1 00:00:05,960 --> 00:00:07,560 >>WELCOME TO 2 00:00:07,560 --> 00:00:09,440 THE WEDNESDAY AFTERNOON LECTURE 3 00:00:09,440 --> 00:00:17,000 SERIES. MY NAME IS MARY DAWSON 4 00:00:17,000 --> 00:00:17,480 SENIOR INVESTIGATOR THE 5 00:00:17,480 --> 00:00:18,080 NATIONAL INSTITUTE OF HUMAN 6 00:00:18,080 --> 00:00:18,640 HEALTH DEVELOPMENT AND I'M 7 00:00:18,640 --> 00:00:19,240 EXCITED TO INTRODUCE TODAY'S 8 00:00:19,240 --> 00:00:23,360 SPEAKER DR. YAMASHITA, A 9 00:00:23,360 --> 00:00:24,000 PIONEER IN THE STUDY OF GENOME 10 00:00:24,000 --> 00:00:24,600 ORGANIZATION PARTICULARLY IN 11 00:00:24,600 --> 00:00:25,360 THE MAIL GERMLINE AND SHE WOULD 12 00:00:25,360 --> 00:00:27,960 PRESENTING THE 2023 PITTMAN 13 00:00:27,960 --> 00:00:28,480 LECTURE AS PART OF THE 14 00:00:28,480 --> 00:00:30,040 WEDNESDAY AFTERNOON SERIES. THE 15 00:00:30,040 --> 00:00:34,480 PITTMAN LECTURE IS GIVEN BY A 16 00:00:34,480 --> 00:00:35,120 LECTURE DEDICATED TO ADVANCING 17 00:00:35,120 --> 00:00:35,720 THE IMPROVEMENT OF CAREERS OF 18 00:00:35,720 --> 00:00:39,360 WOMEN IN SCIENCE. SINCE 1994 19 00:00:39,360 --> 00:00:40,000 WHEN THIS LECTURE SERIES BEGAN, 20 00:00:40,000 --> 00:00:46,920 EVERY SPEAKER HAS EXEMPLIFIED 21 00:00:46,920 --> 00:00:47,520 THE INTELLIGENCE, SCIENTIFIC 22 00:00:47,520 --> 00:00:48,160 EXCELLENCE, AND DRIVE THAT MADE 23 00:00:48,160 --> 00:00:48,760 MARGARET PITTMAN A LEADER AT 24 00:00:48,760 --> 00:00:49,440 THE FIRST FEMALE LABORATORY LAB 25 00:00:49,440 --> 00:00:52,640 CHIEF AT NIH. 26 00:00:52,640 --> 00:00:54,840 I WILL POINT OUT THAT DR. 27 00:00:54,840 --> 00:00:55,400 YAMASHITA WAS NOMINATED FOR 28 00:00:55,400 --> 00:00:56,160 THIS HONOR BY THE NIA WOMEN IN 29 00:00:56,160 --> 00:00:57,800 SCIENCE ADVISORS. 30 00:00:57,800 --> 00:00:59,480 IS A GREAT HONOR 31 00:00:59,480 --> 00:01:02,760 TO HAVE YUKIKO YAMASHITA WITH 32 00:01:02,760 --> 00:01:03,360 US TODAY AND SHE IS CURRENTLY 33 00:01:03,360 --> 00:01:10,000 AN HHMI INVESTIGATOR PROFESSOR 34 00:01:10,000 --> 00:01:10,600 OF BIOLOGY AT MIT AND IS A 35 00:01:10,600 --> 00:01:22,680 MEMBER OF THE WHITEHEAD 36 00:01:22,680 --> 00:01:23,280 INSTITUTE WHERE SHE HELD THE 37 00:01:23,280 --> 00:01:23,920 SUSAN LINDQUIST CHAIR FOR WOMEN 38 00:01:23,920 --> 00:01:24,520 IN SCIENCE AND SHE BEGAN HER 39 00:01:24,520 --> 00:01:26,520 SCIENTIFIC CAREER AT KYOTO 40 00:01:26,520 --> 00:01:27,120 AND STANFORD 41 00:01:27,120 --> 00:01:27,840 RESPECTIVELY BEFORE 42 00:01:27,840 --> 00:01:29,240 HER OWN LAB AT THE 43 00:01:29,240 --> 00:01:32,880 UNIVERSITY OF MICHIGAN AT ANN 44 00:01:32,880 --> 00:01:33,400 ARBOR AND BECAME A FULL 45 00:01:33,400 --> 00:01:34,040 PROFESSOR IN THE DEPARTMENT OF 46 00:01:34,040 --> 00:01:34,640 CELL AND DEVELOPMENT OF BIOLOGY 47 00:01:34,640 --> 00:01:36,640 MICHIGAN WHERE SHE ULTIMATELY 48 00:01:36,640 --> 00:01:37,200 HELD A PROFESSORSHIP IN THE 49 00:01:37,200 --> 00:01:37,840 LIFE SCIENCES INSTITUTE AND WAS 50 00:01:37,840 --> 00:01:39,240 A DIRECTOR OF THE MICHIGAN LAB 51 00:01:39,240 --> 00:01:40,440 SCIENCE FELLOWS PROGRAMS. SHE 52 00:01:40,440 --> 00:01:46,680 MOVED TO MIT IN 2020 WHERE IN 53 00:01:46,680 --> 00:01:47,280 ADDITION TO THE TITLES THAT I 54 00:01:47,280 --> 00:01:47,920 MENTIONED EARLIER SHE SERVES AS 55 00:01:47,920 --> 00:01:48,480 THE COCHAIR OF THE BIOLOGY 56 00:01:48,480 --> 00:01:49,120 DIVERSITY EQUITY AND INCLUSION 57 00:01:49,120 --> 00:01:49,520 COMMITTEE. 58 00:01:49,520 --> 00:01:54,240 DR. YAMASHITA'S WORKERS 59 00:01:54,240 --> 00:01:54,800 BROADEN OUR UNDERSTANDING 60 00:01:54,800 --> 00:01:55,800 REGARDING FUNDAMENTAL ASPECTS 61 00:01:55,800 --> 00:01:57,280 OF MULTICELLULAR ORGANISMS 62 00:01:57,280 --> 00:02:05,080 INCLUDING HOW CELLS ARE 63 00:02:05,080 --> 00:02:05,720 DEMYSTIFIED BY ASYMMETRIC CELL 64 00:02:05,720 --> 00:02:06,200 DIVISION AND GENETIC 65 00:02:06,200 --> 00:02:06,760 INFORMATION IS TRANSMITTED 66 00:02:06,760 --> 00:02:10,360 THROUGH THE GERMLINE. 67 00:02:10,360 --> 00:02:11,000 HER WORK HAS BEEN PARTICULARLY 68 00:02:11,000 --> 00:02:11,600 IMPORTANT FOR THE ELUCIDATION 69 00:02:11,600 --> 00:02:12,920 OF STRUCTURAL GENOMES AND 70 00:02:12,920 --> 00:02:13,440 EXPLORING SUCH IMPORTANT 71 00:02:13,440 --> 00:02:14,040 QUESTIONS AS A MEASURE OF 72 00:02:14,040 --> 00:02:14,560 SATELLITE DNA PREVIOUSLY 73 00:02:14,560 --> 00:02:18,840 CONSIDERED TO BE CONSIDER 74 00:02:18,840 --> 00:02:19,480 GENOMICS JUNK AND HOW IT MIGHT 75 00:02:19,480 --> 00:02:22,680 CONTRIBUTE TOWARDS SPECIATION. 76 00:02:22,680 --> 00:02:23,280 HER WORK IS ALSO BROUGHT UP 77 00:02:23,280 --> 00:02:26,840 LIKABILITY TO UNDERSTANDING 78 00:02:26,840 --> 00:02:27,320 ASYMMETRICAL TELEVISION 79 00:02:27,320 --> 00:02:27,840 QUESTIONS REGARDING THE 80 00:02:27,840 --> 00:02:31,440 IMMORTALITY OF CELLS WITHIN THE 81 00:02:31,440 --> 00:02:32,040 GERMLINE AND I BELIEVE SHE IS 82 00:02:32,040 --> 00:02:32,680 GOING TO ADDRESS SOME OF THESE 83 00:02:32,680 --> 00:02:33,360 QUESTIONS TODAY AND AS YOU 84 00:02:33,360 --> 00:02:39,360 WOULD EXPECT FROM SUCH AN 85 00:02:39,360 --> 00:02:42,040 UPSETTING SCIENTIST TO MENTOR. 86 00:02:42,040 --> 00:02:47,160 IT INCLUDES THE AWARD FROM 87 00:02:47,160 --> 00:02:47,640 MACARTHUR FELLOWSHIP IN 88 00:02:47,640 --> 00:02:53,280 THOUSAND 11 AND THE -- AND 89 00:02:53,280 --> 00:02:53,880 AWARD FROM NAGOYA UNIVERSITY 90 00:02:53,880 --> 00:02:57,160 2016 AND BEING NAMED AS A 91 00:02:57,160 --> 00:02:57,800 FELLOW OF THE AMERICAN SOCIETY 92 00:02:57,800 --> 00:03:00,200 OF CELL BIOLOGY IN 2021 AND SHE 93 00:03:00,200 --> 00:03:00,760 IS CURRENTLY SERVING AS THE 94 00:03:00,760 --> 00:03:01,440 BOARD OF SCIENTIFIC COUNSELORS, 95 00:03:01,440 --> 00:03:05,400 MEMBER FOR THE NICHD INTRAMURAL 96 00:03:05,400 --> 00:03:06,680 PROGRAM. WITHOUT FURTHER ADO 97 00:03:06,680 --> 00:03:10,920 THE TITLE OF YUKIKO'S TALK IS 98 00:03:10,920 --> 00:03:11,440 GERMLINE IMMORTALITY AND 99 00:03:11,440 --> 00:03:15,040 ASYMMETRIC STEM CELL DIVISION. 100 00:03:15,040 --> 00:03:15,680 ONCE AGAIN BECAUSE THEY WANTED 101 00:03:15,680 --> 00:03:22,280 TO EMPHASIZE IT, THE CME CODE 102 00:03:22,280 --> 00:03:24,120 IS 44455. 103 00:03:24,120 --> 00:03:24,720 LOOKING VERY MUCH AND THANKS 104 00:03:24,720 --> 00:03:25,320 SO MUCH FOR BEING HERE. 105 00:03:25,320 --> 00:03:31,000 >> [APPLAUSE] 106 00:03:31,000 --> 00:03:33,480 >>I'M REALLY EXCITED TO BE BACK 107 00:03:33,480 --> 00:03:34,040 THANK YOU SO MUCH FOR THE 108 00:03:34,040 --> 00:03:37,640 INVITATION. 109 00:03:37,640 --> 00:03:38,240 TODAY I'M GOING TO TELL YOU 110 00:03:38,240 --> 00:03:43,240 SOMETHING. IT TOOK 10 YEARS FOR 111 00:03:43,240 --> 00:03:45,440 US TO GET SOME SORT OF THE 112 00:03:45,440 --> 00:03:46,680 FRAME LOG, OR THE WHAT ARE WE 113 00:03:46,680 --> 00:03:48,840 TALKING ABOUT. THAT IS QUITE A 114 00:03:48,840 --> 00:03:51,440 JOURNEY. I AM VERY EXCITED TO 115 00:03:51,440 --> 00:03:54,080 SHARE. 116 00:03:54,080 --> 00:03:54,880 ALMOST AS AN EXCUSE I PUT THIS 117 00:03:54,880 --> 00:04:01,440 QUOTE FROM -- "I DOUBT IT COULD 118 00:04:01,440 --> 00:04:05,800 HAVE BEEN ANTICIPATED..." ABOUT 119 00:04:05,800 --> 00:04:09,240 HOW IT DISCOVERED THE 120 00:04:09,240 --> 00:04:09,840 TRANSPOSALS, AND MANY THINGS 121 00:04:09,840 --> 00:04:12,600 UNEXPECTED IN SCIENCE. 122 00:04:12,600 --> 00:04:13,640 TODAY I AM GOING TO TELL YOU 123 00:04:13,640 --> 00:04:20,400 ABOUT THE GERMLINE IMMORTALITY. 124 00:04:20,400 --> 00:04:29,920 IF YOU REALLY THINK ABOUT THIS, 125 00:04:29,920 --> 00:04:30,520 IT IS QUITE REMARKABLE. 126 00:04:30,520 --> 00:04:31,080 IF YOU ARE A TALKING ABOUT 127 00:04:31,080 --> 00:04:37,280 SOMATIC CELLS, ANY CELLS IN 128 00:04:37,280 --> 00:04:41,840 YOUR BODY-- AND EVEN ACTUALLY 129 00:04:41,840 --> 00:04:48,440 -- TEND TO DIVIDE. IN THE FACE 130 00:04:48,440 --> 00:04:49,040 OF THIS LIMITED LIFESPAN FOR 131 00:04:49,040 --> 00:04:51,520 ANY KIND OF A CELL, IS QUITE 132 00:04:51,520 --> 00:04:55,440 REMARKABLE TO TO THINK ABOUT 133 00:04:55,440 --> 00:05:02,520 THIS LINEAGE. EACH ONE OF YOU 134 00:05:02,520 --> 00:05:04,680 USED TO BE A GERM CELL FROM OUR 135 00:05:04,680 --> 00:05:06,240 PARENTS, SEVERAL DECADES AGO. 136 00:05:06,240 --> 00:05:09,840 AND YOUR PARENTS WERE ALSO 137 00:05:09,840 --> 00:05:16,920 AGAIN, THE TWO GERM CELLS, 138 00:05:16,920 --> 00:05:19,400 SEVERAL DECADES AGO, IT KEEPS 139 00:05:19,400 --> 00:05:22,280 GOING BACK AND DURING THE 140 00:05:22,280 --> 00:05:27,040 JOURNEY OF THE GERM CELLS, THE 141 00:05:27,040 --> 00:05:29,760 GERM CELLS NEVER STOPPED 142 00:05:29,760 --> 00:05:30,400 DECEASING. THAT IS WHAT YOU AND 143 00:05:30,400 --> 00:05:33,000 I ARE HERE. GERM CELLS LASTED 144 00:05:33,000 --> 00:05:43,480 1.5 BILLION YEARS. 145 00:05:46,000 --> 00:05:46,680 IT IS A FASCINATING QUESTION. 146 00:05:46,680 --> 00:05:48,880 HOW DOES GERMLINE ACHIEVE THIS 147 00:05:48,880 --> 00:05:51,000 IMMORTALITY?I DO NOT HAVE A 148 00:05:51,000 --> 00:06:00,680 FULL ANSWER. BUT THERE IS 149 00:06:00,680 --> 00:06:01,280 RESEARCH THAT LEADS TO PART OF 150 00:06:01,280 --> 00:06:04,720 THE QUESTION AND THIS RESEARCH 151 00:06:04,720 --> 00:06:05,400 STARTED WHEN I WAS AN ASSISTANT 152 00:06:05,400 --> 00:06:06,040 PROFESSOR AT THE UNIVERSITY OF 153 00:06:06,040 --> 00:06:20,640 MICHIGAN. THIS IDEA OF THE 154 00:06:20,640 --> 00:06:21,200 NONRANDOM SISTER CHROMATID 155 00:06:21,200 --> 00:06:21,840 SEGREGATION HAS BEEN OUT THERE 156 00:06:21,840 --> 00:06:28,080 QUITE A BIT OF TIME. LET ME 157 00:06:28,080 --> 00:06:29,600 EXPLAIN WHAT IT MEANS BY 158 00:06:29,600 --> 00:06:32,360 CHROMATID SEGREGATION. HERE IS 159 00:06:32,360 --> 00:06:42,200 THE DNA STRAND. DURING DNA 160 00:06:42,200 --> 00:06:42,800 REPLICATION THESE TWO STRANDS 161 00:06:42,800 --> 00:06:43,440 ARE GOING TO SEPARATE FROM EACH 162 00:06:43,440 --> 00:06:50,040 OTHER. SO THE PLUS STRAND WILL 163 00:06:50,040 --> 00:06:54,320 TEMPLATE THE MINUS STRAND, THE 164 00:06:54,320 --> 00:06:59,520 MINUS STRAND TEMPLATES THE 165 00:06:59,520 --> 00:07:02,400 POSITIVE STRAND. IT IS CALLED 166 00:07:02,400 --> 00:07:10,360 SISTER CHROMATIDS. 