1 00:01:24,024 --> 00:01:26,794 WHICH IS TO HONOR DR. CLAUDE 2 00:01:26,794 --> 00:01:29,430 DESPLAN, IN THE FRONT OVER HERE. 3 00:01:29,430 --> 00:01:34,034 AND DR. DESPLAN IS A SILVER 4 00:01:34,034 --> 00:01:35,202 PROFESSOR OF BIOLOGY AND 5 00:01:35,202 --> 00:01:39,273 NEUROSCIENCED A NEW YORK CENTER 6 00:01:39,273 --> 00:01:43,410 AND AT THE NYU IN ABU DHABI. 7 00:01:43,410 --> 00:01:45,512 DR. DESPLAN HAS A RICH 8 00:01:45,512 --> 00:01:47,881 SCIENTIFIC BACKGROUND AND SET OF 9 00:01:47,881 --> 00:01:50,317 EXPERIENCES, HAS DONE WHAT I'D 10 00:01:50,317 --> 00:01:51,852 SAY IS REMARKABLE WORK THAT 11 00:01:51,852 --> 00:01:54,688 INVOLVES THE GENERATION OF 12 00:01:54,688 --> 00:01:55,689 NEURAL DIVERSITY ESPECIALLY 13 00:01:55,689 --> 00:01:57,124 USING DROSOPHILA VISUAL SYSTEM, 14 00:01:57,124 --> 00:01:58,225 AMONG MANY OTHER AREAS. 15 00:01:58,225 --> 00:02:01,161 AND I KNOW YOU'RE GOING TO ENJOY 16 00:02:01,161 --> 00:02:02,396 HIS LECTURE TODAY. 17 00:02:02,396 --> 00:02:04,331 BUT FOR NOW WHAT I REALLY WANT 18 00:02:04,331 --> 00:02:07,201 TO DO IS PASS THIS OFF TO STEVE 19 00:02:07,201 --> 00:02:08,836 HOFFMAN, WHO IS THE VICE 20 00:02:08,836 --> 00:02:10,271 PRESIDENT OF SCIENCE 21 00:02:10,271 --> 00:02:11,138 PARTNERSHIPS AT THE FOUNDATION 22 00:02:11,138 --> 00:02:12,139 OF THE NIH. 23 00:02:12,139 --> 00:02:15,609 STEVE WILL SAY SOME WORDS ABOUT 24 00:02:15,609 --> 00:02:16,577 THE FNIH. 25 00:02:16,577 --> 00:02:18,912 WELCOME, STEVE, AND THANK YOU 26 00:02:18,912 --> 00:02:21,315 AGAIN. 27 00:02:21,315 --> 00:02:22,383 [APPLAUSE] 28 00:02:22,383 --> 00:02:23,851 >> THANK YOU. 29 00:02:23,851 --> 00:02:24,785 WELCOME TODAY. 30 00:02:24,785 --> 00:02:25,619 THANKS, MIKE. 31 00:02:25,619 --> 00:02:27,354 GOOD AFTERNOON. 32 00:02:27,354 --> 00:02:28,889 WELCOME, I'M STEVE HOFFMAN, VICE 33 00:02:28,889 --> 00:02:29,690 PRESIDENT OF SCIENCE 34 00:02:29,690 --> 00:02:31,859 PARTNERSHIPS, AT THE FOUNDATION 35 00:02:31,859 --> 00:02:33,294 FOR THE NIH. 36 00:02:33,294 --> 00:02:34,795 I'VE BEEN THERE FOR 12 1/2 37 00:02:34,795 --> 00:02:37,131 YEARS, SO IT'S BEEN PLEASING IN 38 00:02:37,131 --> 00:02:39,733 A LOT OF PARTNERSHIPS WITH MANY 39 00:02:39,733 --> 00:02:42,036 NIH I.C.s INCLUDING MIKE AND 40 00:02:42,036 --> 00:02:43,771 NEI TO SUPPORT AND HELP BRING 41 00:02:43,771 --> 00:02:44,405 FORWARD EDUCATION AND TRAINING 42 00:02:44,405 --> 00:02:45,839 IN THIS TYPE OF AREA. 43 00:02:45,839 --> 00:02:49,643 I'M DELIGHTED TO JOIN YOU TODAY 44 00:02:49,643 --> 00:02:51,445 FOR THE 2025 JORAM PIATIGORSKY 45 00:02:51,445 --> 00:02:53,080 BASIC SCIENCE LECTURE AND AWARD. 46 00:02:53,080 --> 00:02:55,549 TODAY WE'RE PLEASED TO HONOR AS 47 00:02:55,549 --> 00:02:57,685 MIKE SAID DR. CLAUDE DESPLAN WHO 48 00:02:57,685 --> 00:02:59,119 WILL PARENTHESES THE LECTURE. 49 00:02:59,119 --> 00:03:01,288 MANY OF YOU MAY KNOW, OR NOT, 50 00:03:01,288 --> 00:03:08,962 THAT THE FNI H IS A 5013C 51 00:03:08,962 --> 00:03:09,663 ORGANIZATION ESTABLISHED BY 52 00:03:09,663 --> 00:03:10,831 CONGRESS TO SUPPORT THE MISSION 53 00:03:10,831 --> 00:03:12,800 OF THE NIH. 54 00:03:12,800 --> 00:03:15,769 WE RAISE FUNDS, CREATE AND 55 00:03:15,769 --> 00:03:18,806 MANAGE PROGRAMS AND 56 00:03:18,806 --> 00:03:21,308 PUBLIC/PRIVATE PARTNERSHIPS TO 57 00:03:21,308 --> 00:03:22,643 SUPPORT BASIC SCIENCE, ADVANCE 58 00:03:22,643 --> 00:03:24,078 BIOMEDICAL RESEARCH AND SUPPORT 59 00:03:24,078 --> 00:03:25,713 EDUCATION AND TRAINING LIKE THE 60 00:03:25,713 --> 00:03:27,247 LECTURE WE HAVE TODAY. 61 00:03:27,247 --> 00:03:29,316 OUR FOCUS IS ON TEAM SCIENCE, 62 00:03:29,316 --> 00:03:32,920 CONNECTING NIH WITH THE BEST 63 00:03:32,920 --> 00:03:34,154 ACADEMICS, LIFE SCIENCES AND 64 00:03:34,154 --> 00:03:35,556 NON-PROFIT AND PATIENT RESEARCH 65 00:03:35,556 --> 00:03:37,091 ORGANIZATIONS TO REALLY SOLVE 66 00:03:37,091 --> 00:03:38,625 PROBLEMS THAT NO ONE 67 00:03:38,625 --> 00:03:39,827 ORGANIZATION CAN DO THEMSELVES. 68 00:03:39,827 --> 00:03:42,863 MIKE AND HIS TEAM HAVE BEEN 69 00:03:42,863 --> 00:03:43,964 TREMENDOUS COLLABORATORS WITH 70 00:03:43,964 --> 00:03:44,732 FNIH. 71 00:03:44,732 --> 00:03:48,469 WE WORK WITH THEM ACROSS 72 00:03:48,469 --> 00:03:50,003 AUTOIMMUNITY, RARE DISEASES, 73 00:03:50,003 --> 00:03:51,772 NEUROSCIENCE, OBVIOUSLY VARIOUS 74 00:03:51,772 --> 00:03:53,173 EYE DISEASES, AND OTHER PROGRAMS 75 00:03:53,173 --> 00:03:54,375 THAT WE HAVE IN DEVELOPMENT 76 00:03:54,375 --> 00:03:55,676 THROUGH THEM. 77 00:03:55,676 --> 00:03:56,677 THROUGH THEIR STEWARDSHIP AND 78 00:03:56,677 --> 00:03:59,213 ALSO BASED AGAIN ON THE GENEROUS 79 00:03:59,213 --> 00:04:02,483 SUPPORT OF DR. PIATIGORSKY AND 80 00:04:02,483 --> 00:04:04,351 HIS WIFE LONA WERE ABLE AND 81 00:04:04,351 --> 00:04:06,220 HONORED TO BRING THIS LECTURE 82 00:04:06,220 --> 00:04:08,555 FORWARD IN SUPPORT OF SCIENCE 83 00:04:08,555 --> 00:04:09,423 AND NEI TODAY. 84 00:04:09,423 --> 00:04:13,761 WHAT WE'RE GOING TO HEAR ABOUT 85 00:04:13,761 --> 00:04:17,831 IS THE FUNDAMENTAL MECHANISMS OF 86 00:04:17,831 --> 00:04:22,102 NEUROGENESIS, THE DROSOPHILA, 87 00:04:22,102 --> 00:04:24,838 SIGNALING PATHWAYS, MANY OF 88 00:04:24,838 --> 00:04:26,206 THESE CONSERVED ACROSS SPECIES, 89 00:04:26,206 --> 00:04:27,141 INCLUDING HUMANS. 90 00:04:27,141 --> 00:04:29,109 DR. DESPLAN'S WORK IS AN 91 00:04:29,109 --> 00:04:30,310 EXEMPLARY DEMONSTRATION OF THE 92 00:04:30,310 --> 00:04:32,513 TYPE OF RESEARCH AND AWARDS THAT 93 00:04:32,513 --> 00:04:34,448 THIS AWARD SEEKS TO SUPPORT. 94 00:04:34,448 --> 00:04:35,983 SO PLEASE ENJOY THIS LECTURE. 95 00:04:35,983 --> 00:04:37,751 AGAIN, THANK YOU FOR ALLOWING US 96 00:04:37,751 --> 00:04:44,858 TO SHARE IN THIS VISION, THE 97 00:04:44,858 --> 00:04:49,396 IMPACT EXEMPLIFIED AS WE SET OR 98 00:04:49,396 --> 00:04:54,201 SIGHTS ON FUTURE ADVANCEMENTS. 99 00:04:54,201 --> 00:04:56,537 I'LL TURN IT BACK TO MIKE, AND 100 00:04:56,537 --> 00:04:57,638 THANK YOU AGAIN. 101 00:04:57,638 --> 00:04:58,605 >> STEVE, THANK YOU VERY MUCH 102 00:04:58,605 --> 00:05:01,875 FOR ALL THAT YOU DO WITH US AT 103 00:05:01,875 --> 00:05:05,379 THE FNIH. 104 00:05:05,379 --> 00:05:06,814 THIS GROUP HAS BEEN GREAT 105 00:05:06,814 --> 00:05:08,348 ACADEMIC PARTNERS WITH US AND 106 00:05:08,348 --> 00:05:11,852 ARE REALLY NICE PEOPLE TO WORK 107 00:05:11,852 --> 00:05:12,186 WITH. 108 00:05:12,186 --> 00:05:16,557 WITH WHAT I WANT TO INTRODUCE 109 00:05:16,557 --> 00:05:17,324 DR. JEREMY NATHANS, SCIENTIST, 110 00:05:17,324 --> 00:05:18,992 WHO IS REALLY WELL KNOWN TO ALL 111 00:05:18,992 --> 00:05:21,161 OF US AT THE NATIONAL EYE 112 00:05:21,161 --> 00:05:21,428 INSTITUTE. 113 00:05:21,428 --> 00:05:23,764 JUST BY WAY OF A QUICK 114 00:05:23,764 --> 00:05:25,532 INTRODUCTION, DR. NATHANS IS 115 00:05:25,532 --> 00:05:28,168 PROFESSOR OF MOLECULAR BIOLOGY 116 00:05:28,168 --> 00:05:30,170 AND GENETICS, NEUROSCIENCE AND 117 00:05:30,170 --> 00:05:30,704 OPHTHALMOLOGY AT THE JOHNS 118 00:05:30,704 --> 00:05:32,906 HOPKINS UNIVERSITY SCHOOL OF 119 00:05:32,906 --> 00:05:33,574 MEDICINE. 120 00:05:33,574 --> 00:05:34,975 HE'S DONE GROUNDBREAKING WORK IN 121 00:05:34,975 --> 00:05:37,377 TERMS OF THE MECHANISMS THAT LET 122 00:05:37,377 --> 00:05:38,779 US SEE COLORS. 123 00:05:38,779 --> 00:05:41,081 HE IDENTIFIED GENES THAT CODE 124 00:05:41,081 --> 00:05:42,850 FOR COLOR VISION, RECEPTORS, THE 125 00:05:42,850 --> 00:05:44,818 CONES OF THE RETINA, 126 00:05:44,818 --> 00:05:46,019 GROUND-BREAKING STUFF DECADES 127 00:05:46,019 --> 00:05:46,553 AGO. 128 00:05:46,553 --> 00:05:48,856 THAT WORK HAS LED TO DISCOVERIES 129 00:05:48,856 --> 00:05:49,957 THAT HAVE CHANGED OUR 130 00:05:49,957 --> 00:05:52,025 UNDERSTANDING OF HOW PEOPLE SEE 131 00:05:52,025 --> 00:05:52,893 THE WORLD. 132 00:05:52,893 --> 00:05:57,931 ANDBUT THE REAL REASON THAT 133 00:05:57,931 --> 00:06:00,667 JEREMY IS HERE, HE'S ONE OF THE 134 00:06:00,667 --> 00:06:02,102 MEMBERS OF THE SELECTION 135 00:06:02,102 --> 00:06:04,605 COMMITTEE FOR THE PIATIGORSKY 136 00:06:04,605 --> 00:06:05,372 LECTURE AND AWARD. 137 00:06:05,372 --> 00:06:15,849 I'LL TURN THE MIC TO YOU, SO 138 00:06:16,416 --> 00:06:16,583 WELCOME. 139 00:06:16,583 --> 00:06:17,084 [APPLAUSE] 140 00:06:17,084 --> 00:06:20,521 >> I'M GOING TO SAY A FEW WORDS 141 00:06:20,521 --> 00:06:21,088 ABOUT JEROME. 142 00:06:21,088 --> 00:06:23,156 FIRST LET ME SAY IT'S A GREAT 143 00:06:23,156 --> 00:06:26,960 HONOR TO BE HERE FOR THIS JORAM 144 00:06:26,960 --> 00:06:28,061 PIATIGORSKY BASIC SCIENCE 145 00:06:28,061 --> 00:06:30,130 LECTURE AND AWARD. 146 00:06:30,130 --> 00:06:32,332 THE LECTURE CELEBRATES CREATIVE 147 00:06:32,332 --> 00:06:34,434 SCIENCE AND ALSO CELEBRATES A 148 00:06:34,434 --> 00:06:35,903 CREATIVE SCIENTIST. 149 00:06:35,903 --> 00:06:37,037 JORAM PIATIGORSKY. 150 00:06:37,037 --> 00:06:38,539 JORAM WAS THE FOUNDING DIRECTOR 151 00:06:38,539 --> 00:06:40,841 OF THE LABORATORY OF MOLECULAR 152 00:06:40,841 --> 00:06:41,842 AND DEVELOPMENTAL BIOLOGY HERE 153 00:06:41,842 --> 00:06:44,578 AT THE NATIONAL EYE INSTITUTE AT 154 00:06:44,578 --> 00:06:45,012 NIH. 155 00:06:45,012 --> 00:06:48,949 STARTING IN THE EARLY 198 0s 156 00:06:48,949 --> 00:06:51,051 WHEN NOTHING WAS KNOWN ABOUT 157 00:06:51,051 --> 00:06:58,292 GENE STRUCTURE AND 158 00:06:58,292 --> 00:07:07,367 MULTI-CELLULARRING OR HE 159 00:07:07,367 --> 00:07:09,202 EXPLORED LENS STRUCTURE AND 160 00:07:09,202 --> 00:07:10,437 DEVELOPMENT AND ORGANISMS AS 161 00:07:10,437 --> 00:07:13,173 DIVERSE AS JELLYFISH AND MICE. 162 00:07:13,173 --> 00:07:17,511 THIS WORK LED TO INSIGHT THAT 163 00:07:17,511 --> 00:07:19,479 ANATOMICALLY DIVERSE ORGANISMS 164 00:07:19,479 --> 00:07:20,213 RETAIN EXTRAORDINARY MOLECULAR 165 00:07:20,213 --> 00:07:23,550 SIMILARITIES AND ALSO LED TO HIS 166 00:07:23,550 --> 00:07:24,318 DISCOVERY OF GENE SHARING, 167 00:07:24,318 --> 00:07:25,953 EVOLUTIONARY MECHANISM IN WHICH 168 00:07:25,953 --> 00:07:28,488 A SINGLE PROTEIN PLAYS DISTINCT 169 00:07:28,488 --> 00:07:30,791 ROLES IN DIFFERENT CELL TYPES. 170 00:07:30,791 --> 00:07:33,393 I'VE KNOWN JORAM FOR ALMOST 40 171 00:07:33,393 --> 00:07:33,827 YEARS. 172 00:07:33,827 --> 00:07:36,229 AND I ADMIRE BOTH HIS WORK AND 173 00:07:36,229 --> 00:07:38,532 HIS APPROACH TO LIFE. 174 00:07:38,532 --> 00:07:42,169 IN PARTICULAR, I ADMIRE HIS 175 00:07:42,169 --> 00:07:43,203 SCIENTIFIC ORIGINALITY AND 176 00:07:43,203 --> 00:07:44,037 DETERMINATION TO MARCH TO THE 177 00:07:44,037 --> 00:07:47,207 BEAT OF HIS OWN DRUMMER IF THAT 178 00:07:47,207 --> 00:07:51,345 MEANT FORGOING WHAT MIGHT HAVE 179 00:07:51,345 --> 00:07:54,147 SEEMED TO BE TRENDIER 180 00:07:54,147 --> 00:07:54,982 DIRECTIONS. 181 00:07:54,982 --> 00:07:56,450 HIS INSIGHT YIELDED REWARDS, 182 00:07:56,450 --> 00:07:58,285 MOST DRAMATICALLY IN HIS 183 00:07:58,285 --> 00:08:01,021 DISCOVERY OF GENE SHARING, I 184 00:08:01,021 --> 00:08:03,423 ALSO ADMIRED JORAM'S DRIVE TO 185 00:08:03,423 --> 00:08:04,191 DEVELOP NON-SCIENTIFIC TALENTS, 186 00:08:04,191 --> 00:08:13,667 IN PARTICULAR TALENTS AS A 187 00:08:13,667 --> 00:08:14,768 WRITER, ENCOMINGS SCIENTIFIC 188 00:08:14,768 --> 00:08:18,372 TREATISE, FICTION, COLLECTIONS 189 00:08:18,372 --> 00:08:22,175 OF ESSAYS AND AN AUTOBIOGRAPHY. 190 00:08:22,175 --> 00:08:26,680 JORAM HAS BECOME AN AUTHORITY ON 191 00:08:26,680 --> 00:08:28,548 INUIT SCULPTURE, A CHAMPION OF 192 00:08:28,548 --> 00:08:31,485 THAT KIND OF ART, BEFRIENDED AND 193 00:08:31,485 --> 00:08:40,394 PROMOTED MANY INUIT ARTISTS. 194 00:08:40,394 --> 00:08:43,764 I ADMIRE HIS KIND INSIDE AND 195 00:08:43,764 --> 00:08:44,297 WISDOM. 196 00:08:44,297 --> 00:08:47,701 HE AND LONA MADE A GIFT TO THE 197 00:08:47,701 --> 00:08:50,337 INTELLECTUAL LIFE OF THE NIH 198 00:08:50,337 --> 00:08:51,505 THAT WILL BRING CREATIVE 199 00:08:51,505 --> 00:08:52,639 SCIENTISTS TO THE CAMPUS AND 200 00:08:52,639 --> 00:08:55,375 INSPIRE THE NEXT GENERATION OF 201 00:08:55,375 --> 00:08:56,109 RESEARCHERS. 202 00:08:56,109 --> 00:09:05,218 NOW I'M PLEASED TO INTRODUCE 203 00:09:05,218 --> 00:09:05,619 JORAM PIATIGORSKY. 204 00:09:05,619 --> 00:09:15,829 [APPLAUSE] 205 00:09:25,539 --> 00:09:27,908 >> WELL, THANK YOU ALL FOR 206 00:09:27,908 --> 00:09:28,141 COMING. 207 00:09:28,141 --> 00:09:28,875 EXCUSE ME. 208 00:09:28,875 --> 00:09:31,845 THANK YOU TO THE FNIH AND NEI 209 00:09:31,845 --> 00:09:38,552 FOR ALL THE HELP AND WORK AND 210 00:09:38,552 --> 00:09:39,486 DELIVERANCE YOU'VE BEEN ABLE TO 211 00:09:39,486 --> 00:09:39,986 DO. 212 00:09:39,986 --> 00:09:43,690 I'LL BE A COUPLE MOMENTS HERE. 213 00:09:43,690 --> 00:09:46,860 AND NOT DETRACT FROM THE MAIN 214 00:09:46,860 --> 00:09:51,131 ATTRACTION, DR. DESPLAN. 215 00:09:51,131 --> 00:09:54,067 THE REASON I CREATED THIS 216 00:09:54,067 --> 00:09:56,703 LECTURE AWARD, TWO REASONS. 217 00:09:56,703 --> 00:09:59,806 ONE OF THEM IS JUST I GUESS FOR 218 00:09:59,806 --> 00:10:01,408 MYSELF THAT I WANTED SOME WAY TO 219 00:10:01,408 --> 00:10:04,411 BE ABLE TO GIVE BACK SOMETHING 220 00:10:04,411 --> 00:10:06,980 TO THE NIH, TO THE NEI, WHO HAVE 221 00:10:06,980 --> 00:10:09,916 SUPPORTED MY WORK SO GENEROUSLY 222 00:10:09,916 --> 00:10:12,352 FOR CLOSE TO 50 YEARS I THINK. 223 00:10:12,352 --> 00:10:14,554 AND I THINK THAT THAT'S 224 00:10:14,554 --> 00:10:15,756 ABSOLUTELY EXCEPTIONAL. 225 00:10:15,756 --> 00:10:19,793 IT ALLOWED ME TO DO THINGS THAT 226 00:10:19,793 --> 00:10:21,528 REALLY THINK WOULD BE VERY HARD 227 00:10:21,528 --> 00:10:24,164 TO DO WITHOUT SUCH SUPPORT AND 228 00:10:24,164 --> 00:10:26,366 ALLOWED THE ACADEMIC FREEDOM I 229 00:10:26,366 --> 00:10:29,202 BELIEVE IS SO CRITICAL FOR 230 00:10:29,202 --> 00:10:29,436 SCIENCE. 231 00:10:29,436 --> 00:10:31,705 THEY NEVER TOLD ME WHAT TO DO, 232 00:10:31,705 --> 00:10:34,141 JUST SET ME FREE AND FUNDED MY 233 00:10:34,141 --> 00:10:36,309 WORK, WHICH IS A REASON I WOULD 234 00:10:36,309 --> 00:10:37,978 LIKE TO DO THE SAME TO THEM IN 235 00:10:37,978 --> 00:10:39,279 SOME WAY. 236 00:10:39,279 --> 00:10:43,550 THE OTHER REASON IS MY DEEP 237 00:10:43,550 --> 00:10:45,619 BELIEF IN BASIC RESEARCH. 