1 00:00:08,520 --> 00:00:12,520 I WORK WITH ALAN FOR 12 YEARS. 2 00:00:12,520 --> 00:00:15,400 FIRST AS POSTDOC AND THEN STAFF 3 00:00:15,400 --> 00:00:16,720 SCIENTIST, SO, THIS MORNING'S 4 00:00:16,720 --> 00:00:19,360 SESSION IS REALLY DEDICATED, 5 00:00:19,360 --> 00:00:22,200 CELEBRATING ALAN'S LEADERSHIP IN 6 00:00:22,200 --> 00:00:26,280 THE COLLABORATION AND NIAID 7 00:00:26,280 --> 00:00:27,240 IMMUNOLOGY PROGRAM. 8 00:00:27,240 --> 00:00:30,160 AS SOME OF YOU KNOW, ALAN HAS 9 00:00:30,160 --> 00:00:31,800 LONGSTANDING INTEREST IN MICRO 10 00:00:31,800 --> 00:00:36,520 BACTERIA RESEARCH AND I THINK HE 11 00:00:36,520 --> 00:00:39,240 STARTED WITH MICRO BACTERIA 12 00:00:39,240 --> 00:00:44,800 AVIAN WITH MARK DOUGHERTY AND 13 00:00:44,800 --> 00:00:48,800 2000, ALAN DECIDED TO REALLY 14 00:00:48,800 --> 00:00:53,200 MOVE INTO USE REAL BUGS AND MBT 15 00:00:53,200 --> 00:01:03,680 AND THEN HE HIRED MYSELF TO 16 00:01:04,640 --> 00:01:06,080 REALLY KICK-START THE PROGRAM 17 00:01:06,080 --> 00:01:08,920 AND ALAN USED TO CALL US THREE 18 00:01:08,920 --> 00:01:12,720 MUSKETEERS AND WE REALLY WORKED 19 00:01:12,720 --> 00:01:14,000 FROM SCRATCH AT THE TIME AND I 20 00:01:14,000 --> 00:01:15,680 REMEMBER THAT TIME WHEN YOU EVEN 21 00:01:15,680 --> 00:01:20,000 DON'T HAVE A FUNCTION OF PIECE 22 00:01:20,000 --> 00:01:21,400 OF THREAD SO WE HAVE TO BOR' 23 00:01:21,400 --> 00:01:21,600 SPACE. 24 00:01:21,600 --> 00:01:25,720 I HAD TO WORK WITH KAREN AND 25 00:01:25,720 --> 00:01:30,080 DAMIAN AND CHUCK HAS TO DRIVE TO 26 00:01:30,080 --> 00:01:33,560 TIM BROOKE TO USE TIMBER''S PC3 27 00:01:33,560 --> 00:01:37,640 AND I REMEMBER WE ALWAYS TALK 28 00:01:37,640 --> 00:01:39,360 ABOUT HOW WE CAN MAKE A 29 00:01:39,360 --> 00:01:41,560 CONTRIBUTION TO THE TB RESEARCH 30 00:01:41,560 --> 00:01:44,160 AND HOW TO MARK OUR TERRITORY AS 31 00:01:44,160 --> 00:01:46,360 A NEW KID ON THE BLOCK. 32 00:01:46,360 --> 00:01:50,480 DON'T GET BULLIED BY OTHERS. 33 00:01:50,480 --> 00:01:52,720 SO, ANYWAY, SO THAT IS THE LONG 34 00:01:52,720 --> 00:01:57,160 TIME AGO SO I THINK UNDER ALAN'S 35 00:01:57,160 --> 00:02:00,040 LEADERSHIP, AS YOU CAN SEE NOW, 36 00:02:00,040 --> 00:02:05,760 NIAID PROVIDES THE BEST EQUIPPED 37 00:02:05,760 --> 00:02:09,880 AND LEADER IN THE TB IMMUNOLOGY 38 00:02:09,880 --> 00:02:10,640 IN THE WORLD. 39 00:02:10,640 --> 00:02:18,800 SO THAT IS REALLY REFLECTION OF 40 00:02:18,800 --> 00:02:23,800 ALAN'S LEADERSHIP AND THIS 41 00:02:23,800 --> 00:02:25,400 PROGRAM HAS TRAINED 15 FELLOWS 42 00:02:25,400 --> 00:02:29,720 AND POSTDOCS AND ALL OF US HAVE 43 00:02:29,720 --> 00:02:32,000 GONE TO ESTABLISH OUR OWN 44 00:02:32,000 --> 00:02:32,680 RESEARCH PROGRAMS. 45 00:02:32,680 --> 00:02:37,360 SO I THINK THAT IS TREMENDOUS 46 00:02:37,360 --> 00:02:39,280 CAREER AND GREAT CAREER FOR 47 00:02:39,280 --> 00:02:40,160 ALAN. 48 00:02:40,160 --> 00:02:41,040 WE ALL APPRECIATE IT. 49 00:02:41,040 --> 00:02:43,800 THANK YOU, VERY MUCH, ALAN. 50 00:02:43,800 --> 00:02:47,400 IT'S A GREAT HONOR TO BE PART OF 51 00:02:47,400 --> 00:02:50,360 THIS PROGRAM AND IN YOUR 52 00:02:50,360 --> 00:02:50,840 MENTORSHIP. 53 00:02:50,840 --> 00:02:52,320 IT'S GREAT FUN. 54 00:02:52,320 --> 00:02:55,120 I HAD A GOOD TIME AND WE HAD A 55 00:02:55,120 --> 00:02:59,480 FUN TIME. 56 00:02:59,480 --> 00:03:02,200 SO, BEFORE INTRODUCING AND 57 00:03:02,200 --> 00:03:05,080 INVITING OUR FELLOW FORMER 58 00:03:05,080 --> 00:03:07,000 TRAINEES TO PRESENT THEIR RECENT 59 00:03:07,000 --> 00:03:10,040 WORK, I JUST WANT TO INVITE BOB, 60 00:03:10,040 --> 00:03:15,400 BOB COFFMAN, TO HAVE SEVERAL 61 00:03:15,400 --> 00:03:20,520 WORDS AND OPENING REMARKS FOR 62 00:03:20,520 --> 00:03:21,040 ALAN. 63 00:03:21,040 --> 00:03:23,840 ROBERT COFFMAN HAS BEEN A STRONG 64 00:03:23,840 --> 00:03:32,080 SUPPORTER OF IMMUNO BIOLOGY 65 00:03:32,080 --> 00:03:32,320 SECTION. 66 00:03:32,320 --> 00:03:36,800 [APPLAUSE] 67 00:03:36,800 --> 00:03:38,240 ALL RIGHT. 68 00:03:38,240 --> 00:03:40,160 SO, IT SORT OF FOR THOUSANDS OF 69 00:03:40,160 --> 00:03:43,480 YEARS NOW, I'M SURE, WHEN THE 70 00:03:43,480 --> 00:03:45,360 ELDERS OF ANY TRIBE GOT TOGETHER 71 00:03:45,360 --> 00:03:49,520 AS WE'RE DOING HERE, THEY WOULD 72 00:03:49,520 --> 00:03:52,040 SIT AROUND THE CAMPFIRE OR WHAT 73 00:03:52,040 --> 00:03:54,760 HAVE YOU AND TELL ORIGIN STORIES 74 00:03:54,760 --> 00:03:57,120 TO PASS THEM ON ORALLY TO THE 75 00:03:57,120 --> 00:03:58,400 NEXT GENERATION, I SUPPOSE WAS 76 00:03:58,400 --> 00:03:59,760 THE PURPOSE OF THAT SO THAT'S 77 00:03:59,760 --> 00:04:01,440 WHAT I'LL TRY TO DO IN THE NEXT 78 00:04:01,440 --> 00:04:06,200 FEW MINUTES IS TELL A COUPLE OF 79 00:04:06,200 --> 00:04:06,680 ORIGIN STORIES. 80 00:04:06,680 --> 00:04:07,920 AND PROBABLY IT'S GOOD TO FALL 81 00:04:07,920 --> 00:04:11,600 TO ME SINCE I MAY HAVE KNOWN 82 00:04:11,600 --> 00:04:14,800 ALAN LONGER THAN ANYONE HERE, 83 00:04:14,800 --> 00:04:17,880 HAVING MET HIM ORIGINALLY HERE 84 00:04:17,880 --> 00:04:25,520 AT THE VERY BEGINNING OF 1970. 85 00:04:25,520 --> 00:04:27,240 SO PLAS TA STEEN SO STONE 86 00:04:27,240 --> 00:04:28,960 ARCHITECT TIRE AND IT'S A SOCK 87 00:04:28,960 --> 00:04:29,240 INSTITUTE. 88 00:04:29,240 --> 00:04:32,160 I WAS COMING IN AS A WET BEHIND 89 00:04:32,160 --> 00:04:34,160 THE EARS AND BEGINNING GRADUATE 90 00:04:34,160 --> 00:04:36,800 STUDENT TRYING TO LEARN WHAT 91 00:04:36,800 --> 00:04:37,800 ANTIBODIES WERE. 92 00:04:37,800 --> 00:04:42,640 ALAN WAS ON THE OTHER SIDE OF 93 00:04:42,640 --> 00:04:48,440 TBENCH. 94 00:04:48,440 --> 00:04:49,880 ALAN WAS TRYING TO CRAFT 95 00:04:49,880 --> 00:04:51,680 SOMETHING LIKE A PRESENTABLE 96 00:04:51,680 --> 00:04:58,640 THESIS AND GET OUT AT THE TIME. 97 00:04:58,640 --> 00:04:59,880 WE OVERLAPPED FOR ABOUT 18 98 00:04:59,880 --> 00:05:01,120 MONTHS ACROSS THE BENCH. 99 00:05:01,120 --> 00:05:03,640 I CAN'T SAY I KNEW ALAN 100 00:05:03,640 --> 00:05:04,520 PARTICULARLY WELL. 101 00:05:04,520 --> 00:05:05,760 HE WORKED VERY HARD AND HE 102 00:05:05,760 --> 00:05:07,760 WORKED LATE AND HE WAS VERY 103 00:05:07,760 --> 00:05:08,560 SERIOUS. 104 00:05:08,560 --> 00:05:11,160 CHRIST, HE DIDN'T EVEN SURF SO 105 00:05:11,160 --> 00:05:13,680 WE HAD NO SHARED VALUES AT THAT 106 00:05:13,680 --> 00:05:14,040 POINT. 107 00:05:14,040 --> 00:05:18,280 BUT HE WAS A NICE GUY AND I 108 00:05:18,280 --> 00:05:28,520 ENJOYED TIME. 109 00:05:29,680 --> 00:05:32,120 HE IS LOOKING VERY DAPPER THIS 110 00:05:32,120 --> 00:05:37,560 IS FROM 1967. 111 00:05:37,560 --> 00:05:42,720 EVEN THEN TRYING TO SMILE. 112 00:05:42,720 --> 00:05:47,120 SO, OUR MENTOR WAS ON THE RIGHT, 113 00:05:47,120 --> 00:05:51,640 VERY PROMINENT IMMUNOLOGY AT THE 114 00:05:51,640 --> 00:05:55,840 TIME, VERY BRILLIANT MAN AND HAD 115 00:05:55,840 --> 00:05:57,400 A LOT OF INFLUENCE IN 116 00:05:57,400 --> 00:05:58,640 FORMULATING THE QUESTIONS AND 117 00:05:58,640 --> 00:06:01,280 CELLULAR AND MOLECULAR 118 00:06:01,280 --> 00:06:03,320 IMMUNOLOGY AND THERE IS JOHN 119 00:06:03,320 --> 00:06:05,880 WITH HIS WIFE SUZANNE AND A VERY 120 00:06:05,880 --> 00:06:14,600 YOUNG LOOKING GUS ON THE LEFT. 121 00:06:14,600 --> 00:06:16,640 MEL HAD GROWN UP AND DONE HIS 122 00:06:16,640 --> 00:06:17,640 FORMATIVE TRAINING FOR MANY 123 00:06:17,640 --> 00:06:23,000 YEARS IN PARIS AND STUDYING THE 124 00:06:23,000 --> 00:06:26,480 PIONEERS STUDIES OF BACTERIAL 125 00:06:26,480 --> 00:06:29,080 GENE REGULATION SO HE WAS, 126 00:06:29,080 --> 00:06:30,600 ALTHOUGH INTERESTED IN 127 00:06:30,600 --> 00:06:32,880 IMMUNOLOGY AT THIS POINT, A 128 00:06:32,880 --> 00:06:34,640 REALLY COMMITTED REDUCTIONIST IN 129 00:06:34,640 --> 00:06:36,520 TERMS OF HIS APPROACH TO SCIENCE 130 00:06:36,520 --> 00:06:38,160 AND A VERY MUCH COMMITTED TO 131 00:06:38,160 --> 00:06:40,400 USING SIMPLE SYSTEMS AND MODEL 132 00:06:40,400 --> 00:06:42,640 ORGANISMS AND THE IDEA OF 133 00:06:42,640 --> 00:06:49,560 ACTUALLY SIACTUALSTUDYING THE IE 134 00:06:49,560 --> 00:06:53,040 JUST SENT CHILLS DOWN HIS SPINE. 135 00:06:53,040 --> 00:06:57,960 AT THE SAME TIME, THERE WERE NEW 136 00:06:57,960 --> 00:07:00,800 WINDS BLOWING AROUND EVERYWHERE 137 00:07:00,800 --> 00:07:03,800 IN THE EARLY 70s AND THE ERA 138 00:07:03,800 --> 00:07:05,920 OF VIETNAM WAR PROTEST AND SO 139 00:07:05,920 --> 00:07:09,480 FOURTH AND SO ON AND ALONG WITH 140 00:07:09,480 --> 00:07:12,120 THAT A NEW SENSE OF SOCIAL 141 00:07:12,120 --> 00:07:14,440 RESPONSIBILITY THAT TOOK HOLD IN 142 00:07:14,440 --> 00:07:18,160 A LOT OF THE STUDENTS AND 143 00:07:18,160 --> 00:07:19,080 POSTDOCS AT SOCK INSTITUTE. 144 00:07:19,080 --> 00:07:20,400 I REMEMBER THIS VERY CLEARLY 145 00:07:20,400 --> 00:07:22,840 BECAUSE THIS IS WHAT WAS ALL 146 00:07:22,840 --> 00:07:24,160 FERMENTING OVER MY FIRST YEAR OR 147 00:07:24,160 --> 00:07:24,880 TWO THERE. 148 00:07:24,880 --> 00:07:27,960 I THINK IT INFLUENCED ALAN, 149 00:07:27,960 --> 00:07:33,640 BECAUSE HE MUCH TO THE DISGRACE 150 00:07:33,640 --> 00:07:35,400 OF THE LAB HE DECIDED TO BECOME 151 00:07:35,400 --> 00:07:39,280 A PARA SATOLOGIST WHEN HE LEFT 152 00:07:39,280 --> 00:07:40,480 THE LAB AND TRAINED THERE. 153 00:07:40,480 --> 00:07:44,600 AT THIS POINT, ALAN AND I, OUR 154 00:07:44,600 --> 00:07:45,520 PATHS DIVERGED A LOT. 155 00:07:45,520 --> 00:07:49,400 I WENT AHEAD AND FINISHED 156 00:07:49,400 --> 00:07:50,920 GRADUATE WORK AND DID POSTDOC AT 157 00:07:50,920 --> 00:07:55,600 STANFORD AND GOT INVOLVED IN 158 00:07:55,600 --> 00:07:57,280 STARTING A VERY INTERESTING 159 00:07:57,280 --> 00:07:59,720 RESEARCH INSTITUTE CALLED DEAN 160 00:07:59,720 --> 00:08:01,680 ACTS IN PALO ALTO WHICH SOME OF 161 00:08:01,680 --> 00:08:03,480 THE OLDTIMERS KNOW. 162 00:08:03,480 --> 00:08:06,080 AND I PROBABLY DIDN'T SEE ALAN 163 00:08:06,080 --> 00:08:10,200 FOR 12 OR 13 YEARS AT LEAST. 164 00:08:10,200 --> 00:08:16,960 IN THE MEANTIME, TIM AND I HAD 165 00:08:16,960 --> 00:08:18,520 DONE SOME OF THE WORK THAT WE'VE 166 00:08:18,520 --> 00:08:20,720 BEEN DOING IN OUR RESPECTIVE 167 00:08:20,720 --> 00:08:22,920 LABS ON TRYING TO DEFINE T-CELL 168 00:08:22,920 --> 00:08:25,360 CYTOKINES AND SOME OF THEIR 169 00:08:25,360 --> 00:08:25,680 FUNCTIONS. 170 00:08:25,680 --> 00:08:28,160 AND CAME OUT WITH SOMETHING THAT 171 00:08:28,160 --> 00:08:32,120 LOOKS FAMILIAR NOW AND I WON'T 172 00:08:32,120 --> 00:08:32,440 BELABOR HERE. 173 00:08:32,440 --> 00:08:34,720 WE'RE PROPOSING THAT BASICALLY 174 00:08:34,720 --> 00:08:39,480 THE CD4 T-CELL RESPONSE TO 175 00:08:39,480 --> 00:08:41,120 ANTIGENS COULD REALLY SORT 176 00:08:41,120 --> 00:08:46,280 ITSELF OUT AS TWO MAJOR T-CELL 177 00:08:46,280 --> 00:08:51,800 SUBSETS AND NAMED TH1 AND TH2. 178 00:08:51,800 --> 00:08:52,840 THESE DELIVERED BY THEIR 179 00:08:52,840 --> 00:08:57,760 PATTERNS OF CYTOKINE EXPRESSION 180 00:08:57,760 --> 00:08:59,200 BUT ALSO BY THE DIFFERENCES IN 181 00:08:59,200 --> 00:09:01,240 FUNCTIONS THAT ARE MEDIATED BY 182 00:09:01,240 --> 00:09:03,800 THOSE DIFFERENT EVERY SHALL 183 00:09:03,800 --> 00:09:05,440 CYTOKINE PATTERNS AND IN 184 00:09:05,440 --> 00:09:07,400 ADDITION IT'S SHOWN IN THE BLUE 185 00:09:07,400 --> 00:09:09,840 ARROWS, THERE WERE A NUMBER OF 186 00:09:09,840 --> 00:09:11,160 RECIPROCAL INHIBITORY 187 00:09:11,160 --> 00:09:15,840 INTERACTION THAT'S ALLOWED FOR 188 00:09:15,840 --> 00:09:17,480 INTERESTING POSSIBILITIES FOR 189 00:09:17,480 --> 00:09:21,640 THEIR UNDERSTANDING IMMUNO 190 00:09:21,640 --> 00:09:21,960 REGULATION. 191 00:09:21,960 --> 00:09:23,400 DURING THE BEGINNINGS OF THIS WE 192 00:09:23,400 --> 00:09:25,120 WERE CONVINCED THIS WAS RELEVANT 193 00:09:25,120 --> 00:09:29,040 TO ALLERGIC DISEASES BUT WE'RE 194 00:09:29,040 --> 00:09:31,760 JUST, TIM AND I WERE TRYING TO 195 00:09:31,760 --> 00:09:33,480 FIGURE OUT DOES IT HAVE 196 00:09:33,480 --> 00:09:34,560 RELEVANCE BEYOND THAT? 197 00:09:34,560 --> 00:09:36,440 WHAT ABOUT REAL INFECTIONS AND 198 00:09:36,440 --> 00:09:38,160 CONTROLLING INFECTIONS? 