1 00:00:05,080 --> 00:00:45,240 >>WELCOME TO THE WORKSHOP 2 00:00:45,240 --> 00:00:46,400 STANFORD UNIVERSITY SCHOOL OF 3 00:00:46,400 --> 00:00:47,800 MEDICINE AND POSTGRADUATE 4 00:00:47,800 --> 00:00:51,320 TRAINING IN PEDIATRICS, MEDICAL 5 00:00:51,320 --> 00:00:54,120 GENETICS AND NEONATAL MEDICINE 6 00:00:54,120 --> 00:00:55,840 AT BOSTON CHILDREN'S HOSPITAL 7 00:00:55,840 --> 00:01:00,160 AND HARVARD MEDICAL SCHOOL. 8 00:01:00,160 --> 00:01:03,760 HER FOCUS IS ON PRENATAL 9 00:01:03,760 --> 00:01:07,800 GENOMICS WITH DNA SCREENING AND 10 00:01:07,800 --> 00:01:09,440 DIAGNOSIS TO DEVELOP NEW 11 00:01:09,440 --> 00:01:11,800 THERAPIES FOR GENETIC DISORDERS 12 00:01:11,800 --> 00:01:15,160 TO BE ADMINISTERED PRENATALLY 13 00:01:15,160 --> 00:01:19,720 AND A PAST PRESIDENT OF THE 14 00:01:19,720 --> 00:01:21,680 PERINATAL RESEARCH SOCIETY AND 15 00:01:21,680 --> 00:01:24,840 SOCIETY FOR PRENATAL DIAGNOSIS. 16 00:01:24,840 --> 00:01:25,800 RICHARD HODES HAS DIRECT THE 17 00:01:25,800 --> 00:01:30,560 NATIONAL INSTITUTE ON AGING OR 18 00:01:30,560 --> 00:01:35,120 THE NIA SINCE 1993. 19 00:01:35,120 --> 00:01:38,160 HIS HIS STEWARDSHIP THE BUDGET 20 00:01:38,160 --> 00:01:41,200 HAS GROWN TO $4.2 BILLION 21 00:01:41,200 --> 00:01:43,080 REFLECTING INCREASED PUBLIC 22 00:01:43,080 --> 00:01:44,840 INTEREST IN AGING AS AMERICA AND 23 00:01:44,840 --> 00:01:47,640 THE WORLD GROW OLDER. 24 00:01:47,640 --> 00:01:50,320 DR. HODES HAS DEVOTED HIS TENURE 25 00:01:50,320 --> 00:01:52,200 TO THE DEVELOPMENT OF A STRONG 26 00:01:52,200 --> 00:01:52,840 AND DIVERSE RESEARCH PROGRAM 27 00:01:52,840 --> 00:01:55,840 FOCUSSING ON THE GENETICS AND 28 00:01:55,840 --> 00:01:59,760 BIOLOGY OF AGING, BASIC AND 29 00:01:59,760 --> 00:02:01,080 CLINICAL STUDIES AIMED AT 30 00:02:01,080 --> 00:02:05,400 REDUCING DISEASE AND ALZHEIMER'S 31 00:02:05,400 --> 00:02:07,920 AND RELATED DEMENTIA AND 32 00:02:07,920 --> 00:02:09,200 AGE-RELATED COGNITIVE CHANGE AND 33 00:02:09,200 --> 00:02:10,600 THE BEHAVIORAL AND SOCIAL 34 00:02:10,600 --> 00:02:12,200 ASPECTS OF AGING. 35 00:02:12,200 --> 00:02:16,040 HE'S A GRADUATE OF YALE 36 00:02:16,040 --> 00:02:17,720 UNIVERSITY AND RECEIVED HIS M.D. 37 00:02:17,720 --> 00:02:19,680 FROM HARVARD MEDICAL SCHOOL AND 38 00:02:19,680 --> 00:02:23,800 COMPLETED TRAINING IN INTERNAL 39 00:02:23,800 --> 00:02:28,840 MEDICINE AT MASSACHUSETTS 40 00:02:28,840 --> 00:02:30,760 GENERAL HOSPITAL AND CONTRIBUTED 41 00:02:30,760 --> 00:02:33,840 TO THE FIELD OF IMMUNOLOGY 42 00:02:33,840 --> 00:02:35,200 AUTHORED OVER THAN 250 RESEARCH 43 00:02:35,200 --> 00:02:35,440 PAPERS. 44 00:02:35,440 --> 00:02:38,160 I TURN THE PROGRAM OVER TO 45 00:02:38,160 --> 00:02:38,680 DR. BIANCHI. 46 00:02:38,680 --> 00:02:42,800 >> THANK YOU SO MUCH, DR. PRICE. 47 00:02:42,800 --> 00:02:45,800 I'D LIKE TO WELCOME EVERYONE TO 48 00:02:45,800 --> 00:02:47,320 THE BRAIN ACROSS THE LIFE SPAN 49 00:02:47,320 --> 00:02:49,440 VIRTUAL WORKSHOP AND INCLUDES 50 00:02:49,440 --> 00:02:52,200 THE SPEAKERS AND PANELISTS 51 00:02:52,200 --> 00:02:56,000 JOINING VIA ZOOM AND AUDIENCE 52 00:02:56,000 --> 00:02:58,720 MEMBERS TUNING IN VIA THE NIH 53 00:02:58,720 --> 00:03:00,080 VIDEOCAST AND I BELIEVE IT WILL 54 00:03:00,080 --> 00:03:02,120 BE ARCHIVED AS WELL. 55 00:03:02,120 --> 00:03:14,920 I'M DR. DIANA BIANCHI AND WE'LL 56 00:03:14,920 --> 00:03:17,440 REFER TO NICHD. 57 00:03:17,440 --> 00:03:19,960 THIS HAS COME TOGETHER BETWEEN A 58 00:03:19,960 --> 00:03:22,400 STRONG COLLABORATION THE NIH AND 59 00:03:22,400 --> 00:03:24,880 BILL AND MELINDA GATES 60 00:03:24,880 --> 00:03:26,200 FOUNDATION AND BUILT ON THE 61 00:03:26,200 --> 00:03:28,240 COMMON GOALS OF IMPROVING HEALTH 62 00:03:28,240 --> 00:03:32,080 AND DEVELOPING EFFECTIVE 63 00:03:32,080 --> 00:03:33,840 ASSESSMENTS AND INTERVENTIONS -- 64 00:03:33,840 --> 00:03:35,400 APPROACHES FOR A VARIETY OF 65 00:03:35,400 --> 00:03:38,200 DISEASES IN DIVERSE CULTURAL 66 00:03:38,200 --> 00:03:38,440 CONTEXTS. 67 00:03:38,440 --> 00:03:40,320 SPECIFICALLY NICHD IS ENGAGED 68 00:03:40,320 --> 00:03:42,600 WITH SEVERAL PROJECTS AS PART OF 69 00:03:42,600 --> 00:03:45,800 THE MATERNAL NEONATAL AND CHILD 70 00:03:45,800 --> 00:03:47,200 HEALTH WORKING GROUP ALSO KNOWN 71 00:03:47,200 --> 00:03:49,280 AS THE MUNCHIES. 72 00:03:49,280 --> 00:03:51,920 THE WORKING GROUP IS FOCUSSED ON 73 00:03:51,920 --> 00:03:54,160 PREGNANCY OUTCOMES AND NUTRITION 74 00:03:54,160 --> 00:03:55,760 AND IMPORTANTLY FOR THIS 75 00:03:55,760 --> 00:03:58,800 WORKSHOP NEURAL DEVELOPMENT. 76 00:03:58,800 --> 00:04:02,800 AS A METRIC OF HEALTH AND WELL 77 00:04:02,800 --> 00:04:04,360 BEING THE NEURAL COGNITIVE 78 00:04:04,360 --> 00:04:05,040 DEVELOPMENT IN DIVERSE AND 79 00:04:05,040 --> 00:04:07,760 GLOBAL SETTINGS IS A SHARED 80 00:04:07,760 --> 00:04:10,280 INTEREST BETWEEN NICHD AND THE 81 00:04:10,280 --> 00:04:11,720 GATES FOUNDATION. 82 00:04:11,720 --> 00:04:12,640 NICHD APPRECIATES THE IMPORTANCE 83 00:04:12,640 --> 00:04:17,120 OF TAKING A LIFE SPAN APPROACH 84 00:04:17,120 --> 00:04:18,880 AND LIFE SPAN PERSPECTIVE ON 85 00:04:18,880 --> 00:04:19,200 HEALTH. 86 00:04:19,200 --> 00:04:21,920 IN FACT, AT NICHD'S 2020 87 00:04:21,920 --> 00:04:26,760 STRATEGIC PLAN THERE WAS AN 88 00:04:26,760 --> 00:04:28,800 ASPIRATIONAL GOAL THAT SAID WE 89 00:04:28,800 --> 00:04:31,240 NEED TO IDENTIFY BIOMARKERS OF 90 00:04:31,240 --> 00:04:32,400 ATYPICAL NEURAL DEVELOPMENT TO 91 00:04:32,400 --> 00:04:35,800 ESTABLISH THE LIKELIHOOD OF 92 00:04:35,800 --> 00:04:38,680 NEURO DEGENERATIVE DISORDERS 93 00:04:38,680 --> 00:04:40,680 LATER IN LIFE. 94 00:04:40,680 --> 00:04:42,960 BY IDENTIFYING SENSITIVE PERIODS 95 00:04:42,960 --> 00:04:44,840 WE CAN BETTER UNDERSTAND ORIGINS 96 00:04:44,840 --> 00:04:46,960 OF DISEASE AND CREATE SPECIFIC 97 00:04:46,960 --> 00:04:48,000 INTERVENTIONS TAILORED TO THE 98 00:04:48,000 --> 00:04:51,960 DISRUPTIVE PROCESSES. 99 00:04:51,960 --> 00:04:53,320 NICHD IS AMONG SEVERAL NIH 100 00:04:53,320 --> 00:04:55,000 INSTITUTES AND CENTER SUPPORT 101 00:04:55,000 --> 00:04:57,280 THE ADOLESCENT BRAIN, COGNITIVE 102 00:04:57,280 --> 00:05:00,800 DEVELOPMENT STUDY OR ABCD, THE 103 00:05:00,800 --> 00:05:02,680 LARGEST LONG-TERM STUDY OF BRAIN 104 00:05:02,680 --> 00:05:04,400 DEVELOPMENT IN CHILD HEALTH IN 105 00:05:04,400 --> 00:05:06,200 THE UNITED STATES. 106 00:05:06,200 --> 00:05:07,800 WE'RE ALSO PROUD TO CO-SUPPORT 107 00:05:07,800 --> 00:05:10,600 THE UPCOMING HEALTHY BRAIN AND 108 00:05:10,600 --> 00:05:13,520 CHILD DEVELOPMENT OR HECD STUDY 109 00:05:13,520 --> 00:05:16,000 WHICH WILL RECRUIT A ROBUST 110 00:05:16,000 --> 00:05:18,040 COHORT OF PREGNANT WOMEN FROM 111 00:05:18,040 --> 00:05:20,200 ACROSS THE COUNTRY AND FOLLOW 112 00:05:20,200 --> 00:05:21,720 THE BRAIN, COGNITIVE AND 113 00:05:21,720 --> 00:05:23,440 BEHAVIORAL DEVELOPMENT OF THEIR 114 00:05:23,440 --> 00:05:25,440 CHILDREN THROUGH THE FIRST FEW 115 00:05:25,440 --> 00:05:26,400 YEARS OF LIFE. 116 00:05:26,400 --> 00:05:29,720 STUDIES SUGGEST AS ABCD PROVIDE 117 00:05:29,720 --> 00:05:31,800 A PIVOTAL LOOK AT DIFFERENCES IN 118 00:05:31,800 --> 00:05:32,800 DEVELOPMENT HOWEVER, WHEN IT 119 00:05:32,800 --> 00:05:34,080 COMES TO THE BRAIN, WE'RE 120 00:05:34,080 --> 00:05:36,080 CURRENTLY LIMITED BY THE 121 00:05:36,080 --> 00:05:37,840 AVAILABLE TOOLS TO MEASURE THE 122 00:05:37,840 --> 00:05:40,560 BRAIN OVER LONGER PERIOD OF 123 00:05:40,560 --> 00:05:41,160 TIME. 124 00:05:41,160 --> 00:05:46,520 THUS, WE NEED BETTER APPROACHES 125 00:05:46,520 --> 00:05:49,080 TO LINK DISCREET NEURO DATA TO 126 00:05:49,080 --> 00:05:51,400 UNDERSTAND THE LINK BETWEEN 127 00:05:51,400 --> 00:05:53,280 DIFFERENT LIFE STAGES. 128 00:05:53,280 --> 00:05:54,960 THEREFORE WE'RE PLEASED TO 129 00:05:54,960 --> 00:05:59,400 SUPPORT THE WORK SHOP AS A FIRST 130 00:05:59,400 --> 00:06:01,520 STEP IN AT THE STATE OF THE ART 131 00:06:01,520 --> 00:06:05,840 WAY TO LOOK AT THE BRAIN AND 132 00:06:05,840 --> 00:06:07,160 FOSTER DISCUSSIONS FOR BRAIN 133 00:06:07,160 --> 00:06:08,160 MEASUREMENT ACROSS THE LIFE 134 00:06:08,160 --> 00:06:08,360 SPAN. 135 00:06:08,360 --> 00:06:10,280 HOWEVER, WE DON'T HAVE TO WAIT 136 00:06:10,280 --> 00:06:11,800 FOR FUTURE FUNDING 137 00:06:11,800 --> 00:06:12,280 OPPORTUNITIES. 138 00:06:12,280 --> 00:06:15,000 NICHD ALREADY HAS ACTIVE FUNDING 139 00:06:15,000 --> 00:06:15,800 OPPORTUNITIES RELATIVE TO THE 140 00:06:15,800 --> 00:06:18,440 WORKSHOP AND WE INVITE ALL WHO 141 00:06:18,440 --> 00:06:20,720 ARE INTERESTED TO EXPLORE THE 142 00:06:20,720 --> 00:06:22,800 NIH GUIDE TO IDENTIFY THEM. 143 00:06:22,800 --> 00:06:25,200 THIS WORKSHOP HAS AN EXCITING 144 00:06:25,200 --> 00:06:27,800 AGENDA INCLUDING RESEARCHERS WHO 145 00:06:27,800 --> 00:06:28,640 HAVE DIVERSE EXPERIENCE IN THIS 146 00:06:28,640 --> 00:06:30,800 AREA WOULD ARE WORKING ON 147 00:06:30,800 --> 00:06:33,280 DIFFERENT TIME POINTS WITHIN THE 148 00:06:33,280 --> 00:06:35,400 LIFE SPAN AT DIFFERENT LEVELS OF 149 00:06:35,400 --> 00:06:39,520 RESOLUTION IN BOTH HUMANS AND 150 00:06:39,520 --> 00:06:41,120 NON-HUMAN ANIMAL MODELS I LOOK 151 00:06:41,120 --> 00:06:43,440 FORWARD TO A PRODUCTIVE MEETING 152 00:06:43,440 --> 00:06:44,600 IN WHICH WE CAN EXPLORE EXISTING 153 00:06:44,600 --> 00:06:46,640 AND EMERGING APPROACHES TO 154 00:06:46,640 --> 00:06:53,440 ASSESS CHANGES IN BRAIN CELLULAR 155 00:06:53,440 --> 00:06:54,720 IDENTITY, CONNECTIVITY AND 156 00:06:54,720 --> 00:06:55,600 BETTER UNDERSTAND THEIR 157 00:06:55,600 --> 00:06:56,640 IMPLICATION FOR HEALTH AND 158 00:06:56,640 --> 00:06:58,440 WELLNESS THROUGHOUT LIFE. 159 00:06:58,440 --> 00:07:00,680 AGAIN, I'D LIKE TO THANK THE 160 00:07:00,680 --> 00:07:02,000 SPEAKERS, PANELISTS AND EVERYONE 161 00:07:02,000 --> 00:07:03,200 WHO CONTRIBUTED TO THE PLANNING 162 00:07:03,200 --> 00:07:05,160 OF THIS MEETING AND I WILL NOW 163 00:07:05,160 --> 00:07:09,920 TURN THE PROGRAM OVER TO MY GOOD 164 00:07:09,920 --> 00:07:12,120 COLLEAGUE DR. RICHARD HODES 165 00:07:12,120 --> 00:07:13,120 DIRECTOR OF THE NATIONAL 166 00:07:13,120 --> 00:07:14,640 INSTITUTE OF AGING. 167 00:07:14,640 --> 00:07:18,840 >> AND I JOIN YOU AND IN 168 00:07:18,840 --> 00:07:22,560 WELCOMING THOSE TO THE WORKSHOP. 169 00:07:22,560 --> 00:07:24,640 NICHD AND NIH HAVE BEEN LONG 170 00:07:24,640 --> 00:07:25,800 TERM PARTNERS WITH LIFE SPAN 171 00:07:25,800 --> 00:07:28,400 THAT APPLIES TO THIS WORKSHOP ON 172 00:07:28,400 --> 00:07:29,680 MEASURING BRAIN AND BRAIN 173 00:07:29,680 --> 00:07:34,200 CHANGES ACROSS THE LIFE SPAN. 174 00:07:34,200 --> 00:07:36,400 IT'S IMPORTANT FOR US TO 175 00:07:36,400 --> 00:07:37,800 INCREASE THE MISSION OF THE SPAN 176 00:07:37,800 --> 00:07:39,600 OF LONG AND PRODUCTIVE LIFE AND 177 00:07:39,600 --> 00:07:41,960 UNDERSTAND THE FACTORS THAT 178 00:07:41,960 --> 00:07:48,120 CONTRIBUTE FROM NEOIN A LOTT -- 179 00:07:48,120 --> 00:07:50,080 NEONATAL AND LIFE COURSE EVENTS 180 00:07:50,080 --> 00:07:51,960 AND LOOK AT THE LEVEL OF CLINIC 181 00:07:51,960 --> 00:07:54,080 RESEARCH AND LONGITUDINAL 182 00:07:54,080 --> 00:07:56,400 STUDIES NOW SPANNING THE BIRTH 183 00:07:56,400 --> 00:07:59,200 TO CHILDHOOD THROUGH OLD AGE AND 184 00:07:59,200 --> 00:08:02,200 AN INCREASING EMPHASIS ON THE 185 00:08:02,200 --> 00:08:04,680 COGNITIVE STUDIES OF CHANGES OF 186 00:08:04,680 --> 00:08:07,920 BRAIN AND IMPROVE METHODOLOGIES 187 00:08:07,920 --> 00:08:10,000 AND TOOLS FOR THAT TIME. 188 00:08:10,000 --> 00:08:12,920 AND LOOKING AT THE SPECIAL 189 00:08:12,920 --> 00:08:15,000 EVENTS EARLY IN LIFE TO 190 00:08:15,000 --> 00:08:16,200 PREDISPOSE AND LOOK AT SPECIAL 191 00:08:16,200 --> 00:08:17,440 POPULATIONS INVOLVED AND 192 00:08:17,440 --> 00:08:19,000 DIVERSITY AND SOME SPECIAL 193 00:08:19,000 --> 00:08:20,160 POPULATIONS SUCH AS THOSE 194 00:08:20,160 --> 00:08:22,400 AFFECTED WITH DOWNS SYNDROME 195 00:08:22,400 --> 00:08:23,800 WHICH ARE SO INFORMATIVE AND IN 196 00:08:23,800 --> 00:08:25,320 THEIR OWN RIGHT IN NEED OF 197 00:08:25,320 --> 00:08:26,520 STUDIES ACROSS THE LIFE SPAN AS 198 00:08:26,520 --> 00:08:28,800 WE HAVE PEOPLE LIVING TO LONGER 199 00:08:28,800 --> 00:08:31,560 LIVED WITH INCREASED RISK OF 200 00:08:31,560 --> 00:08:33,600 NEURO DEGENERATIVE DISEASES AND 201 00:08:33,600 --> 00:08:34,880 WE WORK TOGETHER WITH THE BRAIN 202 00:08:34,880 --> 00:08:37,520 INITIATIVE TO LOOK AT EXTENDING 203 00:08:37,520 --> 00:08:42,800 THE ATLAS OF NEURONAL AND GLIAL 204 00:08:42,800 --> 00:08:44,480 CELLS FOR THE LIFE SPAN 205 00:08:44,480 --> 00:08:47,600 PERSPECTIVE AND FOR THE 206 00:08:47,600 --> 00:08:48,440 NEUROSCIENCE BLUEPRINT AT NIH 207 00:08:48,440 --> 00:08:50,200 AND NICHD PARTICIPATING WITH 15 208 00:08:50,200 --> 00:08:53,040 INSTITUTES AND CENTERS TAKE THE 209 00:08:53,040 --> 00:08:55,360 HUMAN CONNECTOME TO LIFE SPAN 210 00:08:55,360 --> 00:08:57,080 CONNECTOME AND STUDYING FROM 211 00:08:57,080 --> 00:09:01,600 CHILDHOOD TO ADULTHOOD AND OLDER 212 00:09:01,600 --> 00:09:02,920 YEARS FOR CHANGES THAT MARK 213 00:09:02,920 --> 00:09:03,880 TRANSITION AND STAGES FROM 214 00:09:03,880 --> 00:09:06,200 HEALTHY TO PATHOLOGIC CHANGE AND 215 00:09:06,200 --> 00:09:09,720 IN DOING SO TO IDENTIFY 216 00:09:09,720 --> 00:09:11,160 INTERVENTIONS TO IMPROVE THE 217 00:09:11,160 --> 00:09:13,000 QUALITY OF LIFE AND BRAIN LIFE 218 00:09:13,000 --> 00:09:14,240 THROUGH THAT TIME. 219 00:09:14,240 --> 00:09:15,520 WITH THIS BACKGROUND I THANK YOU 220 00:09:15,520 --> 00:09:19,000 ALL AND LOOK FORWARD TO THE 221 00:09:19,000 --> 00:09:21,000 EXCITEMENT YOU BRING WITH YOUR 222 00:09:21,000 --> 00:09:22,440 INGENUITY AND EXPERTISE AND LOOK 223 00:09:22,440 --> 00:09:24,040 FORWARD TO THE NEXT FEW DAYS IN 224 00:09:24,040 --> 00:09:26,600 WHICH TO FIND BETTER MEANS OF 225 00:09:26,600 --> 00:09:28,760 TRACKING THE FUNCTION, STRUCTURE 226 00:09:28,760 --> 00:09:30,680 OF BRAIN CHANGES ACROSS AGE AND 227 00:09:30,680 --> 00:09:30,880 LIFE. 228 00:09:30,880 --> 00:09:31,400 THANKS SO MUCH. 229 00:09:31,400 --> 00:09:34,120 I TURN IT BACK TO AMANDA. 230 00:09:34,120 --> 00:09:35,440 >> THANK YOU TO BOTH OF YOU FOR 231 00:09:35,440 --> 00:09:36,200 YOUR WELCOMING REMARKS THIS 232 00:09:36,200 --> 00:09:38,640 MORNING. 233 00:09:38,640 --> 00:09:40,560 >> I'LL GIVE A QUICK OVERVIEW OF 234 00:09:40,560 --> 00:09:42,440 THE WORKSHOP STRUCTURE AND HOW 235 00:09:42,440 --> 00:09:44,040 TO GET THE MOST OUT OF THE 236 00:09:44,040 --> 00:09:45,880 VIRTUAL EVENT TODAY. 237 00:09:45,880 --> 00:09:46,840 FIRST, I'D LIKE TO REMIND 238 00:09:46,840 --> 00:09:49,560 EVERYONE YOU CAN FIND THE AGENDA 239 00:09:49,560 --> 00:09:51,440 AND FULL BIOS FOR ALL THE 240 00:09:51,440 --> 00:09:53,040 SPEAKERS AND PANELISTS ON THE 241 00:09:53,040 --> 00:09:56,280 MEETING WEBSITE AND THE LINK IS 242 00:09:56,280 --> 00:10:03,400 ON THIS SLIDE FOR YOU. 243 00:10:03,400 --> 00:10:05,120 THE OVERALL GOAL WILL BE MEASURE 244 00:10:05,120 --> 00:10:07,400 THE BRAIN OVER TIME AND IDENTIFY 245 00:10:07,400 --> 00:10:08,200 FUTURE DIRECTIONS FOR IMPROVING 246 00:10:08,200 --> 00:10:09,960 OUR ABILITY TO MEASURE THE BRAIN 247 00:10:09,960 --> 00:10:12,000 ACROSS THE LIFE SPAN. 248 00:10:12,000 --> 00:10:13,080 THIS WORKSHOP IS ORGANIZED INTO 249 00:10:13,080 --> 00:10:15,400 THREE SESSIONS OVER TWO DAYS 250 00:10:15,400 --> 00:10:17,240 COVERING THE LATEST AND GREATEST 251 00:10:17,240 --> 00:10:22,040 IN MEASURING BRAIN CELLULAR I'D 252 00:10:22,040 --> 00:10:25,440 IDENTITY AND CONNECTIVITY AND 253 00:10:25,440 --> 00:10:29,240 EACH DAY WILL INCLUDE A PANEL OF 254 00:10:29,240 --> 00:10:31,240 SPECIFIC TOPIC OF INTEREST AND 255 00:10:31,240 --> 00:10:35,200 WE'LL HEAR FROM EXPERTS TO 256 00:10:35,200 --> 00:10:36,040 DISCUSS CONNECTING NEURAL 257 00:10:36,040 --> 00:10:38,880 DEVELOPMENT AND NEURAL 258 00:10:38,880 --> 00:10:40,000 DEGENERATION AND TOMORROW WELL 259 00:10:40,000 --> 00:10:43,040 BE TREATED TO A DISCUSSION ON 260 00:10:43,040 --> 00:10:44,640 SCALING TECHNOLOGIES FROM THE 261 00:10:44,640 --> 00:10:46,040 INDIVIDUAL POPULATION LEVELS 262 00:10:46,040 --> 00:10:48,600 PARTICULARLY IN LOW AND MIDDLE 263 00:10:48,600 --> 00:10:56,320 INCOME SETTINGS. 264 00:10:56,320 --> 00:11:03,480 AND THANK YOU TO DR. SONYA LEED 265 00:11:03,480 --> 00:11:06,000 AS THE CO-LEAD ON THE WORKSHOP 266 00:11:06,000 --> 00:11:09,720 AND TO THE BILL AND MELINDA 267 00:11:09,720 --> 00:11:11,240 FOUNDATION AND WE WANT TO THANK 268 00:11:11,240 --> 00:11:14,800 THE SPEAKERS AND PANELISTS FOR 269 00:11:14,800 --> 00:11:18,000 BEING SO COLLABORATIVE AND FOR 270 00:11:18,000 --> 00:11:30,600 YOUR TIME AND EXPERTISE. 271 00:11:30,600 --> 00:11:34,680 AND THANK YOU FOR THE AUDIENCE 272 00:11:34,680 --> 00:11:37,000 FOR YOUR PARTICIPATION SO WE 273 00:11:37,000 --> 00:11:39,320 HAVE A GREAT DISCUSSION. 274 00:11:39,320 --> 00:11:40,600 NOW I'LL TURN IT OVER TO 275 00:11:40,600 --> 00:11:42,000 DR. HARRY BURGESS. 276 00:11:42,000 --> 00:11:44,880 >> IT'S MY GREAT PLEASURE TO 277 00:11:44,880 --> 00:11:49,680 INTRODUCE DR. OLIVER HOBERT AND 278 00:11:49,680 --> 00:11:52,560 INVESTIGATOR OF THE HOWARD 279 00:11:52,560 --> 00:11:53,120 HUGHES MEDICAL INSTITUTE. 280 00:11:53,120 --> 00:11:56,080 THE BRAIN HAS MILLIONS OF 281 00:11:56,080 --> 00:11:58,440 NEURONS THAT PERFORM DISTINCT 282 00:11:58,440 --> 00:11:59,040 FUNCTIONS. 283 00:11:59,040 --> 00:12:00,440 TAKING ADVANTAGE OF THE 284 00:12:00,440 --> 00:12:02,760 INFORMATION SYSTEM HIS 285 00:12:02,760 --> 00:12:06,480 LABORATORY PROBED MOLECULAR 286 00:12:06,480 --> 00:12:09,600 PATHWAY TO HOW EACH NEURON HAS 287 00:12:09,600 --> 00:12:12,640 UNIQUE IDENTIFIES AND CREATING 288 00:12:12,640 --> 00:12:14,880 THE EXTRAORDINARY DIVERSITY OF 289 00:12:14,880 --> 00:12:16,640 NEURONAL FORM AND FUNCTION SEEN 290 00:12:16,640 --> 00:12:19,040 IN HUMANS WE THANK HIM FOR 291 00:12:19,040 --> 00:12:21,760 ACTING AS CHAIR OF THIS SESSION. 292 00:12:21,760 --> 00:12:26,200 >> THANK YOU SEARCH VERY MUCH 293 00:12:26,200 --> 00:12:27,440 FOR THE INTRODUCTION. 294 00:12:27,440 --> 00:12:30,040 I WANT TO START WITH A QUOTE 295 00:12:30,040 --> 00:12:32,640 FROM SIDNEY BRENNER WHO IS ONCE 296 00:12:32,640 --> 00:12:36,800 SUPPOSED TO HAVE SAID, PROGRESS 297 00:12:36,800 --> 00:12:40,200 IN SCIENCE DEPENDS ON NEW 298 00:12:40,200 --> 00:12:41,680 TECHNIQUES AND DISCOVERIES AND 299 00:12:41,680 --> 00:12:45,160 NEW IDEAS PROBABLY IN THAT 300 00:12:45,160 --> 00:12:45,360 ORDER. 301 00:12:45,360 --> 00:12:49,800 AND I THINK NOWHERE MORE IS THIS 302 00:12:49,800 --> 00:12:51,760 TRUE THAN IN THE FIELD THAT 303 00:12:51,760 --> 00:12:54,360 WE'RE DISCUSSING MEANING THE 304 00:12:54,360 --> 00:12:59,840 FIELD OF DEFINING CELL TYPES IN 305 00:12:59,840 --> 00:13:15,600 THE BRAIN AND AND AWAY HAVE SEEN 306 00:13:15,600 --> 00:13:17,880 OVER THE 150 YEARS OR SO JUMPS 307 00:13:17,880 --> 00:13:21,160 IN TECHNOLOGY AND INTRODUCTION 308 00:13:21,160 --> 00:13:24,920 OF ELECTROPHYSIOLOGY THAT HELPED 309 00:13:24,920 --> 00:13:27,360 DEFINE MORE CELL TYPES FROM 310 00:13:27,360 --> 00:13:30,640 DIFFERENT PHENOTYPIC CRITERIA. 311 00:13:30,640 --> 00:13:32,400 THEN WITH THE INVENT OF THE 312 00:13:32,400 --> 00:13:34,480 MOLECULAR AGE WE'VE SEEN NOVEL 313 00:13:34,480 --> 00:13:36,320 WAYS TO MEASURE CELL TYPE 314 00:13:36,320 --> 00:13:38,400 DIVERSITY BUT I THINK IT'S FAIR 315 00:13:38,400 --> 00:13:41,560 TO STAY IN THE LAST FIVE TO 10 316 00:13:41,560 --> 00:13:46,360 YEARS THERE'S BEEN ENORMOUS 317 00:13:46,360 --> 00:13:49,920 STRIDES BASED ON SINGLE-CELL 318 00:13:49,920 --> 00:13:52,040 TECHNOLOGY HELPING TO DEFINE 319 00:13:52,040 --> 00:13:53,520 CELL TYPES IN MORE COMPLEX 320 00:13:53,520 --> 00:13:54,800 ANNIVERSARY SYSTEMS IN THE 321 00:13:54,800 --> 00:13:55,920 MAMMALIAN AND VERTEBRATE BRAIN 322 00:13:55,920 --> 00:14:00,800 AND WE'LL HEAR A LOT ABOUT THIS 323 00:14:00,800 --> 00:14:02,000 TODAY. 324 00:14:02,000 --> 00:14:07,280 WE'LL HEAR FROM FROM AN 325 00:14:07,280 --> 00:14:15,160 IMPORTANT FIGURE IN THE FIELD ED 326 00:14:15,160 --> 00:14:17,640 LEIN AND HEAR FROM SOMEWHAT MORE 327 00:14:17,640 --> 00:14:22,240 JUNIOR MEMBERS BRINGING IN NEW 328 00:14:22,240 --> 00:14:26,040 TECHNOLOGY ANGLES THAT ARE VERY 329 00:14:26,040 --> 00:14:29,240 EXCITING AND HELP US GO BEYOND 330 00:14:29,240 --> 00:14:31,280 CELL TYPE DEFINITION ON THE 331 00:14:31,280 --> 00:14:33,440 LEVEL OF IDENTIFY FEATURES OF 332 00:14:33,440 --> 00:14:35,960 MATURE CELLS AND LOOKING AT THE 333 00:14:35,960 --> 00:14:39,160 LINEAGE OF INDIVIDUAL CELLS. 334 00:14:39,160 --> 00:14:41,560 IT'S VERY EXCITING. 335 00:14:41,560 --> 00:14:43,840 THERE'S VERY MANY INTERESTING 336 00:14:43,840 --> 00:14:46,200 TECHNOLOGY. 337 00:14:46,200 --> 00:14:51,960 IN FACT OUR FIRST SPEAKER BUSHRA 338 00:14:51,960 --> 00:14:56,560 RAJ HAS NOVEL APPROACHES AS A 339 00:14:56,560 --> 00:14:59,480 POST-DOC IN ALEX SHEERS' LAB. 340 00:14:59,480 --> 00:15:02,120 BUSHRA IS NOW AN ASSISTANT 341 00:15:02,120 --> 00:15:04,640 PROFESSOR AT U-PENN IN THE 342 00:15:04,640 --> 00:15:08,400 DEPARTMENT OF CELL AND 343 00:15:08,400 --> 00:15:10,720 DEVELOPMENT BIOLOGY. 344 00:15:10,720 --> 00:15:16,200 SHE HAS GOTTEN HER Ph.D. AT THE 345 00:15:16,200 --> 00:15:18,080 UNIVERSITY OF TORONTO AT A THEN 346 00:15:18,080 --> 00:15:20,160 CLOSED LAB AND WAS LUCKY ENOUGH 347 00:15:20,160 --> 00:15:32,440 TO NOT TAKE UP AN OFFER AT MY 348 00:15:32,440 --> 00:15:36,080 LAB AND USED CRISPR CAS 9 349 00:15:36,080 --> 00:15:41,000 TECHNOLOGY TO LOOK AT CELL 350 00:15:41,000 --> 00:15:42,840 LINEAGE IN THE ZEBRAFISH BRAIN 351 00:15:42,840 --> 00:15:46,280 WHICH OFFERS UNIQUE 352 00:15:46,280 --> 00:15:48,640 OPPORTUNITIES TO VISUALIZE AND 353 00:15:48,640 --> 00:15:51,040 CATALOG CELLULAR ACTIVITY. 354 00:15:51,040 --> 00:15:56,360 I'LL NOW TURN IT OVER TO BUSHRA 355 00:15:56,360 --> 00:15:58,320 AND I AM MUCH LOOKING FORWARD TO 356 00:15:58,320 --> 00:16:11,120 HEAR HER TALK. 357 00:16:11,120 --> 00:16:13,640 >> THANK YOU FOR THE GENEROUS 358 00:16:13,640 --> 00:16:21,240 INTRODUCTION AND WONDERED IF YOU 359 00:16:21,240 --> 00:16:22,840 REMEMBERED MY APPLICATION TO 360 00:16:22,840 --> 00:16:26,240 YOUR LAB AND I'M HERE TO SHARE 361 00:16:26,240 --> 00:16:31,800 THE INSIGHTS OF MY WORK WITH 362 00:16:31,800 --> 00:16:34,240 ZEBRAFISH AND THE VERTEBRATE 363 00:16:34,240 --> 00:16:34,960 BRAIN DEVELOPMENT. 364 00:16:34,960 --> 00:16:38,240 SO THE TITLE OF MY TALK IS 365 00:16:38,240 --> 00:16:41,960 MOLECULAR ROAD MAPS OF BRAIN 366 00:16:41,960 --> 00:16:42,640 DEVELOPMENT LINEAGE AND 367 00:16:42,640 --> 00:16:45,040 SIGNALLING AND I'D LIKE TO START 368 00:16:45,040 --> 00:16:47,560 OFF BY GIVING YOU AN OVERVIEW OF 369 00:16:47,560 --> 00:16:50,600 THE GENERAL TYPES OF QUESTIONS 370 00:16:50,600 --> 00:16:52,080 THAT ME AS WELL AS OTHER PEOPLE 371 00:16:52,080 --> 00:16:53,840 IN THE FIELD ARE INTERESTED IN. 372 00:16:53,840 --> 00:16:55,560 WHAT ARE WE TRYING TO BUILD AS 373 00:16:55,560 --> 00:17:00,680 WE TRY TO UNDERSTAND BRAIN 374 00:17:00,680 --> 00:17:03,160 DEVELOPMENT? 375 00:17:03,160 --> 00:17:03,280 . 376 00:17:03,280 --> 00:17:12,960 AND THAT WOULD INCLUDE INCLUDE 377 00:17:12,960 --> 00:17:14,880 IDENTIFYING HOW MANY DISCREET 378 00:17:14,880 --> 00:17:17,960 CELL TYPES ARE IN THE BRAIN AND 379 00:17:17,960 --> 00:17:20,920 IDENTIFYING THE GENE EXPRESSION 380 00:17:20,920 --> 00:17:22,600 PROGRAMS IMPORTANT FOR THEIR 381 00:17:22,600 --> 00:17:23,880 DEVELOPMENT, ACTIVITY, 382 00:17:23,880 --> 00:17:25,440 INTERACTION. 383 00:17:25,440 --> 00:17:27,840 IDENTIFYING THE ORIGINS AND 384 00:17:27,840 --> 00:17:28,960 PLACE OF THE BRAIN CELLS. 385 00:17:28,960 --> 00:17:32,200 WHERE DO THEY COME FROM, WHAT 386 00:17:32,200 --> 00:17:35,640 ARE THEIR RELATED ANCESTORS? 387 00:17:35,640 --> 00:17:39,480 AND HOW DO SIGNALLING PATHWAYS 388 00:17:39,480 --> 00:17:41,640 REGULATE NEUROGENESIS AND 389 00:17:41,640 --> 00:17:44,600 LOOKING AT CELL AUTONOMOUS AND 390 00:17:44,600 --> 00:17:45,800 NON-CELL AUTONOMOUS PROGRAMS 391 00:17:45,800 --> 00:17:46,280 THAT CAN IMPACT BRAIN 392 00:17:46,280 --> 00:17:49,960 DEVELOPMENT. 393 00:17:49,960 --> 00:17:51,480 SO THERE'S MULT WALL WAYS OF 394 00:17:51,480 --> 00:17:53,320 ADDRESSING THESE QUESTIONS. 395 00:17:53,320 --> 00:17:56,920 FOR THE PURPOSE OF THIS TALK 396 00:17:56,920 --> 00:17:58,840 I'LL INTRODUCE FOUR METHODS THAT 397 00:17:58,840 --> 00:18:01,680 WE USED COMMONLY IN THE FIELD, 398 00:18:01,680 --> 00:18:09,040 ONE IS IN ORDER TO CATEGORIZE 399 00:18:09,040 --> 00:18:10,000 CELL TYPES WE HAVE 400 00:18:10,000 --> 00:18:14,240 TRANSCRIPTOMICS AND IF WE EXTEND 401 00:18:14,240 --> 00:18:16,960 INTO A FORM OF TIME COURSE WE 402 00:18:16,960 --> 00:18:19,560 CAN DO PROFILING OVER THE LIFE 403 00:18:19,560 --> 00:18:24,960 TIME OR OVER CRITICAL PERIODS OF 404 00:18:24,960 --> 00:18:35,680 DEVELOPMENT AND HOW CELLS CHANGE 405 00:18:35,680 --> 00:18:36,840 OVER TIME AND COMPLEXITY AND 406 00:18:36,840 --> 00:18:38,200 LOOK AT THEIR HISTORY AND 407 00:18:38,200 --> 00:18:39,760 UNDERSTANDING WHERE THEY COME 408 00:18:39,760 --> 00:18:41,920 FROM WE CAN START GENERATING 409 00:18:41,920 --> 00:18:43,840 HIGH DENSITY LINEAGE TREES THAT 410 00:18:43,840 --> 00:18:45,080 MERGE THE CELL IDENTIFY WITH 411 00:18:45,080 --> 00:18:48,440 THEIR CELLULAR ANCESTRY TO GIVE 412 00:18:48,440 --> 00:18:51,920 US A RECORD OF WHERE IN THE 413 00:18:51,920 --> 00:18:53,760 EMBRYO THEY CAME FROM AND WHICH 414 00:18:53,760 --> 00:18:54,480 OTHER CELL TYPES THEY'RE RELATED 415 00:18:54,480 --> 00:19:00,200 TO. 416 00:19:00,200 --> 00:19:02,440 LASTLY I'D LIKE TO INTRODUCE THE 417 00:19:02,440 --> 00:19:04,040 CONCEPT OF ATLASES IN THE 418 00:19:04,040 --> 00:19:05,640 CONTEXT OF A DEVELOPING BRAIN 419 00:19:05,640 --> 00:19:07,280 THOUGH THIS CONCEPT CAN BE 420 00:19:07,280 --> 00:19:10,200 EXTENDED TO ANY ORGAN OF 421 00:19:10,200 --> 00:19:15,280 INTEREST. 422 00:19:15,280 --> 00:19:22,200 I WANT TO TAKE 10, 20 SECONDS 423 00:19:22,200 --> 00:19:24,920 FOR INTRODUCTION OF RNA 424 00:19:24,920 --> 00:19:34,720 SEQUENCING AND WE START WITH 425 00:19:34,720 --> 00:19:35,840 DISASSOCIATED CELLS INTEREST A 426 00:19:35,840 --> 00:19:41,240 TISSUE AND ALLOW FOR THE 427 00:19:41,240 --> 00:19:43,640 ENCAPSULATION OF INDIVIDUAL 428 00:19:43,640 --> 00:19:48,520 CELLS MARK BY UNIQUE BAR CODES 429 00:19:48,520 --> 00:19:52,400 AND THEY CAN THEN BE CONVERTED 430 00:19:52,400 --> 00:19:55,400 INTO LIBRARIES WHICH CAN BE 431 00:19:55,400 --> 00:19:56,080 SEQUENCED AT HIGH THROUGHPUT TO 432 00:19:56,080 --> 00:19:59,280 GIVE AN OVERVIEW OF THE 433 00:19:59,280 --> 00:19:59,920 TRANSCRIPTIONAL LANDSCAPE OF 434 00:19:59,920 --> 00:20:02,680 INDIVIDUAL CELLS AT THE LEVEL OF 435 00:20:02,680 --> 00:20:04,000 TENS TO HUNDREDS OF THOUSANDS OF 436 00:20:04,000 --> 00:20:21,080 CELLS AT A TYPE. 437 00:20:21,080 --> 00:20:30,040 THE FISH GIVES EASY ACCESS TO 438 00:20:30,040 --> 00:20:34,840 THE TISSUES. 439 00:20:34,840 --> 00:20:39,240 AND HAVE VARIABLES AVAILABLE FOR 440 00:20:39,240 --> 00:20:43,280 THE FISH AND HIGHLY TRANSPARENT 441 00:20:43,280 --> 00:20:44,120 IN THE EARLY STAGES OF 442 00:20:44,120 --> 00:20:46,840 EXPERIMENT CONDUCIVE TO IMAGING. 443 00:20:46,840 --> 00:20:48,640 WITH RESPECT TO BRAIN 444 00:20:48,640 --> 00:20:50,520 DEVELOPMENT THE FISH IS 445 00:20:50,520 --> 00:20:54,200 DIFFERENT FROM THE MAMMALIAN 446 00:20:54,200 --> 00:20:56,440 SYSTEM AS IT UNDER GOES 447 00:20:56,440 --> 00:20:57,640 NEUROGENESIS. 448 00:20:57,640 --> 00:21:00,000 THROUGHOUT THE LIFE TIME OF THE 449 00:21:00,000 --> 00:21:02,240 FISH THERE'S POOLS OF CELLS THAT 450 00:21:02,240 --> 00:21:03,560 UNDER GO DIFFERENTIATION AND 451 00:21:03,560 --> 00:21:04,880 EXPANSION AND GIVE RISE TO NEW 452 00:21:04,880 --> 00:21:05,720 NEURONS. 453 00:21:05,720 --> 00:21:10,040 IN ADDITION THE FISH UNDER GOES 454 00:21:10,040 --> 00:21:11,640 REGENERATION QUITE EFFICIENTLY 455 00:21:11,640 --> 00:21:18,440 INCLUDING IN THE BRAIN TISSUE 456 00:21:18,440 --> 00:21:21,200 AND THIS PROVIDES GREAT WAYS TO 457 00:21:21,200 --> 00:21:22,040 ANSWER THE QUESTION. 458 00:21:22,040 --> 00:21:25,440 AND FOR ONE OF MY STUDIES I DID 459 00:21:25,440 --> 00:21:29,160 A PROFILING OF BRAIN DEVELOPMENT 460 00:21:29,160 --> 00:21:29,920 STARTING FROM EARLY STAGE WHEN 461 00:21:29,920 --> 00:21:36,040 THE BRAIN IS JUST ABOUT STARTING 462 00:21:36,040 --> 00:21:41,080 OFF TO A STRUCTURE FROM THE IS 463 00:21:41,080 --> 00:21:43,840 IT HOURS POST FERTILIZATION AND 464 00:21:43,840 --> 00:21:45,840 EXTENDING TO TWO WEEKS POST 465 00:21:45,840 --> 00:21:47,960 FERTILIZATION AT 15 DAYS AND SO 466 00:21:47,960 --> 00:21:53,280 THE FISH HAS UNDER GONE A LOT OF 467 00:21:53,280 --> 00:22:00,480 CHANGE AND IS SELF-SUFFICIENT 468 00:22:00,480 --> 00:22:02,240 AND DISPLAYS DIFFERENT KINDS OF 469 00:22:02,240 --> 00:22:03,400 COMPLEX BEHAVIORS. 470 00:22:03,400 --> 00:22:07,400 THIS REPRESENTS A RANGE OF TIME 471 00:22:07,400 --> 00:22:10,240 POINTS AND HOPEFULLY WILL GIVE 472 00:22:10,240 --> 00:22:13,000 US AN IDEA OF THE INCREASE OF 473 00:22:13,000 --> 00:22:15,840 COMPLEX AT THE FISH'S 474 00:22:15,840 --> 00:22:17,160 DEVELOPMENT. 475 00:22:17,160 --> 00:22:22,040 SO USING SINGLE CELL RNA 476 00:22:22,040 --> 00:22:25,200 SEQUENCING WE LOOKED ACROSS 12 477 00:22:25,200 --> 00:22:27,960 STAGES OF DEVELOPMENT AND THE 478 00:22:27,960 --> 00:22:30,920 FIRST TIME POINT WE IDENTIFIED 479 00:22:30,920 --> 00:22:36,440 20 MAJOR CELL TYPES THAT 480 00:22:36,440 --> 00:22:40,120 CORRESPOND TO NEURO TISSUES AND 481 00:22:40,120 --> 00:22:42,040 IDENTIFIED 100 CELL TYPES 482 00:22:42,040 --> 00:22:43,840 ROUGHLY AND OVERALL IN THE DATA 483 00:22:43,840 --> 00:22:48,840 SET WE ANNOTATED ABOUT 800 484 00:22:48,840 --> 00:22:50,440 CLUSTERS AND ALL THIS IS 485 00:22:50,440 --> 00:22:52,880 AVAILABLE AT A COMMUNITY 486 00:22:52,880 --> 00:22:55,200 DATABASE THAT CAN BE EXPLORED 487 00:22:55,200 --> 00:22:56,440 ESPECIALLY IF YOU'RE INTERESTED 488 00:22:56,440 --> 00:22:58,440 IN CROSS-SPECIES ANALYSIS 489 00:22:58,440 --> 00:23:00,440 LOOKING AT DEVELOPMENT FROM FISH 490 00:23:00,440 --> 00:23:01,800 ALL THE WAY UP TO MAMMALIAN 491 00:23:01,800 --> 00:23:03,840 SYSTEMS AND LOOKING AT THE 492 00:23:03,840 --> 00:23:04,960 SIMILARITIES AND DIFFERENCES. 493 00:23:04,960 --> 00:23:06,400 THIS COULD BE A GREAT RESOURCE 494 00:23:06,400 --> 00:23:39,960 TO LOOK INTO THAT. 495 00:23:39,960 --> 00:23:43,440 AND WE HAVE TIME ANALYSIS DONE 496 00:23:43,440 --> 00:23:45,760 BY RECONSTRUCTING THE GENE 497 00:23:45,760 --> 00:23:50,120 EXPRESSION TRAJECTORY THE CELLS 498 00:23:50,120 --> 00:23:51,840 HAVE THE VARIOUS CELL STATES 499 00:23:51,840 --> 00:23:54,160 HAVE UNDER GONE FROM EARLY TIME 500 00:23:54,160 --> 00:23:56,120 POINTS TO LATER STAGES OF 501 00:23:56,120 --> 00:23:56,440 DEVELOPMENT. 502 00:23:56,440 --> 00:24:05,040 MOST OF THIS IS DONE BY USING 503 00:24:05,040 --> 00:24:06,200 SINGLE CELL RNA SEQUENCE SETS 504 00:24:06,200 --> 00:24:07,600 AND CONNECTING CELLS AS A 505 00:24:07,600 --> 00:24:13,200 MEASURE OF THEIR MATURITY LEVEL, 506 00:24:13,200 --> 00:24:15,440 IF YOU WILL, BASED ON THEIR GENE 507 00:24:15,440 --> 00:24:16,440 EXPRESSION PROFILE. 508 00:24:16,440 --> 00:24:21,960 THIS ALLOWS US TO LOOK AT EARLY 509 00:24:21,960 --> 00:24:30,600 DEVELOPMENT AND STARTING WITH 510 00:24:30,600 --> 00:24:32,720 FOUNDER CELLS AND AS IT CHANGES 511 00:24:32,720 --> 00:24:34,040 FOR LATER AND LATER STAGES OF 512 00:24:34,040 --> 00:24:36,880 DEVELOPMENT AND ALLOWS US TO 513 00:24:36,880 --> 00:24:38,480 CREATE THE SPECIFICATION 514 00:24:38,480 --> 00:24:39,720 TRAJECTORIES OR TREES THAT HAVE 515 00:24:39,720 --> 00:24:45,000 BRANCH LEAD OFF TO DIFFERENT 516 00:24:45,000 --> 00:24:48,640 TISSUE TYPES AND CELL TYPES 517 00:24:48,640 --> 00:24:50,360 WITHIN A PARTICULAR TISSUE. 518 00:24:50,360 --> 00:24:56,240 CELL LINEAGES MEASURE A SLIGHTLY 519 00:24:56,240 --> 00:24:58,920 DIFFERENT ASPECT OF DEVELOPMENT 520 00:24:58,920 --> 00:25:02,840 AND IN THIS CASE WE'RE ACTUALLY 521 00:25:02,840 --> 00:25:04,400 LOOKING AT THE CELL DIVISION 522 00:25:04,400 --> 00:25:05,840 HISTORY. 523 00:25:05,840 --> 00:25:09,640 LOOKING AT WHICH CELLS DIVIDED 524 00:25:09,640 --> 00:25:11,680 FROM WHICH CELL AND HOW THOSE 525 00:25:11,680 --> 00:25:13,680 PATTERNS WERE PASSED ON TO 526 00:25:13,680 --> 00:25:14,360 FUTURE GENERATIONS. 527 00:25:14,360 --> 00:25:19,440 THIS IS MAYBE WHAT'S KNOWN AS 528 00:25:19,440 --> 00:25:27,440 THE CLASSIC LINEAGE TREE AND C. 529 00:25:27,440 --> 00:25:32,600 ELA 530 00:25:32,600 --> 00:25:34,240 ELEGANS IS WHERE WE LOOK TO 531 00:25:34,240 --> 00:25:39,120 EXTEND TO COMPLEX ANIMALS AND 532 00:25:39,120 --> 00:25:39,760 VERTEBRA 533 00:25:39,760 --> 00:25:40,040 VERTEBRATE. 534 00:25:40,040 --> 00:25:41,240 WE THOUGHT THERE WAS A GREAT 535 00:25:41,240 --> 00:25:41,960 OPPORTUNITY TO DEVELOP A 536 00:25:41,960 --> 00:25:46,120 TECHNIQUE TO ALLOW US TO SCALE 537 00:25:46,120 --> 00:25:48,240 LINEAGE TRACING IN A WAY THAT 538 00:25:48,240 --> 00:25:50,280 WOULD BE USEFUL FOR LOOKING AT 539 00:25:50,280 --> 00:25:52,760 HIGHER VERTEBRATES OR IN THE 540 00:25:52,760 --> 00:25:55,160 CASE OF ANIMALS, DISEASE 541 00:25:55,160 --> 00:25:58,240 CONDITIONS OR CANCER PROGRESSION 542 00:25:58,240 --> 00:26:02,240 AND THIS SEEMS LIKE A GREAT 543 00:26:02,240 --> 00:26:06,640 OPPORTUNITY TO IMPLEMENT CRISPR 544 00:26:06,640 --> 00:26:10,240 CAS 9 BAR CODING TO LOOK AT 545 00:26:10,240 --> 00:26:13,040 LINEAGE HISTORY OF CELLS. 546 00:26:13,040 --> 00:26:16,520 WE CREATED THIS METHOD WHICH IS 547 00:26:16,520 --> 00:26:20,200 A WAY OF DYNAMICALLY BAR CODING 548 00:26:20,200 --> 00:26:21,600 CELL LINEAGES DURING THE 549 00:26:21,600 --> 00:26:32,840 DEVELOPMENT OF AN ANIMAL. 550 00:26:32,840 --> 00:26:41,040 WE START WITH THE SEQUENCE AND 551 00:26:41,040 --> 00:26:43,760 IT'S COMPLETELY SYNTHETIC AND WE 552 00:26:43,760 --> 00:26:45,440 CAN START INTRODUCING MUTATIONS 553 00:26:45,440 --> 00:26:48,680 IN THE BAR CODE AND THAT IS DONE 554 00:26:48,680 --> 00:26:52,640 BY ADDING CAS9 PROTEIN AND GUIDE 555 00:26:52,640 --> 00:26:55,080 THE TARGET TO VARIOUS REGIONS ON 556 00:26:55,080 --> 00:26:56,240 THE BAR CODE AND EACH TIME 557 00:26:56,240 --> 00:26:59,000 THERE'S A MUTATION AND THE CELL 558 00:26:59,000 --> 00:27:00,360 DIVIDES THE MUTATION WILL BE 559 00:27:00,360 --> 00:27:02,200 PASSED ON TO DAUGHTER CELLS 560 00:27:02,200 --> 00:27:04,880 WHERE ADDITIONAL MUTATIONS CAN 561 00:27:04,880 --> 00:27:06,760 ACCUMULATE AND PASSED ON TO 562 00:27:06,760 --> 00:27:07,840 GRANDDAUGHTER CELLS WHERE MORE 563 00:27:07,840 --> 00:27:11,280 MUTATIONS CAN ACCUMULATE. 564 00:27:11,280 --> 00:27:14,240 SO ON AND SO FORTH OVER SEVERAL 565 00:27:14,240 --> 00:27:16,760 ROUNDS OF CELL DIVISIONS UNTIL 566 00:27:16,760 --> 00:27:18,720 EVENTUALLY THE BAR CODE BECOMES 567 00:27:18,720 --> 00:27:20,800 FULLY SATURATED WITH MUTATIONS 568 00:27:20,800 --> 00:27:22,920 OR THE RE-AGENTS GET DILUTED 569 00:27:22,920 --> 00:27:24,760 OVER THE COURSE OF DEVELOPMENT. 570 00:27:24,760 --> 00:27:29,280 THESE EDITS ARE CUMULATIVE AND 571 00:27:29,280 --> 00:27:30,080 COMBINATORIAL AND PERMANENT. 572 00:27:30,080 --> 00:27:32,680 THEY'RE MUTATED WITHIN THE 573 00:27:32,680 --> 00:27:34,040 GENOME WHERE THE BAR CODE HAS 574 00:27:34,040 --> 00:27:36,960 BEEN INSERTED SO WE CAN THEN 575 00:27:36,960 --> 00:27:39,080 EXTRACT THE BAR CODES AT A LATER 576 00:27:39,080 --> 00:27:51,760 TIME POINT USING SEQUENCING. 577 00:27:51,760 --> 00:27:54,240 STARTED OFF WITH A CRISPR EDITED 578 00:27:54,240 --> 00:27:54,640 ANIMAL. 579 00:27:54,640 --> 00:27:59,040 IN THIS CASE WE WERE USING FISH 580 00:27:59,040 --> 00:28:02,520 ABOUT THREE WEEKS OLD ISOLATED 581 00:28:02,520 --> 00:28:05,720 THE BRAIN FROM CRISPR EDITED 582 00:28:05,720 --> 00:28:12,720 ANIMAL AND PASSED THEM THROUGH 583 00:28:12,720 --> 00:28:14,920 THE SINGLE CELL PLATFORM AND 584 00:28:14,920 --> 00:28:17,840 LOOKED AT THE LINEAGE BAR CODES 585 00:28:17,840 --> 00:28:19,560 THEMSELVES TO HELP UNDERSTAND 586 00:28:19,560 --> 00:28:21,760 WHAT THE CELL DIVISION HISTORY 587 00:28:21,760 --> 00:28:42,680 OF THESE CELL TYPES WERE LIKE. 588 00:28:42,680 --> 00:28:44,920 AND WE LOOKED AT FUTURE LEVELS 589 00:28:44,920 --> 00:28:47,120 OF COMPLEXITY FOR FUTURE 590 00:28:47,120 --> 00:28:47,440 GENERATION. 591 00:28:47,440 --> 00:28:52,120 I'LL QUICKLY ZOOM INTO ONE OF 592 00:28:52,120 --> 00:28:53,200 THESE TREES. 593 00:28:53,200 --> 00:28:56,440 I'M SHOWING THE TREES EXTENDS 594 00:28:56,440 --> 00:29:00,360 OUT AND EACH LITTLE NODE 595 00:29:00,360 --> 00:29:02,280 REPRESENTS A PERIOD OF CELL 596 00:29:02,280 --> 00:29:12,640 DIVISION HISTORIES. 597 00:29:12,640 --> 00:29:15,720 ARE REPRESENTED AS DELETIONS OR 598 00:29:15,720 --> 00:29:17,240 INSERTIONS AND THE RED BAR 599 00:29:17,240 --> 00:29:19,080 REPRESENT THE SIZE OF THIS 600 00:29:19,080 --> 00:29:21,240 DELETION AND WE CAN ORDER THESE 601 00:29:21,240 --> 00:29:23,960 BAR CODES AND GENERATE A LINEAGE 602 00:29:23,960 --> 00:29:27,360 TREE BY LOOKING AT THE PATTERNS 603 00:29:27,360 --> 00:29:29,640 AND FREQUENCY OF MUTATION AND 604 00:29:29,640 --> 00:29:31,520 THOSE FREQUENT THAT OCCUR IN A 605 00:29:31,520 --> 00:29:33,000 LOT OF CELLS LIKELY ERODE EARLY 606 00:29:33,000 --> 00:29:36,520 ON IN DEVELOPMENT AND WOULD 607 00:29:36,520 --> 00:29:40,800 ANCHOR ONE OF THE EARLY NODES ON 608 00:29:40,800 --> 00:29:45,800 THE TREE AND MUTATIONS MORE RARE 609 00:29:45,800 --> 00:29:46,440 WOULD REPRESENT LATER AND LATER 610 00:29:46,440 --> 00:29:59,240 NODE OF THE TREE. 611 00:29:59,240 --> 00:30:00,800 AND WE CAN DETERMINE GENERALLY 612 00:30:00,800 --> 00:30:03,920 WHAT TYPE OF CELL THEY ARE AND 613 00:30:03,920 --> 00:30:05,840 ALSO GENERALLY THE REGION OF THE 614 00:30:05,840 --> 00:30:07,520 BRAIN THEY CAME FROM BASED ON 615 00:30:07,520 --> 00:30:11,360 EXPRESSION PATTERNS OF LANDMARK 616 00:30:11,360 --> 00:30:13,760 TRANSCRIPTION FACTORS. 617 00:30:13,760 --> 00:30:16,480 SO NOW I'D LIKE TO FOCUS ON THE 618 00:30:16,480 --> 00:30:18,160 LAST ASPECT OF THIS TALK WHICH 619 00:30:18,160 --> 00:30:20,640 IS HOW DO WE START LOOKING AT 620 00:30:20,640 --> 00:30:22,800 SIGNALLING PATHWAYS AND WHAT 621 00:30:22,800 --> 00:30:23,400 THEIR ROLES ARE DURING BRAIN 622 00:30:23,400 --> 00:30:32,440 DEVELOPMENT. 623 00:30:32,440 --> 00:30:36,240 THEY HAVE BEEN LOOKING AT SMALL 624 00:30:36,240 --> 00:30:39,440 PATHWAYS OR PARTICULAR TIME IN 625 00:30:39,440 --> 00:30:41,720 DEVELOPMENT AND MANIPULATING THE 626 00:30:41,720 --> 00:30:43,000 SIGNALLING PATHWAY AND LOOKING 627 00:30:43,000 --> 00:30:44,280 TO SEE WHAT THE EFFECTS ARE. 628 00:30:44,280 --> 00:30:46,640 BUT IF WE WANT TO LOOK AT IT IN 629 00:30:46,640 --> 00:30:48,240 THE CONTEXT OF DEVELOPMENT AND 630 00:30:48,240 --> 00:30:52,040 WHAT'S HAPPENING AS THE ANIMAL'S 631 00:30:52,040 --> 00:30:55,440 GROWING AND LOOK AT IT IN A MORE 632 00:30:55,440 --> 00:30:56,640 UNBIASSED WAY ACROSS MULTIPLE 633 00:30:56,640 --> 00:30:57,920 TYPES OF CELLS AND REGIONS OF 634 00:30:57,920 --> 00:31:03,800 THE BRAIN, HOW CAN WE START 635 00:31:03,800 --> 00:31:05,040 SCALE I 636 00:31:05,040 --> 00:31:07,800 SCALING HOW WE INVESTIGATE 637 00:31:07,800 --> 00:31:08,760 SIGNALLING PATHWAYS DURING 638 00:31:08,760 --> 00:31:09,040 DEVELOPMENT. 639 00:31:09,040 --> 00:31:16,880 I'D LIKE TO PROPOSE WE CAN ONCE 640 00:31:16,880 --> 00:31:20,200 AGAIN WE LIE ON CRISPR CAS TO 641 00:31:20,200 --> 00:31:22,560 LOOK AT SIGNALLING ACTIVITY ON A 642 00:31:22,560 --> 00:31:23,720 LARGER SCALE. 643 00:31:23,720 --> 00:31:27,080 THE IDEA IS SIMILAR WITH THE 644 00:31:27,080 --> 00:31:29,400 RECORD WHICH IS NOW WE CAN 645 00:31:29,400 --> 00:31:30,240 RECORD SIGNALLING HISTORY AND 646 00:31:30,240 --> 00:31:35,720 CELL TYPE IDENTITY AT THIS TIME 647 00:31:35,720 --> 00:31:44,040 AND DO THIS IN COMPLEX TISSUES 648 00:31:44,040 --> 00:31:46,840 AND MAKE IT UPON ACTIVATION OR 649 00:31:46,840 --> 00:31:48,400 INPUT OF THE PATHWAY THE SYSTEM 650 00:31:48,400 --> 00:31:50,240 BECOMES ACTIVATED AND THAT 651 00:31:50,240 --> 00:31:52,440 STARTS INTRODUCING MUTATIONS SO 652 00:31:52,440 --> 00:31:56,280 THAT WE CAN COMBINE THAT WITH 653 00:31:56,280 --> 00:31:59,680 SINGLE CELL RNA SEQUENCING TO 654 00:31:59,680 --> 00:32:02,040 HAVE AN ATLAS WITH THE 655 00:32:02,040 --> 00:32:03,080 SIGNALLING HISTORY AND CELL TYPE 656 00:32:03,080 --> 00:32:06,440 IDENTITY AND LINEAGE 657 00:32:06,440 --> 00:32:16,520 INFORMATION. 658 00:32:16,520 --> 00:32:19,720 AND THERE ARE ADDITIONAL CAS 659 00:32:19,720 --> 00:32:21,680 PROTEINS THAT HAVE BEEN SHOWN TO 660 00:32:21,680 --> 00:32:27,040 WORK FAIRLY EFFICIENTLY IN A 661 00:32:27,040 --> 00:32:28,440 RANGE OF SYSTEMS INCLUDING 662 00:32:28,440 --> 00:32:34,320 ZEBRAFISH AND WE NOW HAVE A 663 00:32:34,320 --> 00:32:43,200 COLLECTION OF ORE CAS PROTEINS 664 00:32:43,200 --> 00:32:48,480 TO INTRODUCE COMPLEXITY IN THE 665 00:32:48,480 --> 00:32:55,480 TIME I 666 00:32:55,480 --> 00:32:57,600 TIMING OUR GOAL IS TO START 667 00:32:57,600 --> 00:33:00,480 LOOKING AT NOTCH SIGNALLING AS A 668 00:33:00,480 --> 00:33:04,480 PROOF OF PRINCIPLE. 669 00:33:04,480 --> 00:33:12,680 IT'S GENERALLY IMPORTANT AND IT 670 00:33:12,680 --> 00:33:15,480 PRESSES THE PRONEURAL GENES AND 671 00:33:15,480 --> 00:33:16,120 HELPS MAINTAIN STEM CELL POOLS. 672 00:33:16,120 --> 00:33:19,200 OUR GOAL IS TO HAVE A SYSTEM TO 673 00:33:19,200 --> 00:33:25,640 TURN ON THE VARIOUS CAS PROTEINS 674 00:33:25,640 --> 00:33:29,880 UPON USING AND WHEN THERE'S 675 00:33:29,880 --> 00:33:31,880 SUFFICIENT SIGNALLING THE CAS 676 00:33:31,880 --> 00:33:37,000 GETS ACTIVATED AND COMPLEX WITH 677 00:33:37,000 --> 00:33:48,040 THEIR AND WE HAVE A PROMOTER 678 00:33:48,040 --> 00:33:50,200 EXPRESSED IN THE NEURAL TUBES 679 00:33:50,200 --> 00:33:54,840 BUT HERE I'M SHOWING GFP 680 00:33:54,840 --> 00:33:57,720 EXPRESSION AND IT LABELS CELLS 681 00:33:57,720 --> 00:33:59,320 ALONG THE FINAL PORT AS WELL AS 682 00:33:59,320 --> 00:34:08,720 THE BRAIN WHERE THE CENTRAL 683 00:34:08,720 --> 00:34:13,920 NERVOUS SYSTEM AND PERIPHERAL 684 00:34:13,920 --> 00:34:15,320 NERVOUS SYSTEM EXISTS AND IT'S 685 00:34:15,320 --> 00:34:17,480 GREAT TO START SCALING THE 686 00:34:17,480 --> 00:34:17,720 ATLASES. 687 00:34:17,720 --> 00:34:36,760 TO THE GOAL IS TO HAVE ORE 688 00:34:36,760 --> 00:34:40,040 ORTHOLOGOUS SYSTEMS AND WE CAN 689 00:34:40,040 --> 00:34:43,000 RECORD TWO OR MORE SIGNALLING 690 00:34:43,000 --> 00:34:44,960 PATHWAYS AT ONES AS LONG AS WE 691 00:34:44,960 --> 00:34:46,560 CAN MAKE THEM RESPONSIVE TO 692 00:34:46,560 --> 00:34:49,840 MULTIPLE SIGNALLING INPUT AND 693 00:34:49,840 --> 00:34:52,560 PROVIDE AS A WAY OF DOING 694 00:34:52,560 --> 00:34:54,520 SCALABLE SINGLE-CELL ATLAS BY 695 00:34:54,520 --> 00:34:57,520 COMBINING WITH SINGLE-CELL RNA 696 00:34:57,520 --> 00:34:57,840 SEQUENCING. 697 00:34:57,840 --> 00:35:00,720 THIS SYSTEM OF COURSE I'M 698 00:35:00,720 --> 00:35:02,840 EXPLAINING IN THE CONTEXT OF THE 699 00:35:02,840 --> 00:35:05,440 ZEBRAFISH BUT WE'D LIKE TO 700 00:35:05,440 --> 00:35:07,160 INTRODUCE THIS INTO OTHER 701 00:35:07,160 --> 00:35:12,120 LINEAGE AND STUDY IT OUTSIDE OF 702 00:35:12,120 --> 00:35:14,880 THIS SUCH AS THE CONTEXT OF 703 00:35:14,880 --> 00:35:16,840 DISEASE AND MEASURE LINEAGE 704 00:35:16,840 --> 00:35:20,040 SIGNALLING, SPLICING AND 705 00:35:20,040 --> 00:35:20,400 TRANSCRIPTION. 706 00:35:20,400 --> 00:35:22,080 SO OF COURSE WE'LL MAKE ALL THIS 707 00:35:22,080 --> 00:35:23,840 AVAILABLE TO THE WIDER COMMUNITY 708 00:35:23,840 --> 00:35:28,440 AS WE MOVE ALONG IN OUR PROJECT 709 00:35:28,440 --> 00:35:29,960 PROJECTS AND I'D LIKE TO QUICKLY 710 00:35:29,960 --> 00:35:31,440 END BY ACKNOWLEDGING EVERYONE 711 00:35:31,440 --> 00:35:34,000 WHO HAS BEEN VERY HELPFUL IN 712 00:35:34,000 --> 00:35:39,400 GETTING VARIOUS ASPECTS OF THIS 713 00:35:39,400 --> 00:35:50,200 PROJECT GOING AND FORMER MENTORS 714 00:35:50,200 --> 00:35:51,280 AND COLLABORATORS. 715 00:35:51,280 --> 00:35:53,240 >> THANK YOU FOR GREAT TALK AND 716 00:35:53,240 --> 00:35:54,080 IN THE SPIRIT OF HOW THE MEETING 717 00:35:54,080 --> 00:36:01,920 WILL RUN WE'LL HAVE QUESTIONS 718 00:36:01,920 --> 00:36:04,240 AFTERWARDS. 719 00:36:04,240 --> 00:36:11,040 AND TIM PETROS AT NICHD GOT HIS 720 00:36:11,040 --> 00:36:15,440 Ph.D. IN COLUMBIA STUDYING AXON 721 00:36:15,440 --> 00:36:18,080 PROJECTIONS OF GANGLION CELLS 722 00:36:18,080 --> 00:36:24,560 AND DID A POST-DOC WITH STEWART 723 00:36:24,560 --> 00:36:30,240 ANDERSON STUDYING INTRINSIC AND 724 00:36:30,240 --> 00:36:31,440 EXTRINSIC PROGRAMS AFFECT 725 00:36:31,440 --> 00:36:34,160 DIVERSITY AND HE'S BEEN AT NICHD 726 00:36:34,160 --> 00:36:36,880 SINCE 2017 AND WE LOOK FORWARD 727 00:36:36,880 --> 00:36:42,240 TO HEAR HIS LATEST. 728 00:36:42,240 --> 00:36:45,440 TIM, TAKE IT AWAY. 729 00:36:45,440 --> 00:37:14,920 >> AND WE STUDY GAB ERIC 730 00:37:14,920 --> 00:37:17,120 INTERNEURONS AND HOW WE GENERATE 731 00:37:17,120 --> 00:37:18,760 THIS DIVERSE POPULATION OF CELLS 732 00:37:18,760 --> 00:37:23,040 THAT ARE LOCALIZED IN ALMOST 733 00:37:23,040 --> 00:37:25,400 EVERY BRAIN WITH DIFFERENT 734 00:37:25,400 --> 00:37:26,040 MORPHOLOGIES AND FUNCTION AND 735 00:37:26,040 --> 00:37:30,240 PLAY IMPORTANT ASPECTS IN NEARLY 736 00:37:30,240 --> 00:37:33,480 EVERY PART OF BRAIN FUNCTION. 737 00:37:33,480 --> 00:37:41,840 TO SUMMARIZE THIS THE INHIBITORY 738 00:37:41,840 --> 00:37:42,880 GABERGIC NEURONS HAVE AN AN 739 00:37:42,880 --> 00:37:45,000 INCREDIBLE DIVERSITY IN TERMS 740 00:37:45,000 --> 00:37:50,200 MUCH THE MORPHOLOGY AND 741 00:37:50,200 --> 00:38:01,640 ELECTROPHYSIOLOGICAL PROPERTIES. 742 00:38:01,640 --> 00:38:02,880 AND YOU CAN HAVE SEE THE 743 00:38:02,880 --> 00:38:05,960 DIFFERENT TYPES OF INHIBITORY 744 00:38:05,960 --> 00:38:08,240 INFORMATION. 745 00:38:08,240 --> 00:38:11,600 HOW DO YOU GENERATE THIS 746 00:38:11,600 --> 00:38:15,320 DIVERSITY IS CHALLENGING AND 747 00:38:15,320 --> 00:38:24,760 EXCITING QUESTION AND WE USED 748 00:38:24,760 --> 00:38:31,880 THE MOUSE AS A DEF -- MODEL AND 749 00:38:31,880 --> 00:38:41,040 THE NEURON BROWN FROM THE 750 00:38:41,040 --> 00:38:41,800 GANGLIONIC EMINENCES AND THEY'RE 751 00:38:41,800 --> 00:38:48,680 BORN FROM THE LATERAL, MEDIAL 752 00:38:48,680 --> 00:38:55,600 AND BECOMEPOST-MITOTIC AND WORK 753 00:38:55,600 --> 00:39:14,200 HAS FOUND AND THERE'S DIFFERENT 754 00:39:14,200 --> 00:39:15,720 GABAERGIC CELLS AND IN THE LAST 755 00:39:15,720 --> 00:39:21,160 DECADE OR SO WITH THE ADVENT OF 756 00:39:21,160 --> 00:39:22,600 SINGLE-CELL TECHNOLOGY ALLOWS TO 757 00:39:22,600 --> 00:39:25,600 IDENTIFY THE TRANSCRIPT OME AND 758 00:39:25,600 --> 00:39:27,680 HEARS ONE FIGURE FROM A SUMMARY 759 00:39:27,680 --> 00:39:30,080 ARTICLE SHOWING YOU CAN DEFINE 760 00:39:30,080 --> 00:39:36,680 DIFFERENT SUB TYPES OF MATURE 761 00:39:36,680 --> 00:39:37,880 GABAERGIC NEURONS AND CORRELATE 762 00:39:37,880 --> 00:39:41,240 THESE OBSERVATIONS TO THE MORE 763 00:39:41,240 --> 00:39:43,680 TRADITIONALLY CELL TYPES BASED 764 00:39:43,680 --> 00:39:54,120 ON THE MORPHOLOGY OR 765 00:39:54,120 --> 00:39:54,960 ELECTROPHYSI 766 00:39:54,960 --> 00:39:59,240 ELECTROPHYSI 767 00:39:59,240 --> 00:40:00,040 ELECTROPHYSI 768 00:40:00,040 --> 00:40:00,720 ELECTROPHYSIOLOGIC PROGRAMS AND 769 00:40:00,720 --> 00:40:01,800 THERE'S EVIDENCE THE 770 00:40:01,800 --> 00:40:03,680 PERTURBATION FUNCTION IS 771 00:40:03,680 --> 00:40:06,200 CRITICAL FOR A WIDE VARIETY OF 772 00:40:06,200 --> 00:40:08,720 BRAIN DISEASES AND DYSFUNCTION 773 00:40:08,720 --> 00:40:11,440 AND IT'S ASSOCIATED WITH 774 00:40:11,440 --> 00:40:14,120 EPILEPSY, AUTISM, BIPOLAR 775 00:40:14,120 --> 00:40:15,880 DISORDER AND OTHER PSYCHIATRIC 776 00:40:15,880 --> 00:40:16,160 DISEASES. 777 00:40:16,160 --> 00:40:18,080 ADDITIONAL STUDIES HAVE ON THE 778 00:40:18,080 --> 00:40:20,960 MANY DISEASES DISASSOCIATED 779 00:40:20,960 --> 00:40:23,320 GENES ARE OFTEN EXPRESSED IN 780 00:40:23,320 --> 00:40:25,120 YOUNG CELLS, SO IMMATURE 781 00:40:25,120 --> 00:40:29,720 DIVIDING CELLS AND IN PARTICULAR 782 00:40:29,720 --> 00:40:32,360 SOME ARE ENRICHING PROGENITORS 783 00:40:32,360 --> 00:40:34,320 AND THERE'S GWAS STUDIES AND 784 00:40:34,320 --> 00:40:36,440 OTHER APPROACHES THAT CHANGES IN 785 00:40:36,440 --> 00:40:40,440 EPIGENETIC MECHANISMS CAN BE 786 00:40:40,440 --> 00:40:43,600 ASSOCIATED WITH NEUROPSYCHIATRIC 787 00:40:43,600 --> 00:40:43,880 DISORDER. 788 00:40:43,880 --> 00:40:46,240 THE MAJORITY OF LOCI WITH 789 00:40:46,240 --> 00:40:47,840 DISEASES ARE NOT FOUND IN CODING 790 00:40:47,840 --> 00:40:50,040 REGIONS BUT OUTSIDE OF THEM 791 00:40:50,040 --> 00:40:53,440 WHICH MEANS SOMEHOW THEY'RE 792 00:40:53,440 --> 00:40:54,920 AFFECTING GENE EXPRESSION THAT 793 00:40:54,920 --> 00:40:57,440 CAN IN TURN LEAD TO DISEASE. 794 00:40:57,440 --> 00:40:59,240 THE SUMMARY OF THIS IN THE 795 00:40:59,240 --> 00:41:00,760 OVERALL THEME HOW I THINK ABOUT 796 00:41:00,760 --> 00:41:03,080 THIS IS WE NEED A BETTER 797 00:41:03,080 --> 00:41:03,640 UNDERSTANDING AND 798 00:41:03,640 --> 00:41:06,200 CHARACTERIZATION OF THE GENETIC 799 00:41:06,200 --> 00:41:10,640 AND EPIGENETIC MECHANISM 800 00:41:10,640 --> 00:41:13,480 REGULATE INTERNEURONAL STATE TO 801 00:41:13,480 --> 00:41:15,520 UNDERSTAND DEVELOPMENT AND 802 00:41:15,520 --> 00:41:16,040 DISEASE ETIOLOGIES. 803 00:41:16,040 --> 00:41:17,240 I'LL SHOW YOU WORK WE'VE DONE TO 804 00:41:17,240 --> 00:41:24,400 TRY TO GENERATE WHAT WE CALL AN 805 00:41:24,400 --> 00:41:25,400 EPIGENOME ATLAS IN THE MOUSE 806 00:41:25,400 --> 00:41:27,840 BRAIN USING TOOLS TO LOOK AT THE 807 00:41:27,840 --> 00:41:30,440 DIFFERENCES BETWEEN THE SPECIFIC 808 00:41:30,440 --> 00:41:31,000 REGIONS. 809 00:41:31,000 --> 00:41:34,880 WE PERFORMED SINGLE NUCLEOTIDE 810 00:41:34,880 --> 00:41:38,040 SEQUENCING AND SINGLE CELL RNA 811 00:41:38,040 --> 00:41:41,200 SEQUENCING THAT BUSHRA 812 00:41:41,200 --> 00:41:43,440 SUMMARIZED IN THE FOUR BRAIN 813 00:41:43,440 --> 00:41:46,160 REGIONS THAT COMPARE AND 814 00:41:46,160 --> 00:41:49,280 CONTRAST GENE AND CHROMATIN 815 00:41:49,280 --> 00:41:49,960 ACCESSIBLE BETWEEN BRAINS. 816 00:41:49,960 --> 00:41:52,440 WE'VE ADDED ON TO THIS BY 817 00:41:52,440 --> 00:41:54,440 PERFORMING SOME NEWER TECHNIQUES 818 00:41:54,440 --> 00:41:57,360 TO CHARACTERIZE THE HISTORY OWN 819 00:41:57,360 --> 00:41:58,720 MODIFICATION TO GET A BETTER 820 00:41:58,720 --> 00:42:00,800 SENSE WHETHER REGIONS ARE 821 00:42:00,800 --> 00:42:04,960 PROMOTERS OR ACTIVE OR REPRESSED 822 00:42:04,960 --> 00:42:07,160 OR ENHANCERS TO UNDERSTAND HOW 823 00:42:07,160 --> 00:42:08,920 GENES ARE REGULATED IN DIFFERENT 824 00:42:08,920 --> 00:42:12,440 PARTS OF THE BRAIN AND PERFORMED 825 00:42:12,440 --> 00:42:16,320 HIGH C TO LOOK AT LARGER 826 00:42:16,320 --> 00:42:17,200 CHROMATIN CONFIRMATION STRUCTURE 827 00:42:17,200 --> 00:42:19,440 AND SEE HOW IT'S ORGANIZED 828 00:42:19,440 --> 00:42:20,760 DIFFERENTLY BETWEEN BRAIN 829 00:42:20,760 --> 00:42:23,280 REGIONS AND UNDER LIES 830 00:42:23,280 --> 00:42:23,960 DIFFERENCES IN GENE EXPRESSION 831 00:42:23,960 --> 00:42:32,840 AND EPIGENETICS. 832 00:42:32,840 --> 00:42:37,960 ATAX HAS HAS A WIDE VARIETY OF 833 00:42:37,960 --> 00:42:39,840 STUDIES WITH DIFFERENT TIME 834 00:42:39,840 --> 00:42:42,040 POINTS OR BRAIN REGIONS TO 835 00:42:42,040 --> 00:42:50,560 UNDERSTAND THE TRANSCRIPTOME IN 836 00:42:50,560 --> 00:42:52,520 THE BRAIN BUT MANY STUDIES HAVE 837 00:42:52,520 --> 00:42:54,240 BEEN CRITICAL WHEN ONE THINGS OF 838 00:42:54,240 --> 00:42:59,560 A HETEROGENEOUS ENVIRONMENT YOU 839 00:42:59,560 --> 00:43:02,920 NEED SINGLE CELL TO UNDERSTAND 840 00:43:02,920 --> 00:43:04,400 DIVERSITY AND UNDERSTAND 841 00:43:04,400 --> 00:43:06,920 DIFFERENCES BETWEEN CELL TYPES. 