238 00:10:45,619 --> 00:10:47,287 OF COURSE, CLINICAL RESEARCH, 239 00:10:47,287 --> 00:10:49,156 MEDICAL RESEARCH, APPLIED 240 00:10:49,156 --> 00:10:50,023 RESEARCH IS ABSOLUTELY CRUCIAL, 241 00:10:50,023 --> 00:10:53,627 IN NO WAY WOULD I LIKE TO SEE 242 00:10:53,627 --> 00:10:55,028 THAT EVEN SLIGHTLY DECREASED. 243 00:10:55,028 --> 00:10:57,030 WE'RE ALL DEPENDENT ON IT, AND 244 00:10:57,030 --> 00:10:58,665 IT'S OF TREMENDOUS VALUE. 245 00:10:58,665 --> 00:11:01,168 BUT IT'S ALSO I THINK IMPORTANT 246 00:11:01,168 --> 00:11:02,702 TO REMEMBER THAT A LOT OF WHAT 247 00:11:02,702 --> 00:11:05,806 WE CAN DO IN MEDICAL RESEARCH 248 00:11:05,806 --> 00:11:08,208 COMES FROM THE WONDERFUL STUDIES 249 00:11:08,208 --> 00:11:11,678 IN BASIC SCIENCE THAT HAS NO 250 00:11:11,678 --> 00:11:13,280 GOAL BEYOND UNDERSTANDING. 251 00:11:13,280 --> 00:11:17,584 IT'S IN A SENSE DESTINATION 252 00:11:17,584 --> 00:11:18,051 FREE, SEEKING GREATER 253 00:11:18,051 --> 00:11:19,119 UNDERSTANDING, FROM WHAT WHAT 254 00:11:19,119 --> 00:11:22,155 YOU NEVER KNOW WHAT'S GOING TO 255 00:11:22,155 --> 00:11:24,491 COME ACROSS AND IT'S A LONG 256 00:11:24,491 --> 00:11:25,926 HISTORY OF EXTRAORDINARY 257 00:11:25,926 --> 00:11:28,962 ADVANCES BECAUSE THERE WERE 258 00:11:28,962 --> 00:11:31,064 PEOPLE BEFORE WHO STUDIED 259 00:11:31,064 --> 00:11:31,832 GENERAL PHENOMENON AND THAT'S 260 00:11:31,832 --> 00:11:34,334 TIED IN A LITTLE BIT WITH THE 261 00:11:34,334 --> 00:11:34,668 EYE. 262 00:11:34,668 --> 00:11:36,837 I WORKED ON THE EYE, ON THE 263 00:11:36,837 --> 00:11:38,572 LENS, CORNEA, FOR MANY YEARS. 264 00:11:38,572 --> 00:11:41,741 BUT IN GENERAL, THE EYE HAS BEEN 265 00:11:41,741 --> 00:11:45,045 SUPPORTED I BELIEVE OR MAIN 266 00:11:45,045 --> 00:11:45,645 INTEREST TO OPHTHALMOLOGISTS, 267 00:11:45,645 --> 00:11:47,047 PEOPLE INTERESTED IN THE EYE, 268 00:11:47,047 --> 00:11:48,448 WHEN DISCOVERIES ARE MADE SEEING 269 00:11:48,448 --> 00:11:49,883 HOW IT APPLIES TO THE EYE AND I 270 00:11:49,883 --> 00:11:52,485 THINK THAT'S BEEN CRUCIAL AND 271 00:11:52,485 --> 00:11:53,386 IT'S TERRIBLY IMPORTANT. 272 00:11:53,386 --> 00:11:54,921 BUT I THINK WHAT ALSO CAN 273 00:11:54,921 --> 00:11:57,090 HAPPEN, AND IT DOES HAPPEN, AND 274 00:11:57,090 --> 00:11:58,558 IS HAPPENING, IS THAT INSTEAD OF 275 00:11:58,558 --> 00:12:01,294 GOING FROM THE WORLD TO THE EYE, 276 00:12:01,294 --> 00:12:03,797 IT'S POSSIBLE WITH REALLY FINE 277 00:12:03,797 --> 00:12:05,532 BASIC SCIENCE YOU CAN GO FROM 278 00:12:05,532 --> 00:12:10,136 THE EYE TO THE WORLD AND WHAT'S 279 00:12:10,136 --> 00:12:11,071 DISCOVERED BY RESEARCHERS IN 280 00:12:11,071 --> 00:12:14,207 VISION AND COMPONENTS OF THE EYE 281 00:12:14,207 --> 00:12:16,810 CAN BE FOUND APPLICABLE TO ALL 282 00:12:16,810 --> 00:12:21,648 KINDS OF OTHER PHENOMENONN , IN 283 00:12:21,648 --> 00:12:23,950 MY OWN STUDIES WITH RESPECT TO 284 00:12:23,950 --> 00:12:25,151 GENE EVOLUTION. 285 00:12:25,151 --> 00:12:29,055 BY SUPPORTING THE IDEA OF BASIC 286 00:12:29,055 --> 00:12:32,359 RESEARCH IT WILL ALLOW IN SOME 287 00:12:32,359 --> 00:12:33,560 WAY TO -- IF THIS LECTURE HELPS 288 00:12:33,560 --> 00:12:35,662 IN SOME WAY TO ALLOW THAT TO 289 00:12:35,662 --> 00:12:38,932 INCREASE AND AT LEAST NOT BE 290 00:12:38,932 --> 00:12:40,166 FORGOTTEN AS THE MEDICAL 291 00:12:40,166 --> 00:12:42,002 RESEARCH IS DEVELOPED, I THINK 292 00:12:42,002 --> 00:12:43,737 IT WILL BE GREAT BENEFIT, NOT 293 00:12:43,737 --> 00:12:47,140 ONLY TO SCIENCE BUT TO THE EYE 294 00:12:47,140 --> 00:12:49,209 INSTITUTE ITSELF BECAUSE THEN 295 00:12:49,209 --> 00:12:50,410 PEOPLE WHO MAYBE NOT HAVE LOOKED 296 00:12:50,410 --> 00:12:55,248 AT THE EYE INSTITUTE BASIC 297 00:12:55,248 --> 00:12:57,183 SCIENTISTS BECAUSE THEY SAID 298 00:12:57,183 --> 00:12:59,052 THAT'S MORE FOR VISION THAN 299 00:12:59,052 --> 00:13:00,587 MEDICINE THEY WILL RECOGNIZE THE 300 00:13:00,587 --> 00:13:01,354 TREMENDOUS COMPLEXITY AND 301 00:13:01,354 --> 00:13:03,523 TREMENDOUS OPPORTUNITIES IN EYE 302 00:13:03,523 --> 00:13:04,591 RESEARCH FROM ALL SORTS OF 303 00:13:04,591 --> 00:13:05,625 LEVELS MAYBE THAT WOULD BE A 304 00:13:05,625 --> 00:13:08,662 GOOD IDEA FOR ME TO APPLY TO THE 305 00:13:08,662 --> 00:13:10,363 EYE INSTITUTE AND I THINK THAT 306 00:13:10,363 --> 00:13:13,466 WOULD ENRICH THE EYE INSTITUTE 307 00:13:13,466 --> 00:13:14,301 WITH NEW GENERATIONS, NEW BLOOD, 308 00:13:14,301 --> 00:13:16,469 AND I'VE SEEN IT WORK IN MY OWN 309 00:13:16,469 --> 00:13:17,804 LAB IN THE SENSE THAT ALMOST 310 00:13:17,804 --> 00:13:21,074 NOBODY WHO HAS COME TO MY LAB AS 311 00:13:21,074 --> 00:13:22,409 A POSTDOC KNEW ANYTHING ABOUT 312 00:13:22,409 --> 00:13:23,944 THE EYE WHEN THEY CAME AND 313 00:13:23,944 --> 00:13:26,112 ALMOST ALL OF THEM HAVE 314 00:13:26,112 --> 00:13:27,047 CONTINUED IN EYE RESEARCH. 315 00:13:27,047 --> 00:13:30,317 SO I HOPE THAT THIS LECTURE WILL 316 00:13:30,317 --> 00:13:32,752 PROMOTE THAT TO SOME EXTENT. 317 00:13:32,752 --> 00:13:34,854 THANK YOU VERY MUCH. 318 00:13:34,854 --> 00:13:45,065 [APPLAUSE] 319 00:14:04,150 --> 00:14:06,653 >> THIS WAS A WELL CHOREOGRAPHED 320 00:14:06,653 --> 00:14:08,188 SET OF INTRODUCTIONS, AND I 321 00:14:08,188 --> 00:14:09,189 DIDN'T MEMORIZE THE SCHEDULE. 322 00:14:09,189 --> 00:14:10,256 I'M BACK HERE. 323 00:14:10,256 --> 00:14:12,559 I'M GOING TO SAY SOME THINGS 324 00:14:12,559 --> 00:14:14,961 ABOUT CLAUDE DESPLAN, OUR 325 00:14:14,961 --> 00:14:17,030 SPEAKER AND AWARDEE. 326 00:14:17,030 --> 00:14:19,232 CLAUDE IS THE SILVER PROFESSOR 327 00:14:19,232 --> 00:14:25,805 OF BIOLOGY NYU, DIRECTOR OF THE 328 00:14:25,805 --> 00:14:26,539 CENTER FOR DEVELOPMENTAL 329 00:14:26,539 --> 00:14:27,007 GENETICS. 330 00:14:27,007 --> 00:14:28,975 HE WAS BORN IN ALGERIA, LIVED 331 00:14:28,975 --> 00:14:30,810 THERE UNTIL HE WAS 9, HIS 332 00:14:30,810 --> 00:14:33,480 PARENTS LEFT AS THE ALGERIAN WAR 333 00:14:33,480 --> 00:14:34,347 FOR INDEPENDENCE FINISHED. 334 00:14:34,347 --> 00:14:40,920 THEY LEFT AND WENT TO FRANCE. 335 00:14:40,920 --> 00:14:43,423 HE WAS EDUCATED AT THE FRENCH 336 00:14:43,423 --> 00:14:44,758 VERSION OF HARVARD, AND THEN AT 337 00:14:44,758 --> 00:14:47,160 THE UNIVERSITY OF PARIS FOR HIS 338 00:14:47,160 --> 00:14:47,494 Ph.D. 339 00:14:47,494 --> 00:14:52,432 ONE OF HIS FIRST PAPERS WAS 340 00:14:52,432 --> 00:14:52,999 DEVELOPING IMMUNOASSAY FOR 341 00:14:52,999 --> 00:14:54,300 PARATHYROID HORMONE, PUBLISHED 342 00:14:54,300 --> 00:14:55,802 IN "THE LANCET" IN 1977. 343 00:14:55,802 --> 00:14:58,238 I MENTIONED THIS BECAUSE I WAS 344 00:14:58,238 --> 00:14:59,973 ALSO WORKING ON PARATHYROID 345 00:14:59,973 --> 00:15:01,941 HORMONE AS UNDERGRADUATE, WE 346 00:15:01,941 --> 00:15:04,477 WERE ALMOST SYNCHRONIZED. 347 00:15:04,477 --> 00:15:05,512 AND THEN CLAUDE DID SOMETHING 348 00:15:05,512 --> 00:15:07,013 QUITE DIFFERENT. 349 00:15:07,013 --> 00:15:10,517 HE WENT TO UCSF AS A 350 00:15:10,517 --> 00:15:13,486 POSTDOCTORAL FELLOW, SWITCHED 351 00:15:13,486 --> 00:15:16,122 INTO DEVELOPMENTAL GENETICS AT 352 00:15:16,122 --> 00:15:18,491 THE MOST EXCITING MOMENT, AS THE 353 00:15:18,491 --> 00:15:20,126 DISCOVERY OF THE HOMEOBOX GENES 354 00:15:20,126 --> 00:15:21,127 HAD BEEN MADE, IT WASN'T CLEAR 355 00:15:21,127 --> 00:15:23,763 WHAT THEY DID. 356 00:15:23,763 --> 00:15:27,267 HE SHOWED THESE WERE 357 00:15:27,267 --> 00:15:28,601 TRANSCRIPTION FACTORS USING GENE 358 00:15:28,601 --> 00:15:29,602 IN DROSOPHILA AND DEFINED NOT 359 00:15:29,602 --> 00:15:31,538 ONLY THE REGION OF THE PROTEIN 360 00:15:31,538 --> 00:15:33,740 THAT BOUND DNA, ALSO DEFINED DNA 361 00:15:33,740 --> 00:15:36,009 BINDING SITE AND THEN AS AN 362 00:15:36,009 --> 00:15:38,111 INDEPENDENT INVESTIGATOR HE DID 363 00:15:38,111 --> 00:15:40,413 A SERIES OF STUDIES OF 364 00:15:40,413 --> 00:15:41,581 DROSOPHILA DEVELOPMENT INITIALLY 365 00:15:41,581 --> 00:15:43,249 IN EMBRYO BUT IN MORE RECENT 366 00:15:43,249 --> 00:15:45,218 YEARS IN THE VISUAL SYSTEM THAT 367 00:15:45,218 --> 00:15:49,489 HAVE BUILT ON THIS MOLECULAR 368 00:15:49,489 --> 00:15:50,356 GENETIC REDUCTIONIST APPROACH, 369 00:15:50,356 --> 00:15:51,991 HOW DID GENES CONTROL 370 00:15:51,991 --> 00:15:53,093 DEVELOPMENT. 371 00:15:53,093 --> 00:15:55,528 THAT'S THE BIG PICTURE. 372 00:15:55,528 --> 00:15:57,597 AND AMONG MANY THINGS CLAUDE HAS 373 00:15:57,597 --> 00:15:59,065 úDOI 374 00:15:59,065 --> 00:16:01,568 CAN'T CITE THEM ALL, BUT I'LL 375 00:16:01,568 --> 00:16:04,637 SAY THAT HE WAS ONE OF THE 376 00:16:04,637 --> 00:16:07,707 ORIGINAL PEOPLE WHO REALIZED THE 377 00:16:07,707 --> 00:16:11,377 IMPORTANCE OF THE PAX FAMILIAR 378 00:16:11,377 --> 00:16:12,712 OF TRANSCRIPTION FACTORED, PACKS 379 00:16:12,712 --> 00:16:17,117 PROTEINS HAVE TWO DNA BINDING 380 00:16:17,117 --> 00:16:19,519 DOMAINS, INTERACTING WITH TARGET 381 00:16:19,519 --> 00:16:20,820 DNAs, IN COLLABORATION WITH 382 00:16:20,820 --> 00:16:23,890 JOHN CORIAN AND CARL PAYBO 383 00:16:23,890 --> 00:16:25,525 SOLVED CRYSTAL STRUCTURES OF 384 00:16:25,525 --> 00:16:27,961 PROTEINS BOUND TO DNA TARGETS. 385 00:16:27,961 --> 00:16:37,470 ONE OF THEM, THE MOST FAMOUS IS 386 00:16:37,470 --> 00:16:41,274 PAX 6, THAT BINDS TO THE 387 00:16:41,274 --> 00:16:42,142 RHODOPSIN PROMOTER IN 388 00:16:42,142 --> 00:16:43,476 DROSOPHILA, KICKED OFF HIS 389 00:16:43,476 --> 00:16:44,777 PASSION FOR THE VISUAL SYSTEM 390 00:16:44,777 --> 00:16:48,715 AND SINCE THEN HAS DONE MANY 391 00:16:48,715 --> 00:16:52,919 THINGS IN VISION, IN FLIES, 392 00:16:52,919 --> 00:16:56,823 DEFINED AT A COMPLETE LEVEL THE 393 00:16:56,823 --> 00:17:00,693 TRANSCRIPTOMES OF DEVELOPING FLY 394 00:17:00,693 --> 00:17:02,028 OPTIC LOBE, HAS DEFINED 395 00:17:02,028 --> 00:17:03,129 TRANSCRIPTIONAL CONTROL UNITS 396 00:17:03,129 --> 00:17:05,532 AND CIRCUITS, HAS ALSO DEFINED 397 00:17:05,532 --> 00:17:06,599 NEURAL CIRCUITS, FUNCTIONAL 398 00:17:06,599 --> 00:17:07,934 NEURAL CIRCUITS THAT CONTROL 399 00:17:07,934 --> 00:17:10,803 SENSATION OF MOVEMENT, MOVEMENT 400 00:17:10,803 --> 00:17:13,306 OF OBJECTS IN THE OUTSIDE WORLD. 401 00:17:13,306 --> 00:17:15,275 RECENTLY EXTENDED HIS INTEREST 402 00:17:15,275 --> 00:17:19,979 TO ANTS, HE'S BEEN WORKING ON 403 00:17:19,979 --> 00:17:22,849 ANT OLFACTION AND CONTROL OF 404 00:17:22,849 --> 00:17:23,716 CAST IN ANTS. 405 00:17:23,716 --> 00:17:26,452 ANTS ARE NOT THE ONLY 406 00:17:26,452 --> 00:17:27,587 NON-DROSOPHILA INTEREST. 407 00:17:27,587 --> 00:17:29,189 HE'S ALWAYS TAKEN THE DROSOPHILA 408 00:17:29,189 --> 00:17:31,724 INSIGHTS AND EXTENDED THEM TO 409 00:17:31,724 --> 00:17:34,327 OTHER INSECTS, FOR EXAMPLE 410 00:17:34,327 --> 00:17:37,530 WORKED ON BUTTERFLIES AND 411 00:17:37,530 --> 00:17:38,398 STOCHASTIC CONTROL OF 412 00:17:38,398 --> 00:17:39,499 PHOTORECEPTOR SIGHT IN 413 00:17:39,499 --> 00:17:42,869 DROSOPHILA AND SUBSEQUENTLY IN 414 00:17:42,869 --> 00:17:43,169 BUTTERFLIES. 415 00:17:43,169 --> 00:17:45,505 CLAUDE, I WANT TO SAY I'VE 416 00:17:45,505 --> 00:17:47,040 WONDERED AT SOME POINTS HOW YOU 417 00:17:47,040 --> 00:17:50,076 HAVE MANAGED TO DO ALL OF THIS 418 00:17:50,076 --> 00:17:51,511 STUFF, WHAT I'VE REALIZED IS 419 00:17:51,511 --> 00:17:55,615 ONLY RECENTLY CLAUDE HAS VERY 420 00:17:55,615 --> 00:17:56,449 GOOD GENES. 421 00:17:56,449 --> 00:17:58,885 HIS MOTHER WAS A YOGA INSTRUCTOR 422 00:17:58,885 --> 00:18:00,086 INTO HER 90s. 423 00:18:00,086 --> 00:18:01,821 YOU'VE GOT BOTH NATURE AND 424 00:18:01,821 --> 00:18:03,923 NURTURE WORKING ON YOUR SIDE. 425 00:18:03,923 --> 00:18:05,425 I'LL JUST CONCLUDE BY SAYING 426 00:18:05,425 --> 00:18:06,993 CLAUDE HAS BEEN WIDELY 427 00:18:06,993 --> 00:18:08,394 RECOGNIZED FOR HIS MANY 428 00:18:08,394 --> 00:18:10,964 CONTRIBUTIONS, A MEMBER OF THE 429 00:18:10,964 --> 00:18:14,000 NATIONAL ACADEMY OF SCIENCES, 430 00:18:14,000 --> 00:18:15,802 WAS AWARDED EDWIN CONKLIN PRIZE 431 00:18:15,802 --> 00:18:18,404 FOR SOCIETY OF DEVELOPMENTAL 432 00:18:18,404 --> 00:18:18,638 BIOLOGY. 433 00:18:18,638 --> 00:18:21,908 HE GOT ONE OF THE SORT OF BEST 434 00:18:21,908 --> 00:18:23,343 TEACHER AWARDS FROM NYU 435 00:18:23,343 --> 00:18:24,744 RECENTLY, AND HERE'S THE ONE I 436 00:18:24,744 --> 00:18:26,079 LIKE THE BEST. 437 00:18:26,079 --> 00:18:28,381 HE GOT THE COOLEST PROFESSOR 438 00:18:28,381 --> 00:18:28,815 AWARD FROM NYU. 439 00:18:28,815 --> 00:18:31,751 I'D LIKE TO HEAR MORE ABOUT THAT 440 00:18:31,751 --> 00:18:32,452 ONE. 441 00:18:32,452 --> 00:18:33,419 SO, CLAUDE, WE'RE LOOKING 442 00:18:33,419 --> 00:18:40,426 FORWARD TO YOUR TALK. 443 00:18:40,426 --> 00:18:48,968 THANK YOU SO MUCH. 444 00:18:48,968 --> 00:18:49,636 [APPLAUSE] 445 00:18:49,636 --> 00:18:52,705 >> IT'S VERY HUMBLING TO BE 446 00:18:52,705 --> 00:18:53,606 HERE. 447 00:18:53,606 --> 00:18:56,009 AS SCIENTISTS WE WORK VERY HARD. 448 00:18:56,009 --> 00:18:57,343 WE GET AMAZING RESULTS 449 00:18:57,343 --> 00:18:59,078 SOMETIMES. 450 00:18:59,078 --> 00:19:00,513 WE SUFFER SOMETIMES ALSO. 451 00:19:00,513 --> 00:19:01,914 ALSO STARTING TRYING TO MAKE 452 00:19:01,914 --> 00:19:05,118 SURE PEOPLE UNDERSTAND WHAT 453 00:19:05,118 --> 00:19:06,986 WE'RE DOING. 454 00:19:06,986 --> 00:19:10,857 SO ACTUALLY I FIRST MET JORAM 455 00:19:10,857 --> 00:19:13,826 WHEN MAYBE 25 YEARS AGO. 456 00:19:13,826 --> 00:19:14,927 HE DESCRIBED THIS MOTION PROTEIN 457 00:19:14,927 --> 00:19:17,897 CAN BE USED FOR TWO DIFFERENT 458 00:19:17,897 --> 00:19:20,233 PURPOSES, FINE TUNING FUNCTIONS 459 00:19:20,233 --> 00:19:21,801 ENZYME AND FUNCTION AS A LENS. 460 00:19:21,801 --> 00:19:24,003 I WAS STRUCK. 461 00:19:24,003 --> 00:19:24,871 I REMEMBER A NICE DISCUSSION AT 462 00:19:24,871 --> 00:19:27,040 THE TIME. 463 00:19:27,040 --> 00:19:29,475 BUT ANYWAY, I WANT TO THANK 464 00:19:29,475 --> 00:19:33,079 JORAM AND LONA FOR BEING HERE 465 00:19:33,079 --> 00:19:35,915 AND THE COMMITTEE AND RECOGNIZED 466 00:19:35,915 --> 00:19:38,251 BY THE PEER SOMETHING WE DO 467 00:19:38,251 --> 00:19:40,520 VALUE VERY MUCH. 468 00:19:40,520 --> 00:19:48,494 WE LIKE TO KNOW PEOPLE RECOGNIZE 469 00:19:48,494 --> 00:19:49,162 WHAT WE'RE DOING. 