167 00:07:10,360 --> 00:07:10,920 IN DNA DUPLICATION YOU ARE 168 00:07:10,920 --> 00:07:12,480 COPYING FROM THE TEMPLATE EVERY 169 00:07:12,480 --> 00:07:26,920 TIME YOU DIVIDE. YOU ARE GOING 170 00:07:26,920 --> 00:07:27,480 TO BE COMPLETELY DEAD OR BE 171 00:07:27,480 --> 00:07:28,120 SOMETHING TO BELIEVE DIFFERENT 172 00:07:28,120 --> 00:07:28,760 IF IT DID NOT DID THAT. DESPITE 173 00:07:28,760 --> 00:07:30,080 THIS IDEA OF THIS REPLICATION 174 00:07:30,080 --> 00:07:30,680 IS ASSOCIATED WITH SOMETHING 175 00:07:30,680 --> 00:07:33,080 YOU NEED, SUCH AS EPIGENETIC 176 00:07:33,080 --> 00:07:36,760 MARKS OR INDUCED MUTATIONS OR 177 00:07:36,760 --> 00:07:37,360 WHATEVER. THERE IS SOMETHING 178 00:07:37,360 --> 00:07:40,880 ELSE. 179 00:07:40,880 --> 00:07:42,440 IF THAT KIND OF SPECIAL 180 00:07:42,440 --> 00:07:43,080 INFORMATION IS ASSOCIATED WITH 181 00:07:43,080 --> 00:08:00,600 ONLY ONE SISTER CHROMATID, AND 182 00:08:00,600 --> 00:08:01,120 IT ONLY GOES TO ONE CELL 183 00:08:01,120 --> 00:08:05,480 DIVISION THAT MIGHT LEAD TO A 184 00:08:05,480 --> 00:08:06,080 MUTATION AND THERE ARE MANY 185 00:08:06,080 --> 00:08:08,520 PAPERS THAT SUPPORT THIS IDEA. 186 00:08:08,520 --> 00:08:09,160 MY GRADUATE STUDENT WANTED TO 187 00:08:09,160 --> 00:08:11,360 TEST THIS IDEA. THEY TESTED 188 00:08:11,360 --> 00:08:15,120 THE POSSIBILITY AS PART OF THE 189 00:08:15,120 --> 00:08:16,720 DNA THAT ALL THE STRAND OF US 190 00:08:16,720 --> 00:08:17,280 HAS THE NEW STRAND OF THE 191 00:08:17,280 --> 00:08:18,880 ENTIRE GENOME. SHE SAW NO 192 00:08:18,880 --> 00:08:20,880 EVIDENCE OF THIS. 193 00:08:20,880 --> 00:08:23,880 BUT THE SAME STUDENT, 194 00:08:23,880 --> 00:08:24,360 CURRENTLY AN ASSISTANT 195 00:08:24,360 --> 00:08:25,000 PROFESSOR AT THE UNIVERSITY OF 196 00:08:25,000 --> 00:08:33,880 MICHIGAN, SWATHI YADLAPALLI, 197 00:08:33,880 --> 00:08:34,520 SHE WANTED TO GET TO THE BOTTOM 198 00:08:34,520 --> 00:08:38,440 AND ADDRESSES POSSIBILITY. SHE 199 00:08:38,440 --> 00:08:39,040 WONDERED IF SHE COULD ADDRESS 200 00:08:39,040 --> 00:08:40,480 THIS AT THE HIGHEST RESOLUTION 201 00:08:40,480 --> 00:08:40,840 POSSIBLE. 202 00:08:40,840 --> 00:08:42,560 IN THIS METHOD, WHEN THE DNA 203 00:08:42,560 --> 00:08:43,760 REPLICATION IS HAPPENING, YOU 204 00:08:43,760 --> 00:08:49,280 ARE GOING TO PUT THE BRDU AND 205 00:08:49,280 --> 00:08:52,480 THE ANALOG DURING THE DNA 206 00:08:52,480 --> 00:08:53,040 REPLICATION AND WHEN THAT 207 00:08:53,040 --> 00:08:54,080 HAPPENS ONLY ONE SIDE OF THE 208 00:08:54,080 --> 00:08:59,560 STRAND IS GOING TO BE BRDU 209 00:08:59,560 --> 00:09:01,600 POSITIVE. UNLESS THE DNA 210 00:09:01,600 --> 00:09:10,160 CONTAINS BRDU, AFTER YOU 211 00:09:10,160 --> 00:09:12,080 DISSECT THE TISSUE IN THIS 212 00:09:12,080 --> 00:09:12,800 EXAMPLE YOU CAN IRRADIATE THE 213 00:09:12,800 --> 00:09:13,400 AFFECTED TISSUE. IF YOU MAKE 214 00:09:13,400 --> 00:09:18,160 THE NEW STRAND YOU CAN DIGEST 215 00:09:18,160 --> 00:09:20,760 THEM AWAY. 216 00:09:20,760 --> 00:09:22,320 THAT LEADS ONLY OLDER 217 00:09:22,320 --> 00:09:22,920 TEMPLATES AS A SINGLE-STRAND 218 00:09:22,920 --> 00:09:25,640 DNA. AND HOW YOU CAN 219 00:09:25,640 --> 00:09:27,200 DIFFERENTIATE THE TWO STRANDS 220 00:09:27,200 --> 00:09:29,920 IN A DIFFERENT-- SO YOU CAN 221 00:09:29,920 --> 00:09:35,200 TELL WHICH CELLS INHERITED THE 222 00:09:35,200 --> 00:09:39,600 CY3 STROBE ANDYOU SEE THE CY5 223 00:09:39,600 --> 00:09:42,120 IN THE BLUE STRAND. THIS IS 224 00:09:42,120 --> 00:09:45,000 CALLED CHROMOSOMAL ORIENTATION 225 00:09:45,000 --> 00:09:53,520 FISH, DEVELOPED BEFORE SWATHI 226 00:09:53,520 --> 00:09:54,080 DECIDED TO DO THIS BUT SHE 227 00:09:54,080 --> 00:09:54,680 DECIDED TO DESIGN AND PRODUCE 228 00:09:54,680 --> 00:09:55,280 CHROMOSOME SPECIFIC. 229 00:09:55,280 --> 00:09:59,920 SHE WAS ABLE TO DESIGN THE X 230 00:09:59,920 --> 00:10:00,680 CHROMOSOME SPECIFIC IN THE RED 231 00:10:00,680 --> 00:10:05,880 AND BLUE AND THE -- --. 232 00:10:05,880 --> 00:10:06,600 AND THEN WE HAVE THE SYSTEM 233 00:10:06,600 --> 00:10:13,440 CALLED THE -- STEM CELL WHERE 234 00:10:13,440 --> 00:10:14,280 WE CAN IDENTIFY THE STEM CELL 235 00:10:14,280 --> 00:10:16,800 DIFFERENTIATED FROM THE DOTA, 236 00:10:16,800 --> 00:10:20,120 SO WE KNOW-- WE HAVE SEEN THE 237 00:10:20,120 --> 00:10:21,080 TISSUE WHICH IS THE STEM CELL, 238 00:10:21,080 --> 00:10:23,880 THE MEDIATED DORA. IN THIS 239 00:10:23,880 --> 00:10:27,080 CONTEXT YOU CAN APPLY THE FISH, 240 00:10:27,080 --> 00:10:29,640 YOU CAN SEE WHICH STRAND, RED 241 00:10:29,640 --> 00:10:31,080 STRAND OR BLUE STRAND WENT TO 242 00:10:31,080 --> 00:10:31,680 THE SIDE OF THE STEM CELL 243 00:10:31,680 --> 00:10:33,960 DIVISION. 244 00:10:33,960 --> 00:10:34,640 THIS IS WHAT WE GET WHEN WE DO 245 00:10:34,640 --> 00:10:37,640 THIS. THIS IS AN EXAMPLE. AS I 246 00:10:37,640 --> 00:10:41,280 SAID YOU CAN IDENTIFY STEM CELL 247 00:10:41,280 --> 00:10:43,880 DIFFERENTIATING CELL IN A 248 00:10:43,880 --> 00:10:44,480 SINGLE RESOLUTION AND IF IT 249 00:10:44,480 --> 00:10:48,360 GETS RED AND THE -- GETS BLUE 250 00:10:48,360 --> 00:10:49,360 YOU CAN HAVE THE 251 00:10:49,360 --> 00:10:50,800 (INCOMPREHENSIBLE) PART OVER 252 00:10:50,800 --> 00:10:54,240 HERE AS WELL. 253 00:10:54,240 --> 00:11:01,840 WHEN SWHATHI DID FISH, THIS IS 254 00:11:01,840 --> 00:11:09,240 WHAT YOU GOT. 255 00:11:09,240 --> 00:11:09,800 FIRST IN THEORY IS THE DNA 256 00:11:09,800 --> 00:11:10,400 STRAND WERE INDEED A COPY OF 257 00:11:10,400 --> 00:11:17,240 EACH STRAND, IT DOES NOT MATTER 258 00:11:17,240 --> 00:11:17,840 IF IT GETS A RED STRAND OR A 259 00:11:17,840 --> 00:11:19,280 BLUE STRAND. IT DOES NOT MATTER. 260 00:11:19,280 --> 00:11:21,280 AND THESE PATTERNS SHOULD BE 261 00:11:21,280 --> 00:11:22,000 OBSERVED WITH EQUAL FREQUENCY 262 00:11:22,000 --> 00:11:24,280 LIKE 50% AND 50%. THAT IS WHAT 263 00:11:24,280 --> 00:11:26,760 YOU EXPECT. 264 00:11:26,760 --> 00:11:29,160 HOWEVER IN THE REAL 265 00:11:29,160 --> 00:11:29,760 EXPERIMENT, WHERE SHE TOOK A 266 00:11:29,760 --> 00:11:31,040 LOOK AT THE X CHROMOSOME THE 267 00:11:31,040 --> 00:11:35,040 SISTER CHROMATID SEGREGATION 268 00:11:35,040 --> 00:11:41,120 PATTERN, ETC., THEN SHE SAW 269 00:11:41,120 --> 00:11:42,200 STRIKING BIAS IN THE 270 00:11:42,200 --> 00:11:42,800 SEGREGATION PATTERN FOR JUST 271 00:11:42,800 --> 00:11:48,880 THE X AND Y CHROMOSOMES. 272 00:11:48,880 --> 00:11:49,480 OF COURSE AT THE BEGINNING WE 273 00:11:49,480 --> 00:11:50,080 WORRIED THAT THIS HAD TO BE 274 00:11:50,080 --> 00:11:50,920 SOME SORT OF ARTIFACT. THIS 275 00:11:50,920 --> 00:12:03,280 SHOULD NOT BE HAPPENING. 276 00:12:03,280 --> 00:12:03,880 HOWEVER, WHEN WE DID EXACT 277 00:12:03,880 --> 00:12:04,360 SAME EXPERIMENT FOR THE 278 00:12:04,360 --> 00:12:09,680 CHROMOSOMES THERE IS NO BIAS. 279 00:12:09,680 --> 00:12:10,280 AT THAT POINT 10 YEARS AGO WE 280 00:12:10,280 --> 00:12:13,160 HAD NO IDEA WHY OR HOW THIS WAS 281 00:12:13,160 --> 00:12:18,640 HAPPENING. THE MAIN PART OF 282 00:12:18,640 --> 00:12:19,200 THE TALK TODAY IS A JOURNEY 283 00:12:19,200 --> 00:12:20,920 OVER THE LAST 10 YEARS. 284 00:12:20,920 --> 00:12:27,400 THEN BACK THEN, GEORGE WATASE 285 00:12:27,400 --> 00:12:30,760 WE JUST LEFT THIS WEEK, THIS 286 00:12:30,760 --> 00:12:31,360 WEEK WAS AS LAST WEEK AND NOW 287 00:12:31,360 --> 00:12:32,600 HE'S HEADING TO HIS NEXT 288 00:12:32,600 --> 00:12:34,440 SEMI-INDEPENDENT POSITION WHERE 289 00:12:34,440 --> 00:12:36,680 HE CAN DO IS INDEPENDENT WORK 290 00:12:36,680 --> 00:12:40,280 CONTINUING THIS WORK. 291 00:12:40,280 --> 00:12:46,080 WHEN GEORGE STARTED, THE FIRST 292 00:12:46,080 --> 00:12:48,880 THING HE DECIDED WAS, WE SHOULD 293 00:12:48,880 --> 00:12:49,960 REALLY MAP SOME SORT OF 294 00:12:49,960 --> 00:12:54,880 CHROMOSOME SPECIFIC PROCESS; 295 00:12:54,880 --> 00:12:55,560 WHEN WE STARTED THIS PROCESS IS 296 00:12:55,560 --> 00:12:57,000 THE ONLY ASSUMPTION WE MADE IS 297 00:12:57,000 --> 00:13:02,880 THAT THERE HAD TO BE A PROBLEM 298 00:13:02,880 --> 00:13:03,480 SPECIFIC (INCOMPREHENSIBLE), 299 00:13:03,480 --> 00:13:04,120 BECAUSE THERE WAS A CHROMOSOME 300 00:13:04,120 --> 00:13:09,480 SPECIFIC PHENOMENA. 301 00:13:09,480 --> 00:13:10,080 WHEN GEORGE DELETED THIS BIG 302 00:13:10,080 --> 00:13:16,080 CHUNK CALL THE BB CHROMOSOME, 303 00:13:16,080 --> 00:13:16,880 THE X CHROMOSOME WAS SEGREGATED 304 00:13:16,880 --> 00:13:18,640 COMPLETELY. 305 00:13:18,640 --> 00:13:20,280 SO WE THOUGHT THERE IS 306 00:13:20,280 --> 00:13:22,000 SOMETHING IN THERE. WHAT IS IN 307 00:13:22,000 --> 00:13:23,520 THEIR? 308 00:13:23,520 --> 00:13:30,880 THE STUDY OF THE SISTER 309 00:13:30,880 --> 00:13:31,440 CHROMATID, YOU GIVE US AN 310 00:13:31,440 --> 00:13:31,920 ANSWER AND WHEN IS THE 311 00:13:31,920 --> 00:13:35,280 (INCOMPREHENSIBLE) -- IF 312 00:13:35,280 --> 00:13:35,880 ANYBODY ASKED ME TO BET MONEY 313 00:13:35,880 --> 00:13:39,640 ON THE -- AND I WOULD'VE SET 314 00:13:39,640 --> 00:13:42,520 MONEY ON THE DNA. BUT FOR THIS 315 00:13:42,520 --> 00:13:46,720 PARTICULAR CASE, I WAS WRONG! 316 00:13:46,720 --> 00:13:47,280 AND IT TURNED OUT TO BE NOT 317 00:13:47,280 --> 00:13:56,680 RIBOSOME DNA. THAT ANSWER CAME 318 00:13:56,680 --> 00:13:57,120 FROM LOOKING AT THE Y 319 00:13:57,120 --> 00:13:58,760 CHROMOSOME WHICH ALSO HAS YBB 320 00:13:58,760 --> 00:14:05,240 DNA. SUCH Y CHROMOSOME ALSO 321 00:14:05,240 --> 00:14:08,280 SEGREGATED. 322 00:14:08,280 --> 00:14:10,280 WE REALLY DID NOT KNOW WHAT TO 323 00:14:10,280 --> 00:14:16,400 MAKE OF THIS. BECAUSE RIBOSOME 324 00:14:16,400 --> 00:14:17,280 DNA IS NOT SPECIFIC TO ANYTHING 325 00:14:17,280 --> 00:14:18,480 THAT HAS A SEX CHROMOSOME. WE 326 00:14:18,480 --> 00:14:24,280 WERE VERY, VERY PUZZLED. BUT 327 00:14:24,280 --> 00:14:24,840 WE HAD TO SAY THIS KIND OF 328 00:14:24,840 --> 00:14:25,320 MAKES SENSE, LOGICALLY 329 00:14:25,320 --> 00:14:33,080 SPEAKING, BECAUSE TWO AUTOSOMES 330 00:14:33,080 --> 00:14:33,520 DO NOT SEGREGATE AND 331 00:14:33,520 --> 00:14:38,680 (INCOMPREHENSIBLE). MORE 332 00:14:38,680 --> 00:14:40,040 RECENTLY WHEN GEORGE TOOK A 333 00:14:40,040 --> 00:14:40,560 LOOK AT THE TRANSLOCATION 334 00:14:40,560 --> 00:14:41,160 CHROMOSOME, WHERE THE SECOND 335 00:14:41,160 --> 00:14:44,520 CHROMOSOME GOT Y CHROMOSOMES 336 00:14:44,520 --> 00:14:45,720 FRAGMENTED THAT CONTAINED 337 00:14:45,720 --> 00:14:48,280 RIBOSOME DNA, THE SECOND 338 00:14:48,280 --> 00:14:52,960 CHROMOSOME NOW SEGREGATES --. 339 00:14:52,960 --> 00:14:57,480 FROM THERE, I MEAN, LED THE 340 00:14:57,480 --> 00:14:59,560 DEFINED RIBOSOME DNA, WE WERE 341 00:14:59,560 --> 00:15:03,360 DOWN TO THE SPECIFIC -- -- 342 00:15:03,360 --> 00:15:04,000 WHICH I'M GOING TO COME INTO A 343 00:15:04,000 --> 00:15:07,160 LITTLE BIT LATER. SO THAT IS 344 00:15:07,160 --> 00:15:08,720 SOMETHING WE FIND VERY HARD. 345 00:15:08,720 --> 00:15:10,760 FROM THERE, IT TOOK LIKE FIVE 346 00:15:10,760 --> 00:15:15,680 YEARS. GEORGE ISOLATED A 347 00:15:15,680 --> 00:15:22,600 PROTEIN WHICH WE NAMED INDRA. 