199 00:09:38,160 --> 00:09:41,000 SO BY CHANCE, I WAS ON THE NIH 200 00:09:41,000 --> 00:09:42,440 CAMPUS AND I THINK WE WERE 201 00:09:42,440 --> 00:09:49,840 REALLY JUST RANDOMLY BUMPED INTO 202 00:09:49,840 --> 00:09:55,080 ALLEN WE GOT TO TALKING AND I 203 00:09:55,080 --> 00:09:57,160 TOLD HIM ABOUT THAT AND HE GOT 204 00:09:57,160 --> 00:09:58,880 EXCITED AND SAID THIS MAY BE THE 205 00:09:58,880 --> 00:10:02,480 ANSWER TO ALL OF THE UNANSWERED 206 00:10:02,480 --> 00:10:04,240 PHENOMENON IN SOME OF THE 207 00:10:04,240 --> 00:10:06,720 PARASITE IMMUNOLOGY SYSTEMS I 208 00:10:06,720 --> 00:10:08,320 STUDIFUL LET'S TRY TO DO SOME 209 00:10:08,320 --> 00:10:11,560 THINGS TOGETHER AND WE DID AND A 210 00:10:11,560 --> 00:10:13,880 NUMBER OF YEARS OF LOVELY AND 211 00:10:13,880 --> 00:10:15,320 VERY FRUITFUL COLLABORATIONS AND 212 00:10:15,320 --> 00:10:16,760 THE FIRST OF THEM I THINK IS 213 00:10:16,760 --> 00:10:18,240 VERY IMPORTANT. 214 00:10:18,240 --> 00:10:19,680 PHIL SCOTT ALLUDED TO IT 215 00:10:19,680 --> 00:10:23,760 YESTERDAY BUT LET ME SHOW YOU 216 00:10:23,760 --> 00:10:24,520 THE BOTTOM LINE. 217 00:10:24,520 --> 00:10:26,520 THIS IS THE FIRST OUTCOME OF THE 218 00:10:26,520 --> 00:10:32,800 WORK WETOGETHER AND THIS IS WITH 219 00:10:32,800 --> 00:10:34,840 PHIL AND PEARCE AND AT THE TIME, 220 00:10:34,840 --> 00:10:37,560 THAT ALAN AND I MET UP THEY WERE 221 00:10:37,560 --> 00:10:39,200 DEVELOPING A T-CELL LINES AND 222 00:10:39,200 --> 00:10:42,040 WE'RE NOT FORMALLY CLONES BUT 223 00:10:42,040 --> 00:10:46,880 CLOSE, T-CELL LINES TO ANTIGENS 224 00:10:46,880 --> 00:10:48,240 THAT HAD INTERESTING PROPERTIES 225 00:10:48,240 --> 00:10:50,200 WHEN YOU TRANSFERRED THEM IN 226 00:10:50,200 --> 00:10:52,160 NORMAL MICE AND INFECTED AND 227 00:10:52,160 --> 00:10:53,320 THIS IS A GOOD EXAMPLE. 228 00:10:53,320 --> 00:10:56,360 THIS IS LYNN ONE ACTUALLY DID 229 00:10:56,360 --> 00:10:58,840 SOMETHING QUITE REMARKABLE WHICH 230 00:10:58,840 --> 00:11:00,400 IT MADE THE FOOT PADS SWELLING 231 00:11:00,400 --> 00:11:02,880 AND THE DISEASE WORSE THAN IF 232 00:11:02,880 --> 00:11:05,240 YOU JUST PUT IN NORMAL T CELLS 233 00:11:05,240 --> 00:11:06,960 OR NO T CELLS AT ALL WHERE 234 00:11:06,960 --> 00:11:10,560 OTHERS SUCHS A THE LINE NINE 235 00:11:10,560 --> 00:11:11,640 GAVE COMPLETE PROTECTION WHEN 236 00:11:11,640 --> 00:11:13,760 YOU CHALLENGED. 237 00:11:13,760 --> 00:11:16,160 THE DIFFERENCES CORRELATED 238 00:11:16,160 --> 00:11:18,960 PRETTY ACCURATELY WITH THE 239 00:11:18,960 --> 00:11:21,320 DISTINCTIONS THAT TIM AND I HAD 240 00:11:21,320 --> 00:11:23,440 PROPOSED AND NOT SHOWN HERE IS 241 00:11:23,440 --> 00:11:25,440 INTERFERON GAMMA BUT ALIGN NINE 242 00:11:25,440 --> 00:11:28,000 AND IN ADDITION TO MAKING IL2 243 00:11:28,000 --> 00:11:31,760 BUT NOT IL4 AND 5 MADE GAMMA AND 244 00:11:31,760 --> 00:11:33,600 LINE ONE DID NOT. 245 00:11:33,600 --> 00:11:35,320 THESE WERE CLASSIC PHENOTYPES 246 00:11:35,320 --> 00:11:37,240 BUT THIS WAS THE FIRST PAPER TO 247 00:11:37,240 --> 00:11:39,520 REALLY SHOW THAT THEY WERE 248 00:11:39,520 --> 00:11:42,120 LEADING TO REALLY DRAMATICALLY 249 00:11:42,120 --> 00:11:43,600 DIFFERENT OUTCOMES IN AN 250 00:11:43,600 --> 00:11:46,200 INFECTIOUS DISEASE SYSTEM. 251 00:11:46,200 --> 00:11:52,640 EVERYTHING ELSE BEING COST IN 252 00:11:52,640 --> 00:11:56,400 THIS FIELD. 253 00:11:56,400 --> 00:11:58,440 IT WAS A LANDMARK TIME. 254 00:11:58,440 --> 00:12:01,360 SO THIS WAS A REAL I AM FLECKION 255 00:12:01,360 --> 00:12:03,520 POINT FOR ALAN AND I. 256 00:12:03,520 --> 00:12:06,520 ALAN BECAME A T-CELL AND 257 00:12:06,520 --> 00:12:10,080 IMMUNOLOGIST HERE AND I BECAME A 258 00:12:10,080 --> 00:12:14,840 LEASH MANIAC AND STARTED FROM 259 00:12:14,840 --> 00:12:20,840 ALAN AND THEY LET ME SET UP A 260 00:12:20,840 --> 00:12:22,000 LEISHMANIA SYSTEM IN MY LAB AND 261 00:12:22,000 --> 00:12:24,880 WE DID STUDIES USE PARTICULAR AS 262 00:12:24,880 --> 00:12:27,360 A COOL FOR STUDYING IMMUNE 263 00:12:27,360 --> 00:12:29,360 REGULATION AND I'LL JUST SHOW 264 00:12:29,360 --> 00:12:30,640 YOU ONE OF THE FAVORITE PAPER 265 00:12:30,640 --> 00:12:37,360 BECAUSE IT'S A GREAT EXAMPLE OF 266 00:12:37,360 --> 00:12:38,360 A YOU DON'T ALWAYS GET WHAT YOU 267 00:12:38,360 --> 00:12:39,760 WANT BUT SOMETIMES YOU GET WHAT 268 00:12:39,760 --> 00:12:46,120 YOU NEED PHENOMENON TO PHOTO 269 00:12:46,120 --> 00:12:48,400 MICK JAGGER AND SO A PAPER WITH 270 00:12:48,400 --> 00:12:50,320 TWO VERY RIGHT PEOPLE, RODRIGO 271 00:12:50,320 --> 00:12:54,760 FROM ALAN'S LAB AND FIONA AND 272 00:12:54,760 --> 00:12:56,760 BASICALLY THEY WERE TRYING TO 273 00:12:56,760 --> 00:13:00,440 CHASE UP WHAT WE AND OTHERS WAS 274 00:13:00,440 --> 00:13:03,600 THE FACT THAT IN MICE THAT DON'T 275 00:13:03,600 --> 00:13:06,480 HEAL AND DEVELOP A THC RESPONSE 276 00:13:06,480 --> 00:13:08,560 WHEN THEY'RE INFECTED WITH LEASH 277 00:13:08,560 --> 00:13:09,640 MANIA THAT THERE'S ALWAYS 278 00:13:09,640 --> 00:13:12,080 EVIDENCE OF SOME LEASH MANIA 279 00:13:12,080 --> 00:13:15,400 SPECIFIC INTERFERON GAM AND 280 00:13:15,400 --> 00:13:18,480 WHETHER IT'S TH1 CELLS AND WHY 281 00:13:18,480 --> 00:13:29,040 IN THEY THERE AND IT WAS REVERSD 282 00:14:06,240 --> 00:14:08,720 BY ANTI-IL4 BUT AN INTERESTING 283 00:14:08,720 --> 00:14:10,480 THING IS THE INTERFERON RESPONSE 284 00:14:10,480 --> 00:14:12,880 WAS AMONG THE PHENOTYPE WHICH 285 00:14:12,880 --> 00:14:14,920 WAS ASSOCIATED WITH NAIVE T 286 00:14:14,920 --> 00:14:22,040 CELLS AND THE RBIT CELLS AND 287 00:14:22,040 --> 00:14:23,200 THEY WERE TRANSFERRED HEALING 288 00:14:23,200 --> 00:14:26,560 TH1 RESPONSE TO THIS ANIMAL AND 289 00:14:26,560 --> 00:14:28,920 THAT WAS ALL VERY INTERESTING 290 00:14:28,920 --> 00:14:31,080 EXCEPT THE MICE THAT HEALED 291 00:14:31,080 --> 00:14:34,760 WEREN'T REALLY OUT OF T WOODS BE 292 00:14:34,760 --> 00:14:36,400 IN SIX OR EIGHT WEEKS THEY 293 00:14:36,400 --> 00:14:38,600 STARTED SUFFERING FROM A SEVERE 294 00:14:38,600 --> 00:14:42,040 INFLAMMATION OF THE COLON, SO 295 00:14:42,040 --> 00:14:45,000 FIONA DID THE OBVIOUS CELL AND 296 00:14:45,000 --> 00:14:47,440 SASS IF THIS HAPPENS IF WE TAKE 297 00:14:47,440 --> 00:14:49,560 LEISHMANIA OUT OF THE EQUATION, 298 00:14:49,560 --> 00:14:51,440 WE DO ISOLATE THE CELLS FROM 299 00:14:51,440 --> 00:14:53,760 LEISHMANIA INFECTED MICE AND WE 300 00:14:53,760 --> 00:14:55,720 JUST DID NORMAL CELLS AND 301 00:14:55,720 --> 00:14:58,880 FRACTION EIGHT THEM AND TRANSFER 302 00:14:58,880 --> 00:15:00,360 THEM INTO SKID MICE NO 303 00:15:00,360 --> 00:15:07,200 LEISHMANIA INFECTION TO THAT AND 304 00:15:07,200 --> 00:15:09,160 YOU GET THE SAME PHENOMENON MANY 305 00:15:09,160 --> 00:15:13,320 OF NORMAL MOUSE COLONS AND IT'S 306 00:15:13,320 --> 00:15:16,600 TYPICAL SECTIONS AND 307 00:15:16,600 --> 00:15:18,880 TRANSFERRING THE CELLS LED TO 308 00:15:18,880 --> 00:15:22,600 GREAT ENLARGEMENT OF THE COLON, 309 00:15:22,600 --> 00:15:25,040 SEVERE DISRUPTION OF THE 310 00:15:25,040 --> 00:15:26,480 ARCHITECTURE AND CELL TYPES AND 311 00:15:26,480 --> 00:15:28,480 LOSS OF T CELLS IN THERE BUT 312 00:15:28,480 --> 00:15:30,080 INTERESTINGLY ENOUGH, IF YOU MIX 313 00:15:30,080 --> 00:15:32,920 BACK IN AND CO TRANSFERRED AN 314 00:15:32,920 --> 00:15:36,600 PRE PRE AT NUMBER OF THE CD45RB 315 00:15:36,600 --> 00:15:38,680 LOW CELLS WITH THOSE, NONE OF 316 00:15:38,680 --> 00:15:39,520 THIS HAPPENS AND THEY WERE 317 00:15:39,520 --> 00:15:42,760 NORMAL AND YOU CAN LET THEM DIE 318 00:15:42,760 --> 00:15:44,040 OF OLD AGE AND SEE ANYTHING. 319 00:15:44,040 --> 00:15:47,600 SO, THIS TURNED OUT AFTER 320 00:15:47,600 --> 00:15:50,360 ANOTHER SERIES OF VERY ELEGANT 321 00:15:50,360 --> 00:15:52,840 EXPERIMENTS FROM GERMAN BUY 322 00:15:52,840 --> 00:15:58,440 FIONA TO BE ONE OF THE THREE OR 323 00:15:58,440 --> 00:16:00,280 OUR DIFFERENT LINES THAT LED TO 324 00:16:00,280 --> 00:16:02,880 OUR CURRENT SYNTHESIS OF 325 00:16:02,880 --> 00:16:04,720 REGULATORY T CELLS THE STORY 326 00:16:04,720 --> 00:16:06,800 BEING THEY'RE LOW POPULATION 327 00:16:06,800 --> 00:16:10,240 CONTAINED A POPULATION OF T 328 00:16:10,240 --> 00:16:15,160 CELLS AND LEISHMANIA THAT WERE 329 00:16:15,160 --> 00:16:15,640 REGULATORY. 330 00:16:15,640 --> 00:16:19,000 NOW, SO, THE LAST BIT OF ORIGIN 331 00:16:19,000 --> 00:16:20,960 AND SET US OFF TO SOME 332 00:16:20,960 --> 00:16:22,560 INTERESTING THING PEOPLE LIKE 333 00:16:22,560 --> 00:16:28,000 ALAN AND STEPHANIE IN PARTICULAR 334 00:16:28,000 --> 00:16:30,120 AND KEEP LOOKING AT OUR DIE A 335 00:16:30,120 --> 00:16:32,840 TRAMS AND LOOKED AT IL5 WHICH WE 336 00:16:32,840 --> 00:16:34,840 KNEW WAS STRONG STIMULATING 337 00:16:34,840 --> 00:16:37,400 FACTS OR AND BUT IT WAS NOT 338 00:16:37,400 --> 00:16:40,120 UNTIL WITH THE ASSISTANCE FROM 339 00:16:40,120 --> 00:16:44,120 TIM'S LAB WE MADE THE FIRST MONO 340 00:16:44,120 --> 00:16:46,240 CLONE ANTIBODY AND ASKED THE 341 00:16:46,240 --> 00:16:48,400 QUESTION, INITIALLY IN A SIMPLE 342 00:16:48,400 --> 00:16:51,360 SYSTEM WHICH WE HAD RUNNING IN 343 00:16:51,360 --> 00:16:54,360 OUR LAB AND SUBSEQUENTLY WITH 344 00:16:54,360 --> 00:16:56,640 ALAN AND IN A MUCH MORE 345 00:16:56,640 --> 00:16:58,000 COMPLICATED, RELEVANT SYSTEM 346 00:16:58,000 --> 00:17:04,520 WHICH IS HERE. 347 00:17:04,520 --> 00:17:08,280 AND WHAT ROLE WAS ID5 AND THE 348 00:17:08,280 --> 00:17:08,880 WISDOM OF THE TIME SMITH IT 349 00:17:08,880 --> 00:17:10,280 WOULD BE A MULTI FACTORIAL 350 00:17:10,280 --> 00:17:12,520 RESPONSE TO REALLY GET THE 351 00:17:12,520 --> 00:17:15,080 DRAMATIC YOU SEE IN A COMPLEX 352 00:17:15,080 --> 00:17:19,000 SIS SEES SUCH AS INFECTION. 353 00:17:19,000 --> 00:17:21,560 AND ANSWER TRYING TO BE SIMPLE 354 00:17:21,560 --> 00:17:26,080 AND ANTI-IL5 BLOCKS AN EFFECTER 355 00:17:26,080 --> 00:17:27,800 AND REDUCED THE BLOOD LEVELS TO 356 00:17:27,800 --> 00:17:32,440 ALMOST ZERO AS YOU SEE HERE. 357 00:17:32,440 --> 00:17:35,400 ANTI-IL4 AS NO EFFECT ON EITHER 358 00:17:35,400 --> 00:17:37,320 OF THESE MODELS AND I'M SHOWING 359 00:17:37,320 --> 00:17:42,640 YOU THE DATA AND RESIP I CANNILY 360 00:17:42,640 --> 00:17:50,640 IT HAS NO EFFECT ON IT BLOCKS 361 00:17:50,640 --> 00:17:51,280 IGE PRODUCTION SO REALLY NAILED 362 00:17:51,280 --> 00:17:52,600 DOWN THE DIFFERENCE BETWEEN 363 00:17:52,600 --> 00:17:54,160 THESE DIFFERENT FUNCTIONS AND 364 00:17:54,160 --> 00:17:58,480 LED TO THE DEVELOPMENT OF 365 00:17:58,480 --> 00:18:00,000 SEVERAL ANTI-IL5 TREATMENTED 366 00:18:00,000 --> 00:18:02,240 WHICH ARE NOW COMMONLY USED IN A 367 00:18:02,240 --> 00:18:04,920 NUMBER OF ALLERGIC DISEASES. 368 00:18:04,920 --> 00:18:07,560 SO ABOUT THIS TIME, 1990s, 369 00:18:07,560 --> 00:18:08,840 ALAN SAID A LOT OF PEOPLE ARE 370 00:18:08,840 --> 00:18:12,040 LOOKING AT THE INFLUENCE OF 371 00:18:12,040 --> 00:18:14,960 CYTOKINES AND T-CELL CYTOKINES 372 00:18:14,960 --> 00:18:17,720 AND T-CELL SUBSETS IN A WIDE 373 00:18:17,720 --> 00:18:19,440 RANGE OF DISEASES. 374 00:18:19,440 --> 00:18:22,400 A LOT OF PEOPLE WORKED A 375 00:18:22,400 --> 00:18:28,120 WORORGANIZED AWORKSHOP SO WITH Y 376 00:18:28,120 --> 00:18:31,800 TAPPING ALL THE PEOPLE, PRESSING 377 00:18:31,800 --> 00:18:33,440 STEPHEN COFFMAN AND I COULD 378 00:18:33,440 --> 00:18:35,840 RAISE MONEY, HE PUT TOGETHER A 379 00:18:35,840 --> 00:18:38,320 WONDERFUL CONFERENCE AND IT WAS 380 00:18:38,320 --> 00:18:40,640 1992, HERE ON THE NIH CAMPUS 381 00:18:40,640 --> 00:18:46,600 THAT I THINK WAS REALLY A 382 00:18:46,600 --> 00:18:48,440 SEMINOLE JUNCTURE OF T-CELL 383 00:18:48,440 --> 00:18:50,320 IMMUNOLOGY BECAUSE IT BROUGHT 384 00:18:50,320 --> 00:18:54,000 TOGETHER WHOLE GROUPS OF PEOPLE 385 00:18:54,000 --> 00:18:56,720 FROM DIFFERENT FIELDS BASIC 386 00:18:56,720 --> 00:18:58,240 IMMUNOLOGY, AUTOIMMUNE DISEASE 387 00:18:58,240 --> 00:18:59,600 O FOURTH THAT REALLY DIDN'T 388 00:18:59,600 --> 00:19:01,360 TALK TO EACH OTHER BUT NEVER GO 389 00:19:01,360 --> 00:19:03,360 TO THE SAME MEETINGS AND WE GOT 390 00:19:03,360 --> 00:19:04,480 TOGETHER FOR SEVERAL DAYS AND IT 391 00:19:04,480 --> 00:19:08,280 WAS REALLY A FORMATIVE TIME. 392 00:19:08,280 --> 00:19:10,800 THERE'S ACTUALLY THE CONFERENCE 393 00:19:10,800 --> 00:19:11,840 PICTURE THERE. 394 00:19:11,840 --> 00:19:13,840 YOU SEE OUR FEAR LESS LEADER 395 00:19:13,840 --> 00:19:23,800 HERE LOCKING VERY GO AHEAD. 