470 00:19:49,162 --> 00:19:51,664 I WANT TO THANK NIH AND NEI 471 00:19:51,664 --> 00:19:54,334 BECAUSE OVER THE LAST 25 YEARS, 472 00:19:54,334 --> 00:19:57,370 NOT 50 BUT 25 YEARS MY LAB HAS 473 00:19:57,370 --> 00:20:00,006 BEEN SUPPORTED BY SEVERAL NEI 474 00:20:00,006 --> 00:20:00,239 GRANTS. 475 00:20:00,239 --> 00:20:01,441 WITHOUT THAT NOTHING HAS BEEN 476 00:20:01,441 --> 00:20:08,681 DONE, EVERYTHING I TALKED ABOUT 477 00:20:08,681 --> 00:20:13,419 WAS SUPPORTED BY NEI. 478 00:20:13,419 --> 00:20:15,822 OF COURSE, I WANT TO RECOGNIZE 479 00:20:15,822 --> 00:20:17,457 MY LAB, HAS DONE SO MUCH. 480 00:20:17,457 --> 00:20:18,758 I'VE BEEN ABLE TO ATTRACT 481 00:20:18,758 --> 00:20:19,859 AMAZING PEOPLE. 482 00:20:19,859 --> 00:20:22,028 SO AT MY LIFE, IN MY LAB, STILL 483 00:20:22,028 --> 00:20:24,464 NOW, I HAVE A LOT OF GREAT 484 00:20:24,464 --> 00:20:27,300 PEOPLE, AT EVERY LEVEL, MANY OF 485 00:20:27,300 --> 00:20:28,601 THEM YOU'LL SEE NOW DEVELOPING 486 00:20:28,601 --> 00:20:31,571 THEIR OWN LAB. 487 00:20:31,571 --> 00:20:35,641 I SHOULD NOT FORGET MY OTHER 488 00:20:35,641 --> 00:20:40,780 PERSON, MY WIFE IS NOT A 489 00:20:40,780 --> 00:20:44,050 SCIENTIST, BUT SHE HELPS ME WITH 490 00:20:44,050 --> 00:20:44,917 BEAUTIFUL PICTURES TO APPRECIATE 491 00:20:44,917 --> 00:20:47,253 WHAT THE VALUE OF ART WOULD BE. 492 00:20:47,253 --> 00:20:49,489 I WILL STOP BEFORE I BECOME TOO 493 00:20:49,489 --> 00:20:50,189 EMOTIONAL AND TELL WHAT YOU 494 00:20:50,189 --> 00:20:51,824 WE'RE DOING IN THE LAB AND WHAT 495 00:20:51,824 --> 00:20:56,996 WE'RE DOING TO FIGURE OUT. 496 00:20:56,996 --> 00:20:57,296 OKAY. 497 00:20:57,296 --> 00:21:00,833 SO, THIS IS A FAMOUS PICTURE 498 00:21:00,833 --> 00:21:07,407 FROM THE SPINAL CORD IN 499 00:21:07,407 --> 00:21:09,242 VERTEBRATE, AND WHEREBY WE KNOW 500 00:21:09,242 --> 00:21:10,910 HOW TO MAKE THE DIFFERENT TYPES 501 00:21:10,910 --> 00:21:15,681 OF NEURONS THAT FORMS THE SPINAL 502 00:21:15,681 --> 00:21:17,617 CORD, FROM THE MOTOR NEURONS TO 503 00:21:17,617 --> 00:21:18,885 THE INTERNEURON TO THE SENSORY 504 00:21:18,885 --> 00:21:22,522 NEURON AND HOW IT'S BEING DONE. 505 00:21:22,522 --> 00:21:27,760 ALL THESE DIFFERENT TYPES OF 506 00:21:27,760 --> 00:21:30,029 CELLS SOME FROM SIMPLE GRADIENT 507 00:21:30,029 --> 00:21:36,102 OF SONIC HEDGEHOG, IN THE FLOOR 508 00:21:36,102 --> 00:21:40,072 PLATE TO DIFFUSE ALONG THE 509 00:21:40,072 --> 00:21:41,707 VENTRAL DORSAL PATH OF THE 510 00:21:41,707 --> 00:21:44,343 SPINAL CORD AND CAN ACTUALLY 511 00:21:44,343 --> 00:21:46,078 LEAD TO THE SPECIFICATION OF ALL 512 00:21:46,078 --> 00:21:46,846 THOSE THINGS. 513 00:21:46,846 --> 00:21:49,715 WE KNOW HOW IT'S HAPPENED AT 514 00:21:49,715 --> 00:21:50,683 MOLECULAR LEVEL. 515 00:21:50,683 --> 00:21:53,986 THE NOTION OF DIFFERENT LEVELS 516 00:21:53,986 --> 00:21:55,655 OF THE TARGET OF THE SIGNALING 517 00:21:55,655 --> 00:21:58,891 PATHWAY HERE ARE ABLE TO INDUCE 518 00:21:58,891 --> 00:22:01,527 GENE EXPRESSION AND HOW 519 00:22:01,527 --> 00:22:03,396 DIFFERENT GENE IN DIFFERENT 520 00:22:03,396 --> 00:22:06,165 COLOR BASICALLY ALLOW THE SYSTEM 521 00:22:06,165 --> 00:22:09,202 TO FUNCTION TO MAKE SPECIFIC 522 00:22:09,202 --> 00:22:11,704 TYPE OF NEURON. 523 00:22:11,704 --> 00:22:13,539 TO THE POINT PEOPLE SPECIAL 524 00:22:13,539 --> 00:22:15,107 INFORMATION WHICH YOU SEE HERE 525 00:22:15,107 --> 00:22:17,643 ALONG THIS AXIS ALMOST 526 00:22:17,643 --> 00:22:21,514 EVERYTHING TO SPECIFY. 527 00:22:21,514 --> 00:22:24,217 HOWEVER, WE KNOW IN FACT FROM 528 00:22:24,217 --> 00:22:26,953 THE WORK OF ANOTHER GRANT, 529 00:22:26,953 --> 00:22:30,823 AMAZING PERSON IN EYE VISION, 530 00:22:30,823 --> 00:22:33,659 MANY YEARS AGO IN FACT THE 531 00:22:33,659 --> 00:22:35,962 RETINA OF MOUSE IS NOT PATTERNED 532 00:22:35,962 --> 00:22:38,898 SO MUCH BY SPECIAL INFORMATION 533 00:22:38,898 --> 00:22:39,999 BUT PATTERNED BY TEMPORAL 534 00:22:39,999 --> 00:22:40,299 INFORMATION. 535 00:22:40,299 --> 00:22:43,936 WHAT I MEAN BY THAT THE FIRST 536 00:22:43,936 --> 00:22:44,904 RETINA GANGLION CELLS BEING 537 00:22:44,904 --> 00:22:47,773 PRODUCED EARLY DURING THE 538 00:22:47,773 --> 00:22:49,075 RETINAL GENESIS, LATER ON ALL 539 00:22:49,075 --> 00:22:54,013 THE CELL TYPE HAVE BEEN 540 00:22:54,013 --> 00:22:55,748 PRODUCED, SO WE KNOW THE TIME IS 541 00:22:55,748 --> 00:22:57,183 VERY IMPORTANT BUT THERE'S A BIG 542 00:22:57,183 --> 00:23:01,254 PROBLEM HERE THAT WE HAVE NO 543 00:23:01,254 --> 00:23:03,956 IDEA TO BE ABLE TO DRIVE 544 00:23:03,956 --> 00:23:04,624 SPECIFICATIONS OF DIFFERENT 545 00:23:04,624 --> 00:23:06,359 TYPES OF NEURONS. 546 00:23:06,359 --> 00:23:08,361 SO MAYBE THIS IS MORE STRIKING 547 00:23:08,361 --> 00:23:10,530 LOOKING AT THE CORTEX OF THE 548 00:23:10,530 --> 00:23:11,430 VERTEBRATE CORTEX, WHEREBY AS 549 00:23:11,430 --> 00:23:15,034 YOU KNOW THE CORTEX IS MADE OF 550 00:23:15,034 --> 00:23:19,305 DIFFERENT LAYERS AND CORTEX MADE 551 00:23:19,305 --> 00:23:22,041 FROM CELLS ORIGINATING FROM THE 552 00:23:22,041 --> 00:23:29,482 BASE OF THE CORTEX AND AS THEY 553 00:23:29,482 --> 00:23:30,149 DIVIDE PRODUCE NEURONS FROM 554 00:23:30,149 --> 00:23:31,450 THESE AREAS AND THAT MEANS THESE 555 00:23:31,450 --> 00:23:33,419 ARE DOING THAT IN A TIME-WISE 556 00:23:33,419 --> 00:23:33,653 MANNER. 557 00:23:33,653 --> 00:23:37,156 TIME IS VERY IMPORTANT HERE. 558 00:23:37,156 --> 00:23:41,294 TO BE CONTROVERSIAL WE KNOW 559 00:23:41,294 --> 00:23:43,930 COMING FROM ONE SINGLE, THAT CAN 560 00:23:43,930 --> 00:23:46,232 DO SIX, FIVE, FOUR, THREE, TWO 561 00:23:46,232 --> 00:23:50,736 IN INSIDE-OUT MANNER, BEAUTIFUL 562 00:23:50,736 --> 00:23:56,976 CLONES SHOW IN THE TABLE YOU CAN 563 00:23:56,976 --> 00:23:58,844 SHOW SINGLE PROGENITOR CAN 564 00:23:58,844 --> 00:24:00,479 PRODUCE LAYER SIX, FIVE, FOUR, 565 00:24:00,479 --> 00:24:02,548 THREE, TWO, BASICALLY YOU CAN 566 00:24:02,548 --> 00:24:04,517 SEE FROM ONE PROGENITOR YOU CAN 567 00:24:04,517 --> 00:24:05,751 MAKE SIX, FIVE DIFFERENT TYPES 568 00:24:05,751 --> 00:24:06,452 OF NEURONS. 569 00:24:06,452 --> 00:24:08,020 AGAIN HERE WE DON'T KNOW THE 570 00:24:08,020 --> 00:24:10,856 MECHANISM WHICH HAS HAPPENED. 571 00:24:10,856 --> 00:24:13,259 HOW DOES TIME TAKE INTO 572 00:24:13,259 --> 00:24:13,593 CONSIDERATION? 573 00:24:13,593 --> 00:24:15,127 TODAY I'LL TELL HOW WE CAN 574 00:24:15,127 --> 00:24:18,731 CONTRIBUTE AND HOW TIME CAN BE 575 00:24:18,731 --> 00:24:19,599 TAKEN INTO CONSIDERATION 576 00:24:19,599 --> 00:24:25,871 INCLUDING SPACE AND HOW NEURONS 577 00:24:25,871 --> 00:24:30,009 CAN BE SPECIFIED BY THE 578 00:24:30,009 --> 00:24:30,676 MECHANISM. 579 00:24:30,676 --> 00:24:37,516 SO THE SYSTEM THAT REVIEWS 580 00:24:37,516 --> 00:24:39,819 VISUAL SYSTEM, FLIES CAN FLY 581 00:24:39,819 --> 00:24:40,686 HIGH SPEED, ACROBATIC FLYING, 582 00:24:40,686 --> 00:24:43,189 NEED VERY GOOD EYES TO DO THAT. 583 00:24:43,189 --> 00:24:45,358 IN FACT DEDICATE MORE THAN 2/3 584 00:24:45,358 --> 00:24:49,095 OF THE BRAIN TO THE VISUAL 585 00:24:49,095 --> 00:24:49,562 SYSTEM. 586 00:24:49,562 --> 00:24:51,297 OLFACTORY IS REDUCED, THE REST 587 00:24:51,297 --> 00:24:53,599 OF THE BRAIN SERVES TO INTERPRET 588 00:24:53,599 --> 00:24:55,267 THE INFORMATION COMING FROM THE 589 00:24:55,267 --> 00:24:55,534 EYE. 590 00:24:55,534 --> 00:25:01,941 SO WHAT YOU HAVE HERE IS 591 00:25:01,941 --> 00:25:02,708 ACTUALLY BEAUTIFUL PICTURE FROM 592 00:25:02,708 --> 00:25:03,676 THE FLY EYE. 593 00:25:03,676 --> 00:25:14,020 YOU CAN SEE AT THE TOP THE 594 00:25:14,020 --> 00:25:17,089 RETINA, ONLY CONTAINS 800 UNITS, 595 00:25:17,089 --> 00:25:18,524 BASICALLY PIXELS. 596 00:25:18,524 --> 00:25:21,127 THE EYE SEES 800 PIXELS YET TRY 597 00:25:21,127 --> 00:25:22,461 TO CATCH A FLY, MUCH BETTER THAN 598 00:25:22,461 --> 00:25:27,366 YOU ARE IN ORDER TO ESCAPE. 599 00:25:27,366 --> 00:25:30,202 PHOTORECEPTOR IN FLIES ARE BOTH 600 00:25:30,202 --> 00:25:31,637 PHOTORECEPTOR AND RETINA 601 00:25:31,637 --> 00:25:32,872 GANGLION CELL, THEY DO PROJECT 602 00:25:32,872 --> 00:25:34,940 LONG PROJECTION HERE TO THE 603 00:25:34,940 --> 00:25:37,677 FIRST LAYER OF THE OPTIC LOBE, 604 00:25:37,677 --> 00:25:40,312 OF COURSE THE LAMINA. 605 00:25:40,312 --> 00:25:43,015 AND WHAT YOU HAVE HERE IS THE 606 00:25:43,015 --> 00:25:45,451 STRONG PROJECTION AS PROJECTION 607 00:25:45,451 --> 00:25:48,054 OF THE PHOTORECEPTOR BASICALLY 608 00:25:48,054 --> 00:25:50,256 THE ROAD OF THE FLY, THE LAMINA 609 00:25:50,256 --> 00:25:53,292 STRUCTURE IS THE FIRST STEP IN 610 00:25:53,292 --> 00:25:54,960 MOTION DETECTION, A SIMPLE 611 00:25:54,960 --> 00:25:58,664 STRUCTURE MADE OF FIVE TYPES OF 612 00:25:58,664 --> 00:26:00,199 NEURONS, HERE COLLECTING 613 00:26:00,199 --> 00:26:01,534 INFORMATION FROM PHOTORECEPTOR, 614 00:26:01,534 --> 00:26:03,069 PROJECT THEM INTO THE NEXT STEP 615 00:26:03,069 --> 00:26:09,742 IN THE VISUAL PATHWAY, CALLED 616 00:26:09,742 --> 00:26:11,477 THE MEDULLA, RECEIVES 617 00:26:11,477 --> 00:26:13,245 INFORMATION FROM THOSE GREEN 618 00:26:13,245 --> 00:26:14,146 PHOTORECEPTORS HERE BASICALLY 619 00:26:14,146 --> 00:26:15,648 THE CONES OF THE FLY, THE CONES 620 00:26:15,648 --> 00:26:19,819 OF THE FLY DON'T STOP IN THE 621 00:26:19,819 --> 00:26:23,589 MEDIA, THEY GO INTO THE MEDULLA, 622 00:26:23,589 --> 00:26:25,725 PROCESS INFORMATION FOR COLOR 623 00:26:25,725 --> 00:26:25,958 VISION. 624 00:26:25,958 --> 00:26:27,760 THIS MEDULLA IS MUCH MORE 625 00:26:27,760 --> 00:26:31,097 COMPLEX STRUCTURE IN THE WHOLE 626 00:26:31,097 --> 00:26:32,298 SYSTEM, IN FACT CONTAINS MORE 627 00:26:32,298 --> 00:26:33,933 THAN ALL THE INDIVIDUAL SYSTEM 628 00:26:33,933 --> 00:26:35,267 WHICH MEANS ONE-THIRD OF ALL THE 629 00:26:35,267 --> 00:26:36,435 NEURONS IN THE BRAIN OF THE 630 00:26:36,435 --> 00:26:36,902 FLIES. 631 00:26:36,902 --> 00:26:38,637 THIS INFORMATION IS BEING 632 00:26:38,637 --> 00:26:41,107 PROCESSED IN MANY WAYS, AND IS 633 00:26:41,107 --> 00:26:43,776 GOING TO LEAD TO THE PROJECTION 634 00:26:43,776 --> 00:26:45,111 TO INTERPRETATION BY OUTPUT 635 00:26:45,111 --> 00:26:46,879 NEURONS, TAKE INFORMATION FROM 636 00:26:46,879 --> 00:26:48,948 THE VISUAL SYSTEM AND SEND IT TO 637 00:26:48,948 --> 00:26:50,683 CENTRAL BRAIN AND BASICALLY 638 00:26:50,683 --> 00:26:52,251 DRIVE THE CORRECT BEHAVIOR OF 639 00:26:52,251 --> 00:26:52,985 THE FLY. 640 00:26:52,985 --> 00:26:56,188 SO I'M GOING TO FOCUS MY 641 00:26:56,188 --> 00:26:58,257 ATTENTION ON THIS MEDULLA 642 00:26:58,257 --> 00:26:59,558 STRUCTURE BECAUSE IT'S ACTUALLY 643 00:26:59,558 --> 00:27:01,293 THE MOST COMPLEX AND MOST 644 00:27:01,293 --> 00:27:02,328 INTERESTING STRUCTURE, WE DO A 645 00:27:02,328 --> 00:27:05,564 LOT OF WORK ON THE OTHER 646 00:27:05,564 --> 00:27:07,333 STRUCTURE BUT AGAIN THINGS, THE 647 00:27:07,333 --> 00:27:08,868 PICTURE MAY BE LESS APPLICABLE 648 00:27:08,868 --> 00:27:09,935 TO THE SYSTEM. 649 00:27:09,935 --> 00:27:14,440 SO, AGAIN WHAT YOU HAVE HERE, 650 00:27:14,440 --> 00:27:16,075 40,000 NEURONS THAT BELONG TO 651 00:27:16,075 --> 00:27:18,711 100 CELL TYPES. 652 00:27:18,711 --> 00:27:20,246 WHICH MEANS INDEED YOU CAN SEE 653 00:27:20,246 --> 00:27:22,982 THAT THERE IS NEED FOR 654 00:27:22,982 --> 00:27:25,518 GENERATING A LOT TO PROCESS THAT 655 00:27:25,518 --> 00:27:29,455 INFORMATION ABOUT MOTION, OBJECT 656 00:27:29,455 --> 00:27:31,423 DETECTION, LOOMING OR COLOR 657 00:27:31,423 --> 00:27:32,091 VISION, OKAY? 658 00:27:32,091 --> 00:27:39,632 SO ABOUT SEVEN OR EIGHT YEARS 659 00:27:39,632 --> 00:27:41,934 AGO, 2017, 2016 OR 2017, WERE 660 00:27:41,934 --> 00:27:43,936 RESISTANT TO THE OMICS KINGDOM, 661 00:27:43,936 --> 00:27:46,839 IN FACT AT THAT TIME HAD NEVER 662 00:27:46,839 --> 00:27:49,141 DONE AN RNAseq OR ATAC-SEQ WAS 663 00:27:49,141 --> 00:27:50,242 THE MOST STUPID THING TO DO, 664 00:27:50,242 --> 00:27:51,877 WHAT DO WE GAIN? 665 00:27:51,877 --> 00:27:58,684 I CHANGED MY MIND, DON'T WORRY. 666 00:27:58,684 --> 00:28:00,085 AND THE FATHER OF THIS PROGRAM 667 00:28:00,085 --> 00:28:05,357 THAT ALLOWS PEOPLE TO INTERPRET 668 00:28:05,357 --> 00:28:07,526 SINGLE CELL, JOINED THE 669 00:28:07,526 --> 00:28:08,961 DEPARTMENT, AMAZING. 670 00:28:08,961 --> 00:28:12,031 BY KNEW YOU ARE TIRED OF SINGLE 671 00:28:12,031 --> 00:28:13,866 SEQUENCING YOU'VE SEEN OF 672 00:28:13,866 --> 00:28:15,668 OTHERS, BUT WE CAN MAKE VERY, 673 00:28:15,668 --> 00:28:17,736 VERY GOOD USE OF IT AND TAKE 674 00:28:17,736 --> 00:28:18,737 ADVANTAGE BECAUSE YOU CAN 675 00:28:18,737 --> 00:28:20,139 PROVIDE A LOT OF INFORMATION 676 00:28:20,139 --> 00:28:23,642 ABOUT WHAT WE WANT TO DO, OKAY? 677 00:28:23,642 --> 00:28:26,178 SO, WHAT YOU HAVE ON THE NEXT 678 00:28:26,178 --> 00:28:28,447 PICTURE IS ACTUALLY THE FIRST 679 00:28:28,447 --> 00:28:30,149 INCLINATION OF A SINGLE CELL 680 00:28:30,149 --> 00:28:33,953 SEQUENCING OF THE WHOLE OPTIC 681 00:28:33,953 --> 00:28:36,155 LOBE OR 270 NEURONS AND YOU CAN 682 00:28:36,155 --> 00:28:36,989 SEE SOMETHING STRIKING. 683 00:28:36,989 --> 00:28:39,225 YOU'VE SEEN A LOT OF SINGLE CELL 684 00:28:39,225 --> 00:28:40,526 SEQUENCING FROM MANY PEOPLE AND 685 00:28:40,526 --> 00:28:42,061 USUALLY IT'S A BLOB WITH 686 00:28:42,061 --> 00:28:42,528 DIFFERENT COLORS. 687 00:28:42,528 --> 00:28:44,897 HERE YOU CAN SEE EVERYTHING IS 688 00:28:44,897 --> 00:28:46,565 VERY WELL SEPARATED, ALL THE 689 00:28:46,565 --> 00:28:47,967 CELL TYPES ARE VERY WELL 690 00:28:47,967 --> 00:28:48,534 DEFINED. 691 00:28:48,534 --> 00:28:51,270 YOU CAN SEE ALL DIFFERENT 692 00:28:51,270 --> 00:28:53,572 COLORS, ALL VERY WELL SPECIFIED, 693 00:28:53,572 --> 00:28:56,408 YOU CAN SEE CLUSTER OF CELLS AT 694 00:28:56,408 --> 00:28:58,377 EACH WELL-CHARACTERIZED BY THEIR 695 00:28:58,377 --> 00:28:59,578 SIZE. 696 00:28:59,578 --> 00:29:06,018 THESE , YOU CAN GET A LOT OF 697 00:29:06,018 --> 00:29:07,019 INFORMATION. 