348 00:15:22,600 --> 00:15:24,880 IT WAS ISOLATED BASED ON ITS 349 00:15:24,880 --> 00:15:25,680 ABILITY TO BIND TO RIBOSOME DNA. 350 00:15:25,680 --> 00:15:27,520 LATER WE FOUND THAT THIS 351 00:15:27,520 --> 00:15:31,600 REQUIRED NONRANDOM SISTER 352 00:15:31,600 --> 00:15:32,200 CHROMATID SEGREGATION AND IN 353 00:15:32,200 --> 00:15:36,960 ADDITION TO THIS ELEMENT WE 354 00:15:36,960 --> 00:15:38,440 HAVE A TRANS FACTOR THAT SEEMS 355 00:15:38,440 --> 00:15:40,840 TO DO SOMETHING ABOUT THE 356 00:15:40,840 --> 00:15:46,760 SISTER CHROMATID SEGREGATION. 357 00:15:46,760 --> 00:15:47,400 YOU HAVE A MOLECULAR MECHANISM 358 00:15:47,400 --> 00:15:47,960 FOR SOME SAY THAT YOU DON'T 359 00:15:47,960 --> 00:15:49,320 EVEN KNOW THE MEANING. THAT IS 360 00:15:49,320 --> 00:15:51,800 A WEIRD SITUATION. WHAT IS 361 00:15:51,800 --> 00:16:01,520 DIFFERENT BETWEEN SISTER 362 00:16:01,520 --> 00:16:02,160 CHROMATID, EVEN THOUGH WHEN WE 363 00:16:02,160 --> 00:16:02,760 KNOW IT IS RIBOSOME DNA AFTER 364 00:16:02,760 --> 00:16:05,400 IT (INCOMPREHENSIBLE)-- WHAT IS 365 00:16:05,400 --> 00:16:07,480 THE DIFFERENCE? THAT IS A 366 00:16:07,480 --> 00:16:10,480 REMAINING LINGERING QUESTION. 367 00:16:10,480 --> 00:16:12,920 TO ADDRESS THIS QUESTION, I 368 00:16:12,920 --> 00:16:13,600 HAVE TO STEP A LITTLE BIT TO 369 00:16:13,600 --> 00:16:17,520 EXPLAIN WHAT RIBOSOME DNA LOOKS 370 00:16:17,520 --> 00:16:20,880 LIKE. 371 00:16:20,880 --> 00:16:21,440 IT IS A PIECE OF THE MANY 372 00:16:21,440 --> 00:16:24,200 COPIES OF THE RIBOSOME DNA 373 00:16:24,200 --> 00:16:27,520 GENE. OR RIBOSOMAL RNA GENES. 374 00:16:27,520 --> 00:16:30,680 80% OF THE ENTIRE 375 00:16:30,680 --> 00:16:32,640 TRANSCRIPTION IN THE CELL IS 376 00:16:32,640 --> 00:16:37,560 GENERATED RIBOSOME RNA. FOR 377 00:16:37,560 --> 00:16:38,120 THAT REASON YOU CANNOT JUST 378 00:16:38,120 --> 00:16:42,120 MAKE A SINGLE COPY. THAT IS WHY 379 00:16:42,120 --> 00:16:45,120 EVERY SINGLE ORGANISM HAS 380 00:16:45,120 --> 00:16:46,200 HUNDREDS AND HUNDREDS-- 381 00:16:46,200 --> 00:16:46,840 SOMETIMES THOUSANDS OF COPIES 382 00:16:46,840 --> 00:16:50,200 OF RIBOSOME RNA. AND IN THE 383 00:16:50,200 --> 00:16:56,360 CASE OF -- ABOUT 200 COPIES OF 384 00:16:56,360 --> 00:16:56,880 EACH X CHROMOSOME AND Y 385 00:16:56,880 --> 00:16:58,080 CHROMOSOME. 386 00:16:59,640 --> 00:17:01,680 IN HUMANS, I THINK THERE IS A 387 00:17:01,680 --> 00:17:07,560 5 RNA ROSI OUT OF 388 00:17:07,560 --> 00:17:09,080 (INCOMPREHENSIBLE) AND EACH 389 00:17:09,080 --> 00:17:10,440 CONTAINS HUNDREDS OF THE 390 00:17:10,440 --> 00:17:13,880 RIBOSOME DNA COPIES. 391 00:17:13,880 --> 00:17:16,080 THAT IS CRITICALLY IMPORTANT 392 00:17:16,080 --> 00:17:24,200 TO SUPPORT OUR CELLULAR, THE 393 00:17:24,200 --> 00:17:24,680 DEMAND OF THE RIBOSOME 394 00:17:24,680 --> 00:17:28,920 BIOGENESIS. THE PROBLEM IS -- 395 00:17:28,920 --> 00:17:30,000 IF YOU HAVE REPEATING COPIES 396 00:17:30,000 --> 00:17:30,640 EVERYWHERE BECAUSE THAT IS THE 397 00:17:30,640 --> 00:17:34,280 SAME THINGS, THEY CAN EASILY 398 00:17:34,280 --> 00:17:35,040 FIND HOMOLOGY BETWEEN THE 399 00:17:35,040 --> 00:17:35,600 DIFFERENT COPIES WITH EACH 400 00:17:35,600 --> 00:17:41,720 OTHER. AND IF THEY END UP 401 00:17:41,720 --> 00:17:42,360 RECOMBINING OVER HERE, YOU LOSE 402 00:17:42,360 --> 00:17:42,920 A COPY NUMBER TWO THE EXTRA 403 00:17:42,920 --> 00:17:46,880 CHROMOSOME OR SACO, REDUCING 404 00:17:46,880 --> 00:17:47,400 THE COPY NUMBER ON YOUR 405 00:17:47,400 --> 00:17:49,840 CHROMOSOME. 406 00:17:49,840 --> 00:17:51,360 THIS COPY NUMBER DEDUCTION IS 407 00:17:51,360 --> 00:17:52,720 KNOWN TO BE ONE OF THE MAJOR 408 00:17:52,720 --> 00:17:55,800 CAUSES OF (INCOMPREHENSIBLE) AT 409 00:17:55,800 --> 00:17:59,880 LEAST IN THE EAST. BUT NOT 410 00:17:59,880 --> 00:18:00,600 MUCH OF IT WAS KNOWN ABOUT WHAT 411 00:18:00,600 --> 00:18:05,880 IS HAPPENING IN THE 412 00:18:05,880 --> 00:18:06,480 MULTICELLULAR ORGANISM. 413 00:18:06,480 --> 00:18:11,000 MY FORMER GRADUATE STUDENT 414 00:18:11,000 --> 00:18:11,640 KEVIN LU DECIDED TO TAKE A LOOK 415 00:18:11,640 --> 00:18:14,520 AT THIS COPY, LOOKING AT THE 416 00:18:14,520 --> 00:18:16,200 (INCOMPREHENSIBLE). 417 00:18:16,200 --> 00:18:20,040 HERE I AM SHYING RDNA COPY 418 00:18:20,040 --> 00:18:23,640 NUMBER ON THE XY AXIS AND THE X 419 00:18:23,640 --> 00:18:27,880 AXIS IS A TIME OR GENERATION. 420 00:18:27,880 --> 00:18:29,920 IF YOU LOOK AT YOUNGER MALES, 421 00:18:29,920 --> 00:18:31,480 THEY START WITH THE GOOD COPY 422 00:18:31,480 --> 00:18:32,040 NUMBER, IS SUFFICIENT COPY 423 00:18:32,040 --> 00:18:34,080 NUMBER HERE. BUT THEN IF YOU 424 00:18:34,080 --> 00:18:37,840 FOLLOW THESE FLIES AS THEY AGE, 425 00:18:37,840 --> 00:18:44,080 THIS GONAD LOSES AN RDNA COPY 426 00:18:44,080 --> 00:18:45,440 NUMBER THAT MEANS ALL THE MALES 427 00:18:45,440 --> 00:18:49,240 END UP HAVING DEDUCED COPY 428 00:18:49,240 --> 00:18:50,120 NUMBERS, BECAUSE THIS HAPPENS 429 00:18:50,120 --> 00:18:58,240 IN THE GERM. THAT MEANS THAT IT 430 00:18:58,240 --> 00:19:06,440 IS PASSING REDUCED RDNA. YOU 431 00:19:06,440 --> 00:19:07,040 CAN SEE THIS YOUNG SON-- THEY 432 00:19:07,040 --> 00:19:13,880 ARE YOUNG!-- BUT THEIR DNA COPY 433 00:19:13,880 --> 00:19:14,480 IS REDUCED AND IF THIS KEEPS 434 00:19:14,480 --> 00:19:17,120 HAPPENING IN THE FUTURE, WE 435 00:19:17,120 --> 00:19:17,720 WILL BE LOSING THE ABILITY TO 436 00:19:17,720 --> 00:19:23,560 KEEP GOING. 437 00:19:23,560 --> 00:19:24,560 SO OBVIOUSLY IT HASN'T 438 00:19:24,560 --> 00:19:25,160 HAPPENED LIKELY TO US, OR TO 439 00:19:25,160 --> 00:19:28,320 FLIES EITHER. HOW IS IT? 440 00:19:28,320 --> 00:19:29,880 ONE SHOCKING OBSERVATION 441 00:19:29,880 --> 00:19:38,000 INDEED THE SON WHO STARTED WITH 442 00:19:38,000 --> 00:19:40,080 THE REDUCED COPY NUMBER, HIS 443 00:19:40,080 --> 00:19:42,480 GRANDSON HAD RECOVERED. TWO 444 00:19:42,480 --> 00:19:43,480 GENERATIONS FROM BEGINNING. 445 00:19:43,480 --> 00:19:46,520 THEIR PROGENY HAS NOW AN OKAY 446 00:19:46,520 --> 00:19:59,200 RDNA COPY NUMBER. 447 00:19:59,200 --> 00:19:59,680 THAT MEANS THERE'S A 448 00:19:59,680 --> 00:20:01,880 FLUCTUATION OF THE COPY NUMBER. 449 00:20:01,880 --> 00:20:02,520 WHEN WE FOUND THIS AND WE SAW 450 00:20:02,520 --> 00:20:04,680 THIS DATA, WE REALIZED WAIT A 451 00:20:04,680 --> 00:20:08,840 MINUTE! THIS POD, IT IS NOT 452 00:20:08,840 --> 00:20:12,520 UNHEARD OF WITH THE RDNA COPY 453 00:20:12,520 --> 00:20:14,200 RECOVERY. THAT GOES BACK 50 454 00:20:14,200 --> 00:20:21,960 YEARS. SO THEN, BACK THEN, THIS 455 00:20:21,960 --> 00:20:22,480 ORIGINAL DISCOVERY OF THE 456 00:20:22,480 --> 00:20:27,000 DEDUCED RDNA COPY NUMBER ON THE 457 00:20:27,000 --> 00:20:28,640 CHROMOSOME WAS DISCOVERED KIND 458 00:20:28,640 --> 00:20:30,280 OF BY (INCOMPREHENSIBLE) A 459 00:20:30,280 --> 00:20:33,440 CENTURY AGO. 460 00:20:33,960 --> 00:20:40,720 LATER, SOMETIMES THE STARTING 461 00:20:40,720 --> 00:20:41,960 CONDITIONS THAT THE DUES THE 462 00:20:41,960 --> 00:20:46,080 MUTANT CHROMOSOME WITH MINIMUM 463 00:20:46,080 --> 00:20:48,760 RDNA COPY NUMBER CAN BE INDUCED 464 00:20:48,760 --> 00:20:49,400 IN THE RECOVERY COPY NUMBER AND 465 00:20:49,400 --> 00:20:53,880 THIS PROCESS IS CALLED RDNA 466 00:20:53,880 --> 00:21:00,280 MAGNIFICATION. 467 00:21:00,280 --> 00:21:00,880 THAT IS A PHENOMENON BACK THEN 468 00:21:00,880 --> 00:21:01,440 THAT PEOPLE WERE STUDYING 469 00:21:01,440 --> 00:21:02,080 BECAUSE IT WAS AN INTERESTING 470 00:21:02,080 --> 00:21:04,800 PHENOMENON. BUT BACK THEN 471 00:21:04,800 --> 00:21:05,400 PEOPLE DID NOT KNOW IF THERE 472 00:21:05,400 --> 00:21:08,280 WERE ANY BIOLOGICAL VARIANCES. 473 00:21:08,280 --> 00:21:10,080 NOW WE THINK THAT THIS 474 00:21:10,080 --> 00:21:10,720 MAGNIFICATION IS A PROCESS TO 475 00:21:10,720 --> 00:21:13,600 RECOVER ANY RDNA THAT LOST A 476 00:21:13,600 --> 00:21:18,000 COPY NUMBER BECAUSE OF THE 477 00:21:18,000 --> 00:21:22,880 AGING. OKAY? 478 00:21:22,880 --> 00:21:23,520 AND THE YOUNGEST PERSON BEFORE 479 00:21:23,520 --> 00:21:28,480 US IF WE STUDY THE PHENOMENA IS 480 00:21:28,480 --> 00:21:33,680 HAWLEY. AND THIS MECHANISM, WE 481 00:21:33,680 --> 00:21:35,160 THINK THAT THIS IS THE 482 00:21:35,160 --> 00:21:36,320 MECHANISM FOR THE TRANS 483 00:21:36,320 --> 00:21:38,480 GENERATION, MAINTENANCE OF THE 484 00:21:38,480 --> 00:21:44,160 RDNA COPY NUMBER IN FLIES. 485 00:21:44,160 --> 00:21:46,080 THE GOOD THING IS PRAYER 486 00:21:46,080 --> 00:21:46,880 STUDIES FIGURED QUITE A BIT OF 487 00:21:46,880 --> 00:21:47,520 THE MOLECULAR MECHANISM AND HOW 488 00:21:47,520 --> 00:21:48,960 THIS MIGHT HAVE HAPPENED. THAT 489 00:21:48,960 --> 00:21:51,040 WAS SOMETHING NEW THAT WE 490 00:21:51,040 --> 00:21:53,040 REALLY BENEFITED FROM, BY GOING 491 00:21:53,040 --> 00:21:54,520 INTO THE LITERATURE. WE 492 00:21:54,520 --> 00:21:55,360 DISCOVERED THIS PHENOMENON IN 493 00:21:55,360 --> 00:21:59,920 THE -- FLIES. 494 00:21:59,920 --> 00:22:02,160 THIS IS HOW NORMATIVE FLIES 495 00:22:02,160 --> 00:22:05,040 RECOVERED THE COPY NUMBER. I 496 00:22:05,040 --> 00:22:08,320 AM SURE IT IS TO EXEMPLIFY, 497 00:22:08,320 --> 00:22:10,000 SHOWING JUST A COPIES BUT IS 498 00:22:10,000 --> 00:22:10,520 TYPICALLY MANY MORE. 499 00:22:10,520 --> 00:22:12,960 LET'S SAY IF YOU HAVE TO EIGHT 500 00:22:12,960 --> 00:22:17,720 COPIES OF RDNA, AFTER 501 00:22:17,720 --> 00:22:18,440 DUPLICATION HAVE A SISTER 502 00:22:18,440 --> 00:22:21,280 CHROMATID HERE. 503 00:22:21,280 --> 00:22:26,400 THIS MISALIGN ON PUPAS. AND 504 00:22:26,400 --> 00:22:31,280 THEY GO ON THE SISTER CHROMATID 505 00:22:31,280 --> 00:22:34,880 EXCHANGE HERE. AFTER THIS, 506 00:22:34,880 --> 00:22:39,280 SISTER CHROMATID STEALS A COPY 507 00:22:39,280 --> 00:22:41,760 FROM IT SISTER. THAT MEANS ONE 508 00:22:41,760 --> 00:22:45,080 SISTER CHROMATID RECOVERS A 509 00:22:45,080 --> 00:22:46,200 COPY NUMBER AT THE EXPENSE OF 510 00:22:46,200 --> 00:22:50,640 ITS SISTER. RIGHT? 511 00:22:50,640 --> 00:22:51,640 AWAY WE DREW THIS DIAGRAM WE 512 00:22:51,640 --> 00:22:54,560 WERE THUNDERSTRUCK. WOW! THIS 513 00:22:54,560 --> 00:22:56,640 IS THE SYMMETRY WE WERE LOOKING 514 00:22:56,640 --> 00:23:01,000 FOR, TO EXPAND SISTER CHROMATID 515 00:23:01,000 --> 00:23:06,000 SEGREGATION. WE WERE VERY 516 00:23:06,000 --> 00:23:07,720 EXCITED AND GEORGE STARTED TO 517 00:23:07,720 --> 00:23:08,360 TAKE A LOOK AT THE COPY NUMBER 518 00:23:08,360 --> 00:23:09,120 DIFFERENCE POTENTIALLY IN THE 519 00:23:09,120 --> 00:23:10,120 STEM CELL DIVISION. 