842 00:43:06,920 --> 00:43:12,840 WHAT A SINGLE ATAC CAN IDENTIFY 843 00:43:12,840 --> 00:43:15,280 OPEN REGIONS OF CHROMATIN AND 844 00:43:15,280 --> 00:43:19,120 THEY CAN INDICATE PROMOTERS OR 845 00:43:19,120 --> 00:43:22,040 ENHANCERS AND THE TRANSPOSEES 846 00:43:22,040 --> 00:43:24,080 CAB ACCESS AND ADAPT TO THEN GO 847 00:43:24,080 --> 00:43:27,000 THROUGH A PROCESS OF GENERATING 848 00:43:27,000 --> 00:43:30,440 SEQUENCING THE REGIONS AT THE 849 00:43:30,440 --> 00:43:32,400 SINGLE-CELL LEVEL KNOW WHETHER 850 00:43:32,400 --> 00:43:35,720 GENOMIC LOCI IS ACCESSIBLE OR 851 00:43:35,720 --> 00:43:37,560 OPEN OR CLOSED OFF. 852 00:43:37,560 --> 00:43:39,160 GOING THROUGH THE WORK FLOW WE 853 00:43:39,160 --> 00:43:43,240 USED IN THE LAB FOR THIS 854 00:43:43,240 --> 00:43:45,920 EXPERIMENT WE TOOK THE MOUSE AND 855 00:43:45,920 --> 00:43:48,720 CAN DISSECT OUT THE REGIONS 856 00:43:48,720 --> 00:43:52,720 VISIBLE AND THE OG, MG AND CG 857 00:43:52,720 --> 00:43:55,440 AND PERFORMED EITHER SINGLE CELL 858 00:43:55,440 --> 00:44:02,840 OR SINGLE LOCI ED -- 859 00:44:02,840 --> 00:44:06,240 ASSOCIATIONS AND LOOK AT THE 860 00:44:06,240 --> 00:44:08,040 SEQUENCING OR MORE RECENTLY 861 00:44:08,040 --> 00:44:10,920 MULTIOMIC EXPERIMENT TO OBTAIN 862 00:44:10,920 --> 00:44:12,480 BOTH SCREEN EXPRESS AND 863 00:44:12,480 --> 00:44:17,200 CHROMATIN ACCESSIBILITY IN THE 864 00:44:17,200 --> 00:44:21,160 SAME CELLS AND GIVE IT TO THE 865 00:44:21,160 --> 00:44:22,240 SEQUENCING CORE TO ANALYZE THE 866 00:44:22,240 --> 00:44:23,840 DATA TO TRY TO UNDERSTAND THE 867 00:44:23,840 --> 00:44:24,760 DIFFERENCES BETWEEN CELL TYPES 868 00:44:24,760 --> 00:44:25,880 AND DIFFERENT REGIONS OR 869 00:44:25,880 --> 00:44:26,880 DIFFERENT TIME POINTS. 870 00:44:26,880 --> 00:44:29,480 THIS IS WHERE WE SPEND A LOT OF 871 00:44:29,480 --> 00:44:31,240 OUR TIME FIGURING OUT THE BEST 872 00:44:31,240 --> 00:44:33,120 WAY TO MASSAGE THE DATA 873 00:44:33,120 --> 00:44:34,640 TO BETTER UNDERSTAND. 874 00:44:34,640 --> 00:44:37,520 THIS IS KIND OF WHAT THE INITIAL 875 00:44:37,520 --> 00:44:41,960 FIRST PASS ANALYSIS LOOKS LIKE. 876 00:44:41,960 --> 00:44:43,840 IN THIS PLOT THE DOT REPRESENTS 877 00:44:43,840 --> 00:44:48,120 A CELL OR IN THIS CASE NUCLEUS 878 00:44:48,120 --> 00:44:54,800 AND CLOESER THE DOTS THE MORE 879 00:44:54,800 --> 00:44:56,720 ACCESSIBILITY AND WE HIGHLIGHT 880 00:44:56,720 --> 00:44:59,640 THE BRAIN REGIONS AND YOU CAN 881 00:44:59,640 --> 00:45:01,440 SEE MOST THE CELLS ARISE FROM 882 00:45:01,440 --> 00:45:04,000 THE CORTEX AND CLUSTER TOGETHER 883 00:45:04,000 --> 00:45:05,760 AND FROM THE MG CLUSTER TOGETHER 884 00:45:05,760 --> 00:45:07,040 AND LESS KNOWN DIFFERENCES 885 00:45:07,040 --> 00:45:08,640 BETWEEN THE LG AND CG AND YOU 886 00:45:08,640 --> 00:45:10,240 CAN SEE THOSE REGIONS ARE 887 00:45:10,240 --> 00:45:16,240 CLUSTERED TOGETHER HERE. 888 00:45:16,240 --> 00:45:19,800 YOU CAN LOOK AT PREDICTED 889 00:45:19,800 --> 00:45:21,200 DISTINCT CELL TYPES AND THERE'S 890 00:45:21,200 --> 00:45:23,000 ABOUT 25 OR SO POTENTIAL 891 00:45:23,000 --> 00:45:25,640 CANDIDATE DIFFERENT CELL TYPES 892 00:45:25,640 --> 00:45:27,400 IN THE DATA SET. 893 00:45:27,400 --> 00:45:29,760 WE CAN ALSO BREAK IT DOWN LOOK 894 00:45:29,760 --> 00:45:34,240 AT DIFFERENT PROGENITORS AND 895 00:45:34,240 --> 00:45:38,360 BLUE IS A POST-MITOTIC NEURON TO 896 00:45:38,360 --> 00:45:41,840 LOOK AT DIFFERENT STAGES AND 897 00:45:41,840 --> 00:45:43,640 PERFORM ANALYSIS THAT CAN GIVE 898 00:45:43,640 --> 00:45:45,680 US INFORMATION FOR THE EARLIER 899 00:45:45,680 --> 00:45:50,040 CELL TYPES VERSUS LATER 900 00:45:50,040 --> 00:45:52,240 IMPORTANT POST-MITOTIC. 901 00:45:52,240 --> 00:45:54,480 I WON'T BORE YOU WITH GENES BUT 902 00:45:54,480 --> 00:45:58,240 HIGHLIGHT WHAT WE CAN OBTAIN 903 00:45:58,240 --> 00:45:58,960 FROM THIS DATA. 904 00:45:58,960 --> 00:46:01,120 IF YOU LOOK AT THE ACCESSIBILITY 905 00:46:01,120 --> 00:46:04,840 OF PROMOTERS OF SOME GENES YOU 906 00:46:04,840 --> 00:46:08,840 SEE DIFFERENTIAL ACCESSIBILITY. 907 00:46:08,840 --> 00:46:11,800 AND THIS IS A SPECIFIC 908 00:46:11,800 --> 00:46:12,360 TRANSCRIPTION FACTOR ONLY 909 00:46:12,360 --> 00:46:14,560 EXPRESSED IN THE MG AND THE 910 00:46:14,560 --> 00:46:17,760 PROMOTER IS ONLY ACCESSIBLE IN 911 00:46:17,760 --> 00:46:21,920 THE MGE AND YOU SEE THE CORTICAL 912 00:46:21,920 --> 00:46:23,160 SPECIFIC TRANSCRIPTION FACTOR 913 00:46:23,160 --> 00:46:25,160 AND IT'S ONLY EXPRESSIBLE IN THE 914 00:46:25,160 --> 00:46:25,400 CORTEX. 915 00:46:25,400 --> 00:46:28,080 WE CAN LOOK AT THE ACCESSIBILITY 916 00:46:28,080 --> 00:46:29,720 DATA IN DIFFERENT WAYS. 917 00:46:29,720 --> 00:46:32,160 IF WE ORGANIZE AND CLUSTER BASED 918 00:46:32,160 --> 00:46:34,200 ON THE REGION YOU CAN SEE THIS 919 00:46:34,200 --> 00:46:38,240 IS ONLY ACCESSIBLE IN THE MG AND 920 00:46:38,240 --> 00:46:41,440 IN THE OTHER REGIONS AND NEUROD6 921 00:46:41,440 --> 00:46:42,880 SHOWS ACCESSIBILITY TO THE 922 00:46:42,880 --> 00:46:45,200 CORTEX AND NOT OTHER REGIONS AND 923 00:46:45,200 --> 00:46:48,760 YOU CAN LINE THESE UP FROM THE 924 00:46:48,760 --> 00:46:52,960 EARLIEST PROGENITORS IT NESTED 925 00:46:52,960 --> 00:46:55,280 AS A GREAT GENE WITH ALLELE 926 00:46:55,280 --> 00:47:05,760 CELLS AND IT'S ACCESSIBLE AND RE 927 00:47:06,200 --> 00:47:07,760 -- DECREASES OVER TIME AND SO 928 00:47:07,760 --> 00:47:09,680 THERE'S A NICE CORRELATION 929 00:47:09,680 --> 00:47:12,280 BETWEEN ACCESSIBILITY OF 930 00:47:12,280 --> 00:47:12,960 PROMOTERS WITH KNOWN GENE 931 00:47:12,960 --> 00:47:15,440 EXPRESSION BOTH IN TERMS OF OVER 932 00:47:15,440 --> 00:47:19,920 DEVELOPMENT OF TIME AND LOOKING 933 00:47:19,920 --> 00:47:22,240 BETWEEN DIFFERENT IMAGES. 934 00:47:22,240 --> 00:47:23,880 THIS SAY PRETTY COMPLICATED 935 00:47:23,880 --> 00:47:26,840 FIGURE AND WE HAVE TAKEN THE 25 936 00:47:26,840 --> 00:47:28,760 CLUSTERS AND GROUPED THEM 937 00:47:28,760 --> 00:47:31,200 TOGETHER TO LOOK AT DIFFERENTIAL 938 00:47:31,200 --> 00:47:33,320 ACCESSIBILITY PEAKS. 939 00:47:33,320 --> 00:47:36,200 FOR EVERY CLUSTER HOW UNIQUE IS 940 00:47:36,200 --> 00:47:37,840 THE ACCESSIBILITY OF THE GENOME. 941 00:47:37,840 --> 00:47:39,840 AND SO WHAT YOU SEE HERE ALONG 942 00:47:39,840 --> 00:47:41,480 THE DIAGONAL IS COMPARING EACH 943 00:47:41,480 --> 00:47:42,720 CLUSTER TO ITSELF AND IF YOU 944 00:47:42,720 --> 00:47:46,200 LOOK AT THE CLUSTER UP HERE THAT 945 00:47:46,200 --> 00:47:47,440 CONTAINS PROGENITORS FROM THE 946 00:47:47,440 --> 00:47:51,080 CORTEX AND HAS A LARGER AMOUNT 947 00:47:51,080 --> 00:47:52,400 OF DIFFERENTIATED EXPRESSED 948 00:47:52,400 --> 00:47:57,840 PEAKS AND IF YOU COMPARE TO A 949 00:47:57,840 --> 00:48:00,840 POSTMITOTIC CELL FROM MG THERE'S 950 00:48:00,840 --> 00:48:02,640 LITTLE SIMILARITY FROM THE 951 00:48:02,640 --> 00:48:04,080 DIFFERENTIALLY EXPRESSED PEAKS. 952 00:48:04,080 --> 00:48:08,760 THIS WOULD LOOK DIFFERENT FROM 953 00:48:08,760 --> 00:48:10,120 RNA TRANSCRIPTION AND EACH 954 00:48:10,120 --> 00:48:15,040 CLUSTER OF CELLS HAVE A UNIQUE 955 00:48:15,040 --> 00:48:17,200 SET OF CELLS DISTINGUISHING IT 956 00:48:17,200 --> 00:48:20,840 FROM DIFFERENT BRAIN REGIONS AND 957 00:48:20,840 --> 00:48:21,960 DIFFERENT SUBSETS. 958 00:48:21,960 --> 00:48:24,280 YOU CAN DIG INTO THIS DATA A 959 00:48:24,280 --> 00:48:24,800 LITTLE BIT MORE. 960 00:48:24,800 --> 00:48:27,040 FOR EACH ACCESSIBLE REGION WE 961 00:48:27,040 --> 00:48:31,240 CAN SAY WITHIN THAT REGION ARE 962 00:48:31,240 --> 00:48:32,360 THERE SPECIFIC SPECIFIC 963 00:48:32,360 --> 00:48:34,240 TRANSCRIPTION FACTOR BINDING 964 00:48:34,240 --> 00:48:34,680 SITES. 965 00:48:34,680 --> 00:48:39,520 THIS IS CRITICAL FOR DEVELOPMENT 966 00:48:39,520 --> 00:48:42,240 OF GABAERGIC CELLS AND THE MOTIF 967 00:48:42,240 --> 00:48:46,240 IS RESTRICTED SPECIFICALLY TO 968 00:48:46,240 --> 00:48:48,760 THE CELLS CONVERSELY THIS IS 969 00:48:48,760 --> 00:48:50,440 CRITICAL FOR CORTICAL 970 00:48:50,440 --> 00:48:53,120 DEVELOPMENT AND THE BINDING SITE 971 00:48:53,120 --> 00:48:55,200 IS ONLY PRESENT IN CORTICAL 972 00:48:55,200 --> 00:48:58,880 CELLS AND NOT PRESENT IN THE 973 00:48:58,880 --> 00:48:59,680 ACCESSIBLE AREAS OF THIS. 974 00:48:59,680 --> 00:49:01,760 THERE'S OTHER WAYS TO DIVE INTO 975 00:49:01,760 --> 00:49:03,000 THE DETE BUT IT GIVES AN 976 00:49:03,000 --> 00:49:10,200 OVERVIEW OF WHAT WE CAN GENERATE 977 00:49:10,200 --> 00:49:23,720 FROM THESE GENES AND WE LOOK AT 978 00:49:23,720 --> 00:49:24,680 REGIONS CO-ACCESSIBLE. 979 00:49:24,680 --> 00:49:31,080 WE HAVE A PROMOTER FOR GENE 980 00:49:31,080 --> 00:49:32,120 EXPRESSION. 981 00:49:32,120 --> 00:49:33,920 AND MOST ARE LOCATED FURTHER 982 00:49:33,920 --> 00:49:35,600 AWAY WE WANTED TO SEE IN THE 983 00:49:35,600 --> 00:49:38,160 DATA CAN WE FIND REGIONS 984 00:49:38,160 --> 00:49:40,040 PROMOTERS AND IN THE SAME CELL 985 00:49:40,040 --> 00:49:46,160 FIND GENOMIC LOCI WHICH COULD BE 986 00:49:46,160 --> 00:49:49,840 INDICATIVE OF A POSSIBLE 987 00:49:49,840 --> 00:49:50,960 ENHANCER. 988 00:49:50,960 --> 00:50:02,040 WE USED THIS ANALYSIS CALLED 989 00:50:02,040 --> 00:50:05,520 CISERO AND ALL THESE BLUE LINES 990 00:50:05,520 --> 00:50:08,400 THE BLUE ARCHES CREATE A REGION 991 00:50:08,400 --> 00:50:10,200 UPSTREAM OF THE GENE AND WITHIN 992 00:50:10,200 --> 00:50:12,640 THE SAME CELL IS OFTEN 993 00:50:12,640 --> 00:50:12,960 CO-ACCESSIBLE. 994 00:50:12,960 --> 00:50:16,200 THIS COULD INDICATE THAT A 995 00:50:16,200 --> 00:50:19,640 REGION COULD POSSIBLY BE AN 996 00:50:19,640 --> 00:50:24,360 ENHANCER AND CHECKS WITH THE 997 00:50:24,360 --> 00:50:27,840 PROMOTER TO REGULATE GENE 998 00:50:27,840 --> 00:50:28,200 EXPRESSION. 999 00:50:28,200 --> 00:50:30,320 YOU ONLY SEE THIS PATTERN IN THE 1000 00:50:30,320 --> 00:50:32,600 MG WHERE THE GREEN IS EXPRESSED 1001 00:50:32,600 --> 00:50:33,840 AND NOT IN OTHER REGIONS. 1002 00:50:33,840 --> 00:50:35,920 WE CAN LOOK AT THIS TYPE OF 1003 00:50:35,920 --> 00:50:37,840 ANALYSIS AND GENE AND ALSO LOOK 1004 00:50:37,840 --> 00:50:39,640 AT IT BETWEEN REGIONS AND LOOK 1005 00:50:39,640 --> 00:50:42,040 AT IT THROUGH DEVELOPMENT OF 1006 00:50:42,040 --> 00:50:42,840 TIME. 1007 00:50:42,840 --> 00:50:46,040 AND THIS IS A POSTMITOTIC GENE 1008 00:50:46,040 --> 00:50:48,240 AND COMES ON LATER IN 1009 00:50:48,240 --> 00:50:56,400 DEVELOPMENT AND THE CHROMATIN 1010 00:50:56,400 --> 00:50:58,000 CO-ACCESSIBILITY DOESN'T EXIST 1011 00:50:58,000 --> 00:50:59,520 BUT IN THIS OTHER CELL YOU SEE A 1012 00:50:59,520 --> 00:51:01,400 MORE MATURE PATTERN AND YOU CAN 1013 00:51:01,400 --> 00:51:02,680 DO THE SAME THING IN YOUR 1014 00:51:02,680 --> 00:51:03,680 FAVORITE GENE. 1015 00:51:03,680 --> 00:51:04,840 THE ACCESSIBILITY INFORMATION IS 1016 00:51:04,840 --> 00:51:06,920 GREAT BUT WE WANT TO MAKE SURE 1017 00:51:06,920 --> 00:51:10,000 IT MAKES SENSE AND FITS WITH THE 1018 00:51:10,000 --> 00:51:11,680 RNA EXPRESSION. 1019 00:51:11,680 --> 00:51:14,200 WE PERFORMED SINGLE CELL RNA 1020 00:51:14,200 --> 00:51:16,800 SIKH AND INTEGRATED THE DATA 1021 00:51:16,800 --> 00:51:19,040 TOGETHER SUCH THAT IN THE SAME 1022 00:51:19,040 --> 00:51:19,680 COMPUTATIONAL SPACE IN DIFFERENT 1023 00:51:19,680 --> 00:51:23,400 CELLS WE CAN LOOK AT GENE 1024 00:51:23,400 --> 00:51:25,080 EXPRESSION PATTERNS AS WELL AS 1025 00:51:25,080 --> 00:51:26,440 ACCESSIBILITY AND YOU CAN DO THE 1026 00:51:26,440 --> 00:51:29,160 SAME ANALYSIS FINDING CLUSTERS 1027 00:51:29,160 --> 00:51:32,760 AND IF WE GROUP GENES WITH 1028 00:51:32,760 --> 00:51:34,480 SIMILAR EXPRESSION PROFILES TO 1029 00:51:34,480 --> 00:51:36,720 SIMILAR FAMILIES WE CAN SEE A 1030 00:51:36,720 --> 00:51:41,440 SET OF GENES THAT ARE EXPRESSED 1031 00:51:41,440 --> 00:51:43,080 HIGHLY DURING NEURO GENIC CELLS 1032 00:51:43,080 --> 00:51:48,080 AND GET DOWN REGULATED WITH 1033 00:51:48,080 --> 00:51:49,200 POST-MITOTIC CELLS AND OTHERS 1034 00:51:49,200 --> 00:51:51,240 GET UPREGULATED OVER TIME. 1035 00:51:51,240 --> 00:51:52,240 AND BECAUSE WE INTEGRATE THE 1036 00:51:52,240 --> 00:51:53,840 DATA TOGETHER WE CAN LOOK AT 1037 00:51:53,840 --> 00:51:58,240 GENE EXPRESSION AND THE GAS AND 1038 00:51:58,240 --> 00:52:01,360 ENHANCERS. 1039 00:52:01,360 --> 00:52:03,520 AND YOU CAN FOLLOW BOTH THE 1040 00:52:03,520 --> 00:52:05,400 GREEN EXPRESSION AND PROMOTER 1041 00:52:05,400 --> 00:52:07,520 AND ACCESSIBILITY AND WHAT WE 1042 00:52:07,520 --> 00:52:10,120 SEE IS THAT GENES ENRICHED EARLY 1043 00:52:10,120 --> 00:52:14,280 IN DEVELOPMENT THEN GO DOWN AS 1044 00:52:14,280 --> 00:52:18,920 THOSE BECOME POST-MITOTIC AND 1045 00:52:18,920 --> 00:52:20,040 HAVE DIFFERENT LEVELS PART OF 1046 00:52:20,040 --> 00:52:24,120 THE PROMOTER ENHANCER BEING 1047 00:52:24,120 --> 00:52:25,880 TURNED OFF AND IF YOU LOOK AT 1048 00:52:25,880 --> 00:52:27,040 GENES UPREGULATED OVER TIME YOU 1049 00:52:27,040 --> 00:52:29,640 CAN SEE BOTH THE PROMOTERS AND 1050 00:52:29,640 --> 00:52:33,280 ENHANCERS START TO BECOME 1051 00:52:33,280 --> 00:52:35,320 ACCESSIBLE PRIOR TO RNA 1052 00:52:35,320 --> 00:52:35,640 EXPRESSION. 1053 00:52:35,640 --> 00:52:38,080 ONE EXAMPLE IS WHERE THE ACTUAL 1054 00:52:38,080 --> 00:52:39,560 MRNA IS EXPRESSED AND SEE BOTH 1055 00:52:39,560 --> 00:52:42,720 IN TERMS OF THE PROMOTER AND 1056 00:52:42,720 --> 00:52:44,760 ENHANCER THE REGIONS BECOME 1057 00:52:44,760 --> 00:52:46,640 ACCESSIBLE PRIOR TO RNA WHICH IS 1058 00:52:46,640 --> 00:52:49,000 A COMMON THEME WE SAW THROUGHOUT 1059 00:52:49,000 --> 00:52:51,840 THE DAY. 1060 00:52:51,840 --> 00:52:54,040 NOW, THIS IS GREAT BUT DOESN'T 1061 00:52:54,040 --> 00:52:56,280 DIRECTLY TELL ANYTHING ABOUT 1062 00:52:56,280 --> 00:53:01,760 ENHANCER AND PROMOTER 1063 00:53:01,760 --> 00:53:04,040 INTERACTIONS AND SO TO DIG INTO 1064 00:53:04,040 --> 00:53:09,800 THIS DIGGER WE WANTED TO UTILIZE 1065 00:53:09,800 --> 00:53:14,400 ANALYSIS OF HISTONE 1066 00:53:14,400 --> 00:53:17,720 MODIFICATIONS WHICH HAS BEEN 1067 00:53:17,720 --> 00:53:21,040 KNOWN TO LABEL ENHANCERS. 1068 00:53:21,040 --> 00:53:26,680 AND WE ANALYZE ONE IS A 1069 00:53:26,680 --> 00:53:28,440 PROMOTER AND ENHANCER AND 1070 00:53:28,440 --> 00:53:30,040 THERE'S A HISTONE MODIFICATION 1071 00:53:30,040 --> 00:53:43,600 THAT INDICATES REPRESSIVE MARKS. 1072 00:53:43,600 --> 00:53:45,560 WE DEVELOPED THIS AND IT'S 1073 00:53:45,560 --> 00:53:46,440 CHEAPER AND HAS LESS CELLS WHICH 1074 00:53:46,440 --> 00:53:49,640 IS WHY IT WAS APPEALING TO US 1075 00:53:49,640 --> 00:53:52,920 AND YOU CAN ADD AN ANTIBODY TO 1076 00:53:52,920 --> 00:53:54,160 YOUR NUCLEI. 1077 00:53:54,160 --> 00:53:55,520 IT RECOGNIZES SPECIFIC 1078 00:53:55,520 --> 00:53:58,040 MODIFICATION AND HISTONE. 1079 00:53:58,040 --> 00:54:02,240 YOU THEN ADD A TRANSPOSING THAT 1080 00:54:02,240 --> 00:54:03,520 RECOGNIZES THE ANTIBODY AND 1081 00:54:03,520 --> 00:54:07,040 ACTIVATE IT TO CUT THE DNA AND 1082 00:54:07,040 --> 00:54:09,520 ADD TAGS ON TO IT AND EXTRACT 1083 00:54:09,520 --> 00:54:10,760 AND SEQUENCE IT AND IT WILL TELL 1084 00:54:10,760 --> 00:54:13,920 YOU WHERE YOU HAVE THIS SPECIFIC 1085 00:54:13,920 --> 00:54:14,800 HISTONE TAG THAT COULD INDICATE 1086 00:54:14,800 --> 00:54:18,240 A PROMOTER OR ACTIVE ENHANCER OR 1087 00:54:18,240 --> 00:54:24,840 REPRESSER. 1088 00:54:24,840 --> 00:54:30,640 THIS IS A MARK ACTIVE GENE 1089 00:54:30,640 --> 00:54:36,400 EXPRESSION AND WE HAD AN RNA 1090 00:54:36,400 --> 00:54:38,520 ACCESSIBILITY AND LOOKING AT 1091 00:54:38,520 --> 00:54:46,200 ACTIVE OR REEXPRESSEXPRESSED AND THIS SAY 1092 00:54:46,200 --> 00:54:48,680 GENE PREDOMINANTLY ENRICHED IN 1093 00:54:48,680 --> 00:54:50,600 THE CG AND EXPRESSED IN LOW 1094 00:54:50,600 --> 00:54:52,440 LEVELS IN THE OTHER BRAIN 1095 00:54:52,440 --> 00:54:52,680 REGION. 1096 00:54:52,680 --> 00:54:55,240 IF YOU LOOK AT THE ATAC DATA YOU 1097 00:54:55,240 --> 00:54:56,760 DON'T SEE ANY DIFFERENCE. 1098 00:54:56,760 --> 00:54:59,840 ONLY LOOKING AT THE CHROMATIN 1099 00:54:59,840 --> 00:55:01,280 ACCESSIBILITY DOES NOT PROVIDE A 1100 00:55:01,280 --> 00:55:05,520 LOT OF INFORMATION ABOUT THE 1101 00:55:05,520 --> 00:55:06,480 GENE EXPRESSION OR FUNCTION. 1102 00:55:06,480 --> 00:55:08,120 WHEN YOU ADD IN THE HIS TONE 1103 00:55:08,120 --> 00:55:10,720 MARKS THE PROMOTER IS ONLY 1104 00:55:10,720 --> 00:55:15,080 ACTIVE IN THE CG AND LOW LEVELS 1105 00:55:15,080 --> 00:55:16,440 OF OTHER GENES AND THE 1106 00:55:16,440 --> 00:55:18,360 REPRESSIVE MARK IS NOT SHOWN BUT 1107 00:55:18,360 --> 00:55:20,000 REPRESSED IN OTHER REGIONS. 1108 00:55:20,000 --> 00:55:22,200 THIS IS A COMMON THEME THAT ONLY 1109 00:55:22,200 --> 00:55:23,400 LOOKING AT ONE MODALITY GIVES A 1110 00:55:23,400 --> 00:55:26,080 LITTLE BIT OF INFORMATION BUT 1111 00:55:26,080 --> 00:55:28,280 WHEN YOU START TO COMBINE 1112 00:55:28,280 --> 00:55:29,640 MULTIPLE MODALITIES TOGETHER YOU 1113 00:55:29,640 --> 00:55:31,360 CAN GET A BETTER UNDERSTANDING 1114 00:55:31,360 --> 00:55:33,440 OF THE STATE OF THE GENE WITH 1115 00:55:33,440 --> 00:55:51,440 THE EXPRESSION AND EPIGENETICS. 1116 00:55:51,440 --> 00:55:57,360 AND THIS IS A CELL ENRICHED AND 1117 00:55:57,360 --> 00:55:58,960 PREVIOUS STUDIES HAVE LOOKED AT 1118 00:55:58,960 --> 00:56:04,440 THIS AS A POSSIBLE ENHANCER OR 1119 00:56:04,440 --> 00:56:06,240 ASCL1 BUT DIDN'T SHOW THE 1120 00:56:06,240 --> 00:56:08,040 EXPRESSIVE PATTERN. 1121 00:56:08,040 --> 00:56:10,040 IT'S CO-ACCESSIBLE WITH THE 1122 00:56:10,040 --> 00:56:15,600 PROMOTER BUT WHEN YOU LOOK TO 1123 00:56:15,600 --> 00:56:17,480 THE SPATIAL RESOLUTION AND IF 1124 00:56:17,480 --> 00:56:22,680 YOU LOOK AT THE ACTIVE ENHANCER 1125 00:56:22,680 --> 00:56:27,880 IT'S STRONGLY K27 ACETYL SIGNAL 1126 00:56:27,880 --> 00:56:31,920 IN THE CORTEX AND THE REGION 1127 00:56:31,920 --> 00:56:33,640 IT'S NOT EXPRESSED AND IT HIT 1128 00:56:33,640 --> 00:56:34,840 DOESN'T LOOK LIKE A GREAT 1129 00:56:34,840 --> 00:56:36,760 CANDIDATE FOR ENHANCER BECAUSE 1130 00:56:36,760 --> 00:56:39,280 THE HISTONE MARK IS NOT ENRICHED 1131 00:56:39,280 --> 00:56:41,520 IN THE AREAS WHERE THE GENE IS 1132 00:56:41,520 --> 00:56:43,160 EXPRESSED AND WE FOUND OTHER 1133 00:56:43,160 --> 00:56:45,200 REGIONS FOR THE DOWN STREAM 1134 00:56:45,200 --> 00:56:47,800 CO-ACCESSIBLE WITH THE PROMOTER 1135 00:56:47,800 --> 00:56:50,200 AND SHOW A HIGHER ENRICHMENT OF 1136 00:56:50,200 --> 00:56:53,920 THIS ACTIVE ENHANCER MARKS 1137 00:56:53,920 --> 00:56:58,160 SPECIFICALLY IN THE GANGLIONIC 1138 00:56:58,160 --> 00:56:59,560 EMINENCES AND THE REGIONS WHICH 1139 00:56:59,560 --> 00:57:01,640 HAVE NOT BEEN STUDIES ARE BETTER 1140 00:57:01,640 --> 00:57:05,480 CANDIDATES FOR ENHANCER TO 1141 00:57:05,480 --> 00:57:09,040 REGULATE THIS GENE COMPARED 1142 00:57:09,040 --> 00:57:11,720 PREVIOUSLY STUDIED THAT DIDN'T 1143 00:57:11,720 --> 00:57:12,840 HAVE THE RESULT. 1144 00:57:12,840 --> 00:57:16,000 WE CAN DO THIS FOR A VARIETY OF 1145 00:57:16,000 --> 00:57:21,280 BRAIN REGIONS AND THE OTHER 1146 00:57:21,280 --> 00:57:23,440 THING WE'VE DONE IS HIGH C 1147 00:57:23,440 --> 00:57:28,000 LOOKING AT HIGHER CHROMATIN 1148 00:57:28,000 --> 00:57:29,040 INTERACTIONS AND TO HIGHLIGHT 1149 00:57:29,040 --> 00:57:30,760 THIS COMPARING THE REGIONS 1150 00:57:30,760 --> 00:57:33,320 HERE'S A REGION WHERE WE SEE A 1151 00:57:33,320 --> 00:57:35,840 DIRECT CONTACT BETWEEN THE 1152 00:57:35,840 --> 00:57:37,680 PROMOTER AND THE REGION UP 1153 00:57:37,680 --> 00:57:38,640 STREAK AND THIS IS SPECIFIC TO 1154 00:57:38,640 --> 00:57:42,000 THE MGE AND NOT FOUND IN OTHER 1155 00:57:42,000 --> 00:57:42,960 BRAIN REGIONS. 1156 00:57:42,960 --> 00:57:44,960 AGAIN, WE CAN COMPARE THIS AND 1157 00:57:44,960 --> 00:57:48,960 COMBINE WITH OTHER DATA SO THAT 1158 00:57:48,960 --> 00:57:52,720 THE NKX REGION WE SEE A DIRECT 1159 00:57:52,720 --> 00:57:54,520 INTERACTION BETWEEN THE PROMOTER 1160 00:57:54,520 --> 00:57:57,040 AND THE LOCI OVER HERE NOT FOUND 1161 00:57:57,040 --> 00:57:58,800 IN THE OTHER BRAIN REGIONS AND 1162 00:57:58,800 --> 00:58:02,560 THE CONVERSE IS TRUE WITH THE 1163 00:58:02,560 --> 00:58:04,280 GENES EXPRESSED AND SEE THE 1164 00:58:04,280 --> 00:58:06,080 INTERACTION WITH THE LOCI WITH 1165 00:58:06,080 --> 00:58:08,040 THE REGION NOT FOUND IN THE MG. 1166 00:58:08,040 --> 00:58:11,080 WE CAN DO THIS IN A VARIETY OF 1167 00:58:11,080 --> 00:58:15,440 BRAIN REGIONS AND REALLY QUICK 1168 00:58:15,440 --> 00:58:17,760 AS IT'S IMPORTANT TO MAKE THE 1169 00:58:17,760 --> 00:58:19,920 INFORMATION PUBLICLY ACCESSIBLE. 1170 00:58:19,920 --> 00:58:23,400 ALL THE DATA IS AVAILABLE ON THE 1171 00:58:23,400 --> 00:58:26,240 UCSD BROWSER WITH ALL THE RNA 1172 00:58:26,240 --> 00:58:28,480 INFORMATION, ACCESSIBLE AND THE 1173 00:58:28,480 --> 00:58:30,920 CONNECTIONS AND THE HISTONE 1174 00:58:30,920 --> 00:58:31,640 MODIFICATIONS AS WELL AS THE 1175 00:58:31,640 --> 00:58:36,840 HIGH C DATA AND CAPTURE SEQ 1176 00:58:36,840 --> 00:58:37,440 BELOW. 1177 00:58:37,440 --> 00:58:38,840 WE LOOKED AT THE FUTURE I WON'T 1178 00:58:38,840 --> 00:58:39,960 GO THROUGH THIS DUE TO TIME 1179 00:58:39,960 --> 00:58:41,320 CONCERNS BUT I DO WANT TO 1180 00:58:41,320 --> 00:58:42,800 HIGHLIGHT THAT I THINK SOME OF 1181 00:58:42,800 --> 00:58:44,520 THE MOST IMPORTANT THINGS ARE 1182 00:58:44,520 --> 00:58:46,160 MAKING THE DATA AS PUBLICLY DATA 1183 00:58:46,160 --> 00:58:48,760 AS POSSIBLE AND INTEGRATING A 1184 00:58:48,760 --> 00:58:51,280 WIDE VARIETY OF MODALITIES IS 1185 00:58:51,280 --> 00:58:53,920 CRITICAL FOR UNDERSTANDING GENE 1186 00:58:53,920 --> 00:58:55,720 AND CELL FUNCTION THROUGHOUT 1187 00:58:55,720 --> 00:58:57,280 DEVELOPMENT AND AT DIFFERENT 1188 00:58:57,280 --> 00:58:57,840 TIME POINTS AND DIFFERENT 1189 00:58:57,840 --> 00:59:01,640 SPATIAL REGIONS AND I THANK MY 1190 00:59:01,640 --> 00:59:03,720 ENTIRE TEAM CRITICAL FOR RUNNING 1191 00:59:03,720 --> 00:59:06,720 THE PROJECT AND THE 1192 00:59:06,720 --> 00:59:08,840 COLLABORATION AND THE 1193 00:59:08,840 --> 00:59:10,520 BIOINFORMATICS SEQUENCING CORE 1194 00:59:10,520 --> 00:59:10,840 AT NICHD. 1195 00:59:10,840 --> 00:59:15,560 THANK YOU FOR THE DATA. 1196 00:59:15,560 --> 00:59:18,280 >> THANK YOU, VERY MUCH, TIM. 1197 00:59:18,280 --> 00:59:22,200 WE'LL MOVE ON TO YE ZHANG FROM 1198 00:59:22,200 --> 00:59:25,160 THE UNIVERSITY OF CALIFORNIA IN 1199 00:59:25,160 --> 00:59:26,200 LOS ANGELES. 1200 00:59:26,200 --> 00:59:30,320 YE DID HER POST-DOCTORAL WORK 1201 00:59:30,320 --> 00:59:35,560 WITH UCSF STUDYING FLY 1202 00:59:35,560 --> 00:59:38,320 DEVELOPMENT AND MOVED ON TO DO A 1203 00:59:38,320 --> 00:59:42,160 POST-DOC WITH BEN BURRIS WHERE 1204 00:59:42,160 --> 00:59:46,040 SHE PIONEERED INTERESTING 1205 00:59:46,040 --> 00:59:49,040 TECHNOLOGY TO SORT DIFFERENT 1206 00:59:49,040 --> 00:59:50,880 CELLS PROVIDING THE OPPORTUNITY 1207 00:59:50,880 --> 00:59:53,120 TO LOOK AT GLIAL CELL TYPE 1208 00:59:53,120 --> 00:59:54,640 DIVERSITY IN GREATER DETAIL. 1209 00:59:54,640 --> 00:59:57,640 AND THIS IS WORK SHE HAS BEEN 1210 00:59:57,640 --> 01:00:00,400 CONTINUING AT UCLA AND WE LOOK 1211 01:00:00,400 --> 01:00:03,440 FORWARD TO HEAR THE LATEST, YE, 1212 01:00:03,440 --> 01:00:04,560 PLEASE, TAKE IT AWAY. 1213 01:00:04,560 --> 01:00:06,120 >> THANK YOU, OLIVER FOR THE 1214 01:00:06,120 --> 01:00:08,760 KIND INTRODUCTION AND I'D LIKE 1215 01:00:08,760 --> 01:00:11,320 TO THANK THE ORGANIZERS FOR 1216 01:00:11,320 --> 01:00:12,800 PUTTING TOGETHER A FANTASTIC 1217 01:00:12,800 --> 01:00:14,640 WORKSHOP AND I'VE HEARD A LOT OF 1218 01:00:14,640 --> 01:00:17,160 FROM THE FIRST TWO TALKS. 1219 01:00:17,160 --> 01:00:21,520 I'M TALK ABOUT IMMUNOPANING FUR 1220 01:00:21,520 --> 01:00:26,440 FICTION AND TRANSCRIPT OME 1221 01:00:26,440 --> 01:00:29,040 PROFILING OF GLIAL CELLS. 1222 01:00:29,040 --> 01:00:34,560 IN THE HUMAN CENTRAL NERVOUS 1223 01:00:34,560 --> 01:00:36,640 SYSTEM HALF THE CELLS ARE GLIAL 1224 01:00:36,640 --> 01:00:39,200 CELLS AND IN RECENT YEARS MANY 1225 01:00:39,200 --> 01:00:42,720 LABS HAVE SHOWN THAT GLIA CELLS 1226 01:00:42,720 --> 01:00:44,040 ARE IMPORTANT FOR THE 1227 01:00:44,040 --> 01:00:51,800 DEVELOPMENT AND FUNCTION CENTRAL 1228 01:00:51,800 --> 01:00:53,640 NERVOUS SYSTEM AND THERE'S THESE 1229 01:00:53,640 --> 01:00:59,760 SYNAPSES AND NEURONS FORM FEW 1230 01:00:59,760 --> 01:01:04,040 SYNAPSES IN VIVO WITHOUT 1231 01:01:04,040 --> 01:01:05,960 ASTROCYTES AND THESE ARE AN 1232 01:01:05,960 --> 01:01:10,400 IMMUNE TYPE AND MICROGLIA ARE 1233 01:01:10,400 --> 01:01:13,920 DEVELOPMENT IN THE SYNAPSE AND 1234 01:01:13,920 --> 01:01:20,360 SCULPTING OF NEUROCIRCUITSES 1235 01:01:20,360 --> 01:01:22,160 AND THESE DENDRITE CRITICAL FOR 1236 01:01:22,160 --> 01:01:24,960 THE METABOLISM AND HEALTH OF 1237 01:01:24,960 --> 01:01:26,600 AXONS. 1238 01:01:26,600 --> 01:01:28,400 SO TO UNDERSTAND BRAIN 1239 01:01:28,400 --> 01:01:30,640 DEVELOPMENT, IT'S ESSENTIAL TO 1240 01:01:30,640 --> 01:01:39,920 UNDERSTAND THE GLIA FUNCTIONDERSTAND THE G LIA FUNCTION.SO TO UNDERSTAND BRAIN 1241 01:01:39,920 --> 01:01:40,560 DEVELOPMENT, IT'S ESSENTIAL TO 1242 01:01:40,560 --> 01:01:45,240 NDERSTAND THE GLIA FUNCTION. 1243 01:01:45,240 --> 01:01:48,760 I'LL GOING TO TALK ABOUT A 1244 01:01:48,760 --> 01:01:52,040 METHOD OF PURIFICATION FOR GLIAL 1245 01:01:52,040 --> 01:01:55,680 CELL AND TWO METHODS AND THE 1246 01:01:55,680 --> 01:01:56,760 TRANSCRIPTOME PROFILING AND WE 1247 01:01:56,760 --> 01:02:00,760 WERE ABLE TO DO CROSS-SPECIES 1248 01:02:00,760 --> 01:02:04,280 COMPARISONS OF HUMAN ASTROCYTES 1249 01:02:04,280 --> 01:02:06,560 AND CHARACTERIZING HUMAN 1250 01:02:06,560 --> 01:02:08,360 ASTROCYTE TRANSCRIPT OME CHANGES 1251 01:02:08,360 --> 01:02:10,280 ACROSS THE LIFE SPAN AND I'LL 1252 01:02:10,280 --> 01:02:12,800 TALK ABOUT STRENGTH AND 1253 01:02:12,800 --> 01:02:27,720 LIMITATIONS OF CURRENT METHODS. 1254 01:02:27,720 --> 01:02:33,240 THIS WAS DONE IN BARRES LAB AND 1255 01:02:33,240 --> 01:02:36,760 NOW WE CAN HAVE THIS APPLICABLE 1256 01:02:36,760 --> 01:02:42,200 TO MANY CELL TYPES AND ACROSS 1257 01:02:42,200 --> 01:02:43,360 MOUSE, AND HUMAN SPECIES. 1258 01:02:43,360 --> 01:02:48,240 BACK WHEN I WAS A POST-DOC WE 1259 01:02:48,240 --> 01:02:52,120 WANTED TO CONSTRUCT A MOUSE 1260 01:02:52,120 --> 01:02:54,440 BRAIN CELL TYPE TRANSCRIPTOME 1261 01:02:54,440 --> 01:02:56,080 DATA SET WITH PURIFICATION OF 1262 01:02:56,080 --> 01:02:59,120 DIFFERENT CELL TYPES AND WERE 1263 01:02:59,120 --> 01:03:00,800 ABLE TO DEVELOP PURIFY METHODS 1264 01:03:00,800 --> 01:03:02,880 AND NEURONS IN THREE STAGES IN 1265 01:03:02,880 --> 01:03:10,240 THE OLIGO DENDRITE CELLS AND THE 1266 01:03:10,240 --> 01:03:21,000 NEURAL FORMED OLIGO DENDROCYTES 1267 01:03:21,000 --> 01:03:25,440 AND WE PERFORMED THE RNA 1268 01:03:25,440 --> 01:03:28,200 SEQUENCING AND HERE'S THE PURITY 1269 01:03:28,200 --> 01:03:30,800 OF THE ISOLATED CELL TYPES. 1270 01:03:30,800 --> 01:03:33,280 THE CELL TYPE MARKERS ARE 1271 01:03:33,280 --> 01:03:34,520 CLEARLY EXPRESSED IN A SPECIFIC 1272 01:03:34,520 --> 01:03:35,480 MANNER. 1273 01:03:35,480 --> 01:03:39,240 AFTER THIS WORK WE WERE HOPING 1274 01:03:39,240 --> 01:03:45,080 TO EXPAND THE TRANSCRIPTOME DATA 1275 01:03:45,080 --> 01:03:50,040 SET OF GLIAL TYPES AND ISOLATED 1276 01:03:50,040 --> 01:03:55,040 MICROGLIA AND OLIGO DENDROCYTES 1277 01:03:55,040 --> 01:04:00,880 AND ASTROCYTES AND DATA SETS. 1278 01:04:00,880 --> 01:04:05,080 TO MAKE DATA ACCESSIBLE WE 1279 01:04:05,080 --> 01:04:08,680 GENERATED A WEBSITE WHICH IS 1280 01:04:08,680 --> 01:04:10,240 SEARCHABLE YOU CAN TYPE THE NAME 1281 01:04:10,240 --> 01:04:12,760 AND SEE THEIR EXPRESSION OF THE 1282 01:04:12,760 --> 01:04:14,240 GENE ACROSS CELL TYPES IN MOUSE 1283 01:04:14,240 --> 01:04:16,440 AS WELL AS IN HUMAN. 1284 01:04:16,440 --> 01:04:20,680 AND SHOWN HERE IS AN EXAMPLE 1285 01:04:20,680 --> 01:04:22,120 WHICH IS AN ALZHEIMER'S RISK 1286 01:04:22,120 --> 01:04:23,080 GENE. 1287 01:04:23,080 --> 01:04:28,760 CAN SEE IT'S TREM 2 IS ENRICHED 1288 01:04:28,760 --> 01:04:31,400 IN MACROPHAGES AND OVER THE 1289 01:04:31,400 --> 01:04:33,840 YEARS WE EXPANDED OUR WEBSITE 1290 01:04:33,840 --> 01:04:37,400 AND MANY FORMER TRAINEES HAVE 1291 01:04:37,400 --> 01:04:38,920 COLLECTED ADDITIONAL DATA SETS 1292 01:04:38,920 --> 01:04:42,600 FOR GLIA AND HERE IF YOU CLICK 1293 01:04:42,600 --> 01:04:47,000 YOU CAN SEE MICROGLIA 1294 01:04:47,000 --> 01:04:47,560 DEVELOPMENT TRANSCRIPTOME 1295 01:04:47,560 --> 01:04:50,640 CHANGES IN MICE FROM THE DATA 1296 01:04:50,640 --> 01:04:53,560 SET AND HERE'S ANOTHER DATA SET 1297 01:04:53,560 --> 01:04:56,880 FOR MOUSE ASTROCYTE CHANGES AND 1298 01:04:56,880 --> 01:05:01,760 WE ADDED A STUDY FROM MY OWN LAB 1299 01:05:01,760 --> 01:05:05,640 LOOKING AT HOW ASTROCYTES CHANGE 1300 01:05:05,640 --> 01:05:06,680 IN THE PERI TUMOR 1301 01:05:06,680 --> 01:05:07,280 MICROENVIRONMENT AND YOU CAN 1302 01:05:07,280 --> 01:05:13,240 CLICK AND FIND OUR DATA THERE. 1303 01:05:13,240 --> 01:05:17,600 OVER THE PAST DECADE OR SO MANY 1304 01:05:17,600 --> 01:05:19,760 LABS HAVE GENERATED USEFUL 1305 01:05:19,760 --> 01:05:22,680 TRANSCRIPTOME SEQUENCING DATA 1306 01:05:22,680 --> 01:05:24,760 SETS AND SOME LABS HAVE NICE 1307 01:05:24,760 --> 01:05:27,680 DATA SET WEBSITES TO MAKE IT 1308 01:05:27,680 --> 01:05:30,640 ACCESSIBLE BUT MANY OTHER LABS 1309 01:05:30,640 --> 01:05:32,720 DO NOT HAVE THE EXPERTISE OR 1310 01:05:32,720 --> 01:05:35,000 BANDWIDTH TO MAKE WEBSITES AND 1311 01:05:35,000 --> 01:05:38,120 MAKE DATA IN SEARCHABLE ACCESS 1312 01:05:38,120 --> 01:05:39,400 ABLE FORM LEAVING USEFUL DATA 1313 01:05:39,400 --> 01:05:41,760 SETS HIDDEN IN SOME REPOSITORIES 1314 01:05:41,760 --> 01:05:44,080 AND ONLY ACCESSIBLE TO PEOPLE 1315 01:05:44,080 --> 01:05:47,880 WITH INFORMATICS EXPERTISE AND 1316 01:05:47,880 --> 01:05:50,800 THE DATA MINING BANDWIDTH. 1317 01:05:50,800 --> 01:05:54,440 WITH OUR ONGOING WORK WE WANTED 1318 01:05:54,440 --> 01:05:57,440 TO MAKE DATA ACCESSIBLE BY 1319 01:05:57,440 --> 01:05:59,360 BUILDING A UNIVERSAL WEBSITE 1320 01:05:59,360 --> 01:06:01,560 BUILDING TOOL SO THE GOAL IS ANY 1321 01:06:01,560 --> 01:06:05,840 LAB CAN UPLOAD AN EXCEL SPREAD 1322 01:06:05,840 --> 01:06:07,520 SHEET FOR THEIR TRANSCRIPTOME 1323 01:06:07,520 --> 01:06:09,360 DATA AND OUR TOOL CAN CONVERT 1324 01:06:09,360 --> 01:06:10,520 THAT TO A SEARCHABLE WEBSITE 1325 01:06:10,520 --> 01:06:13,880 THAT RESEMBLED THE SIMPLICITY OF 1326 01:06:13,880 --> 01:06:15,400 OUR WEBSITE. 1327 01:06:15,400 --> 01:06:18,040 AND ANOTHER TOOL THAT WE'RE 1328 01:06:18,040 --> 01:06:19,960 BUILDING THAT'S MORE SPECIFIC TO 1329 01:06:19,960 --> 01:06:24,240 GLIA RESEARCH IS A WEB HUB FOR 1330 01:06:24,240 --> 01:06:28,560 GLIA TRANSCRIPTOME DATA SET. 1331 01:06:28,560 --> 01:06:30,440 THERE'S MANY GREAT DATA SETS 1332 01:06:30,440 --> 01:06:33,040 PUBLISHED BUT FOR SOMEONE NEW TO 1333 01:06:33,040 --> 01:06:35,080 GLIA MAY NOT KNOW ALL THE DATA 1334 01:06:35,080 --> 01:06:37,120 SETS AND THESE INFORMATION ARE 1335 01:06:37,120 --> 01:06:38,640 DISTRIBUTED IN EACH INDIVIDUAL 1336 01:06:38,640 --> 01:06:40,800 PAPERS AND WHAT WE WANT TO DO IS 1337 01:06:40,800 --> 01:06:43,520 TO HAVE A CURATED WEB HUB SO 1338 01:06:43,520 --> 01:06:45,880 ANYONE NEW TO THIS FIELD CAN GO 1339 01:06:45,880 --> 01:06:48,360 TO THIS DATA SET AND SEE WHAT'S 1340 01:06:48,360 --> 01:06:49,720 AVAILABLE AND PERFORM DATA 1341 01:06:49,720 --> 01:06:50,040 MINING. 1342 01:06:50,040 --> 01:07:05,400 WE WANTED TO NAME THIS TO 1343 01:07:05,400 --> 01:07:09,240 BARRESEQ. 1344 01:07:09,240 --> 01:07:13,840 NEXT, I'LL TELL YOU TWO AUTO 1345 01:07:13,840 --> 01:07:26,560 IMMUNO PANNING AND THIS IS 1346 01:07:26,560 --> 01:07:29,040 INVOLVED IN ENVIRONMENTAL 1347 01:07:29,040 --> 01:07:32,160 SYNAPSE ELIMINATION AND 1348 01:07:32,160 --> 01:07:34,240 REGULATION OF BLOOD FLOW AS WELL 1349 01:07:34,240 --> 01:07:35,640 AS POTASSIUM HOMEOSTASIS. 1350 01:07:35,640 --> 01:07:38,080 AND ASTROCYTES ARE DYNAMIC CELL 1351 01:07:38,080 --> 01:07:38,320 TYPES. 1352 01:07:38,320 --> 01:07:41,240 IN DISEASES AND INJURIES THEY 1353 01:07:41,240 --> 01:07:46,040 UNDER GO A PROCESS AND THEY HAVE 1354 01:07:46,040 --> 01:07:48,000 BENEFICIAL AND DETRIMENTAL ROLES 1355 01:07:48,000 --> 01:07:50,480 IN DISEASE CONTEXT DEPENDENT 1356 01:07:50,480 --> 01:07:51,920 MANNER. 1357 01:07:51,920 --> 01:07:55,040 SO FAR WHAT WE KNOW ABOUT 1358 01:07:55,040 --> 01:08:01,960 ASTROCYTES ARE MOVED -- MOSTLY 1359 01:08:01,960 --> 01:08:03,840 BASED ON MOUSE MODELS AND WE 1360 01:08:03,840 --> 01:08:05,400 WANTED TO DO A COMPARISON BUT 1361 01:08:05,400 --> 01:08:08,280 PREVIOUS METHODS HAVE 1362 01:08:08,280 --> 01:08:08,720 LIMITATION. 1363 01:08:08,720 --> 01:08:10,440 AN EARLIER METHOD DEVELOPED OVER 1364 01:08:10,440 --> 01:08:16,240 40 YEARS AGO AT UCLA CAN OBTAIN 1365 01:08:16,240 --> 01:08:19,440 HUMAN ASTROCYTES AND WITH THIS 1366 01:08:19,440 --> 01:08:21,280 METHOD YOU GROW ALL CELLS FROM 1367 01:08:21,280 --> 01:08:22,840 THE BRAIN IN THE SERUM 1368 01:08:22,840 --> 01:08:24,400 CONTAINING MEDIUM AND AFTER 1369 01:08:24,400 --> 01:08:28,200 WEEKS OF CULTURE, MOST CELL 1370 01:08:28,200 --> 01:08:30,600 TYPES DIE EXCEPT A GROUP OF 1371 01:08:30,600 --> 01:08:32,840 ASTROCYTE PROGENITOR TYPE CELLS 1372 01:08:32,840 --> 01:08:35,400 THAT PROLIFERATE IN VITRO AND 1373 01:08:35,400 --> 01:08:37,240 THEY LOOK POLYGONAL IN SHAPE AND 1374 01:08:37,240 --> 01:08:40,760 DIFFERENT IN THEIR MORPHOLOGY 1375 01:08:40,760 --> 01:08:42,240 FROM THE IN VIVO PROCESS IN 1376 01:08:42,240 --> 01:08:44,440 MORPHOLOGY OF ASTROCYTES. 1377 01:08:44,440 --> 01:08:45,960 IN ADDITION TO MORPHOLOGICAL 1378 01:08:45,960 --> 01:08:47,240 DIFFERENCES THERE'S ALSO OTHER 1379 01:08:47,240 --> 01:08:50,240 LIMITATIONS FOR THIS METHOD. 1380 01:08:50,240 --> 01:08:52,240 FIRST, THIS IS NOT AN ACUTE PUR 1381 01:08:52,240 --> 01:08:53,800 FICTION METHOD. 1382 01:08:53,800 --> 01:08:55,640 YOU ONLY GET ASTROCYTES AFTER 1383 01:08:55,640 --> 01:08:58,200 DAYS TO WEEKS OF CULTURE AND 1384 01:08:58,200 --> 01:08:58,880 EXPANSION. 1385 01:08:58,880 --> 01:09:00,040 IN THIS PROCESS GENE EXPRESSION 1386 01:09:00,040 --> 01:09:01,720 COULD CHANGE. 1387 01:09:01,720 --> 01:09:05,960 INDEED WE ALREADY KNOW SERUM CAN 1388 01:09:05,960 --> 01:09:12,640 INDUCE REACTIVE ASTROGLIOSIS AND 1389 01:09:12,640 --> 01:09:14,320 IT MAKES IT MORE DIFFICULT TO 1390 01:09:14,320 --> 01:09:16,840 STUDY HOW RESTING HEALTHY 1391 01:09:16,840 --> 01:09:18,760 ASTROCYTES CHANGE IN RESPONSE TO 1392 01:09:18,760 --> 01:09:29,800 DISEASE-RELEVANT GENERATION. 1393 01:09:29,800 --> 01:09:32,920 ALSO THESE CELLS RELY ON A 1394 01:09:32,920 --> 01:09:34,840 CERTAIN GROUP OF ASTROCYTES 1395 01:09:34,840 --> 01:09:37,640 MAKING THEM MORE DIFFICULT TO 1396 01:09:37,640 --> 01:09:39,920 STUDY MATURE PROPERTIES AND 1397 01:09:39,920 --> 01:09:40,880 ASSESS PROPERTIES ACROSS THE 1398 01:09:40,880 --> 01:09:42,120 LIFE SPAN. 1399 01:09:42,120 --> 01:09:43,960 SO SINCE WE DEVELOPED 1400 01:09:43,960 --> 01:09:45,040 IMMUNOPANNING METHOD WE OVERCAME 1401 01:09:45,040 --> 01:09:47,640 ALL THE PROBLEMS AND WE WERE 1402 01:09:47,640 --> 01:09:50,200 ABLE TO COMPARE HUMAN VERSUS 1403 01:09:50,200 --> 01:09:52,840 MOUSE ASTROCYTES. 1404 01:09:52,840 --> 01:09:56,200 FIRST, I'LL SHOW YOU 1405 01:09:56,200 --> 01:09:58,640 PURIFICATION OF HUMAN MOUSE 1406 01:09:58,640 --> 01:10:00,000 ASTROCYTE FROM HEALTHY BRAINS 1407 01:10:00,000 --> 01:10:03,880 AND ASSESSING THEIR 1408 01:10:03,880 --> 01:10:06,200 TRANSCRIPTOME PROFILES USING 1409 01:10:06,200 --> 01:10:10,200 WITHOUT CULTURE AND WE FOUND 1410 01:10:10,200 --> 01:10:17,480 THERE ARE SUBSTANTIAL 1411 01:10:17,480 --> 01:10:19,680 CONSERVATION AND HERE I 1412 01:10:19,680 --> 01:10:20,840 HIGHLIGHTED SOME GENES SHOWING 1413 01:10:20,840 --> 01:10:24,400 THE HIGHER EXPRESSION IN MOUSE 1414 01:10:24,400 --> 01:10:30,760 ASTROCYTES AND MANY OF THEM ARE 1415 01:10:30,760 --> 01:10:34,640 LOCATED WITH MITOCHONDRIA 1416 01:10:34,640 --> 01:10:36,240 INVOLVED AND IF YOU LOOK AT 1417 01:10:36,240 --> 01:10:40,120 HIGHER IN HUMAN ASTROCYTES THAN 1418 01:10:40,120 --> 01:10:43,760 IN MOUSE AND MANY GENES ARE 1419 01:10:43,760 --> 01:10:46,160 SECRETED CYTOKINE MOLECULES IN 1420 01:10:46,160 --> 01:10:48,760 DEFENSE RESPONSE AND WE 1421 01:10:48,760 --> 01:10:51,040 IDENTIFIED THE GENE SIGNATURES 1422 01:10:51,040 --> 01:10:54,480 AND WONDERED WHETHER THEY'RE 1423 01:10:54,480 --> 01:10:56,200 INTRINSICALLY PROGRAMMED OR 1424 01:10:56,200 --> 01:10:58,800 INFLUENCED BY THEIR DIFFERENCES 1425 01:10:58,800 --> 01:11:00,440 IN BRAIN ENVIRONMENT SUCH AS 1426 01:11:00,440 --> 01:11:02,120 DIFFERENCES IN NEURONS. 1427 01:11:02,120 --> 01:11:06,240 AND TO ADDRESS THIS QUESTION A 1428 01:11:06,240 --> 01:11:09,040 TALENTED POST-DOC COLLABORATED 1429 01:11:09,040 --> 01:11:10,920 WITH OTHER LABS AND TRANSPLANTED 1430 01:11:10,920 --> 01:11:14,040 HUMAN ASTROCYTES INTO MOUSE 1431 01:11:14,040 --> 01:11:18,040 BRAINS AND ALLOWED THE CELLS TO 1432 01:11:18,040 --> 01:11:20,520 FOR A FEW MONTHS IN MOUSE BRAINS 1433 01:11:20,520 --> 01:11:22,200 AND THEN PERFORMED IMMUNOPANNING 1434 01:11:22,200 --> 01:11:25,640 TO ISOLATE THEM AND THEN 1435 01:11:25,640 --> 01:11:26,920 PERFORMED RNA SEQUENCING AND WE 1436 01:11:26,920 --> 01:11:32,440 FOUND THE HUMAN ASTROCYTES GROWN 1437 01:11:32,440 --> 01:11:34,040 IN THE MOUSE HOST BRAIN 1438 01:11:34,040 --> 01:11:36,320 ENVIRONMENT HIGHLY RESEMBLE 1439 01:11:36,320 --> 01:11:38,960 HUMAN IN VIVO ASTROCYTES 1440 01:11:38,960 --> 01:11:40,840 DEMONSTRATING THE HUMAN 1441 01:11:40,840 --> 01:11:42,440 SIGNATURE ARE LARGELY 1442 01:11:42,440 --> 01:11:44,000 INTRINSICALLY PROGRAMMED. 1443 01:11:44,000 --> 01:11:46,680 AND SINCE ASTROCYTE CHANGED 1444 01:11:46,680 --> 01:11:48,880 THEIR PROPERTIES AND DISEASES IN 1445 01:11:48,880 --> 01:11:50,120 INJURIES WE'RE INTERESTED IN HOW 1446 01:11:50,120 --> 01:11:52,200 THE CHANGES ARE SIMILAR OR 1447 01:11:52,200 --> 01:11:53,640 DIFFERENT BETWEEN HUMAN AND 1448 01:11:53,640 --> 01:11:56,800 MOUSE ASTROCYTES. 1449 01:11:56,800 --> 01:12:00,480 WITH IMMUNOPANNING PURIFICATION 1450 01:12:00,480 --> 01:12:02,280 METHOD WE CAN COMPARE THE MICE 1451 01:12:02,280 --> 01:12:03,760 ON THE CULTURE CONDITIONS AND 1452 01:12:03,760 --> 01:12:06,320 TREAT THEM WITH DISEASE-RELEVANT 1453 01:12:06,320 --> 01:12:07,840 STIMULATIONS AND EXAMINE HOW 1454 01:12:07,840 --> 01:12:09,920 THEY CHANGE AND THIS IS WORK LED 1455 01:12:09,920 --> 01:12:15,040 BY A TALENTED POST-DOC IN THE 1456 01:12:15,040 --> 01:12:15,320 LAB. 1457 01:12:15,320 --> 01:12:18,360 AND THE CELLS WERE TREATED WITH 1458 01:12:18,360 --> 01:12:19,920 STIMULATION AND FOR THE INTEREST 1459 01:12:19,920 --> 01:12:22,040 OF TIME I'LL ONLY MENTION 1460 01:12:22,040 --> 01:12:24,240 HYDROGEN PEROXIDE WHICH 1461 01:12:24,240 --> 01:12:25,720 INTRODUCED OXIDATIVE STRESS. 1462 01:12:25,720 --> 01:12:27,400 WE FOCUSSED ON THIS STRESS 1463 01:12:27,400 --> 01:12:30,200 BECAUSE IT'S A KEY PATHOLOGICAL 1464 01:12:30,200 --> 01:12:34,040 COMPONENT OF MANY TYPES OF 1465 01:12:34,040 --> 01:12:34,520 NEUROLOGICAL CONDITIONS 1466 01:12:34,520 --> 01:12:35,960 INCLUDING NEURODEGENERATION AND 1467 01:12:35,960 --> 01:12:42,760 STROKE AND TRAUMATIC INJURY. 1468 01:12:42,760 --> 01:12:50,800 AND SAW THE STRIKING DIFFERENCE 1469 01:12:50,800 --> 01:12:52,040 IN SURVIVAL. 1470 01:12:52,040 --> 01:12:56,560 THE HUMAN ASTROCYTES ARE MORE 1471 01:12:56,560 --> 01:12:58,240 SUSCEPTIBLE TO OXIDATIVE STRESS 1472 01:12:58,240 --> 01:13:00,800 THAN MOUSE ASTROCYTES AND DID 1473 01:13:00,800 --> 01:13:02,440 METABOLISM AND MOLECULAR STUDIES 1474 01:13:02,440 --> 01:13:03,720 COLORED IN THE RECENTLY 1475 01:13:03,720 --> 01:13:06,240 PUBLISHED PAPER NOT GOING TO 1476 01:13:06,240 --> 01:13:08,640 INTO DETAIL BUT I JUST WANT TO 1477 01:13:08,640 --> 01:13:10,840 SAY THAT THESE DIFFERENCES COULD 1478 01:13:10,840 --> 01:13:13,400 HAVE IMPORTANT IMPLICATIONS FOR 1479 01:13:13,400 --> 01:13:15,040 MODELLING OF DISEASE. 1480 01:13:15,040 --> 01:13:17,720 MANY LABS HAVE NOTICED THAT 1481 01:13:17,720 --> 01:13:22,280 COMMONLY USED MOUSE MODELS OF 1482 01:13:22,280 --> 01:13:23,600 NEURODEGENERATION HAVE MILDER 1483 01:13:23,600 --> 01:13:24,920 PHENOTYPE COMPARED WITH HUMAN 1484 01:13:24,920 --> 01:13:25,320 PATIENTS. 1485 01:13:25,320 --> 01:13:26,200 WHY IS THAT? 1486 01:13:26,200 --> 01:13:28,040 WE THINK IT'S PROBABLY BECAUSE 1487 01:13:28,040 --> 01:13:30,400 MULTIPLE REASONS AND ONE OF THE 1488 01:13:30,400 --> 01:13:32,400 REASONS SUGGESTED BY OUR FUNDING 1489 01:13:32,400 --> 01:13:35,640 IS THAT MOUSE ASTROCYTES MAY BE 1490 01:13:35,640 --> 01:13:37,800 BETTER AT SURVIVING UNDER 1491 01:13:37,800 --> 01:13:39,160 OXIDATIVE STRESS AND IN OUR 1492 01:13:39,160 --> 01:13:40,560 MOLECULAR STUDIES COMPARE THE 1493 01:13:40,560 --> 01:13:41,720 DIFFERENCES IN THE PATHWAYS 1494 01:13:41,720 --> 01:13:43,760 RELATED TO OXIDATIVE STRESS, WE 1495 01:13:43,760 --> 01:13:48,880 CAN SUGGEST WAYS TO IMPROVE 1496 01:13:48,880 --> 01:13:51,240 MODELLING OF NEURODEGENERATION 1497 01:13:51,240 --> 01:13:52,520 INCLUDING MOUSE MODELS. 1498 01:13:52,520 --> 01:13:54,000 IN THE SECOND EXAMPLE OF 1499 01:13:54,000 --> 01:13:57,920 APPLICATION OF IMMUNOPANNING 1500 01:13:57,920 --> 01:13:58,960 PURIFICATION OF GLIAL CELLS 1501 01:13:58,960 --> 01:14:09,160 WE'RE LOOKING AT HOW HUMAN CELL 1502 01:14:09,160 --> 01:14:09,760 TRANSCRIPTOMICS CHANGE WITH 1503 01:14:09,760 --> 01:14:11,280 COLLABORATION WITH UCLA AND 1504 01:14:11,280 --> 01:14:11,840 OTHER INSTITUTIONS. 1505 01:14:11,840 --> 01:14:15,000 OVER THE YEARS WE AND OUR 1506 01:14:15,000 --> 01:14:16,920 COLLABORATORS HAVE COLLECTED 1507 01:14:16,920 --> 01:14:24,480 FRESH SURGICALLY RECEPTED BRAIN 1508 01:14:24,480 --> 01:14:30,200 TISSUE AND WE WERE ABLE TO PURE 1509 01:14:30,200 --> 01:14:32,840 PURIFY THE ASTROCYTE IMMUNO 1510 01:14:32,840 --> 01:14:35,280 IMMUNOPANNING AND WE LOOKED AT 1511 01:14:35,280 --> 01:14:38,680 THE ASTROCYTES ACROSS 1512 01:14:38,680 --> 01:14:41,960 DEVELOPMENT AND WE NOTICED A 1513 01:14:41,960 --> 01:14:44,840 SHIFT AT TRANSCRIPTOME AT ABOUT 1514 01:14:44,840 --> 01:14:46,800 8 TO 12 YEARS OF AGE AND OUR 1515 01:14:46,800 --> 01:14:51,480 FAVORITE HYPOTHESIS IS IT'S THE 1516 01:14:51,480 --> 01:14:54,080 PEAK OF SYNAPTIC GENESIS WHERE 1517 01:14:54,080 --> 01:15:00,320 AFTER IT'S A PEAK OF SYNAPSE 1518 01:15:00,320 --> 01:15:04,760 PRUNING AND AS TROECYTES HAVE 1519 01:15:04,760 --> 01:15:06,360 DIFFERENT DIFFERENT STAGES IN 1520 01:15:06,360 --> 01:15:08,720 SUPPORT OF THE CIRCUITS AND WE 1521 01:15:08,720 --> 01:15:11,640 ALSO LOOKED AT ASTROCYTE CHANGES 1522 01:15:11,640 --> 01:15:14,040 IN YOUNG ADULTS VERSUS MORE 1523 01:15:14,040 --> 01:15:17,280 MATURE ADULTS AND WE SEE WITH 1524 01:15:17,280 --> 01:15:18,800 AGE MANY GENES INVOLVED IN 1525 01:15:18,800 --> 01:15:23,240 ENERGY METABOLISM ARE GOING DOWN 1526 01:15:23,240 --> 01:15:25,000 ALSO ARE GENES INVOLVED IN 1527 01:15:25,000 --> 01:15:27,720 INTERACTIONS BETWEEN ASTROCYTES 1528 01:15:27,720 --> 01:15:30,520 AND SYNAPSES. 1529 01:15:30,520 --> 01:15:36,080 THIS IS A GLUTAMATE TRANSPORTER 1530 01:15:36,080 --> 01:15:47,280 DOWNLETTINGED -- DOWN REGULATED 1531 01:15:47,280 --> 01:15:49,880 WITH SOME ASTROCYTES AND 1532 01:15:49,880 --> 01:15:51,480 INVOLVED IN SENESCENCE. 1533 01:15:51,480 --> 01:15:53,200 I'LL SUMMARIZE THE STRENGTH AND 1534 01:15:53,200 --> 01:15:58,120 LIMITATIONS OF IMMUNOPANNING 1535 01:15:58,120 --> 01:16:00,800 PURIFICATION AND RNA SEQ 1536 01:16:00,800 --> 01:16:01,920 PROFILING OF GLIAL CELLS 1537 01:16:01,920 --> 01:16:03,360 COMPARED TO RELATED METHODS. 1538 01:16:03,360 --> 01:16:06,320 A SIMILAR METHOD TO PURIFY RNA 1539 01:16:06,320 --> 01:16:09,760 FROM A SELECTED CELL POPULATION 1540 01:16:09,760 --> 01:16:13,480 IS RIBOTAG AND HOLD DOWN A 1541 01:16:13,480 --> 01:16:16,400 RIBOSOMAL PROTEIN AND SEQUENCE 1542 01:16:16,400 --> 01:16:18,480 THE RNA ASSOCIATED. 1543 01:16:18,480 --> 01:16:21,040 AND ONE ADVANTAGE OF THE 1544 01:16:21,040 --> 01:16:23,080 IMMUNOPANNING COMPARED TO 1545 01:16:23,080 --> 01:16:26,720 RIBOTAG IS IMMUNOPANNING DOES 1546 01:16:26,720 --> 01:16:30,640 NOT REQUIRE TRANSGENIC MOUSE 1547 01:16:30,640 --> 01:16:32,800 STRAINS OR VIRAL VECTOR 1548 01:16:32,800 --> 01:16:34,240 TRANSDUCTION AND THIS IS 1549 01:16:34,240 --> 01:16:37,840 IMPORTANT FOR GENETICALLY IN 1550 01:16:37,840 --> 01:16:39,040 TRACTABLE SPECIES LIKE HUMANS 1551 01:16:39,040 --> 01:16:42,200 AND FOR MOUSE STUDIES IT'S 1552 01:16:42,200 --> 01:16:43,680 USEFUL WHEN HAVE YOU AGED MICE 1553 01:16:43,680 --> 01:16:46,200 FOR EXAMPLE OR A MOUSE MODEL OF 1554 01:16:46,200 --> 01:16:48,000 DISEASE SO YOU CAN DO 1555 01:16:48,000 --> 01:16:49,000 IMMUNOPANNING WITH THE MICE YOU 1556 01:16:49,000 --> 01:16:50,800 HAVE RIGHT AWAY WITHOUT HAVING 1557 01:16:50,800 --> 01:16:54,200 TO CROSS IT TO ANYTHING. 1558 01:16:54,200 --> 01:16:57,720 WHERE RIBO TAG REQUIRES TRANS 1559 01:16:57,720 --> 01:16:58,040 DISCUSSION. 1560 01:16:58,040 --> 01:17:00,840 AND IMMUNOPANNING OBTAINS WHOLE 1561 01:17:00,840 --> 01:17:04,400 CELLS WHERE IT CAN EXTRACT WHOLE 1562 01:17:04,400 --> 01:17:09,040 RNA AND RIBOTAG IS ACTIVELY 1563 01:17:09,040 --> 01:17:10,880 TRANSLATING RNA AND LOOKING AT A 1564 01:17:10,880 --> 01:17:12,200 DIFFERENT POPULATION IN THE 1565 01:17:12,200 --> 01:17:16,720 DYNAMICS OF RNA. 1566 01:17:16,720 --> 01:17:19,000 AND ONE ADVANTAGE OF RIBOTAG IS 1567 01:17:19,000 --> 01:17:23,840 YOU CAN TARGET ANY CELL TYPE 1568 01:17:23,840 --> 01:17:28,920 LABELLED BY A CREE LINE AND WE 1569 01:17:28,920 --> 01:17:31,480 LOOKED AT IMMUNOPANNING IN MOUSE 1570 01:17:31,480 --> 01:17:33,240 BUT HAVEN'T FOCUSSED ON 1571 01:17:33,240 --> 01:17:35,880 DIFFERENT SUBTYPES OF NEURONS 1572 01:17:35,880 --> 01:17:36,840 AND THAT'S NOT AVAILABLE TO 1573 01:17:36,840 --> 01:17:41,960 DIFFERENT CELL TYPES. 1574 01:17:41,960 --> 01:17:44,360 AND I'D ALSO LIKE TO COMPARE 1575 01:17:44,360 --> 01:17:52,240 IMMUNOPANNING COMPARED TO SINGLE 1576 01:17:52,240 --> 01:17:54,240 CELL NUCLEUS SEQ. 1577 01:17:54,240 --> 01:17:57,960 WE PRODUCED CULTURES OF PURIFIED 1578 01:17:57,960 --> 01:17:59,000 CELLS AND THAT'S IMPORTANT FOR 1579 01:17:59,000 --> 01:18:04,800 OUR STUDY OF GLIA FUNCTION FROM 1580 01:18:04,800 --> 01:18:07,320 MOUSE AND HUMANS WHEREAS FOR 1581 01:18:07,320 --> 01:18:12,840 SINGLE CELL RNA SIEQ THE CULTURE 1582 01:18:12,840 --> 01:18:18,040 NOT ONE OF THE GOALS AND THIS 1583 01:18:18,040 --> 01:18:22,520 METHOD REQUIRES FRESH TISSUE AND 1584 01:18:22,520 --> 01:18:26,680 THAT'S NOT AN ISSUE FOR HUMAN 1585 01:18:26,680 --> 01:18:28,360 STUDIES BUT FOR MOUSE IT'S 1586 01:18:28,360 --> 01:18:30,400 DIFFERENT AND WITH IMMUNOPANNING 1587 01:18:30,400 --> 01:18:32,840 WE GET A POPULATION OF CELLS AND 1588 01:18:32,840 --> 01:18:37,400 WITH SINGLE CELL APPROACHES 1589 01:18:37,400 --> 01:18:38,120 THERE'S MORE INFORMATION FOR SUB 1590 01:18:38,120 --> 01:18:40,040 POPULATION DIVERSITY. 1591 01:18:40,040 --> 01:18:43,640 LASTLY, I WANT TO SAY WITH 1592 01:18:43,640 --> 01:18:48,800 EITHER METHOD IT'S CRITICAL TO 1593 01:18:48,800 --> 01:18:54,240 VALIDATE FINDINGS USING RNA 1594 01:18:54,240 --> 01:19:02,640 SCOPE ORTHOLOGOUS METHODS AND 1595 01:19:02,640 --> 01:19:04,480 I'D LIKE TO THANK OUR 1596 01:19:04,480 --> 01:19:06,880 COLLABORATORS AND THE FORMER 1597 01:19:06,880 --> 01:19:08,560 BARRES LAB MEMBERS AND FUNDING 1598 01:19:08,560 --> 01:19:10,200 AGENCIES. 1599 01:19:10,200 --> 01:19:13,640 THANK YOU. 1600 01:19:13,640 --> 01:19:14,240 >> TERRIFIC, THANK YOU VERY 1601 01:19:14,240 --> 01:19:15,480 MUCH. 1602 01:19:15,480 --> 01:19:18,360 SO WE'LL MOVE ON TO OUR LAST 1603 01:19:18,360 --> 01:19:21,200 SPEAKER IN THIS PART OF THE 1604 01:19:21,200 --> 01:19:21,400 MEETING. 1605 01:19:21,400 --> 01:19:27,040 ED LEIN FROM THE ALLEN INSTITUTE 1606 01:19:27,040 --> 01:19:29,360 IN SEATTLE. 1607 01:19:29,360 --> 01:19:31,840 ED DID HIS Ph.D. AT U.C. 1608 01:19:31,840 --> 01:19:39,160 BERKELEY AND DID HIS POST-DOC 1609 01:19:39,160 --> 01:19:41,800 AND HAS BEEN AT THE ALLEN SINCE 1610 01:19:41,800 --> 01:19:44,400 2004 AND HAS LED A NUMBER OF 1611 01:19:44,400 --> 01:19:47,360 REALLY AMAZING PROJECTS THERE 1612 01:19:47,360 --> 01:19:50,160 THAT OF COURSE LATELY HAVE 1613 01:19:50,160 --> 01:19:53,240 HUGELY PROFITED FROM THE ADVENT 1614 01:19:53,240 --> 01:19:56,240 OF SINGLE CELL TECHNOLOGY. 1615 01:19:56,240 --> 01:20:01,360 THE RESOURCES THE ALLEN 1616 01:20:01,360 --> 01:20:06,200 INSTITUTE AND ED HAVE 1617 01:20:06,200 --> 01:20:07,120 ESTABLISHED REACHING LEGENDARY 1618 01:20:07,120 --> 01:20:09,400 STATUS WE ALL USE IN ONE FORM OR 1619 01:20:09,400 --> 01:20:10,560 ANOTHER AND EXCITED TO HEAR 1620 01:20:10,560 --> 01:20:13,880 ABOUT HIS LATEST EFFORTS. 1621 01:20:13,880 --> 01:20:14,280 ED, TAKE IT AWAY. 1622 01:20:14,280 --> 01:20:44,720 >> THANK YOU. 1623 01:20:44,720 --> 01:20:46,280 THANK YOU FOR THE OPPORTUNITY 1624 01:20:46,280 --> 01:20:49,840 AND FOR THOSE WHO LAID OUT THE 1625 01:20:49,840 --> 01:20:51,920 TOOLS FOR STUDYING DIVERSITY IN 1626 01:20:51,920 --> 01:20:52,960 THE BRAIN. 1627 01:20:52,960 --> 01:20:54,160 I'D LIKE TO TAKE THE OPPORTUNITY 1628 01:20:54,160 --> 01:20:58,240 TO REPRESENT THE WORK WE'VE BEEN 1629 01:20:58,240 --> 01:20:59,520 DOING AS PART OF THE BRAIN 1630 01:20:59,520 --> 01:21:01,000 INITIATE NETWORK WITH A 1631 01:21:01,000 --> 01:21:03,320 PARTICULAR EMPHASIS ON THE ADULT 1632 01:21:03,320 --> 01:21:06,240 BRAIN AND ON USING THE TOOLS TO 1633 01:21:06,240 --> 01:21:08,800 BE ABLE TO UNDERSTAND DIVERSITY 1634 01:21:08,800 --> 01:21:13,960 IN HUMAN TISSUES OR TISSUES IN 1635 01:21:13,960 --> 01:21:17,280 NON-GENETICALLY TRACTABLE MODEL 1636 01:21:17,280 --> 01:21:17,560 ORGANISM. 1637 01:21:17,560 --> 01:21:19,640 THERE'S DEVELOPMENT AND AGING 1638 01:21:19,640 --> 01:21:21,640 STUDIES IN OTHER EFFORTS WHICH 1639 01:21:21,640 --> 01:21:23,920 USE THESE SAME TOOLS AND BUILD 1640 01:21:23,920 --> 01:21:26,200 OFF THE REFERENCE BUT I'LL FOCUS 1641 01:21:26,200 --> 01:21:31,240 MAINLY ON THE ADULT REFERENCE 1642 01:21:31,240 --> 01:21:33,080 TODAY AS THE RELATIVELY STABLE 1643 01:21:33,080 --> 01:21:34,240 MIDDLE POINTS OF THE LIFE SPAN 1644 01:21:34,240 --> 01:21:39,120 THAT COULD BE THE TARGET FOR 1645 01:21:39,120 --> 01:21:41,040 AGING STUDIES. 1646 01:21:41,040 --> 01:21:42,760 OLIVER, TO BUILD OFF YOUR 1647 01:21:42,760 --> 01:21:44,920 COMMENTS, PROGRESS DEPENDS ON 1648 01:21:44,920 --> 01:21:45,240 TECHNOLOGY. 1649 01:21:45,240 --> 01:21:48,560 AND THIS IS CERTAINLY THE CASE 1650 01:21:48,560 --> 01:21:52,240 IN TRYING TO BUILD CELL ATLASES 1651 01:21:52,240 --> 01:21:55,720 AND TRY TO MOVE THEM TO THINGS 1652 01:21:55,720 --> 01:21:58,240 THAT COULD BE STUDIED IN HUMAN 1653 01:21:58,240 --> 01:22:00,760 BRAIN AND THE TECHNOLOGIES HAVE 1654 01:22:00,760 --> 01:22:03,200 DRAMATIC PROCESS FROM THE STATE 1655 01:22:03,200 --> 01:22:05,360 OF FIVE YEARS AGO IN BEING ABLE 1656 01:22:05,360 --> 01:22:07,640 TO DISSECT CELLULAR DIVERSITY IN 1657 01:22:07,640 --> 01:22:12,880 A VARIETY OF BRAIN TISSUES. 1658 01:22:12,880 --> 01:22:14,880 SOME OF THESE ARE FAIRLY MUNDANE 1659 01:22:14,880 --> 01:22:16,480 IN TISSUE PREPARATION BUT 1660 01:22:16,480 --> 01:22:22,200 RELEVANT IN HUMAN STUDIES AND 1661 01:22:22,200 --> 01:22:24,080 THE COHORT OF SINGLE CELL 1662 01:22:24,080 --> 01:22:26,040 TECHNOLOGIES AND TRANSCRIPTOMICS 1663 01:22:26,040 --> 01:22:32,760 AND EPIGENOMICS AND SPECIAL 1664 01:22:32,760 --> 01:22:34,200 TRANSCRIPTOMICS AND FUNCTIONAL 1665 01:22:34,200 --> 01:22:37,280 ANALYSIS IN HUMAN LIVING TISSUES 1666 01:22:37,280 --> 01:22:39,560 OR TISSUES OF OTHER MODEL 1667 01:22:39,560 --> 01:22:42,200 ORGANISM AND GENETIC TOOLS THAT 1668 01:22:42,200 --> 01:22:44,000 COME DIRECTLY OUT OF THE SINGLE 1669 01:22:44,000 --> 01:22:49,440 CELL GENOMIC WORK TO ALLOW CELL 1670 01:22:49,440 --> 01:22:53,240 TYPE SPECIFIC MANIPULATION 1671 01:22:53,240 --> 01:22:56,600 ACROSS SPECIES USING A.V.s WITH 1672 01:22:56,600 --> 01:22:56,840 ENHANCERS. 1673 01:22:56,840 --> 01:23:00,840 THE WORK IS BASED AROUND A 1674 01:23:00,840 --> 01:23:04,080 REMARKABLY PRODUCTIVE AND WELL 1675 01:23:04,080 --> 01:23:09,560 ORCHESTRATED CONSORTIUM OR 1676 01:23:09,560 --> 01:23:09,760 BICCN. 1677 01:23:09,760 --> 01:23:13,360 THIS IS A LARGE CONSORTIUM 1678 01:23:13,360 --> 01:23:14,920 AROUND BUILDING CELL ATLASES IN 1679 01:23:14,920 --> 01:23:15,760 THE MOUSE BRAIN AND DEVELOPING 1680 01:23:15,760 --> 01:23:17,560 THE TECHNOLOGIES TO APPLY TO THE 1681 01:23:17,560 --> 01:23:20,000 HUMAN AND NON-HUMAN PRIMATE 1682 01:23:20,000 --> 01:23:26,520 BRAIN AS THE NEXT STAGE TO BE 1683 01:23:26,520 --> 01:23:30,200 CALLED THE BRAIN ATLAS AND THIS 1684 01:23:30,200 --> 01:23:35,080 CAME OUT WITH 17 ARTICLES AND A 1685 01:23:35,080 --> 01:23:36,480 FLAGSHIP DESCRIPTION SHOWING HOW 1686 01:23:36,480 --> 01:23:39,080 DIFFERENT TECHNOLOGIES CAN GAIN 1687 01:23:39,080 --> 01:23:40,560 INSIGHT INTO THE FINE 1688 01:23:40,560 --> 01:23:42,400 ARCHITECTURE AT THE CELLULAR 1689 01:23:42,400 --> 01:23:44,440 LEVEL OF DIFFERENT BRAIN TISSUES 1690 01:23:44,440 --> 01:23:47,600 AND PRIMARILY THE PRIMARY MOTOR 1691 01:23:47,600 --> 01:23:48,640 CORTEX. 