698 00:29:07,019 --> 00:29:08,020 WE HAVE TRANSCRIPTOME OF ALL OF 699 00:29:08,020 --> 00:29:10,222 THE CELLS THAT YOU HAVE IN THE 700 00:29:10,222 --> 00:29:11,857 VISUAL SYSTEM OF THE FLY. 701 00:29:11,857 --> 00:29:16,695 AND BY NOW YOU MIGHT KNOW THAT 702 00:29:16,695 --> 00:29:17,563 ACTUALLY JANELIA RELEASED 703 00:29:17,563 --> 00:29:19,531 CONNECTOME TO ALL OF THESE 704 00:29:19,531 --> 00:29:21,166 NEURONS, THE WHOLE BRAIN OF THE 705 00:29:21,166 --> 00:29:22,001 FLIES. 706 00:29:22,001 --> 00:29:23,369 WE KNOW EXACTLY HOW THIS NEURON 707 00:29:23,369 --> 00:29:25,771 IN BLUE CONNECTS TO THE NEURON 708 00:29:25,771 --> 00:29:27,539 ORANGE, HOW THEY CONNECT TO EACH 709 00:29:27,539 --> 00:29:28,507 OTHER, AND WE DON'T KNOW WHAT 710 00:29:28,507 --> 00:29:30,876 THEY DO BUT WE KNOW THEY CONNECT 711 00:29:30,876 --> 00:29:31,777 TO EACH OTHER AND OF COURSE 712 00:29:31,777 --> 00:29:34,146 SINCE WE KNOW THE CONNECTOR, 713 00:29:34,146 --> 00:29:35,514 TRANSCRIPTOME, YOU CAN FIGURE 714 00:29:35,514 --> 00:29:36,815 OUT WHAT MIGHT BE INVOLVED IN 715 00:29:36,815 --> 00:29:38,450 BOTH TO ALLOW THE TWO CELLS TO 716 00:29:38,450 --> 00:29:39,551 CONNECT TO EACH OTHER. 717 00:29:39,551 --> 00:29:42,621 SO I DON'T KNOW WHY WE GET SUCH 718 00:29:42,621 --> 00:29:44,156 A GOOD SEPARATION OF THE 719 00:29:44,156 --> 00:29:44,924 DIFFERENT CLUSTER. 720 00:29:44,924 --> 00:29:50,729 IT MIGHT BE THEY ARE GOOD AT 721 00:29:50,729 --> 00:29:52,064 DETERMINING CELL TYPE, 722 00:29:52,064 --> 00:29:53,198 VERTEBRATES ARE MORE FLEXIBLE IN 723 00:29:53,198 --> 00:29:57,102 TERMS OF MORE PLASTICITY AND A 724 00:29:57,102 --> 00:29:58,370 CONTINUUM OF CELLS, I'M NOT SURE 725 00:29:58,370 --> 00:30:02,541 WHAT HAPPENED BUT HERE THINGS 726 00:30:02,541 --> 00:30:08,380 ARE GOOD. 727 00:30:08,380 --> 00:30:10,749 NOW IN BLUE A LITTLE BLOB, BIG 728 00:30:10,749 --> 00:30:13,953 BLOB ACTUALLY IN BLUE, WHICH IS 729 00:30:13,953 --> 00:30:14,820 ACTUALLY HERE. 730 00:30:14,820 --> 00:30:17,222 SO THIS BIG BLOB IS ACTUALLY 731 00:30:17,222 --> 00:30:19,291 USUALLY WHEN YOU SEE A BIG BLOB 732 00:30:19,291 --> 00:30:24,797 LIKE THAT IN SINGLE CELL 733 00:30:24,797 --> 00:30:26,999 SEQUENCING YOU SEE SOME AMBIENTS 734 00:30:26,999 --> 00:30:29,034 IN IT, WE KNOW THE MOST 735 00:30:29,034 --> 00:30:33,339 IMPORTANT CELL TYPES T4 AND T 5 736 00:30:33,339 --> 00:30:36,175 CELLS ARE FIRST CELL SENSITIVE 737 00:30:36,175 --> 00:30:41,880 TO MOTION, T4 TO ON MOTION, T5 738 00:30:41,880 --> 00:30:45,284 TO OFF MOTION, EIGHT CELL TIMES, 739 00:30:45,284 --> 00:30:48,420 44 AND 45 THAT CELL GOES FRONT 740 00:30:48,420 --> 00:30:51,724 TO BACK MOTION, BACK TO FRONT, 741 00:30:51,724 --> 00:30:52,825 DOWN MOTION ON/OFF. 742 00:30:52,825 --> 00:30:54,460 YET IN THIS SITUATION HERE WHAT 743 00:30:54,460 --> 00:30:57,763 YOU CAN SEE ALL GROUPED INTO ONE 744 00:30:57,763 --> 00:31:01,567 SINGLE CLUSTER, YOU CANNOT 745 00:31:01,567 --> 00:31:02,234 DIFFERENTIATE FROM TRANSCRIPTION 746 00:31:02,234 --> 00:31:03,102 POINT OF VIEW. 747 00:31:03,102 --> 00:31:04,870 THEY DID INVOLVE IN DIFFERENT 748 00:31:04,870 --> 00:31:05,404 WAYS. 749 00:31:05,404 --> 00:31:07,072 WE THOUGHT BIT, INDEED MAYBE 750 00:31:07,072 --> 00:31:08,607 THIS MAKES SENSE BECAUSE THOSE 751 00:31:08,607 --> 00:31:10,876 CELLS DO ALL PERFORM THE SAME 752 00:31:10,876 --> 00:31:14,513 COMPUTATION, COMPARE TWO POINTS 753 00:31:14,513 --> 00:31:16,115 IN SPACE, MOTION ARRIVES HERE 754 00:31:16,115 --> 00:31:18,017 BEFORE THAT ONE, OR THAT ONE, OR 755 00:31:18,017 --> 00:31:20,452 THAT ONE, SO DOESN'T MATTER IN 756 00:31:20,452 --> 00:31:23,155 THE ADULT, THEY DO EXACT SAME 757 00:31:23,155 --> 00:31:23,756 THING. 758 00:31:23,756 --> 00:31:24,823 WHAT MATTERS DURING DEVELOPMENT, 759 00:31:24,823 --> 00:31:26,325 WHEN THEY FIND CONNECTION TO 760 00:31:26,325 --> 00:31:28,427 CONNECT FRONT TO BACK, BACK TO 761 00:31:28,427 --> 00:31:28,627 FRONT. 762 00:31:28,627 --> 00:31:29,928 , UP AND DOWN. 763 00:31:29,928 --> 00:31:31,697 WE SAID MAYBE WE SHOULD LOOK AT 764 00:31:31,697 --> 00:31:33,232 THE SAME THING AND NOT DEFINE 765 00:31:33,232 --> 00:31:35,000 NEURON DIVERSITY OF WHAT YOU SEE 766 00:31:35,000 --> 00:31:36,301 HERE BUT BY VIRTUE OF WHAT YOU 767 00:31:36,301 --> 00:31:38,170 SEE IN THE CONTEXT OF THE 768 00:31:38,170 --> 00:31:38,804 DEVELOPMENT. 769 00:31:38,804 --> 00:31:43,642 SO WE SAY, OKAY, LET'S DO THAT. 770 00:31:43,642 --> 00:31:44,743 LET'S GO TO DEVELOPMENT AND 771 00:31:44,743 --> 00:31:45,711 FIGURE OUT WHAT'S HAPPENED. 772 00:31:45,711 --> 00:31:50,983 I WANT TO GO BACK, TO THE SITE 773 00:31:50,983 --> 00:31:53,485 OF THE CLUSTER DOES MATTER. 774 00:31:53,485 --> 00:31:56,121 ALL THOSE CELLS ARE CELLS WHICH 775 00:31:56,121 --> 00:31:58,991 ARE ONE-TO-ONE TO THE BASICALLY 776 00:31:58,991 --> 00:32:01,693 EXONAL PIXEL OF THE VISUAL 777 00:32:01,693 --> 00:32:01,927 SYSTEM. 778 00:32:01,927 --> 00:32:03,896 RUNNING IN PATTERN TO EACH 779 00:32:03,896 --> 00:32:09,068 OTHER, ALL OCCUPIED BY ONE OF 780 00:32:09,068 --> 00:32:12,471 THOSE CELLS, C3, MI9, WHATEVER. 781 00:32:12,471 --> 00:32:16,175 CLUSTER MUCH LARGER RECEPTOR 782 00:32:16,175 --> 00:32:26,118 FIELD, HAVE MUCH LOWER 783 00:32:26,118 --> 00:32:26,452 STOCHIOMETRY. 784 00:32:26,452 --> 00:32:27,653 WE HAVE A LOT OF INFORMATION 785 00:32:27,653 --> 00:32:29,088 HERE, AND THIS IS GREAT. 786 00:32:29,088 --> 00:32:31,490 AGAIN, ONE DAY WE HOPE TO 787 00:32:31,490 --> 00:32:34,226 CONNECT TO THE CONNECT HOME BUT 788 00:32:34,226 --> 00:32:37,296 SO FAR DIFFICULT BECAUSE WE 789 00:32:37,296 --> 00:32:41,767 DON'T KNOW HOW TWO DIFFERENT 790 00:32:41,767 --> 00:32:43,669 TYPES CAN ALLOW CONNECTION, HERE 791 00:32:43,669 --> 00:32:46,171 IT DOESN'T ALWAYS WORK WELL. 792 00:32:46,171 --> 00:32:48,273 SO WE SAY LET'S LOOK TO SEE IF 793 00:32:48,273 --> 00:32:50,309 WE CAN FIND MORE RESOLUTION IN 794 00:32:50,309 --> 00:32:51,643 TERMS OF SPECIFIC IDENTITY OF 795 00:32:51,643 --> 00:32:53,112 THE DIFFERENT CELL TYPES. 796 00:32:53,112 --> 00:32:56,582 WE DID A SINGLE CELL SEQUENCING 797 00:32:56,582 --> 00:32:58,884 AT DIFFERENT TIME OF 798 00:32:58,884 --> 00:33:03,789 DEVELOPMENT, 70% HERE OR 50 AND 799 00:33:03,789 --> 00:33:04,022 BEFORE. 800 00:33:04,022 --> 00:33:05,290 WHEN YOU GO TO THE BEGINNING, 801 00:33:05,290 --> 00:33:07,326 CELL HAS BEEN JUST BORN, THE 802 00:33:07,326 --> 00:33:10,729 NEURON JUST MADE IS A MATURING 803 00:33:10,729 --> 00:33:13,031 AND ACTUALLY GOING TO BE -- IN 804 00:33:13,031 --> 00:33:14,566 THE PROCESS OF BEING FINISHED. 805 00:33:14,566 --> 00:33:19,705 NOW IF YOU LOOK AT THIS TIME OF 806 00:33:19,705 --> 00:33:20,806 DEVELOPMENT HERE AROUND P50, THE 807 00:33:20,806 --> 00:33:23,208 SYNAPSES ARE BEING MADE. 808 00:33:23,208 --> 00:33:24,843 WE SHOULD LOOK TO CONNECT TO THE 809 00:33:24,843 --> 00:33:25,811 DIFFERENT PART. 810 00:33:25,811 --> 00:33:28,680 INDEED YOU CAN LOOK IN DETAIL, 811 00:33:28,680 --> 00:33:31,617 YOU CAN SEE ACTUALLY INDEED 812 00:33:31,617 --> 00:33:33,585 EIGHT CELL TYPES FORMING THIS 813 00:33:33,585 --> 00:33:41,693 BIG BLOB IN THE ADULT FORMING 814 00:33:41,693 --> 00:33:42,060 EIGHT SUBTYPES. 815 00:33:42,060 --> 00:33:45,130 INDEED YOU CAN LOOK AT 816 00:33:45,130 --> 00:33:46,632 RESOLUTION, CREATE RESOLUTION 817 00:33:46,632 --> 00:33:48,934 DEPENDING WHEN YOU LOOK IN 818 00:33:48,934 --> 00:33:49,501 DEVELOPMENT. 819 00:33:49,501 --> 00:33:53,305 ANOTHER LAYER OF COMPLEXITY AND 820 00:33:53,305 --> 00:33:54,506 RESOLUTION TO ADD ATAC-SEQ, 821 00:33:54,506 --> 00:33:56,141 COMBINE WITH SINGLE SEQUENCING 822 00:33:56,141 --> 00:33:58,110 TO FIND WHERE THE GENE NEEDS TO 823 00:33:58,110 --> 00:34:00,979 BE BECAUSE CHROMATIN IS OPEN. 824 00:34:00,979 --> 00:34:02,281 YOU CAN RECAPITULATE HOW EIGHT 825 00:34:02,281 --> 00:34:05,884 CELL TYPES ARE BEING PLAYED 826 00:34:05,884 --> 00:34:07,519 DURING THE DEVELOPMENT. 827 00:34:07,519 --> 00:34:14,927 AMAZING TO ME, A SITUATION WHERE 828 00:34:14,927 --> 00:34:19,464 TWO PROGENITORS HERE -- OKAY. 829 00:34:19,464 --> 00:34:23,068 I'M GOING TO TRY TO USE THE 830 00:34:23,068 --> 00:34:24,403 OTHER POINTER. 831 00:34:24,403 --> 00:34:29,341 SO TWO OF THEM, THEY DIVIDE WITH 832 00:34:29,341 --> 00:34:30,842 ASYMMETRY DIVISION, NOTCH ON, 833 00:34:30,842 --> 00:34:33,812 NOTCH OFF, DIVIDE AGAIN NOTCH 834 00:34:33,812 --> 00:34:36,982 ON, NOTCH OFF, YOU CAN SEE AS A 835 00:34:36,982 --> 00:34:39,518 CONSEQUENCE EIGHT CELL TYPES, 44 836 00:34:39,518 --> 00:34:43,188 AND 45 BEING MADE, SIMPLY BY 837 00:34:43,188 --> 00:34:45,524 COMBINING TRANSCRIPTOMIC AND 838 00:34:45,524 --> 00:34:46,191 ATTACK SEQUENCE, FOLLOW 839 00:34:46,191 --> 00:34:48,493 TRAJECTORY AND KNOW WHICH GENE 840 00:34:48,493 --> 00:34:49,795 EXPRESSED ALONG EACH ONE OF THE 841 00:34:49,795 --> 00:34:51,196 TRAJECTORY, FIGURE OUT HOW THE 842 00:34:51,196 --> 00:34:53,432 NETWORK IS BEING ABLE TO 843 00:34:53,432 --> 00:34:53,966 FUNCTION. 844 00:34:53,966 --> 00:34:54,967 OKAY. 845 00:34:54,967 --> 00:34:56,702 THIS IS VERY NICE, COMPLETE 846 00:34:56,702 --> 00:34:57,603 DESCRIPTION OF TRANSCRIPTOME BUT 847 00:34:57,603 --> 00:34:58,804 THE QUESTION IS, OKAY, HOW DO WE 848 00:34:58,804 --> 00:34:59,671 GET THERE? 849 00:34:59,671 --> 00:35:01,640 HOW DO WE DEVELOP AND GET TO 850 00:35:01,640 --> 00:35:03,475 DEVELOPMENT TO FIGURE OUT WHAT 851 00:35:03,475 --> 00:35:03,909 HAPPENED? 852 00:35:03,909 --> 00:35:06,812 HOW DO YOU GENERATE ALL THESE 853 00:35:06,812 --> 00:35:09,548 MANY CELL TYPES, OKAY? 854 00:35:09,548 --> 00:35:13,785 SO AGAIN FOCUSING ATTENTION TO 855 00:35:13,785 --> 00:35:15,988 MEDULLA, MADE OF 40,000 NEURONS, 856 00:35:15,988 --> 00:35:18,390 AND NEURONS ARE BLUE STUFF YOU 857 00:35:18,390 --> 00:35:22,728 SEE HERE, ALL SEPARATED FROM THE 858 00:35:22,728 --> 00:35:26,331 CONNECTION, AND 40,000 NEURONS, 859 00:35:26,331 --> 00:35:28,467 BASICALLY INNERVATE THOSE 800 IN 860 00:35:28,467 --> 00:35:30,235 GREEN HERE, 800 PIXEL OF THE 861 00:35:30,235 --> 00:35:31,870 VISUAL SYSTEM. 862 00:35:31,870 --> 00:35:39,211 IN MOUSE YOU CAN DIVIDE 40,000 863 00:35:39,211 --> 00:35:43,815 BY 100, AND THEN STOCHIOMETRY, 864 00:35:43,815 --> 00:35:48,320 100 NEURONS THAT PROCESS 865 00:35:48,320 --> 00:35:49,087 INFORMATION. 866 00:35:49,087 --> 00:35:51,590 YOU HAVE 800 REPEATED CIRCUITS 867 00:35:51,590 --> 00:35:53,325 NEXT TO EACH OTHER, REPEAT OVER 868 00:35:53,325 --> 00:35:54,960 AND OVER GENERAL, HELPFUL WHEN 869 00:35:54,960 --> 00:35:57,062 IT COMES TO UNDERSTANDING HOW 870 00:35:57,062 --> 00:36:00,332 THESE THINGS HAPPEN. 871 00:36:00,332 --> 00:36:02,301 HOW DO YOU GENERATE ALL HUNDREDS 872 00:36:02,301 --> 00:36:05,904 OF NEURONS THAT INNERVATE EACH 873 00:36:05,904 --> 00:36:09,875 OF THE HUNDRED HERE. 874 00:36:09,875 --> 00:36:12,277 HOW DO YOU MAKE HUNDRED NEURONS? 875 00:36:12,277 --> 00:36:13,779 SIMPLISTIC VIEW WAS LET'S DO IT 876 00:36:13,779 --> 00:36:14,680 THAT WAY. 877 00:36:14,680 --> 00:36:17,416 YOU'RE GOING TO MAKE ONE NEURAL 878 00:36:17,416 --> 00:36:19,818 STEM CELL, EACH WILL GENERATE 879 00:36:19,818 --> 00:36:21,987 ALL HUNDRED NEURONS THAT OCCUPY 880 00:36:21,987 --> 00:36:22,187 THIS. 881 00:36:22,187 --> 00:36:23,422 YOU UNDERSTAND THIS MAY BE 882 00:36:23,422 --> 00:36:25,090 DIFFICULT TO UNDERSTAND BECAUSE 883 00:36:25,090 --> 00:36:27,259 YOU CAN MAKE HUNDRED CELLS FROM 884 00:36:27,259 --> 00:36:29,561 STEM CELLS BUT NOT HUNDRED CELLS 885 00:36:29,561 --> 00:36:32,164 FROM ONE GIVEN STEM CELL. 886 00:36:32,164 --> 00:36:35,133 LET'S FIGURE OUT WE'RE NOT FAR 887 00:36:35,133 --> 00:36:35,467 HERE. 888 00:36:35,467 --> 00:36:38,970 LET ME GIVE SOME BACKGROUND IN 889 00:36:38,970 --> 00:36:42,140 TERMS OF HOW THIS MEDULLA 890 00:36:42,140 --> 00:36:43,375 STRUCTURE IS BEING MADE, HOW DO 891 00:36:43,375 --> 00:36:45,877 YOU MAKE THIS MADE OF 800 TYPE 892 00:36:45,877 --> 00:36:47,612 OF NEURON? 893 00:36:47,612 --> 00:36:50,148 EVERYTHING START FROM PURPLE 894 00:36:50,148 --> 00:36:56,188 HERE, AND THIS IS GOING TO BE 895 00:36:56,188 --> 00:36:57,389 TRANSFORMING TO NEUROBLASTS, THE 896 00:36:57,389 --> 00:37:01,126 NAME OF STEM CELLS IN FLIES, 897 00:37:01,126 --> 00:37:03,962 NEUROBLASTS IN GREEN. 898 00:37:03,962 --> 00:37:06,164 THERE'S A PROGRESSION OF 899 00:37:06,164 --> 00:37:08,967 NEUROGENESIS, THE PURPLE CELL 900 00:37:08,967 --> 00:37:10,435 WILL BECOME GREEN, GREEN-GREEN, 901 00:37:10,435 --> 00:37:14,139 AFTER THREE OR FOUR DAYS PURPLE 902 00:37:14,139 --> 00:37:17,008 CELLS WILL BE TRANSFORMED INTO 903 00:37:17,008 --> 00:37:17,776 NEURAL CELLS. 904 00:37:17,776 --> 00:37:23,582 OVER A PERIOD OF FOUR DAYS, AN 905 00:37:23,582 --> 00:37:24,349 ADVANTAGE. 906 00:37:24,349 --> 00:37:27,619 SO, IF YOU TAKE A PICTURE OF 907 00:37:27,619 --> 00:37:31,256 THAT SCHEMATIC YOU CAN SEE YOU 908 00:37:31,256 --> 00:37:33,091 HAVE THE NEUROEPITHELIUM IN 909 00:37:33,091 --> 00:37:35,494 PURPLE HERE AND THEN AROUND THE 910 00:37:35,494 --> 00:37:38,363 OUTER EDGE A SET OF NEURAL STEM 911 00:37:38,363 --> 00:37:41,533 CELLS GET PRODUCED, THEN AN HOUR 912 00:37:41,533 --> 00:37:43,368 LATER ANOTHER SET, ANOTHER SET, 913 00:37:43,368 --> 00:37:45,270 ET CETERA, ET CETERA. 914 00:37:45,270 --> 00:37:48,206 AND SO UNTIL ALL THE 915 00:37:48,206 --> 00:37:52,377 NEUROEPITHELIUM HAS BEEN 916 00:37:52,377 --> 00:37:52,844 CONSUMED. 917 00:37:52,844 --> 00:37:54,646 I THOUGHT 800 NEURAL STEM CELLS 918 00:37:54,646 --> 00:37:59,050 ONE FOR EACH ONE OF THE 800 919 00:37:59,050 --> 00:38:03,121 RESPONDING TO 800 PIXEL. 920 00:38:03,121 --> 00:38:04,489 IT'S NOT EXACTLY CORRECT BUT WE 921 00:38:04,489 --> 00:38:05,724 CAN AMEND. 