> 00:40:46,560 FROM MICRO HYPER SPACE AND THIS 861 00:40:46,560 --> 00:40:48,200 MAYBE ROW TYPES ARE TWO LARGE 862 00:40:48,200 --> 00:40:49,920 GROUPS, TWO BENEFICIAL AND TWO 863 00:40:49,920 --> 00:40:51,760 DETRIMENTAL AND ONE OF THESE BAD 864 00:40:51,760 --> 00:40:57,120 GROUPS CAN BE INDUCED BY 865 00:40:57,120 --> 00:40:59,040 TREATMENT AND ALSO WE OBSERVED 866 00:40:59,040 --> 00:41:02,040 THEY CAN REVERSE THE PHENOTYPE 867 00:41:02,040 --> 00:41:03,560 OF NON RESPONDERS AND PATIENTS 868 00:41:03,560 --> 00:41:06,960 TO MAKE THEM RESPONDERS AND THAT 869 00:41:06,960 --> 00:41:09,560 WAS QUITE IMPRESSIVE. 870 00:41:09,560 --> 00:41:13,040 SO YOU WOULD ASK WHAT EXACTLY IS 871 00:41:13,040 --> 00:41:16,840 HAPPENING WITH THESE TYPE OF 872 00:41:16,840 --> 00:41:17,840 RESPONDERS AND NOT RESPONDERS 873 00:41:17,840 --> 00:41:21,200 AND THE FUNCTIONAL SPACE. 874 00:41:21,200 --> 00:41:22,480 GENES FROM BACTERIA ARE DOING 875 00:41:22,480 --> 00:41:23,960 ALL THAT AND YOU ARE RIGHT. 876 00:41:23,960 --> 00:41:26,240 THE PROBLEM IS THAT IT'S VERY 877 00:41:26,240 --> 00:41:26,840 INDICTMENT TO ANSWER. 878 00:41:26,840 --> 00:41:31,920 AND THE REASON IS BECAUSE THE 879 00:41:31,920 --> 00:41:34,680 DIFFERENCES ARE SO BIG THAT VAST 880 00:41:34,680 --> 00:41:37,360 MAJORITY OF THESE GENES 881 00:41:37,360 --> 00:41:38,120 IDENTIFIED THEY WERE DIFFERENT 882 00:41:38,120 --> 00:41:40,320 BETWEEN RESPONDERS AND NON 883 00:41:40,320 --> 00:41:41,920 RESPONDERS WHICH WERE 1,000 884 00:41:41,920 --> 00:41:44,200 SOMETHING GENES, THEY WORE 885 00:41:44,200 --> 00:41:46,600 MARKERS OF THE BACK TER TEE AS 886 00:41:46,600 --> 00:41:50,480 WHAT WE DISCUSSED IN THE MAIN 887 00:41:50,480 --> 00:41:54,200 DRIVERS OF THIS TWO PHENOTYPES. 888 00:41:54,200 --> 00:41:58,480 SO THERE ARE WAYS OF THINKING 889 00:41:58,480 --> 00:42:01,240 ABOUT IT IS IF WE COULD COMPARE 890 00:42:01,240 --> 00:42:03,160 BENEFICIAL SPECIES ON THE LEFT 891 00:42:03,160 --> 00:42:07,560 AND THE SPECIES ON THE RIGHT, 892 00:42:07,560 --> 00:42:09,720 HUNTING DOWN THESE VERY TINY 893 00:42:09,720 --> 00:42:13,160 SPECKS GREENS. 894 00:42:13,160 --> 00:42:14,400 THOSE ARE THE GENES THAT DRIVE 895 00:42:14,400 --> 00:42:16,080 OUR PHENOTYPE OF RESPONSE IN 896 00:42:16,080 --> 00:42:20,680 GROWN AND NO RESPONSE IN RED. 897 00:42:20,680 --> 00:42:26,240 YOU ALSO IDENTIFY A LOT OF PATH 898 00:42:26,240 --> 00:42:28,280 GENES THESE BLUE CIRCLES ON THE 899 00:42:28,280 --> 00:42:30,560 LEFT OR ORANGE CIRCLES ON THE 900 00:42:30,560 --> 00:42:34,080 RIGHT SO HOW DO WE SEG ROW GATE 901 00:42:34,080 --> 00:42:38,320 PASSENGER GENES FROM THE DRIVER 902 00:42:38,320 --> 00:42:40,040 GENES OR FUNCTIONAL GENES AND 903 00:42:40,040 --> 00:42:41,680 THERE ARE MULTIPLE TOOLS ONE CAN 904 00:42:41,680 --> 00:42:43,960 USE AND ONE OF THE WAYS OF DOING 905 00:42:43,960 --> 00:42:48,360 IT IS TO DO THE ANALYSIS WITHIN 906 00:42:48,360 --> 00:42:50,960 THE TOX SO WE CAN TAKE A 907 00:42:50,960 --> 00:42:52,640 SIGNIFICANT TOX THAT WE'RE JUST 908 00:42:52,640 --> 00:42:54,600 SHOWING YOU AND SPLIT IT EVEN 909 00:42:54,600 --> 00:42:58,440 FURTHER USING DIFFERENT TYPE OF 910 00:42:58,440 --> 00:42:59,120 TECHNIQUES INTO THE STRAINS AND 911 00:42:59,120 --> 00:43:02,680 THESE ARE SHOWN IN THESE CIRCLES 912 00:43:02,680 --> 00:43:04,760 AND WITH A DASHED LINE. 913 00:43:04,760 --> 00:43:09,440 WITHIN THE CIRCLE, WE HAVE THESE 914 00:43:09,440 --> 00:43:11,400 GROWN GENES THAT PRESENTED HERE 915 00:43:11,400 --> 00:43:13,320 AND THE GENES OF INTEREST AND IF 916 00:43:13,320 --> 