1692 01:23:48,640 --> 01:23:51,360 THE IDEA WAS TO TAKE A PAGE FROM 1693 01:23:51,360 --> 01:23:53,440 GENOMICS SUCH AS THE ENCODE 1694 01:23:53,440 --> 01:23:55,080 PROJECT WHICH LOOKED AT 1% OF 1695 01:23:55,080 --> 01:23:57,000 THE GENOME INITIALLY TO LOOK AT 1696 01:23:57,000 --> 01:23:58,840 ONE REGION OF THE BRAIN AND HAVE 1697 01:23:58,840 --> 01:24:00,840 A VARIETY OF RESEARCHERS WITH 1698 01:24:00,840 --> 01:24:02,240 DIFFERENT TECHNOLOGY TO FOCUS ON 1699 01:24:02,240 --> 01:24:05,760 THE ONE REGION TO COME TO A 1700 01:24:05,760 --> 01:24:07,000 SYNTHETIC UNDERSTANDING OF THE 1701 01:24:07,000 --> 01:24:10,680 CELLULAR AND SECTOR ARCHITECTURE 1702 01:24:10,680 --> 01:24:17,240 OF THE REGION AND -- CIRCUIT 1703 01:24:17,240 --> 01:24:17,600 ARCHITECTURE. 1704 01:24:17,600 --> 01:24:20,680 AND IT'S CLEARLY HOMOLOGOUS 1705 01:24:20,680 --> 01:24:24,520 ACROSS REGIONS AND AS I'LL 1706 01:24:24,520 --> 01:24:25,960 DESCRIBE BRIEFLY THE DIFFERENT 1707 01:24:25,960 --> 01:24:28,280 CONTRIBUTORS USED DIFFERENT 1708 01:24:28,280 --> 01:24:32,080 TECHNIQUES FROM SINGLE CELL 1709 01:24:32,080 --> 01:24:34,640 GENOMIC TO SPATIAL ANALYSIS AND 1710 01:24:34,640 --> 01:24:38,200 CONNECTIONAL ANALYSIS TO DERIVE 1711 01:24:38,200 --> 01:24:39,840 AT CELLULAR TAXONOMY AND SPATIAL 1712 01:24:39,840 --> 01:24:43,920 MAP AND CHARACTERIZATION OF THE 1713 01:24:43,920 --> 01:24:44,840 PROPERTIES OF THE CELL TEX. 1714 01:24:44,840 --> 01:24:46,600 THE UNDER PINNING FOR THIS WHICH 1715 01:24:46,600 --> 01:24:48,760 YOU HEARD QUITE A BIT ABOUT ARE 1716 01:24:48,760 --> 01:24:51,040 SINGLE CELL GENOMICS. 1717 01:24:51,040 --> 01:24:57,080 THESE HAVE BEEN GAME CHANGERS 1718 01:24:57,080 --> 01:24:58,120 FOR LOOKING AT OTHER MODEL 1719 01:24:58,120 --> 01:25:00,160 SYSTEMS AND IT'S POSSIBLE TO 1720 01:25:00,160 --> 01:25:03,000 TAKE A TISSUE AND DISASSOCIATED 1721 01:25:03,000 --> 01:25:06,240 AND CHANGE IT AND IN ONE FELL 1722 01:25:06,240 --> 01:25:07,840 SWOOP GENERATE A CLASSIFICATION 1723 01:25:07,840 --> 01:25:09,440 OF CELL TYPES. 1724 01:25:09,440 --> 01:25:11,280 I'LL DESCRIBE THE OUTPUT IN A 1725 01:25:11,280 --> 01:25:14,320 LITTLE BIT BUT CONCEPTUALLY, 1726 01:25:14,320 --> 01:25:15,440 THIS BINDS TO THE COMPLEXITY OF 1727 01:25:15,440 --> 01:25:17,280 THE SYSTEM TO A SERIES OF CELL 1728 01:25:17,280 --> 01:25:18,840 TYPES THAT CAN THEN BE PROBED TO 1729 01:25:18,840 --> 01:25:22,520 UNDERSTAND THE PROPERTIES OF THE 1730 01:25:22,520 --> 01:25:25,600 CELLS. 1731 01:25:25,600 --> 01:25:30,200 FURTHERMORE THAT CAN BE USED TO 1732 01:25:30,200 --> 01:25:32,400 HARNESS CELL TYPE DEREGULATION 1733 01:25:32,400 --> 01:25:34,640 TO FUNCTIONALLY MANIPULATE THE 1734 01:25:34,640 --> 01:25:38,960 CELL TYPE POPULATIONS IN A 1735 01:25:38,960 --> 01:25:42,120 VARIETY OF SYSTEMS INCLUDING 1736 01:25:42,120 --> 01:25:42,320 HUMAN. 1737 01:25:42,320 --> 01:25:45,120 BESIDES THE SINGLE CELL 1738 01:25:45,120 --> 01:25:47,120 ASSOCIATED ANALYSIS, ANOTHER 1739 01:25:47,120 --> 01:25:48,800 TRANSFORMATIVE SET OF TECHNOLOGY 1740 01:25:48,800 --> 01:25:50,200 THE TRANSCRIPTOMIC TECHNOLOGIES 1741 01:25:50,200 --> 01:25:52,000 THAT ALLOW US TO TAKE THE 1742 01:25:52,000 --> 01:25:53,200 SOMEWHAT ABSTRACT CLASSIFICATION 1743 01:25:53,200 --> 01:25:56,800 AND MAP IT BACK TO ITS TISSUE 1744 01:25:56,800 --> 01:25:57,200 ARCHITECTURE. 1745 01:25:57,200 --> 01:26:00,640 SO SHOWING HERE ON THE LEFT SIDE 1746 01:26:00,640 --> 01:26:04,400 IS WORK USING A TECHNIQUE TO 1747 01:26:04,400 --> 01:26:08,760 HAVE A 500 GENE PANEL WHICH CAN 1748 01:26:08,760 --> 01:26:11,120 DISCRIMINATE THE MORE THAN 100 1749 01:26:11,120 --> 01:26:12,640 TYPES OF CELLS IN THE MOUSE 1750 01:26:12,640 --> 01:26:15,360 MOTOR CORTEX AND MAP THEM TO GET 1751 01:26:15,360 --> 01:26:18,600 THE SPATIAL STATISTICS OF THEIR 1752 01:26:18,600 --> 01:26:19,640 ORGANIZATION. 1753 01:26:19,640 --> 01:26:22,720 THIS TECHNOLOGY HAS NOW BEEN 1754 01:26:22,720 --> 01:26:24,120 COMMERCIALIZED THROUGH A COMPANY 1755 01:26:24,120 --> 01:26:26,240 AND WE'VE BEEN USING THIS AND 1756 01:26:26,240 --> 01:26:31,320 HAVE SHOWN IT CAN BE APPLIED TO 1757 01:26:31,320 --> 01:26:33,640 MACAQUE AND HUMAN TISSUES AND 1758 01:26:33,640 --> 01:26:35,080 ALLOWS TO YOU MOVE THE FIRST 1759 01:26:35,080 --> 01:26:37,640 STEP OF DEFINING THE TYPES TO 1760 01:26:37,640 --> 01:26:41,000 THE SECOND STEP OF DEFINING THE 1761 01:26:41,000 --> 01:26:42,200 SPATIAL ORGANIZATION IN 1762 01:26:42,200 --> 01:26:46,080 FUNCTIONAL TISSUE ARCHITECTURE. 1763 01:26:46,080 --> 01:26:48,800 A THIRD MAJOR APPROACH HAS BEEN 1764 01:26:48,800 --> 01:26:52,160 TO CHARACTERIZE THE 1765 01:26:52,160 --> 01:26:54,640 TRANSCRIPTOMICLY DEFINED CELL 1766 01:26:54,640 --> 01:26:57,520 TYPES TO LOOK AT THIN SLICES 1767 01:26:57,520 --> 01:27:00,920 WHERE YOU FORD A CELL AND FILL 1768 01:27:00,920 --> 01:27:03,360 IT WITH A DYE AND CAN MEASURE 1769 01:27:03,360 --> 01:27:06,240 THE TRANSCRIPTOME OF THE CELL 1770 01:27:06,240 --> 01:27:08,560 AND MAP IT BACK TO THE 1771 01:27:08,560 --> 01:27:09,560 TRANSCRIPTOMIC CLASSIFICATION. 1772 01:27:09,560 --> 01:27:14,120 THIS CAN BE SCALED UP TO BE DONE 1773 01:27:14,120 --> 01:27:16,680 SYSTEMATICALLY ACROSS THE 1774 01:27:16,680 --> 01:27:18,080 COMPLEX TISSUE. 1775 01:27:18,080 --> 01:27:20,040 THIS IS SHOWING SUMMARY FIGURES 1776 01:27:20,040 --> 01:27:25,800 LOOKING AT THE MOUSE MOTOR 1777 01:27:25,800 --> 01:27:38,240 CORTEX AND LOOKING AT THE 1778 01:27:38,240 --> 01:27:39,200 PROPERTIES OF CELLS WITH THIS 1779 01:27:39,200 --> 01:27:42,240 TYPE OF APPROACH WHICH HAS NEVER 1780 01:27:42,240 --> 01:27:48,800 BEEN POSSIBLE BEFORE TO DO. 1781 01:27:48,800 --> 01:27:52,040 THERE'S A ROBUST TRANSCRIPTIONAL 1782 01:27:52,040 --> 01:27:53,160 TRANSCRIPTIONALLY BASED 1783 01:27:53,160 --> 01:27:53,880 CLASSIFICATION AND CELL TYPES 1784 01:27:53,880 --> 01:27:58,240 FOR WHICH WE KNOW THE IDENTITIES 1785 01:27:58,240 --> 01:27:59,520 AND THE MOLECULAR SIGNATURES OF 1786 01:27:59,520 --> 01:28:01,560 THESE CELLS AND PROPORTIONS, 1787 01:28:01,560 --> 01:28:02,640 SPATIAL ORGANIZATION OF THE 1788 01:28:02,640 --> 01:28:04,680 CELLS AND THE PROPERTIES OF THE 1789 01:28:04,680 --> 01:28:05,760 CELLS FOR ALL THE CELLS YOU 1790 01:28:05,760 --> 01:28:08,400 HEARD ABOUT TODAY FROM THE OTHER 1791 01:28:08,400 --> 01:28:08,640 SPEAKERS. 1792 01:28:08,640 --> 01:28:12,040 THE EXCITATORY AND INHIBITORY 1793 01:28:12,040 --> 01:28:14,480 AND NON-NEURONAL CELL 1794 01:28:14,480 --> 01:28:14,800 POPULATION. 1795 01:28:14,800 --> 01:28:17,880 WE HAVE A GOOD ATLAS TO SERVE AS 1796 01:28:17,880 --> 01:28:18,880 A REFERENCE FOR THE REST OF THE 1797 01:28:18,880 --> 01:28:27,520 COMMUNITY TO BUILD ON. 1798 01:28:27,520 --> 01:28:29,120 I WANT TO HIGHLIGHT THIS IS THE 1799 01:28:29,120 --> 01:28:31,080 FIRST STAGE AND IT'S A BEEN 1800 01:28:31,080 --> 01:28:33,480 LARGELY EXTENDED TO THE BRAIN 1801 01:28:33,480 --> 01:28:34,360 AND ADULT REFERENCE IS VERY 1802 01:28:34,360 --> 01:28:43,200 QUICKLY BECOMING REALITY. 1803 01:28:43,200 --> 01:28:44,640 ANOTHER IMPORTANT THING IS THEY 1804 01:28:44,640 --> 01:28:50,240 CAN BE APPLIED TO HUMAN, 1805 01:28:50,240 --> 01:28:51,880 MARMOSET AND MOUSE AND CAN GO 1806 01:28:51,880 --> 01:28:53,760 ACROSS SPECIES AND WE CAN BEGIN 1807 01:28:53,760 --> 01:28:57,280 TO SEE THE CRAIG LAR 1808 01:28:57,280 --> 01:28:59,680 ARCHITECTURE IS VERY WELL SERVED 1809 01:28:59,680 --> 01:29:02,640 ACROSS MAMMALIAN ORGANISMS AND 1810 01:29:02,640 --> 01:29:03,800 MOST THE SPECIES DIFFERENCES ARE 1811 01:29:03,800 --> 01:29:06,840 DOWN AT THE FINEST OF TYPE LEVEL 1812 01:29:06,840 --> 01:29:09,160 BUT ALL THE MAJOR BRANCHES ARE 1813 01:29:09,160 --> 01:29:10,840 WELL CONSERVED ACROSS SPECIES. 1814 01:29:10,840 --> 01:29:13,040 THIS IS I THINK HUGELY IMPORTANT 1815 01:29:13,040 --> 01:29:14,720 ON THE ONE HAND BECAUSE IT 1816 01:29:14,720 --> 01:29:16,320 ALLOWS US TO INFER PROPERTIES IN 1817 01:29:16,320 --> 01:29:17,640 HUMAN THAT ARE NOT REALLY 1818 01:29:17,640 --> 01:29:20,120 POSSIBLE TO MEASURE AT THIS 1819 01:29:20,120 --> 01:29:22,680 POINT SUCH AS LONG-RANGE 1820 01:29:22,680 --> 01:29:24,560 PROJECTIONS OR DEVELOPMENTAL 1821 01:29:24,560 --> 01:29:27,040 ORIGINS, FOR EXAMPLE, BUT WE CAN 1822 01:29:27,040 --> 01:29:29,280 INFER THEM BASED ON INFORMATION 1823 01:29:29,280 --> 01:29:30,280 FROM MODEL ORGANISM. 1824 01:29:30,280 --> 01:29:33,280 ON THE OTHER, IT ALLOWS US TO 1825 01:29:33,280 --> 01:29:35,640 COMPARE APPLES TO APPLES AND 1826 01:29:35,640 --> 01:29:37,040 UNDERSTAND TO WHAT EXTENT 1827 01:29:37,040 --> 01:29:40,320 CERTAIN CELLULAR PHENOTYPE ARE 1828 01:29:40,320 --> 01:29:42,160 CONSERVED IN SPECIES. 1829 01:29:42,160 --> 01:29:43,960 IF WE CAN DO THIS IN MOUSE, 1830 01:29:43,960 --> 01:29:45,520 MARMOSET AND HUMAN, YOU CAN DO 1831 01:29:45,520 --> 01:29:50,200 THIS IN ANY SPECIES. 1832 01:29:50,200 --> 01:29:52,400 AND WE'VE BEGUN TO EXPLORE WHAT 1833 01:29:52,400 --> 01:29:56,240 CAN BE LEARNED BY TAKING THE 1834 01:29:56,240 --> 01:29:58,720 IDEA OF CELL TYPE MORPHOLOGY AND 1835 01:29:58,720 --> 01:30:00,280 LOOK ACROSS MORE SPECIES AND 1836 01:30:00,280 --> 01:30:05,400 UNDERSTAND EVOLUTIONARY 1837 01:30:05,400 --> 01:30:15,600 VARIATION AND SIMILAR TO LIMB 1838 01:30:15,600 --> 01:30:16,280 HOMOLOGY WHERE YOU HAVE SPECIES 1839 01:30:16,280 --> 01:30:17,600 VARIATION THAT CAN LEAD TO 1840 01:30:17,600 --> 01:30:18,480 DIFFERENT FUNCTION THE SAME IS 1841 01:30:18,480 --> 01:30:20,720 TRUE FOR CELL TYPES. 1842 01:30:20,720 --> 01:30:23,120 THE OVERALL CELLULAR BLUEPRINT 1843 01:30:23,120 --> 01:30:26,640 IS WELL CONSERVED BUT THEN YOU 1844 01:30:26,640 --> 01:30:28,520 GET SPECIES SPECIALIZATIONS THAT 1845 01:30:28,520 --> 01:30:30,640 CAN BE PROFOUND IN SOME CASES. 1846 01:30:30,640 --> 01:30:38,640 TO GIVE A FEW EXAMPLE EXAMPLES WE'VE 1847 01:30:38,640 --> 01:30:42,000 LOOKED AT PRIMARY MOTOR CORTEX 1848 01:30:42,000 --> 01:30:45,120 FROM ARMADILLO TO HUMAN AND AT 1849 01:30:45,120 --> 01:30:47,400 THE INTERMEDIATE LEVEL OF 1850 01:30:47,400 --> 01:30:49,640 GRANULARITY THE CELLULAR 1851 01:30:49,640 --> 01:30:51,400 BLUEPRINT IS EXTREMELY WELL 1852 01:30:51,400 --> 01:30:53,080 CONSERVED AND WE CAN ALIGN SUB 1853 01:30:53,080 --> 01:30:54,360 CLASSES ACROSS THE SPECIES. 1854 01:30:54,360 --> 01:30:56,760 WE CAN ALSO IDENTIFY HIGHLY 1855 01:30:56,760 --> 01:30:59,600 CONSERVED CELL MARKERS ACROSS 1856 01:30:59,600 --> 01:31:01,360 ALL THE SPECIES WHICH INDICATES 1857 01:31:01,360 --> 01:31:04,040 THESE MUST BE UNDER EVOLUTIONARY 1858 01:31:04,040 --> 01:31:06,200 CONSTRAINT LIKELY TO BE 1859 01:31:06,200 --> 01:31:07,960 FUNCTIONALLY ESSENTIAL FOR CELL 1860 01:31:07,960 --> 01:31:10,760 IDENTITY OR CANONICAL CELL 1861 01:31:10,760 --> 01:31:12,840 PROPERTIES AND THIS INCLUDES 1862 01:31:12,840 --> 01:31:15,000 MANY THINGS LIKE TRANSCRIPTION 1863 01:31:15,000 --> 01:31:15,240 FACTORS. 1864 01:31:15,240 --> 01:31:19,960 ON THE OTHER HAND, IT CAN SHOW 1865 01:31:19,960 --> 01:31:20,440 SIGNIFICANT DIFFERENCES. 1866 01:31:20,440 --> 01:31:22,920 IF ONE LOOKS AT THE EXCITATORY 1867 01:31:22,920 --> 01:31:26,880 AND INHIBITORY RATIO IN THE 1868 01:31:26,880 --> 01:31:29,520 MOTOR CORTEX THE TEXTBOOK NUMBER 1869 01:31:29,520 --> 01:31:34,400 FOR THAT RATIO IS 5:1 COME FROM 1870 01:31:34,400 --> 01:31:35,400 RODENT STUDIES. 1871 01:31:35,400 --> 01:31:37,880 WHEN WE FIRST LOOKED AT PRIMATES 1872 01:31:37,880 --> 01:31:41,720 WE DISCOVERED THE RATIO IS MORE 1873 01:31:41,720 --> 01:31:47,040 LIKE 2:1 IN THE HUMAN AND 1874 01:31:47,040 --> 01:31:48,600 MACAQUE. 1875 01:31:48,600 --> 01:31:53,560 IT'S NOT A PRIMATE 1876 01:31:53,560 --> 01:32:02,640 SPECIALIZATION BUT RODENTS. 1877 01:32:02,640 --> 01:32:05,560 AND YOU CAN ONLY GET FOOLED BY 1878 01:32:05,560 --> 01:32:08,320 LOOK AT A COUPLE SPECIES. 1879 01:32:08,320 --> 01:32:10,200 ANOTHER IMPORTANT OBSERVATION IS 1880 01:32:10,200 --> 01:32:13,720 BESIDES THE CONSERVATION OF THE 1881 01:32:13,720 --> 01:32:15,000 CELL TYPES THE GENE EXPRESSION 1882 01:32:15,000 --> 01:32:16,360 WHICH MAY INCLUDE THINGS LIKE 1883 01:32:16,360 --> 01:32:17,400 RECEPTORS FOR DRUG TARGETS ARE 1884 01:32:17,400 --> 01:32:20,240 NOT CONSERVED IN THEIR 1885 01:32:20,240 --> 01:32:20,560 SPECIFICITY. 1886 01:32:20,560 --> 01:32:26,360 IT SEEMS THE MAJORITY OF GENES 1887 01:32:26,360 --> 01:32:28,640 ARE SPECIES SPECIFIC AND THE 1888 01:32:28,640 --> 01:32:30,160 RELATIVE MINORITY CONSERVED 1889 01:32:30,160 --> 01:32:34,880 ACROSS SPECIES. 1890 01:32:34,880 --> 01:32:35,400 FINAL 1891 01:32:35,400 --> 01:32:36,840 FINALLY THERE'S A SOME 1892 01:32:36,840 --> 01:32:41,800 DIVERSITY. 1893 01:32:41,800 --> 01:32:46,160 AND THE UPPER LAYERS OF THE 1894 01:32:46,160 --> 01:32:48,400 CORTEX ARE EXPANDED IN HUMAN 1895 01:32:48,400 --> 01:32:49,640 CORTICAL EVOLUTION TO INCLUDE 1896 01:32:49,640 --> 01:32:52,400 MORE CELLS THAT COMMUNICATE THE 1897 01:32:52,400 --> 01:32:53,880 CORTEX COMMENSURATE WITH THE 1898 01:32:53,880 --> 01:32:55,240 INFECTIOUS IN CORTICAL AREA AND 1899 01:32:55,240 --> 01:32:59,920 IT TURNS OUT THE INCREASE IN 1900 01:32:59,920 --> 01:33:05,080 SIZE AND IN DEPTH IS ACCOMPANIED 1901 01:33:05,080 --> 01:33:09,640 BY AN INCREASE IN DIVERSITY AND 1902 01:33:09,640 --> 01:33:10,840 SOME DON'T APPEAR TO BE IN THE 1903 01:33:10,840 --> 01:33:22,160 DEEPER PARTS OF THE CORTEX. 1904 01:33:22,160 --> 01:33:24,240 AND WHILE THIS ONE REGION OF 1905 01:33:24,240 --> 01:33:25,640 CORTEX WORKED ITS WAY TO 1906 01:33:25,640 --> 01:33:28,440 COMPLETION, THE REST OF THE 1907 01:33:28,440 --> 01:33:30,400 WHOLE MOUSE BRAIN GOT SEQUENCED 1908 01:33:30,400 --> 01:33:36,280 ESSENTIALLY. 1909 01:33:36,280 --> 01:33:39,480 THIS IS ABOUT 3,000 OR SO 1910 01:33:39,480 --> 01:33:40,160 GENOMICCALLY DEFINED CLUSTERS 1911 01:33:40,160 --> 01:33:51,040 ACROSS THE BRAIN. 1912 01:33:51,040 --> 01:33:53,240 AND THIS IS THE NATURE OF THE 1913 01:33:53,240 --> 01:33:55,000 BEAST IF WE WANT TO UNDERSTAND 1914 01:33:55,000 --> 01:33:56,040 THE FULL LIFE SPAN OF A SYSTEM 1915 01:33:56,040 --> 01:34:02,080 THAT COMPLEX. 1916 01:34:02,080 --> 01:34:04,040 AT THE SAME TIME THE TECHNIQUES 1917 01:34:04,040 --> 01:34:05,320 HAVE BEEN APPLIED TO HUMAN WITH 1918 01:34:05,320 --> 01:34:07,080 A SURVEY ACROSS THE BRAIN AND 1919 01:34:07,080 --> 01:34:08,400 ESTABLISHED THIS CAN BE DONE AT 1920 01:34:08,400 --> 01:34:14,600 THE SAME TYPE OF GRANULARITY IN 1921 01:34:14,600 --> 01:34:17,320 HUMAN AND THIS IS NOW ONE OF THE 1922 01:34:17,320 --> 01:34:21,480 MAJOR FOCUSES OF THE CELL ATLAS 1923 01:34:21,480 --> 01:34:23,680 NETWORK OR BICAN. 1924 01:34:23,680 --> 01:34:28,040 I WANT TO QUICKLY ACKNOWLEDGE 1925 01:34:28,040 --> 01:34:29,400 THE CONTRIBUTIONS OF NIA IN 1926 01:34:29,400 --> 01:34:32,320 FUNDING STUDIES IN MOUSE AND 1927 01:34:32,320 --> 01:34:36,840 ALSO IN HUMAN AT THE ALLEN 1928 01:34:36,840 --> 01:34:39,240 INSTITUTE WE HELP TO RUN A GRANT 1929 01:34:39,240 --> 01:34:43,200 FUNDED BY NIA TO BUILD OFF THE 1930 01:34:43,200 --> 01:34:44,360 BRAIN INITIATIVE CELL CENSUS TO 1931 01:34:44,360 --> 01:34:45,400 UNDERSTAND WHAT HAPPENS IN THE 1932 01:34:45,400 --> 01:34:47,360 COURSE OF DISEASE AND ALSO IN 1933 01:34:47,360 --> 01:34:47,560 AGING. 1934 01:34:47,560 --> 01:34:49,840 I'M NOT REALLY GOING TO SHOW AN 1935 01:34:49,840 --> 01:34:51,080 AGING TRAJECTORY HERE BUT I WANT 1936 01:34:51,080 --> 01:34:54,520 TO POINT OUT WE'RE ABLE TO MAP 1937 01:34:54,520 --> 01:34:56,360 CELLS FROM VERY AGED INDIVIDUALS 1938 01:34:56,360 --> 01:35:00,760 AND INDIVIDUALS WITH ALZHEIMER'S 1939 01:35:00,760 --> 01:35:02,080 DISEASE EFFECTIVELY TO THE 1940 01:35:02,080 --> 01:35:02,760 NEUROTYPICAL REFERENCE FROM 1941 01:35:02,760 --> 01:35:04,120 YOUNGER INDIVIDUALS SHOWING IT'S 1942 01:35:04,120 --> 01:35:06,600 A CONSERVED BLUEPRINT CONSERVED 1943 01:35:06,600 --> 01:35:10,000 ACROSS AGING BUT OF COURSE 1944 01:35:10,000 --> 01:35:10,840 THERE'S AGING AND DISEASE 1945 01:35:10,840 --> 01:35:11,520 SIGNATURES ACROSS THAT AND A 1946 01:35:11,520 --> 01:35:13,000 HOPE IT'S A PARADIGM FOR OTHER 1947 01:35:13,000 --> 01:35:19,320 DISEASES AS WELL. 1948 01:35:19,320 --> 01:35:22,400 AND OPEN DATA ACCESS IS AN 1949 01:35:22,400 --> 01:35:24,280 ESSENTIAL COMPONENT OF THE 1950 01:35:24,280 --> 01:35:25,240 WELL-FUNDED EFFORT TO CREATE A 1951 01:35:25,240 --> 01:35:26,840 REFERENCE FOR THE COMMUNITY AND 1952 01:35:26,840 --> 01:35:28,920 THE BRAIN INITIATIVE REFERENCES 1953 01:35:28,920 --> 01:35:30,240 THROUGH THE BRAIN CELL DATA 1954 01:35:30,240 --> 01:35:34,240 CENTER AND ARCHIVES ALSO AT THE 1955 01:35:34,240 --> 01:35:38,040 ALLEN INSTITUTE ASPIRE TO MAKE 1956 01:35:38,040 --> 01:35:39,120 THESE EASILY ACCESSIBLE TO THE 1957 01:35:39,120 --> 01:35:39,400 COMMUNITY. 1958 01:35:39,400 --> 01:35:40,960 I WANT TO END ON ONE FINAL 1959 01:35:40,960 --> 01:35:42,640 OUTCOME OF THESE CELL ATLASES 1960 01:35:42,640 --> 01:35:46,760 WHICH I THINK WAS NOT ENTIRELY 1961 01:35:46,760 --> 01:35:50,040 ANTICIPATED AT THE OUTSET AND 1962 01:35:50,040 --> 01:35:52,960 THAT'S THE EPIGENOME ATLASES 1963 01:35:52,960 --> 01:35:54,840 LEAD DIRECTLY TO FINDING 1964 01:35:54,840 --> 01:35:56,760 FUNCTIONAL ENHANCER ELEMENTS 1965 01:35:56,760 --> 01:35:59,960 THAT CAN FIT INTO ADENO 1966 01:35:59,960 --> 01:36:01,480 ASSOCIATED ANALYSIS TO ALLOW 1967 01:36:01,480 --> 01:36:07,960 CELL-TYPE SPECIFIC MANIPULATION. 1968 01:36:07,960 --> 01:36:09,440 THE SINGLE CELL EPIGENOMICS CAN 1969 01:36:09,440 --> 01:36:11,240 BE USED TO CLUSTER AND ALIGNED 1970 01:36:11,240 --> 01:36:14,240 TO THE TRANSCRIPTOME AND USE IT 1971 01:36:14,240 --> 01:36:19,280 TO FIND SHORT ENHANCER ELEMENTS 1972 01:36:19,280 --> 01:36:21,000 DISTAL TO GENES ONLY OPEN IN A 1973 01:36:21,000 --> 01:36:22,560 CELL TYPE OF INTEREST AND IT 1974 01:36:22,560 --> 01:36:24,840 TURNS OUT MANY OF THESE ARE 1975 01:36:24,840 --> 01:36:27,400 FUNCTIONAL ENHANCER THAT CAN 1976 01:36:27,400 --> 01:36:29,200 CONFER THAT SPECIFICITY IN OF 1977 01:36:29,200 --> 01:36:29,480 THEMSELVES. 1978 01:36:29,480 --> 01:36:32,040 TO GIVE A FEW EXAMPLES OF THESE 1979 01:36:32,040 --> 01:36:38,040 AND THIS IS ONLY A FEW MUCH MANY 1980 01:36:38,040 --> 01:36:40,040 WE SEEM TO BE ABLE TO TARGET ANY 1981 01:36:40,040 --> 01:36:45,840 CELL WE HAVE THIS TYPE OF 1982 01:36:45,840 --> 01:36:49,240 INFORMATION FOR AND INTERNEURONS 1983 01:36:49,240 --> 01:36:51,440 AND MANY ENHANCERS TURN OUT TO 1984 01:36:51,440 --> 01:36:54,840 BE TO MAINTAIN THE SPECIFICITY 1985 01:36:54,840 --> 01:36:55,640 ACROSS SPECIES. 1986 01:36:55,640 --> 01:36:57,200 WHILE WE DEVELOPED INITIALLY IN 1987 01:36:57,200 --> 01:36:59,560 THE MOUSE, THEY FREQUENTLY 1988 01:36:59,560 --> 01:37:01,840 CONFER THE SAME SPECIFICITY IN 1989 01:37:01,840 --> 01:37:04,240 MONKEY OR IN HUMAN SPLICE. 1990 01:37:04,240 --> 01:37:06,240 THAT'S REALLY A KEY OBSERVATION 1991 01:37:06,240 --> 01:37:09,240 AND KEY THING MOVING FORWARD AND 1992 01:37:09,240 --> 01:37:12,360 ANOTHER PRIORITY FOR THE BRAIN 1993 01:37:12,360 --> 01:37:14,000 INITIATIVE WITH THE 1994 01:37:14,000 --> 01:37:22,240 ARMAMENTARIUM IDEA AND WE HAVE 1995 01:37:22,240 --> 01:37:26,600 SPECIFIC MANIPULATION IN MANY 1996 01:37:26,600 --> 01:37:28,960 MODEL ORGANISMS AND CAN BE USED 1997 01:37:28,960 --> 01:37:30,400 IN ANY THAT'S THE RIGHT MODEL 1998 01:37:30,400 --> 01:37:32,320 FOR A PARTICULAR BEHAVIOR OR 1999 01:37:32,320 --> 01:37:32,560 DISEASE. 2000 01:37:32,560 --> 01:37:34,240 AND FURTHERMORE LOOKING FORWARD 2001 01:37:34,240 --> 01:37:40,000 TO HUMAN APPLICATION, WE ALREADY 2002 01:37:40,000 --> 01:37:42,240 HAVE AVs IN THE CLINIC FOR GENE 2003 01:37:42,240 --> 01:37:44,440 REPLACEMENT AND THERAPY BUT SO 2004 01:37:44,440 --> 01:37:45,400 FAR THEY'RE FAIRLY BLUNT 2005 01:37:45,400 --> 01:37:46,840 INSTRUMENTS BUT NOW WE HAVE THE 2006 01:37:46,840 --> 01:37:49,160 OPPORTUNITY TO BE ABLE TO TARGET 2007 01:37:49,160 --> 01:37:53,320 SPECIFIC CELLS AND DELIVER A 2008 01:37:53,320 --> 01:37:54,560 THERAPEUTIC TO A SPECIFIC CELL 2009 01:37:54,560 --> 01:37:56,120 TO A VULNERABLE POPULATION IN 2010 01:37:56,120 --> 01:37:57,040 THAT DISEASE. 2011 01:37:57,040 --> 01:37:58,920 WE'RE ASKED TO PROVIDE GAPS IN 2012 01:37:58,920 --> 01:38:02,640 OPPORTUNITIES AT THE END HERE 2013 01:38:02,640 --> 01:38:03,880 AND I THINK MY FIRST STATEMENT 2014 01:38:03,880 --> 01:38:09,280 WOULD BE I THINK ALL THESE 2015 01:38:09,280 --> 01:38:10,320 TECHNOLOGICAL ADVANCES CAN BE 2016 01:38:10,320 --> 01:38:12,520 EQUALLY APPLIED TO STUDY 2017 01:38:12,520 --> 01:38:18,080 DEVELOPMENT AND AGING WITH 2018 01:38:18,080 --> 01:38:20,200 SPECIES AND IT'S TO CREATE A 2019 01:38:20,200 --> 01:38:21,080 REFERENCE TO EACH LAB DOESN'T 2020 01:38:21,080 --> 01:38:22,520 NEED TO BE DOING THIS ALL OVER 2021 01:38:22,520 --> 01:38:23,960 AGAIN. 2022 01:38:23,960 --> 01:38:25,240 THEY CAN MAP TO THE REFERENCE 2023 01:38:25,240 --> 01:38:29,680 AND BUILDING KNOWLEDGE BASE 2024 01:38:29,680 --> 01:38:30,880 AROUND THAT REFERENCE. 2025 01:38:30,880 --> 01:38:32,400 THAT WILL INTERN PROVIDES A 2026 01:38:32,400 --> 01:38:34,040 FRAMEWORK FOR MORE TARGETED 2027 01:38:34,040 --> 01:38:36,640 QUESTION TO START TO ASK ABOUT 2028 01:38:36,640 --> 01:38:37,800 THE DEVELOPMENT PROCESSES 2029 01:38:37,800 --> 01:38:41,960 RELEVANT TO THE EMERGENCE OF 2030 01:38:41,960 --> 01:38:44,080 CIRCUITRY OR SUSCEPTIBLE TO 2031 01:38:44,080 --> 01:38:46,320 DISEASE AND PHENOTYPES AND BUILD 2032 01:38:46,320 --> 01:38:48,840 FROM THAT FOUNDATIONAL 2033 01:38:48,840 --> 01:38:51,440 STANDPOINT. 2034 01:38:51,440 --> 01:38:53,840 AND SECONDLY, THESE TOOLS OF 2035 01:38:53,840 --> 01:38:58,680 ENHANCERS CAN BE EQUALLY 2036 01:38:58,680 --> 01:39:01,960 DEVELOPED FOR DEVELOPMENT STAGES 2037 01:39:01,960 --> 01:39:02,880 AND HITTING DIFFERENT CELLS 2038 01:39:02,880 --> 01:39:09,040 PERHAPS PROGENITORS OR NEW 2039 01:39:09,040 --> 01:39:11,800 NEURONS EARLY IN DISEASE WHEN 2040 01:39:11,800 --> 01:39:16,400 IT'S RELEVANT TO DISEASE AND 2041 01:39:16,400 --> 01:39:19,040 THESE NEW TECHNOLOGY HAVE OPENED 2042 01:39:19,040 --> 01:39:21,040 THE DOOR TO BEGIN TO 2043 01:39:21,040 --> 01:39:22,000 CHARACTERIZE BUT THERE'S A LOT 2044 01:39:22,000 --> 01:39:25,240 OF WORK TO DO STILL TO FULLY 2045 01:39:25,240 --> 01:39:26,480 CHARACTERIZE THE HUMAN BRAIN TO 2046 01:39:26,480 --> 01:39:30,960 STUDY HUMAN BRAIN DEVELOPMENT IN 2047 01:39:30,960 --> 01:39:32,080 AGING AND UNDERSTAND HOW IT 2048 01:39:32,080 --> 01:39:33,720 UNDER LIES DIFFERENT DISEASES 2049 01:39:33,720 --> 01:39:36,640 AND DEVELOPMENT DISEASE AS IN 2050 01:39:36,640 --> 01:39:39,560 AGING RELATED DISEASES AND A BIG 2051 01:39:39,560 --> 01:39:41,240 GAP I'D LIKE TO HIGHLIGHT IS 2052 01:39:41,240 --> 01:39:42,640 ACCESS TO HIGH-QUALITY TISSUES 2053 01:39:42,640 --> 01:39:45,240 TO STUDY HUMAN BRAIN DEVELOPMENT 2054 01:39:45,240 --> 01:39:46,840 IN PARTICULAR AND STUDYING HUMAN 2055 01:39:46,840 --> 01:39:49,280 BRAIN AS A WHOLE THAT WOULD 2056 01:39:49,280 --> 01:39:51,600 ACCELERATE THE FIELD IF A 2057 01:39:51,600 --> 01:39:52,480 GREATER EFFORT IN BRAIN DONATION 2058 01:39:52,480 --> 01:39:56,360 COULD BE MADE. 2059 01:39:56,360 --> 01:39:58,720 WITH THAT I'D LIKE TO END AND 2060 01:39:58,720 --> 01:39:59,760 THANK MANY PEOPLE. 2061 01:39:59,760 --> 01:40:02,200 I'VE REPRESENT THE WORK OF MANY 2062 01:40:02,200 --> 01:40:11,600 AT THE ALLEN INSTITUTE AND BRAIN 2063 01:40:11,600 --> 01:40:12,320 INSTITUTE AND THE STAFF MANY 2064 01:40:12,320 --> 01:40:13,400 OTHER COLLABORATORS AND THE 2065 01:40:13,400 --> 01:40:14,200 NATIONAL INSTITUTE ON AGING. 2066 01:40:14,200 --> 01:40:19,400 THANK YOU VERY MUCH. 2067 01:40:19,400 --> 01:40:22,960 >> TERRIFIC, THANK YOU, ED. 2068 01:40:22,960 --> 01:40:23,240 ALL RIGHT. 2069 01:40:23,240 --> 01:40:26,240 SO ALL THE SPEAKER NOW ASKED TO 2070 01:40:26,240 --> 01:40:27,960 PLEASE TURN ON THEIR VIDEO AND 2071 01:40:27,960 --> 01:40:35,680 WE'LL GO AND START WITH THE Q&A 2072 01:40:35,680 --> 01:40:35,920 SESSION. 2073 01:40:35,920 --> 01:40:40,400 I HAVE COLLECTED ALL THE 2074 01:40:40,400 --> 01:40:42,960 QUESTIONS SO FAR FROM THE 2075 01:40:42,960 --> 01:40:43,800 AUDIENCE AND I'LL JUST POSE 2076 01:40:43,800 --> 01:40:48,720 THESE QUESTIONS TO THE 2077 01:40:48,720 --> 01:40:50,080 PRESENTERS IN THE ORDER OF THE 2078 01:40:50,080 --> 01:40:50,400 PRESENTATIONS. 2079 01:40:50,400 --> 01:40:55,400 WE HAVE A QUESTION HERE FOR 2080 01:40:55,400 --> 01:40:55,640 BUSHRA. 2081 01:40:55,640 --> 01:40:58,720 I'LL READ THE QUESTION HERE, IS 2082 01:40:58,720 --> 01:41:10,840 IT FEASIBLE TO USE GESTALT FOR 2083 01:41:10,840 --> 01:41:12,520 ZEBRAFISH MODELS? 2084 01:41:12,520 --> 01:41:17,240 >> IT'S POSSIBLE TO USE GESTALT 2085 01:41:17,240 --> 01:41:20,360 TO LOOK AT MUTANT -- DIFFERENT 2086 01:41:20,360 --> 01:41:26,000 DIFFERENCES IN LINEAGES AND THE 2087 01:41:26,000 --> 01:41:30,880 THING YOU'D HAVE TO GENERATE IS 2088 01:41:30,880 --> 01:41:33,240 A TRANSGENIC LINE TO HAVE THE 2089 01:41:33,240 --> 01:41:36,800 BAR CODE SXRIFD 2090 01:41:42,680 --> 01:41:44,320 EXPRESSED IN THE ZEBRAFISH AND 2091 01:41:44,320 --> 01:41:47,440 IT CAN BE APPLIED TO LOOK AT ANY 2092 01:41:47,440 --> 01:41:49,920 ASPECT OF DEVELOPMENT IN THE 2093 01:41:49,920 --> 01:41:51,640 FISH OR ANY OTHER MODEL ORGANISM 2094 01:41:51,640 --> 01:42:00,920 WHERE YOU CAN ADAPT THIS. 2095 01:42:00,920 --> 01:42:06,280 GENERALLY I'D SAY THE LIMITATION 2096 01:42:06,280 --> 01:42:19,600 WITH GESTALT IS THE MUTATIONS 2097 01:42:19,600 --> 01:42:21,440 MAY NOT BE AS IMPORTANT TO 2098 01:42:21,440 --> 01:42:22,400 UNDERSTANDING THE CHANGES OR 2099 01:42:22,400 --> 01:42:27,960 DIFFERENCES IN THE LINEAGE AFTER 2100 01:42:27,960 --> 01:42:29,640 THE MUTATION STARTED SATURATED. 2101 01:42:29,640 --> 01:42:32,480 THE TIMING IS ALWAYS A BIT OF AN 2102 01:42:32,480 --> 01:42:33,120 OOSH AND WE'D LIKE A SYSTEM TO 2103 01:42:33,120 --> 01:42:34,720 HAVE MORE CONTROL OR SLOW DOWN 2104 01:42:34,720 --> 01:42:35,880 THE RATE AT WHICH MUTATIONS 2105 01:42:35,880 --> 01:42:48,360 OCCUR. 2106 01:42:48,360 --> 01:42:49,480 >> THANK YOU. 2107 01:42:49,480 --> 01:42:52,360 AND WE HAVE A QUESTION HOW LEAKY 2108 01:42:52,360 --> 01:42:55,360 ARE THE PROMOTERS YOU USED AND 2109 01:42:55,360 --> 01:43:00,080 IF IT'S A PROBLEM AND IF SO HOW 2110 01:43:00,080 --> 01:43:02,040 DO YOU USE THIS? 2111 01:43:02,040 --> 01:43:03,880 >> THE INDUCIBLE SYSTEMS ALWAYS 2112 01:43:03,880 --> 01:43:05,960 HAVE SOME LEVEL OF LEAKINESS. 2113 01:43:05,960 --> 01:43:07,600 IN GENERAL THE WAY WE ACCOUNT 2114 01:43:07,600 --> 01:43:12,840 FOR THIS IS AT LEAST WITH 2115 01:43:12,840 --> 01:43:17,040 ZEBRAFISH BECAUSE WE END UP 2116 01:43:17,040 --> 01:43:18,520 SCREENING A LOT OF FISH TO LOOK 2117 01:43:18,520 --> 01:43:23,840 FOR TRANSGENIC ANIMALS WHERE WE 2118 01:43:23,840 --> 01:43:24,520 HAVE TITER REGULATION OF 2119 01:43:24,520 --> 01:43:24,840 EXPRESSION. 2120 01:43:24,840 --> 01:43:37,640 THAT'S ONE WAY OF DOING IT. 2121 01:43:37,640 --> 01:43:42,680 THERE ARE BETTER INDUCIBLE 2122 01:43:42,680 --> 01:43:42,960 RECORDERS. 2123 01:43:42,960 --> 01:43:46,200 PERHAPS USING THE CRAE 2 SYSTEM 2124 01:43:46,200 --> 01:43:48,840 WITH TAMOXIFEN HELPS REGULATE 2125 01:43:48,840 --> 01:43:51,280 THE LEAKINESS TO SOME EXTENT AND 2126 01:43:51,280 --> 01:43:56,120 ALSO GENERATING MORE TIGHTLY 2127 01:43:56,120 --> 01:43:59,440 REGULATE 2128 01:43:59,440 --> 01:44:00,640 REGULATED OTHER SYSTEMS WHERE 2129 01:44:00,640 --> 01:44:02,240 THERE'S BASEBALL ENGINEER OR 2130 01:44:02,240 --> 01:44:05,200 SEQUENCE CHANGES MADE TO MAKE IT 2131 01:44:05,200 --> 01:44:06,040 MORE TITER. 2132 01:44:06,040 --> 01:44:08,480 IN GENERAL GAS LEAKINESS WILL 2133 01:44:08,480 --> 01:44:12,880 ALWAYS BE A SMALL ISSUE IN THE 2134 01:44:12,880 --> 01:44:14,240 SYSTEMS. 2135 01:44:14,240 --> 01:44:17,320 FOR US IT'S NOT A HUGE CONCERN 2136 01:44:17,320 --> 01:44:23,240 TO HAVE A LOW BASAL LEVEL OF 2137 01:44:23,240 --> 01:44:29,000 LEAKINESS AND IN THE DAY THE CAS 2138 01:44:29,000 --> 01:44:31,040 9 NEEDS TO BE TURNED ON TO A 2139 01:44:31,040 --> 01:44:32,240 CERTAIN LEVEL IN ORDER FOR THE 2140 01:44:32,240 --> 01:44:40,480 MUTATIONS TO ACCUMULATE AND IF 2141 01:44:40,480 --> 01:44:43,000 THERE'S A LOW LEVEL IT'S NOT 2142 01:44:43,000 --> 01:44:44,560 SUFFICIENT TO SATURATE THE 2143 01:44:44,560 --> 01:44:46,520 SYSTEM AND YOU CAN ALWAYS HAVE 2144 01:44:46,520 --> 01:44:48,040 ADDITIONAL LEVELS OF INFORMATION 2145 01:44:48,040 --> 01:44:50,520 ON TOP OF ANY BASAL ACTIVITY 2146 01:44:50,520 --> 01:44:51,200 THERE. 2147 01:44:51,200 --> 01:44:55,480 OVERALL, IF THERE IS ACTIVITY AS 2148 01:44:55,480 --> 01:44:58,240 A BACKGROUND IT WILL BE LESS 2149 01:44:58,240 --> 01:45:05,640 THAN 5% OF THE POPULATION. 2150 01:45:05,640 --> 01:45:08,080 >> A FOLLOW-UP TO GESTALT AND 2151 01:45:08,080 --> 01:45:11,960 PARTICULARLY WHAT YOU FOUND, 2152 01:45:11,960 --> 01:45:16,040 YOUR LINEAGE CONCLUSION, IF I 2153 01:45:16,040 --> 01:45:16,840 UNDERSTAND CORRECTLY, THERE'S 2154 01:45:16,840 --> 01:45:19,640 QUITE A BIG DEAL OF LINEAGES. 2155 01:45:19,640 --> 01:45:24,480 WHERE YOU BASICALLY HAVE SIMILAR 2156 01:45:24,480 --> 01:45:26,240 CELL TYPES THAT YOU HAVE FROM 2157 01:45:26,240 --> 01:45:27,640 DIFFERENT LINEAGES. 2158 01:45:27,640 --> 01:45:28,440 IF I UNDERSTAND THIS CORRECTLY 2159 01:45:28,440 --> 01:45:31,480 TO WHAT LEVEL OF GRANULARITY CAN 2160 01:45:31,480 --> 01:45:36,600 YOU TAKE THAT WHICH IS BASICALLY 2161 01:45:36,600 --> 01:45:37,920 ASKING HOW SURE YOU ARE ABOUT 2162 01:45:37,920 --> 01:45:39,640 THE CELL TYPE IDENTITY. 2163 01:45:39,640 --> 01:45:42,840 CAN YOU STATE IF YOU HAVE 2164 01:45:42,840 --> 01:45:44,320 IDENTICAL CELL TYPES THAT COME 2165 01:45:44,320 --> 01:45:46,000 FROM DIFFERENT LINEAGE BRANCHES 2166 01:45:46,000 --> 01:45:49,040 OR CAN YOU ONLY SAY THAT THERE 2167 01:45:49,040 --> 01:45:54,880 ARE SOME REGIONAL CONVERGENCES 2168 01:45:54,880 --> 01:45:57,880 WITH CORE NEURON POPULATION 2169 01:45:57,880 --> 01:45:58,520 DESCRIBED FROM THE DIFFERENT 2170 01:45:58,520 --> 01:46:02,600 LINEAGES. 2171 01:46:02,600 --> 01:46:07,000 >> I THINK IT'S AN IMPORTANT 2172 01:46:07,000 --> 01:46:08,200 QUESTION. 2173 01:46:08,200 --> 01:46:14,200 IN TERMS OF CONVERGENCE, SO 2174 01:46:14,200 --> 01:46:20,320 THERE'S A RESOLUTION LIMIT TO 2175 01:46:20,320 --> 01:46:22,640 GESTALT WHERE THE LINEAGE 2176 01:46:22,640 --> 01:46:25,360 RECORDING DID NOT HAPPEN ACROSS 2177 01:46:25,360 --> 01:46:29,360 THE WHOLE PERIOD OF DEVELOPMENT. 2178 01:46:29,360 --> 01:46:30,920 WE LOOKED AT RELATIVELY EARLY 2179 01:46:30,920 --> 01:46:33,200 DURING BRAIN DEVELOPMENT THE 2180 01:46:33,200 --> 01:46:36,600 DECISIONS MADE AND THERE ARE 2181 01:46:36,600 --> 01:46:38,200 MOST LIKELY ADDITIONAL LEVELS OF 2182 01:46:38,200 --> 01:46:39,920 LINEAGE DIVERGENCES THAT 2183 01:46:39,920 --> 01:46:42,840 OCCURRED AFTER WE FINISHED 2184 01:46:42,840 --> 01:46:44,920 RECORDING THEIR HISTORIES. 2185 01:46:44,920 --> 01:46:50,200 AND SO THOSE WERE LIKELY MISSED. 2186 01:46:50,200 --> 01:46:55,240 SO IN SOME WAYS WE CAN'T RULE 2187 01:46:55,240 --> 01:47:00,080 OUT THE POSSIBILITIES THE CELL 2188 01:47:00,080 --> 01:47:01,240 TYPES DIDN'T OCCUR LATER ON AND 2189 01:47:01,240 --> 01:47:02,440 WE DIDN'T CAPTURE THAT 2190 01:47:02,440 --> 01:47:04,040 INFORMATION. 2191 01:47:04,040 --> 01:47:05,640 WITH THE TIMING WE ARE LIMITED 2192 01:47:05,640 --> 01:47:11,240 WITH THE METHOD OF RECORDING AND 2193 01:47:11,240 --> 01:47:14,360 SO ASKING THOSE GRAN YUU 2194 01:47:14,360 --> 01:47:16,560 SO ASKING THOSE GRAN YLAR 2195 01:47:16,560 --> 01:47:18,160 QUESTIONS WHEN THE CELL TYPES 2196 01:47:18,160 --> 01:47:22,920 DIVERGED, I THINK WE NEED ONE 2197 01:47:22,920 --> 01:47:26,080 MORE STEP IN ORDER TO ADDRESS 2198 01:47:26,080 --> 01:47:26,720 THAT QUESTION. 2199 01:47:26,720 --> 01:47:28,200 >> THANK YOU. 2200 01:47:28,200 --> 01:47:39,160 ALL RIGHT, NEXT QUESTION TO TIM. 2201 01:47:39,160 --> 01:47:43,640 DO YOU THE PROPORTION MODIFIED 2202 01:47:43,640 --> 01:47:45,040 OVER TIME AND SECOND OF THE 2203 01:47:45,040 --> 01:47:50,240 DYNAMIC REGIONS AND WHAT'S THE 2204 01:47:50,240 --> 01:47:51,840 DIFFERENCE IN GENETIC 2205 01:47:51,840 --> 01:47:52,560 DIFFERENCES ACROSS THE LIFE 2206 01:47:52,560 --> 01:47:52,760 SPAN. 2207 01:47:52,760 --> 01:47:54,200 >> THOSE ARE GOOD AND IMPORTANT 2208 01:47:54,200 --> 01:47:58,640 QUESTIONS. 2209 01:47:58,640 --> 01:48:02,200 TO THE FIRST ONE IN TERMS OF THE 2210 01:48:02,200 --> 01:48:03,840 CONSISTENCY OVER THE LIFE SPAN I 2211 01:48:03,840 --> 01:48:08,120 SHOWED ONE SNAPSHOT HOW THE 2212 01:48:08,120 --> 01:48:09,720 EPIGENOME LOOKS IN THE DIFFERENT 2213 01:48:09,720 --> 01:48:12,760 BRAIN REGIONS. 2214 01:48:12,760 --> 01:48:13,920 WE'VE DONE SINGLE CELL ATAC IN 2215 01:48:13,920 --> 01:48:15,960 THE MOUSE AND WHEN WE CLUSTER IT 2216 01:48:15,960 --> 01:48:19,600 WITH THE TIME POINT THE 2217 01:48:19,600 --> 01:48:20,520 EMBRYONIC TISSUE CLUSTERS FAR 2218 01:48:20,520 --> 01:48:22,240 FROM THE ADULT. 2219 01:48:22,240 --> 01:48:24,680 THE DIFFERENT BRAIN REGIONS ARE 2220 01:48:24,680 --> 01:48:27,400 MORE SIMILAR TO EACH OTHER AND 2221 01:48:27,400 --> 01:48:29,760 THE EMBRYO THAN TO THE ADULT 2222 01:48:29,760 --> 01:48:33,240 TISSUE AND THAT'S NOT SO 2223 01:48:33,240 --> 01:48:33,520 SURPRISING. 2224 01:48:33,520 --> 01:48:36,240 THIS HITS TO THE BIG CHALLENGE 2225 01:48:36,240 --> 01:48:42,080 IN BIOLOGY IN LINKING DIVIDING 2226 01:48:42,080 --> 01:48:46,160 CELLS WITH AND THERE'S A HUGE 2227 01:48:46,160 --> 01:48:48,400 CHANGE IN TRANSCRIPT AND 2228 01:48:48,400 --> 01:48:50,640 EPIGENOME VERSUS THE EMBRYO AND 2229 01:48:50,640 --> 01:48:52,240 THE MATURE CELL TYPE. 2230 01:48:52,240 --> 01:48:54,200 ONE CAN EITHER DO LOTS OF 2231 01:48:54,200 --> 01:48:56,640 DIFFERENT TIME POINTS OTHER LABS 2232 01:48:56,640 --> 01:49:02,200 HAVE DONE TO LINK EARLY RNA OR 2233 01:49:02,200 --> 01:49:03,400 EPIGENOME OR OTHER COMPUTATIONAL 2234 01:49:03,400 --> 01:49:06,200 TECHNIQUES TO TRY TO INVESTIGATE 2235 01:49:06,200 --> 01:49:12,840 THAT. 2236 01:49:12,840 --> 01:49:15,360 THE MAJORITY WILL BE DIFFERENT 2237 01:49:15,360 --> 01:49:17,760 THAN IN THE MATURE BREAK AND 2238 01:49:17,760 --> 01:49:18,360 THERE'S SOME GENES EXPRESSED 2239 01:49:18,360 --> 01:49:24,960 EARLY ON AND MAINTAINED LIKELY 2240 01:49:24,960 --> 01:49:39,800 BE SIMILAR. 2241 01:49:39,800 --> 01:49:41,560 AND WE ARE NOW INVESTIGATING 2242 01:49:41,560 --> 01:49:43,960 CERTAIN MUTATIONS AND GENES TO 2243 01:49:43,960 --> 01:49:47,320 SEE WHEN A GENE IS PERTURBED, 2244 01:49:47,320 --> 01:49:48,800 HOW DOES THAT AFFECT THE 2245 01:49:48,800 --> 01:49:51,600 EPIGENOME AND YOU CAN LOOK AT 2246 01:49:51,600 --> 01:50:00,280 HOW ACTIVITY AFFECTS THE 2247 01:50:00,280 --> 01:50:02,200 EPIGENOME STATES THOSE ARE THE 2248 01:50:02,200 --> 01:50:04,640 QUESTIONS AND EXPERIMENTS WE 2249 01:50:04,640 --> 01:50:05,640 HOPE FOR THE FUTURE TO 2250 01:50:05,640 --> 01:50:07,520 UNDERSTAND HOW ENVIRONMENTAL 2251 01:50:07,520 --> 01:50:12,720 CHANGES OR BEHAVIOR AFFECT THE 2252 01:50:12,720 --> 01:50:13,200 EPIGENETIC STATE AND 2253 01:50:13,200 --> 01:50:28,760 CONNECTIVITY PATTERNS. 2254 01:50:28,760 --> 01:50:31,120 >> YOU'RE SHOWING ACCESSIBILITY 2255 01:50:31,120 --> 01:50:34,240 AND TRANSCRIPTION AND YOU'VE 2256 01:50:34,240 --> 01:50:44,000 DONE CORRELATION WITH HISTONE 2257 01:50:44,000 --> 01:50:45,960 MODIFICATIONS AND WHERE DO YOU 2258 01:50:45,960 --> 01:50:50,440 NOT SEE ACCESSIBILITY BUT SEE 2259 01:50:50,440 --> 01:50:52,960 TRANSCRIPTION IN THE LOCUS. 2260 01:50:52,960 --> 01:51:02,600 DOES THAT HAPPEN OR IS IT RARE? 2261 01:51:02,600 --> 01:51:04,360 >> WE SEE LOCUS ACCESSIBLE IN 2262 01:51:04,360 --> 01:51:07,840 THE PROMOTER BUT KNOW THE GENE 2263 01:51:07,840 --> 01:51:08,960 IS NOT EXPRESSED AND THAT'S ONE 2264 01:51:08,960 --> 01:51:10,240 THING WE HIGHLIGHTED AND THERE'S 2265 01:51:10,240 --> 01:51:12,880 ONE GENE WHERE THE PROMOTER WAS 2266 01:51:12,880 --> 01:51:14,160 ACCESSIBLE IN ALL FOUR BRAIN 2267 01:51:14,160 --> 01:51:15,720 REGIONS BUT WE AND OTHERS HAVE 2268 01:51:15,720 --> 01:51:17,240 SHOWN THE GREEN IS NOT EXPRESSED 2269 01:51:17,240 --> 01:51:21,040 IN THE CORTEX OR GLE. 2270 01:51:21,040 --> 01:51:24,520 -- LGE AND ONE PIECE OF DATA 2271 01:51:24,520 --> 01:51:25,960 YOU CAN BE FOOLED BUT LOOKING AT 2272 01:51:25,960 --> 01:51:32,960 THE ENTIRETY OF THE DNA IT MAKES 2273 01:51:32,960 --> 01:51:34,240 MORE SENSE AND I DON'T KNOW 2274 01:51:34,240 --> 01:51:37,680 WHERE THE PROMOTER WAS CLEARLY 2275 01:51:37,680 --> 01:51:38,480 REPRESSED BECAUSE IT WOULDN'T 2276 01:51:38,480 --> 01:51:40,800 MAKE A WHOLE LOT OF BIOLOGICAL 2277 01:51:40,800 --> 01:51:43,360 SENSE BUT THE OPPOSITE LOGIC WE 2278 01:51:43,360 --> 01:51:43,520 DO. 2279 01:51:43,520 --> 01:51:46,360 SOMETIMES IT'S THE PROMOTER OPEN 2280 01:51:46,360 --> 01:51:47,960 PRIOR TO RNA AND SOMETIMES THE 2281 01:51:47,960 --> 01:51:49,640 PROMOTERS ARE OPEN IN REGIONS 2282 01:51:49,640 --> 01:51:51,840 WHERE WE KNOW IT'S NOT EXPRESSED 2283 01:51:51,840 --> 01:51:56,360 AND WE DON'T KNOW WHY THAT IS 2284 01:51:56,360 --> 01:51:57,960 BUT TO ANSWER YOUR QUESTION WE 2285 01:51:57,960 --> 01:52:02,360 DO SEE MISMATCHES OF LOGIC BUT 2286 01:52:02,360 --> 01:52:06,880 IN GENERAL THE OVERALL THEME IS 2287 01:52:06,880 --> 01:52:12,920 THE EPIGENOME SEEMS TO BE IN A 2288 01:52:12,920 --> 01:52:13,520 POSITION YOU'D EXPECT ON RNA 2289 01:52:13,520 --> 01:52:14,960 ROLES. 2290 01:52:14,960 --> 01:52:19,280 >> WE HAVE A TECHNOLOGY QUESTION 2291 01:52:19,280 --> 01:52:22,240 TO YOU TIM AND YE. 2292 01:52:22,240 --> 01:52:27,120 WHAT MOUSE STRAINS WERE USED BY 2293 01:52:27,120 --> 01:52:31,000 DOCTORS PETROS AND ZHANG AND ARE 2294 01:52:31,000 --> 01:52:33,280 THERE COMPARISONS ACROSS MOUSE 2295 01:52:33,280 --> 01:52:39,520 STUDIES ON SINGLE USE GENOME? 2296 01:52:39,520 --> 01:52:43,400 >> WE USE THE C57 BLACK MOUSE 2297 01:52:43,400 --> 01:52:46,200 LINE AND NOW INVESTIGATING MOUSE 2298 01:52:46,200 --> 01:53:00,040 MUTANTS WITH THE SAME SCREEN. 2299 01:53:00,040 --> 01:53:01,480 >> WE HAVEN'T DONE THE SAME 2300 01:53:01,480 --> 01:53:02,760 ANALYSIS WITH THE OTHER STRAINS 2301 01:53:02,760 --> 01:53:08,080 AND THE PERSON ASKED ABOUT HUMAN 2302 01:53:08,080 --> 01:53:09,640 STUDIES USING MOUSE STUDIES AND 2303 01:53:09,640 --> 01:53:14,080 SINGLE GENOME, THAT IS TRUE. 2304 01:53:14,080 --> 01:53:17,840 SO IN OUR RNA SEQ DATA WE LOOKED 2305 01:53:17,840 --> 01:53:18,880 AT THE VARIANTS ACROSS 2306 01:53:18,880 --> 01:53:22,000 INDIVIDUALS AND IT'S LARGER FROM 2307 01:53:22,000 --> 01:53:23,560 OUR HUMAN STUDIES THAN FROM OUR 2308 01:53:23,560 --> 01:53:24,880 MOUSE STUDIES. 2309 01:53:24,880 --> 01:53:28,320 BUT WHEN WE FIRST OBTAINED HUMAN 2310 01:53:28,320 --> 01:53:29,600 ASTROCYTE SPECIFIC SIGNATURES WE 2311 01:53:29,600 --> 01:53:37,520 WONDERED WHETHER THAT IS REALLY 2312 01:53:37,520 --> 01:53:38,560 HUMAN VERSUS BLACK 6 MICE OR ALL 2313 01:53:38,560 --> 01:53:42,200 THAT AND WE HAVE AN INDIRECT WAY 2314 01:53:42,200 --> 01:53:45,160 TO LOOK AT THIS. 2315 01:53:45,160 --> 01:53:46,840 WE LOOKED AT ANOTHER DATA SET 2316 01:53:46,840 --> 01:53:50,880 THAT IS NOT ASTROCYTE SPECIFIC 2317 01:53:50,880 --> 01:53:53,160 AND THE WHOLE TISSUE HIPPOCAMPUS 2318 01:53:53,160 --> 01:53:55,640 BRAIN TISSUE FROM A GROUP IN THE 2319 01:53:55,640 --> 01:53:57,520 JACKSON LABS WHERE THEY COMPARED 2320 01:53:57,520 --> 01:53:59,560 MANY MOUSE SCREENS AND WE SEE 2321 01:53:59,560 --> 01:54:03,040 THE TOP HUMAN ASTROCYTES ARE 2322 01:54:03,040 --> 01:54:05,800 HIGH IN HUMAN ASTROCYTE BUT LOW 2323 01:54:05,800 --> 01:54:11,800 IN MOUSE ASTROCYTE GENES ARE 2324 01:54:11,800 --> 01:54:12,920 ACTUALLY CONSISTENT ACROSS 2325 01:54:12,920 --> 01:54:18,680 SPECIES. 2326 01:54:18,680 --> 01:54:28,680 AND IT'S NOT LIMITED BUT MORE 2327 01:54:28,680 --> 01:54:31,400 THOROUGH STUDIES ARE REQUIRED TO 2328 01:54:31,400 --> 01:54:32,360 ADDRESS DIFFERENCES IN MOUSE 2329 01:54:32,360 --> 01:54:33,280 GENES. 2330 01:54:33,280 --> 01:54:34,920 >> IS IT POSSIBLE TO USE 2331 01:54:34,920 --> 01:54:38,080 IMMUNOPANNING AS AN ENRICHMENT 2332 01:54:38,080 --> 01:54:40,000 STEP PRYOR TO SINGLE CELL 2333 01:54:40,000 --> 01:54:40,600 SEQUENCING TO SEE IT CERTAIN 2334 01:54:40,600 --> 01:54:42,680 TYPES OF ASTROCYTES RESPOND 2335 01:54:42,680 --> 01:54:43,480 DIFFERENTLY TO THE ENVIRONMENT 2336 01:54:43,480 --> 01:54:45,200 OR OTHER STIMULI? 2337 01:54:45,200 --> 01:54:46,800 >> YES, THAT'S DEFINITELY A 2338 01:54:46,800 --> 01:54:49,040 REASONABLE THING TO DO. 2339 01:54:49,040 --> 01:54:51,520 IT'S A GOOD IDEA AND WE HAVE 2340 01:54:51,520 --> 01:54:53,960 DONE THAT AND WHEN WE DO THE 2341 01:54:53,960 --> 01:55:01,640 MOTIVATION IS IF YOUR INTEREST 2342 01:55:01,640 --> 01:55:04,600 IS IN SUBTYPES YOU DON'T WANT TO 2343 01:55:04,600 --> 01:55:07,040 SPEND SO MUCH MONEY TO SEQUENCE 2344 01:55:07,040 --> 01:55:08,880 A LOT OF CELLS WHERE THE 2345 01:55:08,880 --> 01:55:11,160 MAJORITY ARE NEURONS SO WE DO 2346 01:55:11,160 --> 01:55:12,920 ENRICHMENT FIRST AND SINGLE CELL 2347 01:55:12,920 --> 01:55:18,920 SEQUENCING. 2348 01:55:18,920 --> 01:55:19,520 >> THANKS. 2349 01:55:19,520 --> 01:55:21,800 AN INTRIGUING QUESTION FROM THE 2350 01:55:21,800 --> 01:55:22,120 AUDIENCE. 2351 01:55:22,120 --> 01:55:27,640 HOW DOES THIS CELL TYPE 2352 01:55:27,640 --> 01:55:28,640 CONSERVATION ACROSS SPECIES MAP 2353 01:55:28,640 --> 01:55:31,200 TO THE ADULT ANIMAL OF HUMAN 2354 01:55:31,200 --> 01:55:36,440 BRAIN DEVELOPMENT. 2355 01:55:36,440 --> 01:55:37,680 ANY COMMENTS ON THAT? 2356 01:55:37,680 --> 01:55:41,960 >> IT'S A TERRIFIC QUESTION I 2357 01:55:41,960 --> 01:55:42,480 THINK ULTIMATELY WILL BE 2358 01:55:42,480 --> 01:55:46,240 ADDRESSED VERY WELL BY 2359 01:55:46,240 --> 01:55:46,760 COMPARATIVE DEVELOPMENT 2360 01:55:46,760 --> 01:55:47,160 ANALYSIS. 2361 01:55:47,160 --> 01:55:49,960 I THINK I DON'T KNOW THE ANSWER 2362 01:55:49,960 --> 01:55:54,560 THERE YET BUT THE HINTS ARE 2363 01:55:54,560 --> 01:55:57,440 THERE FROM PRIOR WORK WE HAVE 2364 01:55:57,440 --> 01:55:58,840 DONE DEVELOPMENT ANALYSES IN 2365 01:55:58,840 --> 01:56:00,960 HUMAN AND NON-HUMAN PRIMATE AND 2366 01:56:00,960 --> 01:56:02,280 DIFFERENT PARTS OF THE CORTEX 2367 01:56:02,280 --> 01:56:07,520 WHICH MATURE AT DIFFERENT RATES 2368 01:56:07,520 --> 01:56:14,040 AS WELL PRE FRONTAL AND AT THE 2369 01:56:14,040 --> 01:56:16,560 MORE BULK LEVEL THIS IS 2370 01:56:16,560 --> 01:56:17,400 EXTREMELY CLEAR. 2371 01:56:17,400 --> 01:56:23,040 YOU CAN SEE THE DEVELOPMENT 2372 01:56:23,040 --> 01:56:27,960 TRAJECTORIES AND EXTEND ED IN 2373 01:56:27,960 --> 01:56:30,240 CERTAIN BRAIN REGIONS. 2374 01:56:30,240 --> 01:56:36,840 I THINK THE PHENOMENON OF 2375 01:56:36,840 --> 01:56:39,680 DIFFERENTIAL MATURATION WOULD BE 2376 01:56:39,680 --> 01:56:42,400 EXTREMELY OBVIOUS WITH THE RIGHT 2377 01:56:42,400 --> 01:56:44,920 ASSAY BUT ARE SOME DEVELOPING 2378 01:56:44,920 --> 01:56:47,520 THE THE SAME RATE AND OTHERS 2379 01:56:47,520 --> 01:56:47,680 NOT. 2380 01:56:47,680 --> 01:56:52,560 I THINK WE'LL SEE SURPRISES. 2381 01:56:52,560 --> 01:56:55,760 SOMETIMES THERE'S THINGS 2382 01:56:55,760 --> 01:56:58,000 GENERATED EARLIER AND HAVE MORE 2383 01:56:58,000 --> 01:56:59,280 PROTRACTED MATURATION. 2384 01:56:59,280 --> 01:57:06,240 SOME ARE COORDINATED ACROSS 2385 01:57:06,240 --> 01:57:17,480 REGIONS SUCH AS SYNAPTOGENESIS 2386 01:57:17,480 --> 01:57:19,920 AND ESPECIALLY FOR DEVELOPMENTAL 2387 01:57:19,920 --> 01:57:22,240 DISORDER WHERE IT MAY WHEREBY 2388 01:57:22,240 --> 01:57:38,160 THINGS BEGIN TO GO WRONG. 2389 01:57:38,160 --> 01:57:41,720 >> IS THERE A WAY TO COMBINE 2390 01:57:41,720 --> 01:57:42,640 OMIC APPROACHES? 2391 01:57:42,640 --> 01:57:45,720 >> IN THE ADULT BRAIN I THINK 2392 01:57:45,720 --> 01:57:46,880 PROBABLY SOME MEMBERS OF THE 2393 01:57:46,880 --> 01:57:49,200 AUDIENCE MAY HAVE A BETTER 2394 01:57:49,200 --> 01:57:51,040 HANDLE ON EXTRA TRICKS THAT CAN 2395 01:57:51,040 --> 01:57:53,720 BE BROUGHT FOR DEVELOPMENT 2396 01:57:53,720 --> 01:57:58,280 CONNECTIVITY. 2397 01:57:58,280 --> 01:58:02,080 WHAT WE TRIED TO DO HAS BEEN TO 2398 01:58:02,080 --> 01:58:04,920 LINK CONNECTIVITY TO THE 2399 01:58:04,920 --> 01:58:09,440 MOLECULARLY DEFINED CELL TYPES. 2400 01:58:09,440 --> 01:58:10,440 SIMILAR TO WHERE YOU SEQUENCE 2401 01:58:10,440 --> 01:58:12,440 WITH PHYSIOLOGY YOU SEQUENCE 2402 01:58:12,440 --> 01:58:17,560 WITH SOME FORM OF ANATOMY AND 2403 01:58:17,560 --> 01:58:21,600 ONE VERSION OF THIS IS TE TO 2404 01:58:21,600 --> 01:58:23,440 RETRO GRADUALLY LABEL CELLS AND 2405 01:58:23,440 --> 01:58:26,120 FIGURE OUT WHO THE CELLS ARE BY 2406 01:58:26,120 --> 01:58:26,520 SEQUENCING THEM. 2407 01:58:26,520 --> 01:58:32,040 ANOTHER IS TO GO IN THE OTHER 2408 01:58:32,040 --> 01:58:37,440 DIRECTION AND TO WHOLE BRAIN 2409 01:58:37,440 --> 01:58:39,720 RECONSTRUCTION AND WHAT MAKES 2410 01:58:39,720 --> 01:58:44,400 THE PROBLEM SO DIFFICULT IS THE 2411 01:58:44,400 --> 01:58:58,240 PROS -- PROMISS 2412 01:58:58,240 --> 01:59:01,440 IT'S A RATHER CHALLENGING THING 2413 01:59:01,440 --> 01:59:02,360 AT THE MOMENT. 2414 01:59:02,360 --> 01:59:05,320 THERE ARE VERY PROMISING 2415 01:59:05,320 --> 01:59:11,560 TECHNIQUES FROM TONY ZADAS'S 2416 01:59:11,560 --> 01:59:13,840 GROUP TO SEQUENCE CELLS TO MANY 2417 01:59:13,840 --> 01:59:14,120 LOCATIONS. 2418 01:59:14,120 --> 01:59:15,560 I THINK THE TECHNOLOGIES ARE 2419 01:59:15,560 --> 01:59:17,640 COMING. 2420 01:59:17,640 --> 01:59:19,240 BUT AT THE MOMENT IT'S STILL 2421 01:59:19,240 --> 01:59:20,560 HARD-FOUGHT INFORMATION TO GET 2422 01:59:20,560 --> 01:59:25,640 CONCRETELY. 2423 01:59:25,640 --> 01:59:29,880 >> SO, HAL BEAT ME TO THE PUNCH 2424 01:59:29,880 --> 01:59:33,920 TO A QUESTION. 2425 01:59:33,920 --> 01:59:36,440 YOU MENTIONED THERE ARE 3,000, 2426 01:59:36,440 --> 01:59:41,840 DO YOU MEAN THIS REFLECTS THE 2427 01:59:41,840 --> 01:59:47,440 NORMAL SUBTYPES. 2428 01:59:47,440 --> 01:59:51,400 ASK YOU TO VENTURE GUESSES FOR 2429 01:59:51,400 --> 01:59:54,440 NUMBERS IN THE HUMAN BRAIN. 2430 01:59:54,440 --> 01:59:56,320 >> ED: OKAY, THAT'S GREAT. 2431 01:59:56,320 --> 01:59:59,360 SO FIRST OF ALL, I HAVE TO SAY 2432 01:59:59,360 --> 02:00:00,720 I'M REPRESENTING OTHERS' WORK 2433 02:00:00,720 --> 02:00:02,840 ON THIS MOUSE BRAIN, SO PLEASE 2434 02:00:02,840 --> 02:00:04,000 TAKE THAT INTO CONSIDERATION. 2435 02:00:04,000 --> 02:00:09,840 THIS IS COMING FROM MY 2436 02:00:09,840 --> 02:00:12,880 COLLEAGUE HONG QI ZHANG'S GROUP. 2437 02:00:12,880 --> 02:00:15,760 WHAT IS USED FOR THE MOTOR 2438 02:00:15,760 --> 02:00:18,360 CORTEX, APPLIED TO SIMILAR DATA 2439 02:00:18,360 --> 02:00:19,400 GENERATED ACROSS THE ENTIRE 2440 02:00:19,400 --> 02:00:22,080 MOUSE BRAIN. 2441 02:00:22,080 --> 02:00:23,840 AND THIS IS SORT OF THE ORDER 2442 02:00:23,840 --> 02:00:26,160 WITH THAT KIND OF THRESHOLDING 2443 02:00:26,160 --> 02:00:28,040 THAT IS OBSERVED ACROSS THE 2444 02:00:28,040 --> 02:00:29,200 ENTIRE BRAIN. 2445 02:00:29,200 --> 02:00:31,440 AND IT TURNS OUT THAT ACTUALLY, 2446 02:00:31,440 --> 02:00:33,120 THE MAJORITY OF THE DIVERSITY 2447 02:00:33,120 --> 02:00:35,240 COMES FROM SUB CORTICAL 2448 02:00:35,240 --> 02:00:35,920 STRUCTURES. 2449 02:00:35,920 --> 02:00:41,600 I THINK A LOT OF THE CORTICAL 2450 02:00:41,600 --> 02:00:44,080 -- WOULD THINK IT WAS IN THE 2451 02:00:44,080 --> 02:00:47,440 CORTEX, BUT IT'S ARCHITECTURE 2452 02:00:47,440 --> 02:00:48,360 THAT GRADES IN DIFFERENT 2453 02:00:48,360 --> 02:00:50,000 FASHIONS IN THE CORTEX. 2454 02:00:50,000 --> 02:00:51,640 THERE ARE MANY TYPES OF CELLS 2455 02:00:51,640 --> 02:00:55,360 THAT DON'T HAVE SUCH A 2456 02:00:55,360 --> 02:00:57,760 HIERARCHICAL ORGANIZATION IN 2457 02:00:57,760 --> 02:00:58,720 SUB CORTICAL STRUCTURES. 2458 02:00:58,720 --> 02:01:00,240 BUT THAT IS KIND OF THE WHOLE 2459 02:01:00,240 --> 02:01:01,520 PICTURE. 2460 02:01:01,520 --> 02:01:03,800 OF COURSE THIS DOESN'T INCLUDE 2461 02:01:03,800 --> 02:01:06,440 OTHER PARTS OF THE CNS, THE 2462 02:01:06,440 --> 02:01:08,560 SPINAL CORD OR RETINA, WHICH 2463 02:01:08,560 --> 02:01:10,200 WOULD ADD TO THAT NUMBER. 2464 02:01:10,200 --> 02:01:11,840 THE SECOND PART OF YOUR 2465 02:01:11,840 --> 02:01:12,800 QUESTION TO VENTURING A 2466 02:01:12,800 --> 02:01:13,520 QUESTION IN HUMAN. 2467 02:01:13,520 --> 02:01:15,640 ONE OF THE THINGS WE HAVE 2468 02:01:15,640 --> 02:01:19,040 REALLY BEEN STRUCK BY IS THE 2469 02:01:19,040 --> 02:01:22,200 CELLULAR DIVERSITY IN A 2470 02:01:22,200 --> 02:01:24,280 HOMOLOGOUS REGION SEEMS TO BE 2471 02:01:24,280 --> 02:01:25,280 EXTREMELY CONSISTENT ACROSS 2472 02:01:25,280 --> 02:01:25,920 MAMMALS. 2473 02:01:25,920 --> 02:01:28,040 IT IS NOT DRAMATICALLY MORE 2474 02:01:28,040 --> 02:01:30,320 DIVERSE IN THE HUMAN CORTEX 2475 02:01:30,320 --> 02:01:32,080 COMPARED TO THE MOUSE CORTEX. 2476 02:01:32,080 --> 02:01:33,560 THERE'S A LOT MORE OF IT. 2477 02:01:33,560 --> 02:01:36,640 AND I THINK YOU CAN GET GREATER 2478 02:01:36,640 --> 02:01:38,040 DIVERSIFICATION, IN THE CORTEX 2479 02:01:38,040 --> 02:01:39,640 BECAUSE YOU HAVE MORE REGIONS 2480 02:01:39,640 --> 02:01:41,240 AND THEY BECOME MORE 2481 02:01:41,240 --> 02:01:42,680 SPECIALIZED TO SOME DEGREE. 2482 02:01:42,680 --> 02:01:45,040 BUT FOR THE MOST PART, THE 2483 02:01:45,040 --> 02:01:50,000 DIVERSITY IS VERY SIMILAR. 2484 02:01:50,000 --> 02:01:51,640 I THINK THAT IS PROFOUND IN ONE 2485 02:01:51,640 --> 02:01:53,720 WAY. 2486 02:01:53,720 --> 02:01:54,920 THE ALSO PRAGMATICALLY REALLY 2487 02:01:54,920 --> 02:01:56,760 IMPORTANT BECAUSE IT MEANS IT'S 2488 02:01:56,760 --> 02:01:58,280 NOT 1,000 TIMES THE PROBLEM TO 2489 02:01:58,280 --> 02:02:01,040 MAKE A HUMAN CELL OUT OF THIS. 2490 02:02:01,040 --> 02:02:02,920 THIS IS A DOABLE THING TO TRY 2491 02:02:02,920 --> 02:02:04,160 TO MATCH THAT LEVEL OF 2492 02:02:04,160 --> 02:02:05,720 DIVERSITY. 2493 02:02:05,720 --> 02:02:07,600 THE PROBLEM BECOMES ONE OF HOW 2494 02:02:07,600 --> 02:02:09,200 DO YOU ADEQUATELY SAMPLE A 2495 02:02:09,200 --> 02:02:11,040 BRAIN WHICH IS 1,000 TIMES 2496 02:02:11,040 --> 02:02:12,120 BIGGER TO CAPTURE THAT 2497 02:02:12,120 --> 02:02:12,680 DIVERSITY. 2498 02:02:12,680 --> 02:02:17,960 BUT IT DOESN'T APPEAR THE 2499 02:02:17,960 --> 02:02:20,040 DRAMATICALLY DIVERSE. 2500 02:02:20,040 --> 02:02:22,960 WE'RE NOT TALKING ABOUT EVEN A 2501 02:02:22,960 --> 02:02:23,760 TWO-FOLD. 2502 02:02:23,760 --> 02:02:25,400 I THINK IT'S NOT MUCH MORE 2503 02:02:25,400 --> 02:02:29,440 DIVERSE IN THE HUMAN. 2504 02:02:29,440 --> 02:02:32,880 >> I WANT TO ELABORATE A LITTLE 2505 02:02:32,880 --> 02:02:38,400 BIT ON THIS, AND THIS IS SORT 2506 02:02:38,400 --> 02:02:40,040 OF BASED WITH -- ALSO ASKING 2507 02:02:40,040 --> 02:02:42,800 WHAT ARE THE LIMITATIONS IN 2508 02:02:42,800 --> 02:02:48,200 IDENTIFYING NEURO TYPES BY 2509 02:02:48,200 --> 02:02:49,040 TRANSCRIPTIONAL PROFILING. 2510 02:02:49,040 --> 02:02:51,800 I WANT TO COMMENT ON WHAT IS 2511 02:02:51,800 --> 02:02:54,040 EMERGING IN -- WE HAVE BASED 2512 02:02:54,040 --> 02:02:56,880 ON OUR SINGLE CELL ATLAS, THE 2513 02:02:56,880 --> 02:02:58,600 GREAT DATA SET. 2514 02:02:58,600 --> 02:03:03,000 WE HAVE VERY NICE -- OF THE 2515 02:03:03,000 --> 02:03:04,440 DIFFERENT DREL TYPES. 2516 02:03:04,440 --> 02:03:08,600 BUT WE ARE LOOKING AT TROJAN, 2517 02:03:08,600 --> 02:03:12,280 WE LOOK BY TAGGING WITH G.F.P. 2518 02:03:12,280 --> 02:03:14,160 AND LOOKING WHETHER PROTEIN IS 2519 02:03:14,160 --> 02:03:14,880 EXPRESSED. 2520 02:03:14,880 --> 02:03:17,240 THERE ARE ACTUALLY INTRIGUING 2521 02:03:17,240 --> 02:03:19,120 DIFFERENCES, MAYBE NOT TOO 2522 02:03:19,120 --> 02:03:20,040 UNEXPECTED BECAUSE OF ALL THE 2523 02:03:20,040 --> 02:03:22,840 STUFF THAT HAS TO HAPPEN WITH 2524 02:03:22,840 --> 02:03:23,840 TRANSCRIPTION AND MAKING OF A 2525 02:03:23,840 --> 02:03:25,400 PROTEIN. 2526 02:03:25,400 --> 02:03:27,840 COMING BACK TO HAL'S QUESTION, 2527 02:03:27,840 --> 02:03:29,120 I'M WONDERING IF YOU HAVE 2528 02:03:29,120 --> 02:03:30,520 THOUGHTS ABOUT WHETHER THEY ARE 2529 02:03:30,520 --> 02:03:32,040 SORT OF, YOU KNOW, DEEPER 2530 02:03:32,040 --> 02:03:34,240 LAYERS OF DIVERSITY SETS THAT 2531 02:03:34,240 --> 02:03:37,600 ARE NOT HAPPENING ON THE 2532 02:03:37,600 --> 02:03:38,920 TRANSCRIPTIONAL LEVEL BUT ON 2533 02:03:38,920 --> 02:03:43,160 THE LEVEL OF TRANSLATION 2534 02:03:43,160 --> 02:03:44,080 CONTROL, MICRONASE AND ALL THAT 2535 02:03:44,080 --> 02:03:45,040 STUFF. 