396 00:19:23,800 --> 00:19:27,640 YES, THAT'S ME WITH A WOMAN ON 397 00:19:27,640 --> 00:19:28,040 MY LAP. 398 00:19:28,040 --> 00:19:33,600 HERE IN THAT AND I REALIZED THAT 399 00:19:33,600 --> 00:19:35,080 WOULD NEVER FLY THESE DAYS. 400 00:19:35,080 --> 00:19:37,800 I GUARANTEE YOU. 401 00:19:37,800 --> 00:19:43,400 IT WAS POLY PATSINGER. 402 00:19:43,400 --> 00:19:44,840 IT'S A LOT OF THINGS HAVE 403 00:19:44,840 --> 00:19:46,200 CHANGED AROUND HERE AND NOT THE 404 00:19:46,200 --> 00:19:47,760 LEAST OF WHICH THAT WOULD NEVER 405 00:19:47,760 --> 00:19:51,400 BE ALLOWED ON THE NIH CAMPUS. 406 00:19:51,400 --> 00:19:53,640 I'LL FINISH BY SAYING ONE THING 407 00:19:53,640 --> 00:19:56,080 AROUND NIH THAT HASN'T CHANGED 408 00:19:56,080 --> 00:20:00,000 AT ALL SINCE THAT TIME, IS ALAN 409 00:20:00,000 --> 00:20:02,040 AND ALAN'S LOVE OF SCIENTISTS 410 00:20:02,040 --> 00:20:04,920 AND HIS ENORMOUS AFFECTION FOR 411 00:20:04,920 --> 00:20:06,360 THE PEOPLE THAT DO SCIENCE, 412 00:20:06,360 --> 00:20:09,200 WHICH COMES OUT AND IT'S COMING 413 00:20:09,200 --> 00:20:10,960 OUT OBVIOUSLY IN SO MANY TALKS 414 00:20:10,960 --> 00:20:12,400 WE'VE HEARD TODAY. 415 00:20:12,400 --> 00:20:15,240 ALAN'S INFECTIOUS ENTHUSIASM AND 416 00:20:15,240 --> 00:20:18,320 HIS LEGENDARY GENEROSITY NOT 417 00:20:18,320 --> 00:20:22,480 MUCH MORE I CAN SAY ON THAT. 418 00:20:22,480 --> 00:20:24,120 THAT HASN'T ALREADY BEEN SAID. 419 00:20:24,120 --> 00:20:26,400 I WANT TO THANK ALAN FOR HAVING 420 00:20:26,400 --> 00:20:28,000 SUCH A STRONG INFLUENCE ON THE 421 00:20:28,000 --> 00:20:31,960 DIRECTION OF MY CAREER TOOK EVER 422 00:20:31,960 --> 00:20:33,640 SINCE AND MANY OF THE PEOPLE IN 423 00:20:33,640 --> 00:20:34,120 MY LAB. 424 00:20:34,120 --> 00:20:34,600 THANK YOU. 425 00:20:34,600 --> 00:20:44,720 [APPLAUSE] 426 00:20:44,720 --> 00:20:46,400 >> THANK YOU, BOB. 427 00:20:46,400 --> 00:20:49,240 SO OUR NEXT SPEAKER IS ALSO A 428 00:20:49,240 --> 00:20:52,000 VERY STRONG SUPPORTER OF IMMUNO 429 00:20:52,000 --> 00:20:54,600 BIOLOGY SECTION AND ANNE O'GARRA 430 00:20:54,600 --> 00:20:59,080 FROM THE CRICK AND ANNE, PLEASE. 431 00:20:59,080 --> 00:21:02,240 ANNE REALLY INTRODUCED SYSTEM 432 00:21:02,240 --> 00:21:08,960 BIOLOGY'S INTO TB FIELD AND MAKE 433 00:21:08,960 --> 00:21:09,120 A -- 434 00:21:09,120 --> 00:21:19,480 >> HOW DO I DO THIS? 435 00:21:19,880 --> 00:21:21,680 >> TECHNOLOGY IS THE MOST 436 00:21:21,680 --> 00:21:23,000 CHALLENGING BUT IT ALL WORKS 437 00:21:23,000 --> 00:21:33,360 HERE, WHICH IS GREAT. 438 00:21:55,000 --> 00:21:58,600 >> SO, IT'S MY HONOR AND MY 439 00:21:58,600 --> 00:22:01,040 PLEASURE TO REALLY BE HERE TO 440 00:22:01,040 --> 00:22:03,600 CELEBRATE ALAN'S CAREER. 441 00:22:03,600 --> 00:22:05,400 WHICH THINK IS GOING TO CONTINUE 442 00:22:05,400 --> 00:22:08,480 FOR A LOT LONGER ANYWAY. 443 00:22:08,480 --> 00:22:11,320 AND THAT I'VE BEEN SELECTED TO 444 00:22:11,320 --> 00:22:13,640 ALSO GIVE A SCIENCE TALK AS WELL 445 00:22:13,640 --> 00:22:16,680 AS MY MEMORIES OF ALL THE 446 00:22:16,680 --> 00:22:18,440 INTERACTIONS WE'VE HAD. 447 00:22:18,440 --> 00:22:20,000 WE KEEP HAVING AND WE'RE GOING 448 00:22:20,000 --> 00:22:21,160 TO KEEP HAVING. 449 00:22:21,160 --> 00:22:23,480 SO, BEFORE I GO ONTO THE WORK 450 00:22:23,480 --> 00:22:27,120 THAT WE'VE BEEN DOING IN 451 00:22:27,120 --> 00:22:28,880 TUBERCULOSIS, I JUST WANT TO SAY 452 00:22:28,880 --> 00:22:32,520 A FEW WORDS ABOUT ALAN SHER. 453 00:22:32,520 --> 00:22:35,120 AND LOOKING AT IT FROM THE POINT 454 00:22:35,120 --> 00:22:40,440 OF VIEW OF ALAN, A PEOPLE 455 00:22:40,440 --> 00:22:42,200 PERSON, COMPLETELY CURIOUS ABOUT 456 00:22:42,200 --> 00:22:46,080 SCIENCE, EXCITED, FINDING NEW 457 00:22:46,080 --> 00:22:49,600 AREAS TO WORK ON AS HIS YOUNG 458 00:22:49,600 --> 00:22:51,160 POSTDOCS GO ON TAKING PROJECTS 459 00:22:51,160 --> 00:22:53,480 AND DEVELOPING THEIR OWN LABS 460 00:22:53,480 --> 00:22:57,000 AND FULLY SUPPORTIVE AND MEETING 461 00:22:57,000 --> 00:22:59,600 WHEN PROJECTS AND DIFFERENT LABS 462 00:22:59,600 --> 00:23:01,520 COME TOGETHER COLLABORATING, 463 00:23:01,520 --> 00:23:05,640 HAVING FUN, AND REALLY BEING 464 00:23:05,640 --> 00:23:06,040 INSPIRED. 465 00:23:06,040 --> 00:23:07,800 SO WITH A SMILE, I'VE BEEN 466 00:23:07,800 --> 00:23:09,480 INSPIRED THROUGH ALL MY 467 00:23:09,480 --> 00:23:10,520 INTERACTIONS WITH ALAN. 468 00:23:10,520 --> 00:23:12,920 I'M GOING TO RECAP JUST A FEW 469 00:23:12,920 --> 00:23:15,120 THINGS THAT'S BEEN SAID BUT JUST 470 00:23:15,120 --> 00:23:18,800 TO SAY HOW WHEN I FIRST METAL 471 00:23:18,800 --> 00:23:23,080 AN, SO, YOU'VE HEARD FROM RON 472 00:23:23,080 --> 00:23:25,360 AND OTHERS THAT ALAN DID A 473 00:23:25,360 --> 00:23:30,000 POSTDOC AT THE NIMR AT MEL HILL 474 00:23:30,000 --> 00:23:32,080 THAT LOVELY OLD BUILDING WITH A 475 00:23:32,080 --> 00:23:33,680 GUY CALLED RON SMITHERS. 476 00:23:33,680 --> 00:23:36,000 I KNEW RON SMITHERS BUT I WASN'T 477 00:23:36,000 --> 00:23:38,440 THERE BETWEEN 70 AND '74 BUT 478 00:23:38,440 --> 00:23:39,880 ALSO HEARD FROM DAVID SACKS WITH 479 00:23:39,880 --> 00:23:44,120 HIS FAMILY TREE THAT HE WAS A 480 00:23:44,120 --> 00:23:48,320 POSTDOC AFTER ALAN IN '77 TO '7S 481 00:23:48,320 --> 00:23:52,640 BECAUSE THEY CAPTURE THE ERA. 482 00:23:52,640 --> 00:23:55,440 SO LOOK AT DAVID SACKS AND THIS 483 00:23:55,440 --> 00:23:57,520 GUY JERRY WAS ACTUALLY THEN 484 00:23:57,520 --> 00:24:03,200 BECAME MY SUPERVISOR SO ED 485 00:24:03,200 --> 00:24:03,960 PEARCE WHO THEN DID HIS PH.D 486 00:24:03,960 --> 00:24:09,720 ALSO AT NIMR IN RON SMITHERS 487 00:24:09,720 --> 00:24:12,840 DIVISION ON SCHISTO SO I WAS 488 00:24:12,840 --> 00:24:16,200 ACQUAINTED WITH PATHOLOGY AND 489 00:24:16,200 --> 00:24:18,360 ALAN SHER AND DAVID SACKS, THE 490 00:24:18,360 --> 00:24:21,080 WORK THERE ALTHOUGH I WAS A 491 00:24:21,080 --> 00:24:23,640 MICROBIOLOGIST LOOKING AT 492 00:24:23,640 --> 00:24:24,880 BACTERIAL ADHESION AND I DID A 493 00:24:24,880 --> 00:24:28,120 POSTDOC ON IMMUNOLOGY AND I HAD 494 00:24:28,120 --> 00:24:32,640 THE LUCK TO BE INTRODUCED TO BOB 495 00:24:32,640 --> 00:24:35,080 COFFMAN AND I CAME AS A POSTDOC 496 00:24:35,080 --> 00:24:41,360 TO DEAN X AND S DNAX. 497 00:24:41,360 --> 00:24:42,840 ALAN IS NOT THERE YET BUT YOU 498 00:24:42,840 --> 00:24:44,760 WILL SEE SOME PICTURES. 499 00:24:44,760 --> 00:24:47,040 SO, IT WAS THAT PAPER THAT BOB 500 00:24:47,040 --> 00:24:49,240 HAS JUST TOLD YOU ABOUT THAT 501 00:24:49,240 --> 00:24:55,080 REALLY STARTED THAT 502 00:24:55,080 --> 00:24:56,720 COLLABORATION WITH BOB AND DNAX 503 00:24:56,720 --> 00:24:59,200 AND I WAS A POSTDOC AT XNAX AND 504 00:24:59,200 --> 00:25:02,320 I WAS LUCKY TO PROGRESS AND GET 505 00:25:02,320 --> 00:25:03,320 A JOB THERE AND INSTEAD OF 506 00:25:03,320 --> 00:25:05,360 SAYING TWO YEARS I STAYED 15 507 00:25:05,360 --> 00:25:08,960 YEARS AND BOB I HAD JOINT LAB 508 00:25:08,960 --> 00:25:10,320 MEETINGS TOGETHER AND WE SAW 509 00:25:10,320 --> 00:25:12,240 ALAN AND ALL HIS LAB MEMBERS, 510 00:25:12,240 --> 00:25:14,080 PHIL SCOTT, EDMONTON PEARCE AND 511 00:25:14,080 --> 00:25:17,520 THROUGH THE YEARS, WE BECAME 512 00:25:17,520 --> 00:25:17,760 FRIENDS. 513 00:25:17,760 --> 00:25:20,240 I DIDN'T COLLABORATE SO MUCH, 514 00:25:20,240 --> 00:25:23,640 ALTHOUGH ON SOME PAPERS I DID ON 515 00:25:23,640 --> 00:25:24,480 THIS ERA. 516 00:25:24,480 --> 00:25:27,600 WE HAVE A COLLABORATION, ALAN 517 00:25:27,600 --> 00:25:32,200 BUT FROM THE BOB COFFMAN DNAX TO 518 00:25:32,200 --> 00:25:36,320 TIM MONTHSMANNIL-10 THIS IS THE 519 00:25:36,320 --> 00:25:42,560 FIRST THINGTHEFIRST PAPER YOU PH 520 00:25:42,560 --> 00:25:47,560 ED PEARCE AND THIS WAS IN 521 00:25:47,560 --> 00:25:49,400 SCHISTO AND SO THAT IS WHEN I 522 00:25:49,400 --> 00:25:51,920 WAS LUCKY TO REALLY NOT HAVE 523 00:25:51,920 --> 00:25:54,520 JUST JOINED DNAX AND INTERACT 524 00:25:54,520 --> 00:25:59,280 WITH BOB AND TIM AND MEET ALAN, 525 00:25:59,280 --> 00:26:00,720 PHIL, DAVID, ED AND I ALREADY 526 00:26:00,720 --> 00:26:02,440 KNEW EACH OTHER. 527 00:26:02,440 --> 00:26:04,560 SO, SPIN FORWARD A LONG WAY 528 00:26:04,560 --> 00:26:05,760 BECAUSE I'LL GET TO THE SCIENCE 529 00:26:05,760 --> 00:26:10,280 BUT I REALLY WANT TO REALLY 530 00:26:10,280 --> 00:26:12,280 EMPHASIS THAT ALAN, YOU KNOW, 531 00:26:12,280 --> 00:26:16,600 I'VE HAD REASONS TO LOOK AT 532 00:26:16,600 --> 00:26:18,120 ALAN, I WON'T GO INTO THEM. 533 00:26:18,120 --> 00:26:20,640 IT'S EASIER THAN LOOKING AT 534 00:26:20,640 --> 00:26:22,800 PUBMED BY I NOTICED LOTS OF 535 00:26:22,800 --> 00:26:25,640 PEOPLE LEAVING HIS LAB TAKE THE 536 00:26:25,640 --> 00:26:27,280 PROGRAMS AND THEN PHIL LEFT TOOK 537 00:26:27,280 --> 00:26:30,040 THE PROGRAM AND THEN TOXO AND 538 00:26:30,040 --> 00:26:31,440 THEN ALL THESE MODELS WE'VE 539 00:26:31,440 --> 00:26:34,480 HEARD OF AND ALAN'S GENEROSITY 540 00:26:34,480 --> 00:26:36,080 AND ALSO CREATIVITY AND 541 00:26:36,080 --> 00:26:38,560 IMAGINATION IN LOOKING FOR OTHER 542 00:26:38,560 --> 00:26:40,520 MODELS EXPERIMENTAL MODELS TO 543 00:26:40,520 --> 00:26:42,920 TELL US ABOUT IMMUNO REGULATION 544 00:26:42,920 --> 00:26:45,440 AND HE HAS BEEN THE KING ON 545 00:26:45,440 --> 00:26:46,840 THIS. 546 00:26:46,840 --> 00:26:50,480 NOW, TB IS WHAT, AS CARL THANKS 547 00:26:50,480 --> 00:26:51,960 FOR THAT INTRODUCTION BECAUSE I 548 00:26:51,960 --> 00:26:54,000 COULDN'T INTRODUCE ALL THE 549 00:26:54,000 --> 00:26:55,800 SEMINOLE PAPERS THAT HAVE BEEN 550 00:26:55,800 --> 00:26:57,840 PUBLISHED FROM ALAN'S LAB I 551 00:26:57,840 --> 00:26:59,280 THINK IT WAS SINCE 2000 THAT YOU 552 00:26:59,280 --> 00:27:03,960 GUYS STARTED WORKING ON TB. 553 00:27:03,960 --> 00:27:05,520 I SUFFER WITH YOU BECAUSE WE 554 00:27:05,520 --> 00:27:07,720 STARTED IN 2003 AND IT WAS HARD 555 00:27:07,720 --> 00:27:11,720 AND IT WAS HARD FOR MANY YEARS 556 00:27:11,720 --> 00:27:13,760 THAT WE'LL DISCUSS IN A BAR OVER 557 00:27:13,760 --> 00:27:15,760 WINE, NOT JUST CONTAINMENT 3 BUT 558 00:27:15,760 --> 00:27:16,600 LOTS OF DIFFERENCE. 559 00:27:16,600 --> 00:27:19,880 SO ALAN'S CONTRIBUTIONS ARE 560 00:27:19,880 --> 00:27:22,160 RECOGNIZED ALL OVER THE WORLD IN 561 00:27:22,160 --> 00:27:24,000 PATHOLOGY AND ALSO IN TB AND 562 00:27:24,000 --> 00:27:27,360 BASICALLY THIS IS EX EMPTIED OF 563 00:27:27,360 --> 00:27:29,960 THIS TWITTER OF FEED WHICH IS A 564 00:27:29,960 --> 00:27:31,200 RESEARCH REBOOT OF TUBERCULOSIS 565 00:27:31,200 --> 00:27:33,160 AT THE SYMPOSIUM 50th 566 00:27:33,160 --> 00:27:38,040 ANNIVERSARY WHICH ALAN IS LED 567 00:27:38,040 --> 00:27:39,720 ORGANIZERS AN AND IT WILL HAPPEN 568 00:27:39,720 --> 00:27:41,160 FROM JANUARY AND THE FACT THAT 569 00:27:41,160 --> 00:27:43,120 ALAN IS LEADING THIS MEETING IS 570 00:27:43,120 --> 00:27:44,280 PRETTY IMPORTANT BECAUSE YOU 571 00:27:44,280 --> 00:27:48,440 KNOW, THE TB FIELD HAS BEEN KIND 572 00:27:48,440 --> 00:27:50,600 OF TRACTION AND HARD AND HERE WE 573 00:27:50,600 --> 00:27:52,800 HAVE CAT AND DAN WHO ARE 574 00:27:52,800 --> 00:27:56,000 CONTINUING THE LEGACY OF WORKING 575 00:27:56,000 --> 00:27:58,400 IN TB AT THE NIH. 576 00:27:58,400 --> 00:28:01,200 SO, WITHOUT FURTHER ADIEU, I 577 00:28:01,200 --> 00:28:03,200 WANT TO SHOW YOU A BIT MORE OF 578 00:28:03,200 --> 00:28:06,160 THE HUMAN ASPECT OF ALAN THAT 579 00:28:06,160 --> 00:28:07,560 LOOK AT HIM SMILING. 580 00:28:07,560 --> 00:28:10,600 AND BOB AND THIS IS A KEYSTONE 581 00:28:10,600 --> 00:28:13,120 WHICH ALAN WAS INSTRUMENTAL 582 00:28:13,120 --> 00:28:14,680 ACTUALLY IN MY BECOMING INVOLVED 583 00:28:14,680 --> 00:28:17,320 AND BOB AND ALAN THERE AND I HAD 584 00:28:17,320 --> 00:28:20,840 SUCH WONDERFUL TIMES AND YOU SEE 585 00:28:20,840 --> 00:28:23,240 US WITH DRINKS AND THIS IS THE 586 00:28:23,240 --> 00:28:27,120 LAKE BY KEYSTONE AND THAT IS THE 587 00:28:27,120 --> 00:28:29,280 PATH MUCH WE WOULD GO FOR A WALK 588 00:28:29,280 --> 00:28:31,920 AND YOU KNOW, ALAN MENTORS IN A 589 00:28:31,920 --> 00:28:35,240 WAY IT DOESN'T COME ACROSS AS 590 00:28:35,240 --> 00:28:36,320 MENTORING BECAUSE HE IS CHATTING 591 00:28:36,320 --> 00:28:40,760 BUT HE IS GIVING YOU WISDOM AND 592 00:28:40,760 --> 00:28:42,080 GEMS OF HOW TO THINK ABOUT THE 593 00:28:42,080 --> 00:28:43,920 WAY FORWARD IN RESEARCH PROGRAMS 594 00:28:43,920 --> 00:28:45,720 AND RUNNING A LAB, THE PEOPLE, 595 00:28:45,720 --> 00:28:50,920 THE DIFFICULTIES, THE HARDSHIPS, 596 00:28:50,920 --> 00:28:53,640 THE JOYS AND SO THAT GIVES ME 597 00:28:53,640 --> 00:28:55,720 SUCH PLEASURE WHEN I LOOK AT 598 00:28:55,720 --> 00:28:57,240 THOSE PHOTOS AND I'LL BE HAPPY 599 00:28:57,240 --> 00:29:02,720 TO SEND YOU SOME OF THESE AS OUR 600 00:29:02,720 --> 00:29:02,960 MEMORIES. 