00:43:15,960 WE DO THIS BETWEEN THE MULTIPLE 917 00:43:15,960 --> 00:43:17,320 DIFFERENT SIGNIFICANT TAX 918 00:43:17,320 --> 00:43:21,160 SEPARATELY FOR BENEFICIAL AND 919 00:43:21,160 --> 00:43:25,760 SEPARATELY FOR DETRIMENTAL AND 920 00:43:25,760 --> 00:43:27,400 THEN WE'LL HAVE THIS TYPE OF 921 00:43:27,400 --> 00:43:32,040 DIAGRAM THAT WILL SAY, YES, YOU 922 00:43:32,040 --> 00:43:34,760 FIND THESE GENES IN MORE THAN 923 00:43:34,760 --> 00:43:37,280 ONE TAXA SO THERE'S A HIGH 924 00:43:37,280 --> 00:43:40,080 PROBABILITY THAT THIS IS A GREN 925 00:43:40,080 --> 00:43:44,080 THAT DRIVES IT. 926 00:43:44,080 --> 00:43:46,360 SO THIS APPROACH HAS ITS OWN 927 00:43:46,360 --> 00:43:47,640 LIMITATIONS BECAUSE IT HAS TO BE 928 00:43:47,640 --> 00:43:51,080 PART OF THE GENOME WHICH IS 929 00:43:51,080 --> 00:43:53,040 COMPRISED UP TO 20% OF THE 930 00:43:53,040 --> 00:43:55,200 BACTERIAL GENOME AND HOWEVER 931 00:43:55,200 --> 00:43:58,160 IT'S NOT ALWAYS THAT HIGH. 932 00:43:58,160 --> 00:43:58,800 NEVERTHELESS, WE FOUND THAT THIS 933 00:43:58,800 --> 00:44:00,600 IS A REALLY GOOD WAVE US TRYING 934 00:44:00,600 --> 00:44:03,560 TO NARROW IT DOWN THESE HUGE 935 00:44:03,560 --> 00:44:05,160 NUMBER OF GENES AND THIS IS WHAT 936 00:44:05,160 --> 00:44:05,520 WOVE GOT. 937 00:44:05,520 --> 00:44:08,360 WHAT YOU WANT TO LOCK AT IS THE 938 00:44:08,360 --> 00:44:10,880 SPECIES IN RED AND THEY WERE 939 00:44:10,880 --> 00:44:12,320 INITIALLY FOUND TO BE 940 00:44:12,320 --> 00:44:15,120 SIGNIFICANT AND THE BLUE GOWNS 941 00:44:15,120 --> 00:44:17,320 THAT ARE COMMONLY DIFFERENT 942 00:44:17,320 --> 00:44:19,240 BETWEEN THE RESPONDERS AND 943 00:44:19,240 --> 00:44:21,080 RESPONDERS IN FAVOR OF THE 944 00:44:21,080 --> 00:44:23,880 RESPONDERS IN THIS SLIDE AND 945 00:44:23,880 --> 00:44:26,960 WHAT WE SEE HERE IS THAT THE 946 00:44:26,960 --> 00:44:29,000 BACTERIA THAT HAVE HIGH LEVELS 947 00:44:29,000 --> 00:44:33,200 OF THE OF DEGRADING ENZYMES ARE 948 00:44:33,200 --> 00:44:38,520 BENEFICIAL SO OUR CYCLIC DI-GMP 949 00:44:38,520 --> 00:44:41,840 STING AGONIST ELSE WHAT MAKES 950 00:44:41,840 --> 00:44:47,320 METABOLIZE RATED TO RIBOFLAVIN 951 00:44:47,320 --> 00:44:49,400 PATHWAY AND WE DID THE SAME 952 00:44:49,400 --> 00:44:52,120 THING WITH THE LPS NON 953 00:44:52,120 --> 00:44:53,160 RESPONDING BACTERIA AND WE 954 00:44:53,160 --> 00:44:54,680 OPENED THERE WAS A LOT OF GENES 955 00:44:54,680 --> 00:44:59,040 THAT WERE RESPONSIBLE FOR 956 00:44:59,040 --> 00:45:00,760 SYNTHESIS WERE DIFFERENT BETWEEN 957 00:45:00,760 --> 00:45:03,920 THE RESPONDERS AND NOT 958 00:45:03,920 --> 00:45:06,400 RESPONDERS AND THIS IS A HEAT 959 00:45:06,400 --> 00:45:08,720 LAMP OF ALL THE LPS GENES AND 960 00:45:08,720 --> 00:45:12,200 NOW DATASETS THAT WERE FOUND 961 00:45:12,200 --> 00:45:13,720 THAT HAVE AND COMPARE RESPONDER 962 00:45:13,720 --> 00:45:15,320 AND NOT RESPONDERS PATIENTS SO 963 00:45:15,320 --> 00:45:18,560 THERE'S A VAST MAJORITY OF LPS 964 00:45:18,560 --> 00:45:22,320 RELATED GENES CONNECTED TO THE 965 00:45:22,320 --> 00:45:27,080 RESPONDERS. 966 00:45:27,080 --> 00:45:32,560 >>HOW THE HOST RESPOND TO THIS 967 00:45:32,560 --> 00:45:34,280 BEHAVIOR OF THE MICROBIOME AND 968 00:45:34,280 --> 00:45:36,800 WE DID SOMETHING THAT IS NOT 969 00:45:36,800 --> 00:45:40,720 TYPICALLY DONE IN THE FIELD 970 00:45:40,720 --> 00:45:43,760 WHICH IS ANALYZING IN THE STOOL 971 00:45:43,760 --> 00:45:46,720 SIM TOSAMPLE. 