520 00:23:10,880 --> 00:23:19,800 DURING THE STEM CELL DIVISION 521 00:23:19,800 --> 00:23:20,440 THE STEM CELLS GOING TO CREATE 522 00:23:20,440 --> 00:23:22,320 A DIFFERENTIATION, CAN WE SEE 523 00:23:22,320 --> 00:23:25,920 THE COPY DIFFERENT? 524 00:23:25,920 --> 00:23:36,280 DIFFERENTIATED CELLS ARE STEM. 525 00:23:36,280 --> 00:23:36,880 WERE KIND OF AGNOSTIC BACK THEN 526 00:23:36,880 --> 00:23:47,800 AND THEN THE DNA FISH CAPTURED 527 00:23:47,800 --> 00:23:50,800 THE CELL DIVIDING ITSELF. IF 528 00:23:50,800 --> 00:23:51,400 YOU WERE TRYING TO LOOK AT A 529 00:23:51,400 --> 00:23:52,920 DIFFERENT-- (INCOMPREHENSIBLE) 530 00:23:52,920 --> 00:23:55,600 -- WE WERE VERY DISAPPOINTED, 531 00:23:55,600 --> 00:23:57,640 THERE IS NO DIFFERENCE! 532 00:23:57,640 --> 00:23:58,160 MAYBE THIS IS BEYOND THE 533 00:23:58,160 --> 00:24:06,880 RESOLUTION OF THE DNA FISH. 534 00:24:06,880 --> 00:24:07,520 BECAUSE A 5% IN THE DIFFERENCE 535 00:24:07,520 --> 00:24:08,120 IN THE COPY NUMBER IS STILL 536 00:24:08,120 --> 00:24:09,920 MEANINGFUL. WE WERE VERY 537 00:24:09,920 --> 00:24:13,560 DISAPPOINTED ABOUT THE -- MAYBE 538 00:24:13,560 --> 00:24:15,480 WE SAID, I DON'T KNOW WHAT IS 539 00:24:15,480 --> 00:24:18,480 THE NEXT STEP FOR THIS PROJECT. 540 00:24:18,480 --> 00:24:23,480 ONE DAY, GEORGE CAME TO ME. I 541 00:24:23,480 --> 00:24:24,120 THINK WE HAVE BEEN LOOKING AT-- 542 00:24:24,120 --> 00:24:25,680 HE TOLD ME-- THE WRONG 543 00:24:25,680 --> 00:24:31,880 CONDITION. THIS IS THE 544 00:24:31,880 --> 00:24:35,680 CONDITION WHERE IT IS NOT 545 00:24:35,680 --> 00:24:36,280 TEMPTED TO INCREASE THE COPY 546 00:24:36,280 --> 00:24:40,880 NUMBER. THEY ARE FINE. WITH 547 00:24:40,880 --> 00:24:41,480 THAT IDEA GEORGE WENT TO TAKE A 548 00:24:41,480 --> 00:24:42,000 LOOK AT THIS MAGNIFYING 549 00:24:42,000 --> 00:24:46,400 CONDITION THAT HAS MINIMAL RDNA 550 00:24:46,400 --> 00:24:46,960 COPY NUMBER AND NOW WE WERE 551 00:24:46,960 --> 00:24:48,640 STARTING TO SEE THE DIFFERENCE 552 00:24:48,640 --> 00:24:49,480 BETWEEN THE STEM CELL SITE AND 553 00:24:49,480 --> 00:24:50,800 THE DIFFERENTIATING SIDE. THE 554 00:24:50,800 --> 00:24:52,680 STEM CELL WAS ALWAYS INHERITING 555 00:24:52,680 --> 00:24:58,040 A LITTLE BIT MORE RDNA. YOU 556 00:24:58,040 --> 00:25:08,600 CAN QUANTIFY OVER HERE. THE 557 00:25:08,600 --> 00:25:09,200 SITUATION ON THE COPY NUMBER 558 00:25:09,200 --> 00:25:13,480 SITUATION WE SEE A NUMBER. AND 559 00:25:13,480 --> 00:25:14,040 ONCE THERE IS A MAGNIFYING 560 00:25:14,040 --> 00:25:20,280 CONDITION HERE. 561 00:25:20,280 --> 00:25:22,280 I AM NOT SURE IF I WILL 562 00:25:22,280 --> 00:25:22,840 BELIEVE THAT THIS IS THREE 563 00:25:22,840 --> 00:25:25,280 TIMES DIFFERENT WITH THE FISH, 564 00:25:25,280 --> 00:25:26,120 IF THIS WERE THE FASTER DATA WE 565 00:25:26,120 --> 00:25:27,120 GOT THERE WE SPENT MANY MONTHS 566 00:25:27,120 --> 00:25:29,280 WANTED TO SEE SOMETHING OVER 567 00:25:29,280 --> 00:25:29,840 HERE AND NO MATTER WHAT WE 568 00:25:29,840 --> 00:25:30,440 WANTED TO SEE WE DID NOT SEE 569 00:25:30,440 --> 00:25:33,200 IT. 570 00:25:33,200 --> 00:25:34,120 AFTER THIS VERY SQUEAKY 571 00:25:34,120 --> 00:25:35,000 NEGATIVE DATA WE WERE ABLE TO 572 00:25:35,000 --> 00:25:36,480 BELIEVE THIS. 573 00:25:36,480 --> 00:25:40,440 ON TOP OF THAT THIS INDRA THAT 574 00:25:40,440 --> 00:25:44,840 IS REQUIRED FOR SISTER 575 00:25:44,840 --> 00:25:45,360 CHROMATID SEGREGATION NOW 576 00:25:45,360 --> 00:25:47,080 REDUCES ASYMMETRY COMPLETELY. 577 00:25:47,080 --> 00:25:49,160 SO I'M GOING TO COME BACK. 578 00:25:49,160 --> 00:25:50,720 THIS IS ACTUALLY HINTING ALSO 579 00:25:50,720 --> 00:25:53,680 AT THE -- FUNCTION. AT THIS 580 00:25:53,680 --> 00:25:58,440 POINT THE INDRA, THE MUTANT 581 00:25:58,440 --> 00:25:58,960 CANNOT DO THIS ASYMMETRIC 582 00:25:58,960 --> 00:26:00,840 SEGREGATION. THAT IS WHAT WE 583 00:26:00,840 --> 00:26:05,760 THINK NOW. SO JUST TO 584 00:26:05,760 --> 00:26:09,000 SUMMARIZE, UP UNTIL THIS POINT, 585 00:26:09,000 --> 00:26:10,520 THIS IS KIND OF LIKE A VERY 586 00:26:10,520 --> 00:26:13,880 EXPECTED AND MEANINGFUL SISTER 587 00:26:13,880 --> 00:26:17,280 CHROMATID SEGREGATION. WE 588 00:26:17,280 --> 00:26:20,080 FOUND FIRST OF ALL RDNA AND IS 589 00:26:20,080 --> 00:26:25,840 BINDING PROTEIN INDRA, PART OF 590 00:26:25,840 --> 00:26:28,240 THE SISTER CHROMATID 591 00:26:28,240 --> 00:26:31,960 SEGREGATION. AND INSTEAD OF 592 00:26:31,960 --> 00:26:32,480 THE GENETIC INFORMATION 593 00:26:32,480 --> 00:26:33,880 DISTRIBUTED ACROSS THE ENTIRE 594 00:26:33,880 --> 00:26:34,480 CHROMOSOMES, WE THINK THIS 595 00:26:34,480 --> 00:26:38,280 ELEMENT IS LOCALIZED, THE RDNA, 596 00:26:38,280 --> 00:26:40,120 AND I EXPECT THAT IS A COPY 597 00:26:40,120 --> 00:26:40,480 NUMBER. 598 00:26:40,480 --> 00:26:44,080 WHAT ARE THEY DOING THIS? WE 599 00:26:44,080 --> 00:26:44,680 THINK IT IS FOR THE SAKE OF 600 00:26:44,680 --> 00:26:48,880 GERM IMMORTALITY OR TO MAKE AN 601 00:26:48,880 --> 00:26:49,400 RDNA COPY NUMBER FOR MANY 602 00:26:49,400 --> 00:26:50,920 GENERATIONS SO THEY DO NOT LOSE 603 00:26:50,920 --> 00:26:51,920 THIS INTEGRITY. 604 00:26:51,920 --> 00:27:05,160 THE GENOME INDRA COMES FROM 605 00:27:05,160 --> 00:27:06,240 THE HINDU GOD WHO LOSSES 606 00:27:06,240 --> 00:27:08,320 IMMORTALITY BECAUSE OF CASTE. 607 00:27:08,320 --> 00:27:10,920 SO THERE IS GERMLINE 608 00:27:10,920 --> 00:27:11,560 IMMORTALITY AND THAT IS WHY WE 609 00:27:11,560 --> 00:27:18,320 NAMED THE GENE INDRA. 610 00:27:18,320 --> 00:27:18,880 BEFORE GOING TO THE NEXT 611 00:27:18,880 --> 00:27:22,000 SECTION OF HOW THE INDRA MIGHT 612 00:27:22,000 --> 00:27:23,280 BE FUNCTIONING IN THE 613 00:27:23,280 --> 00:27:25,040 MECHANISM-- IT IS FAIRLY NEW, 614 00:27:25,040 --> 00:27:28,480 LAST MONTH OR SO-- ALL OF A 615 00:27:28,480 --> 00:27:29,040 SUDDEN WE STARTED GETTING 616 00:27:29,040 --> 00:27:33,440 REALLY INTERESTING DATA. 617 00:27:33,440 --> 00:27:34,040 I WANT TO TELL YOU A LITTLE 618 00:27:34,040 --> 00:27:34,520 BIT ABOUT THE SLIGHTLY 619 00:27:34,520 --> 00:27:35,080 DIFFERENT ASPECT OF THE 620 00:27:35,080 --> 00:27:36,080 MODIFICATION. ANOTHER THING 621 00:27:36,080 --> 00:27:41,280 THAT WE FOUND IS THIS IS WORK 622 00:27:41,280 --> 00:27:42,000 BY POSTDOC JONATHAN NELSON WHO 623 00:27:42,000 --> 00:27:44,920 IS HEADING TO HIS OWN LAB AT 624 00:27:44,920 --> 00:27:45,640 THE STONY BROOK SOMETIME SOON 625 00:27:45,640 --> 00:27:46,680 IN THE NEXT FEW MONTHS. 626 00:27:46,680 --> 00:27:54,680 TO INDUCE THIS SISTER 627 00:27:54,680 --> 00:27:55,320 CHROMATID EXCHANGE INCREASE 628 00:27:55,320 --> 00:27:56,560 COPY NUMBER THE FASTER STEP 629 00:27:56,560 --> 00:27:57,280 THAT YOU HAVE TO DO IS TO BREAK 630 00:27:57,280 --> 00:27:58,880 THE DNA. OTHERWISE NOTHING 631 00:27:58,880 --> 00:28:03,640 WOULD HAPPEN. 632 00:28:03,640 --> 00:28:06,680 JONATHAN FOUND THAT THIS IS 633 00:28:06,680 --> 00:28:10,080 ACTUALLY TRANSPOSAL. THAT HAS 634 00:28:10,080 --> 00:28:14,520 ONLY BEEN KNOWN IN THE RDNA, 635 00:28:14,520 --> 00:28:16,240 AND THAT IS THE KEY TO INDUCE A 636 00:28:16,240 --> 00:28:17,760 MODIFICATION. THAT IS 637 00:28:17,760 --> 00:28:21,040 INTERESTING. THE PHENOMENA 638 00:28:21,040 --> 00:28:23,280 WHERE THE GENETIC PARASITE, THE 639 00:28:23,280 --> 00:28:28,800 TRANSPOSAL HAS ADOPTED AND NOW 640 00:28:28,800 --> 00:28:30,400 HAS A SYMBIOTIC RELATIONSHIP AS 641 00:28:30,400 --> 00:28:33,280 A HOST. 642 00:28:33,280 --> 00:28:33,880 WHEN WE STARTED THIS WORK WE 643 00:28:33,880 --> 00:28:36,680 WERE PUZZLED. HOW WOULD THE 644 00:28:36,680 --> 00:28:42,280 HOST WANT ANY TRANSPOSAL TO GO 645 00:28:42,280 --> 00:28:42,880 SPECIFICALLY INTO THE MOST PART 646 00:28:42,880 --> 00:28:46,840 OF THE GENOME? IT TURNED OUT 647 00:28:46,840 --> 00:28:51,840 INDEED THAT IT IS CO-OPTED AND 648 00:28:51,840 --> 00:28:52,440 INDUCED THE MODIFICATION ONLY 649 00:28:52,440 --> 00:28:54,040 WHEN IT IS REQUIRED. 650 00:28:54,040 --> 00:29:02,640 SO THEN, NOW THERE IS LITTLE 651 00:29:02,640 --> 00:29:09,360 BIT OF A QUESTION, AT THE 652 00:29:09,360 --> 00:29:09,960 BEGINNING WERE AGNOSTIC ABOUT 653 00:29:09,960 --> 00:29:10,440 WHICH CELLS, OR WHICH 654 00:29:10,440 --> 00:29:11,080 DIFFERENTIATED CELLS INHERITED 655 00:29:11,080 --> 00:29:15,480 THE COPY NUMBER. 656 00:29:15,480 --> 00:29:16,040 MANY PEOPLE CAME TO ME AND 657 00:29:16,040 --> 00:29:16,640 SAID HEY IT DOES NOT MAKE ANY 658 00:29:16,640 --> 00:29:17,680 SENSE. YOU HAVE TO BE WRONG! 659 00:29:17,680 --> 00:29:22,040 THE STEM CELL INHERITING MORE 660 00:29:22,040 --> 00:29:29,760 COPIES? THAT DOES NOT MAKE ANY 661 00:29:29,760 --> 00:29:30,200 SENSE BECAUSE THIS 662 00:29:30,200 --> 00:29:30,840 DIFFERENTIATING CELL -- IS MUCH 663 00:29:30,840 --> 00:29:33,600 MORE IMPORTANT THAN THE SPERM 664 00:29:33,600 --> 00:29:36,000 GENERATION CELLS. 665 00:29:36,000 --> 00:29:43,520 IF YOU THINK ABOUT IT IT MAKES 666 00:29:43,520 --> 00:29:46,280 SENSE. IF STEM CELL MAGNIFIES 667 00:29:46,280 --> 00:29:47,280 THE COPY NUMBER, THE STEM CELL 668 00:29:47,280 --> 00:29:48,480 IS GOING TO MAKE THE 669 00:29:48,480 --> 00:29:52,000 DIFFERENTIATED CELL IN THE NEXT 670 00:29:52,000 --> 00:29:57,040 CELL DIVISION. 671 00:29:57,040 --> 00:29:58,120 THIS KEEPS GOING AND THE 672 00:29:58,120 --> 00:29:58,880 DIFFERENTIATED CELL DOWNSTREAM 673 00:29:58,880 --> 00:29:59,440 OF ALL OF THOSE POPULATION 674 00:29:59,440 --> 00:30:00,040 START INHERITING THE RECOVERY 675 00:30:00,040 --> 00:30:01,560 COPY NUMBER. 676 00:30:01,560 --> 00:30:07,160 ON THE OTHER HAND, IF ONE 677 00:30:07,160 --> 00:30:07,720 TIME IN THE INCREASE OF THE 678 00:30:07,720 --> 00:30:10,080 COPY NUMBER GOES TO 679 00:30:10,080 --> 00:30:10,760 DIFFERENTIATING CELL, THIS 680 00:30:10,760 --> 00:30:15,400 DIFFERENTIATING CELL DOES NOT 681 00:30:15,400 --> 00:30:16,000 SUSTAIN. THAT MEANS THAT WITH 682 00:30:16,000 --> 00:30:17,960 THE CELL DIFFERENTIATION KEEPS 683 00:30:17,960 --> 00:30:24,880 GOING DOWN, AND YOU WILL BE 684 00:30:24,880 --> 00:30:25,640 DOWN ONE MAGNIFICATION. 