601 00:29:02,960 --> 00:29:04,160 THANK YOU FOR YOUR GENEROSITY 602 00:29:04,160 --> 00:29:06,040 AND HELPING ME COME INTO THE TB 603 00:29:06,040 --> 00:29:12,640 FIELD BECAUSE IT WASN'T EASY. 604 00:29:12,640 --> 00:29:14,040 I STARTED BECAUSE IT SEEMED 605 00:29:14,040 --> 00:29:15,680 IMPORTANT THAT I WORK ON A 606 00:29:15,680 --> 00:29:17,160 DISEASE THAT ACTUALLY KILLED 607 00:29:17,160 --> 00:29:20,200 PEOPLE AND HAVING COME FROM DNAX 608 00:29:20,200 --> 00:29:22,400 AND I WAS SUPPOSED TO INTERFACE 609 00:29:22,400 --> 00:29:23,160 IMMUNE OLE GOUGH AND INFECTION 610 00:29:23,160 --> 00:29:29,000 SO I'LL COME AND IT WILL 611 00:29:29,000 --> 00:29:31,160 INTERFACE WITH ALAN AND CAT 612 00:29:31,160 --> 00:29:36,760 MAINLY THROUGH THE WORK AND SO, 613 00:29:36,760 --> 00:29:39,240 I'LL TALK TO YOU ABOUT HOW THEY 614 00:29:39,240 --> 00:29:40,720 HELPED US AND TO GIVE YOU 615 00:29:40,720 --> 00:29:43,040 BACKGROUND OF WHAT WE KNEW IN 616 00:29:43,040 --> 00:29:44,680 2003 ABOUT THE IMMUNE RESPONSE 617 00:29:44,680 --> 00:29:53,720 AND MTB AND MTB AND IT WOULDN'T 618 00:29:53,720 --> 00:29:56,360 GO INTO BUT COULD INFECT KNEW 619 00:29:56,360 --> 00:29:57,560 TRA FILLS AND WE FOUND 620 00:29:57,560 --> 00:30:01,200 MACROPHAGES AND THEY MIGRATE TO 621 00:30:01,200 --> 00:30:02,640 THE LYNCH NODE AND THE RIGHT T 622 00:30:02,640 --> 00:30:04,120 CELLS WERE ACTIVATED AND THEY 623 00:30:04,120 --> 00:30:10,320 WOULD ACTIVATE AND THAT COULD 624 00:30:10,320 --> 00:30:11,880 PROTECT AND IT WAS FUNDAMENTAL 625 00:30:11,880 --> 00:30:15,080 IN EXPERIMENTAL MODEL BY ANDREW 626 00:30:15,080 --> 00:30:17,120 COOPER AND JOANNE FLYNN AND 627 00:30:17,120 --> 00:30:20,640 ALAN'S LAB ADVANCED A LOT OF 628 00:30:20,640 --> 00:30:24,640 THAT AND TNF WAS FUNDAMENTAL AND 629 00:30:24,640 --> 00:30:27,080 WHAT WAS REALLY AMAZING IS THESE 630 00:30:27,080 --> 00:30:28,080 FACTORS WERE ALSO SHOWN TO BE 631 00:30:28,080 --> 00:30:30,280 IMPORTANT IN HUMAN DISEASE AND 632 00:30:30,280 --> 00:30:34,560 THE TH1 ACCESS AND SUSCEPTIBLE 633 00:30:34,560 --> 00:30:38,000 DISEASES AND ANTI-TNF HAVE BEEN 634 00:30:38,000 --> 00:30:41,160 SHOWN TO ACTIVATE TD IN 635 00:30:41,160 --> 00:30:44,080 INDIVIDUALS WHO HAD BEEN EXPOSED 636 00:30:44,080 --> 00:30:44,880 BUT THAT WAS IT. 637 00:30:44,880 --> 00:30:47,160 THAT WAS THE TIP OF THE ICEBERG. 638 00:30:47,160 --> 00:30:50,240 I CAME FROM DNAX AND WORKED 639 00:30:50,240 --> 00:30:51,280 COLLABORATE BEING WITH TIM AND 640 00:30:51,280 --> 00:30:55,560 BOB FOR MANY YEARS AND SO, I 641 00:30:55,560 --> 00:30:57,440 THOUGHT OK, LET'S HAVE A LOOK TO 642 00:30:57,440 --> 00:30:59,960 SEE WHAT IL-10 DOES AND STOPS 643 00:30:59,960 --> 00:31:03,000 DEVELOPMENT MUST HAVE A ROLE AND 644 00:31:03,000 --> 00:31:04,200 I'M NOT GOING TO SHOW YOU THE 645 00:31:04,200 --> 00:31:05,920 DATA THIS WAS ALREADY PUBLISHED 646 00:31:05,920 --> 00:31:07,560 AND IN DEED IT DID HAVE A ROLE 647 00:31:07,560 --> 00:31:10,440 AND IN THESE RESIST APARTMENT 648 00:31:10,440 --> 00:31:12,160 MICE THERE WAS A SLIGHT ROLE BUT 649 00:31:12,160 --> 00:31:14,160 IT WASN'T PROFOUND SO THIS WAS A 650 00:31:14,160 --> 00:31:16,480 TIP OF THE ICEBERG. 651 00:31:16,480 --> 00:31:21,280 SO HOW ELSE TO GO AND THIS 652 00:31:21,280 --> 00:31:23,000 BRINGS INTO MIND THE 653 00:31:23,000 --> 00:31:24,200 COLLABORATIVE NATURE OF THIS 654 00:31:24,200 --> 00:31:29,600 FAMILY FOR PEOPLE LIKE ALAN, 655 00:31:29,600 --> 00:31:31,760 BOB, AND JACK WHO RAN THE 656 00:31:31,760 --> 00:31:34,160 INSTITUTE THAT WAS PARALLEL BUT 657 00:31:34,160 --> 00:31:36,160 MOVED TO DAMN AS AND WHERE I 658 00:31:36,160 --> 00:31:39,320 THEN WAS THERE FOR MEETING AND I 659 00:31:39,320 --> 00:31:43,640 SAID TO ALAN, TO TUBERCULOSIS IS 660 00:31:43,640 --> 00:31:45,160 A PROBLEM AND I'M STARTING TO 661 00:31:45,160 --> 00:31:51,280 WORK ON IT AND IT'S DIFFICULT. 662 00:31:51,280 --> 00:31:54,600 THOSE WHO DON'T WORK ON TB 663 00:31:54,600 --> 00:31:56,520 1.5 MILLION DEATHS DIAGNOSIS IS 664 00:31:56,520 --> 00:31:57,560 DIFFICULT AND NOT GOING TO GO 665 00:31:57,560 --> 00:32:00,280 INTO THIS FOR THE SCOPE OF THIS 666 00:32:00,280 --> 00:32:01,800 TALK AND THE FASCINATING POINT 667 00:32:01,800 --> 00:32:03,920 OF IMMUNOLOGIST IS THAT A THIRD 668 00:32:03,920 --> 00:32:06,040 OF THE WORLD ESTIMATED A QUARTER 669 00:32:06,040 --> 00:32:08,240 OF WORLD TO BE LATENT AND THOSE 670 00:32:08,240 --> 00:32:10,560 WILL PROGRESS TO TB AND YOU CAN 671 00:32:10,560 --> 00:32:13,440 SAY BY DEFINED BY IMMUNE 672 00:32:13,440 --> 00:32:14,960 REACTIVITY BUT YOU CAN'T SAY WHO 673 00:32:14,960 --> 00:32:15,640 WILL GO. 674 00:32:15,640 --> 00:32:17,120 I'LL COME BACK TO THAT AT THE 675 00:32:17,120 --> 00:32:20,960 END OF THE MY TALK. 676 00:32:20,960 --> 00:32:22,360 TO GET TO THE QUESTION WE ASKED 677 00:32:22,360 --> 00:32:23,960 AND HOW THE HELP FROM OUR 678 00:32:23,960 --> 00:32:28,760 FRIENDS AND THIS WAS DAMIAN WHO 679 00:32:28,760 --> 00:32:34,080 IS HERE WHO REALLY HELPED THIS 680 00:32:34,080 --> 00:32:37,680 SO THE LINE LINE WAS I WILL HELP 681 00:32:37,680 --> 00:32:39,240 YOU CONQUER TB AND THOSE WHO 682 00:32:39,240 --> 00:32:41,720 KNOW YOU AND OUR QUESTION WAS 683 00:32:41,720 --> 00:32:44,360 MOUSE MODELS AND THEY WEREN'T 684 00:32:44,360 --> 00:32:46,960 AND THEY TOLD US ABOUT RESISTANT 685 00:32:46,960 --> 00:32:48,400 BUT WHY DO INDIVIDUALS REMAIN 686 00:32:48,400 --> 00:32:49,920 LATE ANT AND HEALTHY AND OTHERS 687 00:32:49,920 --> 00:32:52,160 GO ON TO GET TB WHAT FACTORS OF 688 00:32:52,160 --> 00:32:53,880 THE IMMUNE RESPONSE CONTRIBUTE 689 00:32:53,880 --> 00:32:55,280 TO TB AND THAT WAS THE QUESTION 690 00:32:55,280 --> 00:32:57,800 THAT CAME AFTER I LOOKED AT 691 00:32:57,800 --> 00:32:59,000 VIRGINIA PASQUAL'S COMPUTER AND 692 00:32:59,000 --> 00:33:01,520 SEEING THE IMMUNE SIGNATURES SHE 693 00:33:01,520 --> 00:33:03,080 DEFINED IN AUTOIMMUNITY SO 694 00:33:03,080 --> 00:33:04,280 TOGETHER WE ASKED THE QUESTION, 695 00:33:04,280 --> 00:33:07,520 CAN HUMAN BLOOD TRANSCRIPTIONAL 696 00:33:07,520 --> 00:33:08,200 SIGNATURES DISTINGUISH 697 00:33:08,200 --> 00:33:09,960 INDIVIDUALS WITH LATENT AND 698 00:33:09,960 --> 00:33:11,640 ACTIVE TB AND THIS IS PUBLISHED 699 00:33:11,640 --> 00:33:15,680 SO I'M GOING TO GO THROUGH IT 700 00:33:15,680 --> 00:33:17,440 QUICKLY, BUT TO SAY WE DEFINED 701 00:33:17,440 --> 00:33:22,360 AN INTERFERON BLOOD 702 00:33:22,360 --> 00:33:23,080 TRANSCRIPTIONAL SIGNATURES THAT 703 00:33:23,080 --> 00:33:24,120 WAS MISSING IN LAT ENTER AND 704 00:33:24,120 --> 00:33:24,920 HEALTHY INDIVIDUALS AND I'M 705 00:33:24,920 --> 00:33:26,080 GOING TO SHOW YOU A LITTLE BIT 706 00:33:26,080 --> 00:33:29,880 OF THESE DATA AND SHOW THE 707 00:33:29,880 --> 00:33:31,400 CONTRIBUTION THAT THEY HELPED US 708 00:33:31,400 --> 00:33:33,560 TO DECIPHER THIS TOGETHER WITH 709 00:33:33,560 --> 00:33:33,960 VIRGINIA. 710 00:33:33,960 --> 00:33:37,800 SO THIS SIGNATURE OF ACTIVE TB 711 00:33:37,800 --> 00:33:40,560 WAS DOMINATED BY AUGUST 712 00:33:40,560 --> 00:33:41,520 REGULATED GOWNS IN DOWN 713 00:33:41,520 --> 00:33:43,440 REGULATED SCENES IN ACTIVE TB 714 00:33:43,440 --> 00:33:45,120 BUT NOT IN LATENT AND THIS WAS 715 00:33:45,120 --> 00:33:48,880 IN LONDON AND WE REKA PIT RATED 716 00:33:48,880 --> 00:33:51,840 THAT IN SOUTH AFRICA AND THERE 717 00:33:51,840 --> 00:33:53,920 EVERYBODY WAS POSITIVE AND THE 718 00:33:53,920 --> 00:33:55,760 INTERFERON GAMMA AND ANTIGENS 719 00:33:55,760 --> 00:33:57,720 BUT STILL, THEY DIDN'T HAVE THE 720 00:33:57,720 --> 00:34:00,240 SIGNATURE BUT THE ACTIVE TB 721 00:34:00,240 --> 00:34:01,680 PATIENTS DID AND I'LL COME BACK 722 00:34:01,680 --> 00:34:06,280 TO THE HETEROGENEITY LATER. 723 00:34:06,280 --> 00:34:11,160 NOW, HOW DO YOU GET ALL THESE 724 00:34:11,160 --> 00:34:15,360 GENES AND DAMIAN HAD COME UP 725 00:34:15,360 --> 00:34:20,320 WITH A MODULAR APPROACH AND HE 726 00:34:20,320 --> 00:34:22,120 SHOWED IT COULD PUT INTO MODEL 727 00:34:22,120 --> 00:34:25,760 AND THEY COULD BE ANNOTATED 728 00:34:25,760 --> 00:34:27,240 LOOKING THEM AT THEM SO THEY HAD 729 00:34:27,240 --> 00:34:29,640 A APPROACH THAT WE USED IN 730 00:34:29,640 --> 00:34:31,720 TESTING AND OUR TB TRAINING SET 731 00:34:31,720 --> 00:34:34,920 IN LONDON AND OUR SOUTH AFRICA 732 00:34:34,920 --> 00:34:35,840 VALIDATION ZENDAYA SET AND YOU 733 00:34:35,840 --> 00:34:43,560 CAN SEE THIS IS SUPER IMPOSE 734 00:34:43,560 --> 00:34:44,600 ABLE THREE DIFFERENT YEARS AND 735 00:34:44,600 --> 00:34:47,120 THIS WAS GENES AND I TOLD YOU 736 00:34:47,120 --> 00:34:48,840 GAMMA INTER FEWER ON CAME UP IN 737 00:34:48,840 --> 00:34:50,800 TB PROTECTIVE SO COULD BE SEEN 738 00:34:50,800 --> 00:34:53,200 SO I THOUGHT IT'S GAMMA 739 00:34:53,200 --> 00:34:55,360 INTERFERON BUT THIS IS WHY 740 00:34:55,360 --> 00:34:57,520 TOOKING TO COLLABORATORS SAID 741 00:34:57,520 --> 00:35:00,560 NO, NO, IT'S NOT GAMMA 742 00:35:00,560 --> 00:35:01,920 INTERFERON BUT WAS IMPORTANT 743 00:35:01,920 --> 00:35:03,960 THAT S THESE CONFOUNDING DISEASE 744 00:35:03,960 --> 00:35:08,360 OF GROUP A STREP AND STAFF, DID 745 00:35:08,360 --> 00:35:11,000 NOT HAVE THE SIGNATURE BUT THIS 746 00:35:11,000 --> 00:35:12,880 OTHER BLOB WHICH IS A PLASMA 747 00:35:12,880 --> 00:35:15,840 GENE SIGNATURE SO YOU CAN 748 00:35:15,840 --> 00:35:17,600 DISTINGUISH TB FROM OTHER 749 00:35:17,600 --> 00:35:19,240 DISEASES AND WE'VE DONE A LOT 750 00:35:19,240 --> 00:35:21,080 MORE ON OUR WORK SHOW BUT 751 00:35:21,080 --> 00:35:23,000 VIRGINIA'S POINT AND THAT HAS TO 752 00:35:23,000 --> 00:35:24,400 BE TYPE ONE BECAUSE IT'S TYPE 753 00:35:24,400 --> 00:35:26,200 ONE INTERFERON AND I SAID NO, 754 00:35:26,200 --> 00:35:31,000 NO, IT HAS TO BE GAMMA, AND WHEN 755 00:35:31,000 --> 00:35:34,320 THE PHYSICIAN LOOKED AT THIS 393 756 00:35:34,320 --> 00:35:36,120 SIGNATURE IN DETAIL HE FOUND 757 00:35:36,120 --> 00:35:43,160 THAT IT WAS GENESM D AND 758 00:35:43,160 --> 00:35:45,800 INTERFERON ALPHABET TA UP 759 00:35:45,800 --> 00:35:48,240 REGULATED YOU COULDN'T SEE 760 00:35:48,240 --> 00:35:49,960 CYTOKINES THEMSELVES SO THEY 761 00:35:49,960 --> 00:35:51,800 HAVE TO INDUCE THE GOWNS THAT 762 00:35:51,800 --> 00:35:54,000 GIVE THEM THE SIGNATURE AND ON 763 00:35:54,000 --> 00:35:55,080 PURCHASEIFICATION OF CELLS FROM 764 00:35:55,080 --> 00:35:57,320 THE BLOOD WHICH HAD A SIGNATURE, 765 00:35:57,320 --> 00:35:58,920 CHRIS GRAHAM IN THE LAB SHOWED 766 00:35:58,920 --> 00:36:01,080 THAT IT WAS NEWT TRA FILL AND 767 00:36:01,080 --> 00:36:04,280 MONOCYTES THAT EXPRESS THIS 768 00:36:04,280 --> 00:36:05,120 INTERFERON INDUCE ABLE 769 00:36:05,120 --> 00:36:05,800 SIGNATURE. 770 00:36:05,800 --> 00:36:07,360 NOW WHY WERE WE SURPRISED ABOUT 771 00:36:07,360 --> 00:36:09,040 TYPE ONE INTERFERON BECAUSE 772 00:36:09,040 --> 00:36:10,880 NOTHING WAS REALLY TALKED ABOUT 773 00:36:10,880 --> 00:36:14,320 IN TB IN TYPE ONE INTERFERON AND 774 00:36:14,320 --> 00:36:16,000 TB AS YOU KNOW TYPE ONE WAS 775 00:36:16,000 --> 00:36:17,480 FAMOUS FOR PROTECTING AGAINST 776 00:36:17,480 --> 00:36:19,040 VIRUSES AND CANCER AND IT'S 777 00:36:19,040 --> 00:36:22,280 CERTAINLY MODELS LIKE LISTERIA 778 00:36:22,280 --> 00:36:24,560 IT COULD EXACERBATE INFECTION SO 779 00:36:24,560 --> 00:36:28,240 WHAT WAS GOING ON SO THIS MADE 780 00:36:28,240 --> 00:36:29,600 US DIG DOPE INTO THE LITERATURE 781 00:36:29,600 --> 00:36:32,680 AND THERE WERE TWO PAPERS BY 782 00:36:32,680 --> 00:36:34,560 KAPLAN THAT SHOWED THAT TYPE ONE 783 00:36:34,560 --> 00:36:37,800 INTERFERON CORRELATED WITH 784 00:36:37,800 --> 00:36:39,320 SHORTER SURVIVAL TIMES IN MICE 785 00:36:39,320 --> 00:36:43,200 AND THE BLOCKADE COULD GIVE 786 00:36:43,200 --> 00:36:44,320 LONGER SURVIVAL TIMES OF THE 787 00:36:44,320 --> 00:36:47,400 TYPE 1 INTERFERON IF NOT 788 00:36:47,400 --> 00:36:48,040 SIGNALING. 