972 00:45:46,720 --> 00:45:50,120 SO BEFORE I THROW ME OUT OF THIS 973 00:45:50,120 --> 00:45:52,080 PODIUM FOR DOING THAT I WANT TO 974 00:45:52,080 --> 00:45:53,280 CONVINCE YOU THIS IS A GOOD 975 00:45:53,280 --> 00:45:53,640 IDEA. 976 00:45:53,640 --> 00:45:57,080 SO YOU HAVE A LOT OF CELLS SHED 977 00:45:57,080 --> 00:45:58,720 INTO THE GUT, RIGHT. 978 00:45:58,720 --> 00:46:01,520 THESE ARE NOT JUST EPITHELIAL 979 00:46:01,520 --> 00:46:01,920 CELLS. 980 00:46:01,920 --> 00:46:03,760 THESE ARE IMMUNE CELLS THAT WE 981 00:46:03,760 --> 00:46:08,800 JUST SAW EARLIER OCCUPIED. 982 00:46:08,800 --> 00:46:11,440 WHEN THEY SHED, THEY OCCUPY A 983 00:46:11,440 --> 00:46:14,400 HEFTY PREPORTION FROM .5 ALL THE 984 00:46:14,400 --> 00:46:18,040 WAY TO 1% OF THE SCHOOL RNA WITH 985 00:46:18,040 --> 00:46:20,200 THE HOST RNA. 986 00:46:20,200 --> 00:46:24,080 YES, IT'S VERY DEGRADED BUT IT'S 987 00:46:24,080 --> 00:46:27,720 VERY PRECIOUS INFORMATION 988 00:46:27,720 --> 00:46:31,480 BECAUSE YOU HAVE THE EXACT TIME 989 00:46:31,480 --> 00:46:33,040 OF STOOL SAMPLE. 990 00:46:33,040 --> 00:46:36,720 CALL IT LICK SIMILAR TO LIQUID 991 00:46:36,720 --> 00:46:40,360 BIOPSY THAT WE USE FOR HUMAN 992 00:46:40,360 --> 00:46:40,560 BLOOD. 993 00:46:40,560 --> 00:46:44,760 THESE ARE RESULTS. 994 00:46:44,760 --> 00:46:48,440 ON THE LEFT SIDE WE HAVE GENES 995 00:46:48,440 --> 00:46:50,000 WITH NONRESPONSERS AND THE RIGHT 996 00:46:50,000 --> 00:46:52,240 SIDE WE SEE RESPONDERS SO IT'S A 997 00:46:52,240 --> 00:46:52,520 GOOD NUMBER. 998 00:46:52,520 --> 00:46:54,480 IF YOU DO THE PATH 1 ANALYSIS, 999 00:46:54,480 --> 00:46:58,480 YOU SEE MOST OF THE GENES IN NOT 1000 00:46:58,480 --> 00:47:01,520 RESPONDER SIDE ACTUALLY HAVE 1001 00:47:01,520 --> 00:47:03,600 UPSTREAM IN THE PATHWAYS LPS 1002 00:47:03,600 --> 00:47:09,880 THAT WE JUST TALKED ABOUT. 1003 00:47:09,880 --> 00:47:14,360 SO WHAT ELSE CAN YOU DO WITH 1004 00:47:14,360 --> 00:47:15,280 THIS DATA? 1005 00:47:15,280 --> 00:47:19,160 IMPUTE THE CELLS THAT EXIST IN 1006 00:47:19,160 --> 00:47:23,120 THE EXFOLIOME. 1007 00:47:23,120 --> 00:47:25,520 ALSO TRUST COMPRISES OF 1008 00:47:25,520 --> 00:47:27,680 DIFFERENT RNA SPECIES THAT 1009 00:47:27,680 --> 00:47:30,160 RESIDE IN DIFFERENT CELL TYPES 1010 00:47:30,160 --> 00:47:32,960 SO CAN DIFFERENT TECH NECKS AND 1011 00:47:32,960 --> 00:47:35,560 IN THIS CASE CALLED GCA WE CAN 1012 00:47:35,560 --> 00:47:37,120 RECORRECT THESE AND COMPARE 1013 00:47:37,120 --> 00:47:38,320 RESPONDERS WITH NON RESPONDERS 1014 00:47:38,320 --> 00:47:45,000 EX WHAT YOU SEE HERE IS A LOT OF 1015 00:47:45,000 --> 00:47:46,560 INNATE IMMUNE CELLS WERE 1016 00:47:46,560 --> 00:47:48,000 INCREASED IN THE KNOWN 1017 00:47:48,000 --> 00:47:49,760 RESPONDERS COMPARED TO THE 1018 00:47:49,760 --> 00:47:53,880 RESPONDERS THAT HAD A VERY 1019 00:47:53,880 --> 00:47:57,640 REGULAR IS TYPE OF CELL TYPES 1020 00:47:57,640 --> 00:48:01,840 SUCH AS GOBLET CELLS AND ET 1021 00:48:01,840 --> 00:48:02,280 CETERA. 1022 00:48:02,280 --> 00:48:04,800 SO LET'S SUMMARIZE THESE 1023 00:48:04,800 --> 00:48:07,360 FINDINGS TOGETHER AND BRING THIS 1024 00:48:07,360 --> 00:48:08,960 IN ONE PIECE. 1025 00:48:08,960 --> 00:48:11,120 THIS IS OUR WORKING HYPOTHESIS. 1026 00:48:11,120 --> 00:48:16,280 SO WE HAVE BACTERIA SPECIES. 1027 00:48:16,280 --> 00:48:18,760 WE ALSO IDENTIFIED AND THEY 1028 00:48:18,760 --> 00:48:22,720 PRODUCED LPS AND THEN THERE ARE 1029 00:48:22,720 --> 00:48:28,640 SOME 'EM UNION CELLS IN THE GUT 1030 00:48:28,640 --> 00:48:30,240 THAT MAKE THEY TRAVEL DIRECT LOW 1031 00:48:30,240 --> 00:48:35,560 TO THE TUMOR AND THIS EFFECTS 1032 00:48:35,560 --> 00:48:37,720 THE RESPONSE TO THE PD1 THERAPY 1033 00:48:37,720 --> 00:48:39,240 IN A NEGATIVE WAY. 1034 00:48:39,240 --> 00:48:42,200 YOU CAN BLOCK THIS LPS WITH 1035 00:48:42,200 --> 00:48:43,280 ENZYMES THAT HAVE BEEN 1036 00:48:43,280 --> 00:48:51,160 INTERESTEPRODUCEDBY THE GOOD BLS 1037 00:48:51,160 --> 00:48:56,280 BLOCKING THIS PATHWAY. 