922 00:38:05,724 --> 00:38:09,895 IF YOU MAKE A CROSS-SECTION, 923 00:38:09,895 --> 00:38:13,165 FLIP 90-DEGREE, YOU SEE THE 924 00:38:13,165 --> 00:38:14,466 NEUROEPITHELIUM HERE, THE 925 00:38:14,466 --> 00:38:16,134 NEUROEPITHELIUM IS HERE, AND 926 00:38:16,134 --> 00:38:18,203 THIS CELL OUTER EDGE OF THE 927 00:38:18,203 --> 00:38:19,938 CRESCENT SHAPE WILL BECOME 928 00:38:19,938 --> 00:38:22,574 NEUROBLAST, NEURAL STEM CELL. 929 00:38:22,574 --> 00:38:25,677 NEUROBLAST IS A STEM CELL 930 00:38:25,677 --> 00:38:28,313 DIVIDES BY RENEWING THEMSELVES 931 00:38:28,313 --> 00:38:33,452 AND PRODUCING ONE CELL, OKAY, 932 00:38:33,452 --> 00:38:35,754 DIVIDING ONCE MORE, ONLY ONCE 933 00:38:35,754 --> 00:38:36,955 MORE, TWO NEURONS, OKAY? 934 00:38:36,955 --> 00:38:39,357 SO BETWEEN EACH DIVISION OF THE 935 00:38:39,357 --> 00:38:41,593 STEM CELL PRODUCE TWO NEURONS, 936 00:38:41,593 --> 00:38:43,228 NOTCH ON AND NOTCH OFF NEURON, 937 00:38:43,228 --> 00:38:45,831 BASICALLY NOTCH IS A POWERFUL 938 00:38:45,831 --> 00:38:48,467 SYSTEM TO DISTINGUISH TWO CELL 939 00:38:48,467 --> 00:38:51,870 TYPE, NOTCH ON, NOTCH ON. 940 00:38:51,870 --> 00:38:59,144 TWO HOURS LATER THE NEXT 941 00:38:59,144 --> 00:39:00,145 NEUROEPITHELIUM WILL DIVIDE, AND 942 00:39:00,145 --> 00:39:01,179 SO ON AND SO ON. 943 00:39:01,179 --> 00:39:06,751 AT THE END WHAT YOU HAVE, YOU 944 00:39:06,751 --> 00:39:07,953 HAVE YOUNG NEUROBLASTS, THAT 945 00:39:07,953 --> 00:39:11,122 JUST DIVIDE NOW, AND ALL 946 00:39:11,122 --> 00:39:13,625 NEUROBLASTS DIVIDE A WHILE AGO, 947 00:39:13,625 --> 00:39:16,394 AND FROM THIS ALL NEUROBLAST, 948 00:39:16,394 --> 00:39:17,462 AND ALL NEURONS FROM THIS. 949 00:39:17,462 --> 00:39:20,532 WHAT YOU CAN DO IS LABEL ONE OF 950 00:39:20,532 --> 00:39:22,133 THOSE NEUROBLASTS HERE AND THEN 951 00:39:22,133 --> 00:39:23,001 SEE WHAT HAPPENS. 952 00:39:23,001 --> 00:39:26,004 YOU CAN SEE ON THE NEXT SLIDE, 953 00:39:26,004 --> 00:39:28,840 SO IN FACT YOU HAVE EACH 954 00:39:28,840 --> 00:39:30,175 NEUROBLAST MAKES LONG COLUMN OF 955 00:39:30,175 --> 00:39:32,143 TWO NEXT TO EACH OTHER AND 956 00:39:32,143 --> 00:39:33,812 PRODUCES MAYBE 40 OR 50 NEURONS 957 00:39:33,812 --> 00:39:35,447 AT ONCE. 958 00:39:35,447 --> 00:39:35,647 OKAY. 959 00:39:35,647 --> 00:39:36,081 SO GOOD. 960 00:39:36,081 --> 00:39:37,415 THIS IS VERY NICE. 961 00:39:37,415 --> 00:39:42,254 BUT BIG QUESTION IS HOW CAN ONE 962 00:39:42,254 --> 00:39:43,455 NEUROBLAST HERE PRODUCE MANY 963 00:39:43,455 --> 00:39:44,322 DIFFERENT NEURONS AND EACH ONE 964 00:39:44,322 --> 00:39:45,957 OF THEM SHOULD BE DIFFERENT 965 00:39:45,957 --> 00:39:47,292 BECAUSE YOU NEED TO PRODUCE 966 00:39:47,292 --> 00:39:49,561 HUNDRED TYPE OF NEURONS. 967 00:39:49,561 --> 00:39:51,630 IT'S VERY HARD TO UNDERSTAND 968 00:39:51,630 --> 00:39:54,699 EXCEPT ABOUT 25 YEARS AGO MY 969 00:39:54,699 --> 00:39:56,234 COLLEAGUE AND FRIEND CAME OUT 970 00:39:56,234 --> 00:39:57,669 WITH A BEAUTIFUL MODEL TO 971 00:39:57,669 --> 00:39:59,204 EXPLAIN HOW AGAIN EACH 972 00:39:59,204 --> 00:40:05,210 NEUROBLAST CAN PRODUCE MANY CELL 973 00:40:05,210 --> 00:40:07,312 TYPES, HERE AN EXAMPLE, YOU CAN 974 00:40:07,312 --> 00:40:11,983 GET MULTIPLE CELL TYPES BEING 975 00:40:11,983 --> 00:40:12,884 MADE THERE, OKAY? 976 00:40:12,884 --> 00:40:15,987 25 YEARS AGO WAS WORKING ON 977 00:40:15,987 --> 00:40:17,923 VENTRAL NERVE CORD OF THE FLIES, 978 00:40:17,923 --> 00:40:20,091 IDENTIFYING SAME TYPE OF 979 00:40:20,091 --> 00:40:22,127 NEUROBLASTS, NOTICED SOMETHING 980 00:40:22,127 --> 00:40:24,930 INTERESTING THAT EARLY BORN 981 00:40:24,930 --> 00:40:29,534 NEUROBLAST EXPRESS TRANSCRIPTION 982 00:40:29,534 --> 00:40:31,169 FACTOR CALLED HUNCHBACK, DIVIDE, 983 00:40:31,169 --> 00:40:33,705 PRODUCE A NEURON WHICH EXPRESS 984 00:40:33,705 --> 00:40:34,239 HUNCHBACK. 985 00:40:34,239 --> 00:40:36,308 THE SAME NEUROBLAST TIRED OF 986 00:40:36,308 --> 00:40:39,177 EXPRESSING HUNCHBACK WILL TURN 987 00:40:39,177 --> 00:40:47,819 ON HUNCH BARK AND TURN OFF, SAME 988 00:40:47,819 --> 00:40:50,689 THING FOR PDM, VERY NICE, 989 00:40:50,689 --> 00:40:51,723 CONCEPT IS AMAZING. 990 00:40:51,723 --> 00:40:53,758 THE CONCEPT IS THERE. 991 00:40:53,758 --> 00:40:56,962 WE CAN TRY TO SEE WHO UNDERSTAND 992 00:40:56,962 --> 00:40:58,697 HOW YOU CAN PRODUCE HUNDRED 993 00:40:58,697 --> 00:41:00,565 NEURON THAT I DESCRIBED TO YOU 994 00:41:00,565 --> 00:41:02,400 EARLIER. 995 00:41:02,400 --> 00:41:06,671 WHEN THIS CAME OUT PEOPLE WORK 996 00:41:06,671 --> 00:41:08,506 ON THE CORTEX, MOUSE RETINA SAY 997 00:41:08,506 --> 00:41:12,277 IT'S WHAT WE NEED TO EXPLAIN, OR 998 00:41:12,277 --> 00:41:14,346 WHY YOU PRODUCE LAYER SIX, FIVE, 999 00:41:14,346 --> 00:41:15,880 FOUR, THREE, TWO, THIS EXPLAIN 1000 00:41:15,880 --> 00:41:17,182 BUT NOBODY CAN FIND SOMETHING 1001 00:41:17,182 --> 00:41:18,383 LIKE THAT. 1002 00:41:18,383 --> 00:41:20,018 NOT EXACTLY TRUE. 1003 00:41:20,018 --> 00:41:21,886 MICHELLE IN CANADA FINDS 1004 00:41:21,886 --> 00:41:23,855 SOMETHING THAT RESEMBLE SERIES 1005 00:41:23,855 --> 00:41:25,056 OF FOUR THREE GENES IN RETINA 1006 00:41:25,056 --> 00:41:27,025 WHICH KIND OF LOOK LIKE THAT BUT 1007 00:41:27,025 --> 00:41:29,461 I THINK IT'S SLIGHT DIFFERENT 1008 00:41:29,461 --> 00:41:30,195 MECHANISM. 1009 00:41:30,195 --> 00:41:33,698 WE SAY IN FLY, MUCH CLOSER IN 1010 00:41:33,698 --> 00:41:35,233 TERM OF MECHANISM, IMAGING 1011 00:41:35,233 --> 00:41:36,901 SYSTEM, WHAT YOU HAVE HERE IS 1012 00:41:36,901 --> 00:41:40,171 SYSTEM WHEREABOUTS BY IN ONE 1013 00:41:40,171 --> 00:41:41,840 SNAPSHOT EARLY BORN NEUROBLASTS, 1014 00:41:41,840 --> 00:41:43,575 THEN LATE BORN NEUROBLASTS, YOU 1015 00:41:43,575 --> 00:41:47,612 CAN EXPRESS THIS EXPRESSES 1016 00:41:47,612 --> 00:41:49,581 HUNCHBACK, AND IN ONE SNAPSHOT 1017 00:41:49,581 --> 00:41:52,250 YOU COULD SEE EVERYTHING. 1018 00:41:52,250 --> 00:41:53,418 WE FAILED COMPLETELY, NONE WOULD 1019 00:41:53,418 --> 00:41:55,086 EXPRESS HERE BUT WE FIND 1020 00:41:55,086 --> 00:41:57,489 SOMETHING A LOT NICER BECAUSE WE 1021 00:41:57,489 --> 00:41:58,923 FIND THE SAME THING, SAME 1022 00:41:58,923 --> 00:42:00,792 CONCEPT EXCEPT THE GENE WERE 1023 00:42:00,792 --> 00:42:01,259 DIFFERENT. 1024 00:42:01,259 --> 00:42:02,861 INSTEAD OF FOUR GENES WE GET SO 1025 00:42:02,861 --> 00:42:04,529 FAR SIX OR SEVEN AND THEN YOU 1026 00:42:04,529 --> 00:42:06,731 CAN SEE MORE LATER. 1027 00:42:06,731 --> 00:42:13,905 YOU CAN FIND EACH EXPRESSING 1028 00:42:13,905 --> 00:42:15,907 GENE CALLED HOMOTHORAX, ERMs, 1029 00:42:15,907 --> 00:42:21,146 AND THEN HOMEO BRAIN. 1030 00:42:21,146 --> 00:42:23,815 NOW POSSIBILITY OF MAKING SIX OR 1031 00:42:23,815 --> 00:42:24,916 SEVEN TEMPORAL WINDOWS THAT 1032 00:42:24,916 --> 00:42:26,551 COULD PRODUCE SIX OR SEVEN 1033 00:42:26,551 --> 00:42:32,223 DIFFERENT TYPE OF NEURON. 1034 00:42:32,223 --> 00:42:33,458 IT WAS VERY NICE. 1035 00:42:33,458 --> 00:42:34,659 THE PICTURE I SHOWED EARLIER IN 1036 00:42:34,659 --> 00:42:37,395 THE FIRST SLIDE IS EXACTLY THIS. 1037 00:42:37,395 --> 00:42:42,734 TOP VIEW OF THE NEUROREPEATER, 1038 00:42:42,734 --> 00:42:45,036 HERE, NOT CONSUMED, EARLY BORN 1039 00:42:45,036 --> 00:42:51,843 NEUROBLAST EXPRESSED GENE HOMEO 1040 00:42:51,843 --> 00:42:54,913 THORAX, I WANT TO SHOW YOU, YOU 1041 00:42:54,913 --> 00:42:57,082 CAN SEE WHAT HAPPENED IN REAL 1042 00:42:57,082 --> 00:42:59,984 LIFE, INDEED EACH ONE OF THE 1043 00:42:59,984 --> 00:43:02,487 CELL BECOME -- GOES THROUGH THE 1044 00:43:02,487 --> 00:43:05,557 SERIES WHEREBY IT EXPRESSES 1045 00:43:05,557 --> 00:43:09,060 HOMEOTHORAX, AND THE YOUNG 1046 00:43:09,060 --> 00:43:12,530 NEUROBLASTS LATER EXPRESS, NOW 1047 00:43:12,530 --> 00:43:18,002 USED TO BE YOUNG AND EXPRESS 1048 00:43:18,002 --> 00:43:18,303 HOMEOTHORAX. 1049 00:43:18,303 --> 00:43:21,740 SHORT OF THE HUNDRED WE WANT TO 1050 00:43:21,740 --> 00:43:22,006 GENERATE. 1051 00:43:22,006 --> 00:43:23,475 SO, THE RULE OF THE GAME HOW 1052 00:43:23,475 --> 00:43:24,676 DOES THIS FUNCTION? 1053 00:43:24,676 --> 00:43:28,213 HOW CAN SERIES OF TRANSCRIPTION 1054 00:43:28,213 --> 00:43:30,381 FACTOR EXPRESS IN VERY SAME 1055 00:43:30,381 --> 00:43:30,615 CELL? 1056 00:43:30,615 --> 00:43:32,584 THE SYSTEM WORKS QUITE WELL. 1057 00:43:32,584 --> 00:43:35,987 WHAT HAPPENED THERE, AGAIN, 1058 00:43:35,987 --> 00:43:45,630 NEUROBLAST IS BORN AND EXPRESS 1059 00:43:45,630 --> 00:43:49,434 THE TRANSCRIPTION FACTOR. 1060 00:43:49,434 --> 00:43:51,369 IF YOU DO MUTATION, YOU CAN SEE 1061 00:43:51,369 --> 00:43:52,837 WHAT'S GOING HAPPEN. IN FACT, 1062 00:43:52,837 --> 00:43:53,938 YOU KEEP GOING TO THE DIVISION 1063 00:43:53,938 --> 00:44:00,512 BUT YOU GET STUCK INTO THE ITEM 1064 00:44:00,512 --> 00:44:04,015 WORLD WINDOW SIMPLY BECAUSE GENE 1065 00:44:04,015 --> 00:44:07,652 X ACTIVATES GENE X PLUS ONE, X 1066 00:44:07,652 --> 00:44:09,420 MINUS ONE ISLET. 1067 00:44:09,420 --> 00:44:10,922 THERE WAS SLIGHT VARIATION BUT 1068 00:44:10,922 --> 00:44:12,791 THE RULE SEEMS TO APPLY, A WAY 1069 00:44:12,791 --> 00:44:16,761 THE SYSTEM PROGRESS IS SIMPLY 1070 00:44:16,761 --> 00:44:21,866 TRANSCRIPTION NETWORK ACTIVATES, 1071 00:44:21,866 --> 00:44:24,402 B,C,D, IN FACT YOU CAN -- THIS 1072 00:44:24,402 --> 00:44:27,238 IS WHAT HAPPENED HERE. 1073 00:44:27,238 --> 00:44:27,672 SORRY. 1074 00:44:27,672 --> 00:44:29,641 AND WHAT HAPPENED THIS SERIES IS 1075 00:44:29,641 --> 00:44:31,576 GOING TO HAPPEN AND BASICALLY BE 1076 00:44:31,576 --> 00:44:36,114 ABLE TO PRODUCE A NUMBER OF 1077 00:44:36,114 --> 00:44:36,548 NEURON. 1078 00:44:36,548 --> 00:44:38,416 SO AGAIN SHOW YOU SAME PICTURE 1079 00:44:38,416 --> 00:44:40,819 ALL OVER AGAIN TO POINT 1080 00:44:40,819 --> 00:44:42,453 SOMETHING HERE BASICALLY WHAT 1081 00:44:42,453 --> 00:44:44,656 GOES WRONG, THERE'S MANY 1082 00:44:44,656 --> 00:44:50,361 NEUROBLAST HERE, DON'T EXPRESS 1083 00:44:50,361 --> 00:44:51,329 ANY KNOWN TRANSCRIPTION FACTOR. 1084 00:44:51,329 --> 00:44:56,701 THE WAY WE GOT THE HUNCHBACK, 1085 00:44:56,701 --> 00:44:59,537 SIMPLY IN THE FRIDGE, ALSO DEEP 1086 00:44:59,537 --> 00:44:59,771 INSIGHT. 1087 00:44:59,771 --> 00:45:01,172 SO WE SAY LET'S TRY TO SEE 1088 00:45:01,172 --> 00:45:05,243 WHETHER WE CAN FIND A WAY TO GET 1089 00:45:05,243 --> 00:45:06,277 SOMETHING MORE SYSTEMATIC TO 1090 00:45:06,277 --> 00:45:09,080 EXPRESS, TO IDENTIFY ALL OF 1091 00:45:09,080 --> 00:45:10,048 THOSE TRANSCRIPTION FACTOR WHICH 1092 00:45:10,048 --> 00:45:13,751 EXPRESS IN THE NEURONS IN THE 1093 00:45:13,751 --> 00:45:15,086 PICTURE HERE. 1094 00:45:15,086 --> 00:45:16,387 LET'S TAKE THIS STRUCTURE HERE 1095 00:45:16,387 --> 00:45:19,390 AND YOU CAN SEE ONE SNAPSHOT 1096 00:45:19,390 --> 00:45:20,425 AGAIN, ALL NEUROBLASTS, ALL 1097 00:45:20,425 --> 00:45:21,326 STAGE OF DEVELOPMENT. 1098 00:45:21,326 --> 00:45:22,894 LET'S TAKE THIS AND SEQUENCE 1099 00:45:22,894 --> 00:45:24,796 THEM AS A SINGLE CELL LEVEL TO 1100 00:45:24,796 --> 00:45:26,564 SEE WHICH ONE EXPRESS WHICH 1101 00:45:26,564 --> 00:45:28,867 GENE, MAYBE TRY TO ORGANIZE INTO 1102 00:45:28,867 --> 00:45:29,534 A PATHWAY. 1103 00:45:29,534 --> 00:45:30,735 YOU'LL SEE IT WORKS BEAUTIFULLY 1104 00:45:30,735 --> 00:45:31,169 WELL. 1105 00:45:31,169 --> 00:45:32,804 WHAT YOU HAVE HERE AGAIN A 1106 00:45:32,804 --> 00:45:35,006 PICTURE NOT AS PRETTY WITH ALL 1107 00:45:35,006 --> 00:45:36,407 THE BEAUTIFUL YOU SEE BEFORE 1108 00:45:36,407 --> 00:45:38,943 BECAUSE NOW IT'S PROCESS OF 1109 00:45:38,943 --> 00:45:39,477 DEVELOPMENT, BASICALLY 1110 00:45:39,477 --> 00:45:40,578 EVERYTHING IN PROCESS OF 1111 00:45:40,578 --> 00:45:41,012 DEVELOPING. 1112 00:45:41,012 --> 00:45:47,418 WHAT YOU HAVE HERE, YOU HAVE 1113 00:45:47,418 --> 00:45:52,824 THE -- OKAY. 1114 00:45:52,824 --> 00:45:59,163 SO YOU HAVE THE NEUROBLAST HERE, 1115 00:45:59,163 --> 00:45:59,364 OKAY? 1116 00:45:59,364 --> 00:46:00,598 AND NEUROBLAST HERE. 1117 00:46:00,598 --> 00:46:04,202 THEN YOU HAVE THE NEURONS AND 1118 00:46:04,202 --> 00:46:08,573 NOW THE NEURONS THE BEAUTIFUL 1119 00:46:08,573 --> 00:46:10,375 BLOT ELONGATED STRUCTURE 1120 00:46:10,375 --> 00:46:13,177 CORRESPOND TO MATURATION OF THE 1121 00:46:13,177 --> 00:46:14,279 NEURONS, AND UNTIL THE 1122 00:46:14,279 --> 00:46:15,046 TRAJECTORY, AT THE OTHER 1123 00:46:15,046 --> 00:46:17,348 TRAJECTORY IF YOU LOOK AT THE 1124 00:46:17,348 --> 00:46:19,017 NEXT STEPS, ONE GROUP OF CELLS I 1125 00:46:19,017 --> 00:46:20,485 SHOWED YOU BEFORE, IF YOU ADD 1126 00:46:20,485 --> 00:46:22,921 THEM TO THE SYSTEM YOU CAN SEE 1127 00:46:22,921 --> 00:46:25,023 THAT ADDED TO THE TIP OF EACH 1128 00:46:25,023 --> 00:46:26,858 ONE OF THE DIRECTION, OKAY? 1129 00:46:26,858 --> 00:46:29,827 SO YOU CAN SEE NOW YOU CAN 1130 00:46:29,827 --> 00:46:32,463 RECONSTRUCT PRECISELY WHAT 1131 00:46:32,463 --> 00:46:33,798 HAPPENS BETWEEN THE -- SORRY. 1132 00:46:33,798 --> 00:46:35,767 I HAVE SOME PROBLEM WITH THE 1133 00:46:35,767 --> 00:46:36,100 POINTER. 1134 00:46:36,100 --> 00:46:38,803 SO YOU CAN SEE HERE THAT YOU CAN 1135 00:46:38,803 --> 00:46:42,140 GO FROM NEUROBLAST, SO 1136 00:46:42,140 --> 00:46:42,674 NEUROREPEATER, NEUROBLAST, 1137 00:46:42,674 --> 00:46:43,841 DEVELOPING NEURONS, MATURE 1138 00:46:43,841 --> 00:46:45,810 NEURONS, YOU CAN SEE AGAIN 1139 00:46:45,810 --> 00:46:46,678 TRAJECTORY COMPLETELY, YOU CAN 1140 00:46:46,678 --> 00:46:49,180 REALLY UNDERSTAND HOW YOU CAN 1141 00:46:49,180 --> 00:46:50,748 MATURE AND PRODUCE THOSE 1142 00:46:50,748 --> 00:46:50,982 NEURONS. 1143 00:46:50,982 --> 00:46:54,886 BUT LET'S LOOK AT THE 1144 00:46:54,886 --> 00:46:56,521 NEUROBLAST, YOU CAN SEE THERE'S 1145 00:46:56,521 --> 00:46:57,188 SOME STRUCTURE WHICH EXISTS HERE 1146 00:46:57,188 --> 00:47:01,459 IN THE SENSE THEY ARE NOT 1147 00:47:01,459 --> 00:47:02,160 JUST -- IT'S VERY STRUCTURE, 1148 00:47:02,160 --> 00:47:04,329 WHEN YOU CLOSE YOU GET SOMETHING 1149 00:47:04,329 --> 00:47:06,197 VERY SURPRISING BECAUSE YOU SEE 1150 00:47:06,197 --> 00:47:07,832 EXACTLY WHAT YOU EXPECT BECAUSE 1151 00:47:07,832 --> 00:47:11,970 THESE ARE PURE COMPUTER 1152 00:47:11,970 --> 00:47:12,937 RENDERING, JUST WHAT THE 1153 00:47:12,937 --> 00:47:13,604 COMPUTER SPITS OUT. 1154 00:47:13,604 --> 00:47:19,644 YOU CAN SEE AT THE BOTTOM WHAT 1155 00:47:19,644 --> 00:47:20,078 YOU HAVE. 1156 00:47:20,078 --> 00:47:27,085 EXACTLY WHAT YOU SEE ON THIS 1157 00:47:27,085 --> 00:47:27,585 PICTURE. 