789 00:36:48,040 --> 00:36:49,600 WHAT WAS DIFFERENT? 790 00:36:49,600 --> 00:36:51,240 RE RACKED OUR BRAINS SO WE 791 00:36:51,240 --> 00:36:53,600 WEREN'T -- SHE WASN'T USING THE 792 00:36:53,600 --> 00:36:55,880 H37 LAB STRAIN OF TB SHE WAS 793 00:36:55,880 --> 00:36:58,520 USING A CLINICAL ISOLATE AND SHE 794 00:36:58,520 --> 00:37:02,400 WAS USING F-1 INTRA BRED MICE OF 795 00:37:02,400 --> 00:37:04,440 GOD KNOWS WHAT GENETIC 796 00:37:04,440 --> 00:37:07,240 BACKGROUND THEY WERE AND SO 797 00:37:07,240 --> 00:37:09,320 PROBABLY GENETIC BACKGROUND 798 00:37:09,320 --> 00:37:10,800 STARTED TO BE IMPORTANT. 799 00:37:10,800 --> 00:37:13,440 WHAT STARTED TO COME OUT AS WELL 800 00:37:13,440 --> 00:37:16,280 IN PARALLEL, IS THE INCREASING 801 00:37:16,280 --> 00:37:18,760 LEVELS OF TYPE 1 INTERFERON 802 00:37:18,760 --> 00:37:20,920 DURING TB INFECTION BY OTHER 803 00:37:20,920 --> 00:37:28,720 MEANS COULD EXACERBATE TB SO 804 00:37:28,720 --> 00:37:30,360 ALAN, DOING THE TREATMENT TO 805 00:37:30,360 --> 00:37:32,960 PROTECT AGAINST TB AND LOW AND 806 00:37:32,960 --> 00:37:37,280 BOW HOLD IT LED TO TWO LOG FOLD 807 00:37:37,280 --> 00:37:39,960 INCREASE IN THE LUNG TB LOAD BUT 808 00:37:39,960 --> 00:37:42,200 NOT IN THE RECEPTOR KNOCK OUT 809 00:37:42,200 --> 00:37:46,520 MICE SO TYPE 1 INTERFERON IS 810 00:37:46,520 --> 00:37:46,680 BAD. 811 00:37:46,680 --> 00:37:48,520 IN OUR LAB WE HAD TO EXACERBATE 812 00:37:48,520 --> 00:37:49,960 AND THAT WAS A COLLABORATION 813 00:37:49,960 --> 00:37:54,840 WITH ALAN AND ANDRE AS WHERE WE 814 00:37:54,840 --> 00:37:57,960 FOUND THE INFLUENZA VIRUS A WILL 815 00:37:57,960 --> 00:37:59,520 IMPAIR THE PROTECTION AGAINST 816 00:37:59,520 --> 00:38:01,640 MTB AGAIN THROUGH A TYPE ONE 817 00:38:01,640 --> 00:38:04,000 INTERFERON PATHWAY AND A GENETIC 818 00:38:04,000 --> 00:38:06,720 APPROACH GETTING RID OF THIS 819 00:38:06,720 --> 00:38:10,960 TPL2 PATHWAY IN MICE AND WE 820 00:38:10,960 --> 00:38:14,920 FOUND IT WAS ELEVATED AND FIN 821 00:38:14,920 --> 00:38:16,440 MACK NAB SHOW THIS COINCIDED AND 822 00:38:16,440 --> 00:38:19,320 DEPENDED ON TYPE ONE INTERFERON 823 00:38:19,320 --> 00:38:20,640 SIGNALING SO THIS WAS MEANS THAT 824 00:38:20,640 --> 00:38:23,520 YOU HAVE TO USE TO PUT THIS TYPE 825 00:38:23,520 --> 00:38:27,560 ONE INTERFERON UP AND THE MICE 826 00:38:27,560 --> 00:38:29,080 SUCCUMB SO TO SUMMARIZE A LOT OF 827 00:38:29,080 --> 00:38:30,880 WORK PUBLISHED BY A LOT OF 828 00:38:30,880 --> 00:38:34,560 PEOPLE, TYPE 1 INTERFERON COULD 829 00:38:34,560 --> 00:38:37,040 AT EARLY STAGES, MAYBE BE 830 00:38:37,040 --> 00:38:38,000 PROTECTIVE AND THERE'S STILL A 831 00:38:38,000 --> 00:38:39,480 LOT TO LEARN BUT WHEN IT WAS 832 00:38:39,480 --> 00:38:42,240 LATE SUSTAINED HIGH DOSES IN THE 833 00:38:42,240 --> 00:38:45,400 SYSTEMS IT COULD BLOCK IL-12 AND 834 00:38:45,400 --> 00:38:48,120 TNF AND INDUCE IL10 AND MY 835 00:38:48,120 --> 00:38:50,880 PROGRAM HAS A WHOLE PROGRAM ON 836 00:38:50,880 --> 00:38:53,680 IL-10 AND TYPE ONE INTERFERON 837 00:38:53,680 --> 00:38:57,080 COULD ALSO BLOCK ACTIVATION OF 838 00:38:57,080 --> 00:38:59,320 MACROPHAGE BY FAMILIAR A 839 00:38:59,320 --> 00:39:01,120 INTERFERON TO KILL BACTERIA AND 840 00:39:01,120 --> 00:39:04,720 ALSO PRO THESE PROTECTIVE 841 00:39:04,720 --> 00:39:05,600 CYTOKINES. 842 00:39:05,600 --> 00:39:07,800 SO, THAT WAS USING THESE METHODS 843 00:39:07,800 --> 00:39:10,920 TO TURN IT ON. 844 00:39:10,920 --> 00:39:13,160 I WANT TO REMIND YOU THOUGH OF 845 00:39:13,160 --> 00:39:16,800 OF SOME DATA THAT THEN CAT AND 846 00:39:16,800 --> 00:39:20,880 ALAN REALLY LED TO THEIR NEXT 847 00:39:20,880 --> 00:39:23,280 SEM SEMINOLE FINDINGS IS ALAN 848 00:39:23,280 --> 00:39:27,960 HAD FINDINGS IN HIS LAB THAT MY 849 00:39:27,960 --> 00:39:30,680 D88 MICE DEFICIENT MICE DISPLAY 850 00:39:30,680 --> 00:39:35,760 A PROFOUND LOSS IN RESISTANCE TO 851 00:39:35,760 --> 00:39:39,240 MTA AND CAT CAME IN VERY 852 00:39:39,240 --> 00:39:40,560 TENACIOUS AND LIKE HANGING ON 853 00:39:40,560 --> 00:39:42,600 AND I'VE GOT TO WORK THIS OUT 854 00:39:42,600 --> 00:39:44,200 AND I'LL NEVER FORGET SAYING 855 00:39:44,200 --> 00:39:45,640 ANNE, WHAT DO YOU THINK IS GOING 856 00:39:45,640 --> 00:39:46,720 ON? 857 00:39:46,720 --> 00:39:52,080 IT WAS TOUGH TO FIGURE OUT WHY 858 00:39:52,080 --> 00:39:57,880 IL-1 PROTECTION WAS REQUIRED 859 00:39:57,880 --> 00:40:01,080 DOWN TREATMENT MYD88 AND I'LL 860 00:40:01,080 --> 00:40:04,520 TOUCH ON THIS SEMINOLE PAPER 861 00:40:04,520 --> 00:40:06,840 THAT FOLLOWED AFTER A LOT OF 862 00:40:06,840 --> 00:40:08,760 THINKING AND DISCUSSION OF ALAN 863 00:40:08,760 --> 00:40:11,560 AND KAT AND KAT GOING TO CHINA 864 00:40:11,560 --> 00:40:14,040 AND REALLY PUSHING UNTIL THIS 865 00:40:14,040 --> 00:40:15,600 STAGE WHERE SHE'S ABOUT TO HAVE 866 00:40:15,600 --> 00:40:17,320 A BABY AND SHE'S FOUND OUT THE Y 867 00:40:17,320 --> 00:40:20,440 AND THE HOW AND LOOK THEY'RE 868 00:40:20,440 --> 00:40:21,600 SMILING AND CAT, THIS IS A 869 00:40:21,600 --> 00:40:22,880 MIRACLE, SHE WAS SUBMITTING THIS 870 00:40:22,880 --> 00:40:24,880 PAPER AND GOING FOR AN AWARD AND 871 00:40:24,880 --> 00:40:27,960 JUST REALLY PREGNANT. 872 00:40:27,960 --> 00:40:31,800 SO, THIS IS FOR ALL YOUNG PEOPLE 873 00:40:31,800 --> 00:40:36,280 TO KNOW ABOUT. 874 00:40:36,280 --> 00:40:39,560 KAT AND ALAN AND COLLABORATE 875 00:40:39,560 --> 00:40:41,080 HOST DIRECTIVE OF TUBERCULOSIS 876 00:40:41,080 --> 00:40:43,920 WAS BASED ON R1 AND TYPE 1 877 00:40:43,920 --> 00:40:47,960 INTERFERON CROSS TALK AND SO THE 878 00:40:47,960 --> 00:40:50,920 THE KNOCK OUTS DIED YET WHEN YOU 879 00:40:50,920 --> 00:40:52,840 CROSS THEM TO THE KNOCK OUT THEY 880 00:40:52,840 --> 00:40:55,280 GOT BETTER SO THIS CROSS 881 00:40:55,280 --> 00:40:56,800 REGULATION THAT BOB HAD BEEN 882 00:40:56,800 --> 00:40:58,840 TALKING ABOUT WITH GAMMA AND L4 883 00:40:58,840 --> 00:41:01,480 THEN THERE'S BEEN IL-10 AND 884 00:41:01,480 --> 00:41:05,120 GAMMA NOW IT WAS TYPE 1 AND L1 885 00:41:05,120 --> 00:41:07,520 AND THERE'S A HUGE AMOUNT TO BE 886 00:41:07,520 --> 00:41:09,400 DONE AND A LOT OF THINKING HAS 887 00:41:09,400 --> 00:41:11,480 BEEN GOING ON DURING THESE TYPES 888 00:41:11,480 --> 00:41:14,040 AND KAT AND ALAN TOGETHER WITH 889 00:41:14,040 --> 00:41:16,760 ANDRE HE IS, MARK AND MY LAB 890 00:41:16,760 --> 00:41:19,120 MEMBERS WE'VE WRITTEN REVIEWS ON 891 00:41:19,120 --> 00:41:21,160 TYPE 1 FOR INFECTIONION DISEASE 892 00:41:21,160 --> 00:41:23,480 AND TB AND OCCASIONALLY FRIEND 893 00:41:23,480 --> 00:41:26,280 THAT WAS LUCIA WITH KAT AND ALAN 894 00:41:26,280 --> 00:41:31,240 AND THIS IS BEEN SO MANY GREAT 895 00:41:31,240 --> 00:41:32,880 DISCUSSIONS OF WHERE THIS IS 896 00:41:32,880 --> 00:41:37,600 GOING AND TYPE 1 INTERFERON IS 897 00:41:37,600 --> 00:41:39,560 TOUGH AND TB IS TOUGH AND WE 898 00:41:39,560 --> 00:41:41,360 KNOW THAT KAT AND DAN FOLLOWING 899 00:41:41,360 --> 00:41:43,120 ON FROM ALAN WHO WILL BE THERE 900 00:41:43,120 --> 00:41:53,640 TO GIVE TIPS AND WHATEVER, WE 901 00:41:54,760 --> 00:41:56,600 WERE TRYING TO FIND A MODEL 902 00:41:56,600 --> 00:41:58,000 WHERE WE DIDN'T HAVE TO KNOCK 903 00:41:58,000 --> 00:42:00,040 OUT A GENE SO WE LOOKED FOR 904 00:42:00,040 --> 00:42:07,320 MOLDS AND THERE WAS A MOUSE 905 00:42:07,320 --> 00:42:11,840 WHICH HAD BEEN HAVE LUNG 906 00:42:11,840 --> 00:42:18,320 RESEMBLING HUMAN CASES GRANULOM 907 00:42:18,320 --> 00:42:20,440 A AND COULD IT BE THE STRAIN 908 00:42:20,440 --> 00:42:21,680 BASED ON THIS PAST THINKING AND 909 00:42:21,680 --> 00:42:22,680 ALL OUR DISCUSSION. 910 00:42:22,680 --> 00:42:27,200 WHAT WE DID WAS WE FOLLOWED ON 911 00:42:27,200 --> 00:42:28,200 THE BLOOD SIGNATURES OF HUMAN TB 912 00:42:28,200 --> 00:42:29,840 AND I'M TAKING YOU THROUGH A LOT 913 00:42:29,840 --> 00:42:30,200 OF DATA. 914 00:42:30,200 --> 00:42:32,000 THIS IS WHOLE BLOOD OF HUMAN 915 00:42:32,000 --> 00:42:34,760 FROM LONDON, SOUTH AFRICA LESTER 916 00:42:34,760 --> 00:42:36,640 AND I SHOWED YOU BEFORE WITH A 917 00:42:36,640 --> 00:42:38,640 DIFFERENT APPROACH WHERE WE SEE 918 00:42:38,640 --> 00:42:43,240 A NEW TRA FILL SIGNATURE AND 919 00:42:43,240 --> 00:42:45,200 ANOTHER INDUCE ABLE SIGNATURE IN 920 00:42:45,200 --> 00:42:55,360 THE HUMAN. 921 00:43:07,920 --> 00:43:11,440 WE USED LOW AND HIGH DOSE OF THE 922 00:43:11,440 --> 00:43:12,280 BUG AND EACH BUG TOGETHER WITH 923 00:43:12,280 --> 00:43:13,600 EACH STRAIN AND YOU HAVE TO LOOK 924 00:43:13,600 --> 00:43:17,880 ON THE RIGHT-HAND SIDE AND SEE 925 00:43:17,880 --> 00:43:20,280 WHEN IT'S HIT WITH THIS CLINICAL 926 00:43:20,280 --> 00:43:22,080 ISOLATE REALLY STARTS TO LOOK 927 00:43:22,080 --> 00:43:25,840 LIKE HUMAN DISEASE. 928 00:43:25,840 --> 00:43:29,200 AND SO, ALL OF A SUDDEN WE HAD A 929 00:43:29,200 --> 00:43:30,720 MODEL AND SO GOING IN AND 930 00:43:30,720 --> 00:43:33,160 LOOKING AT THIS MODEL, IN FACT 931 00:43:33,160 --> 00:43:35,400 YOU COULD SEE THAT THE B6 WHEN 932 00:43:35,400 --> 00:43:41,800 YOU GAVE IT A HIGH DOSE OF H78 933 00:43:41,800 --> 00:43:45,560 HIGH DOSE, ALSO COULD RESEMBLE A 934 00:43:45,560 --> 00:43:47,840 HUMAN DISEASE SO HIGH DOSE, 935 00:43:47,840 --> 00:43:48,680 DIFFERENT STRAINS, ALL OF THIS 936 00:43:48,680 --> 00:43:50,080 MAKES A DIFFERENCE AND MAKES A 937 00:43:50,080 --> 00:43:53,480 DIFFERENCE IN HUMANS AND SURE 938 00:43:53,480 --> 00:43:57,480 ENOUGH, LOW DOSE IN THE MICE IF 939 00:43:57,480 --> 00:43:59,080 NO KNOCK OUTS HAVE NO EFFECT 940 00:43:59,080 --> 00:44:01,320 HIGH DOSE, YOU CAN SEE THE 941 00:44:01,320 --> 00:44:02,440 BACTERIAL LOAD BUT YOU CAN SEE 942 00:44:02,440 --> 00:44:04,920 THAT IN THE MOUSE ACTUAL LOW 943 00:44:04,920 --> 00:44:08,360 THIS IS EVEN A LOW DOSE YOU SEE 944 00:44:08,360 --> 00:44:10,280 THE ANTI-IF NOT ANTIBODIES SINCE 945 00:44:10,280 --> 00:44:13,360 IT'S THE WRONG BACKGROUND FOR 946 00:44:13,360 --> 00:44:20,640 THE KNOCK OUT CAN HAVE A AN 947 00:44:20,640 --> 00:44:21,360 AMELIORATING EFFECT. 948 00:44:21,360 --> 00:44:23,840 >> THIS WAS AN INTERACTION WITH 949 00:44:23,840 --> 00:44:27,200 CAT AND ALAN HELPING US AND 950 00:44:27,200 --> 00:44:29,720 CONTRIBUTING, PARTICULARLY WHEN 951 00:44:29,720 --> 00:44:31,920 OUR MOUSE CL3 WAS DOWN AND ALSO 952 00:44:31,920 --> 00:44:36,040 ON THE THINKING SO LUCIA SHOWED 953 00:44:36,040 --> 00:44:39,200 THE MICE REDUCTION OF LESION 954 00:44:39,200 --> 00:44:44,520 BURDEN AND CFU AND PRODUCTION OF 955 00:44:44,520 --> 00:44:46,560 KNEW TRA FILL TRAP FORMATION AND 956 00:44:46,560 --> 00:44:51,120 SHOWN BY H3 AND YOU SEE THAT THE 957 00:44:51,120 --> 00:44:54,120 MPO STAINING IS REDUCED BUT 958 00:44:54,120 --> 00:44:57,720 STILL THERE AND IN THAT NOT ALL 959 00:44:57,720 --> 00:45:03,000 THE KNEW TRA FILLS WERE GONE BUT 960 00:45:03,000 --> 00:45:13,360 THE NETS WERE GONE. 961 00:45:34,040 --> 00:45:35,240 THE GREN IS FOR THE B CELLS AND 962 00:45:35,240 --> 00:45:37,360 THE RED YOU SEE THE T CELLS AND 963 00:45:37,360 --> 00:45:40,080 JUST GOING RESISTANCE AND 964 00:45:40,080 --> 00:45:42,560 SUSCEPTIBLE LAB STRAIN CLINICAL 965 00:45:42,560 --> 00:45:44,720 ISOLATE AND YOU CAN SEE AS SOON 966 00:45:44,720 --> 00:45:46,720 AS YOU START GETTING THE 967 00:45:46,720 --> 00:45:49,120 PATHOGENESIS, THE B AND THE T 968 00:45:49,120 --> 00:45:51,880 CELLS DIMINISH AND WE NEED TO 969 00:45:51,880 --> 00:45:53,560 KNOW CHICKEN AND EGG AND WHAT'S 970 00:45:53,560 --> 00:45:55,280 GOING ON SO THERE'S A LOT MORE 971 00:45:55,280 --> 00:45:58,880 TO EXPLORE THAT WE'LL BRANCH IT 972 00:45:58,880 --> 00:46:01,080 AND CONTINUING THE LAB BUT THIS 973 00:46:01,080 --> 00:46:03,520 IS FROM ACTUALLY, THIS IS THE 974 00:46:03,520 --> 00:46:05,720 EARLY FIGURE REMEMBER ALAN IN 975 00:46:05,720 --> 00:46:07,200 THE REVIEW WE'VE JUST WRITTEN 976 00:46:07,200 --> 00:46:11,880 WITH ALAN AND ANDRES AND IT'S 977 00:46:11,880 --> 00:46:15,800 MUCH CHANGED THAT IT ACTIVATES 978 00:46:15,800 --> 00:46:17,720 NEUTROPHIL FOR MICE AND WE STILL 979 00:46:17,720 --> 00:46:20,520 ARE NOT SURE WHERE THE TYPE ONE 980 00:46:20,520 --> 00:46:22,200 INTER FOUR ON DRIVES RECRUITMENT 981 00:46:22,200 --> 00:46:24,560 MONOCYTES AND NEUTROPHIL FROM 982 00:46:24,560 --> 00:46:33,680 THE BONE MARROW TO THE LUNG. 983 00:46:33,680 --> 00:46:35,440 KAT WILL FOLLOW ON THE IL1 AND 984 00:46:35,440 --> 00:46:37,640 HOW THE TYPE ONE INTERFERON 985 00:46:37,640 --> 00:46:40,480 CONTINUES AND WHEN YOU GET 986 00:46:40,480 --> 00:46:42,280 CONTROL VERSUS DEATH AND 987 00:46:42,280 --> 00:46:43,880 SUSCEPTIBLE AND WORE STILL 988 00:46:43,880 --> 00:46:45,280 ASKING THIS QUESTION DOES TYPE 989 00:46:45,280 --> 00:46:47,640 ONE INTERFERON AT A LOW LEVEL 990 00:46:47,640 --> 00:46:49,960 EARLY HELP ON THESE BNT 991 00:46:49,960 --> 00:46:50,960 RESISTANT MICE. 992 00:46:50,960 --> 00:46:52,200 SO THERE'S STILL A LOT TO ANSWER 993 00:46:52,200 --> 00:46:55,840 IN THE EXPERIMENTAL MODELS BUT I 994 00:46:55,840 --> 00:46:57,200 STARTED WORK ONG THE HUMAN TB TO 995 00:46:57,200 --> 00:46:58,400 TRY AND UNDERSTAND WHAT WAS 996 00:46:58,400 --> 00:46:59,000 GOING ON. 997 00:46:59,000 --> 00:47:01,960 AS AN IMMUNOLOGIST, I SAID, WHAT 998 00:47:01,960 --> 00:47:03,640 REALLY WAS FASCINATING IS THE 999 00:47:03,640 --> 00:47:05,400 PROBLEM OF LATENT SEE, A QUARTER 1000 00:47:05,400 --> 00:47:07,160 OF THE WORLD ESTIMATED TO BE 1001 00:47:07,160 --> 00:47:09,080 INFECTED BUT ALL YOU CAN SAY IS 1002 00:47:09,080 --> 00:47:10,800 THAT THEY'RE POSITIVE FOR THIS 1003 00:47:10,800 --> 00:47:14,200 INTERFERON GAMMA RELEASE ASSAY 1004 00:47:14,200 --> 00:47:16,600 AND YOU JUST DON'T KNOW WHO IS 1005 00:47:16,600 --> 00:47:19,160 GOING TO GO AND IN ALL THE 1006 00:47:19,160 --> 00:47:21,200 TEXTBOOKS IT SAID, THESE LATER 1007 00:47:21,200 --> 00:47:22,800 INDIVIDUALS CAN PROGRESS TO 1008 00:47:22,800 --> 00:47:24,280 ACTIVE DUTY AT ANY TIME DURING 1009 00:47:24,280 --> 00:47:26,080 THEIR LIFETIME AND THIS 1010 00:47:26,080 --> 00:47:27,760 SOMETHING THAT I'D LUKE TO 1011 00:47:27,760 --> 00:47:29,320 REVISIT HERE AND SUGGEST THAT 1012 00:47:29,320 --> 00:47:31,440 IT'S A SHORTER WINDOW WHEN 1013 00:47:31,440 --> 00:47:33,520 PEOPLE CAN PROGRESS TO TB AND 1014 00:47:33,520 --> 00:47:36,920 AFTER THAT, IT'S POTENTIALLY 1015 00:47:36,920 --> 00:47:39,080 REINFECTION AND SO HOW DID WE 1016 00:47:39,080 --> 00:47:40,080 GET AT THIS? 1017 00:47:40,080 --> 00:47:43,800 SO THE QUESTION WAS, OF THESE 1018 00:47:43,800 --> 00:47:45,720 LATENT INDIVIDUALS, THEY COULD 1019 00:47:45,720 --> 00:47:47,640 BE FIVE TO 10% PROGRESSIVE AND 1020 00:47:47,640 --> 00:47:49,320 CLEARED THE INFECTION AND IT 1021 00:47:49,320 --> 00:47:50,600 COULD BE CONTROLLED OR 1022 00:47:50,600 --> 00:47:52,400 PERSISTENT AND SUB CLINICAL 1023 00:47:52,400 --> 00:47:53,960 DISEASE AND ALL YOU CAN SAY IS 1024 00:47:53,960 --> 00:47:56,120 THAT THEY'RE POSITIVE FOR THE 1025 00:47:56,120 --> 00:47:57,720 TEST WHICH SHOWS THAT THEY 1026 00:47:57,720 --> 00:47:59,800 REACTED AND LOOKING BACK AT OUR 1027 00:47:59,800 --> 00:48:01,440 OLD DATA, WHAT I DIDN'T POINT 1028 00:48:01,440 --> 00:48:04,480 OUT IS THAT THESE LATENT 1029 00:48:04,480 --> 00:48:06,440 INDIVIDUALS WHERE HETERO GONE 1030 00:48:06,440 --> 00:48:08,760 YUS THAT THEY LOOKED LIKE THE 1031 00:48:08,760 --> 00:48:11,720 ACTIVE TBN AND IF YOU JUST LOOK, 1032 00:48:11,720 --> 00:48:13,240 THESE ARE LATENT BUT THEY HAVE A 1033 00:48:13,240 --> 00:48:15,600 SIGNATURE OF ACTIVE TB SO THIS 1034 00:48:15,600 --> 00:48:16,680 IS STATIC. 1035 00:48:16,680 --> 00:48:19,600 IF YOU LOCK AT A MODULAR LEVEL 1036 00:48:19,600 --> 00:48:21,320 YOU CAN SEE THAT YOU TAKEAWAY 1037 00:48:21,320 --> 00:48:24,040 THE ACTIVE TB OUT LIES, THESE 1038 00:48:24,040 --> 00:48:26,880 THAT WERE THE HETEROGENEOUS ONES 1039 00:48:26,880 --> 00:48:29,600 AND LOOK AT THE ACTIVE TB BLOOD 1040 00:48:29,600 --> 00:48:31,000 SIGNATURE AND YOU SEE THE 1041 00:48:31,000 --> 00:48:32,800 INTERFERON AND THE OUTLIERS AND 1042 00:48:32,800 --> 00:48:37,800 THE OTHER LATE ENTERS, NO 1043 00:48:37,800 --> 00:48:38,080 SIGNATURE. 1044 00:48:38,080 --> 00:48:48,360 THIS IS STATIC. 1045 00:48:48,680 --> 00:48:52,520 CAN TRANSCRIPTOMIC TELL US ABOUT 1046 00:48:52,520 --> 00:48:54,240 PROGRESSION TO TB SO TO DO THAT 1047 00:48:54,240 --> 00:48:55,720 IS QUITE TOUGH AND WE'RE VERY 1048 00:48:55,720 --> 00:49:01,000 LUCKY TO HAVE COLLABORATORS IN 1049 00:49:01,000 --> 00:49:10,160 LESTER WHO ARE THIS MINIMIZES 1050 00:49:10,160 --> 00:49:12,400 REINFECTION OF MTB WITH ANOTHER 1051 00:49:12,400 --> 00:49:15,000 STRAIN AND SO WE DID A 1052 00:49:15,000 --> 00:49:16,440 LONGITUDINAL STUDY WITH THEM 1053 00:49:16,440 --> 00:49:20,360 THAT WE PUBLISHED IN 2018 SO I'M 1054 00:49:20,360 --> 00:49:24,640 SUMMARIZING IN A CARTOON HERE 1055 00:49:24,640 --> 00:49:29,440 AND LED IN LESTER AND IN MY LAB 1056 00:49:29,440 --> 00:49:31,320 LOOKING AT THE ANALYSIS AND THE 1057 00:49:31,320 --> 00:49:35,120 BOTTOM LINE OF THESE 53 ACTIVE 1058 00:49:35,120 --> 00:49:38,520 TB PATIENTS, THESE CONTEXT, 108 1059 00:49:38,520 --> 00:49:41,640 CONTEXT WERE FOLLOWED SOME WERE 1060 00:49:41,640 --> 00:49:42,720 NEGATIVE AND 49 WERE POSITIVE 1061 00:49:42,720 --> 00:49:44,360 BUT STAYED HEALTHY AND THEY'RE 1062 00:49:44,360 --> 00:49:50,560 STILL HEALTHY FIVE YEARS LATER. 1063 00:49:50,560 --> 00:49:52,160 THE NEGATIVE WENT POSITIVE WENT 1064 00:49:52,160 --> 00:49:54,600 ON TO DEVELOP TB AND THIS WAS 1065 00:49:54,600 --> 00:49:56,080 10% AND THEY WERE CHARACTERIZED 1066 00:49:56,080 --> 00:49:58,080 BY A PERSISTENT HIGH BLOOD 1067 00:49:58,080 --> 00:49:59,760 SIGNATURE IN MOST OF THEM. 1068 00:49:59,760 --> 00:50:01,920 SO WE WANTED TO LOOK FORWARD AND 1069 00:50:01,920 --> 00:50:08,320 WE INCREASED THE NUMBERS AND DID 1070 00:50:08,320 --> 00:50:10,600 A QUITE A DETAIL STUDY WHERE 1071 00:50:10,600 --> 00:50:11,760 THEY WERE FUNDAMENTAL AND WE 1072 00:50:11,760 --> 00:50:14,560 LEARNED A LOT AND LINKING 1073 00:50:14,560 --> 00:50:20,040 CLINICAL PHENOTYPES WITH GENOME 1074 00:50:20,040 --> 00:50:23,080 DATA SO THE BUG WAS SEQUENCED IN 1075 00:50:23,080 --> 00:50:25,000 THE ACTIVE TB PATIENTS AND THEN 1076 00:50:25,000 --> 00:50:26,520 IN THE CONTEXT WHEN THEY 1077 00:50:26,520 --> 00:50:30,120 PROGRESS TO TB SO WE GOT THE 1078 00:50:30,120 --> 00:50:31,680 INDEX CASE AND THEY HAD THE SAME 1079 00:50:31,680 --> 00:50:33,920 SEQUENCE WHICH IS NOT BEEN DONE 1080 00:50:33,920 --> 00:50:37,680 IN OTHER STUDIES, WE COULD DO 1081 00:50:37,680 --> 00:50:37,920 IT. 1082 00:50:37,920 --> 00:50:39,920 SO, THIS IS THE DESIGN OF THE 1083 00:50:39,920 --> 00:50:42,280 STUDY THAT WE'VE JUST PUBLISHED 1084 00:50:42,280 --> 00:50:43,600 IN THE JOURNAL OF EXPERIMENTAL 1085 00:50:43,600 --> 00:50:54,160 MEDICINE AND IT WAS HARD AND IT 1086 00:50:59,640 --> 00:51:02,040 CAN TAKE MONTHS TO DETERMINE 1087 00:51:02,040 --> 00:51:05,000 THAT SOMEONE HAS TB BUT, THE 1088 00:51:05,000 --> 00:51:06,840 ONES WHO HAVE TB ARE RECRUITED 1089 00:51:06,840 --> 00:51:12,560 TO THE STUDY AND THEN OF 365 IF 1090 00:51:12,560 --> 00:51:18,960 I CAN FIND MY POINTER. 1091 00:51:18,960 --> 00:51:20,240 THESE WERE MONITORED OVER THREE 1092 00:51:20,240 --> 00:51:21,680 YEARS AND IT'S NOW FIVE YEARS 1093 00:51:21,680 --> 00:51:24,840 AND MEETING WITH HE KNOWS ME 1094 00:51:24,840 --> 00:51:33,080 NONE OF THE OTHER DEVELOP MOST 1095 00:51:33,080 --> 00:51:34,120 OF THEM ONE TIGER WOODS AND TWO 1096 00:51:34,120 --> 00:51:39,800 AND A FEW OF THREE YEARS AND 1097 00:51:39,800 --> 00:51:43,720 THOSE THAT THEY WERE DEFINITELY 1098 00:51:43,720 --> 00:51:45,640 CONTEXT OF THOSE TB AND NOW, 1099 00:51:45,640 --> 00:51:53,960 FROM THE CLINIC, THE PROGRESSIVE 1100 00:51:53,960 --> 00:52:04,440 TL IT COULD BE PEOPLE WHO HAVE 1101 00:52:05,280 --> 00:52:07,000 NO SYMPTOMS AND THEY'RE POSITIVE 1102 00:52:07,000 --> 00:52:10,280 AND NOW CLINICAL AND NO 1103 00:52:10,280 --> 00:52:12,080 RADIOLOGICAL ABNORMALITIES AND 1104 00:52:12,080 --> 00:52:14,200 NO EVIDENCE OF ACTIVITY TB AND 1105 00:52:14,200 --> 00:52:19,120 WE FOUND THAT THESE TOOK BETWEEN 1106 00:52:19,120 --> 00:52:22,440 41, 125 AND SOME 200 TO 300 DAYS 1107 00:52:22,440 --> 00:52:25,840 TO PROGRESS TO T AND THE SUB 1108 00:52:25,840 --> 00:52:28,200 CLINICAL ARE ONES THAT EITHER 1109 00:52:28,200 --> 00:52:29,520 HAVE NO CLINICAL SYMPTOMS. 1110 00:52:29,520 --> 00:52:30,880 THEY REALLY ARE FINE AND THEY'VE 1111 00:52:30,880 --> 00:52:33,480 BEEN TAKEN BECAUSE THEY WERE 1112 00:52:33,480 --> 00:52:35,520 CONTACTS OR FOR SOME OF THE 1113 00:52:35,520 --> 00:52:36,080 REASONS THEY LOOKED AT THEIR 1114 00:52:36,080 --> 00:52:40,200 LUNG AND THESE MAY HAVE A CHANGE 1115 00:52:40,200 --> 00:52:41,280 IN THEIR LUNG X-RAY BUT THIS 1116 00:52:41,280 --> 00:52:42,440 COULD BE ANOTHER LUNG DISEASE, 1117 00:52:42,440 --> 00:52:45,320 IT COULD BE CANCER, PNEUMONIA OR 1118 00:52:45,320 --> 00:52:47,880 THEY COULD HAVE GROWN A BUG FROM 1119 00:52:47,880 --> 00:52:49,080 THESE PATIENTS BUT THEY HAVE NO 1120 00:52:49,080 --> 00:52:50,760 SYMPTOMS AND NO LUNG SYMPTOMS 1121 00:52:50,760 --> 00:52:54,840 AND THAT COULD BE CROSS 1122 00:52:54,840 --> 00:52:58,000 CONTAMINATION OR AN OLD 1123 00:52:58,000 --> 00:52:58,360 SCARRING. 1124 00:52:58,360 --> 00:53:00,200 AND THESE ONES WE FOUND 1125 00:53:00,200 --> 00:53:05,960 DEVELOPED TB WITHIN 20 TO 40 1126 00:53:05,960 --> 00:53:12,440 DAYS AND THEN THEY HAD 1127 00:53:12,440 --> 00:53:13,680 RADIOLOGICAL FEATURES AND 1128 00:53:13,680 --> 00:53:24,040 EVIDENCE OF ACTIVE AND 1129 00:53:27,680 --> 00:53:28,280 PARTICULARLY FOLLOWING THESE 1130 00:53:28,280 --> 00:53:32,920 CONTEXT THE NEW SCENARIO AND SO, 1131 00:53:32,920 --> 00:53:34,440 WE LOGGED AT THE GONE SIGNATURE 1132 00:53:34,440 --> 00:53:36,160 AND I'M ONLY SHOWING YOU PART OF 1133 00:53:36,160 --> 00:53:38,480 WHAT IS IN THE PAPER AND YOU CAN 1134 00:53:38,480 --> 00:53:39,840 SEE CERTAIN GENES ARE STARTING 1135 00:53:39,840 --> 00:53:41,800 TO GO UP AND THEN BY SUB 1136 00:53:41,800 --> 00:53:43,560 CLINICAL, THEY'RE GETTING HIGHER 1137 00:53:43,560 --> 00:53:45,880 AND THEN AT CLINICAL TB THEY'RE 1138 00:53:45,880 --> 00:53:47,320 HIGHER AND THESE ARE THE CONTEXT 1139 00:53:47,320 --> 00:53:52,480 BUT THEY'RE NOT EVEN NEARLY AS 1140 00:53:52,480 --> 00:53:54,720 HIGH OF WHEN YOU HAVE HIGH FULLY 1141 00:53:54,720 --> 00:53:58,320 BLOWN ACTIVE TB AND WE HAD A LOT 1142 00:53:58,320 --> 00:54:00,760 OF THINKING ON THIS AND ANALYZED 1143 00:54:00,760 --> 00:54:02,880 ALL THE DATA AND THERE ARE A 1144 00:54:02,880 --> 00:54:05,680 COMMON PATHWAYS ENRICHED IN UP 1145 00:54:05,680 --> 00:54:06,800 REGULATED GOWNS IN ALL THROW OF 1146 00:54:06,800 --> 00:54:09,240 THE CLINICAL GROUPS THAT ARE 1147 00:54:09,240 --> 00:54:12,320 TYPE ONE INTERFERON TIM YOU 1148 00:54:12,320 --> 00:54:13,960 LATED GOWNS AND HIGHLY ENRICHED 1149 00:54:13,960 --> 00:54:15,040 SO EARLY ON BEFORE ANYBODY HAS 1150 00:54:15,040 --> 00:54:17,840 ANY SYMPTOMS, THESE TYPE 1 ARE 1151 00:54:17,840 --> 00:54:21,520 COMING UP AND THE GLAD SIGNATURE 1152 00:54:21,520 --> 00:54:23,480 IS MORE AND MORE PRONOUNCED AS 1153 00:54:23,480 --> 00:54:32,800 THEY PROGRESS. 1154 00:54:32,800 --> 00:54:36,640 YOU CAN'T -- IT ALSO DEALS US A 1155 00:54:36,640 --> 00:54:38,640 LOT ABOUT THE POTENTIAL 1156 00:54:38,640 --> 00:54:40,200 PATHOGENESIS AND WITH THE 1157 00:54:40,200 --> 00:54:41,520 EXPERIMENTAL MODELS. 