685 00:30:25,640 --> 00:30:30,520 IF STEM CELL ARE INHERITING 686 00:30:30,520 --> 00:30:33,560 THE GOOD COPY, RED IS A COPY 687 00:30:33,560 --> 00:30:35,280 NUMBER AND THE BLUES COPY 688 00:30:35,280 --> 00:30:35,920 NUMBER, YOU START WITH KIND OF 689 00:30:35,920 --> 00:30:39,120 A REDDISH COLOR. AND AFTER 690 00:30:39,120 --> 00:30:39,760 DIFFERENTIATING CELLS THEY GET 691 00:30:39,760 --> 00:30:41,960 A HIT. YOU LOSE THE COPY 692 00:30:41,960 --> 00:30:43,720 NUMBER. 693 00:30:43,720 --> 00:30:50,040 IN THE NEXT DIVISION THE STEM 694 00:30:50,040 --> 00:30:53,920 CELL RECOVERS EVEN MORE AND IN 695 00:30:53,920 --> 00:30:54,400 THE NEXT ROUND OF THE 696 00:30:54,400 --> 00:30:58,080 DIFFERENTIATING CELL, EVEN IF 697 00:30:58,080 --> 00:31:01,400 IT IS SEVERAL DEGREES, IT 698 00:31:01,400 --> 00:31:02,040 STARTS THE TEMPLATE BETTER THAN 699 00:31:02,040 --> 00:31:03,520 PREVIOUS GRADUALLY INCREASES 700 00:31:03,520 --> 00:31:07,840 THE COPY NUMBER AND THE 701 00:31:07,840 --> 00:31:08,440 DIFFERENTIATED CELLS START TO 702 00:31:08,440 --> 00:31:10,680 RECOVER A COPY NUMBER, SEVERAL 703 00:31:10,680 --> 00:31:11,280 CYCLES BACK BUT HE CAN STILL 704 00:31:11,280 --> 00:31:15,360 RECOVER IT. 705 00:31:15,360 --> 00:31:16,000 ON THE CONTRARY IF YOU DO THE 706 00:31:16,000 --> 00:31:18,280 OPPOSITE THEY KEEP LOSING THE 707 00:31:18,280 --> 00:31:18,880 COPY NUMBER, TO GIVE THE BETA 708 00:31:18,880 --> 00:31:19,440 COPY TO THE DIFFERENTIATING 709 00:31:19,440 --> 00:31:22,880 CELL. BUT THE DIFFERENTIATING 710 00:31:22,880 --> 00:31:23,440 CELL CAN KEEP RECEIVING THE 711 00:31:23,440 --> 00:31:25,920 COPIES FROM THE STEM CELL. 712 00:31:25,920 --> 00:31:26,480 THAT HAS A SEVERELY REDUCED 713 00:31:26,480 --> 00:31:29,640 COPY NUMBER; THAT MEANS BOTH OF 714 00:31:29,640 --> 00:31:34,120 THEM KEEP DECREASING THE COPY 715 00:31:34,120 --> 00:31:38,640 NUMBER, EATING THE --. 716 00:31:38,640 --> 00:31:40,720 NO MATTER THE CONDITION THERE 717 00:31:40,720 --> 00:31:41,320 IS NO COPY NUMBER DIFFERENCE 718 00:31:41,320 --> 00:31:42,040 BETWEEN SISTERS, NO MATTER WHAT 719 00:31:42,040 --> 00:31:47,960 HAPPENS. STARTING FROM 200 720 00:31:47,960 --> 00:31:48,560 COPIES, AFTER MANY DIVISIONS 721 00:31:48,560 --> 00:31:49,080 WERE PRETTY MUCH NOTHING 722 00:31:49,080 --> 00:31:51,000 HAPPENS. 723 00:31:53,920 --> 00:31:54,640 BUT IN THE MAGNIFYING 724 00:31:54,640 --> 00:31:55,320 CONDITION, IN THE INITIAL COPY 725 00:31:55,320 --> 00:31:55,880 NUMBER SAY STARTING FROM A 726 00:31:55,880 --> 00:32:00,480 REDUCED 100, BUT THEN THE 727 00:32:00,480 --> 00:32:03,880 SISTER CHROMATID THAT HAPPENS 728 00:32:03,880 --> 00:32:05,480 AFTER 50% IN THE GENERATED STEM 729 00:32:05,480 --> 00:32:08,520 CELL, AFTER THE EXCHANGE STEM 730 00:32:08,520 --> 00:32:09,280 CELLS DO NOT HAVE ANY 731 00:32:09,280 --> 00:32:12,320 PREFERENCE. YOU DON'T GET ANY 732 00:32:12,320 --> 00:32:16,680 COPY NUMBER INCREASE. SOME AND 733 00:32:16,680 --> 00:32:17,240 UP WITH AN INCREASING COPY 734 00:32:17,240 --> 00:32:18,840 NUMBER. SOME OF THEM LOOSE. NET 735 00:32:18,840 --> 00:32:19,880 ZERO INCREASE. 736 00:32:19,880 --> 00:32:26,240 IF STEM CELLS ARE GETTING THE 737 00:32:26,240 --> 00:32:33,040 BETTER COPY, THE -- START TO 738 00:32:33,040 --> 00:32:36,480 RECEIVE A HIGHER COPY NUMBER, 739 00:32:36,480 --> 00:32:37,120 NOT LOSING THE RECOVERED COPIES 740 00:32:37,120 --> 00:32:40,680 AND THE SPERM AFTER TWO WEEKS 741 00:32:40,680 --> 00:32:41,280 -- AVERAGE COPY NUMBER IS SO 742 00:32:41,280 --> 00:32:43,480 MUCH MORE REDUCED. THAT REALLY 743 00:32:43,480 --> 00:32:46,600 TELLS. THIS IS PROBABLY 744 00:32:46,600 --> 00:32:47,200 UNNECESSARY ADDITIONAL 745 00:32:47,200 --> 00:32:51,080 MODELING. 746 00:32:51,080 --> 00:33:01,880 THE KEY MESSAGES THAT IT IS 747 00:33:01,880 --> 00:33:02,480 THE STEM CELL RECEIVES THE 748 00:33:02,480 --> 00:33:03,080 MODIFICATION TO INCREASE THE 749 00:33:03,080 --> 00:33:05,800 COPY NUMBER. 750 00:33:05,800 --> 00:33:09,120 SO IS THIS LIMITED TO -- STEM 751 00:33:09,120 --> 00:33:13,800 CELL? BREAKING THE CELL IS 752 00:33:13,800 --> 00:33:15,080 TRICKY BUSINESS. THAT WAS 753 00:33:15,080 --> 00:33:15,640 ANOTHER THING WE WANTED TO 754 00:33:15,640 --> 00:33:20,320 ADDRESS. WE COULD ACTUALLY 755 00:33:20,320 --> 00:33:21,520 TAKE A LOOK AT THE OCCURRENCE 756 00:33:21,520 --> 00:33:24,480 OF THE SISTER CHROMATID 757 00:33:24,480 --> 00:33:29,960 EXCHANGE BY LOOKING AT THE DNA 758 00:33:29,960 --> 00:33:31,360 ABLUTION BREAK, PROVIDING 759 00:33:31,360 --> 00:33:31,960 PHOSPHORYLATED 760 00:33:31,960 --> 00:33:36,760 (INCOMPREHENSIBLE). 761 00:33:36,760 --> 00:33:40,480 IN A NORMAL CONDITION IN THE 762 00:33:40,480 --> 00:33:44,160 STEM CELL AREA YOU BARELY SEE 763 00:33:44,160 --> 00:33:48,720 THE DNA DAMAGE. IF YOU GIVE 764 00:33:48,720 --> 00:33:51,040 THIS REDUCED COPY NUMBER THE 765 00:33:51,040 --> 00:33:51,560 CONDITION, THE MAGNIFYING 766 00:33:51,560 --> 00:33:52,520 CONDITION YOU START TO SEE THE 767 00:33:52,520 --> 00:33:58,080 DNA DAMAGE AROUND HERE. THIS 768 00:33:58,080 --> 00:34:02,040 IS ONE DATA TO SHOW THAT 769 00:34:02,040 --> 00:34:04,040 TRANSPOSAL IS IMPORTANT. IF YOU 770 00:34:04,040 --> 00:34:08,800 LOOK AT THE TRANSPOSAL TO STOP 771 00:34:08,800 --> 00:34:11,400 SEEING THE DNA DAMAGE. OKAY? 772 00:34:11,400 --> 00:34:15,280 NOT ONLY THAT. THIS COMPARISON 773 00:34:15,280 --> 00:34:18,000 IS BETWEEN STEM CELL AND 774 00:34:18,000 --> 00:34:18,600 DIFFERENTIATED CELL, AND IN 775 00:34:18,600 --> 00:34:22,080 WHAT CONDITION. THE CONTROL 776 00:34:22,080 --> 00:34:23,040 SITUATION, MAGNIFYING 777 00:34:23,040 --> 00:34:28,280 CONDITION, MAGNIFYING PLUS 778 00:34:28,280 --> 00:34:34,520 MINUS 2 IN THIS INHIBITED. 779 00:34:34,520 --> 00:34:36,480 DNA STRAND BREAK HAPPENS. 780 00:34:36,480 --> 00:34:39,280 THERE IS ONE DAY OF 781 00:34:39,280 --> 00:34:42,320 DEREGULATION. ON TOP OF THAT 782 00:34:42,320 --> 00:34:44,080 BY COMPARING THIS OVER HERE, 783 00:34:44,080 --> 00:34:45,440 EVEN UNDER MAGNIFYING 784 00:34:45,440 --> 00:34:47,480 CONDITIONS, DNA BREAK IS PRETTY 785 00:34:47,480 --> 00:34:50,480 MUCH LIMITED TO THE STEM CELL 786 00:34:50,480 --> 00:34:51,080 AND THE DIFFERENTIATING CELLS 787 00:34:51,080 --> 00:34:53,920 DON'T DO IT. AND THAT KIND OF 788 00:34:53,920 --> 00:34:54,440 MAKES SENSE BECAUSE WE 789 00:34:54,440 --> 00:34:57,880 PREVIOUSLY PUBLISHED THAT 790 00:34:57,880 --> 00:35:01,280 DIFFERENTIATING CELLS ARE 791 00:35:01,280 --> 00:35:01,840 ACTUALLY SENSITIVE TO DNA 792 00:35:01,840 --> 00:35:04,840 DAMAGE TO MAKE SURE THAT THE 793 00:35:04,840 --> 00:35:06,280 GENOME INTEGRITY IS PRETTY GOOD 794 00:35:06,280 --> 00:35:06,840 SO THE TEENIEST BIT OF DNA 795 00:35:06,840 --> 00:35:07,480 DAMAGE DOES NOT DO ANYTHING TO 796 00:35:07,480 --> 00:35:11,960 THE SISTER CHROMATID CELLS, BUT 797 00:35:11,960 --> 00:35:12,520 THAT IS ENOUGH TO KILL THE 798 00:35:12,520 --> 00:35:13,440 CELLS. 799 00:35:13,440 --> 00:35:20,560 SO NOT ONLY IS THERE RDNA 800 00:35:20,560 --> 00:35:22,280 BREAKS, AS YOU CAN SEE OVER 801 00:35:22,280 --> 00:35:24,640 HERE ONLY WHEN MAGNIFYING 802 00:35:24,640 --> 00:35:27,480 CONDITIONS HAPPEN, THE RDNA 803 00:35:27,480 --> 00:35:30,040 COPY NUMBERS LOWER, R2 COMES 804 00:35:30,040 --> 00:35:40,320 OUT OVER HEREBUT ONLY IN THE 805 00:35:40,320 --> 00:35:42,040 STEM CELL AND THE EXPRESSION IS 806 00:35:42,040 --> 00:35:42,600 MUCH MORE SUPPRESSED. 807 00:35:42,600 --> 00:35:49,280 SO ONE THING. THE ONE 808 00:35:49,280 --> 00:35:49,760 CHALLENGE WE FACED WHEN 809 00:35:49,760 --> 00:35:52,680 STUDYING THIS, WAS THE OFTEN 810 00:35:52,680 --> 00:35:54,360 MANY PEOPLE ARE SKEPTICAL. 811 00:35:54,360 --> 00:35:58,000 THIS IS TRANSPOSED. THE DATA 812 00:35:58,000 --> 00:36:02,960 GOT PARASITED. THEY CANNOT BE 813 00:36:02,960 --> 00:36:06,040 BENEFICIAL TO THE HOST. BUT 814 00:36:06,040 --> 00:36:06,680 OUR DATA WAS PRETTY CONVINCING, 815 00:36:06,680 --> 00:36:12,080 WE THOUGHT, IN TERMS OF THE 816 00:36:12,080 --> 00:36:12,560 TRANSPOSAL HELPING THE 817 00:36:12,560 --> 00:36:16,160 MODIFICATION AND HELPING RDNA 818 00:36:16,160 --> 00:36:17,880 COPY NUMBER MAINTENANCE. 819 00:36:17,880 --> 00:36:20,960 IF INDEED R2 IS AN IMPORTANT 820 00:36:20,960 --> 00:36:26,000 PART OF THE HOST BIOLOGY, THIS 821 00:36:26,000 --> 00:36:27,200 SHOULD BE SIGNALING PATHWAY 822 00:36:27,200 --> 00:36:28,720 THAT HAS TO BE INTEGRATED, 823 00:36:28,720 --> 00:36:32,240 TOGETHER WITH R2 EXPRESSION SO 824 00:36:32,240 --> 00:36:34,800 WHAT HE DID WITH A SINGLE CELL 825 00:36:34,800 --> 00:36:37,600 RDNA SEQUENCING, WHAT HE DID 826 00:36:37,600 --> 00:36:39,440 WAS COMPARE TWO CONDITIONS. 827 00:36:39,440 --> 00:36:42,600 FIRST OF ALL HE USED A STEM 828 00:36:42,600 --> 00:36:47,440 CELL TUMOR. BECAUSE THIS IS A 829 00:36:47,440 --> 00:36:48,760 SINGLE CELL YOU CAN ISOLATE OR 830 00:36:48,760 --> 00:36:51,160 CONCENTRATE STEM CELL AND ALSO 831 00:36:51,160 --> 00:36:55,240 HE COMPARED LOW RDNA COPY 832 00:36:55,240 --> 00:37:01,480 NUMBER AND THE HIGH RDNA COPY 833 00:37:01,480 --> 00:37:02,160 NUMBER SITUATIONS AND THE 834 00:37:02,160 --> 00:37:04,200 GENIUS UPREGULATED UNDER THE 835 00:37:04,200 --> 00:37:06,440 LOWER DATA COPY NUMBER. 836 00:37:06,440 --> 00:37:07,440 I'M GOING TO GIVE A COUPLE OF 837 00:37:07,440 --> 00:37:10,760 EXAMPLES, DOWN REGULATED RDNA 838 00:37:10,760 --> 00:37:13,680 COPY NUMBER, THE CANDIDATE FOR 839 00:37:13,680 --> 00:37:17,120 THE INHIBITED MODIFICATION, OR 840 00:37:17,120 --> 00:37:18,360 YOU DO NOT HAVE TO MAGNIFY, 841 00:37:18,360 --> 00:37:20,200 THAT IS THE REGULAR DATA. 842 00:37:20,200 --> 00:37:21,440 THAT GIVES A COUPLE OF 843 00:37:21,440 --> 00:37:25,080 INTERESTING GENES. ONE WAS 844 00:37:25,080 --> 00:37:28,640 INSULIN RECEPTOR. WE ARE GOING 845 00:37:28,640 --> 00:37:30,080 TO SKIP OVER THIS, BUT I WILL 846 00:37:30,080 --> 00:37:30,640 TELL YOU THAT IT IS PRETTY 847 00:37:30,640 --> 00:37:36,080 CONVINCING. IF YOU MODULATE 848 00:37:36,080 --> 00:37:38,120 THIS NUTRIENT SENSING PATHWAY, 849 00:37:38,120 --> 00:37:40,280 AND THAT COMPLETELY REGULATES 850 00:37:40,280 --> 00:37:43,200 THIS MAGNIFICATION, THAT MEANS 851 00:37:43,200 --> 00:37:47,160 WE THINK THAT THIS IS PROBABLY 852 00:37:47,160 --> 00:37:48,800 SENSING THE ABILITY TO MAKE 853 00:37:48,800 --> 00:37:54,520 LOTS OF RIBOSOME. IF THAT IS 854 00:37:54,520 --> 00:37:55,080 COMPROMISED THAT IS THE 855 00:37:55,080 --> 00:37:57,200 INCIDENT PATHWAY, IT TELLS R2 856 00:37:57,200 --> 00:38:01,600 TO EXPRESS OR NOT. 857 00:38:01,600 --> 00:38:02,240 I'M NOT GOING TO GET INTO THIS 858 00:38:02,240 --> 00:38:05,680 TO VERY MUCH. ACTUALLY I DON'T 859 00:38:05,680 --> 00:38:11,000 HAVE IT, THAT IS GOOD. THE ONE 860 00:38:11,000 --> 00:38:14,080 THING THE INSULIN RECEPTOR, 861 00:38:14,080 --> 00:38:14,560 THEN WE USE THE INSULIN 862 00:38:14,560 --> 00:38:18,160 RECEPTOR NUTRIENT. IT TOLD IS 863 00:38:18,160 --> 00:38:19,680 THAT THE INSULIN RECEPTOR IS 864 00:38:19,680 --> 00:38:20,240 NEGATIVELY REGULATING THE 865 00:38:20,240 --> 00:38:23,280 MAGNIFICATION PROCESS. THAT 866 00:38:23,280 --> 00:38:27,040 MEANS EVEN WHEN THEY WANT TO 867 00:38:27,040 --> 00:38:29,640 MAGNIFY, IF YOU ACTIVATE 868 00:38:29,640 --> 00:38:36,480 INSULIN PATHWAY -- DON'T CARE. 869 00:38:36,480 --> 00:38:37,080 AND ANOTHER THING IS THAT THE 870 00:38:37,080 --> 00:38:38,160 PATHWAY WAS PUT OUT. THAT MAKES 871 00:38:38,160 --> 00:38:40,480 SENSE. WHY DO YOU HAVE A 872 00:38:40,480 --> 00:38:44,120 PATHWAY TO DEPRESS TRANSPOSAL? 