1038 00:48:56,280 --> 00:49:00,400 WE ALSO FOUND THAT THEY HAVE 1039 00:49:00,400 --> 00:49:02,440 PATHWAY AND INSIDE OF THEM AND 1040 00:49:02,440 --> 00:49:05,640 JUST WANT TO REMIND YOU THAT 1041 00:49:05,640 --> 00:49:09,800 METABOLITES THAT SURROUND THIS 1042 00:49:09,800 --> 00:49:11,400 PATHWAY TALLLY PRIME MATE CELLS 1043 00:49:11,400 --> 00:49:16,040 AND FINALLY, WE SAW THAT 1044 00:49:16,040 --> 00:49:20,960 BACTERIA SUCH AS THESE FROM THE 1045 00:49:20,960 --> 00:49:25,920 GENOUS PRODUCE DJMP. 1046 00:49:25,920 --> 00:49:29,760 PREDICTED TO PRODUCE DJMP AND 1047 00:49:29,760 --> 00:49:31,160 THIS IS STING THAT HAS BEEN 1048 00:49:31,160 --> 00:49:35,440 REPORTED TO MODULATE MONOCYTE 1049 00:49:35,440 --> 00:49:36,240 DIFFERENTIZATION AND FOR THE 1050 00:49:36,240 --> 00:49:40,560 PROOF OF IT, FROM OUR OWN 1051 00:49:40,560 --> 00:49:43,080 INSTITUTE FROM NCI PUBLISHED A 1052 00:49:43,080 --> 00:49:47,560 VERY NICE PAPER IN CELL THAT 1053 00:49:47,560 --> 00:49:49,400 DEMONSTRATED THAT HUAWEI MP 1054 00:49:49,400 --> 00:49:52,920 WHICH IS RELATIVE TO JMP 1055 00:49:52,920 --> 00:49:54,320 PRODUCTS EFFECTS MONOCYTE 1056 00:49:54,320 --> 00:49:56,000 TRANSITION AND EVENT EFFECTS THE 1057 00:49:56,000 --> 00:50:02,440 RESPONSE OF THE TUMOR THERAPY 1058 00:50:02,440 --> 00:50:04,400 AND THERE'S A GROWING BODY OF 1059 00:50:04,400 --> 00:50:06,120 EVIDENCE THAT MAKE CELLS 1060 00:50:06,120 --> 00:50:09,680 IMPORTANT FOR THE RESPONSE TO 1061 00:50:09,680 --> 00:50:13,560 THE THERAPY SO, WITH THAT, I 1062 00:50:13,560 --> 00:50:18,160 WANT TO CONCLUDE MY TALK AND 1063 00:50:18,160 --> 00:50:22,120 THANK MOSTLY GEORGIA WHO IS THE 1064 00:50:22,120 --> 00:50:27,320 BRAIN BEHIND MOST OF OUR 1065 00:50:27,320 --> 00:50:31,640 OPERATIONS FOR HIS INSIDE FULL 1066 00:50:31,640 --> 00:50:35,720 COMMENTS AND IDEAS AND 1067 00:50:35,720 --> 00:50:37,240 PIONEERING THESE MICROBIOME 1068 00:50:37,240 --> 00:50:40,080 STUDIES IN THE FIELD IN GENERAL. 1069 00:50:40,080 --> 00:50:46,520 I WANT TO THANK HASSAN AND 1070 00:50:46,520 --> 00:50:50,040 DIWAKAR AND OUR CLINICAL 1071 00:50:50,040 --> 00:50:51,080 COLLABORATORS WITH WHOM NONE OF 1072 00:50:51,080 --> 00:50:55,560 THIS WORK WOULD HAVE DID NOT 1073 00:50:55,560 --> 00:51:00,160 POSSIBLE AND THE STAFF OF THE 1074 00:51:00,160 --> 00:51:02,760 MICROBIOME CORE. 1075 00:51:02,760 --> 00:51:05,040 HUNDREDS OF SAMPLES. 1076 00:51:05,040 --> 00:51:07,320 I ALSO WANT TO THANK MEMBERS OF 1077 00:51:07,320 --> 00:51:17,840 OUR LAB JOE MAKALIK AND POONAM 1078 00:51:21,720 --> 00:51:22,680 AND MIRIAM WHO WERE INSTRUMENT 1079 00:51:22,680 --> 00:51:28,240 IN THIS WORK AND ALSO ROMINA FOR 1080 00:51:28,240 --> 00:51:32,280 HER EARLIER WORK ON THIS TOPICS 1081 00:51:32,280 --> 00:51:35,920 FOR US AND FOR ALWAYS USEFUL 1082 00:51:35,920 --> 00:51:42,160 ADVICES AS WELL AS ANDRE AND 1083 00:51:42,160 --> 00:51:43,400 OTHERS WHO PLAYED INSTRUMENTAL 1084 00:51:43,400 --> 00:51:47,720 ROLES IN THESE PROJECTS AND THE 1085 00:51:47,720 --> 00:51:53,640 FACILITY AND OF COURSE, JAY WHO 1086 00:51:53,640 --> 00:51:59,040 PLAYED A IMPORTANT ROLE IN OUR 1087 00:51:59,040 --> 00:52:03,320 DENDRITIC CELL STORY AND I WANT 1088 00:52:03,320 --> 00:52:04,480 TO THANK