1158 00:54:41,520 --> 00:54:43,640 USING THE MODELS AGAIN WE COULD 1159 00:54:43,640 --> 00:54:45,200 TEASE OUT A LITTLE BIT MORE AND 1160 00:54:45,200 --> 00:54:47,640 ACTUALLY WHAT WE CAN SEE HERE IS 1161 00:54:47,640 --> 00:54:49,080 THAT IN DEED IN THE SUB CLINICAL 1162 00:54:49,080 --> 00:54:52,400 YOU CAN SEE THE INTERFERON 1163 00:54:52,400 --> 00:54:54,320 SIGNATURE AND THE SECOND 1164 00:54:54,320 --> 00:54:59,080 INTERFERON SIGNATURE WHICH USING 1165 00:54:59,080 --> 00:55:02,120 WGCNA WE TEASE OUT MORE. 1166 00:55:02,120 --> 00:55:03,520 WE SEE THOSE T-CELL GOWNS ARE 1167 00:55:03,520 --> 00:55:06,800 STARTING TO GO DOWN IN THIS 1168 00:55:06,800 --> 00:55:08,960 ACTIVE, IN THIS PROGRESSION FROM 1169 00:55:08,960 --> 00:55:13,040 NO SYMPTOMS TO THEN HIGH 1170 00:55:13,040 --> 00:55:14,920 SYMPTOMS AND THIS IS WHAT NEEDS 1171 00:55:14,920 --> 00:55:16,400 TO BE TEASED OUT MORE BUT OF 1172 00:55:16,400 --> 00:55:17,800 COURSE, THE BLOOD WE WERE LUCKY 1173 00:55:17,800 --> 00:55:19,480 TO SEE A SIGNATURE AT ALL IN THE 1174 00:55:19,480 --> 00:55:23,320 BLOOD OF TB PATIENTS NEVER MIND 1175 00:55:23,320 --> 00:55:24,560 PROGRESSES SO OUR FUTURE STUDIES 1176 00:55:24,560 --> 00:55:26,080 IS WHAT I'M GOING TO LEAVE YOU 1177 00:55:26,080 --> 00:55:27,440 WITH, I'M NOT SHOWING ANY DATA. 1178 00:55:27,440 --> 00:55:29,920 THIS IS WHAT WE'RE IN THE MIDDLE 1179 00:55:29,920 --> 00:55:30,600 OF. 1180 00:55:30,600 --> 00:55:32,840 CONTINUING OUR STUDIES WITH POUR 1181 00:55:32,840 --> 00:55:34,560 COLLABORATORS ON PATIENTS WITH 1182 00:55:34,560 --> 00:55:37,800 ACTIVE TB WHERE SAMPLING 30 1183 00:55:37,800 --> 00:55:40,240 EXPOSURE GET THE RECENT CONTEXT 1184 00:55:40,240 --> 00:55:42,560 IN AND WHEN THEY'RE POSITIVE WE 1185 00:55:42,560 --> 00:55:44,520 WILL BASICALLY TAKE AN AIRWAY 1186 00:55:44,520 --> 00:55:55,040 SAMPLE AT ONE VISIT THAT WE CAN 1187 00:57:18,640 --> 00:57:20,120 DISCUSS SO DEEPLY WITH AND 1188 00:57:20,120 --> 00:57:21,800 REALLY GET TO THE BOTTOM OF IT 1189 00:57:21,800 --> 00:57:23,880 ALL AND THIS IS JUST TAKING US 1190 00:57:23,880 --> 00:57:26,240 THROUGH THE JOURNEY WITH MATTHEW 1191 00:57:26,240 --> 00:57:28,240 BERRY THE FIRST CLINICIANS AND 1192 00:57:28,240 --> 00:57:33,800 LOTS OF CLINICIANS FOLLOWING. 1193 00:57:33,800 --> 00:57:35,640 WE STARTED IN LONDON AND WE HAD 1194 00:57:35,640 --> 00:57:37,440 TO LEAVE THERE BECAUSE THE 1195 00:57:37,440 --> 00:57:38,760 CLINICIAN, THE TB PROFESSOR 1196 00:57:38,760 --> 00:57:40,240 DIDN'T WANT TO SHARE SAMPLES SO 1197 00:57:40,240 --> 00:57:48,240 THEN WE WANT TO LESTER AND IN 1198 00:57:48,240 --> 00:57:49,800 LESTER THEY HAVE SUCH A 1199 00:57:49,800 --> 00:57:52,320 FANTASTIC SET UP FOR GETTING TB 1200 00:57:52,320 --> 00:57:53,560 PATIENTS CONTACTS IN EARLY TO 1201 00:57:53,560 --> 00:57:56,680 THE CLINIC AND OF COURSE NO RISK 1202 00:57:56,680 --> 00:57:59,320 OF REINFECTION AS YOU GET IN 1203 00:57:59,320 --> 00:58:00,800 AFRICA WHEN PEOPLE ARE SUGGEST 1204 00:58:00,800 --> 00:58:03,320 THAT YOU ARE REACTIVATING TB AND 1205 00:58:03,320 --> 00:58:05,600 ROB WILKINSON IS A LONG-TERM 1206 00:58:05,600 --> 00:58:07,800 COLLABORATOR AND THE BEGINNING 1207 00:58:07,800 --> 00:58:13,640 WAS IN THE HUMAN STUDY WAS 1208 00:58:13,640 --> 00:58:14,480 REALLY JAQUES AND VIRGINIA WHO 1209 00:58:14,480 --> 00:58:15,800 GAVE US THE STRENGTH AND THE 1210 00:58:15,800 --> 00:58:17,400 KNOW HOW TO GO FORWARD AND ALL 1211 00:58:17,400 --> 00:58:19,800 MY LAB MEMBERS USED TO GO THERE 1212 00:58:19,800 --> 00:58:21,920 AND GET TRAINED NOW WE'RE VERY 1213 00:58:21,920 --> 00:58:25,600 HAPPY WE DO THE BIO FORMAT TICKS 1214 00:58:25,600 --> 00:58:28,160 OURSELVES WITH OUR OWN LAB AND 1215 00:58:28,160 --> 00:58:30,000 THESE ARE ALL THE PEOPLE 1216 00:58:30,000 --> 00:58:32,120 CONTRIBUTING TO THE MOUSE WORK 1217 00:58:32,120 --> 00:58:37,280 AND THROUGH THE YEARS I 1218 00:58:37,280 --> 00:58:38,880 HIGHLIGHTED FIN SAY LONG-TERM 1219 00:58:38,880 --> 00:58:40,560 MEMBER OF MY LAB WHO IS STILL 1220 00:58:40,560 --> 00:58:42,840 WITH US DURING THE MTB MOUSE 1221 00:58:42,840 --> 00:58:45,440 STUDIES WHICH ARE HARD. 1222 00:58:45,440 --> 00:58:47,960 WE HAD TO GO TO LONDON SCHOOL 1223 00:58:47,960 --> 00:58:49,640 AND TAKE A TAXI AT THE BEGINNING 1224 00:58:49,640 --> 00:58:53,440 OF OUR TB STUDY SO WE EMPATHIZE 1225 00:58:53,440 --> 00:58:55,160 AND WE'RE LUCKY WITH OUR SCIENCE 1226 00:58:55,160 --> 00:58:58,800 TECHNOLOGY PLATFORMS AND ANDRES 1227 00:58:58,800 --> 00:59:01,320 IS A FRIEND AND KAT AND ALAN, I 1228 00:59:01,320 --> 00:59:03,200 HAVE TO SINGLE OUT THIS IS BEEN 1229 00:59:03,200 --> 00:59:05,720 SUCH A REWARDING INTERACTION ON 1230 00:59:05,720 --> 00:59:08,920 WHAT WE ALL AGREE IS A DAMN 1231 00:59:08,920 --> 00:59:10,960 DIFFICULT DISEASE TO WORK ON AT 1232 00:59:10,960 --> 00:59:11,760 ALL LEVELS. 1233 00:59:11,760 --> 00:59:14,080 WE CAN DRINK TO THAT FOR THE 1234 00:59:14,080 --> 00:59:14,320 FUTURE. 1235 00:59:14,320 --> 00:59:17,960 GOOD LUCK TO ALL OF YOU ALUMNI 1236 00:59:17,960 --> 00:59:21,280 OF ALAN'S AND ALL THE TRAINEES 1237 00:59:21,280 --> 00:59:23,960 WHO HAVE NOW GONE OUT TO THE 1238 00:59:23,960 --> 00:59:26,760 WORLD TO CURE TB. 1239 00:59:26,760 --> 00:59:36,960 [APPLAUSE] 1240 00:59:47,240 --> 00:59:53,880 >> DO I HAVE ANY QUESTIONS? 1241 00:59:53,880 --> 00:59:57,440 IT'S TOO ARTICLE IN THE MORNING 1242 00:59:57,440 --> 01:00:01,120 I THINK. 1243 01:00:01,120 --> 01:00:05,120 >> I WOULDN'T TO CONTRIBUTION 1244 01:00:05,120 --> 01:00:15,320 [OFF MIC] 1245 01:00:18,560 --> 01:00:21,880 >> ALAN SAID HE IS GOOD I THINK 1246 01:00:21,880 --> 01:00:24,680 HE WOULD BE PERFECT BUT HE SITS 1247 01:00:24,680 --> 01:00:28,240 AT HIS DESK A LOT. 1248 01:00:28,240 --> 01:00:29,240 [LAUGHTER] 1249 01:00:29,240 --> 01:00:30,280 YOU LED THE WAY. 1250 01:00:30,280 --> 01:00:33,160 AND YOU KNOW WHAT, I THINK IT'S 1251 01:00:33,160 --> 01:00:35,000 WORTH, THANKS FOR HIGHLIGHTING 1252 01:00:35,000 --> 01:00:37,000 THAT BECAUSE DAMIAN IS BACK IN 1253 01:00:37,000 --> 01:00:38,640 NEW YORK SINCE FEBRUARY AND 1254 01:00:38,640 --> 01:00:42,680 WE'RE ALL DELIGHTED THAT WE CAN 1255 01:00:42,680 --> 01:00:43,040 INTERACT. 1256 01:00:43,040 --> 01:00:44,720 NEW YORK IS A HOP FROM LONDON 1257 01:00:44,720 --> 01:00:47,280 AND IT WAS GREAT TO SEE HIS KID 1258 01:00:47,280 --> 01:00:49,840 AND SEE THAT IT'S ALL SETTLING 1259 01:00:49,840 --> 01:00:55,240 AND ANOTHER ALUMNI OF ALAN'S. 1260 01:00:55,240 --> 01:00:59,720 HIM SITTING AT HIS DESK WAS 1261 01:00:59,720 --> 01:01:01,480 USEFUL. 1262 01:01:01,480 --> 01:01:01,880 [LAUGHTER] 1263 01:01:01,880 --> 01:01:03,160 >> THANK YOU FOR THAT 1264 01:01:03,160 --> 01:01:03,640 FASCINATING TALK. 1265 01:01:03,640 --> 01:01:09,400 HAVE YOU LOCKED AT EXTRA PULL 1266 01:01:09,400 --> 01:01:11,920 PULMONARY TB VERSUS DISSEMINATED 1267 01:01:11,920 --> 01:01:12,120 OR. 1268 01:01:12,120 --> 01:01:14,040 >> WE PUBLISHED A PAPER THAT WAS 1269 01:01:14,040 --> 01:01:16,600 SIMON BLACKLY'S WORK WHICH I 1270 01:01:16,600 --> 01:01:18,400 COULDN'T GO INTO EVERYTHING AND 1271 01:01:18,400 --> 01:01:21,200 EXTRA PULMONARY TB HAS AN 1272 01:01:21,200 --> 01:01:22,080 IDENTICAL SIGNATURE AND WE 1273 01:01:22,080 --> 01:01:24,160 THOUGHT IT WAS WEAKER AND 1274 01:01:24,160 --> 01:01:25,960 ACTUALLY WHEN WE STUDIED IT, IT 1275 01:01:25,960 --> 01:01:29,240 WAS MORE SIM POM RELATED. 1276 01:01:29,240 --> 01:01:31,320 SO, WE PUBLISHED IN OUR FIRST 1277 01:01:31,320 --> 01:01:33,360 PAPER AND THEN SUBSEQUENTLY THAT 1278 01:01:33,360 --> 01:01:38,160 THE EXTENT OF LUNG RADIO GRAPHIC 1279 01:01:38,160 --> 01:01:40,880 DISEASE IN PULMONARY TB 1280 01:01:40,880 --> 01:01:42,320 CORRELATES WITH THE SIGNATURE 1281 01:01:42,320 --> 01:01:44,680 AND EXTRA PULMONARY TB WE 1282 01:01:44,680 --> 01:01:46,480 THOUGHT IT WAS HAVING A WEAKER 1283 01:01:46,480 --> 01:01:48,000 SIGNATURE BUT WHEN WE SEPARATED 1284 01:01:48,000 --> 01:01:51,720 THE SYMPTOMS, WE FOUND AGAIN 1285 01:01:51,720 --> 01:01:52,360 STRONG SIGNATURES WHEN THEY HAVE 1286 01:01:52,360 --> 01:01:53,640 BAD DISEASE AND WEAKER. 1287 01:01:53,640 --> 01:01:56,960 IT'S VERY, VERY SIMILAR AND SO 1288 01:01:56,960 --> 01:01:58,520 THIS IS A QUESTION WE'VE ASKED 1289 01:01:58,520 --> 01:01:59,920 FOR MANY YEARS AND THE 1290 01:01:59,920 --> 01:02:01,440 DISSEMINATION AND WHY DOES IT 1291 01:02:01,440 --> 01:02:04,280 HAPPEN AND IT'S SOMETHING WE'RE 1292 01:02:04,280 --> 01:02:05,640 NOT FOLLOWING AND IT'S OBVIOUS 1293 01:02:05,640 --> 01:02:10,240 LOW A HARD ONE BECAUSE IT'S 1294 01:02:10,240 --> 01:02:14,120 DIFFICULT TO DIAGNOSE. 1295 01:02:14,120 --> 01:02:15,880 THERE HERE ARE FOLLOWING TO TRY 1296 01:02:15,880 --> 01:02:17,960 AND GET A SUPPORT FOR DIAGNOSIS 1297 01:02:17,960 --> 01:02:20,360 OF TB IN THE SIGNATURE TO 1298 01:02:20,360 --> 01:02:22,880 SUPPORT OTHER ASPECTS LIKE EXTRA 1299 01:02:22,880 --> 01:02:26,360 PULL MINPULMONARY. 1300 01:02:26,360 --> 01:02:29,720 >> THANK YOU. 1301 01:02:29,720 --> 01:02:30,000 ALL RIGHT. 1302 01:02:30,000 --> 01:02:31,720 THANK YOU. 1303 01:02:31,720 --> 01:02:36,040 [APPLAUSE] 1304 01:02:36,040 --> 01:02:41,920 OUR NEXT SPEAKER IS TRAINEE FROM 1305 01:02:41,920 --> 01:02:52,320 ALAN'S LAB AND ANTONIO 1306 01:02:52,320 --> 01:03:02,480 ROTHCHS. 1307 01:03:23,040 --> 01:03:25,240 >> THESE PODIUMS IN THE U.S. 1308 01:03:25,240 --> 01:03:27,000 MADE FOR MUCH SHORTER PEOPLE 1309 01:03:27,000 --> 01:03:27,840 THAN THE SWEDISH ONES. 1310 01:03:27,840 --> 01:03:33,480 I REALLY APPRECIATE THAT. 1311 01:03:33,480 --> 01:03:37,240 SO, WHERE IS DRAGANA BY THE WAY. 1312 01:03:37,240 --> 01:03:39,240 I HAVE TO START BY SAYING 1313 01:03:39,240 --> 01:03:43,080 DRAGANA FOR ORGANIZING THIS 1314 01:03:43,080 --> 01:03:47,280 FAMILY ROW UNION WHICH HAS BEEN 1315 01:03:47,280 --> 01:03:49,960 AMAZING SO THANK YOU FOR 1316 01:03:49,960 --> 01:03:51,480 ORGANIZING THIS AND IT'S A 1317 01:03:51,480 --> 01:03:53,840 TREMENDOUS HONOR FOR ME TO BE 1318 01:03:53,840 --> 01:03:59,080 HERE AND TO PRESENT. 1319 01:03:59,080 --> 01:04:00,760 WE'VE SEEN A LOT OF PICTURES OF 1320 01:04:00,760 --> 01:04:02,440 ALAN SO I THOUGHT I WOULD BREAK 1321 01:04:02,440 --> 01:04:03,760 THAT TREND AND I START WITH A 1322 01:04:03,760 --> 01:04:05,640 PICTURE OF ME SO FOR THOSE OF 1323 01:04:05,640 --> 01:04:09,640 YOU WHO DO KNOW ME, I'M TONY 1324 01:04:09,640 --> 01:04:10,800 ROTHFUCHS AND THIS IS WHAT I 1325 01:04:10,800 --> 01:04:13,200 LOOKED LIKE BACK IN THE DAY SO 1326 01:04:13,200 --> 01:04:15,200 WHEN I WAS A POSTDOC IN ALAN'S 1327 01:04:15,200 --> 01:04:17,880 LAB I WAS IN BUILDING 50 AND I 1328 01:04:17,880 --> 01:04:19,840 ACTUALLY SAT WHERE DAMIAN SAT 1329 01:04:19,840 --> 01:04:22,280 BUT I DIDN'T SIT MUCH ON THAT 1330 01:04:22,280 --> 01:04:22,480 SEAT. 1331 01:04:22,480 --> 01:04:25,240 I WAS MOSTLY SACKING MICE AND 1332 01:04:25,240 --> 01:04:31,000 ONE OF THE THINGS THAT I DID WAS 1333 01:04:31,000 --> 01:04:36,680 TO DO MICRO BACTERIAL GRAN YOU 1334 01:04:36,680 --> 01:04:38,400 LOMA WHICH WAS A COLLABORATION 1335 01:04:38,400 --> 01:04:39,040 WITH RON'S LAB. 1336 01:04:39,040 --> 01:04:49,600 WHEN I WAS INVITE TODAY AND AND 1337 01:04:50,640 --> 01:04:50,800 SPEAK. 1338 01:04:50,800 --> 01:04:52,640 I HAVET BEEN BACK SINCE 2009. 1339 01:04:52,640 --> 01:04:54,000 I THOUGHT ABOUT THE EXPERIENCES 1340 01:04:54,000 --> 01:04:55,880 AND HOW THIS HAS SHAPED MY 1341 01:04:55,880 --> 01:04:58,640 CAREER AND HOW THIS HAS HELPED 1342 01:04:58,640 --> 01:05:05,720 ME SET UP SHOP BACK IN AND I'VE 1343 01:05:05,720 --> 01:05:09,480 FOR THIS SHORT TALK, I TRIED TO 1344 01:05:09,480 --> 01:05:11,560 CHANNEL THIS TO THREE BASIC 1345 01:05:11,560 --> 01:05:12,600 COMPONENTS THAT CAN GO THROUGH 1346 01:05:12,600 --> 01:05:14,800 IN THE ENTIRE TALK. 1347 01:05:14,800 --> 01:05:18,400 SO, NUMBER ONE, IT'S HERE WERE 1348 01:05:18,400 --> 01:05:20,440 IN ALAN'S LAB WHERE I LEARNED TO 1349 01:05:20,440 --> 01:05:23,080 DO MICRO BACTERIAL WORK AND THIS 1350 01:05:23,080 --> 01:05:27,760 IS SOMETHING THAT MY LAB IN 1351 01:05:27,760 --> 01:05:35,920 STOCKHOLM DOES ON INFECTION X I 1352 01:05:35,920 --> 01:05:38,480 LEARNED BSL3 WORK AND THIS IS 1353 01:05:38,480 --> 01:05:40,280 IMPORTANT TO LAND A KEY 1354 01:05:40,280 --> 01:05:44,280 COMMISSIONS OF TRUST AT 1355 01:05:44,280 --> 01:05:46,040 KAROLINSKA WHICH BASICALLY 1356 01:05:46,040 --> 01:05:49,960 HELPED BRING HOME THE BACON SO 1357 01:05:49,960 --> 01:05:51,520 TO SAY. 1358 01:05:51,520 --> 01:05:55,440 AND THE THIRD POINT IS THAT IT'S 1359 01:05:55,440 --> 01:05:57,240 REALLY -- SO, ONE KEY THING THAT 1360 01:05:57,240 --> 01:05:58,560 I LEARNED WAS LIKE BE TO BE 1361 01:05:58,560 --> 01:05:59,960 AFRAID TO JUMP INTO THE DEEP END 1362 01:05:59,960 --> 01:06:05,000 OF THE POOL SO TO SAY. 1363 01:06:05,000 --> 01:06:08,520 SO TO TRY NEW THING, SET UP NEW 1364 01:06:08,520 --> 01:06:09,560 METHODS, A REPLY NEW TECHNOLOGY 1365 01:06:09,560 --> 01:06:16,960 AND ADDRESS IMPORTANT QUESTIONS. 