2536 02:03:45,040 --> 02:03:48,240 MAYBE TO FOLLOW-UP ON THAT, IS 2537 02:03:48,240 --> 02:03:50,320 THE INSTITUTE THINKING OF 2538 02:03:50,320 --> 02:03:53,280 PURSUING THAT FOR EXAMPLE, 2539 02:03:53,280 --> 02:03:56,080 LARGE SCALE GFP TAGGING OR 2540 02:03:56,080 --> 02:03:59,320 REGISTERING ANTIBODY STAINS OF 2541 02:03:59,320 --> 02:04:01,440 NUCLEAR PROTEINS AGAINST 2542 02:04:01,440 --> 02:04:02,080 TRANSCRIPTIONAL PROFILES TO GET 2543 02:04:02,080 --> 02:04:03,960 A SENSE OF HOW MUCH MORE 2544 02:04:03,960 --> 02:04:07,280 DIVERSITY YOU CAN GET OUT OF A 2545 02:04:07,280 --> 02:04:13,040 TRANSCRIPTION DATA SET? 2546 02:04:13,040 --> 02:04:14,760 >> ED: THOSE ARE ALL REALLY 2547 02:04:14,760 --> 02:04:15,360 GREAT QUESTIONS. 2548 02:04:15,360 --> 02:04:17,480 I WILL START BY SAYING WE SHIED 2549 02:04:17,480 --> 02:04:18,640 AWAY FROM GETTING INTO THE 2550 02:04:18,640 --> 02:04:20,480 PROTEIN SIDE OF THINGS. 2551 02:04:20,480 --> 02:04:23,320 IN PART, BECAUSE VERY OFTEN 2552 02:04:23,320 --> 02:04:26,080 THEY ARE DEPENDENT ON 2553 02:04:26,080 --> 02:04:29,520 ANTIBODIES AND WE HAVE LIMITED 2554 02:04:29,520 --> 02:04:30,200 HIGH-QUALITY ANTIBODIES TO WORK 2555 02:04:30,200 --> 02:04:31,400 WITH. 2556 02:04:31,400 --> 02:04:36,240 COMPARED TO HAVING THE FULLY 2557 02:04:36,240 --> 02:04:36,880 GENERALIZABLE NUCLEOTIDE 2558 02:04:36,880 --> 02:04:41,560 APPROACHES. 2559 02:04:41,560 --> 02:04:43,680 I GUESS LET ME STEP BACK. 2560 02:04:43,680 --> 02:04:46,040 TO ME, ONE OF THE REALLY QUITE 2561 02:04:46,040 --> 02:04:48,200 REMARKABLE THINGS IS THAT, YOU 2562 02:04:48,200 --> 02:04:51,440 CAN TAKE AN UNBIASED VIEW AT 2563 02:04:51,440 --> 02:04:55,080 THE GENOME, AND GET A PRETTY 2564 02:04:55,080 --> 02:04:56,960 CONSISTENT CLUSTERING OR 2565 02:04:56,960 --> 02:04:58,000 CLASSIFICATION OF SUBTYPES AS 2566 02:04:58,000 --> 02:05:00,040 YOU WOULD IF YOU PICKED A SET 2567 02:05:00,040 --> 02:05:02,840 OF GENES YOU THINK WOULD BE 2568 02:05:02,840 --> 02:05:03,400 PARTICULARLY FUNCTIONALLY 2569 02:05:03,400 --> 02:05:03,800 IMPORTANT. 2570 02:05:03,800 --> 02:05:06,840 YOU CAN OFTEN REPLICATE IT WITH 2571 02:05:06,840 --> 02:05:10,040 SOME, NEURONS ARE WELL 2572 02:05:10,040 --> 02:05:13,200 DIFFERENTIATED WITH GENES 2573 02:05:13,200 --> 02:05:15,840 ASSOCIATED, YOU CAN LARGELY 2574 02:05:15,840 --> 02:05:18,200 RECAPITULATE THE WHOLE THING. 2575 02:05:18,200 --> 02:05:21,720 YET, EMBEDDED WITHIN THAT ARE 2576 02:05:21,720 --> 02:05:24,480 PROTEIN CODING GENES, 2577 02:05:24,480 --> 02:05:25,440 NON-CODING RNA'S, VARIOUS OTHER 2578 02:05:25,440 --> 02:05:26,080 THINGS. 2579 02:05:26,080 --> 02:05:27,960 WE GET LARGELY THE SAME RESULTS 2580 02:05:27,960 --> 02:05:31,040 IF WE LOOK WITH METHYLATION 2581 02:05:31,040 --> 02:05:33,120 ANALYSIS OR ATTACK ANALYSIS OR 2582 02:05:33,120 --> 02:05:35,400 SINGLE CELL OR SINGLE NUCLEUS. 2583 02:05:35,400 --> 02:05:38,280 THEY SEEM TO BE PRETTY 2584 02:05:38,280 --> 02:05:39,600 FUNDAMENTAL UNITS THESE ARE 2585 02:05:39,600 --> 02:05:41,000 DIFFERENT ASPECTS OF THEM. 2586 02:05:41,000 --> 02:05:43,080 THAT BEING SAID, I'M SURE THAT 2587 02:05:43,080 --> 02:05:45,240 IF YOU REALLY DOVE IN AND 2588 02:05:45,240 --> 02:05:48,960 FOUND, YOU CAN FIND PLACES YOU 2589 02:05:48,960 --> 02:05:50,840 CAN BETTER DIFFERENTIATE WITH 2590 02:05:50,840 --> 02:05:52,680 RNA'S OR SUB PROTEINS. 2591 02:05:52,680 --> 02:05:57,760 AND THERE ARE PLACES WHERE THE 2592 02:05:57,760 --> 02:05:59,160 TRANSCRIPTON ISN'T CLEARLY 2593 02:05:59,160 --> 02:06:01,440 DESCRIBING EVERYTHING FROM 2594 02:06:01,440 --> 02:06:02,400 PHENOTYPING PERSPECTIVE WHAT WE 2595 02:06:02,400 --> 02:06:03,640 HAVE SEEN SO FAR. 2596 02:06:03,640 --> 02:06:05,240 I WOULDN'T LIKE TO GIVE THE 2597 02:06:05,240 --> 02:06:06,720 IDEA I BELIEVE EVERYTHING IS 2598 02:06:06,720 --> 02:06:08,040 REPRESENTED IN THE 2599 02:06:08,040 --> 02:06:09,040 TRANSCRIPTONE. 2600 02:06:09,040 --> 02:06:12,080 I'M SURE THERE'S MORE, BUT IT'S 2601 02:06:12,080 --> 02:06:13,960 A GOOD EARLY APPROXIMATION. 2602 02:06:13,960 --> 02:06:14,880 >> THANK YOU. 2603 02:06:14,880 --> 02:06:16,600 SO WE HAVE TWO MORE QUESTIONS 2604 02:06:16,600 --> 02:06:18,640 THAT I WOULD ACTUALLY LIKE TO 2605 02:06:18,640 --> 02:06:20,760 TRANSITION NOW TO THE MORE OPEN 2606 02:06:20,760 --> 02:06:23,360 DISCUSSION PART. 2607 02:06:23,360 --> 02:06:24,720 THIS IS ACTUALLY A QUESTION, 2608 02:06:24,720 --> 02:06:26,840 EVEN THOUGH ONE WAS DIRECTED TO 2609 02:06:26,840 --> 02:06:28,240 ED, THAT I WOULD LOVE TO HEAR 2610 02:06:28,240 --> 02:06:30,000 ALL OF THE PRESENTERS COMMENT 2611 02:06:30,000 --> 02:06:31,120 ON. 2612 02:06:31,120 --> 02:06:32,720 THEY ARE BOTH VERY IMPORTANT 2613 02:06:32,720 --> 02:06:33,480 GENERAL QUESTIONS. 2614 02:06:33,480 --> 02:06:35,400 I WILL POSE BOTH OF THEM, AND 2615 02:06:35,400 --> 02:06:36,960 MAYBE EACH ONE OF YOU CAN 2616 02:06:36,960 --> 02:06:41,680 COMMENT ON BOTH. 2617 02:06:41,680 --> 02:06:47,000 ONE IS FOR ALEXANDRIA, WHAT ARE 2618 02:06:47,000 --> 02:06:49,360 THE MAJOR CHALLENGES YOU SEE IN 2619 02:06:49,360 --> 02:06:50,840 INTEGRATING DATA SETS FROM 2620 02:06:50,840 --> 02:06:52,640 DIFFERENT LABS? 2621 02:06:52,640 --> 02:06:54,520 THIS IS, OF COURSE, A VERY 2622 02:06:54,520 --> 02:06:56,160 COMMON QUESTION THAT AFFECTS 2623 02:06:56,160 --> 02:06:57,360 ALL OF YOU. 2624 02:06:57,360 --> 02:07:03,000 I WOULD LOVE TO HEAR ABOUT YOU. 2625 02:07:03,000 --> 02:07:05,280 AND THE SECOND QUESTION AND 2626 02:07:05,280 --> 02:07:07,360 EQUALLY BIG PICTURE QUESTION. 2627 02:07:07,360 --> 02:07:08,760 THAT IS DIFFERENCES BETWEEN THE 2628 02:07:08,760 --> 02:07:14,560 MALE AND THE FEMALE. 2629 02:07:14,560 --> 02:07:17,760 BUSHRA, DO YOU WANT TO START 2630 02:07:17,760 --> 02:07:21,880 WITH COMMENTING ON THAT? 2631 02:07:21,880 --> 02:07:23,760 THERE ARE STILL MULTIPLE -- 2632 02:07:23,760 --> 02:07:27,880 HOW DO YOU FEEL ABOUT DATA 2633 02:07:27,880 --> 02:07:31,800 INTEGRATION. 2634 02:07:31,800 --> 02:07:41,040 VERY INTERESTING SEXUAL 2635 02:07:41,040 --> 02:07:42,440 DINANYSMS IN THE BRAIN. 2636 02:07:42,440 --> 02:07:45,040 >> YEAH, SO WITH RESPECT TO 2637 02:07:45,040 --> 02:07:47,120 INTEGRATING DATA SETS, I THINK, 2638 02:07:47,120 --> 02:07:52,440 YEAH, THAT DOES REMAIN A FAIRLY 2639 02:07:52,440 --> 02:07:53,200 BIG CHALLENGE. 2640 02:07:53,200 --> 02:07:55,080 I THINK ONE OF THE BIGGEST 2641 02:07:55,080 --> 02:07:57,520 THINGS IN TERMS OF THE DATA 2642 02:07:57,520 --> 02:08:00,080 QUALITIES, AND HOW MUCH, YEAH, 2643 02:08:00,080 --> 02:08:01,280 HOW MUCH INFORMATION ARE YOU 2644 02:08:01,280 --> 02:08:03,880 GETTING FROM THE SEQUENCING. 2645 02:08:03,880 --> 02:08:07,280 AND THIS CAN VARY BASED ON THE 2646 02:08:07,280 --> 02:08:09,080 CELL TYPES, SOME ARE EASIER TO 2647 02:08:09,080 --> 02:08:10,960 SEQUENCE, YOU GET A LOT MORE 2648 02:08:10,960 --> 02:08:12,080 INFORMATION, THEY ARE BIGGER, 2649 02:08:12,080 --> 02:08:14,920 THERE'S A LOT MORE RA. 2650 02:08:14,920 --> 02:08:16,040 AND THEN YOU COME TO CELLS LIKE 2651 02:08:16,040 --> 02:08:17,800 THE BRAIN, ESPECIALLY IN THE 2652 02:08:17,800 --> 02:08:19,640 FISH, THEY TEND TO BE REALLY, 2653 02:08:19,640 --> 02:08:21,280 REALLY SMALL. 2654 02:08:21,280 --> 02:08:22,800 AND DATA QUALITY DOES 2655 02:08:22,800 --> 02:08:25,040 DEFINITELY SUFFER. 2656 02:08:25,040 --> 02:08:27,040 I DON'T KNOW IF I HAVE A GREAT 2657 02:08:27,040 --> 02:08:33,240 RESPONSE TO HOW TO, YOU KNOW, 2658 02:08:33,240 --> 02:08:34,240 ADDRESS THIS CHALLENGE. 2659 02:08:34,240 --> 02:08:39,440 I GUESS AS WE ARE WORKING IN 2660 02:08:39,440 --> 02:08:41,520 THE COMMUNITY TO PROVIDE DATA 2661 02:08:41,520 --> 02:08:44,640 SETS THAT OTHER PEOPLE CAN USE, 2662 02:08:44,640 --> 02:08:46,040 THIS DEFINITELY STARTS TO 2663 02:08:46,040 --> 02:08:47,000 BECOME AN ISSUE. 2664 02:08:47,000 --> 02:08:49,080 BUT I DO THINK THAT A LOT OF 2665 02:08:49,080 --> 02:08:51,640 THE NEW GENERATION ANALYSIS 2666 02:08:51,640 --> 02:08:52,720 PIPELINES ARE TAKING THAT INTO 2667 02:08:52,720 --> 02:08:55,360 ACCOUNT. 2668 02:08:55,360 --> 02:08:57,520 AND ARE GENERATING WAYS IN 2669 02:08:57,520 --> 02:08:59,120 WHICH YOU CAN ACCOUNT FOR 2670 02:08:59,120 --> 02:09:00,240 DIFFERENCES IN THE QUALITY OF 2671 02:09:00,240 --> 02:09:01,880 THE DATA TO SOME EXTENT. 2672 02:09:01,880 --> 02:09:04,280 I THINK THAT IS AT LEAST A 2673 02:09:04,280 --> 02:09:05,840 STARTING POINT. 2674 02:09:05,840 --> 02:09:12,120 AS WE HAVE A MORE GENERALIZED 2675 02:09:12,120 --> 02:09:13,520 PROTOCOL AVAILABLE FOR MAYBE 2676 02:09:13,520 --> 02:09:16,080 PREPARATION OF THE VARIOUS 2677 02:09:16,080 --> 02:09:17,240 TISSUES, ASSOCIATION OF 2678 02:09:17,240 --> 02:09:18,920 PARTICULAR CELLS, THAT WOULD 2679 02:09:18,920 --> 02:09:23,280 HELP IN SORT OF AVERAGING OR 2680 02:09:23,280 --> 02:09:24,680 MAINTAINING THE DIFFERENCES TO 2681 02:09:24,680 --> 02:09:26,600 A LOWER LEVEL. 2682 02:09:26,600 --> 02:09:30,840 WITH RESPECT TO THE MALE VERSUS 2683 02:09:30,840 --> 02:09:32,280 FEMALE DIFFERENCES, SO FOR 2684 02:09:32,280 --> 02:09:34,160 EXAMPLE, IN THE STUDIES THAT 2685 02:09:34,160 --> 02:09:35,800 I'VE BEEN INVOLVED IN, WE HAVE 2686 02:09:35,800 --> 02:09:39,480 BEEN LOOKING AT DEVELOPMENT AND 2687 02:09:39,480 --> 02:09:44,360 THAT TIME POINT, THE FISH HAS 2688 02:09:44,360 --> 02:09:48,040 AN ACTUAL SEXUALLY DYNAMICALLY 2689 02:09:48,040 --> 02:09:49,960 MORE, WE CAN'T REALLY TELL. 2690 02:09:49,960 --> 02:09:52,240 THERE'S NO GENETIC, THEY DON'T 2691 02:09:52,240 --> 02:09:53,640 HAVE SEX CHROMOSOMES SO WE 2692 02:09:53,640 --> 02:09:55,320 CAN'T REALLY TELL THEM APART 2693 02:09:55,320 --> 02:09:57,480 BASED ON THAT EITHER. 2694 02:09:57,480 --> 02:10:01,000 SO I THINK WHEN YOU REACH THE 2695 02:10:01,000 --> 02:10:02,200 SEXUAL MATURITY STAGE AND YOU 2696 02:10:02,200 --> 02:10:05,240 ARE LOOKING AT OLDER FISH, THE 2697 02:10:05,240 --> 02:10:07,040 QUESTION OF MALES AND FEMALES 2698 02:10:07,040 --> 02:10:09,400 CAN BE MORE INTERESTING, BUT 2699 02:10:09,400 --> 02:10:10,560 FOR OUR STUDIES WE HAVEN'T 2700 02:10:10,560 --> 02:10:12,240 LOOKED AT IT BECAUSE WE ARE 2701 02:10:12,240 --> 02:10:13,120 LOOKING AT VERY EARLY 2702 02:10:13,120 --> 02:10:14,320 DEVELOPMENT. 2703 02:10:14,320 --> 02:10:15,560 >> UNDERSTOOD, YEAH. 2704 02:10:15,560 --> 02:10:17,840 TIM, DO YOU WANT TO SAY 2705 02:10:17,840 --> 02:10:19,240 SOMETHING ABOUT ACROSS LABS AND 2706 02:10:19,240 --> 02:10:22,800 ALSO SEX AS A PARAMETER? 2707 02:10:22,800 --> 02:10:26,040 >> TIM: DEFINITELY N.I.H. HAS 2708 02:10:26,040 --> 02:10:28,840 MADE A PUSH TO LOOK AT MALES 2709 02:10:28,840 --> 02:10:29,800 AND FEMALES FOR DIFFERENT 2710 02:10:29,800 --> 02:10:30,240 STUDIES. 2711 02:10:30,240 --> 02:10:32,120 WE ARE LOOKING AT 12, WHILE WE 2712 02:10:32,120 --> 02:10:34,000 CAN SEX THE MICE, SOME 2713 02:10:34,000 --> 02:10:35,600 EXPERIMENTS WE HAVE, WE DON'T 2714 02:10:35,600 --> 02:10:37,960 KNOW HOW DIFFERENT THE MALE AND 2715 02:10:37,960 --> 02:10:40,800 FEMALE BRAINS ARE IN 12. 2716 02:10:40,800 --> 02:10:43,480 BUT WHENEVER POSSIBLE, THE 2717 02:10:43,480 --> 02:10:46,040 ASSAYS INVOLVE POOLING MULTIPLE 2718 02:10:46,040 --> 02:10:48,720 EMBRYOS TOGETHER, WE TRY TO 2719 02:10:48,720 --> 02:10:51,480 POOL MALE AND FEMALE TOGETHER. 2720 02:10:51,480 --> 02:10:54,040 BUT ONE COULD BE OPPOSITE, 2721 02:10:54,040 --> 02:10:55,240 SEQUENCED MALES VERSUS FEMALES 2722 02:10:55,240 --> 02:10:57,920 AND LOOK AT THE DIFFERENCES. 2723 02:10:57,920 --> 02:11:00,240 BUT CONCEPTUALLY, ESPECIALLY IN 2724 02:11:00,240 --> 02:11:02,320 ADULT MODEL SYSTEMS AND HUMAN 2725 02:11:02,320 --> 02:11:03,280 PRIMATES AND THINGS THAT 2726 02:11:03,280 --> 02:11:04,720 QUESTION IS VERY IMPORTANT, 2727 02:11:04,720 --> 02:11:08,840 BECAUSE OBVIOUSLY A VARIETY OF 2728 02:11:08,840 --> 02:11:11,360 FACTORS COULD INFLUENCE 2729 02:11:11,360 --> 02:11:12,760 CIRCUITRY DIFFERENT. 2730 02:11:12,760 --> 02:11:16,440 AS FAR AS INTEGRATING DIFFERENT 2731 02:11:16,440 --> 02:11:19,480 DATA FROM DIFFERENT LABS AND 2732 02:11:19,480 --> 02:11:22,240 DIFFERENT SPECIES, PEOPLE AT 2733 02:11:22,240 --> 02:11:24,360 THE -- INSTITUTE, -- GENOME 2734 02:11:24,360 --> 02:11:26,240 CENTER ALSO DOES AN EXCELLENT 2735 02:11:26,240 --> 02:11:28,600 JOB TRYING TO OVERCOME THESE 2736 02:11:28,600 --> 02:11:29,680 CHALLENGES. 2737 02:11:29,680 --> 02:11:34,160 I WON'T SPEAK FOR AT AN, I 2738 02:11:34,160 --> 02:11:35,560 FORGET THE NAME OF THE WEBSITE 2739 02:11:35,560 --> 02:11:37,920 BUT HE IS TRYING TO INTEGRATE 2740 02:11:37,920 --> 02:11:39,520 ALL THESE DIFFERENT DATA SETS. 2741 02:11:39,520 --> 02:11:43,640 IF YOU HAVE SINGLE NUCLEAR TACK 2742 02:11:43,640 --> 02:11:45,720 IN AN ORGAN YOU CAN PUT IT IN 2743 02:11:45,720 --> 02:11:47,360 THEIR DATA SET AND ACTUALLY 2744 02:11:47,360 --> 02:11:52,160 READ OUT WHAT THE RNA 2745 02:11:52,160 --> 02:11:53,920 TRANSCRIPTION IS. 2746 02:11:53,920 --> 02:11:54,800 EVEN THOUGH DIFFERENT CELL 2747 02:11:54,800 --> 02:11:55,480 TYPES. 2748 02:11:55,480 --> 02:11:57,200 THAT KIND OF INTEGRATION IS 2749 02:11:57,200 --> 02:11:59,040 REALLY IMPORTANT FOR 2750 02:11:59,040 --> 02:11:59,920 UNDERSTANDING THESE MULTIONLY 2751 02:11:59,920 --> 02:12:02,520 TYPES OF ANALYSIS, ONE TYPE OF 2752 02:12:02,520 --> 02:12:06,840 DATA IS NOT SUFFICIENT TO DO IT. 2753 02:12:06,840 --> 02:12:11,240 IT'S IMPORTANT, AS BUSHRA SAID, 2754 02:12:11,240 --> 02:12:12,440 THE DATA QUALITY SET NEEDS TO 2755 02:12:12,440 --> 02:12:13,800 BE GOOD. 2756 02:12:13,800 --> 02:12:15,880 MAYBE TEN YEARS AGO THEY DIDN'T 2757 02:12:15,880 --> 02:12:17,760 PROTECT THE WORK WHERE IT WAS 2758 02:12:17,760 --> 02:12:20,040 TODAY, YOU NEED GOOD QUALITY 2759 02:12:20,040 --> 02:12:23,080 DATA SETS, MATCH TIME POINTS 2760 02:12:23,080 --> 02:12:24,760 AND IDEALLY SPATIAL REGIONS, IN 2761 02:12:24,760 --> 02:12:27,360 TERMS OF WHAT WE THINK ABOUT, 2762 02:12:27,360 --> 02:12:28,960 SINGLE CELL DEVELOPING BRAIN, 2763 02:12:28,960 --> 02:12:30,600 TAKING THE ENTIRE FOREBRAIN 2764 02:12:30,600 --> 02:12:32,240 MUSHING IT UP AND LOOKING AT 2765 02:12:32,240 --> 02:12:35,680 IT, WE KIND OF MICRO DISSECTED 2766 02:12:35,680 --> 02:12:36,680 THESE REGIONS. 2767 02:12:36,680 --> 02:12:37,720 THERE ARE QUESTIONS THAT COME 2768 02:12:37,720 --> 02:12:40,680 WITH THAT IN TERMS OF 2769 02:12:40,680 --> 02:12:43,760 INTEGRATING IT, I THINK ED 2770 02:12:43,760 --> 02:12:45,640 MIGHT BE ABLE TO ADDRESS THOSE 2771 02:12:45,640 --> 02:12:46,120 ISSUES. 2772 02:12:46,120 --> 02:12:48,680 >> BEFORE WE GO TO ED FOR THE 2773 02:12:48,680 --> 02:12:50,760 QUESTIONS, LET'S ASK ABOUT YE 2774 02:12:50,760 --> 02:12:56,560 ABOUT THE GLIA PROBLEM. 2775 02:12:56,560 --> 02:12:59,760 >> SO, I SHOULD START WITH SEX 2776 02:12:59,760 --> 02:13:01,760 -- SOMETHING? 2777 02:13:01,760 --> 02:13:02,720 >> UH-HUH. 2778 02:13:02,720 --> 02:13:05,480 >> YEAH, WE ACTUALLY DID 2779 02:13:05,480 --> 02:13:10,520 EXAMINE MALE VERSUS FEMALE 2780 02:13:10,520 --> 02:13:11,440 TRANSCRIPTTOME IN HUMANS. 2781 02:13:11,440 --> 02:13:13,840 THE DIFFERENCES ARE QUITE SUBLE. 2782 02:13:13,840 --> 02:13:19,720 WE HAVE A SHORT GENE LIST THAT 2783 02:13:19,720 --> 02:13:20,840 IS EPIGENETIC, DIFFERENT FROM 2784 02:13:20,840 --> 02:13:22,240 MALE AND FEMALE IN THE HEALTHY 2785 02:13:22,240 --> 02:13:22,960 BRAIN. 2786 02:13:22,960 --> 02:13:25,520 OUR GUESS IS THAT IN THE 2787 02:13:25,520 --> 02:13:28,120 HEALTHY BRAINS, MALE AND FEMALE 2788 02:13:28,120 --> 02:13:29,520 ARE QUITE SIMILAR. 2789 02:13:29,520 --> 02:13:31,120 BUT IN DISEASE CONDITIONS THEY 2790 02:13:31,120 --> 02:13:32,800 COULD BE VASTLY DIFFERENT, AS 2791 02:13:32,800 --> 02:13:34,640 WE ALL KNOW MALE AND FEMALE 2792 02:13:34,640 --> 02:13:35,840 HAVE DIFFERENT SUSCEPTIBILITY 2793 02:13:35,840 --> 02:13:40,280 TO A VARIETY OF DISEASES BUT IN 2794 02:13:40,280 --> 02:13:42,160 THE HEALTHY BRAIN, OUR 2795 02:13:42,160 --> 02:13:43,280 COGNITIVE FUNCTION ARE REALLY 2796 02:13:43,280 --> 02:13:46,040 SIMILAR. 2797 02:13:46,040 --> 02:13:50,280 MANY PEOPLE IN THE FIELD HAVE 2798 02:13:50,280 --> 02:13:53,400 REPORTED MICRO GLIAL, SEXUAL 2799 02:13:53,400 --> 02:13:55,800 MORPHISM WHICH IS INTERESTING, 2800 02:13:55,800 --> 02:13:58,000 WE SEE COMPARED WITH MICRO 2801 02:13:58,000 --> 02:13:59,000 GLIA, AT LEAST UNDER THE 2802 02:13:59,000 --> 02:14:01,440 HEALTHY CONDITION. 2803 02:14:01,440 --> 02:14:02,160 >> OLIVER: GOOD, GOOD. 2804 02:14:02,160 --> 02:14:03,760 GREAT. 2805 02:14:03,760 --> 02:14:05,640 ED, WHY DON'T YOU COMMENT ON 2806 02:14:05,640 --> 02:14:06,760 THESE POINTS. 2807 02:14:06,760 --> 02:14:09,080 THESE SHOULD BE OUR LAST WORDS 2808 02:14:09,080 --> 02:14:10,960 FROM YOU, ACTUALLY EVERYONE FOR 2809 02:14:10,960 --> 02:14:12,240 THIS SESSION BEFORE WE BREAK. 2810 02:14:12,240 --> 02:14:17,040 BUT YOU HAVE A FEW MINUTES TO 2811 02:14:17,040 --> 02:14:18,280 TALK ABOUT THESE IMPORTANT 2812 02:14:18,280 --> 02:14:18,960 ISSUES. 2813 02:14:18,960 --> 02:14:20,480 >> ED: THANK YOU. 2814 02:14:20,480 --> 02:14:22,040 FIRST OF ALL, I REALLY WANT TO 2815 02:14:22,040 --> 02:14:24,040 HIGHLIGHT THIS IS REALLY BIG 2816 02:14:24,040 --> 02:14:26,160 DATA SCIENCE HERE WITH THESE 2817 02:14:26,160 --> 02:14:27,080 ENORMOUS DATA SETS. 2818 02:14:27,080 --> 02:14:29,400 AND IT REQUIRES A LOT OF 2819 02:14:29,400 --> 02:14:30,400 COMPUTATIONAL EXPERTISE. 2820 02:14:30,400 --> 02:14:32,440 AND I THINK ONE OF THE 2821 02:14:32,440 --> 02:14:37,120 SUCCESSES OF SOME OF THE BIGGER 2822 02:14:37,120 --> 02:14:39,320 CONSORTIA HAVE BEEN TO BRING IN 2823 02:14:39,320 --> 02:14:41,240 HARD CORE COMPUTATIONAL 2824 02:14:41,240 --> 02:14:42,840 BIOLOGISTS OR EVEN OUTSIDE OF 2825 02:14:42,840 --> 02:14:44,440 THESE FIELDS TO TACKLE THESE 2826 02:14:44,440 --> 02:14:45,640 KINDS OF QUESTIONS. 2827 02:14:45,640 --> 02:14:48,000 YOU KNOW, THESE SORT OF TRICKLE 2828 02:14:48,000 --> 02:14:49,640 DOWN TO THINGS MANY LIVES CAN 2829 02:14:49,640 --> 02:14:53,880 APPLY TO THEIR OWN RESEARCH. 2830 02:14:53,880 --> 02:15:00,360 AND SO ACTUALLY, -- WORK ON 2831 02:15:00,360 --> 02:15:02,400 AZIMUTH IS THE NAME OF THE TOOL. 2832 02:15:02,400 --> 02:15:04,480 HAVING THIS METHOD AND APPLY TO 2833 02:15:04,480 --> 02:15:06,840 YOU CAN MAP NEW DATA SETS 2834 02:15:06,840 --> 02:15:09,040 AGAINST THE OLD. 2835 02:15:09,040 --> 02:15:12,280 YOU KNOW, WHEN DATA IS MEASURED 2836 02:15:12,280 --> 02:15:13,440 INDEPENDENTLY, EITHER BY THE 2837 02:15:13,440 --> 02:15:15,280 SAME GROUP BUT DIFFERENT 2838 02:15:15,280 --> 02:15:16,680 METHODS OR ACROSS DIFFERENT 2839 02:15:16,680 --> 02:15:18,560 GROUPS THAT CREATES A PROBLEM 2840 02:15:18,560 --> 02:15:23,000 OF TRYING TO NORMALIZE AND 2841 02:15:23,000 --> 02:15:23,920 INTEGRATE THOSE DATA SETS. 2842 02:15:23,920 --> 02:15:25,360 ONE OF THE REALLY POSITIVE 2843 02:15:25,360 --> 02:15:27,440 THINGS FROM THE SINGLE CELL 2844 02:15:27,440 --> 02:15:32,080 WORLD IS THAT IT'S POSSIBLE TO 2845 02:15:32,080 --> 02:15:33,240 INTEGRATE THESE QUITE 2846 02:15:33,240 --> 02:15:34,240 EFFECTIVELY. 2847 02:15:34,240 --> 02:15:36,720 I ALMOST HAD A SLIDE IN MY 2848 02:15:36,720 --> 02:15:37,440 PRESENTATION THAT SHOWED PART 2849 02:15:37,440 --> 02:15:40,440 OF THE CELL CENSUS EFFORT IN 2850 02:15:40,440 --> 02:15:45,600 THE MOUSE WHERE THERE THERE 2851 02:15:45,600 --> 02:15:47,680 WERE MULTIPLE TRANSCRIPTOME 2852 02:15:47,680 --> 02:15:59,480 METHODS, CELLS AND NUCLEI. 2853 02:15:59,480 --> 02:16:01,840 THEY COULD BE COMPARABLE. 2854 02:16:01,840 --> 02:16:04,000 THESE KINDS OF DATA KIND OF 2855 02:16:04,000 --> 02:16:05,800 LEND THEMSELVES WELL TO THAT. 2856 02:16:05,800 --> 02:16:07,400 BUT THERE ARE STILL INTEGRATION 2857 02:16:07,400 --> 02:16:08,000 PROBLEMS. 2858 02:16:08,000 --> 02:16:12,240 IF YOU COULD A TACK SEEK AND 2859 02:16:12,240 --> 02:16:14,120 RNA SEEK, YOU CAN ONLY ALIGN AT 2860 02:16:14,120 --> 02:16:17,160 A CERTAIN LEVEL OF CERTAINTY. 2861 02:16:17,160 --> 02:16:19,440 AND SO I THINK MORE AND MORE WE 2862 02:16:19,440 --> 02:16:21,640 ARE GOING TO BE NEEDING THE 2863 02:16:21,640 --> 02:16:22,760 COMBINED METHODS. 2864 02:16:22,760 --> 02:16:23,760 WHERE WE MEASURE THEM AT THE 2865 02:16:23,760 --> 02:16:25,120 SAME TIME. 2866 02:16:25,120 --> 02:16:26,480 AND THE COMPANIES ARE SEEING 2867 02:16:26,480 --> 02:16:27,920 THIS. 2868 02:16:27,920 --> 02:16:33,240 10 X NOW HAS MULTIOME. 2869 02:16:33,240 --> 02:16:37,320 WE FOUND HAVING A SMALL AMOUNT 2870 02:16:37,320 --> 02:16:40,360 OF MULTIOME ALLOWS YOU TO 2871 02:16:40,360 --> 02:16:42,080 INTEGRATE LARGER SINGLE 2872 02:16:42,080 --> 02:16:42,800 MODALITY SETS. 2873 02:16:42,800 --> 02:16:45,160 I THINK THIS IS GOING TO BE AN 2874 02:16:45,160 --> 02:16:46,560 ONGOING CHALLENGE FOR THE FIELD. 2875 02:16:46,560 --> 02:16:48,400 BUT ONE THAT THERE'S A HUGE 2876 02:16:48,400 --> 02:16:49,600 AMOUNT OF PROGRESS FOR. 2877 02:16:49,600 --> 02:16:52,160 AND I THINK IT REALLY IS WORTH 2878 02:16:52,160 --> 02:16:53,520 SOME SIGNIFICANT INVESTMENT 2879 02:16:53,520 --> 02:16:57,040 FROM N.I.H. IN FOSTERING THE 2880 02:16:57,040 --> 02:16:59,680 COMPUTATIONAL SIDE OF THINGS. 2881 02:16:59,680 --> 02:17:03,600 ON THE QUESTION OF SEXUAL 2882 02:17:03,600 --> 02:17:04,640 DIMORPHISM. 2883 02:17:04,640 --> 02:17:06,000 IT'S A CRITICAL QUESTION AND 2884 02:17:06,000 --> 02:17:08,640 ONE THAT ALL OF THE NAMED ATLAS 2885 02:17:08,640 --> 02:17:10,440 PROJECTS ARE MORE OR LESS 2886 02:17:10,440 --> 02:17:12,680 OBLIGATED TO TAKE ON, FOR GOOD 2887 02:17:12,680 --> 02:17:14,880 REASON. 2888 02:17:14,880 --> 02:17:17,160 AND YOU KNOW, OF COURSE YOU CAN 2889 02:17:17,160 --> 02:17:20,480 DIFFERENTIATE ON SEX CHROMOSOME 2890 02:17:20,480 --> 02:17:21,440 GENE EXPRESSION VERY EASILY. 2891 02:17:21,440 --> 02:17:26,600 BUT YOU CAN SEE SEXUAL 2892 02:17:26,600 --> 02:17:28,200 DIMORPHISMS IN MANY CASES. 2893 02:17:28,200 --> 02:17:30,520 I DON'T KNOW HOW MANY SURPRISES 2894 02:17:30,520 --> 02:17:33,040 HAVE BEEN PROMOTED SO FAR. 2895 02:17:33,040 --> 02:17:35,120 YOU SEE HYPE THALAMIC 2896 02:17:35,120 --> 02:17:36,600 DIFFERENCES DIFFERENTLY. 2897 02:17:36,600 --> 02:17:37,600 BUT THAT'S BEEN DESCRIBED IN 2898 02:17:37,600 --> 02:17:38,960 THE PAST. 2899 02:17:38,960 --> 02:17:40,600 CLEARLY THERE ARE DIFFERENCES, 2900 02:17:40,600 --> 02:17:46,040 PERHAPS THEY WILL MANIFEST MORE 2901 02:17:46,040 --> 02:17:46,760 ROBUSTLY DURING DEVELOPMENT AS 2902 02:17:46,760 --> 02:17:47,200 WELL. 2903 02:17:47,200 --> 02:17:49,240 I THINK THIS IS AN ESSENTIAL 2904 02:17:49,240 --> 02:17:50,920 THING THAT ALL THESE BIG 2905 02:17:50,920 --> 02:17:52,800 EFFORTS SHOULD HAVE AS PART OF 2906 02:17:52,800 --> 02:17:54,200 THE EXPERIMENTAL DESIGN SO WE 2907 02:17:54,200 --> 02:17:55,440 CAN BEGIN TO UNDERSTAND THESE 2908 02:17:55,440 --> 02:17:56,480 THINGS. 2909 02:17:56,480 --> 02:17:59,280 >> ONE QUICK FOLLOW-UP, ED. 2910 02:17:59,280 --> 02:18:01,040 IS THERE A DIFFERENCE, THOSE 2911 02:18:01,040 --> 02:18:03,480 DIFFERENCES THAT YOU SEE THOSE 2912 02:18:03,480 --> 02:18:04,880 RELATIVELY FEW DIFFERENCES, ARE 2913 02:18:04,880 --> 02:18:06,080 THEY WITHIN CELL TYPES? 2914 02:18:06,080 --> 02:18:09,840 OR DO YOU THINK THEY ARE LIKE 2915 02:18:09,840 --> 02:18:11,680 INVERTED NERVOUS SYSTEM 2916 02:18:11,680 --> 02:18:13,080 SEX-SPECIFIC CELL TYPE, THAT 2917 02:18:13,080 --> 02:18:15,640 ONLY EXIST IN ONE SEX VERSUS 2918 02:18:15,640 --> 02:18:17,200 THE OTHER? 2919 02:18:17,200 --> 02:18:19,400 >> ED: I WOULD HATE TO DEFER ON 2920 02:18:19,400 --> 02:18:21,440 THAT QUESTION, BUT I'M 2921 02:18:21,440 --> 02:18:22,800 REPRESENTING OTHERS' WORK THAT 2922 02:18:22,800 --> 02:18:24,840 I WOULD HESITATE TO GET WRONG. 2923 02:18:24,840 --> 02:18:27,240 LET'S JUST SAY THE QUESTION IS 2924 02:18:27,240 --> 02:18:28,160 UNDER ACTIVE INVESTIGATION. 2925 02:18:28,160 --> 02:18:30,040 BUT I THINK THERE ARE MORE 2926 02:18:30,040 --> 02:18:31,240 ROBUST DIFFERENCES IN CERTAIN 2927 02:18:31,240 --> 02:18:32,760 PARTS OF THE BRAIN. 2928 02:18:32,760 --> 02:18:33,440 >> OLIVER: I SEE. 2929 02:18:33,440 --> 02:18:34,320 THANK YOU. 2930 02:18:34,320 --> 02:18:36,120 ALL RIGHT, WE ARE PRETTY MUCH 2931 02:18:36,120 --> 02:18:37,520 AT THE END OF THIS MORNING 2932 02:18:37,520 --> 02:18:38,440 SESSION. 2933 02:18:38,440 --> 02:18:40,600 SO WE WILL NOW TAKE A 20-MINUTE 2934 02:18:40,600 --> 02:18:41,920 BREAK. 2935 02:18:41,920 --> 02:18:47,560 AND THEN WE WILL HAVE SESSION 2 2936 02:18:47,560 --> 02:18:49,600 START AT 1:40. 2937 02:18:49,600 --> 02:18:51,240 WONDERFUL. 2938 02:18:51,240 --> 02:18:52,800 SEE YOU GUYS THEN. 2939 02:18:52,800 --> 02:18:54,240 THANK YOU. 2940 02:18:54,240 --> 02:18:55,320 AND THANKS AGAIN TO THE 2941 02:18:55,320 --> 02:18:58,000 SPEAKERS. 2942 02:18:58,000 --> 02:18:59,040 >> THANKS, OLIVER, FOR RUNNING 2943 02:18:59,040 --> 02:19:00,320 THE SESSION. 2944 02:19:00,320 --> 02:19:02,240 >> ED: THANKS VERY MUCH. 2945 02:19:02,240 --> 02:20:35,240 THAT WAS FUN. 2946 02:20:35,240 --> 02:20:37,160 IT REALLY SHOWS THE PROBLEM WE 2947 02:20:37,160 --> 02:20:39,000 NEED TO ADDRESS IN NEURO 2948 02:20:39,000 --> 02:20:40,560 SCIENCE AND BRAIN SCIENCE. 2949 02:20:40,560 --> 02:20:42,040 PARTICULARLY ON THE LEFT, IF WE 2950 02:20:42,040 --> 02:20:43,920 LOOK AT THE SIZE OF THE 2951 02:20:43,920 --> 02:20:45,560 QUESTIONS WE ARE ASKING, MANY 2952 02:20:45,560 --> 02:20:49,520 OF US ARE WORKING AT DIFFERENT 2953 02:20:49,520 --> 02:20:56,480 LEVELS OF SCALES OF THE BRAIN. 2954 02:20:56,480 --> 02:20:59,560 FROM THE MICRON SYNAPTIC LEVEL, 2955 02:20:59,560 --> 02:21:01,720 NEURON TO THE CELLULAR LEVEL, 2956 02:21:01,720 --> 02:21:03,760 UP TO THE WHOLE BRAIN LEVEL. 2957 02:21:03,760 --> 02:21:05,200 AND THIS IS THE PROBLEM WE HAVE 2958 02:21:05,200 --> 02:21:10,960 TO DEAL WITH AND PART OF THE 2959 02:21:10,960 --> 02:21:12,360 DISCUSSION TODAY IN THIS 2960 02:21:12,360 --> 02:21:13,960 SESSION WILL BE LOOKING AT 2961 02:21:13,960 --> 02:21:22,200 BRAIN STUR STRUCTURE AND 2962 02:21:22,200 --> 02:21:23,640 FUNCTION AT THESE DIFFERENT 2963 02:21:23,640 --> 02:21:25,280 LEVELSMENT BUT DON'T FORGET P 2964 02:21:25,280 --> 02:21:26,880 ABOUT THE FOURTH DIMENSION, 2965 02:21:26,880 --> 02:21:28,320 TIME. 2966 02:21:28,320 --> 02:21:29,720 OUR BRAIN WORKS IN VERY 2967 02:21:29,720 --> 02:21:31,360 DIFFERENT SCALES OF TIME. 2968 02:21:31,360 --> 02:21:39,960 FROM MILLI SECONDS. 2969 02:21:39,960 --> 02:21:42,160 TO HOURS TO DAY, TO MONTHS AND 2970 02:21:42,160 --> 02:21:45,320 YEARS, ESPECIALLY FOR -- 2971 02:21:45,320 --> 02:21:47,000 GENERATION AND OTHER BEHAVIORAL 2972 02:21:47,000 --> 02:21:51,400 PROCESSES. 2973 02:21:51,400 --> 02:21:54,200 SO HERE TERRY SHOWED THE 2974 02:21:54,200 --> 02:21:55,360 STATE-OF-THE-ART IN 1988. 2975 02:21:55,360 --> 02:21:58,120 THIS IS STATE-OF-THE-ART IN 2976 02:21:58,120 --> 02:21:59,920 2014 WHERE HE IS LISTING 2977 02:21:59,920 --> 02:22:02,080 DIFFERENT METHODS TO MEASURE IN 2978 02:22:02,080 --> 02:22:04,280 DIFFERENT TIME SCALES AND 2979 02:22:04,280 --> 02:22:09,800 DIFFERENT SCALES OF SIZE. 2980 02:22:09,800 --> 02:22:11,960 AND I THINK WE CAN FILL THIS IN 2981 02:22:11,960 --> 02:22:15,080 WITH A LOT OF REVOLUTIONARY 2982 02:22:15,080 --> 02:22:16,320 TECHNIQUES DISCUSSED AND 2983 02:22:16,320 --> 02:22:17,200 DEVELOPED TODAY. 2984 02:22:17,200 --> 02:22:19,200 SO CAN I HAVE THE NEXT SLIDE, 2985 02:22:19,200 --> 02:22:19,960 PLEASE. 2986 02:22:19,960 --> 02:22:22,760 SO TODAY WE ARE GOING TO BE 2987 02:22:22,760 --> 02:22:23,960 TALKING ABOUT, BASICALLY TWO 2988 02:22:23,960 --> 02:22:25,360 DIFFERENT LEVELS. 2989 02:22:25,360 --> 02:22:27,920 WE WILL BE TALKING ABOUT 2990 02:22:27,920 --> 02:22:37,920 MEASURING BRAIN CONNECTIVITY. 2991 02:22:37,920 --> 02:22:45,760 AND DR. WILL BE TALKING ABOUT 2992 02:22:45,760 --> 02:22:47,760 -- 2993 02:22:47,760 --> 02:22:50,360 TRYING TO COMBINE MESO 2994 02:22:50,360 --> 02:22:51,840 MEASUREMENTS WITH HIGHER 2995 02:22:51,840 --> 02:22:53,120 RESOLUTION MEASUREMENTS. 2996 02:22:53,120 --> 02:22:56,680 AND THEN WE MOVE TO MODEL 2997 02:22:56,680 --> 02:22:59,640 SYSTEMS WHERE MEI ZHEN WILL BE 2998 02:22:59,640 --> 02:23:01,360 TALKING ABOUT WIRING CHANGES 2999 02:23:01,360 --> 02:23:04,040 ACROSS THE LIFE SPAN. 3000 02:23:04,040 --> 02:23:11,200 AND FINALLY TO SYSTEM WITH 3001 02:23:11,200 --> 02:23:12,840 ELLIE HECKSCHER TALKING FROM 3002 02:23:12,840 --> 02:23:17,080 STEM CELL TO CIRCUIT. 3003 02:23:17,080 --> 02:23:19,360 THIS IS A TALK IN SCALES AND 3004 02:23:19,360 --> 02:23:20,760 SOMETHING I THINK WE CAN 3005 02:23:20,760 --> 02:23:24,480 DISCUSS IN THE DISCUSSION WHAT, 3006 02:23:24,480 --> 02:23:27,680 THERE IS A BIG GAP HERE SO WHAT 3007 02:23:27,680 --> 02:23:29,200 WILL FILL THAT GAP. 3008 02:23:29,200 --> 02:23:39,560 WE WILL START RIGHT OFF WITH 3009 02:23:39,560 --> 02:23:40,800 DR. SETSOMPOP. 3010 02:23:40,800 --> 02:23:44,920 HE RECEIVED HIS MASTERS IN 3011 02:23:44,920 --> 02:23:48,040 SCIENCE FROM OXFORD UNIVERSITY. 3012 02:23:48,040 --> 02:23:51,760 AND COMPUTER SCIENCE FROM M.I.T. 3013 02:23:51,760 --> 02:23:54,920 POSTDOCTORAL FELLOW FROM THE 3014 02:23:54,920 --> 02:23:56,240 MARTINEZ CENTER. 3015 02:23:56,240 --> 02:23:57,600 HIS RESEARCH FOCUSES ON THE 3016 02:23:57,600 --> 02:24:00,600 DEVELOPMENT OF THE NOVEL M.R.I. 3017 02:24:00,600 --> 02:24:01,880 ACQUISITION METHODS AND THE 3018 02:24:01,880 --> 02:24:03,520 GOAL OF CREATING IMAGING 3019 02:24:03,520 --> 02:24:05,400 TECHNOLOGIES THAT COULD BE USED 3020 02:24:05,400 --> 02:24:08,280 TO HELP BETTER UNDERSTAND BRAIN 3021 02:24:08,280 --> 02:24:09,920 STRUCTURE AND FUNCTION FOR 3022 02:24:09,920 --> 02:24:11,160 APPLICATIONS IN HEALTHCARE AND 3023 02:24:11,160 --> 02:24:15,160 HEALTH SCIENCE. 3024 02:24:15,160 --> 02:24:18,480 DR. SETSOMPOP, TAKE IT AWAY. 3025 02:24:18,480 --> 02:24:20,840 >> THANK YOU FOR THAT 3026 02:24:20,840 --> 02:24:21,760 INTRODUCTION. 3027 02:24:21,760 --> 02:24:25,360 LET ME SHARE MY SCREEN. 3028 02:24:25,360 --> 02:24:35,720 CAN EVERYONE SEE MY SCREEN OKAY? 3029 02:24:35,720 --> 02:24:38,560 FOR THE OVERVIEW OF THE 3030 02:24:38,560 --> 02:24:39,960 SECTION, LOOKING FORWARD TO 3031 02:24:39,960 --> 02:24:41,560 LEARNING MORE ABOUT THROUGH 3032 02:24:41,560 --> 02:24:41,880 THESE TALKS. 3033 02:24:41,880 --> 02:24:50,680 SO MY TALK WILL BE TOWARDS 3034 02:24:50,680 --> 02:24:51,840 PRECISION MESOSCALE M.R.I. 3035 02:24:51,840 --> 02:24:53,160 ACROSS THE LIFE SPAN. 3036 02:24:53,160 --> 02:24:54,680 THESE ARE MY DISCLOSURES. 3037 02:24:54,680 --> 02:24:56,760 I WOULD LIKE TO SHOW TECHNOLOGY 3038 02:24:56,760 --> 02:24:59,360 MY LAB HAS BEEN PUSHING FORWARD 3039 02:24:59,360 --> 02:25:02,040 IN TERMS OF M.R.I. ACQUISITION, 3040 02:25:02,040 --> 02:25:05,520 TO ALLOW US AT THE MESOSCALE 3041 02:25:05,520 --> 02:25:08,000 PRECISELY AS WELL AS RAPIDLY. 3042 02:25:08,000 --> 02:25:10,920 I WILL FOCUS ON TWO AREAS IN 3043 02:25:10,920 --> 02:25:12,960 THIS TOPIC, QUANTITATIVE 3044 02:25:12,960 --> 02:25:14,720 IMAGING AND ADVANCED DIFFUSION 3045 02:25:14,720 --> 02:25:16,240 IMAGING. 3046 02:25:16,240 --> 02:25:17,440 STARTING WITH QUANTITATIVE 3047 02:25:17,440 --> 02:25:18,880 IMAGING, I WOULD LIKE TO 3048 02:25:18,880 --> 02:25:20,040 DESCRIBE SOME METHODS WE WOULD 3049 02:25:20,040 --> 02:25:26,920 BE USING TO GET TO RAPID 3050 02:25:26,920 --> 02:25:28,400 REPEATABLE. 3051 02:25:28,400 --> 02:25:29,800 LOOKING AT QUANTITATIVE 3052 02:25:29,800 --> 02:25:33,320 IMAGING, WE WANT TO IMAGE THE 3053 02:25:33,320 --> 02:25:34,280 UNDERLYING QUANTITATIVE TISSUE 3054 02:25:34,280 --> 02:25:36,800 RATHER THAN THE TYPICAL 3055 02:25:36,800 --> 02:25:38,000 CONTRAST WAY IMAGES ARE DONE. 3056 02:25:38,000 --> 02:25:41,040 IN THE HOPE WE COULD MOVE 3057 02:25:41,040 --> 02:25:42,520 TOWARD MORE PRECISE AND 3058 02:25:42,520 --> 02:25:43,600 REPEATABLE INFORMATION. 3059 02:25:43,600 --> 02:25:46,200 AS WELL AS DO MORE QUANTITATIVE 3060 02:25:46,200 --> 02:25:51,040 ANALYSIS. 3061 02:25:51,040 --> 02:25:53,880 THESE THINGS WILL BE IMPORTANT 3062 02:25:53,880 --> 02:25:55,520 WHEN DOING LARGE SCALE STUDY 3063 02:25:55,520 --> 02:25:57,840 AND ACROSS THE LIFE SPAN. 3064 02:25:57,840 --> 02:25:59,000 QUANTITATIVE IMAGING IS A 3065 02:25:59,000 --> 02:26:00,360 PROMISING WAY TO DO THINGS, 3066 02:26:00,360 --> 02:26:03,240 HOWEVER IT COULD TAKE A LONG 3067 02:26:03,240 --> 02:26:05,560 TIME TO DO BECAUSE IT'S MORE 3068 02:26:05,560 --> 02:26:07,400 INTENSIVE IN TERMS OF IMAGING 3069 02:26:07,400 --> 02:26:14,440 ENCODING. 3070 02:26:14,440 --> 02:26:19,160 A POPULAR APPROACH HAS BEEN 3071 02:26:19,160 --> 02:26:20,560 FINGERPRINTING, IMAGING M.R.I. 3072 02:26:20,560 --> 02:26:23,600 IS DONE WITH COHERENT SPACE 3073 02:26:23,600 --> 02:26:25,960 TIME AND CONTRAST TO REALLY 3074 02:26:25,960 --> 02:26:28,480 SPEED THINGS UP AND EACH 3075 02:26:28,480 --> 02:26:32,200 ACQUISITION OF THIS M.R.I. 3076 02:26:32,200 --> 02:26:36,360 SCAN, EACH POPULATION WILL 3077 02:26:36,360 --> 02:26:38,480 POSSESS TEMPORAL FINGERPRINT TO 3078 02:26:38,480 --> 02:26:43,000 ALLOW YOU TO REPLICATE AS SHOWN 3079 02:26:43,000 --> 02:26:44,000 HERE. 3080 02:26:44,000 --> 02:26:49,160 THIS APPROACH WAS INVENTED IN 3081 02:26:49,160 --> 02:26:51,480 2013 BY A GROUP AT CASE WESTERN. 3082 02:26:51,480 --> 02:26:53,360 ONE OF THE MOST EFFICIENT 3083 02:26:53,360 --> 02:26:55,160 ACQUISITION AT THE TIME. 3084 02:26:55,160 --> 02:26:57,080 TAKES AROUND 10 SECONDS PER 3085 02:26:57,080 --> 02:27:01,400 IMAGING SLICE TO GET ALL THESE 3086 02:27:01,400 --> 02:27:01,960 PARAMETERS. 3087 02:27:01,960 --> 02:27:03,560 WHICH IS GREAT BUT AT THE SAME 3088 02:27:03,560 --> 02:27:06,600 TIME TRYING TO TARGET VERY HIGH 3089 02:27:06,600 --> 02:27:08,960 RESOLUTION ACROSS THE WHOLE 3090 02:27:08,960 --> 02:27:10,360 BRAIN OF 200-300 SLICES. 3091 02:27:10,360 --> 02:27:12,480 IT COULD STILL TAKE 30 MINUTES 3092 02:27:12,480 --> 02:27:14,640 OR LONGER MAKING IT HARD TO 3093 02:27:14,640 --> 02:27:16,720 TRANSLATE AND USE ROUTINELY. 3094 02:27:16,720 --> 02:27:18,920 OVER THE LAST FEW YEARS THERE'S 3095 02:27:18,920 --> 02:27:21,240 BEEN A LOT OF ADVANCEMENT TO 3096 02:27:21,240 --> 02:27:23,160 TRY TO IMPROVE ON M.R.I. 3097 02:27:23,160 --> 02:27:23,720 ACQUISITION. 3098 02:27:23,720 --> 02:27:25,560 SOME OF WHICH I WILL FOCUS ON 3099 02:27:25,560 --> 02:27:27,120 HERE IN TERMS OF MAJOR 3100 02:27:27,120 --> 02:27:31,440 ADVANCEMENT. 3101 02:27:31,440 --> 02:27:33,320 FIRST IN TERMS, INSTEAD OF ONE 3102 02:27:33,320 --> 02:27:37,360 SLICE AT A TIME, WE ARE NOW 3103 02:27:37,360 --> 02:27:45,520 DOING MULTIPLE OR 3D IMAGING. 3104 02:27:45,520 --> 02:27:46,880 THESE VOLUMETRIC ALLOWS YOU TO 3105 02:27:46,880 --> 02:27:52,280 UNDERSTAND THE DATA ACROSS MORE 3106 02:27:52,280 --> 02:27:55,000 DIMENSIONS. 3107 02:27:55,000 --> 02:28:01,480 THERE'S ALSO BEEN A LOT OF WORK 3108 02:28:01,480 --> 02:28:02,960 IMPROVING, AS WELL AS PRIOR 3109 02:28:02,960 --> 02:28:04,640 INFORMATION ABOUT OUR SIGNAL 3110 02:28:04,640 --> 02:28:05,360 INFORMATION, PARTICULARLY 3111 02:28:05,360 --> 02:28:08,960 THROUGH THE METHOD OF LOW 3112 02:28:08,960 --> 02:28:10,600 TEMPORAL SUB SPACE, WHERE YOU 3113 02:28:10,600 --> 02:28:12,680 HAVE A SIGNAL EVOLUTION OF 3114 02:28:12,680 --> 02:28:14,760 THESE DIFFERENT TISSUES ACROSS 3115 02:28:14,760 --> 02:28:16,040 500 DIFFERENT TIME POINTS YOU 3116 02:28:16,040 --> 02:28:17,560 ARE TRYING TO RESOLVE. 3117 02:28:17,560 --> 02:28:20,840 BUT YOU CAN NOTE THAT THESE 3118 02:28:20,840 --> 02:28:22,000 SIGNAL EVOLUTION ACTUALLY LIVE 3119 02:28:22,000 --> 02:28:25,280 IN A SMALL SUB SPACE OF THE 3120 02:28:25,280 --> 02:28:27,160 TEMPORAL BASIS, SO INSTEAD OF 3121 02:28:27,160 --> 02:28:29,200 TRYING TO RECONSTRUCT 500 3122 02:28:29,200 --> 02:28:33,360 IMAGING VOLUMES YOU ONLY NEED 3123 02:28:33,360 --> 02:28:37,160 TO RECONSTRUCT 5 VOLUMES OF 3124 02:28:37,160 --> 02:28:39,760 THESE SUB SPACE SPACES, MAKING 3125 02:28:39,760 --> 02:28:41,160 THE RECONSTRUCTION PROBLEM A 3126 02:28:41,160 --> 02:28:43,720 LOT EASIER, ALLOWING YOU TO DO 3127 02:28:43,720 --> 02:28:44,800 MUCH FASTER IMAGING WITH GOOD 3128 02:28:44,800 --> 02:28:45,360 QUALITY. 3129 02:28:45,360 --> 02:28:47,920 WE HAVE DONE A LOT OF WORK IN 3130 02:28:47,920 --> 02:28:50,440 TERMS OF SEQUENCE OPTIMIZATION, 3131 02:28:50,440 --> 02:28:52,520 FLIP ANGLE AND THINGS LIKE 3132 02:28:52,520 --> 02:28:55,640 THAT, TO PROVIDE MORE UNITS OF 3133 02:28:55,640 --> 02:28:59,240 FINGERPRINT TISSUE TO ALLOW FOR 3134 02:28:59,240 --> 02:29:03,640 MORE SIGNAL SEPARABILITY. 3135 02:29:03,640 --> 02:29:05,120 WHERE DOES THIS ADVANCEMENT GET 3136 02:29:05,120 --> 02:29:05,960 US TO? 3137 02:29:05,960 --> 02:29:07,360 THIS IS SOME OF THE LATEST 3138 02:29:07,360 --> 02:29:09,000 RESULTS FROM MY LAB, WHERE WE 3139 02:29:09,000 --> 02:29:12,280 ARE NOW ABLE TO ACHIEVE ORDER 3140 02:29:12,280 --> 02:29:14,600 OF MAGNITUDE FASTER IMAGING 3141 02:29:14,600 --> 02:29:17,160 WITH M.R.F., ONE MILLIMETER 3142 02:29:17,160 --> 02:29:18,800 ISOTROPIC, WE CAN DO THIS IN 3143 02:29:18,800 --> 02:29:22,840 LESS THAN TWO MINUTES, T1 AND 3144 02:29:22,840 --> 02:29:24,360 T2 MAPS. 3145 02:29:24,360 --> 02:29:27,160 USE THIS INCREASE OF EFFICIENCY 3146 02:29:27,160 --> 02:29:29,120 OF IMAGING ENCODING TO PUSH FOR 3147 02:29:29,120 --> 02:29:30,000 HIGHER RESOLUTION. 3148 02:29:30,000 --> 02:29:36,560 THIS IS 0.66 MILLIMETER BRAIN, 3149 02:29:36,560 --> 02:29:37,600 REQUIRING FOUR MINUTES. 3150 02:29:37,600 --> 02:29:38,840 YOU CAN APPRECIATE THE 3151 02:29:38,840 --> 02:29:40,440 INCREASING DETAIL AS WE PUSH 3152 02:29:40,440 --> 02:29:42,320 FOR A HIGHER RESOLUTION WHERE 3153 02:29:42,320 --> 02:29:47,640 WE CAN SEE SOME OF THE 3154 02:29:47,640 --> 02:29:49,520 PARAVASCULAR SPACE HERE. 3155 02:29:49,520 --> 02:29:50,560 IT'S STILL SURPRISING SOMETIMES 3156 02:29:50,560 --> 02:29:54,000 LOOKING AT THIS WE HAVE 3157 02:29:54,000 --> 02:29:54,760 SUFFICIENT SNR ENCODING ABILITY 3158 02:29:54,760 --> 02:29:58,280 TO DO THIS ON A CLINICAL THREE 3159 02:29:58,280 --> 02:30:01,640 TESLA SCANNER. 3160 02:30:01,640 --> 02:30:03,040 AND THE MAIN DRIVE IN OUR 3161 02:30:03,040 --> 02:30:05,800 ABILITY TO DO THIS, WE ARE 3162 02:30:05,800 --> 02:30:08,360 USING M.R.I. SCANNER IN AN 3163 02:30:08,360 --> 02:30:13,920 EFFICIENT WAY, DOING CONTINUOUS 3164 02:30:13,920 --> 02:30:15,320 VOLUMETRIC RESOLUTION, WE ARE 3165 02:30:15,320 --> 02:30:28,480 ACQUIRING DATA AT A TIME AND WE 3166 02:30:28,480 --> 02:30:29,000 ARE POOLING ALL THIS DATA 3167 02:30:29,000 --> 02:30:29,440 TOGETHER IN A NICE 3168 02:30:29,440 --> 02:30:30,080 RECONSTRUCTION TO PROVIDE IVE 3169 02:30:30,080 --> 02:30:30,520 INFORMATION QUICKLY. 3170 02:30:30,520 --> 02:30:31,920 SO NOW THAT I HAVE SHOWN YOU 3171 02:30:31,920 --> 02:30:33,920 SOME OF THE METHODS, LET'S LOOK 3172 02:30:33,920 --> 02:30:35,960 AT SOME OF THE BENEFIT OF 3173 02:30:35,960 --> 02:30:36,760 QUANTITATIVE IMAGING. 3174 02:30:36,760 --> 02:30:39,160 I THINK THIS IS QUITE A NEAT 3175 02:30:39,160 --> 02:30:40,760 EXAMPLE WHERE SHOW 3176 02:30:40,760 --> 02:30:42,320 REPEATABILITY OF SCANS, NOT 3177 02:30:42,320 --> 02:30:44,800 ONLY ACROSS TIME POINTS, BUT 3178 02:30:44,800 --> 02:30:48,080 ALSO ACROSS SCANNER VENDORS ON 3179 02:30:48,080 --> 02:30:50,360 A HEALTHY VOLUNTEER. 3180 02:30:50,360 --> 02:30:52,000 ONE MILLIMETER WHOLE BRAIN 3181 02:30:52,000 --> 02:30:55,360 M.R.I. SCAN TWO MINUTES, 3182 02:30:55,360 --> 02:30:57,240 SIEMENS SCANNER. 3183 02:30:57,240 --> 02:30:59,560 SIX MONTHS LATER, GE PREMIERE 3184 02:30:59,560 --> 02:31:03,320 ON SAME HEALTHY VOLUNTEER. 3185 02:31:03,320 --> 02:31:04,720 DO SUBTRACTION AND SCALE THINGS 3186 02:31:04,720 --> 02:31:06,360 UP BY A FACTOR OF 10. 3187 02:31:06,360 --> 02:31:08,680 YOU CAN SEE THESE MINIMAL 3188 02:31:08,680 --> 02:31:10,760 DIFFERENCES BETWEEN THESE TWO 3189 02:31:10,760 --> 02:31:13,760 SCANS, SHOWING GREAT 3190 02:31:13,760 --> 02:31:15,360 REPEATABILITY AND RELATEBLY 3191 02:31:15,360 --> 02:31:16,360 HIGH RESOLUTION. 3192 02:31:16,360 --> 02:31:18,760 SO OVER THE LAST YEAR OR TWO OF 3193 02:31:18,760 --> 02:31:21,760 ALSO TRYING TO PUSH THIS 3194 02:31:21,760 --> 02:31:22,960 TECHNOLOGY FURTHER, INFUSING IN 3195 02:31:22,960 --> 02:31:26,880 SOME OF THE ADVANCED MACHINE 3196 02:31:26,880 --> 02:31:29,720 LEARNING FOR OUR IMAGING, AS 3197 02:31:29,720 --> 02:31:33,960 WELL AS OUR ABILITY TO PROVIDE 3198 02:31:33,960 --> 02:31:35,360 -- WE ARE STARTING TO RULE 3199 02:31:35,360 --> 02:31:37,960 SOME OF THIS OUT TO THE CLINIC 3200 02:31:37,960 --> 02:31:39,400 AT THE STANFORD HOSPITAL AS 3201 02:31:39,400 --> 02:31:40,640 WELL AS AT THE CHILDREN'S 3202 02:31:40,640 --> 02:31:41,760 HOSPITAL. 3203 02:31:41,760 --> 02:31:45,200 SO HERE IS SOME OF OUR LATEST 3204 02:31:45,200 --> 02:31:46,840 RESULTS OF PRELIMINARY DATA. 3205 02:31:46,840 --> 02:31:51,360 WHILE WE ARE ABLE TO GET ONE 3206 02:31:51,360 --> 02:31:53,440 MILLIMETER ISOTROPIC WHOLE 3207 02:31:53,440 --> 02:31:58,360 BRAIN OF T1, T2 AND SIM PATIC 3208 02:31:58,360 --> 02:32:01,160 CONTRAST WITH ONE MINUTE SCAN 3209 02:32:01,160 --> 02:32:04,240 WITH RECONSTRUCTION, THESE ARE 3210 02:32:04,240 --> 02:32:05,960 THE CLINICAL CONTRASTS WE ARE 3211 02:32:05,960 --> 02:32:10,160 ABLE TO SYNTHESIZE, HAVE GOOD 3212 02:32:10,160 --> 02:32:12,280 CORRESPONDENCE TO A CLINICAL 3213 02:32:12,280 --> 02:32:15,160 SCAN NORMALLY USED, TAKES 3214 02:32:15,160 --> 02:32:16,720 AROUND 30 MINUTES. 3215 02:32:16,720 --> 02:32:19,080 WITH THIS HOPEFULLY I CAN SHOW 3216 02:32:19,080 --> 02:32:20,920 YOU DEVELOPING TECHNOLOGY TO 3217 02:32:20,920 --> 02:32:24,440 MOVE US TO EXAM AT HIGH 3218 02:32:24,440 --> 02:32:25,880 RESOLUTION IN JUST A FEW 3219 02:32:25,880 --> 02:32:27,520 MINUTES WITH FAST ONLINE 3220 02:32:27,520 --> 02:32:29,600 RECONSTRUCTION AND ACCURATE 3221 02:32:29,600 --> 02:32:30,600 SYNTHESIZED CONTRAST WEIGHTED 3222 02:32:30,600 --> 02:32:31,480 IMAGES. 3223 02:32:31,480 --> 02:32:33,360 AND HOPEFULLY THIS WILL BE 3224 02:32:33,360 --> 02:32:35,240 REALLY USEFUL FOR LARGE-SCALE 3225 02:32:35,240 --> 02:32:37,080 STUDY, AS WELL AS IMAGING 3226 02:32:37,080 --> 02:32:41,240 ACROSS THE LIFE SPAN. 3227 02:32:41,240 --> 02:32:43,000 CONTINUING ON THIS THEME, 3228 02:32:43,000 --> 02:32:46,680 MOVING FROM MR DP*, WE ARE ALSO 3229 02:32:46,680 --> 02:32:49,000 DEVELOPING ANOTHER TECHNIQUE, 3230 02:32:49,000 --> 02:32:52,240 ECHO TIME RESULT OR E.P.T.I. 3231 02:32:52,240 --> 02:32:55,080 THIS UTILIZES WHAT I WOULD CALL 3232 02:32:55,080 --> 02:32:56,960 TIME RESULT IMAGING SIMILAR TO 3233 02:32:56,960 --> 02:32:59,280 M.R.F., WE ARE USING SCANNER 3234 02:32:59,280 --> 02:33:02,160 NOT AS A CAMERA WHICH IT WAS 3235 02:33:02,160 --> 02:33:03,200 USED BEFORE, BUT MORE AS A 3236 02:33:03,200 --> 02:33:04,040 VIDEO. 3237 02:33:04,040 --> 02:33:06,160 NOT TAKING A FEW IMAGES AND 3238 02:33:06,160 --> 02:33:08,440 TRYING TO GET TO QUANTITATIVE 3239 02:33:08,440 --> 02:33:11,000 MEASURE BUT CAPTURING A TIME 3240 02:33:11,000 --> 02:33:12,640 SERIES OF 500-1,000 IMAGES AND 3241 02:33:12,640 --> 02:33:14,000 REALLY TRACK THE SIGNAL 3242 02:33:14,000 --> 02:33:16,520 EVOLUTION TO GET REALLY NICE 3243 02:33:16,520 --> 02:33:17,800 QUANTITATIVE INFORMATION. 3244 02:33:17,800 --> 02:33:19,440 SO IN ORDER TO DO THIS, WE HAVE 3245 02:33:19,440 --> 02:33:21,360 TO DO A LOT MORE ENCODING. 3246 02:33:21,360 --> 02:33:24,160 WE HAVE TO DO CASE BASE FOR 3247 02:33:24,160 --> 02:33:27,680 ENCODING, NOT ONLY ACROSS A FEW 3248 02:33:27,680 --> 02:33:30,680 VOLUMES BUT ACROSS THOUSANDS OF 3249 02:33:30,680 --> 02:33:30,920 VOLUMES. 3250 02:33:30,920 --> 02:33:33,240 WE HAVE TO COME UP WITH A WAY 3251 02:33:33,240 --> 02:33:36,160 TO ACQUIRE THIS DATA IN AN 3252 02:33:36,160 --> 02:33:37,960 EFFICIENT MATTER, SO WE COME UP 3253 02:33:37,960 --> 02:33:39,760 WITH ACQUISITION IN THIS TIME 3254 02:33:39,760 --> 02:33:43,000 SPACE WHERE WE CAN HIGHLY 3255 02:33:43,000 --> 02:33:44,640 SAMPLE OUR ACQUISITION USING 3256 02:33:44,640 --> 02:33:52,040 SOME APPROACHES OF SPARSITY AND 3257 02:33:52,040 --> 02:33:56,080 CONTROL ALIASING, AS WELL AS 3258 02:33:56,080 --> 02:33:58,120 SPATIAL TEMPORAL, SO WE CAN 3259 02:33:58,120 --> 02:33:59,960 RESOLVE MORE TIME RESOLVE 3260 02:33:59,960 --> 02:34:01,760 HUNDREDS OF DIFFERENT IMAGES 3261 02:34:01,760 --> 02:34:03,160 ACROSS OUR ACQUISITION. 3262 02:34:03,160 --> 02:34:06,840 HERE IS AN EXAMPLE OF E.P.T.I. 3263 02:34:06,840 --> 02:34:10,320 ACQUIRES DATA FOR 9180 SPIN 3264 02:34:10,320 --> 02:34:11,760 ACQUISITION, TRACKING THE STAR 3265 02:34:11,760 --> 02:34:13,680 SIGNAL EVOLUTION AS WELL AS T2 3266 02:34:13,680 --> 02:34:14,960 RECOVERY. 3267 02:34:14,960 --> 02:34:18,480 WE ARE GETTING MORE THAN 100 3268 02:34:18,480 --> 02:34:21,520 IMAGES, WHICH ARE PRETTY SHARP 3269 02:34:21,520 --> 02:34:24,280 CRISP IMAGES ACROSS THESE 3270 02:34:24,280 --> 02:34:25,120 DIFFERENT SIGNAL. 3271 02:34:25,120 --> 02:34:29,600 SO WE CAN ACQUIRE THIS RAPIDLY. 3272 02:34:29,600 --> 02:34:31,000 UTILIZING THIS TECHNIQUE, OF 3273 02:34:31,000 --> 02:34:32,680 THIS DATA ACQUISITION, WE 3274 02:34:32,680 --> 02:34:36,120 DESIGN OUR SEQUENCE TO BE 3275 02:34:36,120 --> 02:34:39,760 SENSITIVE TO T1, T2 STAR SIGNAL 3276 02:34:39,760 --> 02:34:41,520 VARIATIONS, IN JUST A THREE 3277 02:34:41,520 --> 02:34:44,600 MINUTE SCAN WE CAN GENERATE 3278 02:34:44,600 --> 02:34:47,360 MORE THAN 1,000 WHOLE BRAIN AT 3279 02:34:47,360 --> 02:34:48,600 100 METER ISOTROPIC. 3280 02:34:48,600 --> 02:34:52,280 FROM THIS, WE ARE ABLE TO THEN 3281 02:34:52,280 --> 02:34:55,000 DERIVE ACCURATE QUANTITATIVE 3282 02:34:55,000 --> 02:34:56,280 MEASURES OF TISSUE PARAMETERS 3283 02:34:56,280 --> 02:34:57,160 SHOWN HERE. 3284 02:34:57,160 --> 02:34:59,960 WE HAVE DONE QUITE A BIT OF 3285 02:34:59,960 --> 02:35:02,920 SCAN, RESCAN REPEATABILITY 3286 02:35:02,920 --> 02:35:03,680 ACROSS MULTIPLE HEALTHY 3287 02:35:03,680 --> 02:35:06,200 SUBJECTS OF THIS CASE, E.P.T.I. 3288 02:35:06,200 --> 02:35:08,120 SCAN WE CAN GET THE 3289 02:35:08,120 --> 02:35:11,000 QUANTITATIVE T1 MAP TO DO AUTO 3290 02:35:11,000 --> 02:35:11,840 BRAIN SEGMENTATION INTO 3291 02:35:11,840 --> 02:35:13,280 DIFFERENT REGIONS. 3292 02:35:13,280 --> 02:35:16,360 FROM THESE REGIONS WE THEN LOOK 3293 02:35:16,360 --> 02:35:18,720 AT SCAN/RESCAN REPEATABILITY OF 3294 02:35:18,720 --> 02:35:21,200 THESE QUANTITATIVE MESHS. 3295 02:35:21,200 --> 02:35:25,880 IT HAS GREAT SCAN/REPEAT SCAN 3296 02:35:25,880 --> 02:35:27,760 REPEATABILITY, BIAS SHOWN HERE 3297 02:35:27,760 --> 02:35:28,680 ACROSS THESE PARAMETERS. 3298 02:35:28,680 --> 02:35:30,960 WITH THIS TECHNIQUE WE CAN ALSO 3299 02:35:30,960 --> 02:35:33,680 ACHIEVE HIGH SPATIAL RESOLUTION 3300 02:35:33,680 --> 02:35:36,520 ACCEPTABLE SCAN TIME ON A 3301 02:35:36,520 --> 02:35:39,320 COMMERCIAL THREE TESLA SCANNER. 3302 02:35:39,320 --> 02:35:41,600 0.7 MILLIMETER ISOTROPIC IN 3303 02:35:41,600 --> 02:35:42,440 JUST NINE MINUTES. 3304 02:35:42,440 --> 02:35:44,400 FROM THIS WE CAN ACTUALLY START 3305 02:35:44,400 --> 02:35:48,600 TO LOOK AT CORTICAL DEPTH 3306 02:35:48,600 --> 02:35:51,600 PROFILE. 3307 02:35:51,600 --> 02:35:55,440 T1, T2 AND T2 STAR, WE CAN 3308 02:35:55,440 --> 02:35:57,040 SEGMENT THE BRAIN USING OUR T1 3309 02:35:57,040 --> 02:35:58,680 MAP. 3310 02:35:58,680 --> 02:36:01,640 LOOKING AT DIFFERENT CORTICAL 3311 02:36:01,640 --> 02:36:04,560 LAYERS IN THE CORTEX INFLATE UP 3312 02:36:04,560 --> 02:36:07,360 INTO SURFACES AND THEN LOOK AT 3313 02:36:07,360 --> 02:36:08,960 THESE QUANTITATIVE PARAMETERS 3314 02:36:08,960 --> 02:36:10,600 AT DIFFERENT CORTICAL DEPTHS, 3315 02:36:10,600 --> 02:36:12,480 AS WELL AS DIFFERENT BRAIN 3316 02:36:12,480 --> 02:36:13,640 REGIONS, AS SHOWN HERE. 3317 02:36:13,640 --> 02:36:15,720 YOU CAN START TO PLOT THE -- 3318 02:36:15,720 --> 02:36:17,160 OOPS. 3319 02:36:17,160 --> 02:36:18,880 GO BACK ONE. 3320 02:36:18,880 --> 02:36:22,600 YEP, YOU CAN START TO PLOT THE 3321 02:36:22,600 --> 02:36:24,240 CORTICAL PROFILE AT THESE 3322 02:36:24,240 --> 02:36:25,400 DIFFERENT BRAIN REGIONS AS 3323 02:36:25,400 --> 02:36:28,960 SHOWN HERE AT THESE DIFFERENT 3324 02:36:28,960 --> 02:36:30,120 PARAMETERS, ASSUMING INTO ONE 3325 02:36:30,120 --> 02:36:30,800 OF THESE REGIONS. 3326 02:36:30,800 --> 02:36:32,880 WE CAN LOOK AT REPEATABILITY. 3327 02:36:32,880 --> 02:36:34,520 AGAIN, THESE ARE ACROSS 3328 02:36:34,520 --> 02:36:36,920 SUBJECTS, AS WELL AS 3329 02:36:36,920 --> 02:36:39,160 SCAN/RESCAN WHERE WE HAVE 3330 02:36:39,160 --> 02:36:43,160 CONSISTENT CORTICAL PROFILE OF 3331 02:36:43,160 --> 02:36:44,360 THESE QUANTITATIVES PARAMETERS. 3332 02:36:44,360 --> 02:36:46,160 LOOKING AT THIS DATA A BIT MORE 3333 02:36:46,160 --> 02:36:50,520 CLOSELY WE CAN SEE THAT WE HAVE 3334 02:36:50,520 --> 02:36:54,280 LOWER INTRA SUBJECT VARIABILITY 3335 02:36:54,280 --> 02:36:56,120 THAN INTERSUBJECT VARIABILITY. 3336 02:36:56,120 --> 02:36:57,960 POINTING TO AN EXCITING 3337 02:36:57,960 --> 02:36:59,800 POTENTIAL WE MIGHT BE ABLE TO 3338 02:36:59,800 --> 02:37:01,200 START TO DETECT INDIVIDUAL 3339 02:37:01,200 --> 02:37:03,560 DIFFERENCES IN THESE 3340 02:37:03,560 --> 02:37:05,920 QUANTITATIVE MESHES, EVEN IN 3341 02:37:05,920 --> 02:37:07,560 HEALTHY VOLUNTEER COHORTS. 3342 02:37:07,560 --> 02:37:11,240 SO TO BE ABLE TO DO PRECISION 3343 02:37:11,240 --> 02:37:12,880 QUANTITATIVE M.R., IT'S ALSO 3344 02:37:12,880 --> 02:37:15,440 IMPORTANT TO BE MOTION ROBUST 3345 02:37:15,440 --> 02:37:16,600 PARTICULARLY WHEN IMAGING 3346 02:37:16,600 --> 02:37:18,480 ACROSS THE LIFE SPAN WITH YOUNG 3347 02:37:18,480 --> 02:37:20,080 CHILDREN AS WELL AS OLDER 3348 02:37:20,080 --> 02:37:22,320 ADULTS. 3349 02:37:22,320 --> 02:37:24,160 SO DEVELOP WAYS TO DO THIS 3350 02:37:24,160 --> 02:37:26,960 USING A RAPID 3D NAVIGATOR TO 3351 02:37:26,960 --> 02:37:29,680 BE ABLE TO INSERT THIS INTO THE 3352 02:37:29,680 --> 02:37:31,480 DEAD TIME OF THE SEQUENCE TO 3353 02:37:31,480 --> 02:37:33,560 TRACK MOTION AS WELL AS FIELD 3354 02:37:33,560 --> 02:37:35,880 VARIATION IN THE SCANNER THAT 3355 02:37:35,880 --> 02:37:37,560 CAN BE CAUSED BY SOME OF THESE 3356 02:37:37,560 --> 02:37:39,640 MOTIONS TO GET PRECISION 3357 02:37:39,640 --> 02:37:40,560 IMAGING. 3358 02:37:40,560 --> 02:37:42,440 SO HERE IS SOME OF OUR TRACKING. 3359 02:37:42,440 --> 02:37:43,880 HERE IS SOME OF THE 3360 02:37:43,880 --> 02:37:45,480 QUANTITATIVE MAPS THAT WE ARE 3361 02:37:45,480 --> 02:37:48,480 ABLE TO GET WITHOUT ANY MOTION 3362 02:37:48,480 --> 02:37:52,560 AND WITH MOTION SUBJECT THAT WE 3363 02:37:52,560 --> 02:37:54,680 THEN ESTIMATE AND CORRECT FOR 3364 02:37:54,680 --> 02:37:55,840 IN OUR RECONSTRUCTION AND WE 3365 02:37:55,840 --> 02:38:00,360 CAN SEE HERE THAT YOU ARE ABLE 3366 02:38:00,360 --> 02:38:03,160 TO GET PRETTY GOOD 3367 02:38:03,160 --> 02:38:04,800 CORRESPONDENCE BETWEEN THE 3368 02:38:04,800 --> 02:38:08,360 MOTION-FREE REFERENCE AND 3369 02:38:08,360 --> 02:38:10,360 MOTION-CORRECTED RECONSTRUCTION 3370 02:38:10,360 --> 02:38:13,000 OF MOTION CORRECT DATA. 3371 02:38:13,000 --> 02:38:15,560 WE ARE MOVING TOWARD PRECISION 3372 02:38:15,560 --> 02:38:16,560 QUANTITATIVE M.R.I. WHERE WE 3373 02:38:16,560 --> 02:38:19,360 HAVE RAPID AND REPEATABLE 3374 02:38:19,360 --> 02:38:21,440 QUANTITATIVE IMAGING WITH MORE 3375 02:38:21,440 --> 02:38:24,000 TISSUE PARAMETERS ACQUIRED IN 3376 02:38:24,000 --> 02:38:26,880 MOTION ROBUST WAY AT HIGH 3377 02:38:26,880 --> 02:38:27,920 ISOTROPIC RESOLUTION. 3378 02:38:27,920 --> 02:38:29,360 LET ME GO OVER THE SECOND PART 3379 02:38:29,360 --> 02:38:32,440 OF THIS TALK, ADVANCED EFFUSION 3380 02:38:32,440 --> 02:38:33,280 IMAGING. 3381 02:38:33,280 --> 02:38:36,280 OVER THE LAST DECADE OR SO, MY 3382 02:38:36,280 --> 02:38:38,160 LAB HAS REALLY BEEN TRYING TO 3383 02:38:38,160 --> 02:38:40,480 PUSH THE SPATIAL RESOLUTION 3384 02:38:40,480 --> 02:38:44,360 LIMIT OF IN VIVOM.R.I., TAKING 3385 02:38:44,360 --> 02:38:46,400 ADVANTAGE OF SOME OF THE 3386 02:38:46,400 --> 02:38:48,760 ADVANCED HARDWARE IN 3387 02:38:48,760 --> 02:39:01,320 DEVELOPMENT, IN TERMS OF HIGH 3388 02:39:01,320 --> 02:39:02,720 SHIFTING CAPABILITY AND HARDWARE 3389 02:39:02,720 --> 02:39:04,240 HAVE ALSO DEVELOPED THE 3390 02:39:04,240 --> 02:39:06,360 ACQUISITION AND RECONSTRUCTION 3391 02:39:06,360 --> 02:39:09,680 APPROACHES TO BE ABLE TO ACQUIRE 3392 02:39:09,680 --> 02:39:11,840 DATA MORE PRECISELY AS WELL AS 3393 02:39:11,840 --> 02:39:15,360 BETTER SMR AS WELL AS DEVELOPING 3394 02:39:15,360 --> 02:39:17,760 MOTION CORRECTION AND DENOISING 3395 02:39:17,760 --> 02:39:18,080 APPROACHES. 3396 02:39:18,080 --> 02:39:24,960 SO OUR MOTIVATION FOR THIS STEMS 3397 02:39:24,960 --> 02:39:28,080 MAINLY FIRST FROM THE EX VIVO 3398 02:39:28,080 --> 02:39:30,160 WORK PEOPLE HAVE DONE AT 250 3399 02:39:30,160 --> 02:39:30,680 MICRON. 