873 00:38:44,120 --> 00:38:45,880 IT IS NOT JUST TO DEPRESS. I 874 00:38:45,880 --> 00:38:48,400 WILL REPHRASE THIS. TO FINE 875 00:38:48,400 --> 00:38:51,200 TUNE THE TRANSPOSAL INSTEAD OF 876 00:38:51,200 --> 00:38:52,560 JUST DEPRESS. IF YOU DON'T NEED 877 00:38:52,560 --> 00:38:56,400 THE TRANSPOSAL TO COME OUT 878 00:38:56,400 --> 00:38:57,000 BECAUSE YOU ARE DEPRESSING IT 879 00:38:57,000 --> 00:38:58,160 THAT IS BECAUSE THE CELL HAS A 880 00:38:58,160 --> 00:38:58,760 SITUATION WHERE YOU WANT TO 881 00:38:58,760 --> 00:39:02,680 HAVE A LITTLE BIT OF THE 882 00:39:02,680 --> 00:39:04,160 TRANSPOSAL TO COME OUT THAT IS 883 00:39:04,160 --> 00:39:07,920 WHY THE PATHWAY BECOMES HANDY. 884 00:39:07,920 --> 00:39:09,600 NOW I'M GOING TO GIVE YOU A 885 00:39:09,600 --> 00:39:10,160 LITTLE BIT IN THE LAST TWO 886 00:39:10,160 --> 00:39:10,800 MINUTES ABOUT THE FUNCTION OF 887 00:39:10,800 --> 00:39:13,880 INDRA. WE KNOW THAT INDRA 888 00:39:13,880 --> 00:39:21,840 BINDS TO RIBOSOME DNA. EXACTLY 889 00:39:21,840 --> 00:39:23,480 HOW DOES THAT WORK? THAT IS 890 00:39:23,480 --> 00:39:25,080 GEORGE'S WORK IN THE LAST TWO 891 00:39:25,080 --> 00:39:31,240 MONTHS OR SO. 892 00:39:31,240 --> 00:39:31,840 THIS ONE I TOLD YOU, THIS IS 893 00:39:31,840 --> 00:39:33,520 THE SAME THING, THE ASYMMETRIC 894 00:39:33,520 --> 00:39:37,120 COPY NUMBER, NORMAL CONDITION, 895 00:39:37,120 --> 00:39:40,000 MAGNIFIED, AND MAGNIFIED MUTANT 896 00:39:40,000 --> 00:39:43,160 CONDITION. 897 00:39:43,160 --> 00:39:43,760 IN THIS WHEN YOU CAN SEE NO 898 00:39:43,760 --> 00:39:49,200 SYMMETRY AT ALL. INDRA IS NOT 899 00:39:49,200 --> 00:39:53,920 QUITE SEGREGATION PER SE, BUT 900 00:39:53,920 --> 00:39:54,560 IT IS ABOUT CREATING ASYMMETRY. 901 00:39:54,560 --> 00:39:58,080 RIGHT? BECAUSE IF IT IS SIMPLY 902 00:39:58,080 --> 00:40:00,560 REQUIRED FOR SEGREGATION, YOU 903 00:40:00,560 --> 00:40:01,960 MIGHT CREATE LOTS OF COPY 904 00:40:01,960 --> 00:40:04,440 NUMBER ASYMMETRY. BUT IT MIGHT 905 00:40:04,440 --> 00:40:06,760 GO THE RANDOM WAY. SO I 906 00:40:06,760 --> 00:40:07,560 FABRICATED THIS DATA BY COPYING 907 00:40:07,560 --> 00:40:12,080 THIS FROM THIS DATA LAST NIGHT 908 00:40:12,080 --> 00:40:13,720 TO SHOW WHAT YOU WOULD EXPECT 909 00:40:13,720 --> 00:40:15,760 IF YOU ARE MAKING THAT COPY 910 00:40:15,760 --> 00:40:18,720 NUMBER ASYMMETRY. BUT THEY ARE 911 00:40:18,720 --> 00:40:20,480 NOT SEGREGATING CORRECTLY. 912 00:40:20,480 --> 00:40:24,520 THIS DOES NOT HAPPEN. THAT 913 00:40:24,520 --> 00:40:26,000 MEANS INDRA WAS CREATING A COPY 914 00:40:26,000 --> 00:40:29,720 NUMBER ASYMMETRY. 915 00:40:29,720 --> 00:40:33,960 SO AS I TOLD YOU, AND I 916 00:40:33,960 --> 00:40:34,600 BRIEFLY MENTIONED, INDRA BINDS 917 00:40:34,600 --> 00:40:35,240 TO THIS ONE SPECIFIC SEQUENCE 918 00:40:35,240 --> 00:40:37,680 IGS. THAT IS WHERE THE 919 00:40:37,680 --> 00:40:44,800 PROMOTER OF RIBOSOME DNA GENE. 920 00:40:44,800 --> 00:40:45,360 CURIOUSLY PEOPLE KNOW THAT 921 00:40:45,360 --> 00:40:51,040 THERE ARE TWO RIBOSOME 922 00:40:51,040 --> 00:40:57,560 PROMOTERS. WHY TWO? 923 00:40:57,560 --> 00:40:58,160 BECAUSE IT IS A PROMOTER WE 924 00:40:58,160 --> 00:40:58,760 DECIDED TO TAKE A LOOK TO SEE 925 00:40:58,760 --> 00:40:59,360 IF INDRA HAS ANY FUNCTION IN 926 00:40:59,360 --> 00:41:01,000 THE DISCRETION OF IGS. IT 927 00:41:01,000 --> 00:41:03,120 TURNED OUT THAT INDEED YES. IN 928 00:41:03,120 --> 00:41:03,760 LABORATORY CONDITIONS YOU GET A 929 00:41:03,760 --> 00:41:11,120 LITTLE BIT OF IGS EXPRESSION. 930 00:41:11,120 --> 00:41:11,720 BUT IN THE INDRA MUTANT GETS 931 00:41:11,720 --> 00:41:14,000 REALLY UPREGULATED OVER HERE. 932 00:41:14,000 --> 00:41:16,880 IF YOU DO THIS, FIRST OF ALL 933 00:41:16,880 --> 00:41:20,680 OVER HERE YOU CAN SEE THE INDRA 934 00:41:20,680 --> 00:41:22,320 MUTANT UPGRADES CONSIDERABLY 935 00:41:22,320 --> 00:41:25,360 IGS. INTERESTINGLY THIS UP 936 00:41:25,360 --> 00:41:26,200 REGULATION IS VERY SPECIFIC TO 937 00:41:26,200 --> 00:41:34,800 STEM CELL. THIS IS INDRA 938 00:41:34,800 --> 00:41:35,400 MUTANT, STILL THIS POPULATION 939 00:41:35,400 --> 00:41:37,280 OBSERVED ONLY IN THE STEM CELL. 940 00:41:37,280 --> 00:41:38,000 THAT MEANS WHATEVER THE 941 00:41:38,000 --> 00:41:48,160 TENDENCY IS TO EXPRESS IGS THAT 942 00:41:48,160 --> 00:41:48,760 ITSELF IS LIMITED TO THE 943 00:41:48,760 --> 00:41:51,880 GERMINIZED STEM CELL. 944 00:41:51,880 --> 00:41:57,360 INDRA'S DEPRESSING THE 945 00:41:57,360 --> 00:41:58,000 EXPRESSION WITH THE ABILITY TO 946 00:41:58,000 --> 00:41:58,600 EXPRESS AT ALL IS LIMITED TO 947 00:41:58,600 --> 00:42:00,360 THE STEM CELL, BUT NOT THE 948 00:42:00,360 --> 00:42:08,240 DIFFERENTIATING CELL. THIS WE 949 00:42:08,240 --> 00:42:09,800 DON'T OBSERVE ANY UP REGULATION 950 00:42:09,800 --> 00:42:12,080 AS PART OF THE RDNA. THIS 951 00:42:12,080 --> 00:42:17,080 PROMOTER IS THE SAME, ETS. 952 00:42:17,080 --> 00:42:17,680 THERE IS NO UP REGULATION AT 953 00:42:17,680 --> 00:42:22,040 ALL IN THESE GUYS. SO IGS UP 954 00:42:22,040 --> 00:42:27,640 RELATION BY INDRA IS STEM CELL 955 00:42:27,640 --> 00:42:32,880 SPECIFIC. WHAT DO WE DO? 956 00:42:32,880 --> 00:42:35,880 WE TOOK THE HINT FROM YEAST. 957 00:42:35,880 --> 00:42:39,800 HERE WE HAVE COPIES OF THE RDNA 958 00:42:39,800 --> 00:42:43,480 COPIES AND HERE IT IS ALSO 959 00:42:43,480 --> 00:42:44,080 DEPRESSED. WHEN THE CELL LOSES 960 00:42:44,080 --> 00:42:48,560 A COPY NUMBER IGS INDEED GETS 961 00:42:48,560 --> 00:42:50,080 UPREGULATED. 962 00:42:50,080 --> 00:42:54,480 IF YOU EXPRESS FROM HERE RIGHT 963 00:42:54,480 --> 00:42:56,160 HERE THERE IS A DNA REPLICATION 964 00:42:56,160 --> 00:42:58,800 ORIGIN, THERE IS A CONFLICT OF 965 00:42:58,800 --> 00:43:00,240 TRANSCRIPTION AND DNA 966 00:43:00,240 --> 00:43:00,760 REPLICATION THAT ENDS UP 967 00:43:00,760 --> 00:43:03,600 BREAKING THE DNA. THAT DNA 968 00:43:03,600 --> 00:43:10,000 BREAK IS ACTUALLY USED IN 969 00:43:10,000 --> 00:43:10,600 SISTER CHROMATID EXCHANGE TO 970 00:43:10,600 --> 00:43:13,880 INCREASE THE COPY NUMBER. 971 00:43:13,880 --> 00:43:14,480 SO TRANSPLANTING THIS IDEA TO 972 00:43:14,480 --> 00:43:17,880 WHAT DO WE KNOW IN DROSOPHILA? 973 00:43:17,880 --> 00:43:21,000 INDRA IS OVER HERE. WE STARTED 974 00:43:21,000 --> 00:43:27,080 THINKING THAT MAYBE INDRA IS 975 00:43:27,080 --> 00:43:27,800 DEPRESSING NORMALLY TO DEPRESS 976 00:43:27,800 --> 00:43:28,360 THE MAGNIFICATION AND THAT 977 00:43:28,360 --> 00:43:29,640 BECAME THE IDEA. 978 00:43:29,640 --> 00:43:34,080 WE TESTED THE IDEA. WE FIRST 979 00:43:34,080 --> 00:43:39,280 TOOK A LOOK AT THE IGS 980 00:43:39,280 --> 00:43:39,800 EXPRESSION IN A NORMAL 981 00:43:39,800 --> 00:43:40,440 SITUATION VERSUS THE MAGNIFIED 982 00:43:40,440 --> 00:43:41,240 CONDITION AND THIS IS NOT THE 983 00:43:41,240 --> 00:43:41,840 INDRA MUTATION IF YOU LOOK AT 984 00:43:41,840 --> 00:43:47,720 OVER HERE, THE STEM CELL, THE 985 00:43:47,720 --> 00:43:50,880 UPREGULATED IGS OVER HERE IN 986 00:43:50,880 --> 00:43:51,400 THE MODIFY CONDITION AND 987 00:43:51,400 --> 00:43:52,680 COMPARED TO THE NORMAL 988 00:43:52,680 --> 00:43:55,400 CONDITION YOU GET UP REGULATION. 989 00:43:55,400 --> 00:43:55,880 IF YOU COMPARE AND YOU 990 00:43:55,880 --> 00:44:00,600 NORMALIZE THE IGS EXPRESSION BY 991 00:44:00,600 --> 00:44:04,280 DIFFERENTIATING CELLS, THE STEM 992 00:44:04,280 --> 00:44:06,280 CELL DIVIDED BY DIFFERENTIATING 993 00:44:06,280 --> 00:44:10,120 CELL, IT GETS EVEN CLEARER. THE 994 00:44:10,120 --> 00:44:14,080 STEM CELL EXPRESSES IGS WE NEED 995 00:44:14,080 --> 00:44:19,280 TO MODIFY THE RDNA COPY NUMBER. 996 00:44:19,280 --> 00:44:20,920 IF YOU OVEREXPRESSED INDRA, 997 00:44:20,920 --> 00:44:24,080 YOU CAN SUPPRESS IT. THAT TELLS 998 00:44:24,080 --> 00:44:26,240 US INDRA IS A NEGATIVE UP 999 00:44:26,240 --> 00:44:29,960 REGULATOR FOR IGS EXPRESSION 1000 00:44:29,960 --> 00:44:30,520 AND THAT LEADS TO THE NEXT 1001 00:44:30,520 --> 00:44:38,360 QUESTION. DOES INDRA REPRESS 1002 00:44:38,360 --> 00:44:39,440 MAGNIFICATION? 1003 00:44:39,440 --> 00:44:40,040 I DON'T HAVE A SLOT HERE FOR 1004 00:44:40,040 --> 00:44:44,680 YOU BUT WE ALSO DISCOVERED 1005 00:44:44,680 --> 00:44:45,960 INDRA PROTEIN ON LONG ITSELF 1006 00:44:45,960 --> 00:44:47,400 ACTUALLY GOES DOWN DURING 1007 00:44:47,400 --> 00:44:49,040 MAGNIFICATION. THAT MEANS INDRA 1008 00:44:49,040 --> 00:44:51,480 PROTEIN AMOUNT IS SENSITIVE TO 1009 00:44:51,480 --> 00:45:02,440 THE RDNA COPY NUMBER. 1010 00:45:02,440 --> 00:45:04,320 THIS IS AS IT WAS EXPECTED THE 1011 00:45:04,320 --> 00:45:04,960 MODIFIED CONDITION YOU DESERVE 1012 00:45:04,960 --> 00:45:06,080 THE DNA BREAKING CELL AND IF 1013 00:45:06,080 --> 00:45:08,280 YOU EXPRESS INDRA YOU GET THE 1014 00:45:08,280 --> 00:45:12,720 SAME THING. THIS IS THE CASE 1015 00:45:12,720 --> 00:45:13,280 OF THE MODIFICATION AND THE 1016 00:45:13,280 --> 00:45:17,480 MODIFYING CONDITION, YOU ARE 1017 00:45:17,480 --> 00:45:18,160 OVEREXPRESSING INDRA, YOU WILL 1018 00:45:18,160 --> 00:45:20,920 DEPRESS IT. 1019 00:45:20,920 --> 00:45:25,920 ACTUALLY THIS IS THE DATA. THE 1020 00:45:25,920 --> 00:45:26,560 INDRA AMOUNT ACTUALLY GOES DOWN 1021 00:45:26,560 --> 00:45:29,840 WHEN YOU HAVE A REDUCED RDNA 1022 00:45:29,840 --> 00:45:39,360 COPY NUMBER. 