1158 00:47:27,585 --> 00:47:31,122 WE CAN REPRODUCE WITH COMPUTER 1159 00:47:31,122 --> 00:47:32,557 WHAT HAPPENED IN REAL LIFE. 1160 00:47:32,557 --> 00:47:34,959 EXCEPT ON THE MAP YOU CAN SEE A 1161 00:47:34,959 --> 00:47:38,663 LOT OF NEURAL BLASTS WHITE, 1162 00:47:38,663 --> 00:47:39,931 EXACTLY WHAT THE CONTENT IS 1163 00:47:39,931 --> 00:47:42,834 BECAUSE OF SINGLE CELL 1164 00:47:42,834 --> 00:47:43,134 SEQUENCING. 1165 00:47:43,134 --> 00:47:45,136 YOU HAVE ORGANIZATION DUE TO OUR 1166 00:47:45,136 --> 00:47:46,838 SERIES THAT WE KNEW, YOU CAN SEE 1167 00:47:46,838 --> 00:47:49,974 WHAT IS GOING TO BE ABLE TO 1168 00:47:49,974 --> 00:47:54,946 IDENTIFY ALL THE TRANSCRIPT 1169 00:47:54,946 --> 00:47:56,781 FACTOR IN BETWEEN, AND WHAT YOU 1170 00:47:56,781 --> 00:48:00,485 SEE HERE IS EXACTLY THAT. 1171 00:48:00,485 --> 00:48:06,591 YOU CAN RECOGNIZE ON THE X-AXIS 1172 00:48:06,591 --> 00:48:08,026 HERE, COMES BACK A SECOND TIME, 1173 00:48:08,026 --> 00:48:15,133 I WILL COME BACK THERE'S TWO 1174 00:48:15,133 --> 00:48:17,969 WINDOWS OF EXPRESSION, WE GO 1175 00:48:17,969 --> 00:48:22,807 BACK TO OUR FRIEND ISLET, THE 1176 00:48:22,807 --> 00:48:25,009 NEW ONE, NOW WE HAVE THE 1177 00:48:25,009 --> 00:48:26,077 COMPLETE SERIES OF TRANSCRIPTION 1178 00:48:26,077 --> 00:48:28,279 FACTOR FROM TIME WHEN THE 1179 00:48:28,279 --> 00:48:29,947 NEUROBLASTS WERE BORN TO THE 1180 00:48:29,947 --> 00:48:31,015 TIME BASICALLY THE NEUROBLASTS 1181 00:48:31,015 --> 00:48:32,884 ARE GOING TO DIVIDE AND FINISH 1182 00:48:32,884 --> 00:48:34,118 THEIR LIFE HERE. 1183 00:48:34,118 --> 00:48:36,487 YOU CAN SEE THE POWER OF SINGLE 1184 00:48:36,487 --> 00:48:37,588 CELL SEQUENCING AND SOFTWARE TO 1185 00:48:37,588 --> 00:48:39,123 BE ABLE TO PROCESS THE DATA IN 1186 00:48:39,123 --> 00:48:43,061 SUCH A WAY YOU CAN ORGANIZE INTO 1187 00:48:43,061 --> 00:48:43,928 VERY SPECIFIC WAYS. 1188 00:48:43,928 --> 00:48:47,231 YOU CAN DO THE SAME THING AS I 1189 00:48:47,231 --> 00:48:48,066 DESCRIBED. 1190 00:48:48,066 --> 00:48:54,872 MOST OF THE GENE, X PLUS ONE, 1191 00:48:54,872 --> 00:49:02,447 BASICALLY ARE OPEN. 1192 00:49:02,447 --> 00:49:04,515 INDEED FOR EXAMPLE HOMOTHORAX, 1193 00:49:04,515 --> 00:49:14,592 AT SOME POINT GOING TO OVERLAP 1194 00:49:14,592 --> 00:49:17,562 WITH EACH OTHER, AND TEMPORAL 1195 00:49:17,562 --> 00:49:18,863 WINDOW IS COMBINATION OF TWO OR 1196 00:49:18,863 --> 00:49:20,064 THREE OF THE TRANSCRIPTION 1197 00:49:20,064 --> 00:49:21,365 FACTOR WHICH ACTUALLY I SHOW IN 1198 00:49:21,365 --> 00:49:24,635 THE NEXT SLIDE. 1199 00:49:24,635 --> 00:49:28,806 AGAIN, NEUROBLAST HERE, WHEN 1200 00:49:28,806 --> 00:49:29,907 YOU'RE BORN EXPRESS HOMOTHORAX, 1201 00:49:29,907 --> 00:49:35,613 DITCHED TO -- DIVIDE TO PRODUCE 1202 00:49:35,613 --> 00:49:36,981 A CELL. 1203 00:49:36,981 --> 00:49:39,417 HOMOTHORAX IS STILL THERE. 1204 00:49:39,417 --> 00:49:44,088 THEN WE TURN OFF, TURN ON ERM, 1205 00:49:44,088 --> 00:49:44,689 SO ON. 1206 00:49:44,689 --> 00:49:47,658 I THINK YOU WILL SEE THIS IS NOT 1207 00:49:47,658 --> 00:49:49,293 SO EASY TO DEFINE, EXACTLY DON'T 1208 00:49:49,293 --> 00:49:53,564 KNOW WHEN THE TRANSITION OCCUR. 1209 00:49:53,564 --> 00:49:56,434 BUT NOW WE HAVE TWELVE TEMPORAL 1210 00:49:56,434 --> 00:49:57,602 WINDOWS, SPECIFY AT LEAST TWELVE 1211 00:49:57,602 --> 00:49:58,769 TYPE OF NEURON, SHORT OF THE 1212 00:49:58,769 --> 00:50:00,872 HUNDRED WE WANT TO DO. 1213 00:50:00,872 --> 00:50:05,943 BECAUSE EACH DIVISION HERE YOU 1214 00:50:05,943 --> 00:50:06,844 HAVE ANOTHER DIVISION DIVIDE 1215 00:50:06,844 --> 00:50:09,247 WITH NOTCH ON, NOTCH ON, GREEN 1216 00:50:09,247 --> 00:50:11,949 AND RED NEURON. 1217 00:50:11,949 --> 00:50:14,619 IN FACT CAN MULTIPLY TWELVE 1218 00:50:14,619 --> 00:50:16,787 WINDOW BY TWO, GET 24 CELL 1219 00:50:16,787 --> 00:50:17,421 TYPES. 1220 00:50:17,421 --> 00:50:18,990 WE'RE GETTING THERE. 1221 00:50:18,990 --> 00:50:21,392 WE CAN SPECIFY 24 CELL TYPES BY 1222 00:50:21,392 --> 00:50:23,027 THIS TEMPORAL SERIES OF 1223 00:50:23,027 --> 00:50:25,429 TRANSCRIPTION FACTOR. 1224 00:50:25,429 --> 00:50:29,367 NOW WE HAVE ACTUALLY SOLVED A 1225 00:50:29,367 --> 00:50:30,801 MAJOR ISSUE, WE'VE NOW -- HOW 1226 00:50:30,801 --> 00:50:33,538 TIME CAN BE INVOLVED IN PROCESS, 1227 00:50:33,538 --> 00:50:35,373 WHAT IS THE MECHANISM BY WHICH 1228 00:50:35,373 --> 00:50:37,041 TIME IS INVOLVED BY THE THEORY 1229 00:50:37,041 --> 00:50:38,142 OF TRANSCRIPTION FACTORS THAT 1230 00:50:38,142 --> 00:50:40,778 CONTROL EACH OTHER AND THEN 1231 00:50:40,778 --> 00:50:44,048 GENERATE NEURONS BELOW THEM AS A 1232 00:50:44,048 --> 00:50:45,249 CONSEQUENCE OF BEING SPECIFIC 1233 00:50:45,249 --> 00:50:47,084 TRANSCRIPTION FACTOR IN THE 1234 00:50:47,084 --> 00:50:47,885 GENOME. 1235 00:50:47,885 --> 00:50:53,324 SO BUT WHAT ABOUT THE OTHER 75 1236 00:50:53,324 --> 00:50:55,293 NEURONS WE NEED TO MAKE? 1237 00:50:55,293 --> 00:51:03,100 WE ONLY MAKE 24 YEARS. 1238 00:51:03,100 --> 00:51:06,704 WE OBSERVE WAY BEFORE THE 1239 00:51:06,704 --> 00:51:07,605 NEUROBLASTS ARE BORN, WHAT I 1240 00:51:07,605 --> 00:51:18,082 TOLD YOU IS TRUE FOR ALL THE 1241 00:51:19,584 --> 00:51:20,117 NEUROEPITHELIUM CELLS, HEMO 1242 00:51:20,117 --> 00:51:22,486 THORAX, IN SPITE OF THAT SHOW 1243 00:51:22,486 --> 00:51:24,255 DIFFERENT IN TERMS OF WHERE THEY 1244 00:51:24,255 --> 00:51:24,422 ARE. 1245 00:51:24,422 --> 00:51:28,926 WHICH MEANS TIP OF THE CRESCENT 1246 00:51:28,926 --> 00:51:30,261 EXPRESS RX, FAMOUS FOR ITS ROLE 1247 00:51:30,261 --> 00:51:35,733 IN EYE DEVELOPMENT IN MOUSE. 1248 00:51:35,733 --> 00:51:38,803 OPTIX, VSX, ALSO INVOLVED IN 1249 00:51:38,803 --> 00:51:39,670 DEVELOPMENT. 1250 00:51:39,670 --> 00:51:44,909 YOU CAN SEE DORSO PATH OR 1251 00:51:44,909 --> 00:51:55,453 VENTRAL PART OF THE PATHWAY, SIX 1252 00:51:57,121 --> 00:52:00,925 DOMAINS, RX, OPTIX, VSX VENTRAL. 1253 00:52:00,925 --> 00:52:03,094 DOMAIN DO PLAY A ROLE IN 1254 00:52:03,094 --> 00:52:04,662 SPECIFYING THE NEURON. 1255 00:52:04,662 --> 00:52:08,466 HERE YOU HAVE THIS ILLUSTRATION, 1256 00:52:08,466 --> 00:52:12,637 JUST THE FIRST TEMPORAL WINDOW. 1257 00:52:12,637 --> 00:52:20,444 NEUROBLAST JUST BORN, EXPRESS 1258 00:52:20,444 --> 00:52:23,180 HEMOTHORAX, PRODUCE MI-1, AND 1259 00:52:23,180 --> 00:52:28,753 NOW UNICHROME, ONE FOR EACH. 1260 00:52:28,753 --> 00:52:36,661 AND EACH OF THE NEUROBLASTS ARE 1261 00:52:36,661 --> 00:52:39,930 GOING TO PRODUCE MI-1, ALL 1262 00:52:39,930 --> 00:52:40,698 PRODUCE ONE. 1263 00:52:40,698 --> 00:52:44,302 BUT THEN YOU CAN DO MORE DETAIL 1264 00:52:44,302 --> 00:52:46,937 FOR SERIES, THERE'S ACTUALLY ALL 1265 00:52:46,937 --> 00:52:49,040 THE NEURONS BEING PRODUCED, FOR 1266 00:52:49,040 --> 00:52:54,745 EXAMPLE PM3 ONLY PRODUCED BY THE 1267 00:52:54,745 --> 00:52:58,115 VSX DOMAIN OR PM 2, OR PM 1 1268 00:52:58,115 --> 00:53:01,552 PRODUCED BY THE VENTRAL, WHICH 1269 00:53:01,552 --> 00:53:02,586 MEANS OF COURSE THEY ARE GOING 1270 00:53:02,586 --> 00:53:13,130 TO PRODUCE IN A SMALLER AMOUNT, 1271 00:53:17,268 --> 00:53:18,169 SMALLER STOICHIOMETRY. 1272 00:53:18,169 --> 00:53:21,038 NOW THINGS BECOME CLEAR. 1273 00:53:21,038 --> 00:53:24,208 SINCE YOU HAVE AT LEAST SIX 1274 00:53:24,208 --> 00:53:26,110 DOMAINS OF DIFFERENT, EACH 1275 00:53:26,110 --> 00:53:27,945 DOMAIN APPEAR TO PRODUCE 1276 00:53:27,945 --> 00:53:28,713 DIFFERENT NEURONS, WHAT IS SOME 1277 00:53:28,713 --> 00:53:30,448 OF THE NEURONS APPEAR TO CARE 1278 00:53:30,448 --> 00:53:31,949 WHERE THEY COME FROM, THEREFORE 1279 00:53:31,949 --> 00:53:33,884 WHAT YOU CAN SEE YOU CAN 1280 00:53:33,884 --> 00:53:37,121 MULTIPLY THE 24 TYPES OF NEURONS 1281 00:53:37,121 --> 00:53:43,761 YOU CAN PRODUCE, MULTIPLY SIX 1282 00:53:43,761 --> 00:53:45,329 SPECIAL DOMAINS, GET 144 NEURON 1283 00:53:45,329 --> 00:53:46,097 TYPES, LARGE ENOUGH TO EXPLAIN 1284 00:53:46,097 --> 00:53:49,400 HOW YOU CAN PRODUCE ALL THE 1285 00:53:49,400 --> 00:53:49,633 NEURONS. 1286 00:53:49,633 --> 00:53:52,470 SO I THINK WE HAVE NOW A DEEP 1287 00:53:52,470 --> 00:53:53,437 UNDERSTANDING OF HOW THOSE 1288 00:53:53,437 --> 00:53:55,406 DIFFERENT TYPES OF NEURONS CAN 1289 00:53:55,406 --> 00:53:59,777 BE BORN AND HOW THEY CAN BE 1290 00:53:59,777 --> 00:54:02,413 GENERATED BY COMBINATION OF 1291 00:54:02,413 --> 00:54:04,515 TEMPORAL SERIES, SPECIAL 1292 00:54:04,515 --> 00:54:06,250 INFORMATION, ALSO NOTCH ON/NOTCH 1293 00:54:06,250 --> 00:54:10,121 OFF THAT DOUBLES THE NEURONS. 1294 00:54:10,121 --> 00:54:11,822 SOMETHING TO BE SOLVED HERE, WHY 1295 00:54:11,822 --> 00:54:13,924 DO YOU HAVE NEURONS LIKE RED WE 1296 00:54:13,924 --> 00:54:16,093 KNOW WHERE IT COMES FROM, OR 1297 00:54:16,093 --> 00:54:20,898 BLUE DO CARE WHERE THEY COME 1298 00:54:20,898 --> 00:54:25,169 FROM, FROM VSX, DORSAL OR 1299 00:54:25,169 --> 00:54:25,403 VENTRAL. 1300 00:54:25,403 --> 00:54:27,371 WE TRIED TO IDENTIFY ALL THE 1301 00:54:27,371 --> 00:54:29,140 NEURONS THAT COME FROM EACH ONE 1302 00:54:29,140 --> 00:54:30,975 OF THE DOMAIN. 1303 00:54:30,975 --> 00:54:34,044 WHAT YOU CAN SEE AGAIN CRESCENT 1304 00:54:34,044 --> 00:54:36,547 SHAPE, HERE IN GREEN MARKER ONLY 1305 00:54:36,547 --> 00:54:47,024 LABELS NEURON THAT COME FROM 1306 00:54:48,125 --> 00:54:50,461 DORSAL OR VENTRAL, THE TIP. 1307 00:54:50,461 --> 00:54:52,763 YOU CAN IDENTIFY THE NEURONS 1308 00:54:52,763 --> 00:54:55,733 THAT COME FROM THAT. 1309 00:54:55,733 --> 00:54:58,569 I COULD LIST HUNDRED NEURONS, 1310 00:54:58,569 --> 00:55:02,740 THOSE NEURONS FOR EXAMPLE TM5 1311 00:55:02,740 --> 00:55:04,909 A-B FROM DORSAL OPTICS AND A BIT 1312 00:55:04,909 --> 00:55:07,578 OF THE VSX, SO ON, AND EXPLAIN 1313 00:55:07,578 --> 00:55:10,114 HOW THOSE DIFFERENT NEURONS ARE 1314 00:55:10,114 --> 00:55:14,118 BEING PLAYED FROM DIFFERENT 1315 00:55:14,118 --> 00:55:15,119 DOMAINS. 1316 00:55:15,119 --> 00:55:17,087 A NUMBER OF NEURONS STOCHIOMETRY 1317 00:55:17,087 --> 00:55:20,391 DEMEANT ON THE SIZE OF THE 1318 00:55:20,391 --> 00:55:21,158 NEUROREPEATER. 1319 00:55:21,158 --> 00:55:22,226 WELL ILLUSTRATED HERE FROM THE 1320 00:55:22,226 --> 00:55:24,094 WORK OF A POSTDOC IN THE LAB, 1321 00:55:24,094 --> 00:55:26,530 YOU CAN SEE CRESCENT SHAPE, 1322 00:55:26,530 --> 00:55:30,000 DIFFERENT DOMAIN, SOME OF THE 1323 00:55:30,000 --> 00:55:31,802 NEURON IS ACTUALLY INTERNAL 1324 00:55:31,802 --> 00:55:37,107 NEURON PRODUCED FOR EXAMPLE VERY 1325 00:55:37,107 --> 00:55:40,077 LARGE NUMBER, THE WHOLE 1326 00:55:40,077 --> 00:55:43,147 NEUROREPEATER WHEREBY NEURON 1327 00:55:43,147 --> 00:55:46,851 WHICH HAVE SMALLER STOCHIOMETRY 1328 00:55:46,851 --> 00:55:48,385 PRODUCE SMALLER DOMAIN, THIS 1329 00:55:48,385 --> 00:55:51,255 COMES FROM A VERY TINY DOMAIN. 1330 00:55:51,255 --> 00:55:52,223 YOU CAN ESTABLISH CORRELATION 1331 00:55:52,223 --> 00:55:54,959 BETWEEN THE SIZE OF DOMAIN WHERE 1332 00:55:54,959 --> 00:55:58,229 THEY COME FROM AND STOCHIOMETRY 1333 00:55:58,229 --> 00:55:59,096 OF THE NEURON. 1334 00:55:59,096 --> 00:56:01,398 YOU CAN IMAGINE YOU CAN KNOW HOW 1335 00:56:01,398 --> 00:56:04,969 YOU CAN COMBINE ALL THE FEATURES 1336 00:56:04,969 --> 00:56:05,603 TEMPORAL, SPATIAL, NOTCH, THE 1337 00:56:05,603 --> 00:56:15,613 SITE OF THE DOUGH DOMAIN TO PRE 1338 00:56:15,613 --> 00:56:18,682 ALL IN STOCHIOMETRY. 1339 00:56:18,682 --> 00:56:19,683 EVERYTHING WAS GOOD. 1340 00:56:19,683 --> 00:56:23,254 THERE WAS A PROBLEM WE CAME AT 1341 00:56:23,254 --> 00:56:23,921 SOME POINT, SOMETHING I DIDN'T 1342 00:56:23,921 --> 00:56:25,789 EXPECT VERY MUCH. 1343 00:56:25,789 --> 00:56:27,992 AGAIN, I TEND TO HAVE KIND OF 1344 00:56:27,992 --> 00:56:29,727 DOGMATIC VIEW OF THE WORLD. 1345 00:56:29,727 --> 00:56:31,128 EVERYTHING SHOULD BE GOOD MODEL 1346 00:56:31,128 --> 00:56:32,363 AND SHOULD FIT VERY WELL. 1347 00:56:32,363 --> 00:56:35,699 YOU WORK ON FLIES, THIS WORKS 1348 00:56:35,699 --> 00:56:36,133 QUITE WELL. 1349 00:56:36,133 --> 00:56:38,769 THE MODEL WOULD BE THAT YOU HAVE 1350 00:56:38,769 --> 00:56:40,304 800 NEUROBLASTS THAT PRODUCE ALL 1351 00:56:40,304 --> 00:56:41,438 THOSE NEURONS. 1352 00:56:41,438 --> 00:56:44,875 BUT IN FACT WHEN YOU REALIZE IN 1353 00:56:44,875 --> 00:56:50,114 DETAIL, THIS WASN'T THE CASE. 1354 00:56:50,114 --> 00:56:55,286 YOU HAVE ON THE LEFT SIDE 1355 00:56:55,286 --> 00:56:55,853 NEUROEPITHELIUM IN BLUE, AND 1356 00:56:55,853 --> 00:56:58,355 NEUROBLASTS FORMED AT THE OTHER 1357 00:56:58,355 --> 00:57:01,959 EDGE AS A WAVE FROM THE OUTER 1358 00:57:01,959 --> 00:57:03,494 EDGE OF THE NEUROEPITHELIUM TO 1359 00:57:03,494 --> 00:57:06,564 THE CENTER. 1360 00:57:06,564 --> 00:57:12,903 IN PURPLE, MI1, I SHOWED YOU, 1361 00:57:12,903 --> 00:57:16,507 THERE WAS DISCREPANCY HERE. 1362 00:57:16,507 --> 00:57:18,275 A NUMBER DID NOT CORRESPONDS TO 1363 00:57:18,275 --> 00:57:20,444 NUMBER OF NEUROBLASTS PRODUCED 1364 00:57:20,444 --> 00:57:22,713 HERE, MORE DRAMATIC WHEN THE 1365 00:57:22,713 --> 00:57:27,017 MORE NEUROEPITHELIUM HAS BEEN 1366 00:57:27,017 --> 00:57:31,355 PRODUCED, AND DIGESTED, EATEN BY 1367 00:57:31,355 --> 00:57:35,092 NEUROBLASTS, MANY FOR COMPARED 1368 00:57:35,092 --> 00:57:36,493 TO MI1. 1369 00:57:36,493 --> 00:57:37,928 2,000 FOR 800 MI1. 1370 00:57:37,928 --> 00:57:38,796 THERE'S SOMETHING WRONG HERE. 1371 00:57:38,796 --> 00:57:42,299 WHY DO YOU HAVE MORE NEURONS, 1372 00:57:42,299 --> 00:57:44,068 MORE NEUROBLASTS THAN NEURONS, 1373 00:57:44,068 --> 00:57:45,769 THE MODEL PRODUCED WAS GREAT, IF 1374 00:57:45,769 --> 00:57:49,940 YOU HAVE 2,000 YOU SHOULD SEE AT 1375 00:57:49,940 --> 00:57:51,609 LEAST 2,000 MI1s, WHICH WAS 1376 00:57:51,609 --> 00:57:52,710 NOT THE CASE. 1377 00:57:52,710 --> 00:57:56,780 WAY CAME UP WITH THE -- WE CAME 1378 00:57:56,780 --> 00:58:01,385 UP WITH THE FOLLOWING SITUATION. 1379 00:58:01,385 --> 00:58:03,621 FIRST TEMPORAL MI1, TM1, 4, 1380 00:58:03,621 --> 00:58:05,322 LATER ON 2, 6. 