3400 02:39:30,680 --> 02:39:34,360 HERE'S AN EXAMPLE IN THE CORTEX 3401 02:39:34,360 --> 02:39:36,240 FROM THE LAB WHERE AT THIS TYPE 3402 02:39:36,240 --> 02:39:38,680 OF RESOLUTION YOU START TO BE 3403 02:39:38,680 --> 02:39:42,320 ABLE TO SEE INTRACORTICAL 3404 02:39:42,320 --> 02:39:44,040 FIBERERS RUNNING TANGENTIALLY 3405 02:39:44,040 --> 02:39:44,760 WITHIN THE CORTEX. 3406 02:39:44,760 --> 02:39:47,960 HERE'S WE'RE WORKING HARD TO TRY 3407 02:39:47,960 --> 02:39:50,960 TO PUSH THROUGH THAT RESOLUTION. 3408 02:39:50,960 --> 02:39:55,040 WE'VE GOT TO ABOUT 780 MICRON IN 3409 02:39:55,040 --> 02:39:58,840 THIS CASE WITH GOOD DIFFUSION. 3410 02:39:58,840 --> 02:40:06,880 ZOOMING INTO THE REGION YOU CAN 3411 02:40:06,880 --> 02:40:12,480 SEE MULTIPLE CROSSES IN THE 3412 02:40:12,480 --> 02:40:15,600 REGION AND YOU SEE FIBERS AS 3413 02:40:15,600 --> 02:40:15,880 EXPECTED. 3414 02:40:15,880 --> 02:40:17,040 HERE'S ANOTHER MOTIVATION WHY WE 3415 02:40:17,040 --> 02:40:19,280 WANT TO DO THIS AT HIGHER 3416 02:40:19,280 --> 02:40:20,960 RESOLUTION TO GET TO THE 3417 02:40:20,960 --> 02:40:23,040 INFORMATION SUCH AS THE U FIBERS 3418 02:40:23,040 --> 02:40:24,960 WHICH CANNOT BE SEEN IN THE 3419 02:40:24,960 --> 02:40:29,600 STANDARD SEEING THAT WELL IN THE 3420 02:40:29,600 --> 02:40:35,040 STANDARD DATA AND HERE'S OUR IN 3421 02:40:35,040 --> 02:40:38,360 VIVO ACQUISITION GETTING TO THE 3422 02:40:38,360 --> 02:40:44,400 NEW FIBERS AS SEEN HERE 3423 02:40:44,400 --> 02:40:45,880 INTERESTINGLY THEY MAKE UP MORE 3424 02:40:45,880 --> 02:40:50,320 THAN THE WHITE FIBER PEOPLE HAVE 3425 02:40:50,320 --> 02:40:53,760 BEEN USING DIFFUSION MI TO 3426 02:40:53,760 --> 02:40:54,280 STUDY. 3427 02:40:54,280 --> 02:40:55,920 IT REPRESENTS IMPORTANT MISSING 3428 02:40:55,920 --> 02:40:56,760 INFORMATION WE'RE STARTING TO 3429 02:40:56,760 --> 02:40:59,160 SEE WHEN WE GET TO A HIGH ENOUGH 3430 02:40:59,160 --> 02:41:00,240 RESOLUTION AS WELL. 3431 02:41:00,240 --> 02:41:02,360 SO IN GETTING TO THAT TYPE OF 3432 02:41:02,360 --> 02:41:07,720 RESOLUTION AND GETTING TO IT IN 3433 02:41:07,720 --> 02:41:11,160 A PRECISION, PRECISE MANNER WE 3434 02:41:11,160 --> 02:41:13,520 HAVE TO FIX SOME ARTIFACT 3435 02:41:13,520 --> 02:41:16,800 ASSOCIATED WITH THE DIFFUSION 3436 02:41:16,800 --> 02:41:19,400 AND WE HAVE IMAGE DISTORTION IN 3437 02:41:19,400 --> 02:41:23,280 THE MRI SCANNER ONCE YOU PUT THE 3438 02:41:23,280 --> 02:41:24,960 SUBJECT IN SO WE'LL WORK 3439 02:41:24,960 --> 02:41:28,320 TOGETHER WITH THE GROUP AT NGH 3440 02:41:28,320 --> 02:41:33,320 WHERE THEY'VE DEVELOPED THIS 3441 02:41:33,320 --> 02:41:38,280 AC/DC SHIMMER RAY WHICH 3442 02:41:38,280 --> 02:41:40,240 PERFORMED WITH RECEIVE B ZERO 3443 02:41:40,240 --> 02:41:43,680 FIELD TO ALLOW FOR BETTER 3444 02:41:43,680 --> 02:41:47,080 SHIMMING OF THE HOMOGENEITY. 3445 02:41:47,080 --> 02:41:49,000 THIS IS THE BOTTOM PART OF THE 3446 02:41:49,000 --> 02:41:52,200 BRAIN WHERE IT'S HARD TO IMAGE 3447 02:41:52,200 --> 02:41:53,840 WELL AND YOU GET A LOT OF 3448 02:41:53,840 --> 02:41:55,400 DISTORTION WITH THE DYNAMIC 3449 02:41:55,400 --> 02:42:01,560 SHIMMING FROM THE HARDWARE YOU 3450 02:42:01,560 --> 02:42:02,360 REDUCE THE DISTORTION COMBINED 3451 02:42:02,360 --> 02:42:05,160 WITH ADVANCE POWER AND WE'RE 3452 02:42:05,160 --> 02:42:11,160 GETTING MORE THAN TENFOLD 3453 02:42:11,160 --> 02:42:14,240 REDUCTION IN THE DISTORTION AND 3454 02:42:14,240 --> 02:42:15,640 GET STRUCTURAL IMAGING THAT 3455 02:42:15,640 --> 02:42:18,800 TAKES LONGER TO DO AS SHOWN 3456 02:42:18,800 --> 02:42:19,560 HERE. 3457 02:42:19,560 --> 02:42:22,560 NOW WITH SOME OF THE TECHNIQUES 3458 02:42:22,560 --> 02:42:25,560 WE'RE ABLE TO IMAGE DIFFUSION 3459 02:42:25,560 --> 02:42:28,080 ACQUISITION AT THE BASE OF THE 3460 02:42:28,080 --> 02:42:29,240 BRAIN REALLY WELL AT HIGH 3461 02:42:29,240 --> 02:42:30,360 RESOLUTION. 3462 02:42:30,360 --> 02:42:44,160 THINK THIS IS AROUND 700 MICRON. 3463 02:42:44,160 --> 02:42:48,480 WE'VE GOT DISTORTION-FREE 3464 02:42:48,480 --> 02:42:51,280 DIFFUSION IMAGES AND A SINGLE 3465 02:42:51,280 --> 02:42:55,560 DIRECTION OF DIFFUSION, 3466 02:42:55,560 --> 02:42:58,320 ACQUISITION ACROSS MULTIPLE 3467 02:42:58,320 --> 02:43:04,560 DIRECTION AND YOU CAN SEE GOOD 3468 02:43:04,560 --> 02:43:10,360 REDUCTION AND THE COLOR OF THE 3469 02:43:10,360 --> 02:43:19,760 MAPS AND WE ALSO TRIED TO PUSH 3470 02:43:19,760 --> 02:43:21,040 THE SPATIAL RESOLUTION AND USING 3471 02:43:21,040 --> 02:43:23,000 THE HARDWARE AVAILABLE AT 3472 02:43:23,000 --> 02:43:26,360 STANFORD AND TWEAKING OF OUR 3473 02:43:26,360 --> 02:43:27,240 CONSTRUCTION FURTHER HERE'S 3474 02:43:27,240 --> 02:43:27,960 PRELIMINARY RESULT I'M EXCITED 3475 02:43:27,960 --> 02:43:32,760 TO SHARE WITH YOU AT 500 MICRON 3476 02:43:32,760 --> 02:43:35,160 ISO TROPIC RESOLUTION IN VIVO. 3477 02:43:35,160 --> 02:43:38,240 STILL A BIT NOISY BUT THE DATA 3478 02:43:38,240 --> 02:43:39,960 ALREADY STARTED TO SHOW SOME OF 3479 02:43:39,960 --> 02:43:44,440 THE NICE DETAIL WE CAN SEE AT 3480 02:43:44,440 --> 02:43:46,520 THIS HIGH ISO TROPIC RESOLUTION 3481 02:43:46,520 --> 02:43:46,840 SCAN. 3482 02:43:46,840 --> 02:43:48,280 IT'S IMPORTANT TO GET TO THE 3483 02:43:48,280 --> 02:43:50,320 HIGH RESOLUTION BUT IT'S ALSO 3484 02:43:50,320 --> 02:43:52,720 IMPORTANT TO IMAGE THIS IN A 3485 02:43:52,720 --> 02:43:54,320 CLINICALLY RELEVANT TIME FRAME. 3486 02:43:54,320 --> 02:43:57,400 WE'RE DEVELOP SOME WORK WITH OUR 3487 02:43:57,400 --> 02:44:04,200 COLLABORATOR AT THE BRIGHAM AND 3488 02:44:04,200 --> 02:44:05,200 WOMEN'S HOSPITAL WITH DIFFUSION 3489 02:44:05,200 --> 02:44:08,640 SPACE AND THIS IS OUR TYPICAL 3490 02:44:08,640 --> 02:44:12,520 IMAGING WHERE AT 860 MICRON WE 3491 02:44:12,520 --> 02:44:13,720 CAN APPLY 640 FUSION DIRECTION 3492 02:44:13,720 --> 02:44:16,360 AND IT TAKES 20 MINUTES TO DO 3493 02:44:16,360 --> 02:44:19,240 AND THIS IS ONE OF THE DIFFUSION 3494 02:44:19,240 --> 02:44:21,360 DIRECTION IT'S QUITE NOISY YOU 3495 02:44:21,360 --> 02:44:23,960 CAN DO FOUR AVERAGES OF THIS TO 3496 02:44:23,960 --> 02:44:26,360 GET BETTER SNR OR COMPRESS TO GO 3497 02:44:26,360 --> 02:44:29,120 THE OTHER WAY TO A 10-MINUTE 3498 02:44:29,120 --> 02:44:32,280 SCAN AND GET GOOD SMR SHOWN. 3499 02:44:32,280 --> 02:44:34,480 IS WITH SOME THE TECHNOLOGY 3500 02:44:34,480 --> 02:44:37,160 WE'RE HOPING TO MOVE TOWARD 3501 02:44:37,160 --> 02:44:39,200 DIFFUSION PROTOCOL AND JUST IN A 3502 02:44:39,200 --> 02:44:43,000 10-MINUTE SCAN THAT CAN BE DONE 3503 02:44:43,000 --> 02:44:49,560 ON A CLINICAL SCANNER FOR THE 3504 02:44:49,560 --> 02:44:50,640 STUDY AND LIFE SPAN AND 3505 02:44:50,640 --> 02:44:52,480 HOPEFULLY I'VE SHOWN YOU WE'RE 3506 02:44:52,480 --> 02:44:57,000 MOVING TO DIFFUSION MR AND HAVE 3507 02:44:57,000 --> 02:44:59,080 DIFFUSION IMAGING THAT CAN BE 3508 02:44:59,080 --> 02:45:00,720 OBTAINED IN A CLINICALLY 3509 02:45:00,720 --> 02:45:02,160 RELEVANT TIME FRAME. 3510 02:45:02,160 --> 02:45:03,400 I'VE SHOWN YOU WORK ON PRE 3511 02:45:03,400 --> 02:45:09,520 VISION -- PRECISION 3512 02:45:09,520 --> 02:45:11,160 QUANTITATIVE MR THAT IS ROBUST 3513 02:45:11,160 --> 02:45:13,160 AND REPEATABLE AS WELL AS HAVE 3514 02:45:13,160 --> 02:45:16,760 THE ABILITY TO ROBUSTLY STUDY 3515 02:45:16,760 --> 02:45:19,960 DETAIL INTRACORTICAL DEPTH 3516 02:45:19,960 --> 02:45:21,720 PROFILE FOR CONSTRUCTION AND 3517 02:45:21,720 --> 02:45:24,960 DESCRIBE SOME OF THE ADVANCE 3518 02:45:24,960 --> 02:45:32,040 DIFFUSION IMAGING TO GET HIGH 3519 02:45:32,040 --> 02:45:33,760 SCALE DIFFUSION AND A QUICK END 3520 02:45:33,760 --> 02:45:37,120 HERE IN TERMS OF FUTURE 3521 02:45:37,120 --> 02:45:38,160 DIRECTIONS, STILL QUITE A BIT OF 3522 02:45:38,160 --> 02:45:39,800 WORK TO ALLOW SOME TECHNOLOGIES 3523 02:45:39,800 --> 02:45:50,360 TO HAVE WIDESPREAD USE IN 3524 02:45:50,360 --> 02:45:55,160 CLINICAL STUDY. 3525 02:45:55,160 --> 02:45:57,400 MACHINE LEARNING AND WE WANT OUR 3526 02:45:57,400 --> 02:46:01,360 ACQUISITION TO BE REALLY MOTION 3527 02:46:01,360 --> 02:46:02,760 ROBUST AND MOTION PRONE 3528 02:46:02,760 --> 02:46:04,360 RELATIONS SO WE'RE DEVELOPING 3529 02:46:04,360 --> 02:46:05,640 TECHNIQUES FURTHER THAN THAT. 3530 02:46:05,640 --> 02:46:08,440 THERE'S WORK TO BE DONE IN TERMS 3531 02:46:08,440 --> 02:46:10,400 OF OPTIMIZING, STANDARDIZING 3532 02:46:10,400 --> 02:46:11,960 PROTOCOL AND VALIDATING THE 3533 02:46:11,960 --> 02:46:13,480 TECHNOLOGY AND EXCITINGLY 3534 02:46:13,480 --> 02:46:16,760 MAPPING MORE TISSUE IN TERMS OF 3535 02:46:16,760 --> 02:46:17,640 THE MICROSTRUCTURES THE WORK 3536 02:46:17,640 --> 02:46:22,640 WE'VE STARTED LOOKING AT MYELIN 3537 02:46:22,640 --> 02:46:25,320 WATER AND LOOKING AT THE 3538 02:46:25,320 --> 02:46:27,200 TECHNIQUES MENTIONED AND LASTLY 3539 02:46:27,200 --> 02:46:29,720 AS THIS SECTION HAS ALLUDED TO 3540 02:46:29,720 --> 02:46:32,960 IT'S IMPORTANT TO LOOK INTO 3541 02:46:32,960 --> 02:46:34,840 CROSS-MODALITY ANALYSIS OF SOME 3542 02:46:34,840 --> 02:46:38,360 OF OUR IN VIVO IMAGING WITH 3543 02:46:38,360 --> 02:46:42,960 MICROSCALE EX VIVO IMAGING TO 3544 02:46:42,960 --> 02:46:44,280 UNDERSTAND THE LENGTH OF THE 3545 02:46:44,280 --> 02:46:48,200 DATA SET AND WHAT WE'RE IMAGING 3546 02:46:48,200 --> 02:46:50,320 IN VIVO AS WELL AS BUILDING 3547 02:46:50,320 --> 02:46:50,960 INFORMATION INTO OUR 3548 02:46:50,960 --> 02:46:51,840 CONSTRUCTION AND ANALYSIS TOOL 3549 02:46:51,840 --> 02:46:53,560 TO FURTHER IMPROVE OUR IMAGING. 3550 02:46:53,560 --> 02:46:56,000 WITH THAT I'D LIKE TO THANK MY 3551 02:46:56,000 --> 02:46:59,000 LAB AND THE FOLLOWING 3552 02:46:59,000 --> 02:47:02,440 INSTITUTIONS AND GRANT SUPPORT 3553 02:47:02,440 --> 02:47:02,960 AND THANK YOU FOR YOUR 3554 02:47:02,960 --> 02:47:04,720 ATTENTION. 3555 02:47:04,720 --> 02:47:05,520 >> THANK YOU FOR A BEAUTIFUL 3556 02:47:05,520 --> 02:47:12,600 TALK. 3557 02:47:12,600 --> 02:47:13,720 AS WITH THE PREVIOUS SESSION 3558 02:47:13,720 --> 02:47:15,720 WE'LL HOLD QUESTIONS UNTIL THE 3559 02:47:15,720 --> 02:47:20,920 DISCUSSION BUT PLEASE PUT YOUR 3560 02:47:20,920 --> 02:47:27,560 QUESTIONS IN THE CHAT AND I'LL 3561 02:47:27,560 --> 02:47:31,160 GATHER THEM FOR THE DISCUSSION 3562 02:47:31,160 --> 02:47:31,560 SESSION. 3563 02:47:31,560 --> 02:47:54,360 OUR NEXT SPEAKER IS AANASTASIA 3564 02:47:54,360 --> 02:47:57,360 YENDIKI AND HER POST-DOCTORAL 3565 02:47:57,360 --> 02:48:00,840 TRAINING WAS DONE AT THE MARTIN 3566 02:48:00,840 --> 02:48:01,200 CENTER. 3567 02:48:01,200 --> 02:48:04,600 HER RESEARCH FOCUSES ON 3568 02:48:04,600 --> 02:48:06,400 OBTAINING ACCURATE MODELS OF 3569 02:48:06,400 --> 02:48:10,400 WHITE BUNDLE FIBERS FROM AN 3570 02:48:10,400 --> 02:48:12,120 TOPIC TRACING AND DEVELOPING 3571 02:48:12,120 --> 02:48:15,440 METHODS THAT CAN TAKE ADVANTAGE 3572 02:48:15,440 --> 02:48:18,360 OF THE POSTMORTEM MODELS TO 3573 02:48:18,360 --> 02:48:23,080 INFER CONNECTIONAL ACTIVITY FROM 3574 02:48:23,080 --> 02:48:26,480 IN VIVO DIFFUSION MRI. 3575 02:48:26,480 --> 02:48:26,800 TAKE IT AWAY. 3576 02:48:26,800 --> 02:48:27,360 >> THANK YOU FOR THE KIND 3577 02:48:27,360 --> 02:48:31,320 INTRODUCTION. 3578 02:48:31,320 --> 02:48:34,120 IN VIVO IMAGING WITH MRI WE HAVE 3579 02:48:34,120 --> 02:48:35,720 MANY THINGS AT OUR DISPOSAL TO 3580 02:48:35,720 --> 02:48:38,120 PROBE THE STRUCTURE AND FUNCTION 3581 02:48:38,120 --> 02:48:43,320 OF THE HUMAN BRAIN. 3582 02:48:43,320 --> 02:48:49,200 WITH STRUCTURAL MRI WE GET 3583 02:48:49,200 --> 02:48:50,720 CORTICAL THICKNESS AND WITH 3584 02:48:50,720 --> 02:48:53,440 DIFFUSION MRI WE GET LOCAL 3585 02:48:53,440 --> 02:48:56,120 ESTIMATES AND ORIENTATIONS OF 3586 02:48:56,120 --> 02:48:58,240 BUNDLES TO THEN FOLLOW ACROSS 3587 02:48:58,240 --> 02:49:00,440 THE BRAIN TO RECONSTRUCT 3588 02:49:00,440 --> 02:49:02,120 PATHWAYS THAT CONNECT DIFFERENT 3589 02:49:02,120 --> 02:49:03,760 BRAIN REGIONS AND WITH 3590 02:49:03,760 --> 02:49:05,400 FUNCTIONAL MRI WE GET TIME 3591 02:49:05,400 --> 02:49:10,080 COURSES RELATED TO BLOOD 3592 02:49:10,080 --> 02:49:15,440 OXYGENATION THAT ALLOW US TO 3593 02:49:15,440 --> 02:49:17,560 INFER WHICH ARE ACTUATED IN THE 3594 02:49:17,560 --> 02:49:17,800 SCANNER. 3595 02:49:17,800 --> 02:49:20,640 FOR MOST STUDIES THAT COLLECT 3596 02:49:20,640 --> 02:49:21,640 THE DATA IN VIVO THE RESOLUTION 3597 02:49:21,640 --> 02:49:26,240 IS SOMEWHERE IN THE ORDER OF 1 3598 02:49:26,240 --> 02:49:28,280 TO 2 MILLIMETERS BUT THAT'S THE 3599 02:49:28,280 --> 02:49:28,840 GENERAL SCALE. 3600 02:49:28,840 --> 02:49:32,320 WHAT CAN WE GET AT THAT SCALE 3601 02:49:32,320 --> 02:49:32,920 SPECIFICALLY IF WE WANT TO 3602 02:49:32,920 --> 02:49:38,080 COMBINE LARGE AMOUNTS OF DATA 3603 02:49:38,080 --> 02:49:38,520 ACROSS THE LIFE SPAN? 3604 02:49:38,520 --> 02:49:40,480 THIS IS AN EXAMPLE FROM A VERY 3605 02:49:40,480 --> 02:49:42,560 RECENT AND QUITE REMARKABLE 3606 02:49:42,560 --> 02:49:43,440 STUDY. 3607 02:49:43,440 --> 02:49:44,920 REMARKABLE IN TERMS OF THE 3608 02:49:44,920 --> 02:49:47,960 NUMBER OF DATA SETS THAT WERE 3609 02:49:47,960 --> 02:49:48,960 COMBINED. 3610 02:49:48,960 --> 02:49:52,200 IT WAS 124,000 SCANS FROM ABOUT 3611 02:49:52,200 --> 02:49:54,280 100,000 DIFFERENT SUBJECTS 3612 02:49:54,280 --> 02:49:57,560 RANGING FROM FETAL TO ALL THE 3613 02:49:57,560 --> 02:50:00,320 WAY TO 100 YEARS OF AGE. 3614 02:50:00,320 --> 02:50:02,840 WHEN COMBINING THIS MANY DATA 3615 02:50:02,840 --> 02:50:05,520 SETS ONE HAS TO TYPICALLY 3616 02:50:05,520 --> 02:50:06,640 COMPROMISE IN TERMS OF THE 3617 02:50:06,640 --> 02:50:11,760 QUALITY OF THE DATA AND THE 3618 02:50:11,760 --> 02:50:14,720 ANALYSES POSSIBLE. 3619 02:50:14,720 --> 02:50:17,440 THIS LOOKED AT WHITE MATTER AND 3620 02:50:17,440 --> 02:50:18,640 VENTRICULAR MATTER FROM 3621 02:50:18,640 --> 02:50:20,640 STRUCTURAL MRI. 3622 02:50:20,640 --> 02:50:24,320 SO NOT RELEVANT TO CONNECTIVITY 3623 02:50:24,320 --> 02:50:25,720 PER SE BUT THOSE THE POTENTIAL 3624 02:50:25,720 --> 02:50:27,760 POSSIBILITY, IF WE'RE ABLE TO 3625 02:50:27,760 --> 02:50:31,120 COMBINE THIS MANY DATA SETS. 3626 02:50:31,120 --> 02:50:33,080 THANKFULLY THERE HAVE BEEN 3627 02:50:33,080 --> 02:50:35,760 LARGE-SCALE INITIATIVES 3628 02:50:35,760 --> 02:50:38,040 COLLECTING IN VIVO HUMAN IMAGE 3629 02:50:38,040 --> 02:50:41,520 DATA START FROM THE HUMAN 3630 02:50:41,520 --> 02:50:42,520 CONNECTOME PROJECT WHICH HAS 3631 02:50:42,520 --> 02:50:44,040 NOVEL TECHNOLOGIES FOR MRI AND 3632 02:50:44,040 --> 02:50:46,920 SCANNERS AND GRADIENTS TO 3633 02:50:46,920 --> 02:50:48,720 COLLECT BETTER FUSION MRI AND 3634 02:50:48,720 --> 02:50:51,840 SOME OF THE ACCELERATED 3635 02:50:51,840 --> 02:50:54,520 SEQUENCES TO IMPROVE THE ANGULAR 3636 02:50:54,520 --> 02:50:58,120 RESOLUTION OF THE DIFFUSION MRI 3637 02:50:58,120 --> 02:50:59,800 AND THE TEMPORAL RESOLUTION AND 3638 02:50:59,800 --> 02:51:02,000 THIS IS FROM LARGE-SCALE DATA 3639 02:51:02,000 --> 02:51:03,240 COLLECTION FIRST FOR YOUNG 3640 02:51:03,240 --> 02:51:07,800 ADULTS AND EXTENDED ACROSS THE 3641 02:51:07,800 --> 02:51:09,320 LIFE SPAN AS WELL AS WITH 3642 02:51:09,320 --> 02:51:11,880 ADDITIONAL PROJECTS LIKE THE 3643 02:51:11,880 --> 02:51:17,400 ABCD WHICH FOCUSES IN YOUTH AS 3644 02:51:17,400 --> 02:51:19,240 WELL AS WITH THE U.K. BIO BANK. 3645 02:51:19,240 --> 02:51:22,080 SO WHAT ARE SOME CHALLENGES OF 3646 02:51:22,080 --> 02:51:24,400 COMBINING THE AVAILABLE DATA? 3647 02:51:24,400 --> 02:51:25,920 ONE CHALLENGE HAS TO DO WITH THE 3648 02:51:25,920 --> 02:51:28,320 FACT THAT MOST OF THE AVAILABLE 3649 02:51:28,320 --> 02:51:33,240 DATA SETS ARE CROSS-SECTIONAL. 3650 02:51:33,240 --> 02:51:34,400 EACH SUBJECT IS SCANNED ONLY 3651 02:51:34,400 --> 02:51:36,240 ONCE AND REPRESENTS ONLY ONE 3652 02:51:36,240 --> 02:51:36,400 AGE. 3653 02:51:36,400 --> 02:51:38,400 THE AGE AT WHICH THEY WERE 3654 02:51:38,400 --> 02:51:41,000 SCANNED. 3655 02:51:41,000 --> 02:51:42,880 UNFORTUNATELY WE'RE LOOKING 3656 02:51:42,880 --> 02:51:44,000 SMALL WITHIN SUBJECT EFFECT 3657 02:51:44,000 --> 02:51:46,040 CHANGES ACROSS THE LIFE SPAN IN 3658 02:51:46,040 --> 02:51:50,120 THE PRESENCE OF VERY LARGE 3659 02:51:50,120 --> 02:51:55,240 SUBJECT VARIANTS SO IT'S NOT THE 3660 02:51:55,240 --> 02:51:57,520 BEST AT ALLOWING US TO DETECT 3661 02:51:57,520 --> 02:51:58,920 SMALL CHANGES. 3662 02:51:58,920 --> 02:52:02,120 IF WE WERE ABLE TO INSTEAD OF 3663 02:52:02,120 --> 02:52:03,960 COMPARING TWO DIFFERENT SETS OF 3664 02:52:03,960 --> 02:52:04,760 SUBJECTS REPRESENTING DIFFERENT 3665 02:52:04,760 --> 02:52:07,200 AGE GROUPS IF WE WERE ABLE TO 3666 02:52:07,200 --> 02:52:08,840 SCAN THE SAME SUBJECTS AT 3667 02:52:08,840 --> 02:52:11,040 DIFFERENT AGE GROUPS WE WOULD BE 3668 02:52:11,040 --> 02:52:13,960 ABLE TO TELL IF THERE'S NO TREND 3669 02:52:13,960 --> 02:52:14,960 AT ALL BECAUSE THE BRAIN 3670 02:52:14,960 --> 02:52:16,240 MEASURES ARE GOING UP IN SOME 3671 02:52:16,240 --> 02:52:18,160 SUBJECTS AND DOWN IN OTHERS OR 3672 02:52:18,160 --> 02:52:20,560 IF THERE IS A TREND EVEN IF THAT 3673 02:52:20,560 --> 02:52:23,920 TREND REPRESENTS ONLY A VERY 3674 02:52:23,920 --> 02:52:24,960 SMALL WITHIN SUBJECT CHANGE. 3675 02:52:24,960 --> 02:52:27,040 SO IT HAS BEEN KNOWN FOR A WHILE 3676 02:52:27,040 --> 02:52:31,320 OF COURSE THAT LONGITUDINAL 3677 02:52:31,320 --> 02:52:32,640 DESIGNS INCREASE STATISTICAL 3678 02:52:32,640 --> 02:52:33,880 POWER HOWEVER, IT'S BEEN KNOWN 3679 02:52:33,880 --> 02:52:36,320 THAT WE NEED TAILORED DATA 3680 02:52:36,320 --> 02:52:38,280 ANALYSIS TOOLS TO GET TO THAT 3681 02:52:38,280 --> 02:52:40,240 STATISTICAL POWER OUT OF THE 3682 02:52:40,240 --> 02:52:42,080 LONGITUDINAL DATA. 3683 02:52:42,080 --> 02:52:45,960 AND SO THERE WAS AN EFFORT NOT 3684 02:52:45,960 --> 02:52:48,520 THAT LONG AGO TO DEVELOP TOOLS 3685 02:52:48,520 --> 02:52:51,040 FOR ANALYZING SPECIFICALLY 3686 02:52:51,040 --> 02:52:53,120 LONGITUDINAL DATA AND THIS WAS 3687 02:52:53,120 --> 02:52:56,520 DONE FOR STRUCTURAL DATA BY MY 3688 02:52:56,520 --> 02:52:59,920 COLLEAGUE AND THEN WE EXTENDED 3689 02:52:59,920 --> 02:53:02,120 THAT WORK TO ANALYZING 3690 02:53:02,120 --> 02:53:04,280 LONGITUDINAL DIFFUSION IMAGING 3691 02:53:04,280 --> 02:53:06,880 DATA AND PERFORMING LONGITUDINAL 3692 02:53:06,880 --> 02:53:08,400 TOPOGRAPHY STUDIES. 3693 02:53:08,400 --> 02:53:09,800 THESE TOOLS ARE NOW AVAILABLE TO 3694 02:53:09,800 --> 02:53:11,120 THE COMMUNITY AND HAVE BEEN FOR 3695 02:53:11,120 --> 02:53:17,600 A FEW YEARS. 3696 02:53:17,600 --> 02:53:21,160 AND ANOTHER CHALLENGE WHEN WE 3697 02:53:21,160 --> 02:53:22,520 WANT TO COMBINED LARGE AMOUNTS 3698 02:53:22,520 --> 02:53:23,680 OF DATA SETS THEY WON'T BE 3699 02:53:23,680 --> 02:53:25,320 COLLECTED WITH PROTOCOLS OF HIGH 3700 02:53:25,320 --> 02:53:27,680 ENOUGH QUALITY TO BE PUT THROUGH 3701 02:53:27,680 --> 02:53:30,360 SOME OF THOSE ANALYSIS TOOLS AND 3702 02:53:30,360 --> 02:53:38,000 THIS IS MOTIVATED RECENT EFFORTS 3703 02:53:38,000 --> 02:53:39,640 TO SYNTHESIZE HIGHER RES IMAGES 3704 02:53:39,640 --> 02:53:43,560 TO LOWER RES ALLOWING THE LOWER 3705 02:53:43,560 --> 02:53:47,240 RES IMAGES TO BE PUT THROUGH THE 3706 02:53:47,240 --> 02:53:50,040 SAME ANALYSIS AND SOME WORK 3707 02:53:50,040 --> 02:53:52,960 SHOWED IT'S POSSIBLE TO USE 3708 02:53:52,960 --> 02:53:57,800 HIGH-QUALITY MODELS OF BRAIN 3709 02:53:57,800 --> 02:54:02,720 PATHWAYS FROM FUSION MRI TO 3710 02:54:02,720 --> 02:54:04,680 TRAIN AN ALGORITHM TO LOOK AT 3711 02:54:04,680 --> 02:54:06,000 MORE MODEST QUALITY DATA AND 3712 02:54:06,000 --> 02:54:08,120 THIS ALLOWS US TO EXTEND THE 3713 02:54:08,120 --> 02:54:10,800 BENEFITS OF HAVING ONE OF ONLY A 3714 02:54:10,800 --> 02:54:12,160 HANDFUL OF SUCH SCANNERS IN THE 3715 02:54:12,160 --> 02:54:15,600 WORLD TO ALL THE STUDIES OUT 3716 02:54:15,600 --> 02:54:17,000 THERE THAT DON'T HAVE ACCESS TO 3717 02:54:17,000 --> 02:54:19,880 SUCH A SCANNER. 3718 02:54:19,880 --> 02:54:23,520 HOWEVER, EVEN AFTER WE SOLVED 3719 02:54:23,520 --> 02:54:25,720 ALL THOSE PROBLEMS THERE'S STILL 3720 02:54:25,720 --> 02:54:28,520 LIMITATIONS WITH DIFFUSION MRI 3721 02:54:28,520 --> 02:54:29,760 MEASUREMENT ARE PRESENT EVEN IN 3722 02:54:29,760 --> 02:54:32,600 THE HIGHEST QUALITY DATA WE 3723 02:54:32,600 --> 02:54:32,800 HAVE. 3724 02:54:32,800 --> 02:54:35,680 AND I WOULD ONLY BRIEFLY TRY TO 3725 02:54:35,680 --> 02:54:37,760 EXPLAIN THIS SO WHEN THERE'S 3726 02:54:37,760 --> 02:54:46,240 ONLY A SINGLE AXON BUNDLE SHOWS 3727 02:54:46,240 --> 02:54:49,240 GREATER POWER TO THE AXON BUNDLE 3728 02:54:49,240 --> 02:54:54,120 ALLOWING US TO DETECT THE MAIN 3729 02:54:54,120 --> 02:54:57,120 AXIS OF AXON BUNDLE AND FOLLOW 3730 02:54:57,120 --> 02:54:59,000 IT SUCCESSFULLY. 3731 02:54:59,000 --> 02:55:06,520 WHEN THERE'S MULTIPLE IN A VOXEL 3732 02:55:06,520 --> 02:55:07,960 FUNDING IT WON'T HAVE A CLEAR 3733 02:55:07,960 --> 02:55:10,720 ACCESS TO FOLLOW AND WORK IN THE 3734 02:55:10,720 --> 02:55:13,040 FIELD OVER THE LAST COUPLE 3735 02:55:13,040 --> 02:55:16,520 DECADES FOCUSSED ON WHAT IS 3736 02:55:16,520 --> 02:55:19,560 KNOWN AS AN ODF ORIENTATION 3737 02:55:19,560 --> 02:55:21,920 DISTRIBUTION FUNCTION TO ALLOW 3738 02:55:21,920 --> 02:55:26,320 US TO FIT MULTIPLE AXON 3739 02:55:26,320 --> 02:55:27,760 POPULATION FOR VOXEL. 3740 02:55:27,760 --> 02:55:30,120 A PROB WE HAVE HOWEVER, IS THAT 3741 02:55:30,120 --> 02:55:31,840 EVEN THOUGH WE HAVE DONE VERY 3742 02:55:31,840 --> 02:55:35,240 GOOD AT FITTING THESE ODFs 3743 02:55:35,240 --> 02:55:38,120 BECAUSE WE HAVE HIGH QUALITY 3744 02:55:38,120 --> 02:55:40,960 DATA THANKS TO THE ADVANCES MADE 3745 02:55:40,960 --> 02:55:43,760 POSSIBLE BY THE HUMAN CONNECTOME 3746 02:55:43,760 --> 02:55:46,520 PROJECT TOPOGRAPHY WILL STILL 3747 02:55:46,520 --> 02:55:48,320 GET THINGS WRONG SOMETIMES. 3748 02:55:48,320 --> 02:55:51,120 THAT'S BECAUSE THERE'S MULTIPLE 3749 02:55:51,120 --> 02:55:52,200 CONFIGURATIONS OF DIFFERENT AXON 3750 02:55:52,200 --> 02:55:55,400 POPULATIONS IN A VOXEL THAT CAN 3751 02:55:55,400 --> 02:55:59,840 GIVE RISE TO SIMILAR ODFs SO WE 3752 02:55:59,840 --> 02:56:02,280 DON'T KNOW WHICH OF THE PEAKS TO 3753 02:56:02,280 --> 02:56:04,680 FOLLOW AT A GIVEN VOXEL AND HAVE 3754 02:56:04,680 --> 02:56:07,120 TO CHOOSE WIDELY BECAUSE WE 3755 02:56:07,120 --> 02:56:10,120 DON'T KNOW WHICH OF THE POSSIBLE 3756 02:56:10,120 --> 02:56:12,520 AXON CONFIGURATIONS ON THE LEFT 3757 02:56:12,520 --> 02:56:15,640 GAVE RISE TO THE ODF. 3758 02:56:15,640 --> 02:56:17,040 LEADS TO ERRORS EVEN WITH THE 3759 02:56:17,040 --> 02:56:18,720 HIGHEST QUALITY DATA WE HAVE. 3760 02:56:18,720 --> 02:56:24,920 SO WHAT CAN WE DO MOVING 3761 02:56:24,920 --> 02:56:25,120 FORWARD? 3762 02:56:25,120 --> 02:56:30,120 SOME OF THE HIGH RESOLUTIONS 3763 02:56:30,120 --> 02:56:34,800 METHODS CAN HELP AND SO THIS 3764 02:56:34,800 --> 02:56:40,120 WORK ALSO LED BY OUR GROUP IN 3765 02:56:40,120 --> 02:56:43,320 COLLABORATION SHOWS THAT 3766 02:56:43,320 --> 02:56:46,960 SPECIFIC DEEP BRAIN CIRCUITRY 3767 02:56:46,960 --> 02:56:48,800 REQUIRES RESOLUTION AT THE SUB 3768 02:56:48,800 --> 02:56:49,280 MILLIMETER LEVEL. 3769 02:56:49,280 --> 02:56:51,920 WHAT'S SHOWN ON THE LEFT IS ONE 3770 02:56:51,920 --> 02:56:55,120 OF THE HIGH QUALITY DATA SETS ON 3771 02:56:55,120 --> 02:57:03,560 THE CONNECTOME SCANNER AND THIS 3772 02:57:03,560 --> 02:57:06,520 CAN BE COMBINED AT THE HIGHER 3773 02:57:06,520 --> 02:57:14,920 RESOLUTION BUT THE OTHER BUNDLES 3774 02:57:14,920 --> 02:57:19,720 CAN ONLY BE RECONSTRUCTED IN THE 3775 02:57:19,720 --> 02:57:23,320 SUB MILLIMETER RESOLUTION DATA 3776 02:57:23,320 --> 02:57:26,600 AND NOT IN THE ONE DATA SET 3777 02:57:26,600 --> 02:57:29,000 THOUGH THEY WERE COLLECTED IN 3778 02:57:29,000 --> 02:57:32,920 THE SCANNER AND THIS SHOWS THE 3779 02:57:32,920 --> 02:57:33,960 IMPORTANCE OF HIGH RESOLUTION 3780 02:57:33,960 --> 02:57:37,400 FOR THE DEEPER CIRCUITRY. 3781 02:57:37,400 --> 02:57:39,560 THE SUB MILLIMETER RESOLUTION 3782 02:57:39,560 --> 02:57:42,120 SET WAS SCANNED WITH A SINGLE 3783 02:57:42,120 --> 02:57:44,960 SUBJECT TWO HOURS EACH TIME. 3784 02:57:44,960 --> 02:57:49,200 NOT IN SUBJECTS CAN FOLLOW THIS 3785 02:57:49,200 --> 02:57:50,640 AND POST MORTEM BRAIN SCAN 3786 02:57:50,640 --> 02:57:52,880 TOLERATED IT JUST FINE AND 3787 02:57:52,880 --> 02:57:55,840 WITHIN THE CONNECTOME 2.0 3788 02:57:55,840 --> 02:57:57,040 PROJECT A BRAIN INITIATIVE 3789 02:57:57,040 --> 02:58:05,320 PROJECT LED OUR OTHER GROUP WE 3790 02:58:05,320 --> 02:58:08,000 HAVE LOOK AT THE ACQUISITIONS 3791 02:58:08,000 --> 02:58:11,080 POSSIBLE TO ACHIEVE MESO SCALE 3792 02:58:11,080 --> 02:58:13,080 RESOLUTION DIFFUSION MRI. 3793 02:58:13,080 --> 02:58:15,840 THIS IS NOT EASY EVEN WITH A 3794 02:58:15,840 --> 02:58:18,720 SCANNER AND WITH THE BETTER 3795 02:58:18,720 --> 02:58:22,080 CONNECTOM SCANNER WE WILL GET 3796 02:58:22,080 --> 02:58:25,480 SOON REQUIRES CUSTOM MADE COILS 3797 02:58:25,480 --> 02:58:32,160 AND METHODS TO MITIGATE THE 3798 02:58:32,160 --> 02:58:34,520 ARTIFACTS SPECIFIC TO THE EX 3799 02:58:34,520 --> 02:58:40,120 VIVO ACQUISITIONS AND WE'LL 3800 02:58:40,120 --> 02:58:41,400 ADDRESS THE TECHNOLOGICAL 3801 02:58:41,400 --> 02:58:41,720 CHALLENGE. 3802 02:58:41,720 --> 02:58:44,960 WHAT'S THE CLINICAL RELEVANCE? 3803 02:58:44,960 --> 02:58:47,520 WHAT CAN WE GET OUT IN THE REAL 3804 02:58:47,520 --> 02:58:49,440 WORLD IF WE ARE ABLE TO MAP 3805 02:58:49,440 --> 02:58:52,880 THESE LITTLE BUNDLES DEEP IN THE 3806 02:58:52,880 --> 02:58:53,320 BRAIN? 3807 02:58:53,320 --> 02:58:59,080 ONE EXAMPLE HAS TO DO WITH 3808 02:58:59,080 --> 02:59:02,120 NEUROMODULATION. 3809 02:59:02,120 --> 02:59:06,080 THERE'S FIBERS IN THE DEEP BRAIN 3810 02:59:06,080 --> 02:59:08,720 IF STIMULATED CAN LEAD TO 3811 02:59:08,720 --> 02:59:09,800 OPTIMAL THERAPEUTIC OUTCOMES 3812 02:59:09,800 --> 02:59:13,160 WHERE OTHER BUNDLES NEXT TO THE 3813 02:59:13,160 --> 02:59:15,800 GOOD BUNDLES CAN LEASE TO 3814 02:59:15,800 --> 02:59:19,200 DETERIORATION OF DEPRESSION 3815 02:59:19,200 --> 02:59:19,520 SYMPTOMS. 3816 02:59:19,520 --> 02:59:24,200 SO IT'S VERY CRITICAL TO MAP THE 3817 02:59:24,200 --> 02:59:25,920 DEEP POINT CIRCUITRY ACCURATELY 3818 02:59:25,920 --> 02:59:26,760 AND CHALLENGING. 3819 02:59:26,760 --> 02:59:31,240 SO RIGHT NOW THIS IS BEYOND THE 3820 02:59:31,240 --> 02:59:32,280 CAPABILITIES OF CURRENT IN VIVO 3821 02:59:32,280 --> 02:59:33,120 IMAGING METHODS. 3822 02:59:33,120 --> 02:59:35,320 SO MOST OF WHAT WE KNOW ABOUT 3823 02:59:35,320 --> 02:59:37,120 THE ORGANIZATION OF THESE 3824 02:59:37,120 --> 02:59:39,840 BUNDLES COMES FROM AN ATOMIC 3825 02:59:39,840 --> 02:59:42,640 TRACING EXPERIMENT IN NON-HUMAN 3826 02:59:42,640 --> 02:59:43,080 PRIMATES. 3827 02:59:43,080 --> 02:59:46,040 IN COLLABORATION WITH A GROUP 3828 02:59:46,040 --> 02:59:50,240 HAVE BEEN MAPPING SOME OF THESE 3829 02:59:50,240 --> 02:59:52,920 TOP 3830 02:59:52,920 --> 02:59:53,840 TOPPOGRAPHICAL ORGANIZATIONS 3831 02:59:53,840 --> 02:59:54,480 DEEP IN THE WHITE MATTER AND 3832 02:59:54,480 --> 02:59:57,120 HAVE SHOWN IT'S POSSIBLE TO 3833 02:59:57,120 --> 03:00:00,360 RECREATE SOME OF THOSE 3834 03:00:00,360 --> 03:00:03,400 TOPOGRAPHIES USING DIFFUSION MRI 3835 03:00:03,400 --> 03:00:06,320 DATA POSTMORTEM IN THE MACAQUE 3836 03:00:06,320 --> 03:00:08,520 AND AS WELL AS IN VIVO IN THE 3837 03:00:08,520 --> 03:00:09,960 HUMAN HOWEVER, THERE ARE THINGS 3838 03:00:09,960 --> 03:00:13,000 THAT GO SERIOUSLY WRONG WITH MRI 3839 03:00:13,000 --> 03:00:13,320 MEASUREMENTS. 3840 03:00:13,320 --> 03:00:15,000 TO GET TO THE BOTTOM OF WHAT ARE 3841 03:00:15,000 --> 03:00:16,120 THOSE THINGS THAT ARE GOING 3842 03:00:16,120 --> 03:00:18,800 WRONG AND HOW TO IMPROVE THEM, 3843 03:00:18,800 --> 03:00:23,720 WE HAVE BEEN COLLECTING DATA IN 3844 03:00:23,720 --> 03:00:27,680 THE SAME MRI DATA IN THE SAME 3845 03:00:27,680 --> 03:00:29,320 NON-HUMAN PRIMATE BRAINS THAT 3846 03:00:29,320 --> 03:00:33,920 RECEIVED TRACER INJECTIONS IN 3847 03:00:33,920 --> 03:00:38,080 SUSAN'S LAB SCANNING THE BRAINS 3848 03:00:38,080 --> 03:00:46,040 FOR 40 PLUS HOURS SOMETIMES AND 3849 03:00:46,040 --> 03:00:50,120 AT HIGH RESOLUTION WITH HIGH 3850 03:00:50,120 --> 03:00:51,080 DIFFUSION CONTRAST AND 3851 03:00:51,080 --> 03:00:51,480 RESOLUTION. 3852 03:00:51,480 --> 03:00:52,920 WE HAVE USED SOME OF THE DATA 3853 03:00:52,920 --> 03:01:35,880 SETS TO ENGAGE THE COMMUNITY AND 3854 03:01:35,880 --> 03:01:37,320 THE DISTRIBUTION FUNCTION NOT 3855 03:01:37,320 --> 03:01:39,360 ACCURATE SPECIFICALLY WHERE THE 3856 03:01:39,360 --> 03:01:42,000 AXONS DO NOT CROSS BUT INSTEAD 3857 03:01:42,000 --> 03:01:43,640 TURN OR BRANCH OR FAN. 3858 03:01:43,640 --> 03:01:48,400 THIS POINTS TO A POTENTIAL 3859 03:01:48,400 --> 03:01:51,920 AVENUE FOR FUTURE IMPROVEMENT OF 3860 03:01:51,920 --> 03:01:52,440 METHO 3861 03:01:52,440 --> 03:01:52,680 METHODS. 3862 03:01:52,680 --> 03:01:55,880 HERE WE USED THE TRACING DATAS 3863 03:01:55,880 --> 03:01:59,200 AWAY TO CALIBRATE A POST MORTEM 3864 03:01:59,200 --> 03:02:01,040 IMAGING METHODS THAT CAN BE USED 3865 03:02:01,040 --> 03:02:03,920 IN THE HUMAN BRAIN AND IN THE 3866 03:02:03,920 --> 03:02:08,520 HUMAN BRAIN IN VIVO AND 3867 03:02:08,520 --> 03:02:21,960 SPECIFICALLY DIFFUSION MRI. 3868 03:02:21,960 --> 03:02:26,120 AND WHAT IF WE CAN APPLY IT AT 3869 03:02:26,120 --> 03:02:33,880 THE MICROSCALE AND THIS IS AN 3870 03:02:33,880 --> 03:02:37,440 APPROACH THAT RELIES ON THE 3871 03:02:37,440 --> 03:02:40,920 MYELIN TO OBTAIN MEASUREMENTS AT 3872 03:02:40,920 --> 03:02:42,640 THE MICROSCOPIC SCALE. 3873 03:02:42,640 --> 03:02:47,720 SO THE MAP ON THE RIGHT ARE THE 3874 03:02:47,720 --> 03:02:50,160 DIRECT MEASUREMENTS OF THE 3875 03:02:50,160 --> 03:02:53,400 AXONAL ORIENTATIONS AND ON THE 3876 03:02:53,400 --> 03:02:55,520 LEFT IS MYELIN CONTENT AND IS 3877 03:02:55,520 --> 03:02:58,280 ANOTHER OUTPUT OF THIS 3878 03:02:58,280 --> 03:03:05,680 TECHNIQUE. 3879 03:03:05,680 --> 03:03:10,120 THERE'S SPECIFIC ADVANTAGES OVER 3880 03:03:10,120 --> 03:03:11,520 THE STAINS. 3881 03:03:11,520 --> 03:03:20,000 A PROB -- PROBLEM IS YOU CAN 3882 03:03:20,000 --> 03:03:21,760 HAVE IT HARD TO ALIGN FROM ONE 3883 03:03:21,760 --> 03:03:23,320 SECTION TO THE OTHER WHICH IS 3884 03:03:23,320 --> 03:03:26,120 CRITICAL FOR BEING ABLE TO 3885 03:03:26,120 --> 03:03:28,960 FOLLOW AXONS LONG RANGE ACROSS 3886 03:03:28,960 --> 03:03:32,360 THE BRAIN. 3887 03:03:32,360 --> 03:03:39,320 WE IMAGED THE SUPERFICIAL LAYER 3888 03:03:39,320 --> 03:03:41,960 BEFORE IT'S DISTORTED AND THE 3889 03:03:41,960 --> 03:03:42,520 SECTIONS COME OUT SCANNED 3890 03:03:42,520 --> 03:03:47,920 WITHOUT MISS ALIGNMENTS OR 3891 03:03:47,920 --> 03:03:50,560 DISTORTIONS SO AND IN ADDITION 3892 03:03:50,560 --> 03:03:53,040 TO THAT WE DO NOT ACQUIRE AN 3893 03:03:53,040 --> 03:03:56,440 IMAGE OF THE TISSUE WE THEN 3894 03:03:56,440 --> 03:03:57,960 INTEREST HAVE TO EXTRACT THE 3895 03:03:57,960 --> 03:04:00,680 AXONS AND ESTIMATE THE 3896 03:04:00,680 --> 03:04:01,000 ORIENTATIONS. 3897 03:04:01,000 --> 03:04:03,840 WE GET A DIRECT ESTIMATE OF THE 3898 03:04:03,840 --> 03:04:08,680 VECTORS AND THIS ALLOWS US TO 3899 03:04:08,680 --> 03:04:11,440 RIGHT OUT OF THE BOX PERFORM THE 3900 03:04:11,440 --> 03:04:16,120 TOPOGRAPHY AT SCALE IN THE HUMAN 3901 03:04:16,120 --> 03:04:17,440 BRAIN. 3902 03:04:17,440 --> 03:04:20,920 THE TECHNOLOGY HAS ADVANCED AND 3903 03:04:20,920 --> 03:04:23,760 SO COMPARED TO THE FIRST 3904 03:04:23,760 --> 03:04:26,120 GENERATION SYSTEM WHAT IS 3905 03:04:26,120 --> 03:04:30,120 DEPLOYED AT THE MARTIN CENTER 3906 03:04:30,120 --> 03:04:32,040 HAS BETTER CONTRAST TO NOISE 3907 03:04:32,040 --> 03:04:33,880 RATIO BUT ABOUT SEVEN TIMES 3908 03:04:33,880 --> 03:04:38,080 FASTER SO A TISSUE THAT USED TO 3909 03:04:38,080 --> 03:04:39,720 TAKE FOUR DAYS TO SCAN NOW WE 3910 03:04:39,720 --> 03:04:43,080 CAN SCAN IN LESS THAN A DAY AND 3911 03:04:43,080 --> 03:04:44,080 THIS IS IMPORTANT PARTICULARLY 3912 03:04:44,080 --> 03:04:45,920 WHEN THINKING OF SCALING TO 3913 03:04:45,920 --> 03:04:54,680 LARGER VOLUMES. 3914 03:04:54,680 --> 03:04:56,320 AND YOU DO NOT SEE CONTRASTS 3915 03:04:56,320 --> 03:05:02,720 HERE BUT IT NEEDS TO BE 3916 03:05:02,720 --> 03:05:03,320 ENHANCED. 3917 03:05:03,320 --> 03:05:07,560 AND THIS IS POSSIBLE BY 3918 03:05:07,560 --> 03:05:08,200 SUBMERGING THE TISSUE IN THE 3919 03:05:08,200 --> 03:05:10,080 SOLUTION THAT ALLOWS THE FIBERS 3920 03:05:10,080 --> 03:05:12,880 TO BE FOLLOWED ALL THE WAY INTO 3921 03:05:12,880 --> 03:05:16,560 THE CORTEX SHOWN HERE AT THE 3922 03:05:16,560 --> 03:05:18,120 BOTTOM COMPARED TO THE PBS 3923 03:05:18,120 --> 03:05:33,000 IMMERSED TISSUE ON THE TOP. 3924 03:05:33,000 --> 03:05:35,400 WE EXTRACT THE ORIENTATION OF 3925 03:05:35,400 --> 03:05:42,040 THE AXONS PERPENDICULAR TO THE 3926 03:05:42,040 --> 03:05:52,000 ILLUMINATION AND WE CONNECT WITH 3927 03:05:52,000 --> 03:05:56,880 TWO DIFFERENT ILLUMINATION 3928 03:05:56,880 --> 03:06:02,120 ANGLES AND WORK SHOWS THIS ALLOW 3929 03:06:02,120 --> 03:06:04,360 US TO HAVE THE BENEFIT OF OCT 3930 03:06:04,360 --> 03:06:06,840 THAT WE DO NOT HAVE DISTORTIONS 3931 03:06:06,840 --> 03:06:08,720 ACROSS LICENSE THIS WILL ALLOW 3932 03:06:08,720 --> 03:06:12,120 US TO FOLLOW AXON ORIENTATIONS 3933 03:06:12,120 --> 03:06:14,360 ACROSS SECTIONS AND ACROSS THE 3934 03:06:14,360 --> 03:06:16,920 BRAIN. 3935 03:06:16,920 --> 03:06:19,280 ONE QUESTION SPECIFICALLY 3936 03:06:19,280 --> 03:06:25,200 RELATING TO IMAGING DEVELOPMENT 3937 03:06:25,200 --> 03:06:28,200 SAMPLES IS THAT THIS CONTRAST 3938 03:06:28,200 --> 03:06:32,080 RELIES ON THE MYELIN SO THE 3939 03:06:32,080 --> 03:06:34,240 QUESTION IS IT CAN BE USED IN 3940 03:06:34,240 --> 03:06:36,200 TISSUE NOT FULL MYELIN. 3941 03:06:36,200 --> 03:06:41,280 THIS IS PRELIMINARY RESULTS 3942 03:06:41,280 --> 03:06:45,120 COLLECTED BY DR. WANG'S GROUP 3943 03:06:45,120 --> 03:06:50,400 WHO STUDIES DEVELOPMENT 3944 03:06:50,400 --> 03:06:54,360 POPULATIONS IN OUR CENTER AND 3945 03:06:54,360 --> 03:07:03,520 THIS IS A ONE-MONTH-OLD SAMPLE 3946 03:07:03,520 --> 03:07:06,920 SHOWING THE CONTRAST ON THE 3947 03:07:06,920 --> 03:07:09,240 RIGHT AS WELL AS WHAT ALLOWS 3948 03:07:09,240 --> 03:07:12,880 THEM TO EXTRACT GRANULAR 3949 03:07:12,880 --> 03:07:17,360 THICKNESS IN THE CEREBELLUM. 3950 03:07:17,360 --> 03:07:20,320 GOING FORWARD AND ATOMIC TRACING 3951 03:07:20,320 --> 03:07:22,120 REMAINS THE MAIN SOURCE OF 3952 03:07:22,120 --> 03:07:25,480 INFORMATION WE HAVE ABOUT BRAIN 3953 03:07:25,480 --> 03:07:25,800 CONNECTIVITY. 3954 03:07:25,800 --> 03:07:28,560 IT'S ONLY FEASIBLE IN NON-HUMAN 3955 03:07:28,560 --> 03:07:29,280 PRIMATES BUT WE HAVE AN 3956 03:07:29,280 --> 03:07:31,360 OPPORTUNITY TO USE IT TO 3957 03:07:31,360 --> 03:07:33,320 OPTIMIZE AND CALIBRATE METHODS 3958 03:07:33,320 --> 03:07:38,920 THAT CAN BE USED TO IMAGE POST 3959 03:07:38,920 --> 03:07:40,040 MORTEM ACROSS SPECIES. 3960 03:07:40,040 --> 03:07:54,800 WE HAVE CALIBRATED DIFFUSION MRI 3961 03:07:54,800 --> 03:08:01,680 AND USING ATOMIC TRACING TO 3962 03:08:01,680 --> 03:08:05,320 CALIBRATE TO IMAGE AXONAL 3963 03:08:05,320 --> 03:08:09,520 ORIENTATIONS AT THE MICRO SCAPE 3964 03:08:09,520 --> 03:08:11,920 AND ACROSS VOLUMES AND ALLOWS US 3965 03:08:11,920 --> 03:08:16,120 TO SURVEIL IN THE BRAIN AND 3966 03:08:16,120 --> 03:08:20,840 OBTAIN TRUTH FOR ALGORITHMS FOR 3967 03:08:20,840 --> 03:08:22,440 ANALYZING OUR IN VIVO DIFFUSION 3968 03:08:22,440 --> 03:08:23,920 MRI DATA GOING FORWARD. 3969 03:08:23,920 --> 03:08:26,880 I'D LIKE TONED BY THANKING MY 3970 03:08:26,880 --> 03:08:28,720 COLLABORATORS WHO HAVE MADE THIS 3971 03:08:28,720 --> 03:08:29,400 RESEARCH POSSIBLE AND THANK YOU 3972 03:08:29,400 --> 03:08:34,960 FOR YOUR ATTENTION. 3973 03:08:34,960 --> 03:08:35,320 >> THANK YOU. 3974 03:08:35,320 --> 03:08:40,280 BEAUTIFUL TALK. 3975 03:08:40,280 --> 03:08:44,520 AGAIN, WE'RE GOING TO HOLD 3976 03:08:44,520 --> 03:08:45,920 QUESTIONS UNTIL THE END OF THE 3977 03:08:45,920 --> 03:08:51,480 DISCUSSION BUT UPLOAD THEM 3978 03:08:51,480 --> 03:08:53,720 EITHER IN THE CHAT OR IN THE 3979 03:08:53,720 --> 03:08:54,320 VIDEOCAST SYSTEM YOU CAN UPLOAD 3980 03:08:54,320 --> 03:08:58,080 QUESTIONS AS WELL. 3981 03:08:58,080 --> 03:09:02,800 THANK YOU DR. YENDIKI. 3982 03:09:02,800 --> 03:09:08,280 NOW WE MOVE TO A MUCH DIFFERENT 3983 03:09:08,280 --> 03:09:17,360 SCALE AND I'LL INTRODUCE 3984 03:09:17,360 --> 03:09:20,600 DR. ELLIE HECKSCHER FROM THE 3985 03:09:20,600 --> 03:09:22,560 UNIVERSITY OF CHICAGO. 3986 03:09:22,560 --> 03:09:26,360 SHE RECEIVED HER Ph.D. FROM THE 3987 03:09:26,360 --> 03:09:28,800 UNIVERSITY OF SAN FRANCISCO IN 3988 03:09:28,800 --> 03:09:30,760 THE LAB OF GRAY DAVIS AND 3989 03:09:30,760 --> 03:09:35,240 CONTINUED AT THE UNIVERSITY OF 3990 03:09:35,240 --> 03:09:36,000 OREGON. 3991 03:09:36,000 --> 03:09:38,040 HER GROUP LOOKS AT LINEAGE 3992 03:09:38,040 --> 03:09:40,440 TRACING APPROACHES WITH 3993 03:09:40,440 --> 03:09:41,960 CONNECTOMICS AND STATE OF THE 3994 03:09:41,960 --> 03:09:43,000 ART SYSTEMS, NEUROSCIENCE 3995 03:09:43,000 --> 03:09:44,840 APPROACHES AND HER RESEARCH IS 3996 03:09:44,840 --> 03:09:46,600 FOCUSSED ON HOW MOTOR CIRCUITS 3997 03:09:46,600 --> 03:09:54,120 ARE GENERATED STARTING FROM 3998 03:09:54,120 --> 03:09:59,680 NEURONAL STEM CELLS. 3999 03:09:59,680 --> 03:09:59,840 >> 4000 03:09:59,840 --> 03:10:02,280 >> HI, I'M ELLIE. 4001 03:10:02,280 --> 03:10:04,000 INE ASSIST AND THE PROFESSOR IN 4002 03:10:04,000 --> 03:10:07,720 THE DEPARTMENT OF MOLECULAR DEN 4003 03:10:07,720 --> 03:10:09,640 GENETICS AND CELLULAR BIOLOGY IN 4004 03:10:09,640 --> 03:10:11,240 THE UNIVERSITY OF CHICAGO AND 4005 03:10:11,240 --> 03:10:13,000 TALK ABOUT A DIFFERENT SCALE 4006 03:10:13,000 --> 03:10:15,120 FROM YOU'VE BEEN THINKING ABOUT 4007 03:10:15,120 --> 03:10:18,520 THE MOLECULAR CELLULAR AND 4008 03:10:18,520 --> 03:10:19,120 SUBCELLULAR SCALE. 4009 03:10:19,120 --> 03:10:23,000 SO JUST TO ORIENT YOU TO HOW I 4010 03:10:23,000 --> 03:10:24,120 THOUGHT I'D SPEND MY TIME 4011 03:10:24,120 --> 03:10:25,440 TALKING TODAY. 4012 03:10:25,440 --> 03:10:27,920 I'LL START BY INTRODUCING A 4013 03:10:27,920 --> 03:10:29,040 QUESTION AND THE MODEL SYSTEM 4014 03:10:29,040 --> 03:10:30,920 AND THEN MOVING ON TO HOW WE 4015 03:10:30,920 --> 03:10:33,720 MEASURE BRAIN CONNECTIVITY, 4016 03:10:33,720 --> 03:10:34,960 FUTURE DIRECTIONS OF THE 4017 03:10:34,960 --> 03:10:35,920 APPROACHES IN THE SYSTEM AND BIG 4018 03:10:35,920 --> 03:10:37,680 PICTURE GAPS IN THE SYSTEM. 4019 03:10:37,680 --> 03:10:39,360 SO WE'LL START HERE WITH A 4020 03:10:39,360 --> 03:10:41,160 QUESTION AND THE MODEL SYSTEM. 4021 03:10:41,160 --> 03:10:42,960 AND SO THIS IS THE BRAIN ACROSS 4022 03:10:42,960 --> 03:10:45,120 LIFE SPAN WORKSHOP I THOUGHT I'D 4023 03:10:45,120 --> 03:10:47,000 ORIENT YOU TO THE TIME SPAN THAT 4024 03:10:47,000 --> 03:10:49,200 I'M FOCUSSING ON AND SO 4025 03:10:49,200 --> 03:10:50,920 SPECIFICALLY WE'RE FOCUSSED ON 4026 03:10:50,920 --> 03:10:55,000 THE START OF NEUROGENESIS TO THE 4027 03:10:55,000 --> 03:10:58,920 START OF BEHAVIOR AND I'M A 4028 03:10:58,920 --> 03:11:01,120 DEVELOPMENT BIOLOGIST BY 4029 03:11:01,120 --> 03:11:02,120 TRAINING AND THERE'S THE CARTOON 4030 03:11:02,120 --> 03:11:04,040 OF HUMAN DEVELOPMENT. 4031 03:11:04,040 --> 03:11:07,960 STARTING HERE WITH SPERM AND EGG 4032 03:11:07,960 --> 03:11:09,800 FERTILIZING AND WITHIN A WEEK OR 4033 03:11:09,800 --> 03:11:12,800 SO YOU'LL HAVE RECOGNIZABLE 4034 03:11:12,800 --> 03:11:17,480 EMBRYO AND AT THAT POINT YOU'LL 4035 03:11:17,480 --> 03:11:19,240 SEE STEM CELLS. 4036 03:11:19,240 --> 03:11:20,440 THIS IS WHAT I MEAN BY THE START 4037 03:11:20,440 --> 03:11:21,600 OF NEURO GENESIS. 4038 03:11:21,600 --> 03:11:22,960 IN THE COMING WEEKS THE FETUS 4039 03:11:22,960 --> 03:11:24,400 WILL DEVELOP AND IT WILL START 4040 03:11:24,400 --> 03:11:26,120 TO MOVE AND MOVE BECAUSE THOSE 4041 03:11:26,120 --> 03:11:28,920 NEURONS HAVE STARTED TO MAKE 4042 03:11:28,920 --> 03:11:32,400 SYNAPSES AND WIRE UP IN SPECIFIC 4043 03:11:32,400 --> 03:11:32,800 CIRCUITS. 4044 03:11:32,800 --> 03:11:34,080 THIS THIS PERIOD FROM THE START 4045 03:11:34,080 --> 03:11:36,400 OF NEUROGENESIS TO THE START OF 4046 03:11:36,400 --> 03:11:37,000 BEHAVIOR I'LL BE TELLING YOU 4047 03:11:37,000 --> 03:11:41,800 ABOUT TODAY. 4048 03:11:41,800 --> 03:11:46,040 SO THE SPECIFIC QUESTION I'LL 4049 03:11:46,040 --> 03:11:49,640 FOCUS ON IS HOW IS IT CIRCUITS 4050 03:11:49,640 --> 03:11:50,800 SELF-ASSEMBLE STARTING FROM STEM 4051 03:11:50,800 --> 03:11:51,600 CELLS? 4052 03:11:51,600 --> 03:11:55,240 A STEM CELL SHOWN HERE IN THE 4053 03:11:55,240 --> 03:12:00,280 BIG BLUE CIRCLE IS A PLURIPOTENT 4054 03:12:00,280 --> 03:12:06,080 CELL THAT WILL DIVIDE 4055 03:12:06,080 --> 03:12:09,640 ASYMMETRICALLY WAY AND THIS WILL 4056 03:12:09,640 --> 03:12:12,080 HAPPEN OVER AND OVER AGAIN TO 4057 03:12:12,080 --> 03:12:13,320 GENERATE WHAT WE HAVE A LINEAGE 4058 03:12:13,320 --> 03:12:15,080 OF NEURONS. 4059 03:12:15,080 --> 03:12:17,560 SO ALL OF THESE NEURONS COME 4060 03:12:17,560 --> 03:12:19,200 FROM THE STEM CELL PARENT. 4061 03:12:19,200 --> 03:12:23,080 SO WHY DO WE CARE ABOUT THIS 4062 03:12:23,080 --> 03:12:27,280 PARTICULAR QUESTION AND THE BIG 4063 03:12:27,280 --> 03:12:30,800 REVEAL HERE AND WE LIKE TO KEEP 4064 03:12:30,800 --> 03:12:33,720 OUR QUESTIONS FUNDAMENTAL TO 4065 03:12:33,720 --> 03:12:37,920 HAVE WIDE-RANGING IMPLICATIONS 4066 03:12:37,920 --> 03:12:38,960 FOR A LOT OF FEEL. 4067 03:12:38,960 --> 03:12:40,640 AND FOR DEVELOPMENT WE THINK 4068 03:12:40,640 --> 03:12:44,320 ABOUT HOW THE BRAIN DEVELOPS IS 4069 03:12:44,320 --> 03:12:45,840 PERHAPS ONE OF THE MOST COMPLEX 4070 03:12:45,840 --> 03:12:51,960 ORGAN MORPHOGENESIS QUESTION. 4071 03:12:51,960 --> 03:12:54,400 FROM NEUROBIOLOGY THIS WHAT 4072 03:12:54,400 --> 03:12:56,160 CONSTRAINTS CIRCUIT FUNCTION AND 4073 03:12:56,160 --> 03:12:57,920 THIS IS WHAT CONSTRAINTS 4074 03:12:57,920 --> 03:12:59,040 PERCEPTIONS AND ACTIONS. 4075 03:12:59,040 --> 03:13:05,080 FOR THE FIELD OF ROBOTICS, WE'RE 4076 03:13:05,080 --> 03:13:10,320 HOPING WE CAN GIVE COMPLEX 4077 03:13:10,320 --> 03:13:14,520 NETWORKS AND HOPEFULLY FOR THE 4078 03:13:14,520 --> 03:13:16,520 MEDICAL AUDIENCE UNDERSTANDING 4079 03:13:16,520 --> 03:13:18,640 HOW STEM CELL WIRE UP TO CREATE 4080 03:13:18,640 --> 03:13:20,400 CIRCUITS MAY HELP UNDERSTAND 4081 03:13:20,400 --> 03:13:23,880 WHAT GOES WRONG IN DISEASE AND 4082 03:13:23,880 --> 03:13:26,960 PROVIDE INSIGHT INTO HOW TO USE 4083 03:13:26,960 --> 03:13:27,960 STEM CELLS THERAPEUTICALLY. 4084 03:13:27,960 --> 03:13:28,960 I THINK THIS IS AN IMPORTANT 4085 03:13:28,960 --> 03:13:30,920 QUESTION BUT I WANT TO POINT OUT 4086 03:13:30,920 --> 03:13:32,440 WE REALLY DON'T KNOW MUCH ABOUT 4087 03:13:32,440 --> 03:13:34,320 THE ANSWER AND THAT'S BECAUSE 4088 03:13:34,320 --> 03:13:38,080 THE QUESTION HAS BEEN 4089 03:13:38,080 --> 03:13:45,440 INTRACTABLE FOR A LONG TIME. 4090 03:13:45,440 --> 03:13:48,080 THERE WERE TOOLS BUT COULDN'T 4091 03:13:48,080 --> 03:13:51,120 GET AT THE CIRCUITS BECAUSE THE 4092 03:13:51,120 --> 03:13:52,680 CELLS WERE SMALL BUT WE COULD 4093 03:13:52,680 --> 03:13:55,480 GET ELECTRODES INTO CIRCUITS BUT 4094 03:13:55,480 --> 03:13:57,840 DIDN'T HAVE THE GENETIC TOOLS TO 4095 03:13:57,840 --> 03:13:58,840 STUDY STEM CELL. 4096 03:13:58,840 --> 03:14:02,120 BRIDGING THE DIVIDE WAS 4097 03:14:02,120 --> 03:14:16,480 TECHNICALLY NOT POSSIBLE. 4098 03:14:16,480 --> 03:14:28,000 IS THE SPECIFIC SYSTEM WE USE IS 4099 03:14:28,000 --> 03:14:36,840 THE EGG IS THE STAGE IN WHICH 4100 03:14:36,840 --> 03:14:39,320 DRIVE CIRCUITS AND THE LARVAE 4101 03:14:39,320 --> 03:14:41,560 WILL GROW AND EAT AND SHED THE 4102 03:14:41,560 --> 03:14:45,280 CUTICLE TO MAKE A SECOND LARVAE 4103 03:14:45,280 --> 03:14:47,880 TO GROW AND EAT AND ONCE YOU GET 4104 03:14:47,880 --> 03:14:50,120 TO THE THIRD ENSTAR AND YOU'RE 4105 03:14:50,120 --> 03:14:56,120 BIG ENOUGH YOU WILL BECOME A 4106 03:14:56,120 --> 03:14:57,920 PUPA AND YOU HAVE REMODELLING 4107 03:14:57,920 --> 03:14:59,840 HAPPEN AND HATCH INTO ADULTS. 4108 03:14:59,840 --> 03:15:02,040 AND ADULTS DO NOT GROW. 4109 03:15:02,040 --> 03:15:03,600 THEY'RE ADAPTED JUST FOR MATING 4110 03:15:03,600 --> 03:15:03,920 AND DISPERSAL. 4111 03:15:03,920 --> 03:15:06,040 I WANT TO POINT OUT IT SEEMS 4112 03:15:06,040 --> 03:15:08,920 LIKE A WEIRD MODE OF DEVELOPMENT 4113 03:15:08,920 --> 03:15:12,560 BUT IT'S NOT MUCH DIFFERENT FROM 4114 03:15:12,560 --> 03:15:13,560 WHAT HAPPENS IN MANY LIKE HUMANS 4115 03:15:13,560 --> 03:15:17,520 WHERE YOU HAVE A GROWTH PHASE 4116 03:15:17,520 --> 03:15:20,480 WITHOUT REPRODUCTIVE 4117 03:15:20,480 --> 03:15:20,840 CHARACTERISTICS. 4118 03:15:20,840 --> 03:15:22,800 AS THE MOTHER OF A TEENAGER I 4119 03:15:22,800 --> 03:15:24,440 THINK IT'S GREAT THEY JUST DO 4120 03:15:24,440 --> 03:15:27,920 ALL THE REMODELLING IN THE PUPA 4121 03:15:27,920 --> 03:15:35,680 STAGE. 4122 03:15:35,680 --> 03:15:48,480 THERE'S THE LARVAL STAGE AND I 4123 03:15:48,480 --> 03:15:55,720 WANT TO TALK ABOUT WHAT ARE THE 4124 03:15:55,720 --> 03:15:55,920 PERIODS. 4125 03:15:55,920 --> 03:15:57,600 THERE'S A PERIOD WITHIN 24 HOURS 4126 03:15:57,600 --> 03:15:59,520 WITHIN THE EMBRYO. 4127 03:15:59,520 --> 03:16:00,800 THERE'S APPROXIMATELY 1,000 STEM 4128 03:16:00,800 --> 03:16:03,640 CELLS SET ASIDE AND THEY'LL 4129 03:16:03,640 --> 03:16:06,120 DIVIDE TO GIVE RISE TO NEARLY 4130 03:16:06,120 --> 03:16:07,400 15,000 NEURONS. 4131 03:16:07,400 --> 03:16:10,120 THE 15,000 NEURONS WILL WIRE UP 4132 03:16:10,120 --> 03:16:12,320 TO MAKE CIRCUITS THAT DRIVE THE 4133 03:16:12,320 --> 03:16:14,720 LARVAE AND IT WILL BE ABOUT 3 4134 03:16:14,720 --> 03:16:15,680 MILLION SYNAPSES. 4135 03:16:15,680 --> 03:16:23,680 ONCE THE LARVAE HATCHES THE 4136 03:16:23,680 --> 03:16:25,920 NEURONS WILL DRIVE LARVAL 4137 03:16:25,920 --> 03:16:29,600 BEHAVIOR THROUGHOUT. 4138 03:16:29,600 --> 03:16:30,520 THERE'LL BE NO ADDITIONAL 4139 03:16:30,520 --> 03:16:32,120 NEURONS CONTRIBUTING TO THE 4140 03:16:32,120 --> 03:16:33,320 LARVAL SECTORS. 4141 03:16:33,320 --> 03:16:35,520 THEY'LL JUST GET BIGGER AS THE 4142 03:16:35,520 --> 03:16:36,800 ANIMAL GROWS AND THE NUMBER OF 4143 03:16:36,800 --> 03:16:38,680 SYNAPSES WILL INCREASE. 4144 03:16:38,680 --> 03:16:41,320 OTHER THAN THAT WE DON'T 4145 03:16:41,320 --> 03:16:41,960 ACTUALACTUAL 4146 03:16:41,960 --> 03:16:47,520 LY -- ACTUALLY DON'T KNOW MUCH 4147 03:16:47,520 --> 03:16:49,520 ABOUT THE STEM CELLS AN AS THEY 4148 03:16:49,520 --> 03:16:53,120 GROW BUT AS THE LARVAE STARTS TO 4149 03:16:53,120 --> 03:16:54,480 GROW, THE STEM CELLS WILL COME 4150 03:16:54,480 --> 03:16:56,960 OUT OF QUIESCENCE AND START TO 4151 03:16:56,960 --> 03:16:58,760 MAKE ADDITIONAL NEURONS ON THE 4152 03:16:58,760 --> 03:17:01,520 ORDER OF 100,000 OF THEM. 4153 03:17:01,520 --> 03:17:13,400 THEY'LL BE IMMATURE UNTIL PU 4154 03:17:13,400 --> 03:17:19,440 PUPATION HAPPENS. 4155 03:17:19,440 --> 03:17:22,120 THERE'S A WHOLE OTHER SECOND 4156 03:17:22,120 --> 03:17:27,360 PERIOD OF NEUROGENESIS THAT'S 4157 03:17:27,360 --> 03:17:34,080 INTERESTING TO THINK ABOUT FOOP 4158 03:17:34,080 --> 03:17:57,120 AND MANY HAVE THESE GENES. 4159 03:17:57,120 --> 03:17:59,000 WE HAVE SYSTEMS WHICH HAVE THE 4160 03:17:59,000 --> 03:18:00,080 ROLE OF DROSOPHILA RESEARCH. 4161 03:18:00,080 --> 03:18:01,720 THAT'S WHAT I WANTED TO COVER 4162 03:18:01,720 --> 03:18:04,200 AND NOW I WANT TO GET INTO MORE 4163 03:18:04,200 --> 03:18:06,520 OF THE DETAILS ABOUT HOW WE IN 4164 03:18:06,520 --> 03:18:07,200 OUR SYSTEM MACHINE BRAIN 4165 03:18:07,200 --> 03:18:17,040 CONNECTIVITY. 4166 03:18:17,040 --> 03:18:18,320 AND WE USE THE RESOURCE IN THE 4167 03:18:18,320 --> 03:18:19,080 RESEARCH A LOT. 4168 03:18:19,080 --> 03:18:22,120 I'M SHOWING THE PICTURE OF THE 4169 03:18:22,120 --> 03:18:25,120 DROSOPHILA LARVAL CONNECTOME. 4170 03:18:25,120 --> 03:18:29,520 IT'S A SIX-HOUR OLD FEMALE 4171 03:18:29,520 --> 03:18:30,080 LARVAE. 4172 03:18:30,080 --> 03:18:31,360 YOU THE ESSENTIAL BRAIN AND 4173 03:18:31,360 --> 03:18:34,240 NERVE CORD WHICH IS LIKE YOUR 4174 03:18:34,240 --> 03:18:35,920 SPINAL CORD, HERE ARE CELL 4175 03:18:35,920 --> 03:18:38,520 BODIES AND THE AXONS AND 4176 03:18:38,520 --> 03:18:43,440 DENDRITES FORM SYNAPSES IN THESE 4177 03:18:43,440 --> 03:18:44,000 CENTRAL REGIONS. 4178 03:18:44,000 --> 03:18:47,080 THE YOU CAN SEE THE MEMBRANES 4179 03:18:47,080 --> 03:18:50,080 SECTIONED AND IMAGED BY TEM AND 4180 03:18:50,080 --> 03:18:52,480 THE SECTIONS WERE ALIGNED INTO A 4181 03:18:52,480 --> 03:18:54,640 PLANE AND YOU CAN SEE THEY WERE 4182 03:18:54,640 --> 03:18:56,320 ALIGNED IN THREE DIMENSIONS. 4183 03:18:56,320 --> 03:18:59,280 THIS IS THE WORK OF RICK FETTER 4184 03:18:59,280 --> 03:19:02,480 AND OTHERS AND IT'S A HIGH 4185 03:19:02,480 --> 03:19:04,920 RESOLUTION SINGLE IMAGE AND I'LL 4186 03:19:04,920 --> 03:19:06,040 SHOW A LITTLE BIT MORE IN THE 4187 03:19:06,040 --> 03:19:06,880 NEXT SLIDE. 4188 03:19:06,880 --> 03:19:09,320 HERE'S JUST A SLICE OF THE DATA. 4189 03:19:09,320 --> 03:19:13,560 HERE YOU CAN SEE THE OUTLINES OF 4190 03:19:13,560 --> 03:19:16,400 THE CELLS AND MITOCHONDRIA. 4191 03:19:16,400 --> 03:19:21,080 OVER 20 LABS ALL OVER THE WORLD 4192 03:19:21,080 --> 03:19:22,040 HAVE BEEN MANUALLY 4193 03:19:22,040 --> 03:19:24,440 RECONSTRUCTING THESE AND YOU PUT 4194 03:19:24,440 --> 03:19:27,080 A PINK DOT ON THE CELL OF 4195 03:19:27,080 --> 03:19:29,080 INTEREST AND SCROLL IN THE NEXT 4196 03:19:29,080 --> 03:19:30,800 SLICE AND THIS IS HOW YOU BUILD 4197 03:19:30,800 --> 03:19:33,320 UP THE MORPHOLOGY OF THE NEURON. 4198 03:19:33,320 --> 03:19:37,600 THE OTHER TYPE OF ANNOTATION DO 4199 03:19:37,600 --> 03:19:43,640 AND THE RUN NEED TEM AND THIS IS 4200 03:19:43,640 --> 03:19:45,760 SYNAPSING ON TO THESE THREE. 4201 03:19:45,760 --> 03:19:51,320 TO GIVE INTUITION ABOUT NUMBERS, 4202 03:19:51,320 --> 03:19:53,320 ANY ONE NEURON AND MAKE ABOUT 4203 03:19:53,320 --> 03:20:04,760 100 TO 200 SYNAPSES. 4204 03:20:04,760 --> 03:20:08,720 IT LETS US AND STEM CELLS WE 4205 03:20:08,720 --> 03:20:09,400 ALREADY KNOW ABOUT IN THE 4206 03:20:09,400 --> 03:20:09,720 SYSTEM. 4207 03:20:09,720 --> 03:20:11,240 THINK HOW THEY MAP TO THE 4208 03:20:11,240 --> 03:20:12,640 CONNECTOME AND THE CONNECTOME 4209 03:20:12,640 --> 03:20:15,760 LETS US KNOW HOW THAT RELATES TO 4210 03:20:15,760 --> 03:20:23,440 ANATOMICAL CIRCUITS AND 4211 03:20:23,440 --> 03:20:30,680 FUNCTIONAL BEHAVIOR. 4212 03:20:30,680 --> 03:20:33,440 AND THIS IS ENABLED BY THE VAST 4213 03:20:33,440 --> 03:20:36,200 COLLECTION OF GENETIC TOOLS AND 4214 03:20:36,200 --> 03:20:38,360 HUGE POWER THAT IS DROSOPHILA 4215 03:20:38,360 --> 03:20:44,040 GENETICS AND ENABLED BY THE FACT 4216 03:20:44,040 --> 03:20:46,080 THAT NEURONS INVARIANT. 4217 03:20:46,080 --> 03:20:48,000 I'M SHOWING A STEM CELL CALLED 4218 03:20:48,000 --> 03:20:50,960 3-3 AND SELF-RENEWS BUT WILL 4219 03:20:50,960 --> 03:20:56,760 ALSO MAKE A BUNCH OF NEURONS. 4220 03:20:56,760 --> 03:20:58,200 AND IN LINEAGE TRACING WE INDUCE 4221 03:20:58,200 --> 03:21:03,320 A GENETIC CHANGE IN A STEM CELL 4222 03:21:03,320 --> 03:21:05,840 AS IT'S DIVIDING. 4223 03:21:05,840 --> 03:21:08,840 IT'S GOING TO LABEL ONE CELL IN 4224 03:21:08,840 --> 03:21:10,560 ONE FLUORESCENT COLOR AND THE 4225 03:21:10,560 --> 03:21:13,960 OTHER CELL IN ANOTHER 4226 03:21:13,960 --> 03:21:15,520 FLUORESCENT COLOR BECAUSE IT'S A 4227 03:21:15,520 --> 03:21:16,600 SELF-RENEWING CELL AND PASS IT 4228 03:21:16,600 --> 03:21:18,400 ON TO THE REMAINDER OF THE 4229 03:21:18,400 --> 03:21:18,720 PROGENY. 4230 03:21:18,720 --> 03:21:20,160 IF WE INDUCE THE CHANGE AT A 4231 03:21:20,160 --> 03:21:22,200 DIFFERENT TIME WE GET A 4232 03:21:22,200 --> 03:21:24,480 DIFFERENT PATTERN. 4233 03:21:24,480 --> 03:21:27,280 THIS IS WHAT SOME OF THE DATA 4234 03:21:27,280 --> 03:21:28,920 LOOKS LIKE. 4235 03:21:28,920 --> 03:21:31,160 IN PURPLE YOU SEE CELL BODIES 4236 03:21:31,160 --> 03:21:33,360 AND WHEN YOU INDUCE THE CLONE IN 4237 03:21:33,360 --> 03:21:36,320 THIS PARTICULAR CASE YOU SEE TWO 4238 03:21:36,320 --> 03:21:39,000 RED CELLS AND ONE GREEN CELL 4239 03:21:39,000 --> 03:21:39,280 LABELLED. 