JASMINE WHO ALWAYS 1089 00:52:04,480 --> 00:52:08,080 PROVIDES USEFUL INSIGHTS AND THE 1090 00:52:08,080 --> 00:52:09,160 STORIES THAT ARE PRESENTED SO 1091 00:52:09,160 --> 00:52:13,200 THANK YOU FOR YOUR TIME. 1092 00:52:15,080 --> 00:52:16,800 >>THAT WAS SUCH A GREAT TALK. 1093 00:52:16,800 --> 00:52:19,640 SO I HAD A QUESTION, BASED ON 1094 00:52:19,640 --> 00:52:22,120 THE FACT THAT THERE COULD BE 1095 00:52:22,120 --> 00:52:24,520 GEOGRAPHICAL OR REGIONAL OR 1096 00:52:24,520 --> 00:52:27,280 DIETARY CHANGES, DO YOU SEE THE 1097 00:52:27,280 --> 00:52:29,440 FUTURE FOR BIOMARKERS OF 1098 00:52:29,440 --> 00:52:32,160 RESPONSE AND NONRESPONSE AT THE 1099 00:52:32,160 --> 00:52:36,680 LEVEL OF BACTERIA OR AT THE 1100 00:52:36,680 --> 00:52:38,040 FUNCTION DIFFERENCE THE LPS OR 1101 00:52:38,040 --> 00:52:40,120 THE HUMAN RESPONSE, LIKE WHAT 1102 00:52:40,120 --> 00:52:42,200 YOU ARE SEWING IN THE HUMAN RNA 1103 00:52:42,200 --> 00:52:44,040 SO THAT'S LIKE PART ONE AND PART 1104 00:52:44,040 --> 00:52:46,320 TWO, I WAS CURIOUS ABOUT IN THE 1105 00:52:46,320 --> 00:52:49,480 NON RESPONDERS, BECAUSE YOU SAY 1106 00:52:49,480 --> 00:52:54,440 THAT THERE'S LIKE 1% OF HUMAN 1107 00:52:54,440 --> 00:52:56,880 NUCLEIC CONTENT IN YOUR STOOL 1108 00:52:56,880 --> 00:52:58,240 SAMPLE, DO YOU SEE HIGHER LEVELS 1109 00:52:58,240 --> 00:53:00,760 IN THE NON RESPONDERS, DO THEY 1110 00:53:00,760 --> 00:53:02,320 HAVE A LEAKY GUT IF THERE'S MORE 1111 00:53:02,320 --> 00:53:04,560 INFLAMMATION AND THERE'S JUST 1112 00:53:04,560 --> 00:53:10,000 MORE CELLS LEAKING INTO THE 1113 00:53:10,000 --> 00:53:10,800 STOOL? 1114 00:53:10,800 --> 00:53:11,600 >>Dr. Dzutsev: IF I MAY START 1115 00:53:11,600 --> 00:53:14,400 FROM THE SECOND QUESTION. 1116 00:53:14,400 --> 00:53:14,840 NO. 1117 00:53:14,840 --> 00:53:17,480 WE DID NOT LOOK AT THE HIGH 1118 00:53:17,480 --> 00:53:18,400 NUMBER. 1119 00:53:18,400 --> 00:53:20,440 IN FACT, OUT OF THE PRESENT VERY 1120 00:53:20,440 --> 00:53:22,960 HIGH PREPORTION OF THE SPECIES 1121 00:53:22,960 --> 00:53:24,800 RNA SPECIES IN THE GUT AND IN 1122 00:53:24,800 --> 00:53:26,960 THE STOOL AND IT'S VERY 1123 00:53:26,960 --> 00:53:28,880 DIFFICULT, ACTUALLY TO GET 1124 00:53:28,880 --> 00:53:29,560 ENOUGH PROPER RATES BECAUSE OF 1125 00:53:29,560 --> 00:53:33,160 THE LEVEL OF DEGRADATION AND SO 1126 00:53:33,160 --> 00:53:35,040 WE DIDN'T REALLY DO THESE TYPE 1127 00:53:35,040 --> 00:53:36,640 OF A CORRELATION BUT I THINK 1128 00:53:36,640 --> 00:53:40,040 IT'S A VERY GOOD IDEA, 1129 00:53:40,040 --> 00:53:41,960 ESPECIALLY GIVEN THE FACT THAT 1130 00:53:41,960 --> 00:53:44,240 YES, WE SAW THE NUMBER OF 1131 00:53:44,240 --> 00:53:48,400 VOLUNTARY CELLS GO UP. 1132 00:53:48,400 --> 00:53:53,440 SO VERY REASONABLE IDEA. 1133 00:53:53,440 --> 00:53:54,680 REGARDING THE DIFFERENT 1134 00:53:54,680 --> 00:53:57,800 PREDICTIVE POWER OF DIFFERENT 1135 00:53:57,800 --> 00:53:59,880 TYPES AND IN GENERAL WE RESPOND 1136 00:53:59,880 --> 00:54:01,120 AND NOT RESPOND SIGNATURE YOU 1137 00:54:01,120 --> 00:54:02,680 ARE ASKING EXACTLY THE SAME 1138 00:54:02,680 --> 00:54:04,200 QUESTION AS MANY COMPANIES 1139 00:54:04,200 --> 00:54:06,840 ALREADY TRIED TO DO SO THERE ARE 1140 00:54:06,840 --> 00:54:10,360 A MULTI MILLION BUSINESS AT THE 1141 00:54:10,360 --> 00:54:12,280 MOMENT WHERE PEOPLE TRIED TO PRO 1142 00:54:12,280 --> 00:54:13,520 DICTIONARY DIFFERENT RESPONSES 1143 00:54:13,520 --> 00:54:15,760 IN ORDER TO MODIFY THE TREATMENT 1144 00:54:15,760 --> 00:54:21,480 AND TO CHANGE THE GUT MICROBIOME 1145 00:54:21,480 --> 00:54:22,560 WITH A DIET. 1146 00:54:22,560 --> 00:54:24,240 THEY HUNT FOR GOOD DONORS THAT 1147 00:54:24,240 --> 00:54:26,320 SO LET'S SAY YOU DEFINE A GOOD 1148 00:54:26,320 --> 00:54:27,720 DONOR FROM THIS TYPE OF STUDY 1149 00:54:27,720 --> 00:54:29,680 AND THEN YOU CAN TAKE THIS GOOD 1150 00:54:29,680 --> 00:54:31,520 DONOR FROM THE POOL OF PATIENTS 1151 00:54:31,520 --> 00:54:33,480 BUT JUST FROM PEOPLE WHO ARE 1152 00:54:33,480 --> 00:54:35,720 AROUND YOU FROM YOUR RELATIVES 1153 00:54:35,720 --> 00:54:37,480 OR JUST FROM PEOPLE ON THE 1154 00:54:37,480 --> 00:54:40,960 STREET BY THE FECAL SAMPLES AND 1155 00:54:40,960 --> 00:54:43,360 SO IT'S VERY ACCEPTS OF 1156 00:54:43,360 --> 00:54:44,360 BUSINESS. 1157 00:54:44,360 --> 00:54:45,840 IT SOUNDS LIKE LIKE A VERY CHEAP 1158 00:54:45,840 --> 00:54:47,160 THING TO DO, RIGHT. 1159 00:54:47,160 --> 00:54:52,040 BUT IN FACT, IT COST UPWARDS UP 1160 00:54:52,040 --> 00:54:55,600 TO $2,000 TO PRO A SINGLE FMT 1161 00:54:55,600 --> 00:54:57,400 TRANSPLANT RIGHT NOW. 1162 00:54:57,400 --> 00:54:57,840 YEAH. 1163 00:54:57,840 --> 00:55:00,880 THAT IS THE BIG MONEY AND A LOT 1164 00:55:00,880 --> 00:55:02,400 OF PEOPLE DOING THIS TYPE OF 1165 00:55:02,400 --> 00:55:03,040 STUFF RIGHT NOW. 1166 00:55:03,040 --> 00:55:13,320 >>THANK YOU. 1167 00:55:13,840 --> 00:55:15,400 >>THAT WAS A LOVELY TALK AND 1168 00:55:15,400 --> 00:55:18,560 THIS IS WHAT OUT OF MY STRONG 1169 00:55:18,560 --> 00:55:20,600 SUIT SINCE I'M A CELL SIGNALER. 1170 00:55:20,600 --> 00:55:21,680 THE QUESTION I HAD, WHEN YOU 1171 00:55:21,680 --> 00:55:23,560 LOOK AT THE GEOGRAPHIC 1172 00:55:23,560 --> 00:55:24,680 DISTRIBUTION OF THE DIFFERENT 1173 00:55:24,680 --> 00:55:26,080 BACTERIA AND YOU THINK ABOUT 1174 00:55:26,080 --> 00:55:27,840 CLINICAL TRIALS, DO YOU FIND 1175 00:55:27,840 --> 00:55:30,240 THAT IF YOU DO YOUR CLINICAL 1176 00:55:30,240 --> 00:55:31,400 TRIAL IN HOUSTON YOU WILL BE 1177 00:55:31,400 --> 00:55:34,960 SUCCESSFUL AND IN BETHESDA DON'T 1178 00:55:34,960 --> 00:55:35,880 DO THE TRIAL. 1179 00:55:35,880 --> 00:55:37,680 THE BETTER WAY IS TO CHANGE THE 1180 00:55:37,680 --> 00:55:37,960 BACTERIA. 1181 00:55:37,960 --> 00:55:40,000 >>NO, BECAUSE ALTHOUGH I DID 1182 00:55:40,000 --> 00:55:43,520 PRESENT THIS AS A FACT, THE 1183 00:55:43,520 --> 00:55:45,520 FIELD IS YET TO ACCEPT OUR 1184 00:55:45,520 --> 00:55:48,320 INTERPRETATION OF THE EVENTS 1185 00:55:48,320 --> 00:55:48,760 HERE. 1186 00:55:48,760 --> 00:55:50,560 AND SECOND OF ALL, PEOPLE REALLY 1187 00:55:50,560 --> 00:55:52,080 DON'T WANT TO LIMIT THEIR 1188 00:55:52,080 --> 00:55:54,960 CLINICAL TRIALS BECAUSE OF SOME 1189 00:55:54,960 --> 00:55:56,200 PETTINESS LIKE GOUGH OWE GRAPH I 1190 00:55:56,200 --> 00:55:57,400 CAN LOCATIONS. 1191 00:55:57,400 --> 00:55:58,240 BECAUSE THEY HAVE OTHER THINGS 1192 00:55:58,240 --> 00:56:01,000 TO WORRY ABOUT LIKE PATHOGENS OR 1193 00:56:01,000 --> 00:56:02,720 WHATEVER OR OTHER TYPE OF 1194 00:56:02,720 --> 00:56:04,480 METADATA THAT THEY'RE LIMITED TO 1195 00:56:04,480 --> 00:56:06,440 DO ANYWAY ALREADY. 1196 00:56:06,440 --> 00:56:09,040 N GENERAL, IF WE'RE ACTUALLY 1197 00:56:09,040 --> 00:56:10,840 USING UPS THIS TYPE OF APPROACH, 1198 00:56:10,840 --> 00:56:12,880 AND WE'RE ACTUALLY SCALING THIS 1199 00:56:12,880 --> 00:56:15,600 UP MUCH MORE RIGHT NOW, WE HAVE, 1200 00:56:15,600 --> 00:56:19,320 INSTEAD OF JUST DOING THIS 1201 00:56:19,320 --> 00:56:19,920 MICROBIOME ON SPACE WE'RE DOING 1202 00:56:19,920 --> 00:56:21,360 THIS ALSO ON THE FUNCTIONAL 1203 00:56:21,360 --> 00:56:23,240 SPACE AND USING THOUSANDS OF 1204 00:56:23,240 --> 00:56:25,160 PEOPLE AND TO RECONDUCT ALL 1205 00:56:25,160 --> 00:56:27,880 THESE DIVE TYPE OF GENOMES AND 1206 00:56:27,880 --> 00:56:29,360 HAVING THE DIFFERENT TYPE OF 1207 00:56:29,360 --> 00:56:31,480 LAYOUTS SO WE WANT TO EXPAND 1208 00:56:31,480 --> 00:56:32,840 THIS IDEA EVEN FURTHER. 