1023 00:45:39,360 --> 00:45:40,280 IS THAT REPLICATION 1024 00:45:40,280 --> 00:45:42,720 TRANSCRIPTION CONFLICT THAT 1025 00:45:42,720 --> 00:45:49,080 REGULATES RDNA MAGNIFICATION_ 1026 00:45:49,080 --> 00:45:56,160 THIS IS A GENE ON TOP OF THAT. 1027 00:45:56,160 --> 00:45:56,880 INDRA IS A TRANSCRIPTION 1028 00:45:56,880 --> 00:45:57,400 REGULATED, THAT BECAME A 1029 00:45:57,400 --> 00:46:00,840 QUESTION. PERHAPS INDRA IS 1030 00:46:00,840 --> 00:46:05,160 REPRESSING RDNA EXPRESSION 1031 00:46:05,160 --> 00:46:06,640 ITSELF AND IN THE MUTANT THE 1032 00:46:06,640 --> 00:46:07,240 UPREGULATED ATTITUDE AND ALSO 1033 00:46:07,240 --> 00:46:10,880 IN MAGNIFYING CONDITIONS R2 1034 00:46:10,880 --> 00:46:12,040 SHOULD BE UP BUT THAT CAN BE 1035 00:46:12,040 --> 00:46:13,160 REPRESSED BUT OVEREXPRESSING 1036 00:46:13,160 --> 00:46:18,040 INDRA. 1037 00:46:18,040 --> 00:46:18,640 SO THIS ACTUALLY LEAD TO THE 1038 00:46:18,640 --> 00:46:20,680 SORT OF UNIFY MODEL. 1039 00:46:20,680 --> 00:46:21,280 PREVIOUSLY THIS IS WHAT PEOPLE 1040 00:46:21,280 --> 00:46:26,000 KNEW. WHEN PEOPLE THOUGHT R2 IS 1041 00:46:26,000 --> 00:46:28,560 PURELY A PARASITE, PEOPLE 1042 00:46:28,560 --> 00:46:33,160 FIGURED THAT THE RDNA INSERTED 1043 00:46:33,160 --> 00:46:38,800 IN R2 IS COMPLETELY REPRESSED 1044 00:46:38,800 --> 00:46:41,000 BY AN UNKNOWN MECHANISM BUT IT 1045 00:46:41,000 --> 00:46:43,200 WAS CLEAR THAT RDNA INSERTED 1046 00:46:43,200 --> 00:46:46,240 INTO R2 IS NOT EXPOSING AT ALL 1047 00:46:46,240 --> 00:46:46,800 AND THE ONLY GOOD COPY IS 1048 00:46:46,800 --> 00:46:50,760 EXPRESSED. NOW UPSTREAM 1049 00:46:50,760 --> 00:46:51,360 ADDITIONAL PROMOTER CAME INTO 1050 00:46:51,360 --> 00:46:52,880 THE PICTURE. THAT IS IGS 1051 00:46:52,880 --> 00:46:57,080 BOUNDED BY INDRA. 1052 00:46:57,080 --> 00:46:57,720 AND THIS IS WHAT WE THINK IS 1053 00:46:57,720 --> 00:47:02,640 HAPPENING. UNDER MAGNIFYING 1054 00:47:02,640 --> 00:47:04,880 CONDITION, THIS PROMOTER IS 1055 00:47:04,880 --> 00:47:05,480 ALWAYS REPRESSED UNDER NORMAL 1056 00:47:05,480 --> 00:47:06,080 CONDITIONS. THIS NORMALLY DOES 1057 00:47:06,080 --> 00:47:10,520 NOT COUNT. ONLY TRANSCRIPTION 1058 00:47:10,520 --> 00:47:13,000 THAT ARE HAPPENING BY USING 1059 00:47:13,000 --> 00:47:14,680 THIS PROMOTER ETS OVER HERE IS 1060 00:47:14,680 --> 00:47:15,240 A NORMAL CONDITION BUT NOW 1061 00:47:15,240 --> 00:47:15,800 UNDER MAGNIFYING CONDITION, 1062 00:47:15,800 --> 00:47:21,200 WHEN THIS STEM CELL LOSES AN 1063 00:47:21,200 --> 00:47:26,160 RDNA COPY NUMBER-- NOW THIS NEW 1064 00:47:26,160 --> 00:47:26,800 PROMOTER COMES INTO THE PICTURE 1065 00:47:26,800 --> 00:47:28,200 AND WE THINK THIS EXPRESSION IS 1066 00:47:28,200 --> 00:47:30,560 NONDISCRIMINATORY OF IGS. 1067 00:47:30,560 --> 00:47:34,160 INSERTED IN R2. THIS PROBABLY 1068 00:47:34,160 --> 00:47:39,200 RESULTS IN R2 EXPRESSION WITH 1069 00:47:39,200 --> 00:47:40,240 THE MAGNIFICATION THROUGH THE 1070 00:47:40,240 --> 00:47:43,880 SISTER CHROMATID EXCHANGE AND 1071 00:47:43,880 --> 00:47:45,200 THAT IS ESSENTIALLY THE ENTIRE 1072 00:47:45,200 --> 00:47:45,640 MESSAGE, LEADING TO 1073 00:47:45,640 --> 00:47:48,320 MAGNIFICATION. 1074 00:47:48,320 --> 00:47:51,160 LET ME GIVE YOU THE SURPRISE. 1075 00:47:51,160 --> 00:47:58,400 SO THIS MODEL SAYS BECAUSE RDNA 1076 00:47:58,400 --> 00:48:01,840 TYPICALLY IS IMPORTANT AS S1, 1077 00:48:01,840 --> 00:48:03,680 WHAT ABOUT THE SECOND PROMOTER? 1078 00:48:03,680 --> 00:48:12,800 WHO IS DOING IT? 1079 00:48:12,800 --> 00:48:13,440 IF THE SAME POLYMER IS COMING 1080 00:48:13,440 --> 00:48:13,920 INTO THE TWO DIFFERENT 1081 00:48:13,920 --> 00:48:16,640 PROMOTERS THERE IS NOT MUCH 1082 00:48:16,640 --> 00:48:18,280 DIFFERENTIATION YOU CAN DO AND 1083 00:48:18,280 --> 00:48:19,080 THIS IGS UP REGULATION UNDER 1084 00:48:19,080 --> 00:48:20,440 MAGNIFIED CONDITIONS ENTIRELY 1085 00:48:20,440 --> 00:48:23,080 UP TO POLYMERS TO MODIFY THE 1086 00:48:23,080 --> 00:48:26,280 STEM CELL. 1087 00:48:26,280 --> 00:48:29,800 THIS IS BUSY DATA. IT IS 1088 00:48:29,800 --> 00:48:30,360 SHOCKING. IT IS MUCH MORE 1089 00:48:30,360 --> 00:48:33,320 VISUALLY APPEALING. IT IS A 1090 00:48:33,320 --> 00:48:35,200 SIMPLE IMMUNOFLUORESCENCE 1091 00:48:35,200 --> 00:48:38,200 LOOKING AT THE RDNA POLYMER IN 1092 00:48:38,200 --> 00:48:43,560 LABORATORY. THIS IS BORING. 1093 00:48:43,560 --> 00:48:44,200 WHEN YOU GIVE THIS MAGNIFYING 1094 00:48:44,200 --> 00:48:46,400 CONDITION, THE RDNA COPY NUMBER 1095 00:48:46,400 --> 00:48:51,760 GOES DOWN, ALL OF A SUDDEN RDNA 1096 00:48:51,760 --> 00:48:54,040 POLYMERS COME AROUND, THIS IS 1097 00:48:54,040 --> 00:48:56,240 RDNA SYNTHESIS, THE FACTORY. 1098 00:48:56,240 --> 00:48:59,920 ALL OF A SUDDEN THE RDNA COPY 1099 00:48:59,920 --> 00:49:02,960 NUMBER GOES DOWN AND RDNA DOES 1100 00:49:02,960 --> 00:49:05,680 TOO, GET RECRUITED TO IGS. THAT 1101 00:49:05,680 --> 00:49:10,080 IS POSSIBLE BECAUSE INDRA GOES 1102 00:49:10,080 --> 00:49:14,480 AWAY AND ALLOWS R2 TO COME IN. 1103 00:49:14,480 --> 00:49:19,480 TO SUMMARIZE TODAY'S TALK, 1104 00:49:19,480 --> 00:49:22,280 RDNA LOCUS IS VULNERABLE AND 1105 00:49:22,280 --> 00:49:23,720 SUPER IMPORTANT TO MAINTAIN THE 1106 00:49:23,720 --> 00:49:24,360 CELLS' HELP BECAUSE YOU LOSE A 1107 00:49:24,360 --> 00:49:26,520 COPY NUMBER ALL THE TIME. YOU 1108 00:49:26,520 --> 00:49:32,680 HAVE TO RECOVER TO MAINTAIN THE 1109 00:49:32,680 --> 00:49:33,280 GERMLINE IMMORTALITY TO LAST 1110 00:49:33,280 --> 00:49:35,080 THE 1.5 BILLION YEARS OTHER 1111 00:49:35,080 --> 00:49:37,680 MULTICELLULAR LIFE AND TO DO 1112 00:49:37,680 --> 00:49:38,280 SO, THIS RECOVERY IS MEDIATING 1113 00:49:38,280 --> 00:49:44,200 BY AN SISTER CHROMATID 1114 00:49:44,200 --> 00:49:45,280 EXCHANGE. THAT IS A REAL KEY TO 1115 00:49:45,280 --> 00:49:48,880 REJUVENATE RIBOSOME DNA. I 1116 00:49:48,880 --> 00:49:50,280 ALSO TOLD YOU THAT IS DONE IN 1117 00:49:50,280 --> 00:49:59,480 THE STEM CELL; THIS IS 1118 00:49:59,480 --> 00:50:00,080 HAPPENING SPECIFICALLY IN THE 1119 00:50:00,080 --> 00:50:03,640 GERMANIZED CELL. 1120 00:50:03,640 --> 00:50:04,200 ALSO THE ACTIVATION OF THE 1121 00:50:04,200 --> 00:50:05,720 SPECIFIC PROMOTER THAT BRINGS 1122 00:50:05,720 --> 00:50:13,680 IN RDNA POLYMERS TOO. 1123 00:50:13,680 --> 00:50:14,200 SO THAT LEADS TO 1124 00:50:14,200 --> 00:50:16,200 DIFFERENTIATED COPY NUMBER, 1125 00:50:16,200 --> 00:50:20,680 WHICH IS FURTHER REGULATED BY 1126 00:50:20,680 --> 00:50:27,280 SISTER CHROMATID SEGREGATION 1127 00:50:27,280 --> 00:50:31,880 THAT ALLOWS THE STEM CELL TO 1128 00:50:31,880 --> 00:50:32,480 INHERIT A COPY NUMBER AND SO 1129 00:50:32,480 --> 00:50:35,760 NOW YOU HAVE HOW IT IS 1130 00:50:35,760 --> 00:50:37,720 GERMINATING. 1131 00:50:37,720 --> 00:50:41,680 THIS IS MY LAB. IT TOOK 10 1132 00:50:41,680 --> 00:50:42,240 YEARS. BOTH OF US ARE VERY 1133 00:50:42,240 --> 00:50:44,320 HAPPY. FINALLY WE FIGURED IT 1134 00:50:44,320 --> 00:50:51,880 OUT. THE R2 POD WAS DONE BY 1135 00:50:51,880 --> 00:50:54,880 JONATHAN NELSON. THANK YOU 1136 00:50:54,880 --> 00:50:55,560 VERY MUCH FOR YOUR ATTENTION 1137 00:50:55,560 --> 00:50:56,360 AND NOW AM HAPPY TO TAKE ANY 1138 00:50:56,360 --> 00:50:57,520 QUESTIONS YOU MIGHT HAVE. 1139 00:50:57,520 --> 00:50:58,200 THANK YOU. 1140 00:50:58,200 --> 00:51:14,480 >> [APPLAUSE] 1141 00:51:14,480 --> 00:51:15,560 >> YOU DON'T WANT-- LIKE 1142 00:51:15,560 --> 00:51:17,320 INDRA-- 1143 00:51:17,320 --> 00:51:19,320 >> DR. YAMASHITA: YOU ARE RIGHT. 1144 00:51:19,320 --> 00:51:21,960 FOR LONGEST TIME WE THOUGHT 1145 00:51:21,960 --> 00:51:23,600 INDRA WAS REQUIRED FOR 1146 00:51:23,600 --> 00:51:26,640 SEGREGATION PER SE. BUT WHAT 1147 00:51:26,640 --> 00:51:30,040 IS HAPPENING WITH INDRA IS THAT 1148 00:51:30,040 --> 00:51:36,520 IN ABSENCE OF INDRA I JUST 1149 00:51:36,520 --> 00:51:37,160 EXPRESS SO MUCH. ACTUALLY THEY 1150 00:51:37,160 --> 00:51:37,800 ENDED UP RECOMBINING MANY, MANY 1151 00:51:37,800 --> 00:51:39,600 TIMES. AND THAT EQUALIZED TO 1152 00:51:39,600 --> 00:51:43,400 CHROMATID AND THAT IS 1153 00:51:43,400 --> 00:51:43,920 WHY THE CHROMOSOMES GET 1154 00:51:43,920 --> 00:51:44,600 CONFUSED ABOUT WHICH STRAND TO 1155 00:51:44,600 --> 00:51:48,480 BRING TO THE CELL SO INDRA DOES 1156 00:51:48,480 --> 00:51:50,520 NOT SEEM TO BE THE MACHINERY TO 1157 00:51:50,520 --> 00:51:55,120 DIFFERENTIATE THE DNA. WE HAVE 1158 00:51:55,120 --> 00:52:01,600 TO REALLY STUDY HOW-- THE 1159 00:52:01,600 --> 00:52:02,080 DIVISION APPARATUSES 1160 00:52:02,080 --> 00:52:02,680 DIFFERENTIATING ONE COPY FROM 1161 00:52:02,680 --> 00:52:03,760 THE OTHER. AND THAT IS STILL A 1162 00:52:03,760 --> 00:52:04,880 BIG QUESTION. 1163 00:52:04,880 --> 00:52:07,120 >> THANK YOU. 1164 00:52:07,120 --> 00:52:10,080 >> HI THAT WAS FASCINATING. 1165 00:52:10,080 --> 00:52:14,160 THANK YOU VERY MUCH. I HAVE AN 1166 00:52:14,160 --> 00:52:16,600 GENERAL EVOLUTIONARY QUESTION. 1167 00:52:16,600 --> 00:52:19,600 IF YOU HAVE 200 COPIES, PER 1168 00:52:19,600 --> 00:52:20,200 GENE THERE IS SLOW SELECTION 1169 00:52:20,200 --> 00:52:20,680 PRESSURE TO KEEP THAT 1170 00:52:20,680 --> 00:52:24,760 CONSISTENT. HOW DOES THAT WORK? 1171 00:52:24,760 --> 00:52:26,360 IS THERE ANY DIFFERENCE IN THE 1172 00:52:26,360 --> 00:52:27,360 MUTATION RATES AT THE END 1173 00:52:27,360 --> 00:52:27,880 VERSUS THE MIDDLE? 1174 00:52:27,880 --> 00:52:31,400 >> DR. YAMASHITA: EXACTLY SO 1175 00:52:31,400 --> 00:52:32,840 TYPICALLY THE MIDDLE COPIES ARE 1176 00:52:32,840 --> 00:52:37,400 WELL MAINTAINED. THAT IS 1177 00:52:37,400 --> 00:52:37,960 BECAUSE-- ACTUALLY THAT IS 1178 00:52:37,960 --> 00:52:44,320 BECAUSE OF THE SISTER CHROMATID 1179 00:52:44,320 --> 00:52:45,760 EXCHANGE AND IF YOU DO THAT 1180 00:52:45,760 --> 00:52:46,400 EXCHANGE OVER HERE, THE MIDDLE 1181 00:52:46,400 --> 00:52:50,720 COPY GETS DUPLICATED. RIGHT? AS 1182 00:52:50,720 --> 00:52:51,320 A RESULT THEY HOMOGENIZE THE 1183 00:52:51,320 --> 00:52:54,720 MIDDLE COPY. IF YOU GO TO THE 1184 00:52:54,720 --> 00:52:55,400 END, SAME THING FOR EXAMPLE 1185 00:52:55,400 --> 00:53:02,080 WITH (INCOMPREHENSIBLE) -- 1186 00:53:02,080 --> 00:53:04,120 TOWARDS THE END THEY USE STUDY 1187 00:53:04,120 --> 00:53:05,600 SEQUENCE THAT ARE DEGRADING BUT 1188 00:53:05,600 --> 00:53:06,160 IN THE MIDDLE IT IS WELL 1189 00:53:06,160 --> 00:53:10,560 CONTROLLED. THAT MEANS IF 1190 00:53:10,560 --> 00:53:14,320 ANYTHING GETS THE MUTATION THAT 1191 00:53:14,320 --> 00:53:14,920 IS GOING TO SWEEP MOST OF THE 1192 00:53:14,920 --> 00:53:18,000 MIDDLE PART OF THE SEGMENT. IN 1193 00:53:18,000 --> 00:53:21,000 CASE OF RDNA, IF YOU'RE MUTATED 1194 00:53:21,000 --> 00:53:21,600 IN A WAY THAT IS GOING TO 1195 00:53:21,600 --> 00:53:26,400 COMPROMISE OUR RDNA FUNCTION 1196 00:53:26,400 --> 00:53:28,000 THAT WILL BE SELECTED OUT. 1197 00:53:28,000 --> 00:53:30,840 >> THANK YOU. 1198 00:53:30,840 --> 00:53:31,480 >> THANKS THAT WAS A GREAT 1199 00:53:31,480 --> 00:53:34,800 TALK. HOW MUCH OF THIS IS 1200 00:53:34,800 --> 00:53:35,560 CONSERVED IN FEMALES? 