4240 03:21:39,280 --> 03:21:41,080 IT TELLS US THE GREEN CELL IS 4241 03:21:41,080 --> 03:21:42,040 THE THIRD FROM LAST CELL BORN 4242 03:21:42,040 --> 03:21:42,920 FROM THE STEM CELL. 4243 03:21:42,920 --> 03:21:45,240 YOU CAN ALSO GO IN AND LOOK AT 4244 03:21:45,240 --> 03:21:48,280 HIGH RESOLUTION AT THE ANATOMY 4245 03:21:48,280 --> 03:21:53,440 OF THIS CELL AND IN THIS 4246 03:21:53,440 --> 03:21:57,480 PARTICULAR CASE AND SO INVARIANT 4247 03:21:57,480 --> 03:21:59,280 YOU CAN FIND THE MATCH IN THE 4248 03:21:59,280 --> 03:22:00,080 CONNECTOME. 4249 03:22:00,080 --> 03:22:02,480 SO ONCE WE FOUND THE NEURON -- 4250 03:22:02,480 --> 03:22:04,760 LET THE JUST ORIENT YOU, THIS IS 4251 03:22:04,760 --> 03:22:07,280 THE SAME ONE IN YELLOW BUT NOW 4252 03:22:07,280 --> 03:22:07,840 IT'S SHOWN IN BLACK. 4253 03:22:07,840 --> 03:22:10,080 WHAT YOU CAN DO IS GO TO THE 4254 03:22:10,080 --> 03:22:13,720 CONNECTOME AND ASK WHO ARE THE 4255 03:22:13,720 --> 03:22:15,520 ANATOMICAL INPUTS. 4256 03:22:15,520 --> 03:22:17,040 IN THIS CASE THE NEURON IS 4257 03:22:17,040 --> 03:22:18,920 GETTING INPUTS FROM THE SENSORY 4258 03:22:18,920 --> 03:22:20,320 NEURON AND MAKING SYNAPSES, 13 4259 03:22:20,320 --> 03:22:23,720 HERE AND TWO HERE. 4260 03:22:23,720 --> 03:22:26,600 YOU CAN DO THE SAME THING ASKING 4261 03:22:26,600 --> 03:22:29,920 THE OUTPUTS AND YOU CAN SEE THE 4262 03:22:29,920 --> 03:22:33,120 NEURON E3 IS ACROSS THE MID LINE 4263 03:22:33,120 --> 03:22:40,120 AND WILL OUTPUT ON THE GREEN 4264 03:22:40,120 --> 03:22:40,320 CELL. 4265 03:22:40,320 --> 03:22:43,200 GENERATING A CONNECTOME IS LABOR 4266 03:22:43,200 --> 03:22:47,400 IN SENSE BUT WE KNOW THE LEFT 4267 03:22:47,400 --> 03:22:49,320 AND RIGHT SIDES ARE MIR IMAGES 4268 03:22:49,320 --> 03:22:52,040 AND WE CAN LOOK OR THE SAME 4269 03:22:52,040 --> 03:22:54,520 NEURON THE OTHER SIDE OF THE CNS 4270 03:22:54,520 --> 03:22:55,680 AS A TECHNICAL REPLICATE AND A 4271 03:22:55,680 --> 03:22:57,840 WANT YOU TO NOTICE IT LOOKS 4272 03:22:57,840 --> 03:23:00,080 SIMILAR THOUGH THE NUMBERS OF 4273 03:23:00,080 --> 03:23:00,720 SYNAPSES BETWEEN ANY TWO CELLS 4274 03:23:00,720 --> 03:23:03,400 ARE DIFFERENT. 4275 03:23:03,400 --> 03:23:05,720 SO FROM THESE TYPES OF DATA WE 4276 03:23:05,720 --> 03:23:07,560 CAN BUILD UP A WIRING DIAGRAM 4277 03:23:07,560 --> 03:23:10,080 AND I DON'T CARE YOU THINK ABOUT 4278 03:23:10,080 --> 03:23:11,320 THE DETAILS HERE BUT THERE'S THE 4279 03:23:11,320 --> 03:23:13,360 CELL E3 AND SOME OF ITS 4280 03:23:13,360 --> 03:23:14,080 SIBLINGS. 4281 03:23:14,080 --> 03:23:20,760 THEY ALL GET INPUT FROM 4282 03:23:20,760 --> 03:23:25,840 PROPREPR 4283 03:23:25,840 --> 03:23:30,400 PROPREPRIOCREEPTORS AND WE CAN USE 4284 03:23:30,400 --> 03:23:35,760 IT AND MAKE PREDICTIONS. 4285 03:23:35,760 --> 03:23:40,960 WE THINK THESE EL NEURONS GET 4286 03:23:40,960 --> 03:23:48,560 INFORMATION FROM PROPRIOCEPTORS 4287 03:23:48,560 --> 03:24:12,800 AND MAYBE WE CAN GET ASYMMETRY. 4288 03:24:12,800 --> 03:24:17,320 AND WE HAVE ACTIVATED ALL THE 4289 03:24:17,320 --> 03:24:19,960 ELs USING OPTOGENETICS AND WE 4290 03:24:19,960 --> 03:24:22,800 CAN ABLATE THEM AND THINK IN 4291 03:24:22,800 --> 03:24:41,480 THIS CASE WE SCRAMBLED THE P E 4292 03:24:41,480 --> 03:24:42,080 PROPRIOCEPTOR INFORMATION AND 4293 03:24:42,080 --> 03:24:44,480 THE FIRST THING WE LEARNED IS 4294 03:24:44,480 --> 03:24:48,560 THE RULE AND THAT'S LINEAGES ARE 4295 03:24:48,560 --> 03:24:52,720 REORGANIZED AND AS IT A GROUP OF 4296 03:24:52,720 --> 03:24:53,320 NEURONS BORN FROM A STEM CELL 4297 03:24:53,320 --> 03:24:58,120 OVER TIME. 4298 03:24:58,120 --> 03:25:02,080 PROPRIOVENT 4299 03:25:02,920 --> 03:25:05,520 AND WE HAVE SOME THAT ALL 4300 03:25:05,520 --> 03:25:13,760 PARTICIPATE IN A PROPRIOCEPTOR 4301 03:25:13,760 --> 03:25:16,320 CIRCUIT AND HERE'S WE HAVE A 4302 03:25:16,320 --> 03:25:17,560 MECHANO SENSORY STIMULATION. 4303 03:25:17,560 --> 03:25:23,120 THAT LEADS TO THE IDEA THERE'S 4304 03:25:23,120 --> 03:25:25,400 LITTLE DEVELOPMENT CHUNKS OF 4305 03:25:25,400 --> 03:25:26,440 LINEAGES ORGANIZATIONAL UNITS. 4306 03:25:26,440 --> 03:25:29,720 SO IT'S THESE KINDS OF RULES 4307 03:25:29,720 --> 03:25:30,800 WE'RE INTERESTED IN DISCOVERING 4308 03:25:30,800 --> 03:25:33,360 USING THE METHODOLOGY. 4309 03:25:33,360 --> 03:25:35,680 MORE BROADLY I WANT TO DRAW YOUR 4310 03:25:35,680 --> 03:25:36,480 ATTENTION TO WHAT WE CAN DO IN 4311 03:25:36,480 --> 03:25:38,400 THE SYSTEM WHICH IS TO INTEGRATE 4312 03:25:38,400 --> 03:25:40,800 DIFFERENT LEVELS OF ANALYSIS. 4313 03:25:40,800 --> 03:25:44,280 I HAVEN'T GOTTEN MUCH IN THE 4314 03:25:44,280 --> 03:25:46,080 MOLECULAR BUT WE HAVE EXCELLENT 4315 03:25:46,080 --> 03:25:50,600 TOOLS IN DROSOPHILA AND WE CAN 4316 03:25:50,600 --> 03:25:53,160 GET TO SYNAPTIC CONNECTIVITY AND 4317 03:25:53,160 --> 03:25:55,320 I SHOW YOU THE CELLULAR DATA AND 4318 03:25:55,320 --> 03:25:58,040 WE CAN MAKE PREDICTIONS ABOUT 4319 03:25:58,040 --> 03:25:58,320 BEHAVIOR. 4320 03:25:58,320 --> 03:26:02,240 WE ALSO ARE BEGINNING TO BE ABLE 4321 03:26:02,240 --> 03:26:06,080 TO DO THIS STANDING TIME. 4322 03:26:06,080 --> 03:26:08,920 I SHOWED YOU DATA LINKING 4323 03:26:08,920 --> 03:26:10,680 EMBRYONIC TO LARVAL. 4324 03:26:10,680 --> 03:26:11,840 THAT'S SORT OF WHAT I WANTED TO 4325 03:26:11,840 --> 03:26:13,080 TELL YOU ABOUT THE APPROACHES 4326 03:26:13,080 --> 03:26:16,160 AND WHAT WE CAN DO IN THE SYSTEM 4327 03:26:16,160 --> 03:26:17,520 AND I ALSO THOUGHT THE FRAMEWORK 4328 03:26:17,520 --> 03:26:18,880 WOULD BE A GOOD WAY TO INTRODUCE 4329 03:26:18,880 --> 03:26:19,960 WHAT A THINK ARE SOME OF THE 4330 03:26:19,960 --> 03:26:21,240 FUTURE DIRECTIONS OF THE 4331 03:26:21,240 --> 03:26:22,320 APPROACHES WE NEED TO USE IN THE 4332 03:26:22,320 --> 03:26:27,280 SYSTEM. 4333 03:26:27,280 --> 03:26:31,440 AND SO THIS LINKS BACK TO THE 4334 03:26:31,440 --> 03:26:33,160 FIRST SET OF TALKS MEASURING 4335 03:26:33,160 --> 03:26:34,080 CELL IDENTITY AND CHROMATIN 4336 03:26:34,080 --> 03:26:35,000 STATES AND OTHER THINGS. 4337 03:26:35,000 --> 03:26:37,080 NOW THAT WE HAVE THIS CONNECTOME 4338 03:26:37,080 --> 03:26:38,840 WE HAVE A DETAILED RESOURCE. 4339 03:26:38,840 --> 03:26:43,200 WE ALSO NEED TO BE ABLE TO LINK 4340 03:26:43,200 --> 03:26:50,200 IT SINGLE CELL LEVEL AND LINK IT 4341 03:26:50,200 --> 03:26:58,600 TO CIRCUIT BEHAVIOR. 4342 03:26:58,600 --> 03:27:02,120 AND CAN WE GET CONNECTIVITY 4343 03:27:02,120 --> 03:27:04,400 INFORMATION OVER TIME FROM 4344 03:27:04,400 --> 03:27:10,120 EMBRYOS FROM LATE LARVAE AND 4345 03:27:10,120 --> 03:27:12,920 FROM PERTURBATIONS? 4346 03:27:12,920 --> 03:27:14,360 LIKE ZEBRAFISH LARVAE ARE 4347 03:27:14,360 --> 03:27:14,720 OPTICALLY CLEAR. 4348 03:27:14,720 --> 03:27:16,120 ON THE WISH LIST IS THE ABILITY 4349 03:27:16,120 --> 03:27:17,800 AND PEOPLE ARE MAKING GREAT 4350 03:27:17,800 --> 03:27:20,040 STRIDES FOR THIS BEING ABLE TO 4351 03:27:20,040 --> 03:27:24,480 IMAGE ACTIVITY OF ANIMALS -- 4352 03:27:24,480 --> 03:27:26,920 SORRY, ACTIVITY OF NEURONS IN 4353 03:27:26,920 --> 03:27:28,760 ANIMALS AND FINALLY I THINK 4354 03:27:28,760 --> 03:27:30,360 BECAUSE WE HAVE SUCH HIGH 4355 03:27:30,360 --> 03:27:32,720 RESOLUTION INFORMATION ABOUT 4356 03:27:32,720 --> 03:27:34,480 CONNECTIVITY WE NEED HIGHER 4357 03:27:34,480 --> 03:27:35,920 RESOLUTION INFORMATION ABOUT 4358 03:27:35,920 --> 03:27:36,400 BEHAVIOR. 4359 03:27:36,400 --> 03:27:37,560 IN PARTICULAR WE NEED TO 4360 03:27:37,560 --> 03:27:38,520 UNDERSTAND BEHAVIOR AT THE LEVEL 4361 03:27:38,520 --> 03:27:41,040 OF SINGLE MUSCLE CONTRACTIONS 4362 03:27:41,040 --> 03:27:43,080 BECAUSE THAT'S REALLY THE 4363 03:27:43,080 --> 03:27:46,240 INTERMEDIATE BETWEEN THE NERVOUS 4364 03:27:46,240 --> 03:27:47,680 SYSTEM AND BEHAVIOR. 4365 03:27:47,680 --> 03:27:47,880 OKAY. 4366 03:27:47,880 --> 03:27:49,720 I'LL WRAP UP IN THE LAST 30 4367 03:27:49,720 --> 03:27:52,240 SECONDS WITH WHAT I THINK ARE 4368 03:27:52,240 --> 03:27:54,920 BIG PICTURE GAPS IN THE SYSTEM. 4369 03:27:54,920 --> 03:27:55,960 SO WE'RE BEGINNING TO UNDERSTAND 4370 03:27:55,960 --> 03:27:58,960 WHAT THE RELATIONSHIPS ARE 4371 03:27:58,960 --> 03:27:59,840 BETWEEN STEM CELL AND CIRCUIT 4372 03:27:59,840 --> 03:28:01,640 AND WE HAVE MORE TO LEARN BUT WE 4373 03:28:01,640 --> 03:28:04,560 ALSO NEED TO KNOW HOW THE 4374 03:28:04,560 --> 03:28:06,200 RELATIONSHIPS VARY AT DIFFERENT 4375 03:28:06,200 --> 03:28:06,480 CONTEXTS. 4376 03:28:06,480 --> 03:28:08,600 WE TOLD YOU WHAT'S HAPPENING IN 4377 03:28:08,600 --> 03:28:10,680 ONE SEGMENT BUT WE'RE INTERESTED 4378 03:28:10,680 --> 03:28:13,720 IN ALL THE SEGMENTS AND HOW IT 4379 03:28:13,720 --> 03:28:15,080 VARIES ACROSS LIFE STAGE AND 4380 03:28:15,080 --> 03:28:15,480 ORGANISMS. 4381 03:28:15,480 --> 03:28:17,160 WE NEED TO UNDERSTAND HOW THE 4382 03:28:17,160 --> 03:28:19,440 RELATIONSHIPS ARE BUILT ON THE 4383 03:28:19,440 --> 03:28:20,880 MOLECULAR AND CELLULAR LEVEL AND 4384 03:28:20,880 --> 03:28:23,000 THE THREE THINGS WE NEED TO KNOW 4385 03:28:23,000 --> 03:28:24,320 ARE WHAT'S GOING ON IN THE STEM 4386 03:28:24,320 --> 03:28:27,320 CELL AND THE NEURON AND IN THE 4387 03:28:27,320 --> 03:28:27,960 ENVIRONMENT AND THEN THE LAST 4388 03:28:27,960 --> 03:28:35,920 SET OF THINGS WE NEED TO DO IS 4389 03:28:35,920 --> 03:28:40,800 PERTURBTIVE ANALYSIS AND HOW'S 4390 03:28:40,800 --> 03:28:43,920 IT BREAK AND WHEN AND WITH THAT 4391 03:28:43,920 --> 03:28:44,480 HERE'S MY LAB. 4392 03:28:44,480 --> 03:28:47,880 THANK YOU FOR FUNDING FOR PEOPLE 4393 03:28:47,880 --> 03:28:50,280 WHAT CAN DO ANNOTATION AND FOR 4394 03:28:50,280 --> 03:28:54,080 THE ATTENTION. 4395 03:28:54,080 --> 03:28:56,920 >> THANK YOU, ELLIE, BEAUTIFUL. 4396 03:28:56,920 --> 03:29:11,480 I WISH WE COULD ALL CLAP. 4397 03:29:11,480 --> 03:29:18,200 I'LL INTRODUCE DR. MAI ZHEN A 4398 03:29:18,200 --> 03:29:22,080 SENIOR SCIENTIST AT THE 4399 03:29:22,080 --> 03:29:23,800 LUNENFELD-TANNENBAUM INSTITUTE 4400 03:29:23,800 --> 03:29:26,440 AND VISITING PROFESSOR OF 4401 03:29:26,440 --> 03:29:28,400 PHYSICS AT HARVARD 4402 03:29:28,400 --> 03:29:28,800 INVESTIGATION. 4403 03:29:28,800 --> 03:29:34,000 SHE GOT HER Ph.D. AT UNIVERSITY 4404 03:29:34,000 --> 03:29:35,720 OF COLUMBIA AND DID HER 4405 03:29:35,720 --> 03:29:37,800 POST-DOCTORAL AT UCSD. 4406 03:29:37,800 --> 03:29:44,040 HER WORK COMBINES ELECTRON 4407 03:29:44,040 --> 03:29:54,080 MICROSCOPY AND HOW THE NERVOUS 4408 03:29:54,080 --> 03:29:57,520 SYSTEM WORKS IN C ELEGANS AND 4409 03:29:57,520 --> 03:29:57,840 OTHER MODELS. 4410 03:29:57,840 --> 03:30:36,920 TAKE IT AWAY. 4411 03:30:36,920 --> 03:30:40,360 >> THE FOCUS OF MY TALK IS AN 4412 03:30:40,360 --> 03:30:41,240 EMERGING AREA THAT ADDRESS THE 4413 03:30:41,240 --> 03:30:43,800 FUNDAMENTAL QUESTION IN BIOLOGY, 4414 03:30:43,800 --> 03:30:48,760 HOW DOES WIRING AND FINDING A 4415 03:30:48,760 --> 03:30:49,480 SYNAPTIC CONNECTIVITY CHANGES 4416 03:30:49,480 --> 03:31:02,440 ACROSS THE ANIMAL'S LIFE SPAN. 4417 03:31:02,440 --> 03:31:04,080 TO UNDERSTAND THE ARCHITECTURE 4418 03:31:04,080 --> 03:31:05,920 OF THE BRAIN SPECIFICALLY HOW 4419 03:31:05,920 --> 03:31:07,520 IT'S FORMED AND THE CHANGE OF 4420 03:31:07,520 --> 03:31:09,280 THE FORM FACILITATING THE 4421 03:31:09,280 --> 03:31:12,320 ANIMAL'S ABILITY TO ADAPT TO ITS 4422 03:31:12,320 --> 03:31:12,880 GROWING BODY AS WELL AS THE 4423 03:31:12,880 --> 03:31:17,080 CHANGING ENVIRONMENT. 4424 03:31:17,080 --> 03:31:19,640 DURING DEVELOPMENT THE WIRING 4425 03:31:19,640 --> 03:31:22,600 MATURES DRIVEN BOTH BY THE 4426 03:31:22,600 --> 03:31:24,880 ANIMAL'S GENETIC PROGRAMS, 4427 03:31:24,880 --> 03:31:29,320 INTRINSIC PROGRAM AND THE 4428 03:31:29,320 --> 03:31:32,560 ANIMAL'S INTERACTION WITH THE 4429 03:31:32,560 --> 03:31:32,880 ENVIRONMENT. 4430 03:31:32,880 --> 03:31:35,360 WE HAVE USED HIGH RESOLUTION TO 4431 03:31:35,360 --> 03:31:37,680 RECONSTRUCT EVERY CELL AND MAP 4432 03:31:37,680 --> 03:31:40,560 EVERY SINGLE CHEMICAL SYNAPSE OF 4433 03:31:40,560 --> 03:31:46,440 THE C. ELEGAN'S BRAIN TO 4434 03:31:46,440 --> 03:31:47,520 ADULTHOOD AND LOOKING AT THE 4435 03:31:47,520 --> 03:31:51,080 STAGES WE'RE ABLE TO INFER A FEW 4436 03:31:51,080 --> 03:31:53,200 POTENTIAL RULES THAT MAY GOVERN 4437 03:31:53,200 --> 03:32:06,600 THE MATURATION PROCESS. 4438 03:32:06,600 --> 03:32:11,160 TO ME THERE'S A FRAMEWORK UPON 4439 03:32:11,160 --> 03:32:15,440 WHICH THE CONNECTIVELY TO UNDER 4440 03:32:15,440 --> 03:32:18,880 LINE THE ANIMAL BEHAVIOR. 4441 03:32:18,880 --> 03:32:23,120 CONNECTOMICS HAS BEEN ACTIVE 4442 03:32:23,120 --> 03:32:28,600 ACROSS ANIMAL SPECIES MOST 4443 03:32:28,600 --> 03:32:35,720 NOTABLY IN THE C. ELEGANS AND 4444 03:32:35,720 --> 03:32:37,360 OTHERS AND THERE'S THE ABILITY 4445 03:32:37,360 --> 03:32:39,400 TO GENERATE SENSORIMOTOR 4446 03:32:39,400 --> 03:32:39,960 BEHAVIORS BOTH ROBUST AND 4447 03:32:39,960 --> 03:32:44,360 ADAPTIVE. 4448 03:32:44,360 --> 03:32:52,040 C. ELEGANS ALLOWS TO US COMPARE 4449 03:32:52,040 --> 03:33:05,200 AT A SINGLE SYNAPSE RESOLUTION 4450 03:33:05,200 --> 03:33:11,080 AND LOOK AT THE ENVIRONMENT. 4451 03:33:11,080 --> 03:33:19,520 THE C. ELEGANS NERVOUS HAS A 4452 03:33:19,520 --> 03:33:22,080 BRAIN AND THE C. ELEGANS HAS THE 4453 03:33:22,080 --> 03:33:28,920 PROCESS WHY IT'S SENSORY AND 4454 03:33:28,920 --> 03:33:30,520 INTERNEURONS WORK IN THE SENSORY 4455 03:33:30,520 --> 03:33:30,840 PROCESSING. 4456 03:33:30,840 --> 03:33:34,960 THE OTHER IS THE BODY COURSE. 4457 03:33:34,960 --> 03:33:37,240 THE C. ELEGANS EQUIPMENT OF THE 4458 03:33:37,240 --> 03:33:44,960 PERIPHERAL NERVOUS SYSTEM AND 4459 03:33:44,960 --> 03:33:59,160 ASCENDING AND ESCENDING SYSTEMS 4460 03:33:59,160 --> 03:34:04,080 AND THEY COMPLIED THE CONNECTOME 4461 03:34:04,080 --> 03:34:07,080 AND THIS CLASSIFIES 300 NEURONS 4462 03:34:07,080 --> 03:34:10,680 INTO 117 CELL TYPES. 4463 03:34:10,680 --> 03:34:14,240 THIS IS PURELY MORPHOLOGY AND 4464 03:34:14,240 --> 03:34:16,600 CONNECTIVITY AND IT SEEMS TO 4465 03:34:16,600 --> 03:34:18,920 HAVE FAIRLY GOOD CORRELATION 4466 03:34:18,920 --> 03:34:22,520 WITH THE MOLECULAR FINGERPRINTS 4467 03:34:22,520 --> 03:34:26,560 NOW THAT WE HAVE THE SINGLE CELL 4468 03:34:26,560 --> 03:34:29,320 RNA SEQ DATA AND WE HAVE 4469 03:34:29,320 --> 03:34:31,600 CELL-CELL CONNECTIONS MOST 4470 03:34:31,600 --> 03:34:39,120 DRIVEN BY CLEM -- CHEMICAL 4471 03:34:39,120 --> 03:34:43,000 SYNAPSES AND LIKE ALL ANIMALS, 4472 03:34:43,000 --> 03:34:48,800 THE NEWLY MATCHED C. ELEGANS HAS 4473 03:34:48,800 --> 03:34:51,000 TO UNDER GO SEVERAL STAGES 4474 03:34:51,000 --> 03:34:53,160 BEFORE BECOME BEING ADULT AND 4475 03:34:53,160 --> 03:34:57,080 IT'S MAPPED BY THE CELL 4476 03:34:57,080 --> 03:34:58,920 LINEAGES, HARD WIRING INVOLVES 4477 03:34:58,920 --> 03:34:59,920 DURING THE STAGES AND HOW LONG 4478 03:34:59,920 --> 03:35:03,000 REMAINS UNKNOWN. 4479 03:35:03,000 --> 03:35:09,840 MOREOVEDURING THE STAGES AND HOW LONG 4480 03:35:09,840 --> 03:35:14,640 MOREOVER,MOREOVER, KNOW ENVIRONMENT CAN 4481 03:35:14,640 --> 03:35:15,600 CHANGE THE C. ELEGANS' 4482 03:35:15,600 --> 03:35:21,000 ENVIRONMENTAL DECISIONS AT A 4483 03:35:21,000 --> 03:35:23,160 CRITICAL DEVELOPMENT STAGE WHEN 4484 03:35:23,160 --> 03:35:26,720 ANIMALS ARE CHALLENGED WITH A 4485 03:35:26,720 --> 03:35:28,080 HARSH ENVIRONMENT THEY CAN HALT 4486 03:35:28,080 --> 03:35:30,400 UNTIL THE ENVIRONMENT IMPROVES. 4487 03:35:30,400 --> 03:35:36,520 THIS STAGE HAS BEEN ANALYZED 4488 03:35:36,520 --> 03:35:40,520 METABOLICALLY BUT PRECISELY HOW 4489 03:35:40,520 --> 03:35:43,120 THIS IS AFFECT THE ENVIRONMENT 4490 03:35:43,120 --> 03:35:45,520 IS UNKNOWN. 4491 03:35:45,520 --> 03:35:46,960 WE ASKED HOW DOES THE NERVOUS 4492 03:35:46,960 --> 03:35:48,600 SYSTEM CHANGE DURING 4493 03:35:48,600 --> 03:35:50,080 DEVELOPMENT? 4494 03:35:50,080 --> 03:35:52,320 WHAT MECHANISMS MAY GOVERN THIS 4495 03:35:52,320 --> 03:35:54,760 MATURATION PROCESS AND WHETHER 4496 03:35:54,760 --> 03:35:55,640 THE ENVIRONMENT CAN ALTER THE 4497 03:35:55,640 --> 03:35:59,560 WIRING. 4498 03:35:59,560 --> 03:36:02,120 THE APPROACH WE TOOK IS HIGH 4499 03:36:02,120 --> 03:36:14,960 RESOLUTION AND THEN HIGH 4500 03:36:14,960 --> 03:36:16,240 SEMI-MICROSCOPY TO RECONSTRUCT 4501 03:36:16,240 --> 03:36:18,040 THE EVERY CHEMICAL SYNAPSE OF 4502 03:36:18,040 --> 03:36:20,040 THE ANIMAL FROM BIRTH TO 4503 03:36:20,040 --> 03:36:20,320 ADULTHOOD. 4504 03:36:20,320 --> 03:36:25,840 ALL THE DATA SETS HAVE BEEN MADE 4505 03:36:25,840 --> 03:36:29,120 AVAILABLE THROUGH AN INTERACTIVE 4506 03:36:29,120 --> 03:36:31,680 WEBSITE WHERE WE POST THE 4507 03:36:31,680 --> 03:36:34,080 NETWORK AS WELL AS THE 3-D 4508 03:36:34,080 --> 03:36:35,520 STRUCTURE THAT PROVIDES THE 4509 03:36:35,520 --> 03:36:37,800 SPATIAL LOCATION OF ALL THE 4510 03:36:37,800 --> 03:36:38,080 SYNAPSES. 4511 03:36:38,080 --> 03:36:43,800 IN THE CONTEXT OF THE REST OF MY 4512 03:36:43,800 --> 03:36:48,920 TALK THE C. ELEGANS HAS 180 4513 03:36:48,920 --> 03:36:51,960 NEURON 4514 03:36:51,960 --> 03:36:53,320 NEURONS AND THE MAJORITY OF THE 4515 03:36:53,320 --> 03:36:54,800 CELLS IS ALREADY PRESENT AT 4516 03:36:54,800 --> 03:36:57,120 BIRTH AND FOR EIGHT INDIVIDUALS 4517 03:36:57,120 --> 03:36:58,720 OF A DIFFERENT DEVELOPMENT TIME 4518 03:36:58,720 --> 03:37:00,080 POINT WE HAVE CONSTRUCTED EVERY 4519 03:37:00,080 --> 03:37:02,120 SINGLE CELL AND THEN WE 4520 03:37:02,120 --> 03:37:05,160 IDENTIFIED EVERY SINGLE CELL TO 4521 03:37:05,160 --> 03:37:11,560 COMPARE THEM. 4522 03:37:11,560 --> 03:37:14,680 OUR FINAL DATA SET HAS THE 4523 03:37:14,680 --> 03:37:20,000 LOCATION AND SIZE OF THE 4524 03:37:20,000 --> 03:37:23,480 PHYSICAL CONTEXT FOR EACH CELLS 4525 03:37:23,480 --> 03:37:24,720 IN THE BRAIN AND THIS CAN INFORM 4526 03:37:24,720 --> 03:37:27,760 THE TOPOLOGY OF THE BRAIN OF 4527 03:37:27,760 --> 03:37:29,920 SEVEN INDIVIDUALS STAGE FROM L1 4528 03:37:29,920 --> 03:37:30,400 TO ADULT. 4529 03:37:30,400 --> 03:37:32,400 THE SECOND DATA SET THE 4530 03:37:32,400 --> 03:37:34,080 CONNECTOME WHERE THE LOCATION 4531 03:37:34,080 --> 03:37:36,360 AND THE NUMBERS OF EACH 4532 03:37:36,360 --> 03:37:39,520 CONNECTIONS IS DEPICTED AND THEY 4533 03:37:39,520 --> 03:37:43,280 REPRESENT THE Y DIAGRAMS OF THE 4534 03:37:43,280 --> 03:37:45,080 EIGHT INDIVIDUALS TO ADULT ALSO. 4535 03:37:45,080 --> 03:37:50,000 WITH THE DATA SETS WE ADDRESS 4536 03:37:50,000 --> 03:37:51,800 THE PROCESS AT FOUR DIFFERENT 4537 03:37:51,800 --> 03:37:52,520 LEVELS. 4538 03:37:52,520 --> 03:37:54,120 THE SCAFFOLD, SYNAPSE, 4539 03:37:54,120 --> 03:37:55,600 CONNECTION AND THE NETWORK. 4540 03:37:55,600 --> 03:37:57,840 AND THE APPROACH WE TOOK IS TO 4541 03:37:57,840 --> 03:37:59,640 EXAMINE THE RELATIONSHIPS ACROSS 4542 03:37:59,640 --> 03:38:03,240 AND BETWEEN THE TWO PHYSICAL 4543 03:38:03,240 --> 03:38:07,440 MATRICES THE COMPACTOME AND 4544 03:38:07,440 --> 03:38:07,720 CONNECTOME. 4545 03:38:07,720 --> 03:38:10,120 FROM THE COMPACTOME FROM 4546 03:38:10,120 --> 03:38:11,840 COMPARING ACROSS DEVELOPMENT WE 4547 03:38:11,840 --> 03:38:14,760 KNOW WHEN AND WHERE AND HOW MUCH 4548 03:38:14,760 --> 03:38:17,560 NEURON MAKES PHYSICAL CONTACT 4549 03:38:17,560 --> 03:38:19,880 AND COMPARING THOSE CHANGES 4550 03:38:19,880 --> 03:38:22,320 ALLOWS US TO ASSESS THE TOPOLOGY 4551 03:38:22,320 --> 03:38:22,720 CHANGES. 4552 03:38:22,720 --> 03:38:25,560 AND FROM THE HORIZONTAL 4553 03:38:25,560 --> 03:38:28,080 COMPARISON WE KNOW WHERE AND HOW 4554 03:38:28,080 --> 03:38:31,240 MANY SYNAPSES ARE PRESENT AND 4555 03:38:31,240 --> 03:38:32,640 HOW MUCH OF THE NETWORK REQUIRES 4556 03:38:32,640 --> 03:38:34,720 EXCHANGES. 4557 03:38:34,720 --> 03:38:35,680 FINALLY, BY COMPARING THE 4558 03:38:35,680 --> 03:38:38,080 EXCHANGES WE CAN ADDRESS THE 4559 03:38:38,080 --> 03:38:40,800 RELATIONSHIPS BETWEEN THE 4560 03:38:40,800 --> 03:38:41,400 TOPOLOGY AND CONNECTIVITY 4561 03:38:41,400 --> 03:38:44,000 DEVELOPMENT. 4562 03:38:44,000 --> 03:38:45,720 FOLLOWING THE SUM OF OUR KEY 4563 03:38:45,720 --> 03:38:51,720 FINDINGS, FIRST, WE FIND THE C. 4564 03:38:51,720 --> 03:38:55,160 ELEGANS BRAIN WE FIND THE 4565 03:38:55,160 --> 03:38:59,880 NEURONS OF EXTEND LINEARLY AND 4566 03:38:59,880 --> 03:39:03,480 BY FIVEFOLD AND ALL REACH OUT TO 4567 03:39:03,480 --> 03:39:06,080 EACH OTHER AND MAINTAIN THE 4568 03:39:06,080 --> 03:39:08,080 RELATIVE PHYSICAL CONTACT WITH 4569 03:39:08,080 --> 03:39:10,120 EACH OTHER AT THE SAME 4570 03:39:10,120 --> 03:39:12,360 GEOLOGICAL LOCATIONS BUILDING 4571 03:39:12,360 --> 03:39:15,400 THE STABLE SCAFFOLD. 4572 03:39:15,400 --> 03:39:18,720 UPON THIS SCAFFOLD THE NUMBER OF 4573 03:39:18,720 --> 03:39:22,080 SYNAPSES INCREASES LINEARLY AND 4574 03:39:22,080 --> 03:39:24,360 THIS FIVEFOLD SYNAPSE INCREASE 4575 03:39:24,360 --> 03:39:27,320 FROM L1 TO ADULTHOOD SERVE TWOS 4576 03:39:27,320 --> 03:39:28,640 TURN. 4577 03:39:28,640 --> 03:39:31,440 THEY STRENGTHEN THE EXISTING 4578 03:39:31,440 --> 03:39:32,160 SYNAPTIC CONDITIONS ALREADY 4579 03:39:32,160 --> 03:39:34,360 PRESENT AT BIRTH. 4580 03:39:34,360 --> 03:39:38,920 YOU SEE THE AVERAGE NUMBER OF 4581 03:39:38,920 --> 03:39:41,720 CONNECTION INCREASES AND SECOND 4582 03:39:41,720 --> 03:39:44,080 A SMALL NUMBER OF THE SYNAPSES 4583 03:39:44,080 --> 03:39:46,080 ARE USED TO BUILD MANY NEW 4584 03:39:46,080 --> 03:39:48,720 CONNECTIONS AND THE NUMBER OF 4585 03:39:48,720 --> 03:39:50,640 CONNECTIONS HAS INCREASED BY 4586 03:39:50,640 --> 03:39:52,440 TWOFOLD EXPANDING THE 4587 03:39:52,440 --> 03:39:53,520 CONNECTIVITY AMONG THE SAME 4588 03:39:53,520 --> 03:39:54,920 NUMBER OF NEURON. 4589 03:39:54,920 --> 03:39:57,000 THE CHANGES OCCUR THROUGH A 4590 03:39:57,000 --> 03:39:59,320 GLOBAL ADDITION OF SYNAPSES WITH 4591 03:39:59,320 --> 03:40:02,080 ALMOST COMPLETE ABSENCE OF 4592 03:40:02,080 --> 03:40:03,160 SYNAPSE PRUNING. 4593 03:40:03,160 --> 03:40:05,560 BEING ABLE TO IDENTIFY THE 4594 03:40:05,560 --> 03:40:07,760 GLOBAL TREND OF SYNAPSE WEIGHT 4595 03:40:07,760 --> 03:40:11,800 CHANGES ALLOWS US TO DESIGN 4596 03:40:11,800 --> 03:40:12,720 STRATEGIES TO COMPARE 4597 03:40:12,720 --> 03:40:16,960 DIFFERENCES BETWEEN CONNECTOMES. 4598 03:40:16,960 --> 03:40:18,920 THE PREMISE IS TO EVALUATE EACH 4599 03:40:18,920 --> 03:40:24,320 CELL-CELL CONNECTION BY THE 4600 03:40:24,320 --> 03:40:25,520 SYNAPTIC WEIGHT AGAINST THE 4601 03:40:25,520 --> 03:40:27,080 CONNECTIONS THAT EXHIBIT A 4602 03:40:27,080 --> 03:40:28,320 FASTER INCREASE REPRESENTING 4603 03:40:28,320 --> 03:40:30,160 CONNECTIONS THAT ARE ADDED 4604 03:40:30,160 --> 03:40:35,760 DURING DEVELOPMENT, CONNECTION 4605 03:40:35,760 --> 03:40:40,920 WITH NO INCREASE OF THE C. 4606 03:40:40,920 --> 03:40:43,000 ELEGANS PRUNING AND BECAUSE EACH 4607 03:40:43,000 --> 03:40:44,440 TIME POINT WE ONLY HAVE ONE 4608 03:40:44,440 --> 03:40:46,680 SAMPLE THAT MEANS ONE 4609 03:40:46,680 --> 03:40:47,160 CONNECTOME. 4610 03:40:47,160 --> 03:40:48,200 WE WANTED TO INCREASE THE 4611 03:40:48,200 --> 03:40:50,320 CONFIDENCE OF OUR CONCLUSIONS BY 4612 03:40:50,320 --> 03:40:51,320 TWO MEANS. 4613 03:40:51,320 --> 03:40:53,800 FIRST WAS MENTIONED BY ELLIE, WE 4614 03:40:53,800 --> 03:40:57,120 INCREASE THE STATISTIC POWER OF 4615 03:40:57,120 --> 03:40:58,200 OUR DATA SETS BY EXAMINING 4616 03:40:58,200 --> 03:41:01,160 INDIVIDUAL CONNECTIONS OF THE 4617 03:41:01,160 --> 03:41:02,520 LEFT-RIGHT CELL PAIR FOR EACH 4618 03:41:02,520 --> 03:41:04,640 CLASSES AND INCREASING THE 4619 03:41:04,640 --> 03:41:07,040 SAMPLE SIZE FROM 1-2. 4620 03:41:07,040 --> 03:41:11,160 SECOND, BECAUSE ADULT CONNECTOME 4621 03:41:11,160 --> 03:41:13,160 REPRESENT THE MATURE FORM WE ARE 4622 03:41:13,160 --> 03:41:15,520 ALLOWED TO SEPARATELY CONNECT 4623 03:41:15,520 --> 03:41:16,480 AND ASSESS THE SIMILARITY 4624 03:41:16,480 --> 03:41:18,400 DIFFERENCE BETWEEN ADULT 4625 03:41:18,400 --> 03:41:21,160 CONNECTOMES AND OVERLAP OF THE 4626 03:41:21,160 --> 03:41:22,720 CONNECTIONS REGARDLESS OF THE 4627 03:41:22,720 --> 03:41:24,760 SYNAPTIC WEIGHT. 4628 03:41:24,760 --> 03:41:26,520 FORCE THIS PURPOSE WE RECRUIT 4629 03:41:26,520 --> 03:41:29,240 THE LEGACY DATA SET FROM JOHN 4630 03:41:29,240 --> 03:41:31,560 WHITE THUS GENERATING MORE THAN 4631 03:41:31,560 --> 03:41:33,600 30 YEARS AGO. 4632 03:41:33,600 --> 03:41:35,560 TOGETHER THE ANALYSIS REVEALED 4633 03:41:35,560 --> 03:41:37,600 EACH CONNECTOME OF INDIVIDUALS 4634 03:41:37,600 --> 03:41:39,240 CONSISTENT OF THREE TYPES OF 4635 03:41:39,240 --> 03:41:39,720 CONNECTIONS. 4636 03:41:39,720 --> 03:41:43,920 STABLE CONNECTIONS THAT ARE 4637 03:41:43,920 --> 03:41:46,920 PRESENT AND INCREASES STEADILY 4638 03:41:46,920 --> 03:41:48,360 IN SYNAPTIC STRENGTH. 4639 03:41:48,360 --> 03:41:51,560 AND THE DYNAMIC CONNECTIONS 4640 03:41:51,560 --> 03:41:53,680 SELECTIVELY ADDED, PROMINENT 4641 03:41:53,680 --> 03:41:55,680 DURING THE EARLY OR LATE 4642 03:41:55,680 --> 03:41:58,080 DEVELOPMENT STAGES AND THE 4643 03:41:58,080 --> 03:42:06,480 VARIABLE CONNECTIONS THAT ARE 4644 03:42:06,480 --> 03:42:08,880 FORMED AND EXHIBIT NO OBVIOUS 4645 03:42:08,880 --> 03:42:09,080 TREND. 4646 03:42:09,080 --> 03:42:11,080 TOGETHER, WE CONCEDED A STABLE 4647 03:42:11,080 --> 03:42:12,840 AND DEVELOPMENTALLY DYNAMIC 4648 03:42:12,840 --> 03:42:16,280 CONNECTIONS MAKE UP THE CORE OR 4649 03:42:16,280 --> 03:42:19,320 THE PORTION OF THE C. ELEGANS 4650 03:42:19,320 --> 03:42:22,320 CONNECTOME AND FORM THE VARIABLE 4651 03:42:22,320 --> 03:42:25,840 PORTIONS OF INDIVIDUALS. 4652 03:42:25,840 --> 03:42:29,000 TO ASSESS WHERE THE VARIABLE AND 4653 03:42:29,000 --> 03:42:33,520 INVARIABLE CONNECTION 4654 03:42:33,520 --> 03:42:38,080 DISTRIBUTES WE LOOK AT 4655 03:42:38,080 --> 03:42:40,000 MODULATORY CONNECTOMES AND WE 4656 03:42:40,000 --> 03:42:43,080 CAN SEE FROM THE WIRING DIAGRAMS 4657 03:42:43,080 --> 03:42:46,240 THE VARIABLE CONNECTION MORE 4658 03:42:46,240 --> 03:42:48,280 BROADLY PRESENT BETWEEN AND 4659 03:42:48,280 --> 03:42:51,280 ACROSS MOST CELL TYPES WHEREAS 4660 03:42:51,280 --> 03:42:54,600 THE STABLE CONNECTIONS ARE 4661 03:42:54,600 --> 03:42:54,920 DISTRIBUTED. 4662 03:42:54,920 --> 03:42:57,040 TO VISUALIZE THIS MORE CLEARLY 4663 03:42:57,040 --> 03:42:58,200 PLOTTED ONLY THE INVARIABLE 4664 03:42:58,200 --> 03:43:00,480 CONNECTIONS IN THE ADULT 4665 03:43:00,480 --> 03:43:03,480 CONNECTOME BY THE SYNAPTIC 4666 03:43:03,480 --> 03:43:05,600 WEIGHT AND WE COLOR CODED THE 4667 03:43:05,600 --> 03:43:06,080 CONNECT. 4668 03:43:06,080 --> 03:43:11,160 FROM THIS DIAGRAM YOU CAN SEE 4669 03:43:11,160 --> 03:43:16,000 CLEARLY WHERE THE MOST PROMINENT 4670 03:43:16,000 --> 03:43:16,960 DEVELOPMENT CHANGES OCCUR SLOWLY 4671 03:43:16,960 --> 03:43:19,520 AND IN CONTRAST CONNECTIONS 4672 03:43:19,520 --> 03:43:21,840 AMONG MOST INTERNEURONS WHICH 4673 03:43:21,840 --> 03:43:24,480 CONSTITUTE THE CORE DECISION 4674 03:43:24,480 --> 03:43:26,160 MAKING SECTOR IS REMARKABLY 4675 03:43:26,160 --> 03:43:27,600 STABLE. 4676 03:43:27,600 --> 03:43:29,360 THUS, THIS ANALYSIS REVEALS TWO 4677 03:43:29,360 --> 03:43:31,520 UNEXPECTED PROPERTIES OF THE 4678 03:43:31,520 --> 03:43:33,360 DEVELOPMENT WIRING CHANGES. 4679 03:43:33,360 --> 03:43:36,880 ISO GENIC INDIVIDUALS CAN 4680 03:43:36,880 --> 03:43:41,760 ACTUALLY RAISE UNDER THE SAME 4681 03:43:41,760 --> 03:43:43,560 CONDITION AND STILL DEMONSTRATE 4682 03:43:43,560 --> 03:43:45,080 WIRING PROCESSING AND THEY'RE 4683 03:43:45,080 --> 03:43:46,680 LARGELY ESTABLISHED ALREADY AT 4684 03:43:46,680 --> 03:43:48,200 BIRTH BY SENSORY INTEGRATION AND 4685 03:43:48,200 --> 03:43:51,160 MOTOR REASONS CAN REMAIN PLASTIC 4686 03:43:51,160 --> 03:43:53,200 AFTER BIRTH. 4687 03:43:53,200 --> 03:43:53,920 LASTLY, WE FOUND THAT THE 4688 03:43:53,920 --> 03:43:56,720 SYNAPSE CHANGES CAN ALTER THE 4689 03:43:56,720 --> 03:43:59,800 NETWORK STRUCTURE. 4690 03:43:59,800 --> 03:44:03,520 WE USED WEIGHTED BLOCK MODELLING 4691 03:44:03,520 --> 03:44:05,680 TO BLOCK NEURONS INTO 4692 03:44:05,680 --> 03:44:07,840 DISTINCTIVE MODULES AND APPLIED 4693 03:44:07,840 --> 03:44:11,160 IS AND THIS RESULTED IN SIX 4694 03:44:11,160 --> 03:44:13,160 DISTINCTIVE MODULE AND EACH CAN 4695 03:44:13,160 --> 03:44:14,960 BE NAMED BY THE KNOWN BIOLOGICAL 4696 03:44:14,960 --> 03:44:17,160 FUNCTION OF THE CELLS THEY'RE 4697 03:44:17,160 --> 03:44:18,280 ENRICHED IN. 4698 03:44:18,280 --> 03:44:21,920 AND WHEN WE ARE APPLY THIS 4699 03:44:21,920 --> 03:44:24,200 CONNECTOME WE FOUND THE MODULAR 4700 03:44:24,200 --> 03:44:26,320 STRUCTURE FORMS DURING LATER 4701 03:44:26,320 --> 03:44:26,640 DEVELOPMENT. 4702 03:44:26,640 --> 03:44:31,680 FOR EXAMPLE, THE TWO DIFFERENCE 4703 03:44:31,680 --> 03:44:33,240 OF MODULES THAT ARE SEPARATED IN 4704 03:44:33,240 --> 03:44:37,000 THE ADULT CONNECTOME ONLY EMERGE 4705 03:44:37,000 --> 03:44:39,640 DURING THE LATE LARVAL STAGE. 4706 03:44:39,640 --> 03:44:42,320 THEREFORE THE SYNAPTIC GROWTH 4707 03:44:42,320 --> 03:44:48,200 REFINES SOME NETWORKS FOR 4708 03:44:48,200 --> 03:44:50,560 SENSORY OR MOTOR SENSES AND 4709 03:44:50,560 --> 03:44:52,800 THEY'RE BUILD STRONGER AND MORE 4710 03:44:52,800 --> 03:44:59,160 INVARIABLE CONNECTIVITY AND THEY 4711 03:44:59,160 --> 03:45:02,200 WANTED TO BECOME MORE MODULAR. 4712 03:45:02,200 --> 03:45:03,800 THIS MEANS SYNAPTIC GROWTH OR 4713 03:45:03,800 --> 03:45:06,280 ADDITION IS NOT RANDOM. 4714 03:45:06,280 --> 03:45:08,720 THEY'RE TARGETED WITH THE 4715 03:45:08,720 --> 03:45:09,520 COLLECTIVE GOAL. 4716 03:45:09,520 --> 03:45:11,520 THE REASON THAT WE'RE EXCITE 4717 03:45:11,520 --> 03:45:13,320 ABOUT THIS IS THIS EFFECTIVELY 4718 03:45:13,320 --> 03:45:14,640 TRANSLATES THE SECOND QUESTION, 4719 03:45:14,640 --> 03:45:17,080 WHAT MECHANISMS MAY GOVERN THE 4720 03:45:17,080 --> 03:45:18,520 MATURATION PROCESS INTO A 4721 03:45:18,520 --> 03:45:19,320 CONCRETE RESEARCH QUESTION. 4722 03:45:19,320 --> 03:45:23,160 WHAT ARE THE SYNAPSE AND HOW HAS 4723 03:45:23,160 --> 03:45:27,440 THE SIGNALLING MOLECULES TARGET 4724 03:45:27,440 --> 03:45:28,120 THIS ADDITION? 4725 03:45:28,120 --> 03:45:29,640 THERE'S MANY APPROACHES TO GO 4726 03:45:29,640 --> 03:45:30,400 ABOUT THIS. 4727 03:45:30,400 --> 03:45:33,120 THE BEGINNING APPROACH WE TOOK 4728 03:45:33,120 --> 03:45:34,920 WAS TO FURTHER EXAMINE THE 4729 03:45:34,920 --> 03:45:35,800 RELATIONSHIP. 4730 03:45:35,800 --> 03:45:37,720 IN THIS CASE WE'RE EXAMINING THE 4731 03:45:37,720 --> 03:45:40,520 CORRELATION OF THE PROPERTY OF 4732 03:45:40,520 --> 03:45:44,520 THE NEWBORN BRAIN OF THE 4733 03:45:44,520 --> 03:45:46,320 COMPACTOME AND CONNECTOME AND 4734 03:45:46,320 --> 03:45:50,920 IDENTIFY THE FEATURES OF THE L1 4735 03:45:50,920 --> 03:45:52,960 TOPOLOGY AND SYNAPTIC 4736 03:45:52,960 --> 03:45:54,040 CONNECTIVELY THAT CAN PREDICT 4737 03:45:54,040 --> 03:45:56,640 THE STRUCTURE OF THE ADULT 4738 03:45:56,640 --> 03:45:59,200 CONNECTO 4739 03:45:59,200 --> 03:46:00,120 CONNECTOME. 4740 03:46:00,120 --> 03:46:05,200 WE IDENTIFIED SOME POTENTIAL 4741 03:46:05,200 --> 03:46:07,160 ROLES. 4742 03:46:07,160 --> 03:46:14,080 WE KNOW UNIFORM NEURO ITE GROWTH 4743 03:46:14,080 --> 03:46:17,920 IN GROWTH NON-UNIFORM 4744 03:46:17,920 --> 03:46:19,280 SELECTIVELY STRENGTHENS THE 4745 03:46:19,280 --> 03:46:22,040 FINDING AND THE CONTEXT SIZE CAN 4746 03:46:22,040 --> 03:46:25,360 PREDICT THE LIKELIHOOD TO HAVE 4747 03:46:25,360 --> 03:46:28,240 NEW SYNAPSES AND THE NEW NEURONS 4748 03:46:28,240 --> 03:46:33,000 AT BIRTH HAVE HIGHER PROPENSITY 4749 03:46:33,000 --> 03:46:36,440 TO HAVE NEW CONNECTIVITY INPUT 4750 03:46:36,440 --> 03:46:38,080 AND OUTPOUT AND STRENGTHEN 4751 03:46:38,080 --> 03:46:39,920 EXISTING CONDITIONS WITHOUT 4752 03:46:39,920 --> 03:46:42,360 ADDING MORE CONNECTIVITY AND 4753 03:46:42,360 --> 03:46:44,160 SYNAPTIC CONNECTIONS RECEIVE 4754 03:46:44,160 --> 03:46:46,360 MORE SYNAPSES TO STRENGTHEN 4755 03:46:46,360 --> 03:46:56,320 THEM. 4756 03:46:56,320 --> 03:46:58,320 IN THE LAST QUESTION I'D LIKE TO 4757 03:46:58,320 --> 03:47:01,800 POINT TO A GENETIC FINGERPRINT 4758 03:47:01,800 --> 03:47:05,120 THAT DETERMINES THE WIRING 4759 03:47:05,120 --> 03:47:05,360 DIAGRAM. 4760 03:47:05,360 --> 03:47:07,040 AND THE ENVIRONMENT ALTER THE 4761 03:47:07,040 --> 03:47:08,000 WIRING. 4762 03:47:08,000 --> 03:47:11,200 FOR THIS WE RETURN TO THIS MOST 4763 03:47:11,200 --> 03:47:12,320 HARSH ENVIRONMENTAL CONDITIONS 4764 03:47:12,320 --> 03:47:14,080 THAT C. ELEGANS CAN FACE. 4765 03:47:14,080 --> 03:47:15,760 YOU RECALL I SAID AT THE 4766 03:47:15,760 --> 03:47:16,920 BEGINNING WE ALREADY KNOW 4767 03:47:16,920 --> 03:47:18,120 EXPOSURE TO THE HARSH 4768 03:47:18,120 --> 03:47:21,120 ENVIRONMENT AT THE END OF R1 4769 03:47:21,120 --> 03:47:25,960 STAGE HOW THE POST-EMBRYONIC 4770 03:47:25,960 --> 03:47:28,320 DEVELOPMENT CAN GET BETTER AND 4771 03:47:28,320 --> 03:47:32,120 THE ANIMALS CAN STOP FEEDING BUT 4772 03:47:32,120 --> 03:47:33,480 DEMONSTRATE DIFFERENT MORPHOLOGY 4773 03:47:33,480 --> 03:47:34,960 AND BEHAVIOR. 4774 03:47:34,960 --> 03:47:40,240 WE PERFORMED CONNECTOME BEHAVIOR 4775 03:47:40,240 --> 03:47:45,160 AND RECALL WE IDENTIFIED OVER 4776 03:47:45,160 --> 03:47:46,600 1,000 CONNECTIONS. 4777 03:47:46,600 --> 03:47:49,160 REGARDLESS OF THE STAGES THOSE 4778 03:47:49,160 --> 03:47:52,080 CONNECTIONS ARE THERE AND THEN 4779 03:47:52,080 --> 03:47:55,680 HAVE A SIMILAR RATE IN THE 4780 03:47:55,680 --> 03:47:56,000 NETWORK. 4781 03:47:56,000 --> 03:47:59,080 AND TO OUR SURPRISE THAT THOSE 4782 03:47:59,080 --> 03:48:03,320 CONNECTIONS ONLY ABOUT 4783 03:48:03,320 --> 03:48:06,000 TWO-THIRDS IS SHARED IN THE 4784 03:48:06,000 --> 03:48:06,320 CONNECTOME. 4785 03:48:06,320 --> 03:48:08,640 ABOUT 237 CONNECTIONS IS ABSENT 4786 03:48:08,640 --> 03:48:14,120 IN THE DATA SET AND IN ADDITION, 4787 03:48:14,120 --> 03:48:17,040 AT LEAST THREE OUT OF FOUR HAVE 4788 03:48:17,040 --> 03:48:19,960 NEW CONNECTIONS ABSENT FROM OUR 4789 03:48:19,960 --> 03:48:21,920 CORE CONNECTOME. 4790 03:48:21,920 --> 03:48:25,960 SO THIS REALLY SUGGESTIONS THAT 4791 03:48:25,960 --> 03:48:27,880 ENVIRONMENT CAN FUNCTION 4792 03:48:27,880 --> 03:48:30,080 TOGETHER WITH GENES TO SHAPE THE 4793 03:48:30,080 --> 03:48:32,800 SECTOR MATURATION OF THE PATIENT 4794 03:48:32,800 --> 03:48:35,400 AND SOMETHING CORE TO WHAT I'M 4795 03:48:35,400 --> 03:48:38,080 INTERESTED IN THE QUESTION OF 4796 03:48:38,080 --> 03:48:41,920 DESTINY IN PLASTICITY. 4797 03:48:41,920 --> 03:48:45,080 IN CLOSING NEED OF THE NERVOUS 4798 03:48:45,080 --> 03:48:48,640 SYSTEM TO GROW AND ADAPT IS 4799 03:48:48,640 --> 03:48:51,280 UNIVERSAL I DO AGREE WITH 4800 03:48:51,280 --> 03:48:56,080 EVERYBODY HERE THAT COMPARATIVE 4801 03:48:56,080 --> 03:49:00,600 STUDIES ARE CRUCIAL TO UNLOCK 4802 03:49:00,600 --> 03:49:02,080 WIRING RESOLUTION AND I WAS 4803 03:49:02,080 --> 03:49:04,920 REQUESTED TO IDENTIFY THE 4804 03:49:04,920 --> 03:49:05,720 REMAINING GAPS AND FUTURE 4805 03:49:05,720 --> 03:49:06,160 OPPORTUNITIES. 4806 03:49:06,160 --> 03:49:08,840 THESE ARE THE REMAINING GAPS IN 4807 03:49:08,840 --> 03:49:11,160 WHICH WE'RE ACTIVELY WORKING ON. 4808 03:49:11,160 --> 03:49:15,160 WE NEED TO GET ELECTRICAL CLEM 4809 03:49:15,160 --> 03:49:18,080 CAL SYNAPSES NOBODY TALKED ABOUT 4810 03:49:18,080 --> 03:49:20,560 AND MOLECULAR MAPPING AND USING 4811 03:49:20,560 --> 03:49:23,040 MUTANT MAPPING TOFIDE THE 4812 03:49:23,040 --> 03:49:27,720 GENETIC MECHANISMS OF THE WIRING 4813 03:49:27,720 --> 03:49:30,080 AND INTERPLAY BETWEEN GENES AND 4814 03:49:30,080 --> 03:49:30,640 ENVIRONMENT. 4815 03:49:30,640 --> 03:49:32,320 WITH THIS I WANTED TO THANK 4816 03:49:32,320 --> 03:49:32,920 EVERYBODY AND MY WONDERFUL 4817 03:49:32,920 --> 03:49:34,040 COLLEAGUES AND COLLABORATORS TO 4818 03:49:34,040 --> 03:49:35,560 MAKE THE WORK POSSIBLE AND I 4819 03:49:35,560 --> 03:49:37,080 WANT TO THANK JOHN WHITE WHO HAS 4820 03:49:37,080 --> 03:49:39,320 BEEN A MENTOR AND AN EXTREMELY 4821 03:49:39,320 --> 03:49:44,120 SUPPORTIVE MEMBER WHO HAS BEEN 4822 03:49:44,120 --> 03:49:44,760 TREMENDOUSLY SUPPORTIVE IN THE 4823 03:49:44,760 --> 03:49:46,720 LAST FEW YEARS WHEN THIS WORK 4824 03:49:46,720 --> 03:49:50,160 WAS ACTUALLY PRETTY DIFFICULT TO 4825 03:49:50,160 --> 03:49:50,320 DO. 4826 03:49:50,320 --> 03:49:56,280 THANK YOU VERY MUCH. 4827 03:49:56,280 --> 03:49:57,960 >> THANK YOU VERY MUCH. 4828 03:49:57,960 --> 03:49:59,800 BEAUTIFUL DATA. 4829 03:49:59,800 --> 03:50:00,000 GREAT. 4830 03:50:00,000 --> 03:50:01,560 IT'S TIME FOR SOME DISCUSSION. 4831 03:50:01,560 --> 03:50:02,960 I HAVE A FEW QUESTIONS. 4832 03:50:02,960 --> 03:50:04,680 I ENCOURAGE PEOPLE TO HAD MORE 4833 03:50:04,680 --> 03:50:10,080 QUESTIONS TO THE CHAT OR SEND 4834 03:50:10,080 --> 03:50:13,840 THEM THROUGH US AND CAN ALL THE 4835 03:50:13,840 --> 03:50:17,120 SPEAKERS TURN ON THEIR VIDEO AND 4836 03:50:17,120 --> 03:50:21,960 UNMUTE. 4837 03:50:21,960 --> 03:50:25,520 GREAT. 4838 03:50:25,520 --> 03:50:34,080 SO I HAVE A COUPLE QUESTIONS. 4839 03:50:34,080 --> 03:50:38,680 I'LL START WITH DR. SETS OMPOP. 4840 03:50:38,680 --> 03:50:40,680 BOTH SUGGESTIONS SUGGEST HIGH 4841 03:50:40,680 --> 03:50:44,280 RESOLUTION DWI CAN ALLOW ONE TO 4842 03:50:44,280 --> 03:50:47,080 RESOLVE FIBERS EITHER U OR SUB 4843 03:50:47,080 --> 03:50:48,440 CORTICAL TRACTS. 4844 03:50:48,440 --> 03:50:50,600 THAT CLINICAL RESEARCH QUALITIES 4845 03:50:50,600 --> 03:50:51,520 CANNOT. 4846 03:50:51,520 --> 03:50:58,520 I WAS WONDERING IF THE 4847 03:50:58,520 --> 03:51:00,320 INTERPOLATION OF SCANS OF 4848 03:51:00,320 --> 03:51:02,040 MILLIMETER RESOLUTION WAS TESTED 4849 03:51:02,040 --> 03:51:04,600 TO SEE IF THE SCANS COULD WE 4850 03:51:04,600 --> 03:51:06,520 INVOLVE THE TRACKS. 4851 03:51:06,520 --> 03:51:07,240 >> THANK YOU. 4852 03:51:07,240 --> 03:51:10,080 I'LL START A LITTLE BIT IF 4853 03:51:10,080 --> 03:51:26,360 THAT'S OKAY. 4854 03:51:26,360 --> 03:51:30,080 >> WE'RE LOOKING AT IT'S TYPES 4855 03:51:30,080 --> 03:51:40,280 OF TRACTS WE ARE LOOK AT THE 4856 03:51:40,280 --> 03:51:43,080 FIBERS AND IT WOULD BE A WAY TO 4857 03:51:43,080 --> 03:51:45,080 INFER HIGHER TO LOWER RESOLUTION 4858 03:51:45,080 --> 03:51:48,440 TO HELP WITH SOME OF THAT. 4859 03:51:48,440 --> 03:51:52,120 SO THERE'S TWO PRONGS TO WORK 4860 03:51:52,120 --> 03:51:52,800 WITH BETTER ACQUISITION AND 4861 03:51:52,800 --> 03:51:54,080 UTILIZE THE BEST DATA WE HAVE 4862 03:51:54,080 --> 03:51:58,080 AND TRY TO USE THAT AS PRIOR TO 4863 03:51:58,080 --> 03:52:00,720 RECONSTRUCT THE LOWER RESOLUTION 4864 03:52:00,720 --> 03:52:00,920 DATA. 4865 03:52:00,920 --> 03:52:03,440 I'LL LEAVE IT AT THAT BECAUSE 4866 03:52:03,440 --> 03:52:06,000 I'M SURE ANASTASIA HAS QUITE A 4867 03:52:06,000 --> 03:52:08,080 FEW THINGS TO SAY AS WELL. 4868 03:52:08,080 --> 03:52:11,720 >> THANKS, KAWIN. 4869 03:52:11,720 --> 03:52:13,040 THAT'S A GREAT QUESTION, 4870 03:52:13,040 --> 03:52:13,400 ACTUALLY. 4871 03:52:13,400 --> 03:52:18,120 WE HAVE A PROPOSAL TO DO 4872 03:52:18,120 --> 03:52:30,000 REVIEWED THAT AND SUPER 4873 03:52:30,000 --> 03:52:32,640 RESOLUTION TECHNIQUES CAN HELP 4874 03:52:32,640 --> 03:52:34,560 IN THAT REGARD AND I THINK IT'S 4875 03:52:34,560 --> 03:52:43,520 AN EXCITING DIRECTION TO USE WE 4876 03:52:43,520 --> 03:52:45,600 HAVE THE LUXURY TO COLLECT 4877 03:52:45,600 --> 03:52:50,800 HIGH-QUALITY DATA SETS TO 4878 03:52:50,800 --> 03:52:53,320 ENHANCE MORE CLINICALLY FEASIBLE 4879 03:52:53,320 --> 03:53:02,760 PROTOCOLS. 4880 03:53:02,760 --> 03:53:05,920 >> FOR DR. YENDIKI WHAT DO YOU 4881 03:53:05,920 --> 03:53:09,680 THINK THE ROLE OF POST MORTEM 4882 03:53:09,680 --> 03:53:10,720 CONNECTIVELY ROLE WILL BE GIVEN 4883 03:53:10,720 --> 03:53:12,640 THE LIMITATION OF RESOLUTION IN 4884 03:53:12,640 --> 03:53:15,360 FUNCTIONAL IMAGING STUDIES? 4885 03:53:15,360 --> 03:53:17,720 >> THAT'S ALWAYS A TOUGH ONE AND 4886 03:53:17,720 --> 03:53:20,440 A FAVORITE ONE. 4887 03:53:20,440 --> 03:53:23,680 HOW THE FUNCTIONAL CONNECTIVITY 4888 03:53:23,680 --> 03:53:25,920 RELATES TO STRUCTURAL 4889 03:53:25,920 --> 03:53:26,240 CONNECTIONS. 4890 03:53:26,240 --> 03:53:30,520 SINCE WE'RE ON THE TOPIC OF 4891 03:53:30,520 --> 03:53:34,080 CHANGES OVER THE LIFE SPAN, 4892 03:53:34,080 --> 03:53:35,000 DEFINITELY FUNCTIONAL 4893 03:53:35,000 --> 03:53:39,800 CONNECTIVITY AND STRUCTURAL 4894 03:53:39,800 --> 03:53:41,520 CONNECTIVITY ARE DIFFERENT TIME 4895 03:53:41,520 --> 03:53:44,800 SCALES AND STRUCTURAL 4896 03:53:44,800 --> 03:53:45,440 CONNECTIVITY TENDS TO CHANGE 4897 03:53:45,440 --> 03:53:47,120 MUCH SLOWER OVER TIME AND 4898 03:53:47,120 --> 03:53:50,000 FUNCTIONAL CONNECTIVITY IS 4899 03:53:50,000 --> 03:53:51,600 HIGHLY DYNAMIC EVEN WITHIN A DAY 4900 03:53:51,600 --> 03:53:54,240 DEPENDING ON HOW MUCH COFFEE YOU 4901 03:53:54,240 --> 03:53:55,360 HAD THAT DAY OR HOW MUCH SLEEP 4902 03:53:55,360 --> 03:53:58,080 YOU HAD, ETCETERA. 4903 03:53:58,080 --> 03:54:01,200 WE DEFINITELY DO NOT EXPECT THE 4904 03:54:01,200 --> 03:54:05,920 TWO TO AGREE AND THEY CONVEY 4905 03:54:05,920 --> 03:54:07,840 COMPLIMENTARY INFORMATION. 4906 03:54:07,840 --> 03:54:10,080 DEFINITELY STRUCTURAL 4907 03:54:10,080 --> 03:54:12,080 CONNECTIVITY HAS SPECIFICALLY AT 4908 03:54:12,080 --> 03:54:15,400 THE HIGHER RESOLUTIONS WE CAN 4909 03:54:15,400 --> 03:54:24,240 ACHIEVE MOST -- POST MORTEM CAN 4910 03:54:24,240 --> 03:54:27,480 INFORM FUNCTIONAL STUDIES AND 4911 03:54:27,480 --> 03:54:34,080 THERE'S PARALLEL AND SEGREGATED 4912 03:54:34,080 --> 03:54:37,360 CIRCUITS TO JUSTIFY WHERE 4913 03:54:37,360 --> 03:54:39,800 SOMETIMES THE PICTURE IS MORE 4914 03:54:39,800 --> 03:54:40,040 COMPLEX. 4915 03:54:40,040 --> 03:54:42,080 SO BEING ABLE TO DO THAT KIND OF 4916 03:54:42,080 --> 03:54:44,920 MAPPING AND HIGH RESOLUTION IN 4917 03:54:44,920 --> 03:54:47,680 THE HUMAN BRAIN WILL ALLOW US TO 4918 03:54:47,680 --> 03:54:48,880 SHED LIGHT ON SOME OF THESE 4919 03:54:48,880 --> 03:54:55,360 QUESTIONS. 4920 03:54:55,360 --> 03:54:57,960 >> I HAVE ONE FROM DANIEL GLEN 4921 03:54:57,960 --> 03:55:00,000 WHICH IS RATHER LONG BUT 4922 03:55:00,000 --> 03:55:00,400 INTERESTING. 4923 03:55:00,400 --> 03:55:01,680 >> I THINK IT MUST HAVE GOTTEN 4924 03:55:01,680 --> 03:55:08,640 CUT BECAUSE I DIDN'T SEE THE 4925 03:55:08,640 --> 03:55:11,400 QUESTION. 4926 03:55:11,400 --> 03:55:13,000 >> A FEW COMMENTS. 4927 03:55:13,000 --> 03:55:15,480 EFFORTS WITH PETER BASSLER AND 4928 03:55:15,480 --> 03:55:19,680 DR. SALIM ON HIGH RESOLUTION 4929 03:55:19,680 --> 03:55:22,080 MACAQUE WITH MATCHING HISTOLOGY 4930 03:55:22,080 --> 03:55:25,040 INTEGRATION ALLOWED US TO 4931 03:55:25,040 --> 03:55:26,400 RECENTLY CREATE A NEW HIGH 4932 03:55:26,400 --> 03:55:29,160 RESOLUTION ATLAS FOR THE MACAQUE 4933 03:55:29,160 --> 03:55:29,640 BRAIN. 4934 03:55:29,640 --> 03:55:32,520 I AGREE WITH THE ADVANTAGES OF 4935 03:55:32,520 --> 03:55:35,040 LONGITUDINAL CHANGES VERSE THIS 4936 03:55:35,040 --> 03:55:36,480 H DIFFERENCES THOUGH IT'S 4937 03:55:36,480 --> 03:55:38,080 IMPORTANT TO REALIZE THE ERROR 4938 03:55:38,080 --> 03:55:39,360 ASSOCIATED WITH EACH MEASUREMENT 4939 03:55:39,360 --> 03:55:43,320 AND CORTICAL THICKNESS IS OFTEN 4940 03:55:43,320 --> 03:55:48,000 CALCULATED ON THE CORTEX. 4941 03:55:48,000 --> 03:55:49,480 THOSE ARE SENSITIVE TO THE 4942 03:55:49,480 --> 03:55:52,760 INCONSISTENCY ACROSS SESSIONS OR 4943 03:55:52,760 --> 03:55:56,040 EVEN EXTRA ZERO SLICES AT THE 4944 03:55:56,040 --> 03:56:02,640 LARGEST POINT OF POINT 4945 03:56:02,640 --> 03:56:04,640 MILLIMETER AND IT MAY STILL 4946 03:56:04,640 --> 03:56:05,280 REACH STATISTICAL SIGNIFICANCE 4947 03:56:05,280 --> 03:56:11,000 ON A LARGE GROUP. 4948 03:56:11,000 --> 03:56:14,320 DO EITHER OF YOU WANT TO 4949 03:56:14,320 --> 03:56:23,080 RESPOND? 4950 03:56:23,080 --> 03:56:24,240 >> WHAT'S THE QUESTION? 4951 03:56:24,240 --> 03:56:29,920 >> HE'S CONCERNED ABOUT THE 4952 03:56:29,920 --> 03:56:31,720 VARIABILITY ACROSS TIME IS 4953 03:56:31,720 --> 03:56:34,080 LOOKING FOR DIFFERENCES IS 4954 03:56:34,080 --> 03:56:36,920 SENSITIVE TO ACQUISITION AND 4955 03:56:36,920 --> 03:56:39,720 RESAMPLING ON THE GRID. 4956 03:56:39,720 --> 03:56:46,920 >> YEAH, IT IS. 4957 03:56:46,920 --> 03:56:51,000 >> THAT'S THE ONE THING WE WORK 4958 03:56:51,000 --> 03:56:52,280 HARD AT TRYING TO HIGH 4959 03:56:52,280 --> 03:56:54,400 RESOLUTION AND REMOVING SOME OF 4960 03:56:54,400 --> 03:56:55,960 THE BIAS. 4961 03:56:55,960 --> 03:56:57,000 A LARGE PART OF THE WORK IN THE 4962 03:56:57,000 --> 03:56:58,720 LAB IS LOOKING AT THE 4963 03:56:58,720 --> 03:57:01,160 QUANTITATIVE IMAGING AT VERY 4964 03:57:01,160 --> 03:57:01,600 HIGH RESOLUTION. 4965 03:57:01,600 --> 03:57:04,280 SO WE'RE GETTING RID OF THE 4966 03:57:04,280 --> 03:57:07,120 VARIABILITY IN TERMS OF THE 4967 03:57:07,120 --> 03:57:11,720 VOXEL SIZE RESAMPLING AS WELL AS 4968 03:57:11,720 --> 03:57:13,200 DIFFERENT SCAN CASES AND 4969 03:57:13,200 --> 03:57:14,200 HOPEFULLY THAT WILL HELP IN 4970 03:57:14,200 --> 03:57:17,320 TERMS OF THE LARGE-SCALE STUDIES 4971 03:57:17,320 --> 03:57:21,480 AND ANALYSIS. 4972 03:57:21,480 --> 03:57:24,320 >> AND TO CLARIFY THAT WAS NOT 4973 03:57:24,320 --> 03:57:26,400 FROM DANIEL GLEN JUST FROM 4974 03:57:26,400 --> 03:57:36,000 COMMENTS. 4975 03:57:36,000 --> 03:57:38,600 I HAVE A QUESTION. 4976 03:57:38,600 --> 03:57:40,120 HOW MUCH DO YOU THINK THAT 4977 03:57:40,120 --> 03:57:42,080 MACHINE LEARNING AND ARTIFICIAL 4978 03:57:42,080 --> 03:57:44,920 NATURAL GAS CAN HELP GOING 4979 03:57:44,920 --> 03:57:45,720 FORWARD IN INCREASING THE 4980 03:57:45,720 --> 03:57:49,720 RESOLUTION AND POSSIBLY EVEN 4981 03:57:49,720 --> 03:57:54,520 BRIDGING THE GAP BETWEEN MRI AND 4982 03:57:54,520 --> 03:57:57,040 OTHER MODAL ANALYZING STRUCTURE 4983 03:57:57,040 --> 03:57:57,920 IN POSTMORTEM SAMPLES, FOR 4984 03:57:57,920 --> 03:58:05,440 EXAMPLE. 4985 03:58:05,440 --> 03:58:08,920 >> WE NEED THE POST MORTEM 4986 03:58:08,920 --> 03:58:11,200 MAPPING BECAUSE WE CANNOT TAKE 4987 03:58:11,200 --> 03:58:12,520 ADVANTAGE OF METHODS BECAUSE WE 4988 03:58:12,520 --> 03:58:13,640 DON'T HAVE THE GROUND TRUTH. 4989 03:58:13,640 --> 03:58:16,120 WHAT WE CAN USE AS THE GROUND 4990 03:58:16,120 --> 03:58:22,000 TRUTH AS A SUBSTITUTE OF THE 4991 03:58:22,000 --> 03:58:23,600 GROUND TRUTH IS MAYBE HIGHER 4992 03:58:23,600 --> 03:58:24,440 RESOLUTION SCANS, FOR EXAMPLE. 4993 03:58:24,440 --> 03:58:28,240 BUT STILL IT DOESN'T GET TO EVEN 4994 03:58:28,240 --> 03:58:29,320 THE HIGHER RESOLUTION MRI SCANS 4995 03:58:29,320 --> 03:58:32,080 HAVE THEIR OWN LIMITATIONS. 4996 03:58:32,080 --> 03:58:37,080 AND SO UNTIL WE REALLY HAVE THE 4997 03:58:37,080 --> 03:58:39,600 GROUND TRUTH OF THE CIRCUITRY OF 4998 03:58:39,600 --> 03:58:41,920 THE BRAIN WE WILL NOT TRULY BE 4999 03:58:41,920 --> 03:58:44,080 ABLE TO HARNESS THESE MACHINE 5000 03:58:44,080 --> 03:58:47,080 LEARNING APPROACHES AND THAT'S 5001 03:58:47,080 --> 03:58:48,360 EXACTLY ONE IMPORTANT DIRECTION 5002 03:58:48,360 --> 03:58:56,600 OF THE POST MORTEM WORK. 5003 03:58:56,600 --> 03:58:57,920 >> I'LL ADD THE IMPORTANCE OF 5004 03:58:57,920 --> 03:58:59,600 THE GROUND TRUTH IS IMPORTANCE 5005 03:58:59,600 --> 03:59:05,080 SO THE MACHINE LEARNING 5006 03:59:05,080 --> 03:59:08,920 APPROACHES SO GET IN VIVO DATA 5007 03:59:08,920 --> 03:59:10,920 THAT ANASTASIA MENTIONED SOME 18 5008 03:59:10,920 --> 03:59:12,240 HOURS OF SCANNING ACROSS NINE 5009 03:59:12,240 --> 03:59:14,080 SESSIONS FOR SOME OF THE 5010 03:59:14,080 --> 03:59:15,440 DIFFUSION SCAN BUT STILL IT'S 5011 03:59:15,440 --> 03:59:19,840 NOT AT A RESOLUTION WHERE WE 5012 03:59:19,840 --> 03:59:22,400 HAVE SOME OF THESE EX VIVO 5013 03:59:22,400 --> 03:59:24,520 SAMPLES WE CAN DO. 5014 03:59:24,520 --> 03:59:26,080 DEVELOPING THE RIGHT MACHINE 5015 03:59:26,080 --> 03:59:27,760 LEARNING TOOL TO UTILIZE THAT 5016 03:59:27,760 --> 03:59:29,240 WILL BE IMPORTANT. 5017 03:59:29,240 --> 03:59:31,120 IN TERMS OF THE ACQUISITION SIDE 5018 03:59:31,120 --> 03:59:34,040 AND MRI, I WOULD WANT TO USE IT 5019 03:59:34,040 --> 03:59:36,320 MAINLY FOR SPEEDING UP THE 5020 03:59:36,320 --> 03:59:38,480 RECONSTRUCTION RATHER THAN USING 5021 03:59:38,480 --> 03:59:40,160 IT AS AN EXTRA PRIOR. 5022 03:59:40,160 --> 03:59:41,520 I THINK WE HAVE AN APPROACH 5023 03:59:41,520 --> 03:59:43,920 BASED ON PHYSICS TO DO WELL IN 5024 03:59:43,920 --> 03:59:45,800 TERMS OF ACQUISITION BUT WE'RE 5025 03:59:45,800 --> 03:59:48,800 GETTING DATA AT A RATE THAT IS 5026 03:59:48,800 --> 03:59:49,880 CRAZY NOW. 5027 03:59:49,880 --> 03:59:51,760 YOU'RE GETTING SUBMILLIMETER 5028 03:59:51,760 --> 03:59:52,840 VOXEL ACROSS THE WHOLE BRAIN. 5029 03:59:52,840 --> 03:59:58,000 HAVE YOU 500, 600 TIME POINTS IN 5030 03:59:58,000 --> 03:59:59,920 A COUPLE MINUTES AND HOW DO YOU 5031 03:59:59,920 --> 04:00:01,240 RECONSTRUCT THAT PARALLEL. 5032 04:00:01,240 --> 04:00:03,160 YOU CAN SCAN FOR TWO MINUTES BUT 5033 04:00:03,160 --> 04:00:04,840 YOU CAN'T WAIT FOR 10 HOURS TO 5034 04:00:04,840 --> 04:00:07,080 DO THE RECONSTRUCTION AND GIVE 5035 04:00:07,080 --> 04:00:07,800 IT TO ANALYSIS. 5036 04:00:07,800 --> 04:00:11,480 YOU NEED TO BE ABLE TO HAVE 5037 04:00:11,480 --> 04:00:12,120 INSTANTANEOUS ONLINE 5038 04:00:12,120 --> 04:00:14,120 RECONSTRUCTION OF THE DATA AND A 5039 04:00:14,120 --> 04:00:17,120 THINK THAT'S WHERE MACHINE 5040 04:00:17,120 --> 04:00:29,120 LEARNING WILL HELP US A LOT. 5041 04:00:29,120 --> 04:00:31,800 >> DID YOU WANT TO ASK A 5042 04:00:31,800 --> 04:00:32,080 QUESTION? 5043 04:00:32,080 --> 04:00:34,920 >> I'M A MOLECULAR GENETICISTS 5044 04:00:34,920 --> 04:00:36,640 AND WHEN THE HUMAN GENOME DATA 5045 04:00:36,640 --> 04:00:40,160 AND WE WORKED TO IDENTIFY THE 5046 04:00:40,160 --> 04:00:41,640 FIRST POSITIVE MUTATIONS FROM 5047 04:00:41,640 --> 04:00:43,920 SOME THINGS WE'RE TESTING AND WE 5048 04:00:43,920 --> 04:00:47,880 STARTED TO DO DE NOVO SEQUENCING 5049 04:00:47,880 --> 04:00:52,720 THAT COMPARED THE MOLECULAR 5050 04:00:52,720 --> 04:00:53,520 CHANGES SIBLINGS AND THEIR 5051 04:00:53,520 --> 04:00:56,720 PARENTS I WONDERED WITH THE 5052 04:00:56,720 --> 04:01:01,920 BRAIN IMAGING APPROACH AND SOME 5053 04:01:01,920 --> 04:01:02,880 APPROACHES LIKE THAT, THAT'S A 5054 04:01:02,880 --> 04:01:06,400 BIT MORE TARGETED BUT WOULD THAT 5055 04:01:06,400 --> 04:01:09,960 BE MORE HELPFUL TO IDENTIFY -- I 5056 04:01:09,960 --> 04:01:12,120 WOULDN'T SAY POSITIVE BUT 5057 04:01:12,120 --> 04:01:15,440 SOMETHING THAT REDUCED LIKE 5058 04:01:15,440 --> 04:01:17,680 PINPOINT MORE SPECIFIC 5059 04:01:17,680 --> 04:01:22,840 POTENTIALLY PATHOLOGICAL OR 5060 04:01:22,840 --> 04:01:29,120 MORPHOLOGICAL MORE RELIABLE 5061 04:01:29,120 --> 04:01:30,440 CONNECTIVITY CHANGES? 5062 04:01:30,440 --> 04:01:32,640 >> I THINK ONE OPEN QUESTION AT 5063 04:01:32,640 --> 04:01:35,480 WHAT SCALE DO WE NEED TO 5064 04:01:35,480 --> 04:01:35,880 OPERATE? 5065 04:01:35,880 --> 04:01:39,720 DO WE REALLY NEED EVERY SINGLE 5066 04:01:39,720 --> 04:01:42,520 AXON IN THE HUMAN BRAIN? 5067 04:01:42,520 --> 04:01:44,920 I THINK IT'S QUITE POSSIBLY WE 5068 04:01:44,920 --> 04:01:46,040 DO NOT BECAUSE IT'S NOT GOING TO 5069 04:01:46,040 --> 04:01:50,120 BE A SINGLE AXON THAT MAKES THE 5070 04:01:50,120 --> 04:01:53,440 DIFFERENCE BETWEEN PATHOLOGICAL 5071 04:01:53,440 --> 04:02:01,800 BRAIN AND A HEALTHY BRAIN. 5072 04:02:01,800 --> 04:02:03,400 AND IT'S UNLIKELY THERE'S ONE 5073 04:02:03,400 --> 04:02:05,520 SINGLE AXON THAT DIFFERENTIATES 5074 04:02:05,520 --> 04:02:07,040 US FROM OTHER BRAINS. 5075 04:02:07,040 --> 04:02:22,520 ONE PERSON'S BRAIN FROM ANOTHER. 5076 04:02:22,520 --> 04:02:27,640 I THINK IT'S OPERATING AT A 5077 04:02:27,640 --> 04:02:30,440 SCALE TO CLINICAL REFERENCE AND 5078 04:02:30,440 --> 04:02:31,600 IS THE SWEET SPOT WHERE WE NEED 5079 04:02:31,600 --> 04:02:31,800 TO BE. 5080 04:02:31,800 --> 04:02:53,720 >> GREAT. 5081 04:02:53,720 --> 04:02:59,880 HOW DO THEY REWIRE TO INNERVATE 5082 04:02:59,880 --> 04:03:05,480 ADULT MUSCLES? 5083 04:03:05,480 --> 04:03:10,080 IS THERE ANY GENETIC 5084 04:03:10,080 --> 04:03:16,120 RELATIONSHIP TO REGENERATION? 5085 04:03:16,120 --> 04:03:19,920 >> 10% OF OUR ADULT SYSTEM IS 5086 04:03:19,920 --> 04:03:26,520 BORN IN THE EMBRYO AND GETS 5087 04:03:26,520 --> 04:03:29,120 REMODELLED AND AS THE MOTE MOTOR 5088 04:03:29,120 --> 04:03:30,840 NEURONS AND THE AXONS RETRACT 5089 04:03:30,840 --> 04:03:34,080 INTO THE CELL BODY AND THEY GROW 5090 04:03:34,080 --> 04:03:45,400 OUT AGAIN DE NOVO. 5091 04:03:45,400 --> 04:03:50,720 THERE'S THE MUSHROOM BODY WHICH 5092 04:03:50,720 --> 04:03:52,200 GETS MASSIVELY REMODELLED PEOPLE 5093 04:03:52,200 --> 04:03:56,520 HAVE USED TO STUDY THE 5094 04:03:56,520 --> 04:03:56,800 QUESTIONS. 