1209 00:56:32,840 --> 00:56:35,680 WHEN WE HAVE THAT, PEOPLE CAN 1210 00:56:35,680 --> 00:56:37,840 JUST SIMPLY ADJUST THEIR RESULT 1211 00:56:37,840 --> 00:56:43,000 BASED ON THIS TYPE OF DATA AND 1212 00:56:43,000 --> 00:56:45,400 THAT WILL BE WAY MORE'S YEAR 1213 00:56:45,400 --> 00:56:47,120 THAN CHANGING THE OF CLINICAL 1214 00:56:47,120 --> 00:56:47,880 TRIALS. 1215 00:56:47,880 --> 00:56:49,640 BECAUSE PEOPLE ALSO TRAVEL FROM 1216 00:56:49,640 --> 00:56:50,760 OUTSIDE. 1217 00:56:50,760 --> 00:56:51,920 ESPECIALLY TO NIH. 1218 00:56:51,920 --> 00:56:54,400 EVEN IN THE PLACES LIKE 1219 00:56:54,400 --> 00:56:55,000 PITTSBURG. 1220 00:56:55,000 --> 00:57:04,000 THAT IS WHY IT'S VERY. 1221 00:57:04,000 --> 00:57:06,360 >>IF YOU GO BACK AND LOOK AND 1222 00:57:06,360 --> 00:57:08,000 SEE WHOSE TRIALS WERE SUCCESSFUL 1223 00:57:08,000 --> 00:57:08,920 AND WHOSE WEREN'T? 1224 00:57:08,920 --> 00:57:11,320 >>WE DEFINITELY PLAN TO DO THAT 1225 00:57:11,320 --> 00:57:13,360 BECAUSE WE SPECIFICALLY GO BACK 1226 00:57:13,360 --> 00:57:16,680 TO THE OTHER PEOPLE'S DATA. 1227 00:57:16,680 --> 00:57:18,760 THAT'S OUR -- THAT'S OUR 1228 00:57:18,760 --> 00:57:19,880 PIPELINE RIGHT NOW. 1229 00:57:19,880 --> 00:57:22,080 THAT'S WHAT WE DO THIS NOW EVERY 1230 00:57:22,080 --> 00:57:22,280 TIME. 1231 00:57:22,280 --> 00:57:22,800 >>THANK YOU. 1232 00:57:22,800 --> 00:57:28,040 >>YEAH. 1233 00:57:28,040 --> 00:57:32,960 >>SO LET ME ASK YOU JUST ONE 1234 00:57:32,960 --> 00:57:33,680 QUESTION. 1235 00:57:33,680 --> 00:57:35,560 WHICH YOU HAVEN'T TOUCHED UPON 1236 00:57:35,560 --> 00:57:38,280 THIS. 1237 00:57:38,280 --> 00:57:40,840 THE MICROBIOME ARE IN THE TUMOR 1238 00:57:40,840 --> 00:57:42,800 CELLS. 1239 00:57:42,800 --> 00:57:44,160 OBVIOUSLY, THAT IS A WHOLE 1240 00:57:44,160 --> 00:57:45,400 DIFFERENT STORY AND THERE'S A 1241 00:57:45,400 --> 00:57:47,480 LOT OF DISCUSSION WHETHER YOU 1242 00:57:47,480 --> 00:57:50,480 KNOW, ABOUT THE BIOMARKERS, ET 1243 00:57:50,480 --> 00:57:52,360 CETERA, HOW THIS IS EFFECTED. 1244 00:57:52,360 --> 00:57:56,520 WHAT I WAS WONDERING IS IF YOU 1245 00:57:56,520 --> 00:57:58,600 CAN JUST BASICALLY PROVIDE SOME 1246 00:57:58,600 --> 00:58:00,920 COMMENTS THERE? 1247 00:58:00,920 --> 00:58:02,440 >>Dr. Dzutsev: YEAH, SO, I'M 1248 00:58:02,440 --> 00:58:05,320 GOING TO -- I HAVE ACTUALLY 1249 00:58:05,320 --> 00:58:08,680 SLIDES READY. 1250 00:58:08,680 --> 00:58:12,640 I SEE WHAT HE IS GOING TO SHOW. 1251 00:58:12,640 --> 00:58:18,240 >>WE'RE NOT -- SO ACTUALLY 1252 00:58:18,240 --> 00:58:21,520 THERE'S A STUDY THAT WAS DONE BY 1253 00:58:21,520 --> 00:58:28,480 IN COLLABORATION WITH POONAM IN 1254 00:58:28,480 --> 00:58:33,520 THE LAB AND WE LOOKED AT THE 1255 00:58:33,520 --> 00:58:38,960 DIFFERENCES IN MICRO BIO TOM AND 1256 00:58:38,960 --> 00:58:49,320 IN THIS SLIDE YOU HAVE 1257 00:58:50,400 --> 00:58:50,760 MICROBIOME. 1258 00:58:50,760 --> 00:58:52,880 WE DEVELOPED OUR OWN PROTOCOLS 1259 00:58:52,880 --> 00:58:54,440 TO HAVE A HIGH SENSITIVITY 1260 00:58:54,440 --> 00:58:55,640 BECAUSE IT'S A VERY DIFFICULT 1261 00:58:55,640 --> 00:58:58,080 THINGS TO DO TO ACTUALLY 1262 00:58:58,080 --> 00:59:01,160 SEQUENCE VERY TINY NUMBER OF 1263 00:59:01,160 --> 00:59:02,960 MICROBES WITHIN THE TUMOR. 