1201 00:53:35,560 --> 00:53:37,280 >> DR. YAMASHITA: SUPER 1202 00:53:37,280 --> 00:53:42,000 QUESTION. WE HAVE NOT BEEN 1203 00:53:42,000 --> 00:53:45,240 ABLE TO REALLY DO THE CO-FISH 1204 00:53:45,240 --> 00:53:47,840 IN A FEMALE. BUT THERE IS AN 1205 00:53:47,840 --> 00:53:51,400 INTERESTING OBSERVATION FROM 50 1206 00:53:51,400 --> 00:53:57,600 YEARS AGO. FEMALE DOES NOT 1207 00:53:57,600 --> 00:53:58,200 UNDERGO MODIFICATION. THAT IS 1208 00:53:58,200 --> 00:54:00,880 REALLY INTERESTING. WHY IS IT? 1209 00:54:00,880 --> 00:54:02,840 WE DO NOT KNOW, BUT THE FEMALE 1210 00:54:02,840 --> 00:54:05,040 DOES NOT DO IT. 1211 00:54:05,600 --> 00:54:09,360 >> THAT WAS FANTASTIC. I AM 1212 00:54:09,360 --> 00:54:09,960 CURIOUS SINCE YOU RAISED THE 1213 00:54:09,960 --> 00:54:12,400 SPECTER OF -- SATELLITE IS 1214 00:54:12,400 --> 00:54:16,560 THERE ANY ROLE FOR INDRA IN 1215 00:54:16,560 --> 00:54:17,520 MITOSIS? OR IS IT SPECIFIC JUST 1216 00:54:17,520 --> 00:54:18,680 FOR RDNA? 1217 00:54:18,680 --> 00:54:20,640 >> DR. YAMASHITA: IT REALLY 1218 00:54:20,640 --> 00:54:24,800 LOOKS LIKE IT IS JUST RDNA. 1219 00:54:26,080 --> 00:54:26,680 >> SO I WAS PUZZLED BY THAT. 1220 00:54:26,680 --> 00:54:28,600 WHY IS IT SO SPECIFIC FOR RDNA? 1221 00:54:28,600 --> 00:54:31,480 >> DR. YAMASHITA: WE DON'T 1222 00:54:31,480 --> 00:54:32,440 KNOW. WE DO NOT KNOW ABOUT 1223 00:54:32,440 --> 00:54:49,240 INDRA. BUT IT IS ONE NEW GENE 1224 00:54:49,240 --> 00:54:49,880 THAT WE STARTED WORKING ON. WE 1225 00:54:49,880 --> 00:54:55,400 STARTED WORKING ON IT. THIS 1226 00:54:55,400 --> 00:54:58,120 GENE (INCOMPREHENSIBLE) -- THIS 1227 00:54:58,120 --> 00:55:05,840 PROTEIN BINDS TO ALL THE 1228 00:55:05,840 --> 00:55:14,320 OVERSATURATED DNA PLUS THE RDNA 1229 00:55:14,320 --> 00:55:17,920 DNA. IT WAS A GOOD CONNECTION. 1230 00:55:17,920 --> 00:55:19,240 >> I HAVE A COUPLE OF QUESTIONS 1231 00:55:19,240 --> 00:55:22,280 ONLINE. THE PROBLEM IS I DON'T 1232 00:55:22,280 --> 00:55:23,520 KNOW WHAT THE PRONOUN "IT" 1233 00:55:23,520 --> 00:55:28,680 MEANS. THE QUESTION IS HOW 1234 00:55:28,680 --> 00:55:29,280 DOES IT HAPPEN IN HUMAN GERM 1235 00:55:29,280 --> 00:55:29,760 CELLS AS WELL? 1236 00:55:29,760 --> 00:55:31,240 >> DR. YAMASHITA: I WOULD LOVE 1237 00:55:31,240 --> 00:55:38,600 TO KNOW THAT. JUST BY 1238 00:55:38,600 --> 00:55:40,200 LOGICALLY DEDUCING IT HAS TO BE 1239 00:55:40,200 --> 00:55:43,000 HAPPENING. WE HAVE NOT LOST OUR 1240 00:55:43,000 --> 00:55:45,880 DNA COPIES YET OBVIOUSLY. BUT 1241 00:55:45,880 --> 00:55:47,600 THE HUMAN AS WELL AS MOUSE 1242 00:55:47,600 --> 00:55:53,400 SPERM CELLS, THERE BELIEVED TO 1243 00:55:53,400 --> 00:55:56,000 DIVIDE SYMMETRICALLY. WHEN YOU 1244 00:55:56,000 --> 00:56:05,600 IDENTIFY SPERM -- STEM CELL, 1245 00:56:05,600 --> 00:56:06,160 THEY DON'T EXHIBIT ANY SIGN 1246 00:56:06,160 --> 00:56:06,640 THAT THEY ARE DIVINING 1247 00:56:06,640 --> 00:56:07,600 ASYMMETRICALLY IN TERMS OF THE 1248 00:56:07,600 --> 00:56:10,800 WEIGHT. PEOPLE HAVE DONE 1249 00:56:10,800 --> 00:56:17,120 LINEAGE TRACING AND MODELING 1250 00:56:17,120 --> 00:56:18,600 USING RODENT SPERMODOGONIA 1251 00:56:18,600 --> 00:56:22,480 (SOUNDS LIKE) STEM CELL. SOME 1252 00:56:22,480 --> 00:56:23,160 OF THE CELLS TAKE OVER AND THEY 1253 00:56:23,160 --> 00:56:28,120 BECOME STEM CELLS, SO THEIR 1254 00:56:28,120 --> 00:56:29,280 FATE VERY PLASTIC. ARE YOU A 1255 00:56:29,280 --> 00:56:36,720 STEM CELL? ARE YOU 1256 00:56:36,720 --> 00:56:38,240 SPERMODOGONIA? DOES NOT MATTER. 1257 00:56:38,240 --> 00:56:40,920 BUT IF YOU THINK ABOUT THE RDNA 1258 00:56:40,920 --> 00:56:41,800 COPY NUMBER THAT IS NOT PART OF 1259 00:56:41,800 --> 00:56:45,520 THE FATE. IF YOU HAVE A LITTLE 1260 00:56:45,520 --> 00:56:46,160 BIT MORE OR LESS OF COPY NUMBER 1261 00:56:46,160 --> 00:56:49,600 YOU HAVE THE SAME 1262 00:56:49,600 --> 00:56:50,160 "TRANSCRIPTION," AND YOU 1263 00:56:50,160 --> 00:56:51,160 IDENTIFY THEM AS EQUAL STEM 1264 00:56:51,160 --> 00:56:54,040 CELLS. 1265 00:56:54,040 --> 00:56:59,480 BUT I BET THERE SHOULD BE SOME 1266 00:56:59,480 --> 00:57:00,120 POPULATION THAT IS DOING THIS, 1267 00:57:00,120 --> 00:57:04,640 INCREASING THE COPY NUMBER. 1268 00:57:04,640 --> 00:57:05,200 THERE IS A BEAUTY IN THE 1269 00:57:05,200 --> 00:57:07,560 REPEATEDLY DOING THIS. IF YOU 1270 00:57:07,560 --> 00:57:09,800 ARE SUPPOSED TO HAVE 200 1271 00:57:09,800 --> 00:57:12,000 COPIES, AND IF YOU GO DOWN TO 1272 00:57:12,000 --> 00:57:14,760 50, IF YOU DO ONLY ONE DIVISION 1273 00:57:14,760 --> 00:57:17,440 YOU MIGHT RECOVER ONLY 60. AND 1274 00:57:17,440 --> 00:57:29,400 THAT'S IT. BUT WHEN THE CELLS 1275 00:57:29,400 --> 00:57:29,960 CAN DO THIS REPEATEDLY 60 1276 00:57:29,960 --> 00:57:33,360 BECOMES 70 AND BECOMES 80. IN 1277 00:57:33,360 --> 00:57:34,000 THAT KIND OF REASONING MAKES ME 1278 00:57:34,000 --> 00:57:34,600 WONDER THAT IF YOU ARE LOOKING 1279 00:57:34,600 --> 00:57:36,320 AT THE RDNA COPY NUMBER I THINK 1280 00:57:36,320 --> 00:57:40,400 THE HUMAN STEM CELL SHOULD BE 1281 00:57:40,400 --> 00:57:42,000 DIVIDING ASYMMETRICALLY. THAT 1282 00:57:42,000 --> 00:57:45,600 WOULD BE MY GUESS. 1283 00:57:45,600 --> 00:57:46,200 >> ONE MORE QUESTION FROM OUR 1284 00:57:46,200 --> 00:57:54,600 LINE. IS POLE 2 USED IN MAKING 1285 00:57:54,600 --> 00:57:55,200 RIBOSOMES OR DOES IT SERVE 1286 00:57:55,200 --> 00:57:55,640 OTHER PURPOSES? 1287 00:57:55,640 --> 00:58:00,120 >> DR. YAMASHITA: TYPICALLY FOR 1288 00:58:00,120 --> 00:58:00,960 2, IT DOES NOT BELIEVE TO DO 1289 00:58:00,960 --> 00:58:04,600 ANY TRANSCRIPTION FOR RDNA. I 1290 00:58:04,600 --> 00:58:07,920 MEAN THAT IS WHAT WE KNOW. 1291 00:58:07,920 --> 00:58:08,560 BUT NOT MANY PEOPLE HAVE REALLY 1292 00:58:08,560 --> 00:58:17,760 LOOKED AT DIFFERENT CONDITIONS. 1293 00:58:17,760 --> 00:58:18,360 THERE IS ONE PAPER THAT SAID 1294 00:58:18,360 --> 00:58:18,960 DURING STRESS CONDITIONS-- I 1295 00:58:18,960 --> 00:58:29,840 DON'T REMEMBER -- IT IS NOT LOW 1296 00:58:29,840 --> 00:58:32,520 COPY NUMBER STRESS CONDITION. 1297 00:58:32,520 --> 00:58:34,200 -- WAS OBSERVED COMING INTO THE 1298 00:58:34,200 --> 00:58:36,960 NUCLEUS. AT THAT POINT R2 1299 00:58:36,960 --> 00:58:43,960 TRANSCRIBED INTO RDNA BECOMES 1300 00:58:43,960 --> 00:58:47,800 RIBOZYME? THAT I DON'T KNOW. 1301 00:58:47,800 --> 00:58:48,360 >> I HAVE A QUESTION IN THE 1302 00:58:48,360 --> 00:58:50,440 HOPE THIS DOESN'T MEAN THAT I 1303 00:58:50,440 --> 00:58:52,720 DID NOT SYNTHESIZE ALL THE 1304 00:58:52,720 --> 00:58:54,000 PARTS BUT I THOUGHT FROM YOUR 1305 00:58:54,000 --> 00:58:54,600 CO-FISH IN THE BEGINNING THAT 1306 00:58:54,600 --> 00:59:04,920 WAS NOT FROM THE RDNA LOCUS. IT 1307 00:59:04,920 --> 00:59:05,560 IS THE METHOD OF MAGNIFICATION 1308 00:59:05,560 --> 00:59:06,160 TRANSPACIFIC SO THE LONGER IS 1309 00:59:06,160 --> 00:59:06,720 ALWAYS GOING TO HIT ON ONE 1310 00:59:06,720 --> 00:59:07,040 STREAM? 1311 00:59:07,040 --> 00:59:08,240 >> DR. YAMASHITA: I THINK I DO 1312 00:59:08,240 --> 00:59:14,720 HAVE THE SLIDE UP. I TYPICALLY 1313 00:59:14,720 --> 00:59:17,880 KEEP THAT SLIDE SOMEWHERE. YES, 1314 00:59:17,880 --> 00:59:21,960 FIRST OF ALL WE DISCOVERED -- 1315 00:59:21,960 --> 00:59:27,840 SEGREGATION. 1316 00:59:27,840 --> 00:59:29,280 HOW IT GOT THE SAME COPY 1317 00:59:29,280 --> 00:59:33,720 NUMBER, STILL SEGREGATING --? 1318 00:59:33,720 --> 00:59:34,240 INDEED I ACTUALLY ALMOST 1319 00:59:34,240 --> 00:59:35,520 SKIPPED ONE PIECE OF CRITICAL 1320 00:59:35,520 --> 00:59:42,400 INFORMATION WHEN I SAID, OH, WE 1321 00:59:42,400 --> 00:59:43,040 REALIZED THERE WAS ASYMMETRY IN 1322 00:59:43,040 --> 00:59:47,800 THE COVER NUMBER. TO BE MUCH 1323 00:59:47,800 --> 00:59:48,440 MORE PRECISE THAT IS ASYMMETRY 1324 00:59:48,440 --> 00:59:49,000 IN THE PROPENSITY OF THE 1325 00:59:49,000 --> 00:59:49,800 INCREASE IN THE COPY NUMBER. 1326 00:59:49,800 --> 00:59:51,920 THAT MEANS-- WHAT WE THINK IS 1327 00:59:51,920 --> 00:59:58,120 THAT BECAUSE RDNA REPLICATE IN 1328 00:59:58,120 --> 01:00:02,000 THE UNIQUE DIRECTIONAL WAY, 1329 01:00:02,000 --> 01:00:02,600 BECAUSE OF THAT SPECIFICALLY 1330 01:00:02,600 --> 01:00:13,000 FOR RDNA LOCUS, THE STRAND IS 1331 01:00:13,000 --> 01:00:13,680 (INCOMPREHENSIBLE). IN THE CASE 1332 01:00:13,680 --> 01:00:24,600 OF YEAST, NOBODY DETECTED WHICH 1333 01:00:24,600 --> 01:00:25,240 COPY GOES TO WHICH SIDE, BUT IN 1334 01:00:25,240 --> 01:00:30,080 CASE OF YEAST TYPICALLY THE 1335 01:00:30,080 --> 01:00:30,680 BRAKES HAPPENS AT THE LEADING 1336 01:00:30,680 --> 01:00:31,480 STRAND AND REVIEWED DREW THE 1337 01:00:31,480 --> 01:00:32,120 CARTOON, YOU WOULD SEE THAT IF 1338 01:00:32,120 --> 01:00:34,360 YOU'RE LEADING STRAND BREAKS, 1339 01:00:34,360 --> 01:00:36,520 YOU CANNOT GO BEYOND THE 1340 01:00:36,520 --> 01:00:37,120 REPLICATION WHERE REPLICATION 1341 01:00:37,120 --> 01:00:42,240 IS NOT COMPLETED. IF YOU BREAK 1342 01:00:42,240 --> 01:00:50,280 AND TRIED TO GO BEYOND THE -- 1343 01:00:50,280 --> 01:00:50,800 YOU END UP BREAKING THE 1344 01:00:50,800 --> 01:00:52,200 CHROMOSOME AND THE ONLY WAY YOU 1345 01:00:52,200 --> 01:00:52,680 CAN REPAIR THE BREAKING 1346 01:00:52,680 --> 01:00:54,840 CHROMOSOME IS AT THE POINT OF 1347 01:00:54,840 --> 01:00:55,480 THE BREAKING THE LEADING STRAND 1348 01:00:55,480 --> 01:00:56,080 HAVE TO GO BACK AND INCREASE 1349 01:00:56,080 --> 01:00:59,920 THE COPY NUMBER. IF SOMEBODY 1350 01:00:59,920 --> 01:01:00,560 WOULD ASK ME TO BED I WOULD BET 1351 01:01:00,560 --> 01:01:01,120 THAT THE LEADING STRAND IS 1352 01:01:01,120 --> 01:01:05,240 GOING TO THE STEM CELL. THAT 1353 01:01:05,240 --> 01:01:06,160 IS PURE SPECULATION BASED ON 1354 01:01:06,160 --> 01:01:06,800 WHAT WOULD MAKE SENSE. WE DON'T 1355 01:01:06,800 --> 01:01:08,400 KNOW. 1356 01:01:08,400 --> 01:01:09,920 >> THANK YOU. 1357 01:01:09,920 --> 01:01:10,600 >> I WANT TO END THE SESSION BY 1358 01:01:10,600 --> 01:01:11,600 THANKING DR. YAMASHITA. THANK 1359 01:01:11,600 --> 01:01:12,080 YOU EVERYONE FOR YOUR 1360 01:01:12,080 --> 01:01:13,080 PARTICIPATION. 1361 01:01:13,080 --> 01:01:14,720 >> DR. YAMASHITA: THANK YOU SO 1362 01:01:14,720 --> 00:00:00,000 MUCH.