5095 04:03:56,800 --> 04:03:59,920 THERE'S ALSO SENSORY NEURON 5096 04:03:59,920 --> 04:04:03,560 DENDRITE GET MASSIVELY 5097 04:04:03,560 --> 04:04:05,160 REMODELLED. 5098 04:04:05,160 --> 04:04:07,720 THEY LOOK LIKE THE NEURON 5099 04:04:07,720 --> 04:04:10,080 BETWEEN DR. HUGANIR'S HEAD AND 5100 04:04:10,080 --> 04:04:12,080 YOU CAN DO STUDIES OF 5101 04:04:12,080 --> 04:04:17,040 REMODELLING AND REGENERATION IN 5102 04:04:17,040 --> 04:04:23,000 THOSE CONTEXTS. 5103 04:04:23,000 --> 04:04:24,360 THERE'S A HUGE NUMBER THAT ARE 5104 04:04:24,360 --> 04:04:26,240 INTERESTING HAVING TO DO WITH 5105 04:04:26,240 --> 04:04:29,160 THE REMODELLING EVENTS. 5106 04:04:29,160 --> 04:04:34,080 >> HERE'S A QUESTION FOR 5107 04:04:34,080 --> 04:04:34,640 DR. ZHEN. 5108 04:04:34,640 --> 04:04:34,920 THANK YOU. 5109 04:04:34,920 --> 04:04:37,120 I'D LIKE TO KNOW WHAT DO YOU 5110 04:04:37,120 --> 04:04:40,520 SPECULATE ABOUT WHY CONNECTIONS 5111 04:04:40,520 --> 04:04:43,080 AMONG INTERNEURONS ARE MOST 5112 04:04:43,080 --> 04:04:43,760 STABLE? 5113 04:04:43,760 --> 04:04:47,960 COULD THIS EXPLAIN INTERNEURON'S 5114 04:04:47,960 --> 04:04:49,920 VULNERABILITY DURING AGING AND 5115 04:04:49,920 --> 04:04:50,400 AGE-RELATED DISEASES? 5116 04:04:50,400 --> 04:04:54,320 >> THAT'S A GREAT QUESTION. 5117 04:04:54,320 --> 04:05:00,080 WE HAVE DIFFERENT OPINIONS WHAT 5118 04:05:00,080 --> 04:05:09,400 THIS MEANS. 5119 04:05:09,400 --> 04:05:14,080 AND THIS IS A C. ELEGANS 5120 04:05:14,080 --> 04:05:15,600 CEREBELLUM AND DIFFERENT REGIONS 5121 04:05:15,600 --> 04:05:24,480 THAT LOOK AT THE BEHAVIOR. 5122 04:05:24,480 --> 04:05:28,160 MY PERSONAL TAKE IS MAYBE THIS 5123 04:05:28,160 --> 04:05:29,360 IS AN ENVIRONMENTAL STRATEGY 5124 04:05:29,360 --> 04:05:31,840 TAKEN FROM A SPECIES WITH A 5125 04:05:31,840 --> 04:05:33,520 SHORT LIFE SPAN AND SHORT TIME 5126 04:05:33,520 --> 04:05:36,400 AND THEN THE MOMENT IT GETS OUT 5127 04:05:36,400 --> 04:05:37,760 IT NEEDS TO MOVE AROUND. 5128 04:05:37,760 --> 04:05:42,920 WHEN YOU LOOK AT THE 5129 04:05:42,920 --> 04:05:46,600 DISTRIBUTION OF INVARIABLE 5130 04:05:46,600 --> 04:05:48,000 CONNECTION AND THOSE WITH 5131 04:05:48,000 --> 04:05:51,720 DEVELOPMENT PLASTICITY BUT IS 5132 04:05:51,720 --> 04:05:53,760 NOT VARIABLE IS CONNECTIONS 5133 04:05:53,760 --> 04:05:57,320 BETWEEN SENSORY NURNZ AND ALSO 5134 04:05:57,320 --> 04:06:03,640 THE CONNECTIONS FROM THE LAST 5135 04:06:03,640 --> 04:06:05,800 LAYER SENSORY INTERNEURONS INTO 5136 04:06:05,800 --> 04:06:08,960 THE FIRST LAYERS ARE THE MOST 5137 04:06:08,960 --> 04:06:10,080 DEVELOPMENTALLY PLASTIC. 5138 04:06:10,080 --> 04:06:11,360 MY INTERPRETATION IS THEY THINK 5139 04:06:11,360 --> 04:06:13,920 THE BEST THING TO DO IS TO BUILD 5140 04:06:13,920 --> 04:06:17,000 UP HOW THE SENSORY IS PROCESSED 5141 04:06:17,000 --> 04:06:19,080 AND THEY DON'T CHANGE IT AND 5142 04:06:19,080 --> 04:06:20,560 ONCE THEY COME OUT BECAUSE THE 5143 04:06:20,560 --> 04:06:21,840 ENVIRONMENT IS A LITTLE BIT 5144 04:06:21,840 --> 04:06:22,680 UNPREDICTABLE THEY CAN FURTHER 5145 04:06:22,680 --> 04:06:25,520 DELAY OR ACCELERATE OR EVEN 5146 04:06:25,520 --> 04:06:28,560 CHANGE THE CONNECTIONS THROUGH 5147 04:06:28,560 --> 04:06:31,080 THE OTHER CIRCUIT LAYER. 5148 04:06:31,080 --> 04:06:31,920 THAT'S WAY THEY'RE CHANGING THE 5149 04:06:31,920 --> 04:06:34,320 WAY THEY CROSS-TALK AND GET 5150 04:06:34,320 --> 04:06:36,000 INPUT FROM THE BRAIN BUT THE 5151 04:06:36,000 --> 04:06:36,960 PROCESSING ITSELF DOES NOT NEED 5152 04:06:36,960 --> 04:06:38,080 TO CHANGE. 5153 04:06:38,080 --> 04:06:40,320 THIS MAY BE A VERY ECONOMICAL 5154 04:06:40,320 --> 04:06:45,080 WAY TO MAINTAIN STABILITY AND 5155 04:06:45,080 --> 04:06:45,640 WITHOUT COMPLETELY LEAVING 5156 04:06:45,640 --> 04:06:53,840 EVERYTHING UNNEUURTURED BECAUSE 5157 04:06:53,840 --> 04:06:56,320 THEY DON'T HAVE THE TIME WINDOW. 5158 04:06:56,320 --> 04:06:59,920 I'M HAPPY TO TALK ABOUT. 5159 04:06:59,920 --> 04:07:01,200 AND ONE THING ABOUT AGING, I 5160 04:07:01,200 --> 04:07:02,720 DON'T KNOW ABOUT AGING WE 5161 04:07:02,720 --> 04:07:04,120 HAVEN'T DONE THAT BUT WE KNOW 5162 04:07:04,120 --> 04:07:09,600 THIS PART NEEDS TO BE PROTECTED 5163 04:07:09,600 --> 04:07:12,680 BECAUSE THAT'S THE THING WE WERE 5164 04:07:12,680 --> 04:07:15,280 SURPRISED HALF THE CONNECTIONS 5165 04:07:15,280 --> 04:07:19,880 ARE IN THE SO-CALLED INVARIANT 5166 04:07:19,880 --> 04:07:22,720 THE COMPLETE INTERNEURON 5167 04:07:22,720 --> 04:07:24,400 CONNECTIONS AND LIKE THEY CAN 5168 04:07:24,400 --> 04:07:25,720 CHANGE WHEN THEY'VE BEEN PUSHED 5169 04:07:25,720 --> 04:07:27,680 TO THE EXTREME. 5170 04:07:27,680 --> 04:07:29,040 THAT WAS ENCOURAGING NEWS AND WE 5171 04:07:29,040 --> 04:07:31,120 CAN PROBABLY FIND OUT A BIT MORE 5172 04:07:31,120 --> 04:07:33,520 WHAT THEY DO ONCE WITH WE 5173 04:07:33,520 --> 04:07:40,440 CONFIRM THE UNPUBLISHED STUDIES. 5174 04:07:40,440 --> 04:07:44,840 >> BECAUSE OF THE MENTION OF 5175 04:07:44,840 --> 04:07:50,000 ABSENCE OF SYNAPTIC PRUNING IS 5176 04:07:50,000 --> 04:07:51,760 SYNAPSE MAINTENANCE HARD WIRED 5177 04:07:51,760 --> 04:07:53,200 AND STABLE? 5178 04:07:53,200 --> 04:07:58,080 >> GOOD QUESTION. 5179 04:07:58,080 --> 04:07:59,240 WE HAVEN'T DONE THOSE EXPERIMENT 5180 04:07:59,240 --> 04:08:06,120 S -- EXPERIMENTS WITH THE 5181 04:08:06,120 --> 04:08:09,080 DIFFERENT INVERTEBRATE STUDIES 5182 04:08:09,080 --> 04:08:11,600 AND THE LACK OF PRUNING IT COULD 5183 04:08:11,600 --> 04:08:14,720 BE FOR ECONOMICAL REASONS. 5184 04:08:14,720 --> 04:08:16,720 YOU CAN IMAGINE C. ELEGANS WAS 5185 04:08:16,720 --> 04:08:18,320 PRETTY MUCH BORN IN THE GOOD 5186 04:08:18,320 --> 04:08:19,400 ENVIRONMENT AND ALMOST READY TO 5187 04:08:19,400 --> 04:08:20,920 GO IN THE BRAIN. 5188 04:08:20,920 --> 04:08:23,000 THE BODY'S A DIFFERENT STORY I 5189 04:08:23,000 --> 04:08:28,680 DON'T HAVE TIME TO TALK ABOUT. 5190 04:08:28,680 --> 04:08:31,080 BECAUSE THEY HAVE TO FEND FOR 5191 04:08:31,080 --> 04:08:32,960 THEMSELVES IT DOESN'T MEAN THE 5192 04:08:32,960 --> 04:08:34,080 PLASTICITY DOESN'T HAPPEN IN THE 5193 04:08:34,080 --> 04:08:35,720 EARLIER STAGE. 5194 04:08:35,720 --> 04:08:37,720 WE HAVE TO PUSH BACK THE TIME 5195 04:08:37,720 --> 04:08:40,680 WINDOW SEE IF THERE'S SYNAPTIC 5196 04:08:40,680 --> 04:08:45,600 PRUNING OR WHAT BEEN OBSERVED IN 5197 04:08:45,600 --> 04:08:48,000 THE VERTEBRATE SYSTEM AND 5198 04:08:48,000 --> 04:08:50,440 CONVINCINGLY HAPPENS IN THE 5199 04:08:50,440 --> 04:08:50,920 EMBRYONIC STAGE. 5200 04:08:50,920 --> 04:08:53,760 WE JUST DID NOT EXPECT IT WHEN 5201 04:08:53,760 --> 04:08:54,240 WE STARTED TO DO THE 5202 04:08:54,240 --> 04:09:02,640 EXPERIMENTS. 5203 04:09:02,640 --> 04:09:04,280 SENSORY PERCEPTION, I COME FROM 5204 04:09:04,280 --> 04:09:06,080 A LAB WHERE WE DEVELOPED THE 5205 04:09:06,080 --> 04:09:11,920 FIRST GENETIC MARKERS TO SCREEN 5206 04:09:11,920 --> 04:09:12,600 SYNAPSE FORMATION IN C. ELEGANS. 5207 04:09:12,600 --> 04:09:18,800 I HAVE DONE SOME. 5208 04:09:18,800 --> 04:09:21,520 AND OTHER GROUP WERE ABLATING 5209 04:09:21,520 --> 04:09:23,120 SOME NEURONS AND CHANGES THE 5210 04:09:23,120 --> 04:09:27,680 MECHANO SENSORY NEURONS AND SOME 5211 04:09:27,680 --> 04:09:28,800 SEEM TO SO THE A LOT OF 5212 04:09:28,800 --> 04:09:29,720 PLASTICITY AT THAT LEVEL. 5213 04:09:29,720 --> 04:09:32,800 I WOULD NOT BE SURPRISED THEY 5214 04:09:32,800 --> 04:09:34,920 ARE NOT -- THEY'RE NOT HARD 5215 04:09:34,920 --> 04:09:45,840 WIRED AND THEY'RE NOT STABLE. 5216 04:09:45,840 --> 04:09:47,600 >> HERE'S A QUESTION FROM DAVID 5217 04:09:47,600 --> 04:09:53,600 AND IT WAS ANSWERED IN THE CHAT. 5218 04:09:53,600 --> 04:09:57,000 AND LOTS OF PEOPLE DON'T SEE THE 5219 04:09:57,000 --> 04:09:58,080 CHAT. 5220 04:09:58,080 --> 04:10:01,080 THE ADVANCES IN FUNCTIONAL MRI 5221 04:10:01,080 --> 04:10:06,080 COMPARABLE TO WHAT YOU SHOWED 5222 04:10:06,080 --> 04:10:08,720 FOR INSTRUCTIONAL DIFFUSION MRI. 5223 04:10:08,720 --> 04:10:09,360 >> THANK YOU. 5224 04:10:09,360 --> 04:10:12,040 WE'VE BEEN WORK QUITE A BIT ON 5225 04:10:12,040 --> 04:10:13,080 THAT AS WELL. 5226 04:10:13,080 --> 04:10:15,200 I JUST DIDN'T HAVE ENOUGH TIME 5227 04:10:15,200 --> 04:10:17,160 TO SHOW THAT IN THE TALK. 5228 04:10:17,160 --> 04:10:18,920 WE HAVE BEEN PUSHING FUNCTIONAL 5229 04:10:18,920 --> 04:10:22,080 MRI AND IN THAT SENSE THERE'S 5230 04:10:22,080 --> 04:10:23,160 LIMITATION IN TERMS OF SPATIAL 5231 04:10:23,160 --> 04:10:24,240 AND TEMPORAL RESOLUTION WHICH WE 5232 04:10:24,240 --> 04:10:27,120 HAVE TO OVERCOME IN TERMS OF THE 5233 04:10:27,120 --> 04:10:28,920 IMAGING BUT THERE'S ALSO THE 5234 04:10:28,920 --> 04:10:29,640 BIOLOGICAL RESOLUTION AND WHAT I 5235 04:10:29,640 --> 04:10:34,120 MEAN BY THAT IS THAT WE'RE 5236 04:10:34,120 --> 04:10:36,160 MEASURING BLOOD SIGNAL AND THE 5237 04:10:36,160 --> 04:10:44,080 ABILITY OF THAT TO CORRELATE IS 5238 04:10:44,080 --> 04:10:45,960 NOT PERFECT. 5239 04:10:45,960 --> 04:10:47,120 THERE'S SOME SPATIAL SPREADING 5240 04:10:47,120 --> 04:10:52,400 AS WELL AS TEMPORAL DELAY IN 5241 04:10:52,400 --> 04:10:53,160 CHANGES AND WE'RE LOOKING TO 5242 04:10:53,160 --> 04:11:02,560 OVERCOME THOSE. 5243 04:11:02,560 --> 04:11:04,920 >> WE ONLY HAVE A FEW MORE 5244 04:11:04,920 --> 04:11:08,600 MINUTES LEFT MAYBE I CAN OPEN 5245 04:11:08,600 --> 04:11:09,920 THE DISCUSSION TO THE WHOLE 5246 04:11:09,920 --> 04:11:10,080 PANEL. 5247 04:11:10,080 --> 04:11:15,000 ONE THING I'M PARTICULARLY 5248 04:11:15,000 --> 04:11:18,920 INTERESTED IN HOW DO WE BRIDGE 5249 04:11:18,920 --> 04:11:23,120 THE GAP BETWEEN THE LEVELS OF 5250 04:11:23,120 --> 04:11:23,520 ANALYSIS? 5251 04:11:23,520 --> 04:11:24,920 EVEN WITH ARTIFICIAL 5252 04:11:24,920 --> 04:11:25,880 INTELLIGENCE I DON'T THINK WE'LL 5253 04:11:25,880 --> 04:11:33,520 BE ABLE TO DO THAT. 5254 04:11:33,520 --> 04:11:34,840 THIS IS ASKING YOU TO BE 5255 04:11:34,840 --> 04:11:35,400 SPECULATIVE AND DISCUSS THE 5256 04:11:35,400 --> 04:11:45,240 TOPIC. 5257 04:11:45,240 --> 04:11:47,120 >> I'LL START BY SAYING I THINK 5258 04:11:47,120 --> 04:11:49,280 ONE THING I THINK ABOUT IS 5259 04:11:49,280 --> 04:11:55,200 REALLY WHAT IS THE SYSTEM GOOD 5260 04:11:55,200 --> 04:11:58,880 FOR AND WE'RE NEVER GOING TO PUT 5261 04:11:58,880 --> 04:12:03,120 A LARVA INTO AN MRI MACHINE AND 5262 04:12:03,120 --> 04:12:04,520 BE ABLE TO DO THAT AND PART OF 5263 04:12:04,520 --> 04:12:05,840 THE ANSWER IS WHAT IT IS DO YOU 5264 04:12:05,840 --> 04:12:10,040 WANT TO LEARN FROM YOUR SYSTEM. 5265 04:12:10,040 --> 04:12:16,080 ONE GUESS -- QUESTION I HAVE FOR 5266 04:12:16,080 --> 04:12:19,200 THE MRI FOLKS AND THIS MAY BE 5267 04:12:19,200 --> 04:12:20,840 PRETTY NAIVE BUT TO WHAT EXTENT 5268 04:12:20,840 --> 04:12:23,160 DO YOU THINK IT WILL EVER BE 5269 04:12:23,160 --> 04:12:25,680 POSSIBLE TO GET PRIOR KNOWLEDGE 5270 04:12:25,680 --> 04:12:28,080 A DISEASE STATE WAS COMING? 5271 04:12:28,080 --> 04:12:30,080 YOU MENTIONED MAYBE ONE AXON -- 5272 04:12:30,080 --> 04:12:31,240 YOU DON'T NEED THAT LEVEL OF 5273 04:12:31,240 --> 04:12:32,640 RESOLUTION TO REALLY TELL THE 5274 04:12:32,640 --> 04:12:40,080 BRAIN IS DYSFUNCTIONAL BUT WHERE 5275 04:12:40,080 --> 04:12:42,320 DO YOU THINK YOU'D NEED TO GO TO 5276 04:12:42,320 --> 04:12:45,640 HAVE PREDICTIVE POWER FROM 5277 04:12:45,640 --> 04:12:46,280 IMAGING BEFORE THINGS GO REALLY 5278 04:12:46,280 --> 04:12:52,720 WRONG? 5279 04:12:52,720 --> 04:12:58,080 >> WITH THE INCREASE RESOLUTION 5280 04:12:58,080 --> 04:13:04,640 AND ACCURACY OF MRI WILL WE BE 5281 04:13:04,640 --> 04:13:05,760 ABLE TO SEE SMALL CHANGES IN 5282 04:13:05,760 --> 04:13:12,000 BRAIN STRUCTURE AND FOR EXAMPLE 5283 04:13:12,000 --> 04:13:13,360 DO MORE RAPID CLINICAL TRIALS OR 5284 04:13:13,360 --> 04:13:22,080 DETECT MORE SUBTLE CHANGES IN IN 5285 04:13:22,080 --> 04:13:24,680 BRAIN STRUCTURE FOR A VARIETY OF 5286 04:13:24,680 --> 04:13:26,520 DISEASES, SCHIZOPHRENIA OR EVEN 5287 04:13:26,520 --> 04:13:26,840 DEPRESSION. 5288 04:13:26,840 --> 04:13:29,120 WHAT ARE YOUR THOUGHTS ABOUT 5289 04:13:29,120 --> 04:13:37,280 THAT? 5290 04:13:37,280 --> 04:13:39,200 >> I HOPE SO AND THAT'S THE 5291 04:13:39,200 --> 04:13:40,520 MOTIVATION FOR THE WORK WE'VE 5292 04:13:40,520 --> 04:13:42,480 BEEN PUSHING. 5293 04:13:42,480 --> 04:13:46,080 WITH MRI YOU CAN HAVE A LARGE 5294 04:13:46,080 --> 04:13:48,840 NUMBER OF FLURRY IMAGES WITH 5295 04:13:48,840 --> 04:13:53,920 LARGE-SCALE STUDY TO DETECT 5296 04:13:53,920 --> 04:14:01,240 SOMETHING OR POLISH THE LENS AND 5297 04:14:01,240 --> 04:14:02,440 TO THE QUESTION OF WHAT WE NEED 5298 04:14:02,440 --> 04:14:04,760 TO DETECT THESE THINGS. 5299 04:14:04,760 --> 04:14:06,120 THIS IS AN OPEN QUESTION AND 5300 04:14:06,120 --> 04:14:08,120 HAVING THE LARGE SCALE STUDIES 5301 04:14:08,120 --> 04:14:11,240 IS HELPFUL BECAUSE IF YOU ARE 5302 04:14:11,240 --> 04:14:14,120 ABLE TO MINE THAT DATA AND LOOK 5303 04:14:14,120 --> 04:14:17,040 AT BOTH MRI AND OTHER DATA 5304 04:14:17,040 --> 04:14:17,800 MODALITY THAT HAVE BEEN 5305 04:14:17,800 --> 04:14:19,080 COLLECTED YOU CAN START TO LOOK 5306 04:14:19,080 --> 04:14:24,920 AT SOME OF THESE AND SEE WHAT 5307 04:14:24,920 --> 04:14:31,000 ARE WE SENSITIVE TO I THINKS 5308 04:14:31,000 --> 04:14:35,720 THIS IS AN AREA ANASTASIA IS AN 5309 04:14:35,720 --> 04:14:39,480 EXPERT IN SO I'LL LET HER TALK. 5310 04:14:39,480 --> 04:14:41,040 >> WHAT I'M SOMETIMES CALLED IS 5311 04:14:41,040 --> 04:14:42,160 A PESSIMIST AND I DON'T KNOW IF 5312 04:14:42,160 --> 04:14:47,680 YOU CAN PREDICT THE FUTURE FROM 5313 04:14:47,680 --> 04:14:53,080 A MAP I THINK A MAP FOR 5314 04:14:53,080 --> 04:14:54,080 MODULATION APPROACHES IS A 5315 04:14:54,080 --> 04:14:55,120 FEASIBLE TARGET. 5316 04:14:55,120 --> 04:14:57,120 I DON'T KNOW IF WE'LL EVER HAVE 5317 04:14:57,120 --> 04:14:58,120 A MAP OF THE BRAIN THAT CAN 5318 04:14:58,120 --> 04:15:08,000 PREDICT THE FUTURE. 5319 04:15:08,000 --> 04:15:10,120 >> YOU'RE LOOKING AT 5320 04:15:10,120 --> 04:15:12,080 LONGITUDINAL STUDIES AND IF YOU 5321 04:15:12,080 --> 04:15:17,240 LOOK AT STRUCTURE US SHOULD BE 5322 04:15:17,240 --> 04:15:18,600 ABLE TO DETECT BETTER, RIGHT? 5323 04:15:18,600 --> 04:15:22,200 >> AND IN ACUTE STAGES OF FOR 5324 04:15:22,200 --> 04:15:24,560 EXAMPLE, TRAUMATIC BRAIN INJURY 5325 04:15:24,560 --> 04:15:27,040 WHERE YOU HAVE STRUCTURAL 5326 04:15:27,040 --> 04:15:30,160 CHANGES THAT OCCUR AT A SLIGHTLY 5327 04:15:30,160 --> 04:15:33,000 SHORTER TIME SCALE THAN NORMAL, 5328 04:15:33,000 --> 04:15:35,160 THAT WOULD BE ANOTHER POTENTIAL 5329 04:15:35,160 --> 04:15:35,760 OPPORTUNITY FOR USING THESE 5330 04:15:35,760 --> 04:15:48,560 METHODS. 5331 04:15:48,560 --> 04:15:50,160 >> THE INTRIGUING THING FOR ME 5332 04:15:50,160 --> 04:15:53,520 IS HOW DOES THE FUNCTIONAL MRI 5333 04:15:53,520 --> 04:15:54,720 STRUCTURE OR TRACK CORRELATE TO 5334 04:15:54,720 --> 04:15:57,160 THE 3,000 CELL TYPES IDENTIFIED 5335 04:15:57,160 --> 04:16:00,320 BY MOLECULAR FINGERPRINTS 5336 04:16:00,320 --> 04:16:01,960 BECAUSE TO ME I FOUND THE ONLY 5337 04:16:01,960 --> 04:16:05,200 WAY TO TACKLE WITH LARGE BRAINS 5338 04:16:05,200 --> 04:16:07,320 WITH HUGE NUMBER OF NEURONS IS 5339 04:16:07,320 --> 04:16:12,440 TO FIRST IDENTIFY THE DEGREE OF 5340 04:16:12,440 --> 04:16:14,600 REDUNDANCY SO YOU KNOW HOW MUCH 5341 04:16:14,600 --> 04:16:17,240 ANATOMICAL ACTIVITY YOU NEED TO 5342 04:16:17,240 --> 04:16:23,240 GO INTO DETAILS. 5343 04:16:23,240 --> 04:16:25,880 I WAS INTRIGUED BY DIFFERENT 5344 04:16:25,880 --> 04:16:28,400 OMICS DATA YOU CAN CROSS INTO 5345 04:16:28,400 --> 04:16:31,320 CELL TYPES BUT IT'S ALSO KNOWN 5346 04:16:31,320 --> 04:16:36,920 BY SINGLE CELL TECHNOLOGY ALONE 5347 04:16:36,920 --> 04:16:45,640 YOU CAN HAVE MORE BECAUSE ION 5348 04:16:45,640 --> 04:16:46,880 CHANNELS CAN CREATE THE SAME 5349 04:16:46,880 --> 04:16:48,120 SYSTEM APPROACH. 5350 04:16:48,120 --> 04:16:51,920 SO THE SAME THING HERE. 5351 04:16:51,920 --> 04:16:54,160 BY PROJECTIONS CAN YOU NARROW 5352 04:16:54,160 --> 04:16:57,160 DOWN TO SEE IF THERE'S SOME WAY 5353 04:16:57,160 --> 04:16:58,640 TO CORRELATE TO ME I THINK IF 5354 04:16:58,640 --> 04:16:59,680 YOU CAN CORRELATE THE 5355 04:16:59,680 --> 04:17:03,280 TRAJECTORIES THAT YOU CAN 5356 04:17:03,280 --> 04:17:04,440 IDENTIFY DISSECTING THE BRAIN 5357 04:17:04,440 --> 04:17:06,320 INTO HUNDREDS OF BRAIN REGIONS 5358 04:17:06,320 --> 04:17:08,880 AND HAVE A BETTER OVERLAP WITH 5359 04:17:08,880 --> 04:17:12,080 THE MOLECULAR FINGERPRINTS. 5360 04:17:12,080 --> 04:17:15,120 FROM THERE YOU ARE GOING TO A 5361 04:17:15,120 --> 04:17:16,800 SYNAPSE LEVEL. 5362 04:17:16,800 --> 04:17:20,680 THAT MIGHT BE SOMETHING I SAW 5363 04:17:20,680 --> 04:17:23,080 THAT I WOULD LIKE TO SEE HOW IT 5364 04:17:23,080 --> 04:17:29,880 WORKS IF IT'S POSSIBLE. 5365 04:17:29,880 --> 04:17:36,000 >> I DON'T STUDY CELLS, I STUDY 5366 04:17:36,000 --> 04:17:39,920 AXONS AND I THINK THE ANSWER 5367 04:17:39,920 --> 04:17:41,520 LIKELY VARES DEPENDING ON WHAT 5368 04:17:41,520 --> 04:17:44,520 SCALE YOU NEED TO LOOK AT. 5369 04:17:44,520 --> 04:17:47,680 THERE'S SOME PATHWAYS MORE 5370 04:17:47,680 --> 04:18:03,960 CLEANLY TOPOGRAPHICALLY 5371 04:18:03,960 --> 04:18:06,040 ORGANIZED AND WHEREAS THERE ARE 5372 04:18:06,040 --> 04:18:08,960 OTHER PATHWAYS MESSIER AND 5373 04:18:08,960 --> 04:18:10,000 POTENTIALLY IN THOSE PATHWAYS 5374 04:18:10,000 --> 04:18:13,320 YOU NIGHT TO LOOK AT A -- NEED 5375 04:18:13,320 --> 04:18:14,600 TO LOOK AT A HIGHER SCALE. 5376 04:18:14,600 --> 04:18:22,080 I THINK THERE ISN'T A SINGLE 5377 04:18:22,080 --> 04:18:24,320 ANSWER THAT WOULD BE OPTIMAL FOR 5378 04:18:24,320 --> 04:18:25,520 THE ENTIRE BRAIN. 5379 04:18:25,520 --> 04:18:26,480 AT LEAST FOR SOMETHING AS 5380 04:18:26,480 --> 04:18:31,600 COMPLEX AS THE HUMAN BRAIN. 5381 04:18:31,600 --> 04:18:33,480 >> THINK THAT'S PROBABLY A GOOD 5382 04:18:33,480 --> 04:18:35,240 PLACE TO STOP. 5383 04:18:35,240 --> 04:18:47,080 I THINK IF WE COULD MERGE MRI 5384 04:18:47,080 --> 04:18:49,320 WITH SPECIFICITY WE COULD GET 5385 04:18:49,320 --> 04:18:49,600 THERE. 5386 04:18:49,600 --> 04:18:51,400 WE'RE RIGHT ON 3:40. 5387 04:18:51,400 --> 04:18:53,200 WE'LL TAKE A BREAK FOR 10 5388 04:18:53,200 --> 04:18:53,440 MINUTES. 5389 04:18:53,440 --> 04:18:54,280 GREAT TALKS, EVERYBODY. 5390 04:18:54,280 --> 04:19:08,760 THANK YOU AND FUN DISCUSSION. 5391 04:19:08,760 --> 04:19:09,920 >> WELCOME BACK. 5392 04:19:09,920 --> 04:19:11,720 I'M A PROGRAM DIRECTOR AT NICHD 5393 04:19:11,720 --> 04:19:14,240 AND I'M IT'S PLEASURE TO 5394 04:19:14,240 --> 04:19:18,160 INTRODUCE DAVID van ESSEN 5395 04:19:18,160 --> 04:19:21,800 ENDOWED PROFESSOR AT WASHINGTON 5396 04:19:21,800 --> 04:19:25,000 IN ST. LOUIS AND LOOKS AT THE 5397 04:19:25,000 --> 04:19:30,280 CONNECTIVITY AND DEVELOPMENT OF 5398 04:19:30,280 --> 04:19:34,680 CEREBRAL CORTEX AND IN RECENT 5399 04:19:34,680 --> 04:19:39,080 YEAR THE LAB USED NEUROIMAGING 5400 04:19:39,080 --> 04:19:40,880 AND DATA COLLABORATIVELY WITH 5401 04:19:40,880 --> 04:19:42,080 OTHER INSTITUTIONS. 5402 04:19:42,080 --> 04:19:43,680 THE MAJOR EMPHASIS IS ON THE 5403 04:19:43,680 --> 04:19:46,720 DEVELOPMENT AND UTILIZATION OF 5404 04:19:46,720 --> 04:19:48,920 METHODS FOR COMPUTERIZED BRAIN 5405 04:19:48,920 --> 04:19:51,840 MAPPING AND NEUROINFORMATICS 5406 04:19:51,840 --> 04:19:54,920 TOOL TO INFORM DATA MINING AND 5407 04:19:54,920 --> 04:19:57,520 SERVED AS THE HUMAN INVESTIGATOR 5408 04:19:57,520 --> 04:20:01,080 FOR A LARGE SCALE EFFORT THAT 5409 04:20:01,080 --> 04:20:03,240 ACQUIRED AND ANALYZED DATA FROM 5410 04:20:03,240 --> 04:20:06,400 1200 HEALTHY ADULTS AND 5411 04:20:06,400 --> 04:20:08,960 CURRENTLY A CO-P.I. OF THE HUMAN 5412 04:20:08,960 --> 04:20:10,200 CONNECTOME PROJECTS. 5413 04:20:10,200 --> 04:20:11,920 THE MAJOR FOCUS OF THE LAB IS TO 5414 04:20:11,920 --> 04:20:14,000 USE THE HUMAN CONNECTOME 5415 04:20:14,000 --> 04:20:16,720 PROJECTS AND OTHER HIGH-QUALITY 5416 04:20:16,720 --> 04:20:21,920 DATA SETS TO BETTER UNDERSTAND 5417 04:20:21,920 --> 04:20:26,840 CORTICOPARSLATION IN HUMAN AND 5418 04:20:26,840 --> 04:20:27,440 NON-HUM 5419 04:20:27,440 --> 04:20:28,240 NON-HUM 5420 04:20:28,240 --> 04:20:30,280 NON-HUMAN PRIMATES. 5421 04:20:30,280 --> 04:20:31,760 HE MOVED TO WASHINGTON 5422 04:20:31,760 --> 04:20:33,120 UNIVERSITY IN 1992 WHERE THE 5423 04:20:33,120 --> 04:20:39,200 CHAIRED THE DEPARTMENT OF ANAT 5424 04:20:39,200 --> 04:20:43,200 ANY AND NEURAL BIOLOGY AND 5425 04:20:43,200 --> 04:20:45,720 SERVED IN THE ORGANIZATION FOR 5426 04:20:45,720 --> 04:20:48,120 HUMAN BRAIN MAPPING AND RECEIVED 5427 04:20:48,120 --> 04:20:50,120 THE CORTICAL DISCOVERY AWARD AND 5428 04:20:50,120 --> 04:20:51,880 THE GLASS BRAIN AWARD FROM THE 5429 04:20:51,880 --> 04:20:53,480 ORGANIZATION FOR HUMAN BRAIN 5430 04:20:53,480 --> 04:20:55,920 MAPPING AND THE GEORGE A. MILLER 5431 04:20:55,920 --> 04:20:56,520 PRIZE FROM THE COGNITIVE 5432 04:20:56,520 --> 04:20:58,440 NEUROSCIENCE SOCIETY AND THE 5433 04:20:58,440 --> 04:21:00,200 CARL AND CORY FACULTY 5434 04:21:00,200 --> 04:21:01,000 ACHIEVEMENT AWARD FROM 5435 04:21:01,000 --> 04:21:02,200 WASHINGTON UNIVERSITY SCHOOL OF 5436 04:21:02,200 --> 04:21:02,480 MEDICINE. 5437 04:21:02,480 --> 04:21:04,400 HE'S A FELLOW OF THE AMERICAN 5438 04:21:04,400 --> 04:21:05,760 ASSOCIATION FOR THE ADVANCEMENT 5439 04:21:05,760 --> 04:21:07,200 THE SCIENCE AND MEMBER OF THE 5440 04:21:07,200 --> 04:21:10,800 NATIONAL ACADEMY OF SCIENCES. 5441 04:21:10,800 --> 04:21:12,600 DR. VAN ESSEN. 5442 04:21:12,600 --> 04:21:18,080 >> THANK YOU, DR. HARTMAN FOR 5443 04:21:18,080 --> 04:21:19,760 THE OPPORTUNITY TO PRESENT AT 5444 04:21:19,760 --> 04:21:22,520 THIS SESSION AND TO INTRODUCE 5445 04:21:22,520 --> 04:21:25,480 THE NEXT LEVEL OF DISCUSSION OF 5446 04:21:25,480 --> 04:21:28,400 THE BRAIN ACROSS THE LIFE SPAN. 5447 04:21:28,400 --> 04:21:31,920 I'M GOING TO GIVE YOU TWO 5448 04:21:31,920 --> 04:21:35,080 PERSPECTIVES. 5449 04:21:35,080 --> 04:21:46,320 FIRST IS AS A NEUROANATAMISCT 5450 04:21:46,320 --> 04:21:47,600 AND ACCURATE SPATIAL 5451 04:21:47,600 --> 04:21:48,480 LOCALIZATION IS VITAL AND 5452 04:21:48,480 --> 04:21:50,400 DIFFICULT BUT CAN BE DONE AND IT 5453 04:21:50,400 --> 04:22:03,120 HAS TO DO WITH THE TOPOLOGY AND 5454 04:22:03,120 --> 04:22:05,320 THERE'S CONVOLUTED CEREBELLUM 5455 04:22:05,320 --> 04:22:11,240 AND THE SUBCORTICAL NUCLEI AND 5456 04:22:11,240 --> 04:22:15,120 THEY'RE CONNECTED BY WHITE 5457 04:22:15,120 --> 04:22:18,360 MATTER TRACTS YOU HEARD ABOUT 5458 04:22:18,360 --> 04:22:18,720 EARLIER. 5459 04:22:18,720 --> 04:22:19,760 ANOTHER LEVEL OF COMPLEXITY 5460 04:22:19,760 --> 04:22:21,320 RELIES ON OVERLAID ON THE 5461 04:22:21,320 --> 04:22:26,160 STRUCTURE AND UNFOLDING OF THE 5462 04:22:26,160 --> 04:22:29,320 CORTEX IS A VERY ELEGANT BUT 5463 04:22:29,320 --> 04:22:30,200 FUNCTIONAL FUNCTIONAL 5464 04:22:30,200 --> 04:22:32,600 ORGANIZATION KNOWN AS A 5465 04:22:32,600 --> 04:22:34,880 PARSLATION THAT CONTAINS 180 5466 04:22:34,880 --> 04:22:37,600 AREAS OF THE LATEST HEMISPHERE 5467 04:22:37,600 --> 04:22:39,600 AND IN THE SUBCORTICAL DOMAIN 5468 04:22:39,600 --> 04:22:41,760 THERE'S HUNDREDS OF NUCLEI AND 5469 04:22:41,760 --> 04:22:47,320 UNKNOWN NUMBER OF PARCELS IN THE 5470 04:22:47,320 --> 04:22:48,680 CEREBELLUM. 5471 04:22:48,680 --> 04:22:54,520 AND ADD TO THAT THE CORTICAL 5472 04:22:54,520 --> 04:22:56,920 FOLD S ARE VARIABLE AND VARIABLE 5473 04:22:56,920 --> 04:23:00,200 IN THEIR SIZE, TWO TO THREE FOLD 5474 04:23:00,200 --> 04:23:05,280 VARIABILITY AND IN THE 5475 04:23:05,280 --> 04:23:06,600 RELATIONSHIP TO THE FOLDS. 5476 04:23:06,600 --> 04:23:08,720 AND THERE'S CHANGES THAT OCCUR 5477 04:23:08,720 --> 04:23:10,320 ACROSS THE LIFE SPAN PROFOUNDLY 5478 04:23:10,320 --> 04:23:12,400 IN EARLY DEVELOPMENT AND 5479 04:23:12,400 --> 04:23:17,520 SUBSTANTIAL CHANGES OCCURRING IN 5480 04:23:17,520 --> 04:23:20,800 LATE AGING AS WELL. 5481 04:23:20,800 --> 04:23:25,520 WE HEARD EXAMPLES OF HOW THE 5482 04:23:25,520 --> 04:23:27,720 EXPLOSION OF DATA FROM MEGABYTES 5483 04:23:27,720 --> 04:23:32,480 WHEN I WAS YOUNGER TO GIGABYTES, 5484 04:23:32,480 --> 04:23:35,120 PETABYTES AND COMING SOON LOTS 5485 04:23:35,120 --> 04:23:40,120 OF EXBYTES THE WORLD WILL HAVE 5486 04:23:40,120 --> 04:23:42,640 TO DEAL WITH. 5487 04:23:42,640 --> 04:23:46,000 THERE'S GENE EXPRESSION ATLASES 5488 04:23:46,000 --> 04:23:47,400 FROM THE ALLEN INSTITUTE AND 5489 04:23:47,400 --> 04:23:59,320 OTHERS AND I'LL LOOK AT EXPAND 5490 04:23:59,320 --> 04:24:05,680 THE LIFE SPAN. 5491 04:24:05,680 --> 04:24:07,720 AND THE HUMAN CONNECTOME PROJECT 5492 04:24:07,720 --> 04:24:11,880 SCANNED ADULTS AND INTRODUCED 5493 04:24:11,880 --> 04:24:17,720 THE CONCEPT OF HDP STYLE 5494 04:24:17,720 --> 04:24:22,880 NEUROIMAGING AND GETTING THE 5495 04:24:22,880 --> 04:24:27,760 HIGHEST DATA POSSIBLE AND REMOVE 5496 04:24:27,760 --> 04:24:31,640 NOISE AND SHARE THE DATA WITH 5497 04:24:31,640 --> 04:24:31,920 OPENNESS. 5498 04:24:31,920 --> 04:24:33,120 THAT APPROACH HAD BEEN CONTINUED 5499 04:24:33,120 --> 04:24:39,320 WITH NOW MANY OTHER PROJECTS. 5500 04:24:39,320 --> 04:24:42,280 AND THE NIH CONNECTOME AND THE 5501 04:24:42,280 --> 04:24:44,400 LIFE SPAN PROJECTS MENTIONED A 5502 04:24:44,400 --> 04:24:47,000 LITTLE WHILE AGO FOR DEVELOPMENT 5503 04:24:47,000 --> 04:24:49,000 IN AGING AND MORE ACRONYM SOUP 5504 04:24:49,000 --> 04:24:52,920 WITH THE ABCD PROJECT AND THE 5505 04:24:52,920 --> 04:24:53,320 HBCD. 5506 04:24:53,320 --> 04:24:57,360 THEY'RE ALL WONDERFUL PROJECTS 5507 04:24:57,360 --> 04:25:00,400 WITH THE BRITISH BIO BANK 5508 04:25:00,400 --> 04:25:00,920 EFFORT. 5509 04:25:00,920 --> 04:25:04,280 THE DATA IN THE NEUROIMAGING 5510 04:25:04,280 --> 04:25:05,720 DOMAIN HAS ONE SET OF DATA 5511 04:25:05,720 --> 04:25:09,440 RESOURCES LIKE CONNECTOME DB AND 5512 04:25:09,440 --> 04:25:17,200 THE NIMH DATABASE AND THERE'S A 5513 04:25:17,200 --> 04:25:21,040 GROWING NEED FOR RESOURCES TO 5514 04:25:21,040 --> 04:25:23,480 SHARE EXTENSIVELY ANALYZE DATA 5515 04:25:23,480 --> 04:25:27,160 SUCH AS THE DEAP ABCD PROJECT 5516 04:25:27,160 --> 04:25:30,640 AND OUR LAB'S EFFORT. 5517 04:25:30,640 --> 04:25:32,760 ANOTHER MAJOR CHALLENGE TOUCHED 5518 04:25:32,760 --> 04:25:36,160 UPON IS THE DATA HARMONIZATION 5519 04:25:36,160 --> 04:25:37,800 IS A HUGE CHALLENGE TO DEAL WITH 5520 04:25:37,800 --> 04:25:41,120 PROJECT SCANNERS AND PROTOCOLS 5521 04:25:41,120 --> 04:25:42,320 WHEN USED TO COMPARE ACROSS 5522 04:25:42,320 --> 04:25:52,320 GROUPS AND AGES. 5523 04:25:52,320 --> 04:25:56,320 HAVE AN ASPIRATION THAT GOOGLE 5524 04:25:56,320 --> 04:25:58,440 EARTH AND GPS POSITIONING 5525 04:25:58,440 --> 04:25:59,320 SATELLITES THAT CHANGE THE WAY 5526 04:25:59,320 --> 04:26:00,880 WE INTERACT WITH THE WORLD 5527 04:26:00,880 --> 04:26:03,200 AROUND US WILL HAVE COMPARABLE 5528 04:26:03,200 --> 04:26:04,600 DEVELOPMENTS IN THE COMING 5529 04:26:04,600 --> 04:26:06,160 DECADES FOR THE BRAIN WHERE 5530 04:26:06,160 --> 04:26:09,800 WE'LL BE ABLE TO QUERY ANY 5531 04:26:09,800 --> 04:26:12,040 REGION OF INTEREST AND ANY 5532 04:26:12,040 --> 04:26:14,400 SPECIES THAT HAS BEEN CAREFULLY 5533 04:26:14,400 --> 04:26:17,320 STUDIED AND OBTAIN VAST AMOUNTS 5534 04:26:17,320 --> 04:26:19,600 OF INFORMATION ABOUT STRUCTURE 5535 04:26:19,600 --> 04:26:20,800 DEVELOPMENT AND CONNECTIVITY AND 5536 04:26:20,800 --> 04:26:21,600 THE LIKE. 5537 04:26:21,600 --> 04:26:25,040 WITH THAT AS AN ASPIRATION, 5538 04:26:25,040 --> 04:26:28,320 LET'S MOVE ON TO OUR FIVE 5539 04:26:28,320 --> 04:26:28,600 SPEAKERS. 5540 04:26:28,600 --> 04:26:29,520 YOU'LL EACH HAVE FIVE MINUTES 5541 04:26:29,520 --> 04:26:31,000 FOR THEIR PERSPECTIVE BEFORE WE 5542 04:26:31,000 --> 04:26:35,120 GO INTO OPEN DISCUSSION MODE. 5543 04:26:35,120 --> 04:26:40,400 OUR FIRST SPEAKER IS ALEXANDER 5544 04:26:40,400 --> 04:26:41,920 BADEA AT DUKE UNIVERSITY. 5545 04:26:41,920 --> 04:26:43,520 HER RESEARCH FOCUSES ON 5546 04:26:43,520 --> 04:26:45,520 ALZHEIMER'S DISEASE WHICH SHE 5547 04:26:45,520 --> 04:26:47,400 STUDIES USING DIFFUSION IMAGING 5548 04:26:47,400 --> 04:26:49,720 COMBINED WITH GENETICS AND 5549 04:26:49,720 --> 04:26:51,920 BEHAVIOR AND OTHER METRICS THAT 5550 04:26:51,920 --> 04:26:54,000 LEADS TO BIOMARKER 5551 04:26:54,000 --> 04:26:54,360 IDENTIFICATION. 5552 04:26:54,360 --> 04:26:56,960 I'LL STOP SHARING MY SCREEN AND 5553 04:26:56,960 --> 04:27:12,720 HAND IT TO ALEX AN DRA. 5554 04:27:12,720 --> 04:27:14,560 >> THANK YOU FOR BEING HERE AT 5555 04:27:14,560 --> 04:27:16,360 THE AND OF A BUSY AND EXCITING 5556 04:27:16,360 --> 04:27:18,960 DAY AND FOR THE FUNDERS TO MAKE 5557 04:27:18,960 --> 04:27:19,720 THE WORK POSSIBLE. 5558 04:27:19,720 --> 04:27:34,040 I'LL TALK TO MY LINE OF RESEARCH 5559 04:27:34,040 --> 04:27:37,720 AND WE HAVE LOOKED AT MODELLING 5560 04:27:37,720 --> 04:27:41,600 AND OUR BIG CLINICAL IMAGING 5561 04:27:41,600 --> 04:27:44,640 USING HIGH FIELD MRI AT THE 100 5562 04:27:44,640 --> 04:27:45,120 MICRON RESOLUTION -- 5563 04:27:45,120 --> 04:27:46,160 >> CAN YOU USE THE WHOLE SCREEN, 5564 04:27:46,160 --> 04:27:49,360 PLEASE. 5565 04:27:49,360 --> 04:27:50,880 >> I WILL DO MY BEST. 5566 04:27:50,880 --> 04:27:55,160 >> GREAT, THANK YOU. 5567 04:27:55,160 --> 04:28:00,560 >> WE DO USE EX VIVO IMAGING AT 5568 04:28:00,560 --> 04:28:04,280 5.4 TESLA AND WE ENHANCE IMAGING 5569 04:28:04,280 --> 04:28:05,960 CONTRAST AND SIGNAL TO NOISE 5570 04:28:05,960 --> 04:28:10,960 RATIO TO ACQUIRE FASTER IMAGES. 5571 04:28:10,960 --> 04:28:13,840 WE HAVE USED COMPRESS TESTING 5572 04:28:13,840 --> 04:28:17,600 FOR DIFFUSION AND YOU CAN SEE WE 5573 04:28:17,600 --> 04:28:19,360 CAN DISCERN CORTICAL AND 5574 04:28:19,360 --> 04:28:21,160 CELLULAR LAYERS AT THIS LEVEL OF 5575 04:28:21,160 --> 04:28:24,240 RESOLUTION EX VIVO AND GET THE 5576 04:28:24,240 --> 04:28:26,600 DENSE CONNECTIVITY IN EX VIVO 5577 04:28:26,600 --> 04:28:27,920 DIFFUSION IMAGES. 5578 04:28:27,920 --> 04:28:31,920 SO WE HAVE USED OUR EFFORTS TO 5579 04:28:31,920 --> 04:28:34,320 GENERATE HIGH SPATIAL RESOLUTION 5580 04:28:34,320 --> 04:28:37,240 DIFFUSION IMAGING AND THAT 5581 04:28:37,240 --> 04:28:39,120 ALLOWED US TO LABEL A MOUSE 5582 04:28:39,120 --> 04:28:42,000 BRAIN WITH 332 REGIONS TO 5583 04:28:42,000 --> 04:28:44,080 GENETIC POPULATION AND 5584 04:28:44,080 --> 04:28:47,520 CONNECTOMES AND WE HAVE 5585 04:28:47,520 --> 04:28:54,040 COLLABORATED TO CREATE AND APPLY 5586 04:28:54,040 --> 04:28:58,480 METHODS FOR DISCRIMINATING FOR 5587 04:28:58,480 --> 04:28:59,560 DIFFERENT MODELS OF ALZHEIMER'S 5588 04:28:59,560 --> 04:29:00,640 DISEASE AND LOOKING AT COMPONENT 5589 04:29:00,640 --> 04:29:03,400 ANALYSIS AND IT ALLOWS DEFINED 5590 04:29:03,400 --> 04:29:06,200 THE TOP CONNECTIONS 5591 04:29:06,200 --> 04:29:07,920 DISCRIMINATING GENOTYPES AND WE 5592 04:29:07,920 --> 04:29:08,840 CAN COMPARE FURTHER DOWN THE 5593 04:29:08,840 --> 04:29:13,600 LINE PROPERTIES OF TEXTURE. 5594 04:29:13,600 --> 04:29:15,760 AND WE CAN SEE WHEN WE LOOK AT 5595 04:29:15,760 --> 04:29:19,600 BRAIN CONNECTIVITY IN MOUSE 5596 04:29:19,600 --> 04:29:23,600 MODELS HAVING TARGETED 5597 04:29:23,600 --> 04:29:26,040 REPLACEMENT FOR APOE GENOTYPES 5598 04:29:26,040 --> 04:29:27,720 THE WIRING IS DIFFERENT FOR THE 5599 04:29:27,720 --> 04:29:31,080 CONNECTION BETWEEN THE CORTEX 5600 04:29:31,080 --> 04:29:36,000 AND HIPPOCAMPUS AND THIS REFERS 5601 04:29:36,000 --> 04:29:38,440 TO THE COMBINING IN THE 5602 04:29:38,440 --> 04:29:38,960 CONNECTION. 5603 04:29:38,960 --> 04:29:39,960 THERE'S DIFFERENT WIRING AND 5604 04:29:39,960 --> 04:29:41,920 DIFFERENT RELATIVE SIZING IN 5605 04:29:41,920 --> 04:29:44,040 BETWEEN THE TWO GENOTYPES. 5606 04:29:44,040 --> 04:29:46,000 MOREOVER THE GENOTYPES TEND TO 5607 04:29:46,000 --> 04:29:48,240 CLUSTER THE CONNECTOME AND MAYBE 5608 04:29:48,240 --> 04:29:55,120 THERE'S A TYPE FOR CLUSTERING 5609 04:29:55,120 --> 04:29:56,520 REPRESENTED WITH BLINDS FOR 5610 04:29:56,520 --> 04:29:59,320 MALES AND CIRCLES FOR FEMALES. 5611 04:29:59,320 --> 04:30:01,280 ONCE WE ALIGN THE DIFFERENT 5612 04:30:01,280 --> 04:30:03,960 GENOTYPES WE CAN COMPARE THE 5613 04:30:03,960 --> 04:30:07,880 DISTRIBUTION OF DIAMETERS AND 5614 04:30:07,880 --> 04:30:10,400 ONCE WE START DISCRIMINATING WE 5615 04:30:10,400 --> 04:30:11,880 CAN SEE SOME OF THE UNIFORM 5616 04:30:11,880 --> 04:30:13,320 DIFFERENCES AND SOME ARE 5617 04:30:13,320 --> 04:30:15,120 NON-UNIFORM DIFFERENCES ALONG 5618 04:30:15,120 --> 04:30:18,920 THE TRACKS. 5619 04:30:18,920 --> 04:30:22,720 WE HAVE USED APPROACHES THAT ARE 5620 04:30:22,720 --> 04:30:26,320 ANALOGOUS ONCE USED IN HUMANS IN 5621 04:30:26,320 --> 04:30:28,840 A MOUSE MODEL EXPRESSING THE 5622 04:30:28,840 --> 04:30:32,240 MUTATIONS GENERATED AND WE CAN 5623 04:30:32,240 --> 04:30:33,880 SEE THAT WE HAVE EFFECT OF 5624 04:30:33,880 --> 04:30:37,520 GENOTYPE AND AFFECT OF AGE IN 5625 04:30:37,520 --> 04:30:39,280 THE TRANSGENIC MICE ALLOWING FOR 5626 04:30:39,280 --> 04:30:41,800 CONTROLS WE CAN DETECT ON A 5627 04:30:41,800 --> 04:30:43,960 RELATIVELY SHORT TIME FRAME, 5628 04:30:43,960 --> 04:30:44,680 SEVEN WEEKS AFTER EXPRESSION AND 5629 04:30:44,680 --> 04:30:48,400 WE CAN LOOK AT THE INTERACTION 5630 04:30:48,400 --> 04:30:51,240 BETWEEN PHENOTYPE. 5631 04:30:51,240 --> 04:30:54,240 WE HAVE ALSO USED ENHANCED MRI 5632 04:30:54,240 --> 04:30:59,800 IN CONJUNCTION WITH BEHAVIOR 5633 04:30:59,800 --> 04:31:10,880 WHEN WE IMPLANT EIMPLANTED MANGANESE AND 5634 04:31:10,880 --> 04:31:13,280 LOOKED AT SUSCEPTIBILITY OF THE 5635 04:31:13,280 --> 04:31:15,720 IRON DEPOSITION AND WE DEVELOPED 5636 04:31:15,720 --> 04:31:18,200 APPROACHES TO MODEL BEHAVIOR 5637 04:31:18,200 --> 04:31:20,360 USING THE REPRESENTATION OF THE 5638 04:31:20,360 --> 04:31:22,200 IMAGING PHENOTYPES AND WE'VE 5639 04:31:22,200 --> 04:31:24,200 DISCOVERED WE HAVE BETTER 5640 04:31:24,200 --> 04:31:26,120 PREDICTIVE ABILITIES FOR 5641 04:31:26,120 --> 04:31:28,160 BEHAVIOR IF WE COMBINE THE THREE 5642 04:31:28,160 --> 04:31:30,080 BIOMARKERS. 5643 04:31:30,080 --> 04:31:32,920 AND WE ARE APPLYING MORE SIMILAR 5644 04:31:32,920 --> 04:31:35,960 METHODS TO LOOK AT NEURO IMAGING 5645 04:31:35,960 --> 04:31:36,720 GENETIC RISK FOR ALZHEIMER'S 5646 04:31:36,720 --> 04:31:38,360 RISK IN HUMAN POPULATIONS. 5647 04:31:38,360 --> 04:31:42,280 WE'RE DOING IMAGING TO GET 5648 04:31:42,280 --> 04:31:44,000 VARIOUS CONTRAST FOR EXAMPLE T1 5649 04:31:44,000 --> 04:31:47,920 WEIGHTED IMAGE FOR VOLUME 5650 04:31:47,920 --> 04:31:51,640 CHANGES AND SUSCEPTIBILITY AND 5651 04:31:51,640 --> 04:31:55,120 DIFFUSION AND WE CAN SEE WE CAN 5652 04:31:55,120 --> 04:31:58,440 OBSERVE ACTIONS IN BOTH VOLUME 5653 04:31:58,440 --> 04:32:01,720 BETWEEN APOE AND APOE 3 AND 4 AT 5654 04:32:01,720 --> 04:32:03,360 RISK FOR ALZHEIMER'S DISEASE 5655 04:32:03,360 --> 04:32:06,880 BEFORE ANY OTHER DISEASE. 5656 04:32:06,880 --> 04:32:08,360 SIMILARLY WE HAVE DEVELOPED RISK 5657 04:32:08,360 --> 04:32:12,640 SIGNATURE THAT INCORPORATED 5658 04:32:12,640 --> 04:32:13,880 COGNITION. 5659 04:32:13,880 --> 04:32:16,120 AND APOE GENOTYPE AND AGE AND 5660 04:32:16,120 --> 04:32:17,120 LOOK PRINCIPLE COMPONENT 5661 04:32:17,120 --> 04:32:18,080 ANALYSIS TO LOOK AT BRAIN 5662 04:32:18,080 --> 04:32:20,280 NETWORKS THAT DIFFERENTIATE APOE 5663 04:32:20,280 --> 04:32:27,120 3 AND APOE 4 CARRIERS AND 5664 04:32:27,120 --> 04:32:27,680 IDENTIFYING THE VULNERABLE 5665 04:32:27,680 --> 04:32:32,320 NETWORKS. 5666 04:32:32,320 --> 04:32:35,640 AND THIS CAN GENERATE HYPOTHESIS 5667 04:32:35,640 --> 04:32:39,120 FOR LARGER COHORTS FROM PUBLIC 5668 04:32:39,120 --> 04:32:41,520 DATABASES BUT IT CAN BE APPLIED 5669 04:32:41,520 --> 04:32:42,360 TO DIFFERENT TIME POINTS ACROSS 5670 04:32:42,360 --> 04:32:42,600 SPACES. 5671 04:32:42,600 --> 04:33:05,840 THANK YOU. 5672 04:33:05,840 --> 04:33:09,080 >> NEXT IS IRINA CONBOY LOOKING 5673 04:33:09,080 --> 04:33:11,200 AT TISSUE MAINTENANCE AND 5674 04:33:11,200 --> 04:33:11,440 REPAIR. 5675 04:33:11,440 --> 04:33:25,640 DR. CONBOY. 5676 04:33:25,640 --> 04:33:28,240 >> I GLAD WE CAN DO REMOTE 5677 04:33:28,240 --> 04:33:30,240 BECAUSE I HAVE AN OLD FASHIONED 5678 04:33:30,240 --> 04:33:30,760 COLD TODAY. 5679 04:33:30,760 --> 04:33:32,120 THANK YOU FOR ORGANIZING THE 5680 04:33:32,120 --> 04:33:32,360 MEETING. 5681 04:33:32,360 --> 04:33:33,480 WHAT WE HAVE BEEN FOCUSSING ON 5682 04:33:33,480 --> 04:33:36,160 FOR A WHILE IS THE EFFECTS OF 5683 04:33:36,160 --> 04:33:41,640 YOUNG OR OLD BLOOD ON 5684 04:33:41,640 --> 04:33:42,320 NEUROGENESIS, BRAIN INFLAMMATION 5685 04:33:42,320 --> 04:33:44,120 AND CAPACITY USING SMALL ANIMALS 5686 04:33:44,120 --> 04:33:45,840 SUCH AS MICE AS EXPERIMENTAL 5687 04:33:45,840 --> 04:33:46,280 SYSTEM. 5688 04:33:46,280 --> 04:33:50,800 RECENTLY WE EXPANDED OUR WORK TO 5689 04:33:50,800 --> 04:33:52,040 CLINICAL STUDIES AND THE WORK IS 5690 04:33:52,040 --> 04:33:53,400 STILL UNPUBLISHED AND HOPEFULLY 5691 04:33:53,400 --> 04:33:54,440 I'LL BE ABLE TO SHARE IT NEXT 5692 04:33:54,440 --> 04:33:55,760 TIME AROUND. 5693 04:33:55,760 --> 04:34:01,440 SO WHAT YOU CAN SEE HERE IS THE 5694 04:34:01,440 --> 04:34:02,640 MINIATURIZED PROCEDURE OF 5695 04:34:02,640 --> 04:34:09,840 EXCHANGE IN BLOOD BETWEEN MICE 5696 04:34:09,840 --> 04:34:16,960 WHICH IS A PROCEDURE THAT LAST 5697 04:34:16,960 --> 04:34:19,720 30 MINUTES AND THEY GO SEPARATE 5698 04:34:19,720 --> 04:34:24,240 WAYS AND WE SEE NEUROGENESIS OF 5699 04:34:24,240 --> 04:34:27,120 THE HIPPOCAMPUS OR THE NUMBERS 5700 04:34:27,120 --> 04:34:34,720 OF PROLIFERATING CELLS DECLINE 5701 04:34:34,720 --> 04:34:37,120 NOT ONLY WITH AGE, THIS IS YOUNG 5702 04:34:37,120 --> 04:34:41,680 EXCHANGE ANIMALS AND INJURED 5703 04:34:41,680 --> 04:34:44,320 EXCHANGE THAT ARE INJURED BUT 5704 04:34:44,320 --> 04:34:47,720 DECLINES WHEN YOUNG MICE ARE 5705 04:34:47,720 --> 04:34:48,920 EXCHANGED WITH OLD BLOOD JUST 5706 04:34:48,920 --> 04:34:51,120 ONCE AND PARTICULARLY WHEN THESE 5707 04:34:51,120 --> 04:34:55,120 ANIMALS ARE INJURED IN THEIR 5708 04:34:55,120 --> 04:34:56,360 SKELETAL MUSCLE. 5709 04:34:56,360 --> 04:34:59,120 THE COMBINATION OF INJURY AND 5710 04:34:59,120 --> 04:35:09,240 OLD BLOOD DIMINISHING 5711 04:35:09,240 --> 04:35:12,560 HIPPOCAMPUS NEUROGENESIS VERY 5712 04:35:12,560 --> 04:35:14,520 QUICKLY. 5713 04:35:14,520 --> 04:35:16,720 OLD ANIMALS DO NOT BECOME 5714 04:35:16,720 --> 04:35:20,560 BETTER, THEY'RE NOT REGENERATED 5715 04:35:20,560 --> 04:35:33,600 WITH RESPECT TO THE HIPPOCAMPAL 5716 04:35:33,600 --> 04:35:34,480 REGENESIS EVEN WITH YOUNGER 5717 04:35:34,480 --> 04:35:40,320 BLOOD AND MICE ARE PUT IN AN 5718 04:35:40,320 --> 04:35:44,000 INVERTED POSITION AND IT'S NOT 5719 04:35:44,000 --> 04:35:45,520 THE BRUT FORCE TEST SO IN THE 5720 04:35:45,520 --> 04:35:47,400 TRAINING SESSION YOUNG MICE ARE 5721 04:35:47,400 --> 04:35:52,760 NOT DOING MUCH BETTER THAN OLD 5722 04:35:52,760 --> 04:35:52,960 MICE. 5723 04:35:52,960 --> 04:36:02,720 THEN IN THE TEST IF YOUNG MICE 5724 04:36:02,720 --> 04:36:04,040 HAVE YOUNG BLOOD THEY LEARN HOW 5725 04:36:04,040 --> 04:36:05,920 TO HANG AND WITH RESPECT TO THE 5726 04:36:05,920 --> 04:36:08,920 OLD ANIMALS YOUNG BLOOD DOES NOT 5727 04:36:08,920 --> 04:36:13,200 IMPROVE THIS COGNITIVE SHORT 5728 04:36:13,200 --> 04:36:15,160 MEMORY RESPONSE TO REMEMBER THEY 5729 04:36:15,160 --> 04:36:21,360 DON'T WANT TO DROP AND DOES NOT 5730 04:36:21,360 --> 04:36:23,360 AFFECT AGILITY AND THIS IS 5731 04:36:23,360 --> 04:36:26,960 DIFFERENT WHERE IF YOU 5732 04:36:26,960 --> 04:36:28,320 PHYSICALLY SUTURE THE ANIMALS 5733 04:36:28,320 --> 04:36:30,120 TOGETHER AND THEY RUN AROUND 5734 04:36:30,120 --> 04:36:34,320 SEVERAL WEEKS THEN YOU SEE BOTH 5735 04:36:34,320 --> 04:36:39,160 DECLINE OF HIPPOCAMPAL 5736 04:36:39,160 --> 04:36:45,400 NEUROGENESIS IN THE PAIR AND 5737 04:36:45,400 --> 04:36:47,480 SLIGHT INCREASE BUT IF YOU LOOK 5738 04:36:47,480 --> 04:36:50,920 AT THE SCALE YOU LOOK AT THE 5739 04:36:50,920 --> 04:36:51,520 PRECURSOR CELLS. 5740 04:36:51,520 --> 04:36:54,600 INTERESTINGLY WE KNEW THIS 5741 04:36:54,600 --> 04:37:01,120 OUTCOME BY 2003 BUT THIS WAS 5742 04:37:01,120 --> 04:37:06,280 REVIEWED A COUPLE TIMES IN 5743 04:37:06,280 --> 04:37:12,040 NATURE BUT WE SHARED THE DATA 5744 04:37:12,040 --> 04:37:12,720 WITH OUR STANFORD NEIGHBOR AND 5745 04:37:12,720 --> 04:37:16,520 HE FOLLOWED UP AND PUBLISHED ED AED AS 5746 04:37:16,520 --> 04:37:23,120 YOU KNOW INTERESTING WORK IN 5747 04:37:23,120 --> 04:37:25,520 NEUROPLASTICITY BUT SIX YEARS 5748 04:37:25,520 --> 04:37:27,000 LATER THIS WAS PUBLISHED IN 5749 04:37:27,000 --> 04:37:27,880 NATURE. 5750 04:37:27,880 --> 04:37:31,360 THE BOTTOM LINE IS THERE'S A 5751 04:37:31,360 --> 04:37:32,080 DIFFERENCE BETWEEN BLOOD 5752 04:37:32,080 --> 04:37:34,880 EXCHANGE AND I'LL BE HAPPY TO 5753 04:37:34,880 --> 04:37:36,640 SPECULATE AS TO WHY. 5754 04:37:36,640 --> 04:37:41,920 THE BLOOD EXCHANGE IS YOU DO NOT 5755 04:37:41,920 --> 04:37:43,880 NEED TO EXCHANGE YOUNG OR OLD 5756 04:37:43,880 --> 04:37:46,720 BLOOD YOU CAN THE CIRCUITRY 5757 04:37:46,720 --> 04:37:47,520 ENVIRONMENT WITH ANY FLUID YOU'D 5758 04:37:47,520 --> 04:37:49,640 LIKE TO TEST AND IN THE FIRST 5759 04:37:49,640 --> 04:37:55,920 TEST WE SIMPLY DILUTED OLD 5760 04:37:55,920 --> 04:37:58,200 PLASMA USING SALINE AND WHAT 5761 04:37:58,200 --> 04:38:00,200 HAPPENS THERE IS THERE WAS 5762 04:38:00,200 --> 04:38:04,480 IMPROVEMENT IN COGNITION OF OLD 5763 04:38:04,480 --> 04:38:06,360 ANIMALS IN NOVEL COGNITION 5764 04:38:06,360 --> 04:38:06,640 TESTS. 5765 04:38:06,640 --> 04:38:09,720 SO TYPICALLY YOUNG MICE ARE 5766 04:38:09,720 --> 04:38:14,280 INQUISITIVE AND EXPLORE THEIR 5767 04:38:14,280 --> 04:38:18,280 ENVIRONMENT AND AFTER SINGLE 5768 04:38:18,280 --> 04:38:23,960 PROCEDURE OF OLD PLASMA DILUTION 5769 04:38:23,960 --> 04:38:36,040 THEY BEHAVE AS YOUNG. 5770 04:38:36,040 --> 04:38:38,520 THIS RESULT IS ARE 5771 04:38:38,520 --> 04:38:39,880 NEUROINFLAMMATION AND SUDDENLY 5772 04:38:39,880 --> 04:38:42,080 YOU GET BRAIN SENESCENCE SIMILAR 5773 04:38:42,080 --> 04:38:48,800 TO THAT AS WHEN THEY USED THIS 5774 04:38:48,800 --> 04:38:52,920 63 AND THESE ARE SMALL IMAGES 5775 04:38:52,920 --> 04:38:58,720 THAT SHOW THE PROFILE OF THE 5776 04:38:58,720 --> 04:39:00,560 CIRCUITRY PROTEOME OF MICE AND 5777 04:39:00,560 --> 04:39:03,000 PEOPLE UNDERGOING THE PROCEDURE. 5778 04:39:03,000 --> 04:39:08,000 THE REMAINING PROTEINS WHICH ARE 5779 04:39:08,000 --> 04:39:14,640 NOW UP REGULATED AND SO WHAT WE 5780 04:39:14,640 --> 04:39:17,760 THINK IS GOING ON IS THAT WE 5781 04:39:17,760 --> 04:39:20,920 INITIALLY DILUTE THE CIRCUITRY 5782 04:39:20,920 --> 04:39:23,200 PROTEIN AT THIS STAGE AND THE 5783 04:39:23,200 --> 04:39:25,920 PROTEIN IS AN INHIBITOR OF ALL 5784 04:39:25,920 --> 04:39:29,640 THOSE YOUNG FACTORS THAT DECLINE 5785 04:39:29,640 --> 04:39:31,720 WITH AGE AND SO ONCE IT'S 5786 04:39:31,720 --> 04:39:34,960 DILUTED AT THE LEVEL OF GENE 5787 04:39:34,960 --> 04:39:36,200 EXPRESSION AND EPIGENOME YOU 5788 04:39:36,200 --> 04:39:38,560 THEN UNLEASH MORE PRODUCTIVE 5789 04:39:38,560 --> 04:39:41,800 LEVELS OF SO-CALLED POSITIVE 5790 04:39:41,800 --> 04:39:42,840 REGULATORS OF FUNCTION, 5791 04:39:42,840 --> 04:39:44,720 MAINTENANCE AND REPAIR. 5792 04:39:44,720 --> 04:39:47,760 SO THIS IS THE SIMULATION WHICH 5793 04:39:47,760 --> 04:39:51,120 IS JUST FOR ILLUSTRATIVE 5794 04:39:51,120 --> 04:40:14,800 PURPOSES BUT HAVE A CAPACITY TO 5795 04:40:14,800 --> 04:40:17,280 AND YOUNG PROTEINS HOPEFULLY 5796 04:40:17,280 --> 04:40:21,400 ONCE YOU PHASE OUT THEY NEED FOR 5797 04:40:21,400 --> 04:40:23,120 PLASMA EXCHANGE AND DEVELOP 5798 04:40:23,120 --> 04:40:27,720 RATIONALE PHARMACOLOGIC 5799 04:40:27,720 --> 04:40:28,040 APPROACHES. 5800 04:40:28,040 --> 04:40:30,240 I'D LIKE TO REACH OUT TO THE 5801 04:40:30,240 --> 04:40:31,080 REGENERATION RESEARCH AND 5802 04:40:31,080 --> 04:40:35,000 STARTING AS THE NEW 5803 04:40:35,000 --> 04:40:35,360 EDITOR-IN-CHIEF. 5804 04:40:35,360 --> 04:40:35,920 THANK YOU SO MUCH FOR YOUR 5805 04:40:35,920 --> 04:40:46,000 ATTENTION. 5806 04:40:46,000 --> 04:40:46,160 >> 5807 04:40:46,160 --> 04:40:47,560 >> JILL GOLDSTEIN AT HARVARD 5808 04:40:47,560 --> 04:40:51,240 MEDICAL SCHOOL AND FOUNDER AND 5809 04:40:51,240 --> 04:40:55,120 DIRECTOR ON SEX CHANGES IN 5810 04:40:55,120 --> 04:40:57,920 MEDICINE AT MASS GENERAL AND 5811 04:40:57,920 --> 04:41:01,360 LOOKS AT ENDOCRINOLOGY WITH THE 5812 04:41:01,360 --> 04:41:03,080 AIM OF UNDERSTANDING SEX 5813 04:41:03,080 --> 04:41:04,840 DIFFERENCES AND DISORDERS OF THE 5814 04:41:04,840 --> 04:41:07,720 BRAIN AND THE CO-OCCURRENCE WITH 5815 04:41:07,720 --> 04:41:11,120 OTHER EVENTS SUCH AS CARDIO 5816 04:41:11,120 --> 04:41:22,920 VASCULAR DISEASE. 5817 04:41:22,920 --> 04:41:25,000 >> I'M GOING ASK FOR MENTAL 5818 04:41:25,000 --> 04:41:27,000 FLEXIBILITY BECAUSE I'M SHIFTING 5819 04:41:27,000 --> 04:41:32,760 GEARS HERE TO A MORE HIGHER 5820 04:41:32,760 --> 04:41:47,120 LEVEL DISCUSSION AROUND AND WE 5821 04:41:47,120 --> 04:41:48,320 UNDERSTAND NEURO DEVELOPMENT IS 5822 04:41:48,320 --> 04:41:49,560 UNDERSTANDING THE BRAIN AND WE 5823 04:41:49,560 --> 04:41:54,080 STUDY SEX DIFFERENCES IN THE 5824 04:41:54,080 --> 04:41:56,960 RISK OF THE DISORDERS OF THE 5825 04:41:56,960 --> 04:42:00,680 BRAIN AND CO-OCCURRENCE WITH THE 5826 04:42:00,680 --> 04:42:03,120 DISORDERS OF THE HEART AND WE 5827 04:42:03,120 --> 04:42:05,640 FOUND SHARED PATHOPHYSIOLOGY 5828 04:42:05,640 --> 04:42:08,680 ACROSS THE DISORDERS THAT 5829 04:42:08,680 --> 04:42:11,120 DIFFERS BY SEX AND THEN BEGINS 5830 04:42:11,120 --> 04:42:14,000 IN FETAL DEVELOPMENT AND MY LAB 5831 04:42:14,000 --> 04:42:15,560 FOCUSES ON SEX DIFFERENCES IN 5832 04:42:15,560 --> 04:42:17,880 THE RISK FOR DEPRESSION AND 5833 04:42:17,880 --> 04:42:20,120 CO-OCCURRENCE WITH CARDIO 5834 04:42:20,120 --> 04:42:21,560 METABOLIC DISEASE AND THE RISK 5835 04:42:21,560 --> 04:42:37,000 FOR ALZHEIMER'S DISEASE. 5836 04:42:37,000 --> 04:42:38,840 AND THERE'S DISORDERS OF THE 5837 04:42:38,840 --> 04:42:43,920 BRAIN AND HEART AND 5838 04:42:43,920 --> 04:42:44,280 AUTOIMMUNITY. 5839 04:42:44,280 --> 04:42:45,880 ARE THERE WINDOWS OF 5840 04:42:45,880 --> 04:42:46,720 OPPORTUNITIES FOR SEX 5841 04:42:46,720 --> 04:42:48,280 DIFFERENCES WHEN THEY EMERGE 5842 04:42:48,280 --> 04:42:55,440 WHEN THE BRAIN IN THE BODY ARE 5843 04:42:55,440 --> 04:43:04,200 FLOODED WITH GAN ANNAN -- 5844 04:43:04,200 --> 04:43:06,320 GHANANO HORMONES AND WE CAN USE 5845 04:43:06,320 --> 04:43:08,360 THESE WHEN SEX DIFFERENCES 5846 04:43:08,360 --> 04:43:09,200 EMRERJ TO NOT ONLY UNDERSTAND 5847 04:43:09,200 --> 04:43:10,120 THE DIFFERENCES OF THE CAUSES OF 5848 04:43:10,120 --> 04:43:12,680 THE DIFFERENCES BUT TO DEVELOP 5849 04:43:12,680 --> 04:43:16,280 THERAPEUTICS WHAT WE CALL 5850 04:43:16,280 --> 04:43:17,080 SEX-DEPENDENT THERAPEUTICS 5851 04:43:17,080 --> 04:43:18,480 TARGETED EARLY EVEN PRIOR TO THE 5852 04:43:18,480 --> 04:43:26,720 MANIFESTATION OF DISEASE. 5853 04:43:26,720 --> 04:43:29,920 HAVE USED THE PRENATAL STRESS 5854 04:43:29,920 --> 04:43:31,800 IMMUNE MODELS OF STRESS AND IT 5855 04:43:31,800 --> 04:43:33,400 AFFECTS EVERY CHRONIC DISEASE WE 5856 04:43:33,400 --> 04:43:36,040 KNOW AND THE CIRCUITRY THAT 5857 04:43:36,040 --> 04:43:41,280 REGULATES STRESS IS SOME OF THE 5858 04:43:41,280 --> 04:43:43,720 MOST HIGHLY DIMORPHIC STRESS IN 5859 04:43:43,720 --> 04:43:48,520 THE BRAIN AND REGULATES ES -- 5860 04:43:48,520 --> 04:43:50,920 REGULATES ANXIETY AND THE MOOD 5861 04:43:50,920 --> 04:43:53,360 AND THE HEART AND STEROID 5862 04:43:53,360 --> 04:43:57,640 HORMONE PHYSIOLOGY AND THE 5863 04:43:57,640 --> 04:44:04,600 GANANO AXIS AND THE IMMUNE 5864 04:44:04,600 --> 04:44:05,480 PHYSIOLOGY AND SOME OF THE SAME 5865 04:44:05,480 --> 04:44:07,800 BRAIN REGIONS THAT REGULATE 5866 04:44:07,800 --> 04:44:10,400 STRESS, MOOD AND THE HEART ALSO 5867 04:44:10,400 --> 04:44:10,760 REGULATE MEMORY. 5868 04:44:10,760 --> 04:44:15,600 SO THE MODELS WE HAVE BEEN USING 5869 04:44:15,600 --> 04:44:19,720 WE USE PRENATAL STRESS MODELS 5870 04:44:19,720 --> 04:44:21,040 AND PREGNANCY COMPLICATIONS AS 5871 04:44:21,040 --> 04:44:26,960 OUR MODELS OF PRE-NATAL STRESS 5872 04:44:26,960 --> 04:44:28,520 PREECLAMPSIA AND FETAL GROWTH 5873 04:44:28,520 --> 04:44:30,240 RESTRICTION AND WE HAVE FOUND 5874 04:44:30,240 --> 04:44:32,520 AND OF COURSE BOTH AT THE HUMAN 5875 04:44:32,520 --> 04:44:34,400 AND ANIMAL LEVEL THAT THIS 5876 04:44:34,400 --> 04:44:37,120 CHANGES THE MATERNAL IMMUNE 5877 04:44:37,120 --> 04:44:37,960 RESPONSE. 5878 04:44:37,960 --> 04:44:42,320 SHE THEN MOUNTS THE 5879 04:44:42,320 --> 04:44:46,960 GLUCOCORTICOID RESPONSE AND WHEN 5880 04:44:46,960 --> 04:44:54,320 THAT OCCURS DURING CRITICAL 5881 04:44:54,320 --> 04:45:11,320 PERIODS AND THE PHYSIOLOGY 5882 04:45:11,320 --> 04:45:14,400 ASSOCIATED WITH THE CIRCUITRY 5883 04:45:14,400 --> 04:45:21,720 MEDIATES THE DIFFERENCES THROUGH 5884 04:45:21,720 --> 04:45:22,880 CARDIOVASCULAR RISK THROUGH 5885 04:45:22,880 --> 04:45:23,640 DYSREGULATION OF THE HEART AND 5886 04:45:23,640 --> 04:45:26,160 WE'RE LOOKING AT SOME OF THE 5887 04:45:26,160 --> 04:45:28,080 SAME PHYSIOLOGIC AND EARLY 5888 04:45:28,080 --> 04:45:30,320 PREOCCURERS ARE RISKS FOR MEMORY 5889 04:45:30,320 --> 04:45:32,360 DECLINE AND ALZHEIMER'S DISEASE. 5890 04:45:32,360 --> 04:45:36,440 WE WORK WITH ANIMAL MODELS 5891 04:45:36,440 --> 04:45:38,120 WORKING OUT SOME OF THE BASIC 5892 04:45:38,120 --> 04:45:38,600 MOLECULAR MECHANISMS. 5893 04:45:38,600 --> 04:45:40,760 I DON'T HAVE TIME TO GO INTO 5894 04:45:40,760 --> 04:45:42,960 THOSE NOW BUT HAPPY TO DO SO IF 5895 04:45:42,960 --> 04:45:48,240 PEOPLE HAVE QUESTIONS ABOUT WHAT 5896 04:45:48,240 --> 04:46:21,800 WE HAVE DONE. 5897 04:46:21,800 --> 04:46:22,920 AND THE MOTHERS WERE FOLLOWED 5898 04:46:22,920 --> 04:46:25,480 THROUGH THEIR PREGNANCIES, BLOOD 5899 04:46:25,480 --> 04:46:26,640 WAS STORED. 5900 04:46:26,640 --> 04:46:28,920 IT'S NOW AT NICHD AND THE KIDS 5901 04:46:28,920 --> 04:46:31,080 WERE FOLLOWED FOR SEVEN YEARS. 5902 04:46:31,080 --> 04:46:32,840 ALL SORTS OF ASSESSMENTS WERE 5903 04:46:32,840 --> 04:46:34,320 DONE THROUGH THIS PERIOD OF 5904 04:46:34,320 --> 04:46:35,120 TIME. 5905 04:46:35,120 --> 04:46:37,600 IT'S A PUBLIC DATA SET AND THE 5906 04:46:37,600 --> 04:46:39,440 ORIGINAL STUDIES WERE ABOUT 5907 04:46:39,440 --> 04:46:40,680 NEUROLOGICAL DISORDERS IN KIDS. 5908 04:46:40,680 --> 04:46:44,400 AND OVER THE LAST 30 YEARS MY 5909 04:46:44,400 --> 04:46:45,920 COLLEAGUES AND I HAVE BEEN 5910 04:46:45,920 --> 04:46:49,680 FOLLOWING THESE ADULT OFFSPRING 5911 04:46:49,680 --> 04:46:53,120 IN THEIR 20s, 30s, 40s, 50s AND 5912 04:46:53,120 --> 04:46:55,600 NOW TURNING TO THEIR 60s AND WE 5913 04:46:55,600 --> 04:46:58,920 DO DEEP PHENOTYPING. 5914 04:46:58,920 --> 04:47:00,680 WE DO CLINICAL AND COGNITIVE 5915 04:47:00,680 --> 04:47:03,000 ASSESSMENTS AND DO STRUCTURAL 5916 04:47:03,000 --> 04:47:05,720 AND FUNCTIONAL IMAGING AND A LOT 5917 04:47:05,720 --> 04:47:06,080 OF PHYSIOLOGY. 5918 04:47:06,080 --> 04:47:07,360 WE'RE INTERESTED IN THE 5919 04:47:07,360 --> 04:47:08,800 PHYSIOLOGY AND WE COLLECTED 5920 04:47:08,800 --> 04:47:13,360 BLOOD NOT ONLY FOR DNA BUT NOW 5921 04:47:13,360 --> 04:47:15,160 WE COLLECT CELLS AND 5922 04:47:15,160 --> 04:47:16,240 TRANSCRIPTION WE'RE PARTICULARLY 5923 04:47:16,240 --> 04:47:18,320 INTERESTED IN SHARED IMMUNE 5924 04:47:18,320 --> 04:47:23,120 PATHWAYS SO WE'VE BEEN ANALYZING 5925 04:47:23,120 --> 04:47:25,200 MONOCYTE CELLS AND TRANSCRIBING 5926 04:47:25,200 --> 04:47:29,520 THEM TO LOOK AT THE PATHWAY 5927 04:47:29,520 --> 04:47:30,320 DYSREGULATI 5928 04:47:30,320 --> 04:47:30,680 DYSREGULATION. 5929 04:47:30,680 --> 04:47:31,480 LASTLY I THINK MY FIVE MINUTES 5930 04:47:31,480 --> 04:47:34,880 IS LIKELY UP, I JUST WANT TO SAY 5931 04:47:34,880 --> 04:47:37,600 THAT THESE TYPES OF STUDIES, THE 5932 04:47:37,600 --> 04:47:39,240 DEEP PHENOTYPING STUDIES OF 5933 04:47:39,240 --> 04:47:41,120 HUMANS REALLY TAKE A VILLAGE. 