1264 00:59:02,960 --> 00:59:07,480 NEVERTHELESS, THIS IS A VERY, 1265 00:59:07,480 --> 00:59:09,720 VERY GROWING FIELD AND IT MAKES 1266 00:59:09,720 --> 00:59:10,720 SENSE. 1267 00:59:10,720 --> 00:59:12,800 WE FOUND BACTERIA REPORTED TO BE 1268 00:59:12,800 --> 00:59:15,000 INVOLVED IN THE LIVER CANCER 1269 00:59:15,000 --> 00:59:17,400 DEVELOPMENT AND IT'S ALMOST 1270 00:59:17,400 --> 00:59:18,720 UNIVERSALLY ACCEPTED AND ON ONE 1271 00:59:18,720 --> 00:59:21,400 SIDE AND WE ALSO FOUND A WHOLE 1272 00:59:21,400 --> 00:59:25,840 BUNCH OF OTHER THAT ARE JUST 1273 00:59:25,840 --> 00:59:26,920 INCREASINGLY CONSIDERED TO BE 1274 00:59:26,920 --> 00:59:27,720 PART OF THE DEVELOPMENTS 1275 00:59:27,720 --> 00:59:30,640 SPECIFICALLY FOR CCA AND ONE OF 1276 00:59:30,640 --> 00:59:32,640 MY FAVORITE SLIDES ACTUALLY IN 1277 00:59:32,640 --> 00:59:34,960 THESE TOPICS IS ACTUALLY SEEN 1278 00:59:34,960 --> 00:59:36,040 HERE ON THE RIGHT. 1279 00:59:36,040 --> 00:59:38,920 THESE ARE THE SLIDES THAT POONAM 1280 00:59:38,920 --> 00:59:41,400 DID BY SUSTAINING THE TUMORS, 1281 00:59:41,400 --> 00:59:44,280 LIVER TUMORS THAT WERE PROVIDED 1282 00:59:44,280 --> 00:59:44,960 BY TIM HERE. 1283 00:59:44,960 --> 00:59:47,560 THANK YOU, VERY MUCH. 1284 00:59:47,560 --> 00:59:53,040 AND HIS COLLABORATORS WITH THE 1285 00:59:53,040 --> 00:59:57,640 16S PROBE IN GREEN. 1286 00:59:57,640 --> 01:00:00,840 AS YOU CAN SEE, THE BACTERIA 1287 01:00:00,840 --> 01:00:04,080 ACTUALLY LOCALIZES INTRA CELL IN 1288 01:00:04,080 --> 01:00:05,280 LARGE QUANTITIES. 1289 01:00:05,280 --> 01:00:07,000 INTER TUMORAL BEHAVIOR BEHAVES 1290 01:00:07,000 --> 01:00:09,880 AS IF IT'S EFFECTING THE TUMOR 1291 01:00:09,880 --> 01:00:13,000 SAMPLES SO THERE ARE MULTIPLE 1292 01:00:13,000 --> 01:00:14,160 EXAMPLES FROM THE SLIDES 1293 01:00:14,160 --> 01:00:15,560 COLLECTED TO CLAIM THAT THIS IS 1294 01:00:15,560 --> 01:00:16,960 CORRECT MANY OF ALTHOUGH I'M 1295 01:00:16,960 --> 01:00:20,120 SHOWING YOU AS IF IT'S A 1296 01:00:20,120 --> 01:00:22,200 UNIVERSAL HIGHLY DISPUTED 1297 01:00:22,200 --> 01:00:23,440 PHENOMENON BUT THOSE CELLS ARE 1298 01:00:23,440 --> 01:00:26,200 VERY REAR SO THEY'RE LESS THAN 1299 01:00:26,200 --> 01:00:27,800 1/5,000 CELLS THAT ARE 1300 01:00:27,800 --> 01:00:29,640 INFECTIONED PER SLIDE. 1301 01:00:29,640 --> 01:00:30,880 NEVERTHELESS, THEY EXIST AND 1302 01:00:30,880 --> 01:00:33,280 THEY DO HAVE A PHENOTYPE. 1303 01:00:33,280 --> 01:00:35,240 PEOPLE DID REPORT IT ALREADY 1304 01:00:35,240 --> 01:00:37,960 THAT IN SOME CANCERS, MICROBIOME 1305 01:00:37,960 --> 01:00:38,800 CONTROLS THE RESPONSE TO A 1306 01:00:38,800 --> 01:00:40,640 DIFFERENT TYPE OF THERAPY. 1307 01:00:40,640 --> 01:00:44,720 THIS IS A VERY EXCITING, VERY 1308 01:00:44,720 --> 01:00:48,600 NOBLE FIELD OF STUDY THAT MY 1309 01:00:48,600 --> 01:00:50,560 TEAM ACTUALLY STUDIED A WHILE 1310 01:00:50,560 --> 01:00:55,160 AGO IN THE LIVER CANCER MODELS 1311 01:00:55,160 --> 01:01:00,280 AND IT'S BEEN GAINING A LOT OF 1312 01:01:00,280 --> 01:01:00,480 STEAM. 1313 01:01:00,480 --> 01:01:01,080 >>SO IT'S 1:00. 1314 01:01:01,080 --> 01:01:02,800 I WOULD LIKE TO THANK YOU AGAIN. 1315 01:01:02,800 --> 01:01:06,560 THAT WAS A SUPER EXCITING TALK 1316 01:01:06,560 --> 01:01:09,920 AND I HOPE THERE'S WAY MORE TO 1317 01:01:09,920 --> 01:01:10,280 COME. 1318 01:01:10,280 --> 01:01:10,840 THANK YOU. 1319 01:01:10,840 --> 01:01:12,480 >>Dr. Dzutsev: THANK YOU, TIM. 1320 01:01:12,480 --> 00:00:00,000 [APPLAUSE]