1381 00:58:05,322 --> 00:58:09,460 AND THE IDEA WILL BE THAT THIS 1382 00:58:09,460 --> 00:58:10,561 HAPPEN WHENEVER CELL CYCLE 1383 00:58:10,561 --> 00:58:13,897 DIVISION OCCURS IN THE MI1 1384 00:58:13,897 --> 00:58:18,102 WINDOW OR TM1, ET CETERA. 1385 00:58:18,102 --> 00:58:20,604 YOU THINK THERE'S NO REASON WHY 1386 00:58:20,604 --> 00:58:26,543 IT COULD BE COORDINATED CAN 1387 00:58:26,543 --> 00:58:27,077 TEMPORAL WINDOWS. 1388 00:58:27,077 --> 00:58:28,946 YOU NEED TO REGROW TO BE ABLE TO 1389 00:58:28,946 --> 00:58:31,115 DIVIDE AGAIN. 1390 00:58:31,115 --> 00:58:37,354 THERE'S NO REASON THIS SHOULD BE 1391 00:58:37,354 --> 00:58:41,492 SYNCHRONIZED WHICH DEPENDS ON 1392 00:58:41,492 --> 00:58:44,795 THE NETWORK WHERE HEMO THORAX 1393 00:58:44,795 --> 00:58:45,696 ACTIVATE ISLETS. 1394 00:58:45,696 --> 00:58:48,298 WHAT HAPPENS IF YOU DISCONNECT 1395 00:58:48,298 --> 00:58:53,570 CELL CYCLE FROM TEMPORAL WINDOW 1396 00:58:53,570 --> 00:58:53,871 PROGRESSION? 1397 00:58:53,871 --> 00:58:55,539 INDEED IN PARTICULAR CELL CYCLE, 1398 00:58:55,539 --> 00:58:59,677 THEN THE PROGRESSION OF THE 1399 00:58:59,677 --> 00:59:01,412 TEMPORAL WINDOW YOU COULD 1400 00:59:01,412 --> 00:59:04,281 IMAGINE IN FACT NOT EVERY 1401 00:59:04,281 --> 00:59:05,582 TEMPORAL WINDOW WILL BE HIT BY 1402 00:59:05,582 --> 00:59:06,684 CELL CYCLE BY DIVISION AND 1403 00:59:06,684 --> 00:59:08,986 THEREFORE FOR EXAMPLE IN THIS 1404 00:59:08,986 --> 00:59:10,754 CASE MI1 WINDOW WILL NOT BE HIT 1405 00:59:10,754 --> 00:59:15,726 BY A CELL CYCLE, NOT PRODUCED 1406 00:59:15,726 --> 00:59:20,497 HERE BUT TM 1 OR 4, MAYBE NO TM 1407 00:59:20,497 --> 00:59:21,765 6, AND SO ON. 1408 00:59:21,765 --> 00:59:25,936 LET'S TRY TO SEE THAT. 1409 00:59:25,936 --> 00:59:28,238 TO SOME EXTENT, TM 6 HERE, MAYBE 1410 00:59:28,238 --> 00:59:32,409 THE NEXT NEUROBLAST WILL 1411 00:59:32,409 --> 00:59:34,912 INTRODUCE A TM 6 AND NOT A TM 2. 1412 00:59:34,912 --> 00:59:38,749 IT WILL AVERAGE WHEN 2,000 1413 00:59:38,749 --> 00:59:41,118 NEUROBLASTS ONLY PRODUCE MI 1 1414 00:59:41,118 --> 00:59:44,121 EVERY 2 1/2 NEUROBLASTS 1415 00:59:44,121 --> 00:59:49,059 BASICALLY YOU WILL GET BASICALLY 1416 00:59:49,059 --> 00:59:51,028 THE CORRECT STOCHIOMETRY FOR 1417 00:59:51,028 --> 00:59:52,329 EACH OF THE NEURON. 1418 00:59:52,329 --> 00:59:53,664 VERY NICE BUT CAN WE TEST 1419 00:59:53,664 --> 00:59:54,298 WHETHER TRUE? 1420 00:59:54,298 --> 00:59:55,699 WE CAN DO THAT BECAUSE YOU CAN 1421 00:59:55,699 --> 00:59:57,267 TEST WHAT HAPPENED TO THE 1422 00:59:57,267 --> 01:00:02,206 LINEAGE EACH OF THE SINGLE 1423 01:00:02,206 --> 01:00:02,506 NEUROBLASTS. 1424 01:00:02,506 --> 01:00:06,009 YOU CAN SEE THE NEURON IS BORN, 1425 01:00:06,009 --> 01:00:14,017 PRODUCE MI 1 NOTCH ON, A FEW 1426 01:00:14,017 --> 01:00:17,654 CELL TYPES HERE. 1427 01:00:17,654 --> 01:00:18,856 TM 2 AND TM 6. 1428 01:00:18,856 --> 01:00:24,661 DO WE SEE EVERY NEUROBLAST 1429 01:00:24,661 --> 01:00:26,630 PRODUCE ALL THOSE EXPECT ALL 1430 01:00:26,630 --> 01:00:26,930 THESE? 1431 01:00:26,930 --> 01:00:29,233 AND IN FACT THE WAY WE DO THAT 1432 01:00:29,233 --> 01:00:31,969 WE LOOK ONLY ON THE NOTCH ON 1433 01:00:31,969 --> 01:00:33,170 LINEAGE, GREEN LINEAGE, BECAUSE 1434 01:00:33,170 --> 01:00:36,673 WE HAVE A MOCKUP FOR THAT AND 1435 01:00:36,673 --> 01:00:37,207 TRANSCRIPTION FACTOR WHICH 1436 01:00:37,207 --> 01:00:39,643 REMEMBER I TOLD YOU THERE WAS 1437 01:00:39,643 --> 01:00:41,311 THIS TEMPORAL TRANSCRIPTION 1438 01:00:41,311 --> 01:00:43,614 FACTOR WHICH EXPRESSED ONLY IN 1439 01:00:43,614 --> 01:00:48,085 TWO DIFFERENT WINDOWS OF THE 1440 01:00:48,085 --> 01:00:50,721 TEMPORAL SERIES, AND TURNS ON 1441 01:00:50,721 --> 01:00:52,923 ANOTHER GENE, SO FOUR CELL 1442 01:00:52,923 --> 01:00:57,594 TYPES, TM 1, TM 4, TM 2, TM 6, 1443 01:00:57,594 --> 01:01:02,733 WITH JUST ONE MARKING YOU CAN 1444 01:01:02,733 --> 01:01:04,067 IDENTIFY LINEAGE, NOT BECAUSE 1445 01:01:04,067 --> 01:01:05,903 IT'S GREEN AND SO FOUR CELLS YOU 1446 01:01:05,903 --> 01:01:06,770 EXPECT TO FIND. 1447 01:01:06,770 --> 01:01:10,073 NOW WE'RE GOING TO LOOK ONE BY 1448 01:01:10,073 --> 01:01:10,974 ONE AT MULTIPLE DIFFERENT 1449 01:01:10,974 --> 01:01:12,843 NEUROBLAST LINEAGE TO SEE 1450 01:01:12,843 --> 01:01:14,478 WHETHER THEY FOLLOW THIS FULLY 1451 01:01:14,478 --> 01:01:16,680 HERE, OKAY? 1452 01:01:16,680 --> 01:01:19,716 SO, YOU CAN GENERATE IN FLIES, 1453 01:01:19,716 --> 01:01:21,051 ANALYZE IN DETAIL. 1454 01:01:21,051 --> 01:01:25,622 HERE TWO EXAMPLE OF CLONES, THE 1455 01:01:25,622 --> 01:01:26,757 CLONES STARTED HERE, PRODUCED 1456 01:01:26,757 --> 01:01:27,958 THIS, AND NEUROBLAST WAS AT THE 1457 01:01:27,958 --> 01:01:32,329 END, IN FACTS JUST DISAPPEARED 1458 01:01:32,329 --> 01:01:33,964 BECAUSE IT DIED. 1459 01:01:33,964 --> 01:01:37,134 AND FOUR TYPE OF NEURONS, 1460 01:01:37,134 --> 01:01:39,102 BASICALLY LET ME TRY TO SHOW YOU 1461 01:01:39,102 --> 01:01:42,105 IN DETAIL THE RESULTS IN YOU 1462 01:01:42,105 --> 01:01:42,906 INTERPRET THEM. 1463 01:01:42,906 --> 01:01:45,776 AGAIN THE CLONE, YOU CAN SEE 1464 01:01:45,776 --> 01:01:47,744 THIS CLONE CONTAIN TM 1 AND TM 4 1465 01:01:47,744 --> 01:01:52,783 AS EXPECTED BUT CONTAIN NO TM 2, 1466 01:01:52,783 --> 01:01:54,718 NO TM 6. 1467 01:01:54,718 --> 01:01:57,120 THIS ONE CONTAINS 1 TM 2, NO 6, 1468 01:01:57,120 --> 01:01:59,790 AND SO ON AND SO ON WHICH IS 1469 01:01:59,790 --> 01:02:02,192 EXACTLY WHAT YOU EXPECT, EACH 1470 01:02:02,192 --> 01:02:03,760 NEUROBLAST LINEAGE DEFER FROM 1471 01:02:03,760 --> 01:02:06,163 NEXT BUT OVERALL THE WHOLE THING 1472 01:02:06,163 --> 01:02:08,332 DISCOVERED, THAT MEANS ALL THE 1473 01:02:08,332 --> 01:02:10,968 NEUROBLASTS TOGETHER WILL 1474 01:02:10,968 --> 01:02:12,736 PRODUCE ALL THE NEURONS YOU NEED 1475 01:02:12,736 --> 01:02:13,136 MAKE. 1476 01:02:13,136 --> 01:02:14,938 THE INTERPRETATION WILL BE THIS 1477 01:02:14,938 --> 01:02:19,610 WILL BE THE LINEAGE EVERY 1478 01:02:19,610 --> 01:02:20,611 NEURON, EVERY TEMPORAL WINDOW 1479 01:02:20,611 --> 01:02:23,780 WAS BEING USED BUT IN FACT YOU 1480 01:02:23,780 --> 01:02:25,916 CAN SEE DEEPENING EACH ONE OF 1481 01:02:25,916 --> 01:02:33,991 THE LINEAGE ONLY SOME SUBSETS 1482 01:02:33,991 --> 01:02:34,758 BEING USED? 1483 01:02:34,758 --> 01:02:37,394 WHY DO WE HAVE THE 1484 01:02:37,394 --> 01:02:38,428 STOCHASTICITY? 1485 01:02:38,428 --> 01:02:40,330 IT MIGHT BE FOR PLASTICITY, 1486 01:02:40,330 --> 01:02:41,865 ROBUSTNESS OF SYSTEM, MIGHT BE 1487 01:02:41,865 --> 01:02:43,600 BECAUSE IT'S DIFFICULT TO 1488 01:02:43,600 --> 01:02:45,035 COORDINATE THE NUMBER OF CELL 1489 01:02:45,035 --> 01:02:46,436 CYCLE WITH NUMBER OF CELL 1490 01:02:46,436 --> 01:02:48,739 DIVISION, AND OF COURSE THIS 1491 01:02:48,739 --> 01:02:50,073 WILL REQUIRE ADJUSTMENT AT THE 1492 01:02:50,073 --> 01:02:52,676 END, WHAT YOU CAN SEE YOU NEVER 1493 01:02:52,676 --> 01:02:55,312 PRODUCE MORE THAN THE NUMBER OF 1494 01:02:55,312 --> 01:02:59,683 NEURONS AND SEE YOU'RE GOING TO 1495 01:02:59,683 --> 01:03:00,350 ELIMINATE THEM. 1496 01:03:00,350 --> 01:03:04,388 SO, IT SEEMS WHAT WE'VE DONE 1497 01:03:04,388 --> 01:03:10,027 HERE IS GO INTO DETAIL, AND THE 1498 01:03:10,027 --> 01:03:11,295 ONLY THING WE DON'T KNOW REALLY 1499 01:03:11,295 --> 01:03:13,997 WHAT HAPPENS, WHY DO WE HAVE THE 1500 01:03:13,997 --> 01:03:17,868 TEMPORALS WE DESCRIBE HERE AND I 1501 01:03:17,868 --> 01:03:20,938 MADE THEM AS TEMPORAL WINDOWS, 1502 01:03:20,938 --> 01:03:23,707 YOU OPEN AND CLOSE BECAUSE IT'S 1503 01:03:23,707 --> 01:03:24,441 A TRANSCRIPTION NETWORK, 1504 01:03:24,441 --> 01:03:25,542 TRANSITION FROM ONE TO THE NEXT 1505 01:03:25,542 --> 01:03:28,745 IS NOT A SHARP WINDOW. 1506 01:03:28,745 --> 01:03:31,348 IT'S A DIFFUSE WINDOW AND WE 1507 01:03:31,348 --> 01:03:34,184 DON'T KNOW HOW YOU CONNECT 1508 01:03:34,184 --> 01:03:35,419 SYSTEM WITH POSITIVE FEEDBACK 1509 01:03:35,419 --> 01:03:38,355 WHERE YOU'RE GOING TO MAKE A 1510 01:03:38,355 --> 01:03:39,256 DECISION, THIS WINDOW, THAT 1511 01:03:39,256 --> 01:03:40,123 WINDOW, NOTHING IN BETWEEN. 1512 01:03:40,123 --> 01:03:41,758 WE DON'T KNOW WHAT HAPPENS AND 1513 01:03:41,758 --> 01:03:42,960 WE'RE STILL WORKING ON FIGURING 1514 01:03:42,960 --> 01:03:50,267 OUT WHAT'S GOING ON THERE. 1515 01:03:50,267 --> 01:03:57,074 SO, OOPS. 1516 01:03:57,074 --> 01:03:58,608 WHAT'S GOING ON? 1517 01:03:58,608 --> 01:04:00,143 I WANT TO GIVE CREDIT TO PEOPLE 1518 01:04:00,143 --> 01:04:02,746 THAT HAVE DONE THE WORK IN THE 1519 01:04:02,746 --> 01:04:02,913 LAB. 1520 01:04:02,913 --> 01:04:13,457 THIS WAS INITIATED BY NIKOS, NOW 1521 01:04:14,758 --> 01:04:21,898 A PROFESSOR IN PARIS. 1522 01:04:21,898 --> 01:04:24,368 ALL THE LATER WORK DONE BY 1523 01:04:24,368 --> 01:04:28,572 FELIX, A STUDENT IN THE LAB, 1524 01:04:28,572 --> 01:04:38,115 ALSO JOINED NIKOS IN PARIS, AND 1525 01:04:38,115 --> 01:04:40,851 TOOK A JOB, AND A CURRENT 1526 01:04:40,851 --> 01:04:41,451 Ph.D. STUDENT. 1527 01:04:41,451 --> 01:04:43,553 ONE DAY I TELL YOU EVERYTHING 1528 01:04:43,553 --> 01:04:46,523 ELSE WE DO ON THE FLIES, 1529 01:04:46,523 --> 01:04:48,191 DIFFERENT SYSTEM ON THE FLIES, 1530 01:04:48,191 --> 01:04:50,927 ALSO THE WORK IN COLLABORATION 1531 01:04:50,927 --> 01:04:51,461 ON THE ANTS. 1532 01:04:51,461 --> 01:04:53,864 I WANT TO THANK YOU VERY MUCH. 1533 01:04:53,864 --> 01:04:55,499 AGAIN, VERY PROUD TO BE HERE 1534 01:04:55,499 --> 01:04:57,934 TODAY AND TO BE ABLE TO TELL YOU 1535 01:04:57,934 --> 01:05:00,570 THIS STORY AND THANKS TO ALL OF 1536 01:05:00,570 --> 01:05:00,804 YOU. 1537 01:05:00,804 --> 01:05:03,073 [APPLAUSE] 1538 01:05:03,073 --> 01:05:13,116 1539 01:05:16,987 --> 01:05:18,188 >> ALL RIGHT. 1540 01:05:18,188 --> 01:05:19,489 CLAUDE, WONDERFUL, AND VERY 1541 01:05:19,489 --> 01:05:20,424 COMPLEX TALK. 1542 01:05:20,424 --> 01:05:21,925 I MEAN, I HAD QUESTIONS ALONG 1543 01:05:21,925 --> 01:05:26,630 THE WAY BUT YOU ANSWERED SOME OF 1544 01:05:26,630 --> 01:05:27,964 THEM, BUT SOME REMAINING. 1545 01:05:27,964 --> 01:05:30,333 LET ME BEGIN FROM THE BOTTOM UP. 1546 01:05:30,333 --> 01:05:32,736 ONE OF THE THINGS YOU SAID THERE 1547 01:05:32,736 --> 01:05:36,606 ARE A LOT OF NEUROBLASTS, 2,000 1548 01:05:36,606 --> 01:05:38,575 OR SO. 1549 01:05:38,575 --> 01:05:40,243 AND YOU EXPECTED ONLY 800, ONE 1550 01:05:40,243 --> 01:05:40,677 FOR EACH. 1551 01:05:40,677 --> 01:05:42,879 I'M NOT SO SURE WHY BECAUSE YOU 1552 01:05:42,879 --> 01:05:44,514 ANSWERED THAT QUESTION OBVIOUSLY 1553 01:05:44,514 --> 01:05:46,483 THAT NOT EVERY NEUROBLAST HAS TO 1554 01:05:46,483 --> 01:05:48,885 PRODUCE ALL THE CELL TYPES, 1555 01:05:48,885 --> 01:05:49,753 RIGHT? 1556 01:05:49,753 --> 01:05:55,492 ALONG THE SAME WAY, DID YOU 1557 01:05:55,492 --> 01:05:56,126 CONSIDER THE POSSIBILITY THAT 1558 01:05:56,126 --> 01:06:01,631 CELL CYCLE TIME CAN BE DIFFERENT 1559 01:06:01,631 --> 01:06:02,732 AT DIFFERENT TEMPORAL AND 1560 01:06:02,732 --> 01:06:03,967 SPATIAL REGIONS? 1561 01:06:03,967 --> 01:06:06,770 IT DOESN'T HAVE TO BE PRECISELY 1562 01:06:06,770 --> 01:06:07,304 IDENTICAL. 1563 01:06:07,304 --> 01:06:09,639 AND THAT ALSO CAN CREATE 1564 01:06:09,639 --> 01:06:11,808 DIFFERENT ISSUES, SIMILAR THERE 1565 01:06:11,808 --> 01:06:14,111 COULD BE SOME MIGRATION OF CELLS 1566 01:06:14,111 --> 01:06:16,313 AT DIFFERENT TIMES AS WELL, 1567 01:06:16,313 --> 01:06:18,815 WHICH COULD CHANGE THEIR NATURE. 1568 01:06:18,815 --> 01:06:21,251 AND THEN AGAIN THERE MAY BE 1569 01:06:21,251 --> 01:06:22,853 CELLS WHICH INTERACT WITH EACH 1570 01:06:22,853 --> 01:06:26,123 OTHER, THEY MAY BE GIVING 1571 01:06:26,123 --> 01:06:27,057 DIFFERENT SIGNALS, AND THAT 1572 01:06:27,057 --> 01:06:29,226 COULD CREATE FURTHER NEURONAL 1573 01:06:29,226 --> 01:06:30,227 DIVERSITY, SO MANY DIFFERENT 1574 01:06:30,227 --> 01:06:32,963 WAYS, SO I'M NOT SURE WHY SUCH A 1575 01:06:32,963 --> 01:06:35,699 MATHEMATICAL WAY WE HAVE TO SHOW 1576 01:06:35,699 --> 01:06:37,334 THIS, AND ON TOP OF ALL THAT 1577 01:06:37,334 --> 01:06:40,270 MOST OF THE TIME YOU TALKED 1578 01:06:40,270 --> 01:06:42,506 ABOUT QUALITATIVE STUFF, AMOUNT 1579 01:06:42,506 --> 01:06:44,441 OF TRANSCRIPTION FACTOR, BASED 1580 01:06:44,441 --> 01:06:49,045 ON IN SOME CASES ISC BUT SR RNA 1581 01:06:49,045 --> 01:06:52,649 YOU WERE TALKING ABOUT RNA. 1582 01:06:52,649 --> 01:06:53,416 BUT QUANTITATIVE ISSUES, 1583 01:06:53,416 --> 01:06:54,217 TRANSCRIPTION FACTORS IN 1584 01:06:54,217 --> 01:06:56,953 DIFFERENT QUANTITIES CAN HAVE 1585 01:06:56,953 --> 01:06:57,487 DIFFERENT FUNCTIONS. 1586 01:06:57,487 --> 01:07:00,590 SO THERE ARE LOTS OF THINGS, MY 1587 01:07:00,590 --> 01:07:02,425 FRIEND, WE STILL HAVE TO ANSWER. 1588 01:07:02,425 --> 01:07:04,294 A LONG WAYS TO GO. 1589 01:07:04,294 --> 01:07:06,930 >> YOU ASK FIVE OR TEN QUESTIONS 1590 01:07:06,930 --> 01:07:10,534 AT THE SAME TIME. 1591 01:07:10,534 --> 01:07:13,470 AND IT WOULD TAKE AN HOUR TO 1592 01:07:13,470 --> 01:07:15,939 ANSWER TO YOU, FIRST THING I CAN 1593 01:07:15,939 --> 01:07:17,407 ANSWER THAT CELL TYPE. 1594 01:07:17,407 --> 01:07:19,276 YOU SAY THERE MAY BE MODULATION 1595 01:07:19,276 --> 01:07:21,478 OF CELL TYPE OR PLASTICITY, AND 1596 01:07:21,478 --> 01:07:24,314 I THINK TO SOME EXTENT WE CAN 1597 01:07:24,314 --> 01:07:26,616 START IN FLIES BECAUSE FLIES 1598 01:07:26,616 --> 01:07:27,684 HAVE NO PLASTICITY. 1599 01:07:27,684 --> 01:07:29,119 THEY ARE BORN, LIVE FOR A FEW 1600 01:07:29,119 --> 01:07:35,025 DAYS OR WEEKS AND DIE. 1601 01:07:35,025 --> 01:07:41,965 THEY DON'T CARE ABOUT 1602 01:07:41,965 --> 01:07:42,399 PLASTICITY. 1603 01:07:42,399 --> 01:07:48,438 WHETHER THE CELL CYCLE CAN VARY 1604 01:07:48,438 --> 01:07:49,172 IN SPEED, WHETHER TEMPORAL 1605 01:07:49,172 --> 01:07:50,707 WINDOW CAN BE LONGER OR SHORTER 1606 01:07:50,707 --> 01:07:52,709 I AGREE. 1607 01:07:52,709 --> 01:07:54,144 WE SEE DIFFERENT IN CELL CYCLE. 