5934 04:47:41,120 --> 04:47:43,440 AND SO I WANT TO THANK MY 5935 04:47:43,440 --> 04:47:45,240 COLLEAGUES PARTICULARLY STEVEN 5936 04:47:45,240 --> 04:47:47,520 BUCCA AT BROWN AND HE AND I HAVE 5937 04:47:47,520 --> 04:47:48,880 BEEN FOLLOWING THESE ADULT 5938 04:47:48,880 --> 04:47:51,160 OFFSPRING OVER THE LAST 30 YEARS 5939 04:47:51,160 --> 04:47:56,000 AND FINALLY I WANT TO THANK THE 5940 04:47:56,000 --> 04:48:04,600 FUNDING SOURCES AT NIH AND NIMPH 5941 04:48:04,600 --> 04:48:06,720 AND THE OFFICE OF RESEARCH OF 5942 04:48:06,720 --> 04:48:09,080 HUMAN HEALTH AT THE NIA BECAUSE 5943 04:48:09,080 --> 04:48:11,720 THESE STUDIES TAKE A VILLAGE AND 5944 04:48:11,720 --> 04:48:13,480 THEY'RE VERY LABOR INTENSIVE AND 5945 04:48:13,480 --> 04:48:15,320 TAKE A LOT OF FUNDING. 5946 04:48:15,320 --> 04:48:19,880 WE'RE INCREDIBLY GRATE FWLFUL 5947 04:48:19,880 --> 04:48:21,320 FOR FUNDING THE OVER SO MANY 5948 04:48:21,320 --> 04:48:23,120 YEARS AND WANT TO CREATE THIS 5949 04:48:23,120 --> 04:48:24,760 UNIQUE COHORT AS A RESOURCE FOR 5950 04:48:24,760 --> 04:48:26,480 THE NEXT GENERATION TO BE 5951 04:48:26,480 --> 04:48:27,240 STUDYING INTO OLDER AGE. 5952 04:48:27,240 --> 04:48:29,720 SO THANK YOU VERY MUCH. 5953 04:48:29,720 --> 04:48:31,600 AND PLEASE COME VISIT US BY THE 5954 04:48:31,600 --> 04:48:33,320 WAY AT OUR WEBSITES AND YOU'D 5955 04:48:33,320 --> 04:48:35,120 LIKE TO JOIN THE EFFORT. 5956 04:48:35,120 --> 04:48:44,120 THANK YOU. 5957 04:48:44,120 --> 04:48:48,720 LET'S MOVE TO OUR FOURTH 5958 04:48:48,720 --> 04:48:50,320 PANELIST MARISA SPANN AT 5959 04:48:50,320 --> 04:48:53,600 COLUMBIA UNIVERSITY. 5960 04:48:53,600 --> 04:48:55,080 HER EXPERTISE IS IN CLINICAL 5961 04:48:55,080 --> 04:48:58,000 NEUROPSYCHOLOGY AND PERINATAL 5962 04:48:58,000 --> 04:48:58,320 EPIDEMIOLOGY. 5963 04:48:58,320 --> 04:49:01,240 HER RESEARCH AIMS TO IDENTIFY 5964 04:49:01,240 --> 04:49:04,520 EARLY IMMUNE, BRAIN AND EARLY 5965 04:49:04,520 --> 04:49:06,240 PSYCHOLOGICAL RISKS. 5966 04:49:06,240 --> 04:49:11,080 DR. SPANN. 5967 04:49:11,080 --> 04:49:12,840 >> THANK YOU AND THANK YOU FOR 5968 04:49:12,840 --> 04:49:14,920 THE INVITATION TO BE HERE. 5969 04:49:14,920 --> 04:49:17,680 I'LL HIGHLIGHT A FEW THINGS FROM 5970 04:49:17,680 --> 04:49:20,720 MY WORK THAT ARE REALLY SORT OF 5971 04:49:20,720 --> 04:49:24,880 REASONS I THINK TO THINK ABOUT 5972 04:49:24,880 --> 04:49:27,560 THE DEVELOPING BRAIN AS JILL 5973 04:49:27,560 --> 04:49:30,480 MENTIONED IN THE CONTEXT OF THE 5974 04:49:30,480 --> 04:49:32,960 EARLY STAGES OF DEVELOPMENT 5975 04:49:32,960 --> 04:49:35,000 THROUGH SENESCENCE. 5976 04:49:35,000 --> 04:49:36,800 WE KNOW THE BRAIN GROWS RAPIDLY 5977 04:49:36,800 --> 04:49:40,560 DURING THE PERINATAL PERIOD AND 5978 04:49:40,560 --> 04:49:43,480 MY WORK PARTICULARLY FOCUSES ON 5979 04:49:43,480 --> 04:49:45,320 THE FETAL PERIOD THROUGH BRAIN 5980 04:49:45,320 --> 04:49:47,160 DEVELOPMENT WITHIN THE FIRST 5981 04:49:47,160 --> 04:49:54,280 YEAR OF LIFE TO IDENTIFY EARLY 5982 04:49:54,280 --> 04:49:55,560 PSYCHIATRIC RISK MARKERS. 5983 04:49:55,560 --> 04:50:05,360 I'M NOT DOING WORK ON THE NEURO 5984 04:50:05,360 --> 04:50:08,320 NEURODEGENERATION SIDE THERE'S 5985 04:50:08,320 --> 04:50:09,280 NEUROCOGNITION AND DEVELOPMENT 5986 04:50:09,280 --> 04:50:10,920 THAT THIS EARLY WINDOW IN LIFE 5987 04:50:10,920 --> 04:50:12,480 COULD BE POTENTIALLY PREDICTIVE 5988 04:50:12,480 --> 04:50:13,760 AND IMPORTANT TO THINK ABOUT IN 5989 04:50:13,760 --> 04:50:15,120 THE CONTEXT OF LATER STAGES IN 5990 04:50:15,120 --> 04:50:19,920 DEVELOPMENT. 5991 04:50:19,920 --> 04:50:24,000 AND OBVIOUSLY THERE'S EXPANSIVE 5992 04:50:24,000 --> 04:50:26,040 GROWTH AND SYNAPSE FORMATION 5993 04:50:26,040 --> 04:50:32,560 THAT ARE PRETTY PRETT -- 5994 04:50:32,560 --> 04:50:34,320 CRITICAL TO EARLY STAGE FUTURE 5995 04:50:34,320 --> 04:50:34,640 DEVELOPMENT. 5996 04:50:34,640 --> 04:50:38,080 WE OBVIOUSLY LOOKED AT PRENATAL 5997 04:50:38,080 --> 04:50:38,920 EXPOSURES AND PARTICULARLY 5998 04:50:38,920 --> 04:50:42,120 IMMUNE BUT ALSO ONE OF THE 5999 04:50:42,120 --> 04:50:47,120 THINGS WE'VE BEEN THINKING ABOUT 6000 04:50:47,120 --> 04:50:48,440 IS HOW COMPLEX THE ENVIRONMENT 6001 04:50:48,440 --> 04:50:51,520 THAT CHILDREN GROW UP IN ARE. 6002 04:50:51,520 --> 04:50:54,120 AND SO WE STARTED TO TRY TO LOOK 6003 04:50:54,120 --> 04:50:56,160 AT AND CONSIDER THE COMPLEX 6004 04:50:56,160 --> 04:50:59,120 ENVIRONMENT IN TERMS OF 6005 04:50:59,120 --> 04:50:59,760 POTENTIALLY IDENTIFYING COMMON 6006 04:50:59,760 --> 04:51:01,640 BRAIN REGIONS THAT MIGHT BE 6007 04:51:01,640 --> 04:51:03,720 REALLY CRITICAL OR ASSOCIATED 6008 04:51:03,720 --> 04:51:05,720 WITH PSYCHIATRIC ARREST. 6009 04:51:05,720 --> 04:51:07,200 AND SOME OF MY COLLEAGUES TODAY 6010 04:51:07,200 --> 04:51:10,400 HAVE MENTIONED THE VALUE OF THE 6011 04:51:10,400 --> 04:51:10,720 ENVIRONMENT. 6012 04:51:10,720 --> 04:51:12,880 AND THINKING OF THE CONTEXT OF 6013 04:51:12,880 --> 04:51:15,240 MENTAL HEALTH IN OUR WORK 6014 04:51:15,240 --> 04:51:19,240 RECENTLY IN PSYCHO PHARMACOLOGY 6015 04:51:19,240 --> 04:51:21,080 AND WE IDENTIFIED SOME COMMON 6016 04:51:21,080 --> 04:51:25,440 BRAIN REGIONS THAT WERE 6017 04:51:25,440 --> 04:51:27,160 ASSOCIATED WITH FRATERNAL 6018 04:51:27,160 --> 04:51:28,880 STRESS, DEPRESSION AS WELL AS A 6019 04:51:28,880 --> 04:51:35,000 MEASURE OF PREGNANCY, ANXIETY 6020 04:51:35,000 --> 04:51:35,320 A 6021 04:51:35,320 --> 04:51:59,600 AND CORTISOL AND ALSO CHRONIC 6022 04:51:59,600 --> 04:52:00,520 HEALTH CONDITIONS. 6023 04:52:00,520 --> 04:52:09,000 WE LOOKED AT FRATERNAL B MMI AND 6024 04:52:09,000 --> 04:52:13,400 WE IDENTIFIED INCREASED 6025 04:52:13,400 --> 04:52:14,080 CONNECTIVITY BETWEEN AN 6026 04:52:14,080 --> 04:52:16,320 ASSOCIATION WITH INCREASED BMI 6027 04:52:16,320 --> 04:52:18,560 OF THE MOM AND INCREASED 6028 04:52:18,560 --> 04:52:20,760 THALAMIC CONNECTIVITY AND THIS 6029 04:52:20,760 --> 04:52:23,600 WAS AN IMPORTANT FINDING BECAUSE 6030 04:52:23,600 --> 04:52:26,200 THERE WERE MODELS THAT WERE ABLE 6031 04:52:26,200 --> 04:52:28,520 TO IDENTIFY THE HYPOTHALAMUS 6032 04:52:28,520 --> 04:52:30,680 ROLE IN FOOD RESOLUTION. 6033 04:52:30,680 --> 04:52:32,960 -- REGULATION AND THINKING OF 6034 04:52:32,960 --> 04:52:33,760 SOCIAL FACTORS. 6035 04:52:33,760 --> 04:52:36,040 THERE'S RECENTLY UNPUBLISHED 6036 04:52:36,040 --> 04:52:38,520 WORK UNDER REVIEW AT PRESENT. 6037 04:52:38,520 --> 04:52:41,120 WE LOOKED AT THE AFFECTS OF 6038 04:52:41,120 --> 04:52:42,320 MATERNAL AFFECTS OF 6039 04:52:42,320 --> 04:52:43,920 DISCRIMINATION DURING PREGNANCY 6040 04:52:43,920 --> 04:52:45,680 AND FOUND REDUCED CONNECTIVITY 6041 04:52:45,680 --> 04:52:49,760 BETWEEN AMYGDALA AND THE 6042 04:52:49,760 --> 04:52:51,520 PREFRONTAL CORTEX. 6043 04:52:51,520 --> 04:52:53,320 THE GOAL ULTIMATELY WITH THE 6044 04:52:53,320 --> 04:52:54,920 FIRST PAPER THE DATA I SHOWED IS 6045 04:52:54,920 --> 04:52:59,320 TO REALLY TRY TO LOOK AT THE 6046 04:52:59,320 --> 04:53:03,120 FACTORS IN CONCERT AND HAVE MORE 6047 04:53:03,120 --> 04:53:08,160 COMPLEX MODELLING TO IDENTIFY 6048 04:53:08,160 --> 04:53:11,880 PATHWAYS THAT MAY INCREASE RISK. 6049 04:53:11,880 --> 04:53:14,080 AND I HINTED AT THE IMMUNE 6050 04:53:14,080 --> 04:53:15,480 SYSTEM MY LAB IS PARTICULARLY 6051 04:53:15,480 --> 04:53:17,680 INTERESTED IN PRENATALLY. 6052 04:53:17,680 --> 04:53:20,080 BOTH THE INNATE AND ADAPTIVE 6053 04:53:20,080 --> 04:53:22,000 IMMUNE SYSTEMS AND LOOKING AT 6054 04:53:22,000 --> 04:53:23,520 INFECTIONS AS WELL. 6055 04:53:23,520 --> 04:53:27,120 SOME OF OUR RECENT WORK USING 6056 04:53:27,120 --> 04:53:32,520 MULTI-MODAL IMAGING AND THE ME 6057 04:53:32,520 --> 04:53:42,040 BORN BRAIN IDENTIFIED THE 6058 04:53:42,040 --> 04:54:18,320 INTERLEUKIN AND CONSIDERING THE 6059 04:54:18,320 --> 04:54:20,000 METABOLITES IN THE BRAIN AND WE 6060 04:54:20,000 --> 04:54:22,920 ALSO IDENTIFIED SIMILAR BRAIN 6061 04:54:22,920 --> 04:54:25,720 REGIONS AND THIS IS ONE EXAMPLE 6062 04:54:25,720 --> 04:54:29,560 OF METABOLITE AND AGAIN THIS IS 6063 04:54:29,560 --> 04:54:33,360 ASSOCIATED WITH INCREASED 6064 04:54:33,360 --> 04:54:33,760 INTERLEUKIN SETS. 6065 04:54:33,760 --> 04:54:37,520 THAT'S ALL I HAVE FOR YOU. 6066 04:54:37,520 --> 04:54:39,720 AND I WANT TO THANK ANY 6067 04:54:39,720 --> 04:54:43,160 COLLABORATORS AND BRADLEY 6068 04:54:43,160 --> 04:54:48,480 PETERSON AND COLLABORATINING MY 6069 04:54:48,480 --> 04:54:53,880 DATA AND NIHM AND NICHD AND THE 6070 04:54:53,880 --> 04:54:54,240 LEE FOUNDATION. 6071 04:54:54,240 --> 04:54:55,120 >> THANK YOU. 6072 04:54:55,120 --> 04:55:00,520 THE LAST OF OUR FIVE PANELISTS 6073 04:55:00,520 --> 04:55:05,080 IS DR. MORIAH THOMASSON IN 6074 04:55:05,080 --> 04:55:05,720 POPULATION HEALTH IN THE NEW 6075 04:55:05,720 --> 04:55:08,120 YORK UNIVERSITY SCHOOL OF 6076 04:55:08,120 --> 04:55:08,880 MEDICINE. 6077 04:55:08,880 --> 04:55:10,320 HER RESEARCH ADDRESSES 6078 04:55:10,320 --> 04:55:13,440 PRINCIPLES OF NEURODEVELOPMENT 6079 04:55:13,440 --> 04:55:17,000 BEGINNING IN UTERO AND 6080 04:55:17,000 --> 04:55:18,640 ENVIRONMENTAL FACTORS THAT 6081 04:55:18,640 --> 04:55:19,200 AFFECT THE CIRCUITRY OF THE 6082 04:55:19,200 --> 04:55:44,680 DEVELOPING BRAIN. 6083 04:55:44,680 --> 04:55:47,400 >> WE'RE LOOKING AT THE F MERES 6084 04:55:47,400 --> 04:55:48,600 AND HUMAN BEHAVIOR AND THAT 6085 04:55:48,600 --> 04:55:51,440 PLAYS A BIG ROLE IN OUR 6086 04:55:51,440 --> 04:55:52,680 RESEARCH. 6087 04:55:52,680 --> 04:55:54,280 WE HAVE WEARABLES AND 6088 04:55:54,280 --> 04:55:57,200 NATURALISTIC ASSESSMENTS IN THE 6089 04:55:57,200 --> 04:55:58,240 HOME AND FINALLY THE 6090 04:55:58,240 --> 04:55:59,920 OPPORTUNITIES AVAILABLE TO ALL 6091 04:55:59,920 --> 04:56:07,240 OF US IN TERMS OF BIO SPECIMENS 6092 04:56:07,240 --> 04:56:09,880 PRETTY REMARKABLE AND 6093 04:56:09,880 --> 04:56:11,440 DR. SPANN'S WORK IS INTEGRATING 6094 04:56:11,440 --> 04:56:12,520 WHAT WE UNDERSTAND ABOUT THE 6095 04:56:12,520 --> 04:56:13,920 BODY WITH WHAT WE OBSERVE IN THE 6096 04:56:13,920 --> 04:56:14,120 BRAIN. 6097 04:56:14,120 --> 04:56:16,600 MY PRINCIPLE APPROACH IS TO USE 6098 04:56:16,600 --> 04:56:18,040 PERSPECTIVE LONGITUDINAL 6099 04:56:18,040 --> 04:56:18,280 STUDIES. 6100 04:56:18,280 --> 04:56:21,400 THIS IS A SCHEMATIC REPRESENTING 6101 04:56:21,400 --> 04:56:24,240 A DETROIT COHORT WE BEGAN TO 6102 04:56:24,240 --> 04:56:27,960 RECRUIT IN 2021 AND THE KIDDOS 6103 04:56:27,960 --> 04:56:30,280 HAD MULTIPLE BRAIN STUDIES AS 6104 04:56:30,280 --> 04:56:38,440 THE PLACENTAL STUDIES AND MANY 6105 04:56:38,440 --> 04:56:51,440 FOLLOW-UP 6106 04:56:51,440 --> 04:56:53,680 FOLLOW-UPS AND THERE'S A NEW 6107 04:56:53,680 --> 04:56:58,440 YORK BASED COHORT COMPROMISED OF 6108 04:56:58,440 --> 04:57:00,400 MORE THAN 1,000 WOMEN AND HALF 6109 04:57:00,400 --> 04:57:01,600 RECRUITED IN THE EARLY 6110 04:57:01,600 --> 04:57:03,400 POST-NATAL PERIOD AND WE CAN SEE 6111 04:57:03,400 --> 04:57:06,400 HOW DENSE THE SAMPLING IS AND 6112 04:57:06,400 --> 04:57:08,120 HOW MUCH TIME WE'RE SPENDING 6113 04:57:08,120 --> 04:57:11,960 WITH THE FAMILIES AND NOW HAVE 6114 04:57:11,960 --> 04:57:14,520 FUNDING TO FOLLOW UP A SUBSET 6115 04:57:14,520 --> 04:57:18,560 AND WE'RE CONTINUING TO DO THAT. 6116 04:57:18,560 --> 04:57:19,480 OVERALL THE GOAL OF OUR RESEARCH 6117 04:57:19,480 --> 04:57:24,200 IS TO UNDERSTAND THE IMPACT OF 6118 04:57:24,200 --> 04:57:36,640 PSYCHOSOCIAL DIVERSITY AN NEURO 6119 04:57:36,640 --> 04:57:39,120 NEURODEVELOPMENTAL AFFECTS AND 6120 04:57:39,120 --> 04:57:40,520 INTOXICANTS AND I KNOW WE'RE 6121 04:57:40,520 --> 04:57:41,760 EXCITED TO HAVE A DISCUSSION 6122 04:57:41,760 --> 04:57:43,400 HERE AND I WANT TO THINK ABOUT 6123 04:57:43,400 --> 04:57:47,720 HOW THE BRAIN AS A NON-LINEAR 6124 04:57:47,720 --> 04:57:49,680 ORGAN AND DEVELOPMENT REGIONALLY 6125 04:57:49,680 --> 04:57:49,920 SPECIFIC. 6126 04:57:49,920 --> 04:57:51,480 THESE ARE EXAMPLES AT THE TOP AT 6127 04:57:51,480 --> 04:57:54,080 THE CELLULAR LEVEL AND 6128 04:57:54,080 --> 04:57:55,360 FUNCTIONAL LEVEL AND AT THE 6129 04:57:55,360 --> 04:57:56,320 WHITE MATTER LEVEL. 6130 04:57:56,320 --> 04:57:58,680 WE SEE THE BRAIN IS DEVELOPING 6131 04:57:58,680 --> 04:58:00,520 AT DIFFERENT RATES AT DIFFERENT 6132 04:58:00,520 --> 04:58:00,760 PLACES. 6133 04:58:00,760 --> 04:58:05,120 THIS IS SOMETHING IMPORTANT TO 6134 04:58:05,120 --> 04:58:08,320 ATTEND TO AND THIS IS AN IMAGE 6135 04:58:08,320 --> 04:58:11,040 FROM A NATURALLY LOST CHILD 6136 04:58:11,040 --> 04:58:13,560 TOOTH WHERE WE'RE MAPPING OUT 6137 04:58:13,560 --> 04:58:14,720 LEVELS OF LEAD. 6138 04:58:14,720 --> 04:58:17,640 THE BABY TEETH BEGIN TO FORM 6139 04:58:17,640 --> 04:58:24,640 DURING WEEK 15 INFESTATION AND 6140 04:58:24,640 --> 04:58:26,200 HAVE RINGS LIKE A TREE AND WE 6141 04:58:26,200 --> 04:58:28,920 CAN LINK THEM UP TO HOW THE 6142 04:58:28,920 --> 04:58:34,320 CHILD DEVELOPS AND I HAVEN'T 6143 04:58:34,320 --> 04:58:35,720 SHOWN SPECIFIC TOPICS BUT THIS 6144 04:58:35,720 --> 04:58:41,200 IS THE GOAL UNDERSTANDING THE 6145 04:58:41,200 --> 04:58:48,920 EXPOSURES OF THE INDIVIDUAL WE 6146 04:58:48,920 --> 04:58:52,080 CAN MEASURE LEAD AT EVERY 6147 04:58:52,080 --> 04:58:55,720 PREGNANCY AND SEEING THE 6148 04:58:55,720 --> 04:58:58,440 TEMPORAL SAMPLING AND WHEN I 6149 04:58:58,440 --> 04:58:59,440 MEASURE A PARTICULAR PREDICTOR 6150 04:58:59,440 --> 04:59:01,360 IT MAY HAVE AN ASSOCIATION WITH 6151 04:59:01,360 --> 04:59:02,960 AN OUTCOME EXTERNALIZING 6152 04:59:02,960 --> 04:59:04,400 BEHAVIOR IN CHILDHOOD. 6153 04:59:04,400 --> 04:59:07,520 YOU HAVE ON THE VERTICAL AXIS 6154 04:59:07,520 --> 04:59:17,720 THE AGE AND YOU SEE MANGANESE IS 6155 04:59:17,720 --> 04:59:19,680 PREDICTIVE AND LEAD IS 6156 04:59:19,680 --> 04:59:20,760 PREDICTIVE OF LOWER EXECUTIVE 6157 04:59:20,760 --> 04:59:21,320 FUNCTION SCORES. 6158 04:59:21,320 --> 04:59:23,800 AND SOMETHING TO THINK ABOUT AS 6159 04:59:23,800 --> 04:59:25,920 WE TALK ABOUT THE DEVELOPMENT 6160 04:59:25,920 --> 04:59:27,120 PERSPECTIVE, WHAT IS OUR 6161 04:59:27,120 --> 04:59:28,400 POTENTIAL FOR SAMPLING. 6162 04:59:28,400 --> 04:59:30,680 THE CHARGE OF THIS PANEL AND 6163 04:59:30,680 --> 04:59:36,120 WE'LL TURN TO THIS NOW IS TO 6164 04:59:36,120 --> 04:59:43,160 BRIDGE THE LIFE SPAN PERSPECTIVE 6165 04:59:43,160 --> 04:59:46,640 HOW WE WEAVE THESE TOGETHER IN 6166 04:59:46,640 --> 04:59:49,040 IN EARLY LIFE THE PRESSURES ARE 6167 04:59:49,040 --> 04:59:52,280 DIFFERENT LATER AND WE'LL MOVE 6168 04:59:52,280 --> 04:59:54,040 THROUGH THE PRESSURES 6169 04:59:54,040 --> 04:59:55,800 POTENTIALLY HAVING A NOT-SMOOTH 6170 04:59:55,800 --> 04:59:56,440 FUNCTION. 6171 04:59:56,440 --> 04:59:57,640 THIS HAS COME UP IN SOME OTHER 6172 04:59:57,640 --> 04:59:59,520 TALKS BUT IT'S NOT LIKE WE'RE 6173 04:59:59,520 --> 05:00:00,320 GETTING A SMOOTH FUNCTION OVER 6174 05:00:00,320 --> 05:00:00,960 THE LIFE SPAN. 6175 05:00:00,960 --> 05:00:03,120 WE'RE LOOKING AT PERIODS WHERE 6176 05:00:03,120 --> 05:00:04,920 THERE'S BURSTS OF PLASTICITY, 6177 05:00:04,920 --> 05:00:06,280 PERIODS OF PROGRESSION AND 6178 05:00:06,280 --> 05:00:11,680 REGRESSION. 6179 05:00:11,680 --> 05:00:13,920 AN IT SEEMS TO ME THEY LINE UP 6180 05:00:13,920 --> 05:00:15,120 WITH SOCIAL TRANSITION. 6181 05:00:15,120 --> 05:00:16,960 WE THINK OF ADOLESCENTS, 6182 05:00:16,960 --> 05:00:18,400 PARENTHOOD WAS MENTIONED 6183 05:00:18,400 --> 05:00:18,720 EARLIER. 6184 05:00:18,720 --> 05:00:20,560 THERE'S ALSO CHANGES THAT HAPPEN 6185 05:00:20,560 --> 05:00:23,320 WHEN THE FAMILIES REORGANIZE AND 6186 05:00:23,320 --> 05:00:24,720 THE CHILDREN LEAVE THE HOME OR 6187 05:00:24,720 --> 05:00:25,200 IN RETIREMENT. 6188 05:00:25,200 --> 05:00:26,600 SO HOW DO WE THINK ABOUT THE 6189 05:00:26,600 --> 05:00:28,200 BRAIN IN THE CONTEXT OF THE 6190 05:00:28,200 --> 05:00:29,120 SOCIAL WORLD THAT PROGRAMS IT 6191 05:00:29,120 --> 05:00:33,200 AND HOW DO WE THINK ABOUT HOW WE 6192 05:00:33,200 --> 05:00:34,920 STUDIED ALL THESE WITH POTENTIAL 6193 05:00:34,920 --> 05:00:36,520 AND FINALLY ANOTHER TOPIC WE 6194 05:00:36,520 --> 05:00:38,640 WANT TO EXPLORE SOME OF WHICH 6195 05:00:38,640 --> 05:00:40,800 HAS COME UP IS SEX AND 6196 05:00:40,800 --> 05:00:41,880 DEMOGRAPHIC DIFFERENCES. 6197 05:00:41,880 --> 05:00:42,560 SOMETHING REALLY IMPORTANT FOR 6198 05:00:42,560 --> 05:00:45,280 US TO DO IN OUR STUDIES IS TO 6199 05:00:45,280 --> 05:00:48,160 THINK ABOUT NEURAL DIVERSITY AND 6200 05:00:48,160 --> 05:00:53,640 MAKE SURE THE PARTICIPANTS IN 6201 05:00:53,640 --> 05:00:56,040 OUR RESEARCH REPRESENT THE 6202 05:00:56,040 --> 05:00:59,120 DIFFERENCES IN THE PLANET AND 6203 05:00:59,120 --> 05:01:08,440 RESOURCES AND HEALTH DISPARITYIES 6204 05:01:08,440 --> 05:01:12,000 AND LOOKING AT THE TOPICS WITH 6205 05:01:12,000 --> 05:01:15,120 THE HIGHLY QUALIFIED GROUP OF 6206 05:01:15,120 --> 05:01:19,120 PEOPLE. 6207 05:01:19,120 --> 05:01:22,640 >> THANK YOU FOR SETTING UP THE 6208 05:01:22,640 --> 05:01:27,960 STAGE FOR THE DISCUSSION PERIOD 6209 05:01:27,960 --> 05:01:33,360 WE'RE ENTERING INTO. 6210 05:01:33,360 --> 05:01:34,520 AND THINKING OF PARTICIPANTS IN 6211 05:01:34,520 --> 05:01:36,040 THE VIRTUAL WORLD TO COME UP 6212 05:01:36,040 --> 05:01:40,320 WITH QUESTIONS YOU CAN PUT IN 6213 05:01:40,320 --> 05:01:41,320 THE CHAT AND DISCUSS THOSE AS 6214 05:01:41,320 --> 05:01:48,000 THEY COME ONLINE. 6215 05:01:48,000 --> 05:01:53,600 I HAVE QUESTION CAME IN PRIOR TO 6216 05:01:53,600 --> 05:01:59,800 THE MEETING TO GET OURSELVES 6217 05:01:59,800 --> 05:02:04,160 ENERGIZED IN DISCUSSION MODE. 6218 05:02:04,160 --> 05:02:05,680 AND CHALLENGING EACH OTHER AS 6219 05:02:05,680 --> 05:02:09,120 WELL AS RESPOND TO THE INPUTS 6220 05:02:09,120 --> 05:02:09,680 COMING FROM THE LARGER 6221 05:02:09,680 --> 05:02:12,280 COMMUNITY. 6222 05:02:12,280 --> 05:02:15,360 LET ME START WITH A QUESTION 6223 05:02:15,360 --> 05:02:18,280 THAT CAME UP IN ADVANCE OF THE 6224 05:02:18,280 --> 05:02:18,520 MEETING. 6225 05:02:18,520 --> 05:02:20,120 THE QUESTION I DON'T KNOW WHO 6226 05:02:20,120 --> 05:02:22,720 IT'S FROM BUT SAYS CAN WE BEGIN 6227 05:02:22,720 --> 05:02:26,040 TO USE NEUROIMAGING TECHNIQUES 6228 05:02:26,040 --> 05:02:28,080 COMBINED WITH PHENOTYPING TO 6229 05:02:28,080 --> 05:02:30,240 DETERMINE NEW BIOMARKERS AND 6230 05:02:30,240 --> 05:02:31,360 MILESTONES FOR DEVELOPMENT IN 6231 05:02:31,360 --> 05:02:34,160 COGNITIVE DECLINE. 6232 05:02:34,160 --> 05:02:37,160 HOW CAN INFORMATIVE BIOMARKERS 6233 05:02:37,160 --> 05:02:38,960 SERVE AS AN OUTCOME MEASURE AND 6234 05:02:38,960 --> 05:02:40,560 INTERVENTION STUDY WHICH IS 6235 05:02:40,560 --> 05:02:41,120 ACCEPTABLE TO REGULATORY 6236 05:02:41,120 --> 05:02:46,600 AGENCIES. 6237 05:02:46,600 --> 05:02:48,800 I'D LIKE TO ASK ALEXANDRA TO BE 6238 05:02:48,800 --> 05:02:51,880 THE FIRST TO RESPOND TO THAT 6239 05:02:51,880 --> 05:02:54,320 SINCE IT IS IN HER WHEELHOUSE SO 6240 05:02:54,320 --> 05:02:58,720 TO SPEAK. 6241 05:02:58,720 --> 05:03:01,720 >> WE STARTED LOOKING INTO 6242 05:03:01,720 --> 05:03:03,520 COMBINING BIOMARKERS IN 6243 05:03:03,520 --> 05:03:06,280 BEHAVIOR-BASED PHENOTYPES. 6244 05:03:06,280 --> 05:03:09,080 WE STARTED TO DEFINE A RISK 6245 05:03:09,080 --> 05:03:10,720 FACTOR IN THE CONTEXT OF 6246 05:03:10,720 --> 05:03:15,280 ALZHEIMER'S DISEASE THAT 6247 05:03:15,280 --> 05:03:18,280 INCLUDES GENOTYPE WITH AGE AND 6248 05:03:18,280 --> 05:03:22,520 SEX AND WE INTEGRATE THIS WITH 6249 05:03:22,520 --> 05:03:23,920 IMAGING WITH CORRELATION WHICH 6250 05:03:23,920 --> 05:03:26,320 BASICALLY RESULTS IN A RANK 6251 05:03:26,320 --> 05:03:29,120 ASSIGNED TO EACH OF THE RISK 6252 05:03:29,120 --> 05:03:30,760 FACTORS INCLUDING TRAITS OR 6253 05:03:30,760 --> 05:03:32,880 PHENOTYPES AND THESE ARE 6254 05:03:32,880 --> 05:03:34,360 GENERALIZABLE AND ON THE OTHER 6255 05:03:34,360 --> 05:03:35,400 SIZE TO BRAIN NETWORKS. 6256 05:03:35,400 --> 05:03:37,280 SO THIS IS MY APPROACH. 6257 05:03:37,280 --> 05:03:39,200 IT'S CERTAINLY NOT UNIQUE SO I 6258 05:03:39,200 --> 05:03:47,200 WELCOME OTHER COMMENTS. 6259 05:03:47,200 --> 05:03:51,120 >> ANYONE ELSE WANT TO CHIME IN 6260 05:03:51,120 --> 05:04:06,120 ON THIS ISSUE. 6261 05:04:06,120 --> 05:04:08,120 >> IT DEPENDS ON YOUR BIOMARKER. 6262 05:04:08,120 --> 05:04:11,120 CAN GET DOWN TO THE MOLECULAR 6263 05:04:11,120 --> 05:04:19,320 LEVEL. 6264 05:04:19,320 --> 05:04:20,360 WE HAVE USED THE DEEP 6265 05:04:20,360 --> 05:04:22,760 PHENOTYPING TO GET AT PHYSIOLOGY 6266 05:04:22,760 --> 05:04:25,440 AND HOW THE BRAIN REGULATES THE 6267 05:04:25,440 --> 05:04:27,400 PHYSIOLOGY AND USING PHYSIOLOGIC 6268 05:04:27,400 --> 05:04:28,760 MARKERS AS SOME OF THE 6269 05:04:28,760 --> 05:04:29,400 BIOMARKERS FOR WHAT'S HAPPENING 6270 05:04:29,400 --> 05:04:31,520 IN THE BRAIN. 6271 05:04:31,520 --> 05:04:33,920 AND SO THEY'RE ACCESSIBLE, FOR 6272 05:04:33,920 --> 05:04:35,080 EXAMPLE, BY BLOOD PANELS AND BY 6273 05:04:35,080 --> 05:04:38,280 CELLS. 6274 05:04:38,280 --> 05:04:46,360 ONE WAY TO GET AT IN THE NEVER 6275 05:04:46,360 --> 05:04:53,880 HUMAN BIOMARKERS IN ASSESSING 6276 05:04:53,880 --> 05:04:55,520 IMMUNE AND METABOLIC FUNCTION 6277 05:04:55,520 --> 05:04:56,960 AND VASCULAR FUNCTION AND LOOK 6278 05:04:56,960 --> 05:04:58,880 AT IT IN TANDEM WITH WHAT THE 6279 05:04:58,880 --> 05:04:59,480 BRAIN'S DOING WHILE WE IMAGE 6280 05:04:59,480 --> 05:05:00,920 THEM. 6281 05:05:00,920 --> 05:05:02,600 THAT'S ONE WAY WE DO THIS AND WE 6282 05:05:02,600 --> 05:05:09,600 DO IT ACROSS THE LIFE SPAN. 6283 05:05:09,600 --> 05:05:12,960 >> SO ONE OF THE THINGS THAT I 6284 05:05:12,960 --> 05:05:15,120 TEACH MY STUDENTS IN THE LAB IS 6285 05:05:15,120 --> 05:05:16,320 THAT WE DON'T HAVE A GROUND 6286 05:05:16,320 --> 05:05:19,800 TRUTH FOR THE FETUS. 6287 05:05:19,800 --> 05:05:23,440 SO A LOT OF TIMES THERE'S AI 6288 05:05:23,440 --> 05:05:26,680 TENDENCY TO ANTHROPOMORPHIZE THE 6289 05:05:26,680 --> 05:05:28,120 BRAIN AND UNDERSTAND THE 6290 05:05:28,120 --> 05:05:31,520 BEHAVIOR FROM OUR COGNITION AND 6291 05:05:31,520 --> 05:05:32,440 OBSERVATIONS AND PLAYS THESE 6292 05:05:32,440 --> 05:05:33,320 FUNCTION ON THE BRAIN BUT A 6293 05:05:33,320 --> 05:05:35,720 FETAL BRAIN IS TRYING TO DO A 6294 05:05:35,720 --> 05:05:38,240 DIFFERENT JOB THAN SAY EVEN AN 6295 05:05:38,240 --> 05:05:40,440 INFANT BRAIN OR AN AGING BRAIN 6296 05:05:40,440 --> 05:05:41,400 IS TRYING TO DO. 6297 05:05:41,400 --> 05:05:43,160 WHAT A PARTICULAR AREA OF THE 6298 05:05:43,160 --> 05:05:46,120 CORTEX MAY BE TRYING TO DO IN 6299 05:05:46,120 --> 05:05:49,640 THE FETUS MAY NOT LOOK LIKE ITS 6300 05:05:49,640 --> 05:05:50,640 FUTURE DESTINY. 6301 05:05:50,640 --> 05:05:51,960 I FIND A LOT I HAVE TO SEPARATE 6302 05:05:51,960 --> 05:05:54,360 THE STUDENTS FROM THE IDEA THE 6303 05:05:54,360 --> 05:05:55,480 AMYGDALA KNOWS WHAT IT'S GOING 6304 05:05:55,480 --> 05:05:57,480 TO DO IN THE FUTURE. 6305 05:05:57,480 --> 05:05:58,960 RIGHT, LIKE IT'S STILL THE SAME 6306 05:05:58,960 --> 05:05:59,200 SYSTEMS. 6307 05:05:59,200 --> 05:06:02,160 IT'S STILL WIRING UP TO HAVE THE 6308 05:06:02,160 --> 05:06:04,000 SAME FUNCTIONS BUT WE SHOULDN'T 6309 05:06:04,000 --> 05:06:11,400 NECESSARILY PUSH THESE CAN ONIC 6310 05:06:11,400 --> 05:06:14,000 ONICONI 6311 05:06:14,000 --> 05:06:14,680 ONICONI 6312 05:06:14,680 --> 05:06:19,120 ONIC -- CANONICAL VIEW VIEWS AND 6313 05:06:19,120 --> 05:06:20,320 SOME WILL SAY HOW CAN THIS 6314 05:06:20,320 --> 05:06:21,320 REGION BE DOING THIS THING AND 6315 05:06:21,320 --> 05:06:23,800 I'M SAYING, I DON'T KNOW IF IT'S 6316 05:06:23,800 --> 05:06:25,600 DOING THAT THING. 6317 05:06:25,600 --> 05:06:30,280 WE HAVE TO TEST OUR HIGH BOTH 6318 05:06:30,280 --> 05:06:32,720 THESE IN A MORE DATA-DRIVEN 6319 05:06:32,720 --> 05:06:33,720 APPROVE WHICH MAKES IT MORE 6320 05:06:33,720 --> 05:06:35,120 CHALLENGING TO STUDY THESE PARTS 6321 05:06:35,120 --> 05:06:43,440 OF DEVELOPMENT. 6322 05:06:43,440 --> 05:06:45,240 >> PERHAPS I DID NOT EXPLAIN 6323 05:06:45,240 --> 05:06:47,760 THINGS BECAUSE I HAVE A SHORT 6324 05:06:47,760 --> 05:06:50,240 TIME LIKE EVERYBODY ELSE. 6325 05:06:50,240 --> 05:06:53,440 BUT IN OUR PREDICTIVE MODELLING 6326 05:06:53,440 --> 05:06:54,560 APPROACHES AND I HAVEN'T SHOWN A 6327 05:06:54,560 --> 05:06:58,040 LOT OF RESULTS WE FOUND IF YOU 6328 05:06:58,040 --> 05:06:59,160 STUCK BIOMARKERS RELATED TO 6329 05:06:59,160 --> 05:07:02,600 BRAIN ATROPHY TO SIGNAL 6330 05:07:02,600 --> 05:07:07,120 INTENSITY AND SIGNAL ACTIVITY 6331 05:07:07,120 --> 05:07:09,240 BECAUSE REDUCING MANGANESE TAKEN 6332 05:07:09,240 --> 05:07:12,320 UP THROUGH CALCIUM CHANNELS AND 6333 05:07:12,320 --> 05:07:20,520 MAGNETIC SUSCEPTIBLE CAN BETTER 6334 05:07:20,520 --> 05:07:23,120 PREDICT THE TRAITS LIKE MEMORY 6335 05:07:23,120 --> 05:07:27,320 WE ASSESS THAN USING ANY SINGLE 6336 05:07:27,320 --> 05:07:38,560 BIOMARKER. 6337 05:07:38,560 --> 05:07:50,480 >> I'M A Ph.D. NEURO ANATAMIST 6338 05:07:50,480 --> 05:07:56,920 AND I GOT INVOLVED IN STUDYING 6339 05:07:56,920 --> 05:08:05,840 fMRI TO STUDY AUTISM AND WAS 6340 05:08:05,840 --> 05:08:11,520 NAIVE HOW COULD SEE AN AUTISTIC 6341 05:08:11,520 --> 05:08:14,480 CHILD -- IT SEEMED LIKE A SLAM 6342 05:08:14,480 --> 05:08:17,480 DUNK WE'D SEE BEHAVIORAL 6343 05:08:17,480 --> 05:08:21,200 DEFICITS AS PROFOUND AS AUTISM 6344 05:08:21,200 --> 05:08:23,160 COULD BE AND TWO DECADES LATER 6345 05:08:23,160 --> 05:08:24,800 THE FIELD IS STILL STRUGGLING TO 6346 05:08:24,800 --> 05:08:27,120 GET ANYTHING CONVINCING. 6347 05:08:27,120 --> 05:08:33,760 THERE'S A LOT OF IDEAS BUT WE'VE 6348 05:08:33,760 --> 05:08:39,120 RAN UP AGAINST THE HURDLES OF 6349 05:08:39,120 --> 05:08:41,280 TECHNICAL ARTIFACTS LIKE 6350 05:08:41,280 --> 05:08:42,280 AUTISTIC KIDS TEND TO WIGGLE 6351 05:08:42,280 --> 05:08:46,480 MORE IN THE SCANNER AND WE HAVE 6352 05:08:46,480 --> 05:08:48,160 COME TO THE REALIZATION THAT 6353 05:08:48,160 --> 05:08:50,040 AUTISM IS BY NO MEANS A SINGLE 6354 05:08:50,040 --> 05:08:51,720 DISORDER OF DISEASE IT'S A 6355 05:08:51,720 --> 05:08:55,120 SPECTRUM MUCH BETTER CALLED THAT 6356 05:08:55,120 --> 05:08:57,120 THAT IS VERY MULTI-DIMENSIONAL 6357 05:08:57,120 --> 05:08:59,120 AND ONE AUTISTIC BRAIN IS NOT 6358 05:08:59,120 --> 05:09:01,320 GOING TO BE LIKE ANOTHER ONE. 6359 05:09:01,320 --> 05:09:04,560 WE HAVE TO FACTOR IN THE 6360 05:09:04,560 --> 05:09:05,400 INCREDIBLE INDIVIDUAL 6361 05:09:05,400 --> 05:09:08,160 VARIABILITY THAT I TOUCHED UPON 6362 05:09:08,160 --> 05:09:12,520 AND OTHERS HAVE MENTIONED TODAY. 6363 05:09:12,520 --> 05:09:15,840 AND THEN THE HARSH REALITY ALSO 6364 05:09:15,840 --> 05:09:21,720 IS THAT THE OBSERVATIONS WE MAKE 6365 05:09:21,720 --> 05:09:27,200 ABOUT USING TRACTS TO IDENTIFY 6366 05:09:27,200 --> 05:09:28,720 STRUCTURAL CONNECTIVITY IT'S AN 6367 05:09:28,720 --> 05:09:31,160 ESTIMATE OF PATTERNS OF CONNECTS 6368 05:09:31,160 --> 05:09:32,320 BUT AS WE'VE SEEN ALREADY THE 6369 05:09:32,320 --> 05:09:34,640 NUMBER OF WAYS IN WHICH ONE 6370 05:09:34,640 --> 05:09:38,560 COULD HAVE FALSE POSITIVES AND 6371 05:09:38,560 --> 05:09:39,600 FALSE NEGATIVES IN CURRENT TOP 6372 05:09:39,600 --> 05:09:47,920 OGRAPHY -- TOPOGRAPHY DATA IS 6373 05:09:47,920 --> 05:09:49,920 LARGE AND WE HAVE FUNCTIONAL 6374 05:09:49,920 --> 05:09:51,720 CONNECTIVITY BUT THOSE ARE A 6375 05:09:51,720 --> 05:09:53,800 LONG WAYS FROM ANATOMICAL 6376 05:09:53,800 --> 05:09:54,120 CONNECTIONS. 6377 05:09:54,120 --> 05:09:56,720 THE SOBERING REALITY IS THAT 6378 05:09:56,720 --> 05:09:59,680 IT'S AN IMMENSELY COMPLEX 6379 05:09:59,680 --> 05:10:00,320 PROBLEM. 6380 05:10:00,320 --> 05:10:01,840 I'M STILL AN OPTIMIST BUT NOT 6381 05:10:01,840 --> 05:10:03,320 WITH A SENSE THAT WE'RE A YEAR 6382 05:10:03,320 --> 05:10:06,960 OR TWO AWAY FROM MAKING A 6383 05:10:06,960 --> 05:10:08,720 DRAMATIC EVENT BUT RATHER THAT 6384 05:10:08,720 --> 05:10:11,520 WE NEED TO ABSOLUTELY PERSEVERE 6385 05:10:11,520 --> 05:10:13,640 AND ABSOLUTELY PUSH TO THE 6386 05:10:13,640 --> 05:10:18,040 LIMITS TO GET BETTER DATA, 6387 05:10:18,040 --> 05:10:22,840 BETTER ANALYZED AND BETTER 6388 05:10:22,840 --> 05:10:24,680 SHARED ASSESSED IN RELATION TO 6389 05:10:24,680 --> 05:10:27,080 COMPLEX DISORDERS. 6390 05:10:27,080 --> 05:10:29,320 I WAS PARTICULARLY AMONG THE 6391 05:10:29,320 --> 05:10:31,080 MANY FASCINATING PRESENTATIONS 6392 05:10:31,080 --> 05:10:35,880 WE HEARD OVER THE DAY I WAS 6393 05:10:35,880 --> 05:10:39,160 PARTICULARLY IMPRESSED ON THE 6394 05:10:39,160 --> 05:10:45,840 ADVANCED MADE IN GETTING HIGHER 6395 05:10:45,840 --> 05:10:49,000 QUALITY, FASTER, ACQUISITION, 6396 05:10:49,000 --> 05:10:53,840 HIGHER RELEVANT SCANNING IS ONE 6397 05:10:53,840 --> 05:10:59,000 WAY IN WHICH CONTINUED POUNDING 6398 05:10:59,000 --> 05:11:05,960 HARD ON METHODOLOGICAL ADVANCES 6399 05:11:05,960 --> 05:11:07,240 EXTEND THE FIELD FORWARD AND 6400 05:11:07,240 --> 05:11:10,440 THAT'S MY VIEW ON BIOMARKERS. 6401 05:11:10,440 --> 05:11:11,120 JILL. 6402 05:11:11,120 --> 05:11:15,120 >> THERE'S ALSO THE ROLE OF 6403 05:11:15,120 --> 05:11:16,520 CONVERGENCE OF USING DIFFERENT 6404 05:11:16,520 --> 05:11:18,800 LEVELS OF ANALYSIS WHETHER WE 6405 05:11:18,800 --> 05:11:20,120 WORK WITH BASIC SCIENTISTS 6406 05:11:20,120 --> 05:11:21,440 WHETHER WE WORK AT ONE LEVEL OF 6407 05:11:21,440 --> 05:11:23,920 ANALYSIS AND WE TRY TO TAKE 6408 05:11:23,920 --> 05:11:24,240 INFORMATION. 6409 05:11:24,240 --> 05:11:26,160 WE LEARN ABOUT MECHANISMS FROM 6410 05:11:26,160 --> 05:11:28,360 THEM AND TEST IT AT THE HUMAN 6411 05:11:28,360 --> 05:11:30,720 LEVEL AND VICE VERSA. 6412 05:11:30,720 --> 05:11:32,920 I THINK USING MULTIPLE 6413 05:11:32,920 --> 05:11:35,120 STRATEGIES TO TACKLE THESE 6414 05:11:35,120 --> 05:11:36,560 ISSUES OF QUESTIONS OF 6415 05:11:36,560 --> 05:11:39,440 BIOMARKERS AND THE TIMING OF 6416 05:11:39,440 --> 05:11:42,800 THOSE BIOMARKERS WHICH IS A 6417 05:11:42,800 --> 05:11:43,960 CRITICAL DEVELOPING THERAPEUTICS 6418 05:11:43,960 --> 05:11:47,680 AT DIFFERENT POINTS ACROSS THE 6419 05:11:47,680 --> 05:11:50,720 LIFE SPAN WILL BE AN IMPORTANT 6420 05:11:50,720 --> 05:11:56,360 TOOL WE CAN USE NOW WHILE WE 6421 05:11:56,360 --> 05:12:01,880 WAIT FOR HIGHER LEVEL 6422 05:12:01,880 --> 05:12:04,640 TECHNOLOGIC ADVANCES OF IMAGING 6423 05:12:04,640 --> 05:12:05,720 ACROSS THE LIFE SPAN. 6424 05:12:05,720 --> 05:12:06,760 >> THANK YOU. 6425 05:12:06,760 --> 05:12:07,840 LET ME MOVE TO ANOTHER QUESTION 6426 05:12:07,840 --> 05:12:08,600 THAT CAME IN. 6427 05:12:08,600 --> 05:12:11,800 WHAT ARE METHODS WE CAN USE TO 6428 05:12:11,800 --> 05:12:13,960 APPROACH CO-MORBIDITY WHEN 6429 05:12:13,960 --> 05:12:15,160 STUDYING HOW BEHAVIOR CHANGES 6430 05:12:15,160 --> 05:12:17,320 RELATE TO STRUCTURAL AND 6431 05:12:17,320 --> 05:12:18,440 FUNCTIONAL CHANGES TO BRAIN AS 6432 05:12:18,440 --> 05:12:20,240 WE AGE. 6433 05:12:20,240 --> 05:12:23,760 I HAVE MY FINGER FIRST POINTED 6434 05:12:23,760 --> 05:12:26,640 TO JILL, GIVEN YOUR INTEREST IN 6435 05:12:26,640 --> 05:12:28,840 COMORBIDITIES CAN YOU TAKE A 6436 05:12:28,840 --> 05:12:29,920 STAB AT THAT? 6437 05:12:29,920 --> 05:12:32,720 >> YES. 6438 05:12:32,720 --> 05:12:33,920 AND THEY WERE ASKING ABOUT 6439 05:12:33,920 --> 05:12:39,720 SHARED PATHOPHYSIOLOGY ACROSS 6440 05:12:39,720 --> 05:12:45,920 THESE. 6441 05:12:45,920 --> 05:12:47,120 I DID NOT PUT THE QUESTION IN 6442 05:12:47,120 --> 05:12:48,000 THE QUESTION BANK. 6443 05:12:48,000 --> 05:12:49,760 IT'S A FANTASTIC QUESTION. 6444 05:12:49,760 --> 05:12:54,240 I THINK IT'S UNDER STUDIED BUT 6445 05:12:54,240 --> 05:12:56,920 OF COURSE THE COMORBIDITY OF 6446 05:12:56,920 --> 05:12:58,240 PSYCHIATRIC DISORDER WITH 6447 05:12:58,240 --> 05:13:00,440 GENERAL MEDICINE IS JUST HUGE. 6448 05:13:00,440 --> 05:13:03,120 ALL YOU HAVE TO DO IS LOOK AT 6449 05:13:03,120 --> 05:13:06,280 SIDE EFFECTS OF PSYCHIATRIC 6450 05:13:06,280 --> 05:13:09,200 MEDICINES ON OTHER SYSTEMS, THE 6451 05:13:09,200 --> 05:13:11,520 GUT AND THE HEART AND THE LIVER 6452 05:13:11,520 --> 05:13:16,120 AND ALL SORTS OF ORGAN SYMPTOMS 6453 05:13:16,120 --> 05:13:19,120 TO KNOW COMORBIDITY DOES EXIST 6454 05:13:19,120 --> 05:13:21,080 BUT MEDICINE HAS GROWN UP IN 6455 05:13:21,080 --> 05:13:23,680 SILOS AND THAT IS SORT OF HOW 6456 05:13:23,680 --> 05:13:27,760 NOT ONLY MEDICINE HAS GROWN OUT 6457 05:13:27,760 --> 05:13:29,080 UP BUT HOW WE DEVELOP 6458 05:13:29,080 --> 05:13:30,120 THERAPEUTIC TO ONE ORGAN SYSTEM. 6459 05:13:30,120 --> 05:13:32,120 I THINK REALLY BRINGING IN ONE 6460 05:13:32,120 --> 05:13:33,520 OF THAT'S ONE OF THE REASONS WE 6461 05:13:33,520 --> 05:13:37,160 TALK ABOUT THE HEART AND HOW THE 6462 05:13:37,160 --> 05:13:39,360 BRAIN REGULATES THE HEART AND IT 6463 05:13:39,360 --> 05:13:41,080 TURNS OUT IT DOESN'T ONLY 6464 05:13:41,080 --> 05:13:46,920 REGULATE THE HEART ELECTRICALLY 6465 05:13:46,920 --> 05:13:50,280 TO THE VAGUS NERVE BUT IT GOES 6466 05:13:50,280 --> 05:13:54,120 TO THE GUT AND THE AXIS AND 6467 05:13:54,120 --> 05:13:56,280 PEOPLE ARE STUDYING NOW. 6468 05:13:56,280 --> 05:13:57,200 IT'S IMPORTANT WE BELIEVE 6469 05:13:57,200 --> 05:13:58,520 VARIABILITY IN THE FUNCTIONING 6470 05:13:58,520 --> 05:14:02,280 OF THESE AND THE REGULATION OF 6471 05:14:02,280 --> 05:14:03,160 THESE CIRCUITS NOT ONLY DIFFERS 6472 05:14:03,160 --> 05:14:07,240 BY SEX WHICH WE STUDY OF COURSE 6473 05:14:07,240 --> 05:14:09,440 BUT ALSO HAS DIFFERENTIAL 6474 05:14:09,440 --> 05:14:15,120 AFFECTS ON THE DIFFERENT ORGAN 6475 05:14:15,120 --> 05:14:15,880 SYSTEMS. 6476 05:14:15,880 --> 05:14:18,080 BRINGING IN ORGAN SYSTEM THE 6477 05:14:18,080 --> 05:14:20,440 FAVORITE BRAIN REGIONS ARE 6478 05:14:20,440 --> 05:14:26,080 REGULATING WE BELIEVE IS REALLY 6479 05:14:26,080 --> 05:14:29,120 CRITICAL TO UNDERSTANDING AU THE 6480 05:14:29,120 --> 05:14:30,080 BODY AND BRAIN DELIVER. 6481 05:14:30,080 --> 05:14:36,280 >> DO YOU WANT TO EXPAND ON 6482 05:14:36,280 --> 05:14:36,920 THAT? 6483 05:14:36,920 --> 05:14:39,680 >> I WANT TO TALK ABOUT THE 6484 05:14:39,680 --> 05:14:44,120 COMORBIDITIES OF OTHER ORGAN 6485 05:14:44,120 --> 05:14:48,520 SYMPTOMS AND HOW TO THEY AFFECT 6486 05:14:48,520 --> 05:14:51,640 BRAIN AND IF PERIPHERAL TISSUE 6487 05:14:51,640 --> 05:14:55,120 IS INJURED AND THE SYSTEMIC 6488 05:14:55,120 --> 05:14:58,040 ENVIRONMENT IS ALSO OLD AND 6489 05:14:58,040 --> 05:15:04,720 ELEVATION OF SENESCENT CELLS AND 6490 05:15:04,720 --> 05:15:07,200 PERHAPS OTHER PATHOLOGICAL 6491 05:15:07,200 --> 05:15:09,720 ORGANS AND CAN HELP UNDERSTAND 6492 05:15:09,720 --> 05:15:13,800 PROGRESSION THROUGH LIFE. 6493 05:15:13,800 --> 05:15:15,720 >> THANK YOU. 6494 05:15:15,720 --> 05:15:16,760 MARISA DO YOU WANT TO ADD 6495 05:15:16,760 --> 05:15:18,320 ANYTHING TO THE TOPIC OF 6496 05:15:18,320 --> 05:15:31,120 COMORBIDITIES? 6497 05:15:31,120 --> 05:15:33,720 >> AS MORIAH WAS SAYING IN EARLY 6498 05:15:33,720 --> 05:15:36,040 DEVELOPMENT WE DON'T NECESSARILY 6499 05:15:36,040 --> 05:15:40,400 KNOW WHAT BRAIN REGION IS 6500 05:15:40,400 --> 05:15:41,880 ASSOCIATED WITH WHAT PARTICULAR 6501 05:15:41,880 --> 05:15:43,400 FUNCTION IN EARLY DEVELOPMENT 6502 05:15:43,400 --> 05:15:46,200 AND SIMILARLY WHEN WE'RE WORKING 6503 05:15:46,200 --> 05:15:48,840 WITH INFANTS, WE DON'T 6504 05:15:48,840 --> 05:15:51,320 NECESSARILY KNOW THAT THEY'LL GO 6505 05:15:51,320 --> 05:15:54,080 ON TO HAVE A PARTICULAR 6506 05:15:54,080 --> 05:15:56,560 PSYCHIATRIC DISORDER OR WHETHER 6507 05:15:56,560 --> 05:15:59,120 THEY'LL HAVE COMORBID DISORDERS. 6508 05:15:59,120 --> 05:16:02,120 OUR APPROACH WHERE WE'RE LOOKING 6509 05:16:02,120 --> 05:16:05,480 AT A DIFFERENT SYSTEM SUCH AS 6510 05:16:05,480 --> 05:16:06,120 BEHAVIORAL REGULATION AND 6511 05:16:06,120 --> 05:16:07,640 FOCUSSING ON SORT OF THE 6512 05:16:07,640 --> 05:16:09,800 FUNCTIONAL DEVELOPMENT AND 6513 05:16:09,800 --> 05:16:12,200 NOTALLY PUTTING IT INTO POCKETS 6514 05:16:12,200 --> 05:16:14,120 OF DISEASE AND I'M NOT SAYING 6515 05:16:14,120 --> 05:16:19,200 THAT WILL NECESSARILY WORK WITH 6516 05:16:19,200 --> 05:16:20,440 ADULTS ACROSS THE LIFE SPAN BUT 6517 05:16:20,440 --> 05:16:21,920 IT'S AN APPROACH THAT HAS WORKED 6518 05:16:21,920 --> 05:16:23,800 AND ONCE WE STARTED TO BUILD 6519 05:16:23,800 --> 05:16:25,600 AROUND THE FRAMEWORK I THINK THE 6520 05:16:25,600 --> 05:16:30,320 WORK HAS MADE IT MORE SENSE THAN 6521 05:16:30,320 --> 05:16:31,960 IF WE HAD MORE IMPACTFUL 6522 05:16:31,960 --> 05:16:32,240 FINDINGS. 6523 05:16:32,240 --> 05:16:34,360 >> CAN I MAKE ONE MORE COMMENT? 6524 05:16:34,360 --> 05:16:35,120 >> PLEASE. 6525 05:16:35,120 --> 05:16:36,760 >> I'M ACTUALLY RATHER EXCITED 6526 05:16:36,760 --> 05:16:42,320 THAT WE'RE LEARNING ABOUT 6527 05:16:42,320 --> 05:16:43,040 COMORBIDI 6528 05:16:43,040 --> 05:16:45,480 COMORBIDITIES SOME WE'VE KNOWN A 6529 05:16:45,480 --> 05:16:47,600 LOT FOR A TIME BUT PERHAPS 6530 05:16:47,600 --> 05:16:49,800 HAVEN'T DONE ENOUGH AS A 6531 05:16:49,800 --> 05:16:50,920 COMMUNITY TO ADDRESS THOSE AND 6532 05:16:50,920 --> 05:16:52,880 I'M TALKING ABOUT THE CONTEXT OF 6533 05:16:52,880 --> 05:16:53,800 ALZHEIMER'S DISEASE WHICH ARE 6534 05:16:53,800 --> 05:16:56,080 LATE ONSET TYPE OF DISEASE. 6535 05:16:56,080 --> 05:17:04,920 HOWEVER, WE KNOW HYPERTENSION, 6536 05:17:04,920 --> 05:17:13,160 AR THEIRO -- ATHEROCLEROSIS I 6537 05:17:13,160 --> 05:17:17,240 CAN HAPPEN EARLY ON AND 6538 05:17:17,240 --> 05:17:18,120 REPURPOSING DRUGS CAN BE USED 6539 05:17:18,120 --> 05:17:22,080 LATER FOR THE DISEASES OF OLD 6540 05:17:22,080 --> 05:17:22,240 AGE. 6541 05:17:22,240 --> 05:17:23,520 I THINK THERE'S OPPORTUNITIES 6542 05:17:23,520 --> 05:17:36,760 THAT SHOULD BE EXPLOITED. 6543 05:17:36,760 --> 05:17:41,600 >> HOW CAN WE HAVE MODELLING AT 6544 05:17:41,600 --> 05:17:42,360 MULTI-SCALE. 6545 05:17:42,360 --> 05:17:46,720 THIS IS A QUESTION THAT CAME UP 6546 05:17:46,720 --> 05:17:57,560 IN THE PRECEDING SCLUGS 6547 05:18:00,120 --> 05:18:01,520 AND ONE WAY TO BRING THAT INTO 6548 05:18:01,520 --> 05:18:02,920 THE DISCUSSION IS BRIDGING THE 6549 05:18:02,920 --> 05:18:05,560 GAP NOT SO MUCH BETWEEN EARLY 6550 05:18:05,560 --> 05:18:08,720 DEVELOPMENT IN AGING BUT BETWEEN 6551 05:18:08,720 --> 05:18:12,680 MACRO CONNECTOMES AND MESO 6552 05:18:12,680 --> 05:18:16,920 CONNECTOMES AND MICROCONNECTOMES 6553 05:18:16,920 --> 05:18:19,200 WE HEARD SPECTACULAR PROGRESS ON 6554 05:18:19,200 --> 05:18:20,960 EARLIER BUT STILL A WIDE RANGE 6555 05:18:20,960 --> 05:18:24,280 BETWEEN THOSE DOMAINS. 6556 05:18:24,280 --> 05:18:26,600 ANY THOUGHTS? 6557 05:18:26,600 --> 05:18:28,080 >> MORIAH. 6558 05:18:28,080 --> 05:18:29,920 >> ANOTHER PLACE WHERE IT'S BEEN 6559 05:18:29,920 --> 05:18:32,200 HELPFUL AND YOU MENTIONED DATA 6560 05:18:32,200 --> 05:18:34,080 SHARING AS BEING AN IMPORTANT 6561 05:18:34,080 --> 05:18:36,520 STEP FOR MOVING THE SCIENCE 6562 05:18:36,520 --> 05:18:38,520 FORWARD, DR. VAN ESSEN, I SEE IT 6563 05:18:38,520 --> 05:18:40,520 HELPING IN TWO WAYS. 6564 05:18:40,520 --> 05:18:43,120 ONE IN UNDERSTANDING THE 6565 05:18:43,120 --> 05:18:45,800 FUNDAMENTAL BIOLOGICAL QUESTIONS 6566 05:18:45,800 --> 05:18:49,280 THAT IS MUCH OF THE FOCUS WE'RE 6567 05:18:49,280 --> 05:18:51,760 TALKING ABOUT TODAY AND TWO IS 6568 05:18:51,760 --> 05:18:55,120 TO AID OUR METHODOLOGIES AND AS 6569 05:18:55,120 --> 05:18:57,320 AN EXAMPLE, IN MY LAB WE'VE 6570 05:18:57,320 --> 05:18:58,800 FACED THE CHALLENGE OF 6571 05:18:58,800 --> 05:19:00,360 EXTRACTING THE FETAL BRAIN FROM 6572 05:19:00,360 --> 05:19:01,960 THE SURROUNDING TISSUE WHICH 6573 05:19:01,960 --> 05:19:03,680 SOUNDS VERY BASIC BUT WHEN 6574 05:19:03,680 --> 05:19:05,960 YOU'RE TRYING TO REMOVE 360 6575 05:19:05,960 --> 05:19:09,120 INDIVIDUAL TIME POINTS THAT ARE 6576 05:19:09,120 --> 05:19:12,960 THREE-DIMENSIONAL IT'S A BIG 6577 05:19:12,960 --> 05:19:16,320 PROBLEM WE USED DEEP LEARNING TO 6578 05:19:16,320 --> 05:19:17,520 DO THAT EXTRACTION PROCESS 6579 05:19:17,520 --> 05:19:17,760 ITSELF. 6580 05:19:17,760 --> 05:19:19,600 SO IT'S GOING TO SPEED UP THE 6581 05:19:19,600 --> 05:19:22,040 SCIENCE BECAUSE WE NOW ARE ABLE 6582 05:19:22,040 --> 05:19:23,520 TO KIND OF BYPASS SOME OF THE 6583 05:19:23,520 --> 05:19:29,000 THINGS WE COULDN'T DO AND I KNOW 6584 05:19:29,000 --> 05:19:31,920 THAT APPLIES TO A LOT OF THE 6585 05:19:31,920 --> 05:19:34,760 TALKS AND HOW WE'VE ACCELERATED 6586 05:19:34,760 --> 05:19:36,520 OUR ABILITY TO ANALYZE THE DATA 6587 05:19:36,520 --> 05:19:39,120 IN MORE OBJECTIVE WAYS AND MORE 6588 05:19:39,120 --> 05:19:39,480 RAPIDLY. 6589 05:19:39,480 --> 05:19:40,320 IT'S TWO THINGS THAT IT'S GOING 6590 05:19:40,320 --> 05:19:42,840 TO DO FOR US AND CONTINUE TO DO 6591 05:19:42,840 --> 05:19:45,440 IS ONE OUR METHODOLOGIES AND TWO 6592 05:19:45,440 --> 05:19:46,560 IS TO ACTUALLY ANSWER DEEPER 6593 05:19:46,560 --> 05:19:56,200 QUESTIONS ABOUT BIOLOGY. 6594 05:19:56,200 --> 05:20:02,640 >> I'D LIKE TO ADD ANOTHER LAYER 6595 05:20:02,640 --> 05:20:05,360 THAT AND HOW TO USE SOME OF THE 6596 05:20:05,360 --> 05:20:06,920 TECHNOLOGIES OVER TIME WITHIN 6597 05:20:06,920 --> 05:20:07,800 THE SAME INDIVIDUAL WHICH IS 6598 05:20:07,800 --> 05:20:10,560 WHAT WE DO AND THIS IS A BIG 6599 05:20:10,560 --> 05:20:15,000 CHALLENGE FOR AN IMAGEER LIKE 6600 05:20:15,000 --> 05:20:17,640 OUR LAB WHICH IS IF YOU HAVE 6601 05:20:17,640 --> 05:20:22,440 RECRUITED PEOPLE INTO THE 6602 05:20:22,440 --> 05:20:23,120 LONGITUDINAL STUDIES AND NOW IN 6603 05:20:23,120 --> 05:20:25,840 THEIR 20s AND 30s AND NOW 6604 05:20:25,840 --> 05:20:29,120 THEY'RE 50 AND 60 OVER THE LAST 6605 05:20:29,120 --> 05:20:32,280 20 ODD YEARS THE METHODOLOGIES 6606 05:20:32,280 --> 05:20:35,080 HAVE CHANGED. 6607 05:20:35,080 --> 05:20:37,240 IF YOU START WITH THE 1.5T AND 6608 05:20:37,240 --> 05:20:38,840 NOW WE'RE UP TO 7 I LOVED THE 6609 05:20:38,840 --> 05:20:39,400 TALK. 6610 05:20:39,400 --> 05:20:40,920 I WAS TRYING TO LOOK THROUGH MY 6611 05:20:40,920 --> 05:20:46,320 NOTES QUICKLY TO SEE WHICH 6612 05:20:46,320 --> 05:20:53,240 PERSON HAD DESCRIBED IT OF AND 6613 05:20:53,240 --> 05:20:57,080 HOW TO MERGE THAT WITH THE 3T 6614 05:20:57,080 --> 05:20:59,040 TESLA AND INTERESTED THERE WERE 6615 05:20:59,040 --> 05:21:01,120 NEW METHODOLOGIES AROUND DO THAT 6616 05:21:01,120 --> 05:21:03,240 BUT NEED THAT KIND OF WORK TO BE 6617 05:21:03,240 --> 05:21:04,760 FOLLOWING THE SAME INDIVIDUAL 6618 05:21:04,760 --> 05:21:05,840 BECAUSE THAT'S REALLY WHERE 6619 05:21:05,840 --> 05:21:11,240 YOU'RE GOING TO SEE SOME OF THE 6620 05:21:11,240 --> 05:21:17,200 EARLY BIOMARKERS, FOR EXAMPLE 6621 05:21:17,200 --> 05:21:19,120 THEY WERE TALKING ABOUT FOR 6622 05:21:19,120 --> 05:21:20,320 ALZHEIMER'S DISEASE LATER IN 6623 05:21:20,320 --> 05:21:22,520 LIFE SINCE WE KNOW 15 TO 20 6624 05:21:22,520 --> 05:21:25,520 YEARS EARLIER ARE THE PRE 6625 05:21:25,520 --> 05:21:27,080 CURSORS TO ALZHEIMER'S DISEASE. 6626 05:21:27,080 --> 05:21:29,160 THAT'S WHERE WE WANT TO BE 6627 05:21:29,160 --> 05:21:30,280 FOCUSSING FOR OUR THERAPEUTICS. 6628 05:21:30,280 --> 05:21:35,800 SO HOW DO WE DO THAT IN A 6629 05:21:35,800 --> 05:21:36,720 TECHNOLOGIC WAY AND IT'S 6630 05:21:36,720 --> 05:21:39,880 IMPORTANT AS AN IMAGEER THAT WE 6631 05:21:39,880 --> 05:21:45,440 HAVE PEOPLE FOCUSSING ON THAT. 6632 05:21:45,440 --> 05:21:48,120 I'D LOVE PEOPLE TO CONTACT ME IF 6633 05:21:48,120 --> 05:21:50,520 THEY HAVE APPROACHES FOR DOING 6634 05:21:50,520 --> 05:21:52,240 THIS SINCE WE HAVE 1.5 AND 3T 6635 05:21:52,240 --> 05:21:54,560 DATA IN THE SAME INDIVIDUALS IN 6636 05:21:54,560 --> 05:21:56,160 THE COHORT. 6637 05:21:56,160 --> 05:22:01,000 >> JILL, THERE'S SOMETHING I CAN 6638 05:22:01,000 --> 05:22:04,840 TELL YOU WHICH IS HYPER FINE 6639 05:22:04,840 --> 05:22:07,000 THIS LOW-FIELD MRI IMAGING IS 6640 05:22:07,000 --> 05:22:09,280 PICKING UP NOW AS A REMARKABLE 6641 05:22:09,280 --> 05:22:11,240 TOOL AND THERE'S INCREDIBLE WORK 6642 05:22:11,240 --> 05:22:12,320 BEING DONE THERE I THINK WOULD 6643 05:22:12,320 --> 05:22:20,120 BE IMPORTANT TO YOU. 6644 05:22:20,120 --> 05:22:22,320 >> THAT LEADS US TO ANOTHER 6645 05:22:22,320 --> 05:22:23,880 QUESTION THAT WAS OPPOSED WHICH 6646 05:22:23,880 --> 05:22:35,080 IS SHOULD WE BE EMPHASIZING 6647 05:22:35,080 --> 05:22:38,480 LONGITUDINAL STUDIES OR 6648 05:22:38,480 --> 05:22:39,520 CROSS-SECTIONAL AND YOUR 6649 05:22:39,520 --> 05:22:43,120 PERSPECTIVE ON THE STRENGTHS AND 6650 05:22:43,120 --> 05:22:43,880 LIMITATIONS. 6651 05:22:43,880 --> 05:22:45,800 JILL, YOU POINTED OUT ONE OF THE 6652 05:22:45,800 --> 05:22:47,400 CHALLENGES BUT WHERE THERE'S 6653 05:22:47,400 --> 05:22:50,240 HOPE FOR GETTING AT LEAST PART 6654 05:22:50,240 --> 05:22:53,760 WAY AROUND SOME OF THE 6655 05:22:53,760 --> 05:22:59,120 LIMITATIONS OF TECHNOLOGY NOT 6656 05:22:59,120 --> 05:23:07,520 DRIFT BUT TECHNOLOGY ADVANCES. 6657 05:23:07,520 --> 05:23:09,520 YOUR THOUGHTS ON THE AXIS. 6658 05:23:09,520 --> 05:23:12,200 >> I AGREE BOTH APPROACH ARE 6659 05:23:12,200 --> 05:23:15,120 REALLY IMPORTANT AND FROM A 6660 05:23:15,120 --> 05:23:16,200 CROSS-SECTIONAL POINT OF VIEW 6661 05:23:16,200 --> 05:23:20,600 YOU CAN INCORPORATE LARGER DATA 6662 05:23:20,600 --> 05:23:23,120 SETS AND USING THE DATA MINING 6663 05:23:23,120 --> 05:23:24,760 AND MACHINE LEARNING STRATEGIES 6664 05:23:24,760 --> 05:23:25,920 IN THE LARGE SAMPLES. 6665 05:23:25,920 --> 05:23:27,600 BUT THERE REALLY IS AN IMPORTANT 6666 05:23:27,600 --> 05:23:28,240 VALUE TO FOLLOWING PEOPLE OVER 6667 05:23:28,240 --> 05:23:31,480 TIME. 6668 05:23:31,480 --> 05:23:32,960 AND ONE OF THE OBVIOUS ONES IS 6669 05:23:32,960 --> 05:23:38,160 THAT IT'S AN AMAZING CONTROL FOR 6670 05:23:38,160 --> 05:23:40,200 CONFOUNDING AND THAT'S REALLY 6671 05:23:40,200 --> 05:23:42,120 CRITICAL IN UNDERSTANDING 6672 05:23:42,120 --> 05:23:43,120 BECAUSE WE KNOW THE BRAIN 6673 05:23:43,120 --> 05:23:44,040 CHANGES BASED ON LOTS OF THINGS 6674 05:23:44,040 --> 05:23:48,320 HAPPENING IN THE ENVIRONMENT. 6675 05:23:48,320 --> 05:23:50,520 SO REALLY HAVING THE SAME PERSON 6676 05:23:50,520 --> 05:23:53,560 IMAGED OVER TIME JUST A GIFT 6677 05:23:53,560 --> 05:23:55,160 FROM REALLY SEEING INDIVIDUAL 6678 05:23:55,160 --> 05:23:57,200 VARIABILITY AND BEING ABLE TO 6679 05:23:57,200 --> 05:23:59,720 UNDERSTAND THAT WITHOUT SOME AND 6680 05:23:59,720 --> 05:24:02,120 DOING IT WITHIN A COHORT THAT'S 6681 05:24:02,120 --> 05:24:03,680 A CERTAIN AGE RANGE AGAIN SO 6682 05:24:03,680 --> 05:24:05,520 YOUR FOLLOWING A CERTAIN AGE 6683 05:24:05,520 --> 05:24:06,760 RANGE OVER TIME AS WELL. 6684 05:24:06,760 --> 05:24:10,160 SO THAT WILL LIMIT A LOT OF THE 6685 05:24:10,160 --> 05:24:15,120 VARIABILITY AGAIN WITH AGING. 6686 05:24:15,120 --> 05:24:17,960 WITHIN THE COHORT. 6687 05:24:17,960 --> 05:24:18,640 >> OKAY. 6688 05:24:18,640 --> 05:24:21,840 SO WE HAVE A QUESTION THAT JUST 6689 05:24:21,840 --> 05:24:22,920 CAME IN FROM CHAT. 6690 05:24:22,920 --> 05:24:24,680 WE HAVE ONLY FIVE MINUTES LEFT 6691 05:24:24,680 --> 05:24:28,920 SO THIS MIGHT BE OUR ULTIMATE OR 6692 05:24:28,920 --> 05:24:30,080 PENULTIMATE QUESTION DEPENDING 6693 05:24:30,080 --> 05:24:33,800 ON HOW DEEP WE DIVE INTO IT. 6694 05:24:33,800 --> 05:24:35,520 A VA M. ASKS WHAT WOULD IT TAKE 6695 05:24:35,520 --> 05:24:42,320 TO CREATE A STANDARDIZED METHOD 6696 05:24:42,320 --> 05:24:46,680 FOR BIOLOGICAL SOCIAL ADVERSITY 6697 05:24:46,680 --> 05:24:49,440 AND AFFECTS ON DIFFERENT 6698 05:24:49,440 --> 05:24:49,720 POPULATIONS. 6699 05:24:49,720 --> 05:24:52,520 THAT'S A SERIOUS QUESTION. 6700 05:24:52,520 --> 05:24:54,680 DEFINITELY WORTHY OF POND IRG. 6701 05:24:54,680 --> 05:24:56,320 -- PONDERING. 6702 05:24:56,320 --> 05:24:59,120 WHAT DO PEOPLE THINK ABOUT WHAT 6703 05:24:59,120 --> 05:25:05,400 WOULD IT TAKE? 6704 05:25:05,400 --> 05:25:12,120 >> I CAN SAY SMALL ANIMAL MODELS 6705 05:25:12,120 --> 05:25:18,880 CAN OFFER A WAY AND I'M AWARE OF 6706 05:25:18,880 --> 05:25:25,120 COHORTS STUDYING CHILDREN IN LOW 6707 05:25:25,120 --> 05:25:25,680 ECONOMIC STATUS AND IT'S 6708 05:25:25,680 --> 05:25:28,160 VALUABLE BUT WE SHOULD NOT 6709 05:25:28,160 --> 05:25:30,320 NEGLECT THE SMALL ANIMAL MODELS. 6710 05:25:30,320 --> 05:25:35,120 I WANTED TO PRESENT ANOTHER 6711 05:25:35,120 --> 05:25:43,720 STATEMENT AWAY NEED TO 6712 05:25:43,720 --> 05:25:47,200 ACKNOWLEDGE BOTH SIDES AS WE 6713 05:25:47,200 --> 05:25:52,440 MOVE FORWARD. 6714 05:25:52,440 --> 05:25:53,720 >> THAT'S A GOOD START. 6715 05:25:53,720 --> 05:25:54,920 TWO QUICK THOUGHTS. 6716 05:25:54,920 --> 05:26:00,920 ONE IS THAT IT CAN BE HELPFUL TO 6717 05:26:00,920 --> 05:26:03,320 SQUASH IN A VARIABILITY IN A 6718 05:26:03,320 --> 05:26:06,520 COFOUNDER THAT MAY AFFECT THE 6719 05:26:06,520 --> 05:26:07,040 VARIABLE. 6720 05:26:07,040 --> 05:26:10,960 STRESS AND SES ARE CORRELATED IF 6721 05:26:10,960 --> 05:26:13,840 YOU CAN MITIGATE THE VARIABLE IT 6722 05:26:13,840 --> 05:26:15,920 MAKES IT EASY TO STUDY ANOTHER. 6723 05:26:15,920 --> 05:26:17,160 IT DOESN'T GIVE A REPRESENTATIVE 6724 05:26:17,160 --> 05:26:18,640 LOOK AT A POPULATION BUT IF 6725 05:26:18,640 --> 05:26:21,360 THAT'S YOUR GOAL THAT CAN BE A 6726 05:26:21,360 --> 05:26:23,120 USEFUL STRATEGY. 6727 05:26:23,120 --> 05:26:29,800 THE SECOND IS A PANDEMIC. 6728 05:26:29,800 --> 05:26:35,000 I PANDEMIC WILL POSE ACROSS 6729 05:26:35,000 --> 05:26:36,400 SOCIETY AND EXPERIMENTALLY IT'S 6730 05:26:36,400 --> 05:26:37,960 AN INTERESTING OPPORTUNITY IN 6731 05:26:37,960 --> 05:26:39,480 THE SENSE THAT A LOT OF 6732 05:26:39,480 --> 05:26:41,480 INDIVIDUALS IN OUR SOCIETY WENT 6733 05:26:41,480 --> 05:26:41,720 THROUGH. 6734 05:26:41,720 --> 05:26:43,320 THE DUTCH HUNGER WINTER IS 6735 05:26:43,320 --> 05:26:44,920 ANOTHER EXAMPLE WHERE WE SAW 6736 05:26:44,920 --> 05:26:47,920 PART OF THE NETHERLANDS WAS CUT 6737 05:26:47,920 --> 05:26:50,520 OFF WITH FOOD SUPPLIES DURING 6738 05:26:50,520 --> 05:26:50,880 WORLD WAR II. 6739 05:26:50,880 --> 05:26:51,560 THESE ARE QUICK RESPONSES 6740 05:26:51,560 --> 05:26:53,120 BECAUSE I KNOW WE'RE AT THEN OF 6741 05:26:53,120 --> 05:26:57,920 THE HOUR BUT THERE ARE WAYS IN 6742 05:26:57,920 --> 05:27:02,520 WHICH HUMAN STUDIES IMPRECISELY 6743 05:27:02,520 --> 05:27:03,840 COMPARED TO ANIMAL MODELS BUT 6744 05:27:03,840 --> 05:27:05,320 CAN GIVE A STRATEGY TO APPROACH 6745 05:27:05,320 --> 05:27:06,520 THESE THINGS IF THAT'S THE 6746 05:27:06,520 --> 05:27:15,480 ULTIMATE GOAL. 6747 05:27:15,480 --> 05:27:19,520 >> VERY GOOD. 6748 05:27:19,520 --> 05:27:22,120 >> ONE OF THE APPROACHES WHICH 6749 05:27:22,120 --> 05:27:25,600 IS ALSO NOT PERFECT, THERE'S A 6750 05:27:25,600 --> 05:27:27,320 MULTITUDE OF ENVIRONMENTAL 6751 05:27:27,320 --> 05:27:30,360 EXPOSURES AT A GIVEN TIME BUT 6752 05:27:30,360 --> 05:27:32,640 USING AN EPIDEMIOLOGIC APPROACH 6753 05:27:32,640 --> 05:27:34,240 AND THERE'S A SMALLER SAMPLE WE 6754 05:27:34,240 --> 05:27:36,320 WOULD INVITE TO DO IMAGING AND 6755 05:27:36,320 --> 05:27:38,920 MAYBE SOME OF THE OTHER LASHTRY 6756 05:27:38,920 --> 05:27:41,280 ASSESSMENTS SO YOUR CAPTURING A 6757 05:27:41,280 --> 05:27:43,160 LARGER SAMPLE OF INDIVIDUALS BUT 6758 05:27:43,160 --> 05:27:46,920 THEN TAKING A DEEPER DIVE. 6759 05:27:46,920 --> 05:27:47,360 I WANTED TO ADD THAT. 6760 05:27:47,360 --> 05:27:50,720 >> THANK YOU. 6761 05:27:50,720 --> 05:27:53,800 >> WELL, WE'RE AT THE END OF THE 6762 05:27:53,800 --> 05:27:54,960 HOUR AND DAY BUT NOT THE END OF 6763 05:27:54,960 --> 05:27:56,320 THE WORKSHOP. 6764 05:27:56,320 --> 05:27:58,720 TO REMIND EVERYONE THERE'S 6765 05:27:58,720 --> 05:28:02,680 ANOTHER DAY FULL OF INTERESTING 6766 05:28:02,680 --> 05:28:04,480 TALKS LOOMING AHEAD WE CAN LOOK 6767 05:28:04,480 --> 05:28:05,080 FORWARD TO. 6768 05:28:05,080 --> 05:28:09,720 I'D LIKE TO THANK ALL THE 6769 05:28:09,720 --> 05:28:13,160 PANELIST FOR YOUR COMMENTS AND 6770 05:28:13,160 --> 05:28:15,080 THOUGHT IF THE DISCUSSIONS AND 6771 05:28:15,080 --> 05:28:16,160 THANK THE ORGANIZERS FOR PUTTING 6772 05:28:16,160 --> 05:28:17,120 THIS ALL TOGETHER. 6773 05:28:17,120 --> 05:28:18,720 IT'S BEEN A FASCINATING DAY AND 6774 05:28:18,720 --> 05:28:23,080 THANKS TO ALL THE ATTENDEES WHO 6775 05:28:23,080 --> 05:28:24,200 HAVE HELPED CONTRIBUTE TO THE 6776 05:28:24,200 --> 05:28:26,400 LIVELY SET OF DISCUSSIONS. 6777 05:28:26,400 --> 05:28:27,800 >> THANK YOU, VAN ESSEN. 6778 05:28:27,800 --> 05:28:28,200 >> YES, THANK YOU. 6779 05:28:28,200 --> 05:28:28,320 6780 05:28:35,560 --> 05:28:38,120 >> THANK YOU ALL FOR YOUR HARD 6781 05:28:38,120 --> 05:28:39,320 WORK TODAY AND WE'LL RETURN AT 6782 05:28:39,320 --> 05:28:42,320 NOON TOMORROW EASTERN TIME. 6783 05:28:42,320 --> 05:30:30,000 >> THANK YOU.