1608 01:07:54,144 --> 01:07:55,779 IN FACT CELL CYCLE GETS LONGER 1609 01:07:55,779 --> 01:07:56,880 WITH TIME. 1610 01:07:56,880 --> 01:08:00,617 BUT, YOU KNOW, SIMPLY NATURE FOR 1611 01:08:00,617 --> 01:08:02,352 EXAMPLE MAKING LONGER TEMPORAL 1612 01:08:02,352 --> 01:08:05,088 WINDOW, CELL CYCLE SLOWS DOWN. 1613 01:08:05,088 --> 01:08:07,057 OR MAKING SMALLEST DOCUMENTARY 1614 01:08:07,057 --> 01:08:08,258 BECAUSE YOU CAN ALSO ADDRESS 1615 01:08:08,258 --> 01:08:09,859 DOCUMENTARY BY THE SPACE BY 1616 01:08:09,859 --> 01:08:12,295 WHICH THEY COME FROM BUT THE 1617 01:08:12,295 --> 01:08:15,031 FREQUENCY AT WHICH THEY ARE HIT 1618 01:08:15,031 --> 01:08:16,466 BY TEMPORAL WINDOW, WE CAN 1619 01:08:16,466 --> 01:08:18,535 DISCUSS MAYBE TONIGHT OR ANOTHER 1620 01:08:18,535 --> 01:08:25,242 DAY, WE SEE EACH OTHER. 1621 01:08:25,242 --> 01:08:26,676 THANK YOU. 1622 01:08:26,676 --> 01:08:30,046 >> SO IF THE SPATIAL WINDOWS FOR 1623 01:08:30,046 --> 01:08:33,016 THE MORE RARE CELL TYPES ARE SO 1624 01:08:33,016 --> 01:08:34,551 RESTRICTED, YOU WOULD THINK 1625 01:08:34,551 --> 01:08:44,961 THERE HAS TO BE A LOT OF 1626 01:08:48,765 --> 01:08:51,201 TANGENTIAL MIGRATION GOING ON. 1627 01:08:51,201 --> 01:08:53,169 >> THE CELLS ARE BEING MADE IN 1628 01:08:53,169 --> 01:08:57,340 THE SAME PLACE, I'M TALK BECOME 1629 01:08:57,340 --> 01:08:59,609 THE VERTICAL, LOWEST COMING FROM 1630 01:08:59,609 --> 01:09:00,910 THE SMALL DOMAIN. 1631 01:09:00,910 --> 01:09:04,814 ONE CLONE, THEY STAY THERE, THEY 1632 01:09:04,814 --> 01:09:06,316 SEND PROJECTION THAT COVER THE 1633 01:09:06,316 --> 01:09:08,518 WHOLE RETINA, THEN THEY DO WHAT 1634 01:09:08,518 --> 01:09:10,353 YOU SAY, DON'T MIGRATE. 1635 01:09:10,353 --> 01:09:15,392 I THINK THEY MOVE, I THINK, 1636 01:09:15,392 --> 01:09:18,461 BECAUSE SHORTEN AXONS TO BE 1637 01:09:18,461 --> 01:09:22,032 CLOSER TO PROJECTION. 1638 01:09:22,032 --> 01:09:25,368 THEY DO THE CELL MOVEMENT. 1639 01:09:25,368 --> 01:09:28,305 WE'RE INTERESTING TO FIGURE OUT 1640 01:09:28,305 --> 01:09:30,273 RETINOPATHY, WE'RE WORKING QUITE 1641 01:09:30,273 --> 01:09:31,941 HARD, MY NEXT GRANT FROM NEI 1642 01:09:31,941 --> 01:09:34,878 WILL BE ON THIS TOPIC, AND WE 1643 01:09:34,878 --> 01:09:36,680 IDENTIFY THE FACT THAT PCP 1644 01:09:36,680 --> 01:09:37,814 PATHWAY APPEARS TO BE INVOLVED 1645 01:09:37,814 --> 01:09:41,985 IN THE PROCESS OF FINDING OUT 1646 01:09:41,985 --> 01:09:42,986 WHERE PROJECT AXONS. 1647 01:09:42,986 --> 01:09:44,521 THERE'S EXAMPLE OF CELL 1648 01:09:44,521 --> 01:09:46,690 MIGRATION IN FLIES. 1649 01:09:46,690 --> 01:09:49,659 AGAIN ALSO TOPIC OF ANOTHER 1650 01:09:49,659 --> 01:09:50,960 GRANT, BUT IT'S ACTUALLY A 1651 01:09:50,960 --> 01:09:57,000 SPECIAL TYPE OF CELL THAT DOES 1652 01:09:57,000 --> 01:09:58,301 MIGRATES, THE WAY YOU EXPECT 1653 01:09:58,301 --> 01:10:04,007 CELL TO MIGRATES AND SENDS 1654 01:10:04,007 --> 01:10:04,674 PROJECTIONS. 1655 01:10:04,674 --> 01:10:05,208 >> THANKS. 1656 01:10:05,208 --> 01:10:07,344 >> THIS IS REALLY A FANTASTIC 1657 01:10:07,344 --> 01:10:09,145 LECTURE AND I HAVE TO 1658 01:10:09,145 --> 01:10:14,718 CONGRATULATE YOU ON YOUR COLOR 1659 01:10:14,718 --> 01:10:16,252 SELECTION. 1660 01:10:16,252 --> 01:10:16,519 BRILLIANT. 1661 01:10:16,519 --> 01:10:18,455 I'M MORE INTERESTED IN THE 1662 01:10:18,455 --> 01:10:21,191 PROCESS OF HOW NOTCH IS TURNING 1663 01:10:21,191 --> 01:10:23,259 ON AND OFF IN YOUR VERY FIRST 1664 01:10:23,259 --> 01:10:24,894 STEP. 1665 01:10:24,894 --> 01:10:27,864 WE KNOW A LITTLE MORE ABOUT 1666 01:10:27,864 --> 01:10:31,468 SEGMENTATION OF THE DORSAL CORD 1667 01:10:31,468 --> 01:10:32,769 AND VERTEBRAL DEVELOPMENT WHEN 1668 01:10:32,769 --> 01:10:39,042 THE NOTCHES TURN ON AND OFF, 1669 01:10:39,042 --> 01:10:45,982 ESPECIALLY ON THE EPIGENETICS OF 1670 01:10:45,982 --> 01:10:47,117 CHROMATIN MODELING. 1671 01:10:47,117 --> 01:10:48,151 IS THERE SIMILARITY OF THE NOTCH 1672 01:10:48,151 --> 01:10:51,354 ON AND OFF IN YOUR SYSTEM? 1673 01:10:51,354 --> 01:10:52,155 HAVE YOU LOOKED -- 1674 01:10:52,155 --> 01:10:54,991 >> SO NOTCH HAS BEEN DISCOVERED 1675 01:10:54,991 --> 01:10:56,526 IN FLIES, MOSTLY WHAT'S CALLED 1676 01:10:56,526 --> 01:11:05,235 LATERAL INHIBITION, TWO CELLS 1677 01:11:05,235 --> 01:11:06,803 DIVIDE EXACTLY THE SAME, THIS 1678 01:11:06,803 --> 01:11:09,572 TUG OF WAR ONE WILL BE NOTCH ON, 1679 01:11:09,572 --> 01:11:11,875 ONE NOTCH OFF. 1680 01:11:11,875 --> 01:11:13,410 BECOME A NEURON, THE WAY TO 1681 01:11:13,410 --> 01:11:14,944 DESCRIBE WHAT I TEACH MY 1682 01:11:14,944 --> 01:11:15,211 STUDENTS. 1683 01:11:15,211 --> 01:11:18,248 WHAT HAPPENS TWO CELLS DIVIDE, 1684 01:11:18,248 --> 01:11:20,116 ONE BECOMES NOTCH ON, ONE NOTCH 1685 01:11:20,116 --> 01:11:20,383 OFF. 1686 01:11:20,383 --> 01:11:22,185 THIS IS A STRONG DECISION 1687 01:11:22,185 --> 01:11:24,254 BECAUSE BEING NOTCH ON IS 1688 01:11:24,254 --> 01:11:31,127 DIFFERENT FROM NOTCH OFF. 1689 01:11:31,127 --> 01:11:41,671 ALL NOTCH-ON NEURONS -- NOTCH -- 1690 01:11:45,675 --> 01:11:49,913 VERY STRONG DECISION, INHIBITORY 1691 01:11:49,913 --> 01:11:52,148 PATHWAY, CRITICAL NOTCH PATHWAY, 1692 01:11:52,148 --> 01:11:53,950 I'M A, YOU MUST BE B. 1693 01:11:53,950 --> 01:11:56,152 I'M A, YOU'RE GOING TO BE B. 1694 01:11:56,152 --> 01:11:58,455 TUG OF WAR BETWEEN TWO CELLS. 1695 01:11:58,455 --> 01:12:02,926 ACTUALLY THE MOLECULAR NATURE OF 1696 01:12:02,926 --> 01:12:05,562 THE REGULATION, AUTOREGULATION, 1697 01:12:05,562 --> 01:12:07,330 NOTCH ACTIVATES ACTIVITY, NOTCH 1698 01:12:07,330 --> 01:12:10,834 RECEPTOR, LACK OF NOTCH ACTIVITY 1699 01:12:10,834 --> 01:12:13,603 INHIBITS NOTCH, ACTIVATES DELTA, 1700 01:12:13,603 --> 01:12:18,842 OKAY? 1701 01:12:18,842 --> 01:12:21,010 >> GREAT TALK. 1702 01:12:21,010 --> 01:12:23,947 I'M WORKING ON GENETICS, I KNOW 1703 01:12:23,947 --> 01:12:26,382 FLY IS GREAT MODEL FOR GENETICS 1704 01:12:26,382 --> 01:12:26,683 TOO. 1705 01:12:26,683 --> 01:12:28,985 I'M JUST WONDERING IS THERE ANY 1706 01:12:28,985 --> 01:12:33,289 STUDY WHERE PEOPLE HAVE LOOKED 1707 01:12:33,289 --> 01:12:35,258 AT THE MUTANTS, THE STUDY, 1708 01:12:35,258 --> 01:12:38,394 WHETHER A PARTICULAR TYPE OF 1709 01:12:38,394 --> 01:12:38,862 CELL -- 1710 01:12:38,862 --> 01:12:41,197 >> YEAH, VERY COMPLEX QUESTION, 1711 01:12:41,197 --> 01:12:43,700 WE CAN MAKE MUTATION AT WILL, 1712 01:12:43,700 --> 01:12:45,335 CELL SPECIFIC NATURE OF THE 1713 01:12:45,335 --> 01:12:47,670 MUTATION, OVERALL I MEAN YOU CAN 1714 01:12:47,670 --> 01:12:49,806 SAY THINGS FOLLOW WHAT TRY TO 1715 01:12:49,806 --> 01:12:51,808 DESCRIBE SO SKIPPED A LOT OF 1716 01:12:51,808 --> 01:12:53,243 STEPS WHERE WE MADE SURE THIS 1717 01:12:53,243 --> 01:12:54,677 WAS ACTUALLY CORRECT SO, FOR 1718 01:12:54,677 --> 01:12:56,312 EXAMPLE, IF YOU INTERRUPT THE 1719 01:12:56,312 --> 01:12:59,382 TEMPORAL SERIES YOU CAN SEE THE 1720 01:12:59,382 --> 01:13:01,050 TEMPORAL SERIES BLOCKED BECAUSE 1721 01:13:01,050 --> 01:13:01,684 YOU CANNOT PROGRESS BUT CELL 1722 01:13:01,684 --> 01:13:03,553 CYCLE DIVIDE. 1723 01:13:03,553 --> 01:13:05,388 YOU CAN ALSO PREVENT CELL CYCLE 1724 01:13:05,388 --> 01:13:07,190 FROM OCCURRING, BLOCK CELL 1725 01:13:07,190 --> 01:13:09,259 CYCLE, TEMPORAL IS GOING. 1726 01:13:09,259 --> 01:13:11,327 OR YOU CAN ACTUALLY CHANGE THE 1727 01:13:11,327 --> 01:13:12,428 SPECIFIC NEURON, MAKE TWO 1728 01:13:12,428 --> 01:13:16,466 NEURONS OF THE SAME CELL TYPE, 1729 01:13:16,466 --> 01:13:19,002 ONE DIE, A LOT OF THINGS CAN 1730 01:13:19,002 --> 01:13:22,038 DESCRIBE WHICH I CANNOT DO IN 1731 01:13:22,038 --> 01:13:22,505 THIS TALK. 1732 01:13:22,505 --> 01:13:25,475 MOST OF THE WORK WE DO IS, YOU 1733 01:13:25,475 --> 01:13:27,343 KNOW, BESIDE SINGLE CELL 1734 01:13:27,343 --> 01:13:29,946 SEQUENCING IS DOING CROSS IN FLY 1735 01:13:29,946 --> 01:13:31,080 WITH MUTANTS, LOOKING AT 1736 01:13:31,080 --> 01:13:31,948 MICROSCOPE. 1737 01:13:31,948 --> 01:13:32,382 >> GREAT. 1738 01:13:32,382 --> 01:13:41,824 THANK YOU. 1739 01:13:41,824 --> 01:13:43,893 >> CLAUDE, THANK YOU SO MUCH. 1740 01:13:43,893 --> 01:13:45,495 ANY OTHER QUESTIONS HERE THAT 1741 01:13:45,495 --> 01:13:48,398 PEOPLE WANT TO ASK ABOUT OR TALK 1742 01:13:48,398 --> 01:13:51,768 ABOUT? 1743 01:13:51,768 --> 01:13:51,968 OKAY. 1744 01:13:51,968 --> 01:13:53,403 LET ME TRY TO SUM THINGS UP 1745 01:13:53,403 --> 01:13:53,736 HERE. 1746 01:13:53,736 --> 01:13:56,706 I THOUGHT THIS WAS A BEAUTIFUL 1747 01:13:56,706 --> 01:13:56,906 TALK. 1748 01:13:56,906 --> 01:13:58,775 JUST THANK YOU VERY MUCH, AND 1749 01:13:58,775 --> 01:14:00,577 CONGRATULATIONS FOR DOING THIS. 1750 01:14:00,577 --> 01:14:03,079 YOU KNOW, FOR US. 1751 01:14:03,079 --> 01:14:04,547 YOU KNOW, JORAM, YOU MENTIONED 1752 01:14:04,547 --> 01:14:09,118 AT THE BEGINNING HAD YOU A 1753 01:14:09,118 --> 01:14:09,352 PHRASE. 1754 01:14:09,352 --> 01:14:12,055 TAKING THE WORLD TO THE EYE. 1755 01:14:12,055 --> 01:14:14,791 AND TAKING THE EYE TO THE WORLD. 1756 01:14:14,791 --> 01:14:16,225 AND I REALLY LIKE THAT. 1757 01:14:16,225 --> 01:14:17,327 I'VE BEEN THINKING ABOUT THAT 1758 01:14:17,327 --> 01:14:19,062 FOR THE PAST HALF HOUR. 1759 01:14:19,062 --> 01:14:22,131 AND I THINK THERE WERE SOME 1760 01:14:22,131 --> 01:14:23,433 GREAT EXAMPLES, CLAUDE, THAT YOU 1761 01:14:23,433 --> 01:14:28,304 GAVE OF BOTH OF THOSE 1762 01:14:28,304 --> 01:14:29,606 DIRECTIONALITIES. 1763 01:14:29,606 --> 01:14:33,343 YOU KNOW, ANATOMY, PHYSIOLOGY, 1764 01:14:33,343 --> 01:14:34,644 DEVELOPMENTAL, NEUROSCIENCE. 1765 01:14:34,644 --> 01:14:35,745 STOCHASTIC PROCESSES, SEEMED 1766 01:14:35,745 --> 01:14:37,180 LIKE SORT OF MACHINE LEARNING. 1767 01:14:37,180 --> 01:14:40,116 I THOUGHT THIS WAS A BEAUTIFUL 1768 01:14:40,116 --> 01:14:40,883 EXAMPLE OF ALL THOSE THINGS, 1769 01:14:40,883 --> 01:14:43,820 WHAT I HOPE THIS IS REALLY ALL 1770 01:14:43,820 --> 01:14:44,253 ABOUT. 1771 01:14:44,253 --> 01:14:49,058 AND SO JUST A BIG WORD OF THANKS 1772 01:14:49,058 --> 01:14:50,059 TO YOU. 1773 01:14:50,059 --> 01:14:53,229 AND JORAM AND LONA, THANK YOU 1774 01:14:53,229 --> 01:14:54,897 FOR YOUR WORK IN MAKING THIS 1775 01:14:54,897 --> 01:14:55,498 POSSIBLE. 1776 01:14:55,498 --> 01:15:00,236 TO STEVE AND THE FNIH GROUP, 1777 01:15:00,236 --> 01:15:01,237 THANK YOU FOR WHAT YOU'VE DONE 1778 01:15:01,237 --> 01:15:02,905 WITH THIS. 1779 01:15:02,905 --> 01:15:07,143 BEHIND THIS IS A SELECTION 1780 01:15:07,143 --> 01:15:08,077 COMMITTEE. 1781 01:15:08,077 --> 01:15:10,013 AND JEREMY NATE ANSWER, KAPIL 1782 01:15:10,013 --> 01:15:17,553 AND OTHERS WHO AREN'T HERE. 1783 01:15:17,553 --> 01:15:18,821 CONNIE, BOB, CAROL, DAN, THEY 1784 01:15:18,821 --> 01:15:21,157 HAVE DONE A LOT OF WORK LEADING 1785 01:15:21,157 --> 01:15:21,824 UP TO THIS. 1786 01:15:21,824 --> 01:15:24,027 AND OF COURSE THERE ARE PEOPLE 1787 01:15:24,027 --> 01:15:26,863 FROM STEVE'S CREW AT THE FNIH 1788 01:15:26,863 --> 01:15:29,732 AND OUR CREW WHO WORKED ON THIS. 1789 01:15:29,732 --> 01:15:32,902 STEVE, I KNOW THAT THERE WAS 1790 01:15:32,902 --> 01:15:35,071 REGINA, MOLLY, ASHLEY IN THE 1791 01:15:35,071 --> 01:15:36,839 BACK THERE. 1792 01:15:36,839 --> 01:15:42,412 AND FROM THE NEI GROUP, FROM 1793 01:15:42,412 --> 01:15:46,049 KAPIL'S GROUP, DAVID, PRINCESS, 1794 01:15:46,049 --> 01:15:48,317 CHARLES, AND KATHERINE, YOU 1795 01:15:48,317 --> 01:15:51,921 KNOW, DEMOTT, GREAT WORK. 1796 01:15:51,921 --> 01:15:54,023 I HAVE TO SAY THAT, YOU KNOW, 1797 01:15:54,023 --> 01:15:56,626 THOSE OF YOU WHO ARE AT NEI KNOW 1798 01:15:56,626 --> 01:15:59,929 I'VE REALLY BEEN TRYING TO 1799 01:15:59,929 --> 01:16:01,664 COMMUNICATE THE REALLY NEED WORK 1800 01:16:01,664 --> 01:16:04,067 THAT HAPPENS IN THE VISION SPACE 1801 01:16:04,067 --> 01:16:05,935 TO PEOPLE OUT THERE. 1802 01:16:05,935 --> 01:16:08,671 AND SOMETIMES I SEE A PAPER THAT 1803 01:16:08,671 --> 01:16:10,740 IS REALLY NEAT, I'LL MAKE A FLAG 1804 01:16:10,740 --> 01:16:15,244 AND POST IT ON SOCIAL MEDIA. 1805 01:16:15,244 --> 01:16:21,918 SOMETIMES KATHERINE DEMOTT AND 1806 01:16:21,918 --> 01:16:23,453 MARIA WILL POST BIT. 1807 01:16:23,453 --> 01:16:26,055 A LOT OF PEOPLES HAVE BEEN FROM 1808 01:16:26,055 --> 01:16:27,390 CLAUDE DESPLAN'S GROUP TO THE 1809 01:16:27,390 --> 01:16:28,825 POINT A COUPLE TIMES I 1810 01:16:28,825 --> 01:16:31,761 INTERCEPTED AND SAID WE HAVE TO 1811 01:16:31,761 --> 01:16:33,396 POST ABOUT SOMEBODY ELSE. 1812 01:16:33,396 --> 01:16:34,597 AND KATHERINE WILL CONFIRM THIS 1813 01:16:34,597 --> 01:16:36,466 IS TRUE, THAT I'VE ACTUALLY 1814 01:16:36,466 --> 01:16:39,302 INTERCEPTED A COUPLE OF THESE. 1815 01:16:39,302 --> 01:16:41,170 BUT REALLY APPRECIATE YOUR 1816 01:16:41,170 --> 01:16:44,240 COMING HERE AND SHARING THAT 1817 01:16:44,240 --> 01:16:44,774 WITH US. 1818 01:16:44,774 --> 01:16:46,409 YOU KNOW, I THINK WHAT I'M GOING 1819 01:16:46,409 --> 01:16:48,277 TO SAY TO CLOSE THIS OUT AND SAY 1820 01:16:48,277 --> 01:16:50,680 THAT WE'RE GOING TO HAVE A 1821 01:16:50,680 --> 01:16:51,547 RECEPTION THAT'S OUTSIDE. 1822 01:16:51,547 --> 01:16:55,118 AND TO ALL OF YOU, ESPECIALLY 1823 01:16:55,118 --> 01:16:57,587 TRAINEES, PLEASE TAKE A MOMENT 1824 01:16:57,587 --> 01:16:59,756 AND INTRODUCE YOURSELF TO DR. 1825 01:16:59,756 --> 01:17:00,490 DESPLAN HERE. 1826 01:17:00,490 --> 01:17:03,159 THAT'S REALLY WHAT THIS IS ALL 1827 01:17:03,159 --> 01:17:03,826 ABOUT. 1828 01:17:03,826 --> 01:17:07,096 JUST EXCHANGING IDEAS, MEETING 1829 01:17:07,096 --> 01:17:08,197 PEOPLE. 1830 01:17:08,197 --> 01:17:10,500 TO THOSE ON THE COMMITTEE, WHICH 1831 01:17:10,500 --> 01:17:11,734 IS BASICALLY GOING TO BE CLAUDE 1832 01:17:11,734 --> 01:17:15,304 BEFORE YOU GO OUT THERE, PLEASE, 1833 01:17:15,304 --> 01:17:19,375 WITH JORAM AND LONA AND JEREMY, 1834 01:17:19,375 --> 01:17:20,476 STEPHEN, KAPIL, STAY HERE AND 1835 01:17:20,476 --> 01:17:22,111 WE'LL TAKE A FEW PICTURES. 1836 01:17:22,111 --> 01:17:27,049 WITH THAT, PLEASE ENJOY THE 1837 01:17:27,049 --> 01:17:27,517 RECEPTION. 1838 01:17:27,517 --> 01:17:29,352 THANK YOU FOR COMING. 1839 01:17:29,352 --> 01:17:29,886 CLAUDE, THANK YOU AGAIN. 1840 01:17:29,886 --> 01:17:30,153 [APPLAUSE] 1841 01:17:30,153 --> 01:17:32,722 [END OF PROGRAM] 1842 01:17:32,722 --> 01:17:38,761 1843 01:17:38,761 --> 01:17:48,805