1366 01:06:16,960 --> 01:06:23,200 AND I AM NOT DOING SO MUCH 1367 01:06:23,200 --> 01:06:25,960 IMMUNOLOGY ANYMORE SO I AM IN 1368 01:06:25,960 --> 01:06:28,280 THE FIELD OF TB ARROW BIOLOGY SO 1369 01:06:28,280 --> 01:06:30,200 THAT IS REALLY IN THE DEEP END 1370 01:06:30,200 --> 01:06:32,040 FOR IMMUNOLOGY SO I THOUGHT I 1371 01:06:32,040 --> 01:06:35,280 WOULD START A LITTLE BIT BY 1372 01:06:35,280 --> 01:06:37,080 INTRODUCING THIS FIELD WHICH IS 1373 01:06:37,080 --> 01:06:39,520 REALLY A VERY OLD FIELD IN TB 1374 01:06:39,520 --> 01:06:42,320 AND YET IT'S STILL AT THE SAME 1375 01:06:42,320 --> 01:06:45,520 TIME A REEMERGING FIELD SO THIS 1376 01:06:45,520 --> 01:06:50,520 TB ARROW BIOLOGY WAS KICKED OFF 1377 01:06:50,520 --> 01:07:01,040 BY CARL IN GERMANY AND AND HE 1378 01:07:08,160 --> 01:07:09,480 GUINEA PIG TRANSMIT 1379 01:07:09,480 --> 01:07:09,880 COUGHING. 1380 01:07:09,880 --> 01:07:16,000 THIS KICKED OFF THE AEROBIOLOGY 1381 01:07:16,000 --> 01:07:16,280 FIELD. 1382 01:07:16,280 --> 01:07:21,320 SO TODAY, WE'VE PRETTY MUCH 1383 01:07:21,320 --> 01:07:23,320 REPLACED FLUGGE'S GUINEA PIGS 1384 01:07:23,320 --> 01:07:26,680 WITH AIR SAMPLERS TO DO THE SAME 1385 01:07:26,680 --> 01:07:27,480 THING. 1386 01:07:27,480 --> 01:07:30,120 SO, THROUGH AIR SAMPLING, IT'S 1387 01:07:30,120 --> 01:07:32,480 SO IMPORTANT FOR THIS BECAUSE IT 1388 01:07:32,480 --> 01:07:34,560 A US TO COLLECT THE ARROW SOLE 1389 01:07:34,560 --> 01:07:36,680 AND DETECT AND ANALYZE THE 1390 01:07:36,680 --> 01:07:46,280 PATHOGEN COMPONENT. 1391 01:07:46,280 --> 01:07:50,360 WE'RE STUDYING IMPORTANT GAPS IN 1392 01:07:50,360 --> 01:07:51,520 TB ARROW BIOLOGY AND 1393 01:07:51,520 --> 01:08:02,080 TRANSMISSION SO I WILL TOUCH SO 1394 01:08:06,640 --> 01:08:08,840 YOU CAN IDENTIFY HOTSPOTS OF 1395 01:08:08,840 --> 01:08:09,680 COMMUNITY TRANSMISSION. 1396 01:08:09,680 --> 01:08:10,760 WHERE IS TRANSMISSION TAKING 1397 01:08:10,760 --> 01:08:13,440 PLACE IN A CERTAIN COMMUNITY BY 1398 01:08:13,440 --> 01:08:14,520 SAMPLING THE AIR. 1399 01:08:14,520 --> 01:08:16,520 YOU CAN USE IT TO IDENTIFY NEW 1400 01:08:16,520 --> 01:08:18,560 CASES OF TB BASED ON THE 1401 01:08:18,560 --> 01:08:20,920 INFECTIOUS AEROSOLS OF THE 1402 01:08:20,920 --> 01:08:22,360 GENERATED BY PATIENTS AND THIS 1403 01:08:22,360 --> 01:08:24,560 IS WORK THAT KEVIN FENLY HERE AT 1404 01:08:24,560 --> 01:08:27,920 NIH HAS REALLY BEEN PIONEERING. 1405 01:08:27,920 --> 01:08:29,920 AND THE THIRD POINT WHICH IS 1406 01:08:29,920 --> 01:08:33,360 REALLY EASIER SAID THAN DONE, IS 1407 01:08:33,360 --> 01:08:35,400 THAT THROUGH AIR SAMPLING WE CAN 1408 01:08:35,400 --> 01:08:38,080 STUDY THE BUG IN ITS 1409 01:08:38,080 --> 01:08:39,400 TRANSMISSIBLE FORM AND BY THE 1410 01:08:39,400 --> 01:08:41,520 WAY THE WORD "BUG" IN CONNECTION 1411 01:08:41,520 --> 01:08:44,280 TO PATHOGENS I JUST REALIZE IS 1412 01:08:44,280 --> 01:08:45,960 SOMETHING I PICKED UP FROM YOU, 1413 01:08:45,960 --> 01:08:46,240 ALAN. 1414 01:08:46,240 --> 01:08:47,440 PROBLEM THE VERY FIRST THING I 1415 01:08:47,440 --> 01:08:49,080 PICKED UP FROM YOU AND I HAVEN'T 1416 01:08:49,080 --> 01:08:52,400 DROPPED IT AND IT DOESN'T 1417 01:08:52,400 --> 01:08:53,560 TRANSLATE WELL IN SWEDISH. 1418 01:08:53,560 --> 01:08:55,400 IT SOUNDS LIKE A BUG BUT I USE 1419 01:08:55,400 --> 01:08:55,600 IT. 1420 01:08:55,600 --> 01:08:57,440 I JUST REALIZED THAT NOW. 1421 01:08:57,440 --> 01:09:02,560 SO ANYWAY, SO, WE'RE DEVELOPING 1422 01:09:02,560 --> 01:09:06,800 AIR SAMPLERS TO ADDRESS THESE 1423 01:09:06,800 --> 01:09:08,160 POINTS. 1424 01:09:08,160 --> 01:09:09,120 SO, WE'VE DEVELOPED SOMETHING 1425 01:09:09,120 --> 01:09:14,840 CALLED A TB HOTSPOT DETECT ERROR 1426 01:09:14,840 --> 01:09:23,000 4 AND I CAME UP WITH THE NAME 1427 01:09:23,000 --> 01:09:23,200 THOR. 1428 01:09:23,200 --> 01:09:25,000 WORE IN SWEDEN AND WE HAVE TO A 1429 01:09:25,000 --> 01:09:27,840 COOL NAME SO THOR IS A PORTABLE 1430 01:09:27,840 --> 01:09:31,720 AIR SAMPLER AND IT'S COMPACT AND 1431 01:09:31,720 --> 01:09:33,360 EASY TO USE AND YOU CAN SEE IT'S 1432 01:09:33,360 --> 01:09:39,720 HAND PORTABLE AND IT DOESN'T 1433 01:09:39,720 --> 01:09:41,360 REQUIRE POWER AND THE PARTS ARE 1434 01:09:41,360 --> 01:09:51,400 CHEAP AND YOU CAN REPLACE THEM. 1435 01:09:51,400 --> 01:09:55,680 THE WAY IT WORKS FROM THESE 1436 01:09:55,680 --> 01:09:57,480 HEADS THERE'S A CORONA DISCHARGE 1437 01:09:57,480 --> 01:10:00,320 AND IT CHARGES PART ALS IN THE 1438 01:10:00,320 --> 01:10:02,120 CARE AND THEY GET COLLECTED 1439 01:10:02,120 --> 01:10:04,840 THROUGH A ON TO THIS COLLECT OR 1440 01:10:04,840 --> 01:10:06,600 PEACE AND WE REMOVE THIS PIECE 1441 01:10:06,600 --> 01:10:11,560 AND WE CAN PERFORM ANALYSIS. 1442 01:10:11,560 --> 01:10:15,960 THIS IS WHAT IT LOOKS LIKE WHEN 1443 01:10:15,960 --> 01:10:17,000 YOUR SUBPOENA POLL SMOKE. 1444 01:10:17,000 --> 01:10:17,920 THEY ACCELERATE TOWARDS THE 1445 01:10:17,920 --> 01:10:19,000 COLLECT OR PEACE AND IT'S 1446 01:10:19,000 --> 01:10:20,560 CHANGING COLOR AND GETTING A 1447 01:10:20,560 --> 01:10:22,640 LAYER OF SMOKE AND LET'S WATCH 1448 01:10:22,640 --> 01:10:23,640 THAT AGAIN. 1449 01:10:23,640 --> 01:10:25,440 SEE IT'S SHINY AND ON AND THEN 1450 01:10:25,440 --> 01:10:29,560 THERE IT GOES. 1451 01:10:29,560 --> 01:10:33,240 THE SMOKE GETS COLLECTED. 1452 01:10:33,240 --> 01:10:35,480 SO, YOU KNOW, HOW DO WE IDENTIFY 1453 01:10:35,480 --> 01:10:36,440 NEW INFECTION? 1454 01:10:36,440 --> 01:10:39,960 SO, A COUPLE OF EXPERIMENTS SO 1455 01:10:39,960 --> 01:10:43,360 WE STARTED THIS OUT WITH 1456 01:10:43,360 --> 01:10:48,800 EXPERIMENTS IN BSL2 USING BCG SO 1457 01:10:48,800 --> 01:10:52,440 THE LIVE VACCINE AND SO THE SET 1458 01:10:52,440 --> 01:10:56,600 UP THAT WE DEVELOPED THAT WAS 1459 01:10:56,600 --> 01:10:59,680 FUNDED BY THE GATES FOUNDATION 1460 01:10:59,680 --> 01:11:02,000 WAS WE SET UP A HUGE PLASTIC CAN 1461 01:11:02,000 --> 01:11:06,320 PEE IN WHICH WE AR SOLLIZED BCG 1462 01:11:06,320 --> 01:11:08,880 AND PERFORMED EXPERIMENTS WITH 1463 01:11:08,880 --> 01:11:16,400 OUR DEVISE AND THIS WE STARTED A 1464 01:11:16,400 --> 01:11:19,680 COLLABORATION FOR THOSE THAT ARE 1465 01:11:19,680 --> 01:11:21,000 NOT FAMILIAR WITH GONE EXPERT 1466 01:11:21,000 --> 01:11:25,160 THIS IS YOU BASICALLY A 1467 01:11:25,160 --> 01:11:30,480 AUTOMATED PCR SYSTEM USED FOR 1468 01:11:30,480 --> 01:11:31,800 MOLECULAR DETECTION. 1469 01:11:31,800 --> 01:11:33,080 IT'S A CARTRIDGE AND YOU PUT IT 1470 01:11:33,080 --> 01:11:37,160 IN AND IT GOES INTO A LITTLE 1471 01:11:37,160 --> 01:11:39,400 MACHINE AND IT GIVES YOU A 1472 01:11:39,400 --> 01:11:41,080 RESULT BACK AND WE MANAGED TO 1473 01:11:41,080 --> 01:11:43,160 GET CT VALUES FOR THAT BECAUSE 1474 01:11:43,160 --> 01:11:44,800 NORMALLY WE GET HIGH, LOW, 1475 01:11:44,800 --> 01:11:46,720 MEDIUM DETECTION AND SO WE 1476 01:11:46,720 --> 01:11:48,960 PERFORMED THIS EXPERIMENT AND 1477 01:11:48,960 --> 01:11:52,200 BCG ACROSS VARIOUS 1478 01:11:52,200 --> 01:11:53,320 CONCENTRATIONS AND WITH THE 1479 01:11:53,320 --> 01:11:55,000 DEVICE TURNED ON AND TURNED OFF, 1480 01:11:55,000 --> 01:11:57,120 AND WE WERE ABLE TO EXTRACT THE 1481 01:11:57,120 --> 01:11:59,800 CT VALUES AS WELL AND SO IT 1482 01:11:59,800 --> 01:12:02,560 TURNS OUT THAT THE COMBINATION 1483 01:12:02,560 --> 01:12:04,200 OF THOR AND GENE EXPERT IS AWE 1484 01:12:04,200 --> 01:12:06,480 SHOULD SO IT GIVES YOU QUITE A 1485 01:12:06,480 --> 01:12:09,920 SENSITIVE DETECTION AND ABOUT .5 1486 01:12:09,920 --> 01:12:12,360 COPIES OF BCG PER LITER OF AIR 1487 01:12:12,360 --> 01:12:15,120 SO THIS IS KIND OF A -- WHEN THE 1488 01:12:15,120 --> 01:12:16,320 DEVIS IS TURNED ON, THAT'S WHEN 1489 01:12:16,320 --> 01:12:20,280 YOU GET THE SENSITIVE DETECTION 1490 01:12:20,280 --> 01:12:21,600 SO IT IT IS ACTIVE COLLECTION 1491 01:12:21,600 --> 01:12:24,680 REQUIRED FOR THIS AND SO THIS IS 1492 01:12:24,680 --> 01:12:29,120 WE THOUGHT OK, THIS SOUNDS GOOD 1493 01:12:29,120 --> 01:12:30,480 AND BECAUSE WE HAVE NO IDEA OF 1494 01:12:30,480 --> 01:12:33,480 TRUE CONCENTRATION OF TB IN THE 1495 01:12:33,480 --> 01:12:36,600 AIR SO IT'S GUESSWORK IN THE 1496 01:12:36,600 --> 01:12:38,120 AEROBIOLOGY AND WE THOUGHT OK, 1497 01:12:38,120 --> 01:12:43,160 THIS IS LOW ENOUGH SO LET'S TRY 1498 01:12:43,160 --> 01:12:45,080 TO DO THIS WITH PATIENTS SO WE 1499 01:12:45,080 --> 01:12:48,520 TURNED TO COLLEAGUES AT 1500 01:12:48,520 --> 01:12:49,200 KAROLINSKA UNIVERSITY HOSPITAL 1501 01:12:49,200 --> 01:12:53,840 AND THIS WAS A SURPRISE TO ME 1502 01:12:53,840 --> 01:12:54,960 AND THERE'S NEVER GOING TO BE 1503 01:12:54,960 --> 01:12:57,200 ABLE TO DO THIS IN AND JUST FOR 1504 01:12:57,200 --> 01:12:59,160 A TRY AND IT TURNS OUT THAT YES, 1505 01:12:59,160 --> 01:13:01,000 WE HAVE TB IN SWEDEN AND UNFORT 1506 01:13:01,000 --> 01:13:02,320 LOW THERE'S NOT ENOUGH SWEDES IN 1507 01:13:02,320 --> 01:13:04,000 THE AUDIENCE HERE FOR ME TO MAKE 1508 01:13:04,000 --> 01:13:05,800 THAT AS A SUCCESSFUL PITCH THAT 1509 01:13:05,800 --> 01:13:07,840 YES, WE DO HAVE TUBERCULOSIS 1510 01:13:07,840 --> 01:13:11,400 EVEN IN SWEDEN AND AT ANY GIVEN 1511 01:13:11,400 --> 01:13:15,320 DAY OF THE WEEK, AND KAROLINSKA 1512 01:13:15,320 --> 01:13:16,120 UNIVERSITY HOSPITAL YOU WILL 1513 01:13:16,120 --> 01:13:18,120 HAVE FOUR PEOPLE WITH TB IN THE 1514 01:13:18,120 --> 01:13:22,160 WARD, AT LEAST. 1515 01:13:22,160 --> 01:13:24,920 TODAY WE HAVE MORE TB CASES THAN 1516 01:13:24,920 --> 01:13:35,280 COVID CASES ACTUALLY. 1517 01:13:49,640 --> 01:13:51,760 AND WE PERFORMED GENE EXPERT ON 1518 01:13:51,760 --> 01:13:54,480 THIS AND SO, WE, THIS IS REALLY 1519 01:13:54,480 --> 01:13:58,000 PRELIMINARY SO WE WERE ABLE TO 1520 01:13:58,000 --> 01:14:00,480 TRY FOUR PEOPLE AND WHERE DOING 1521 01:14:00,480 --> 01:14:02,440 THIS AND SO IF YOU LOOK HERE FOR 1522 01:14:02,440 --> 01:14:10,800 EXAMPLE, SO, YOU SEE THIS. 1523 01:14:10,800 --> 01:14:12,920 WE TRIED TO SAMPLE PEOPLE FOR 1524 01:14:12,920 --> 01:14:18,640 SIX DAYS SO WE FIND THIS 1525 01:14:18,640 --> 01:14:20,440 TRIANGLE, THIS INDIVIDUAL WAS 1526 01:14:20,440 --> 01:14:21,480 POSITIVE BY COUGH TWICE AND THE 1527 01:14:21,480 --> 01:14:24,320 ROOM AIR WAS ALSO POSITIVE AT 1528 01:14:24,320 --> 01:14:26,640 THE SAME TIME, AT THE SAME EVENT 1529 01:14:26,640 --> 01:14:30,120 OF COUGH SAMPLING AND THIS WAS 1530 01:14:30,120 --> 01:14:31,720 THE CASE FOR ALL OF THESE 1531 01:14:31,720 --> 01:14:32,400 INDIVIDUALS. 1532 01:14:32,400 --> 01:14:33,720 THEY'RE POSITIVE, MOST OF THE 1533 01:14:33,720 --> 01:14:36,120 TIME THEY'RE POSITIVE TWICE OUT 1534 01:14:36,120 --> 01:14:41,400 OF FOUR OR FIVE SAMPLE OCCASIONS 1535 01:14:41,400 --> 01:14:43,600 AND WHICH IS REALLY COOL THAT WE 1536 01:14:43,600 --> 01:14:46,160 ARE ABLE TO MAKE A POSITIVE 1537 01:14:46,160 --> 01:14:47,400 MOLECULAR DETECTION JUST BY 1538 01:14:47,400 --> 01:14:49,280 HAVING A PERSON COUGH ONTO THE 1539 01:14:49,280 --> 01:14:49,560 DEVICE. 1540 01:14:49,560 --> 01:14:53,640 BUT THIS IS, I MEAN, THIS IS 1541 01:14:53,640 --> 01:14:57,120 EARLY DAYS AND NEVERTHELESS, THE 1542 01:14:57,120 --> 01:14:59,080 CONCEPT, WHERE AND HOW COULD WE 1543 01:14:59,080 --> 01:15:00,920 USE THIS? 1544 01:15:00,920 --> 01:15:03,160 SO, IN THE ONE END WOULD BE TO 1545 01:15:03,160 --> 01:15:06,280 USE A POINT OF CARE SO YOU GO 1546 01:15:06,280 --> 01:15:12,880 OUT AND THIS DEVICE AND YOU ARE 1547 01:15:12,880 --> 01:15:15,160 ASKING YOU HAVE THIS AND YOU CAN 1548 01:15:15,160 --> 01:15:25,200 DO IT ANYWHERE. 1549 01:15:25,200 --> 01:15:35,280 THE OTHER APPROACH AN YOU CAN 1550 01:15:35,280 --> 01:15:36,320 SAMPLE THE AIR. 1551 01:15:36,320 --> 01:15:38,760 FOR EXAMPLE, HERE WOULD BE A 1552 01:15:38,760 --> 01:15:41,280 GOOD EXAMPLE TO SEE IF WE CAN 1553 01:15:41,280 --> 01:15:44,160 MAKE POSITIVE DOUGH TEXT AND SO 1554 01:15:44,160 --> 01:15:45,840 THAT WOULD BE MORE MONITORING OR 1555 01:15:45,840 --> 01:15:47,320 AN ENVIRONMENTAL SURVEILLANCE 1556 01:15:47,320 --> 01:15:50,040 FOR TB AND EVEN IN THIS SETTING, 1557 01:15:50,040 --> 01:15:51,720 YOU COULD FOLLOW ON WITH THE 1558 01:15:51,720 --> 01:15:54,240 POINT OF CARE SETTING TO 1559 01:15:54,240 --> 01:15:56,360 IDENTIFY INFECTIOUS INDIVIDUALS 1560 01:15:56,360 --> 01:16:04,040 IN THAT SETTING. 1561 01:16:04,040 --> 01:16:05,800 IT'S ON GOING HERE AND WE'RE 1562 01:16:05,800 --> 01:16:07,560 FOCUSING MORE ON THE POINT OF 1563 01:16:07,560 --> 01:16:09,680 CARE ASPECT AND IN COLLABORATION 1564 01:16:09,680 --> 01:16:13,720 WITH PARTNERS AT STELLEN BUSH 1565 01:16:13,720 --> 01:16:14,880 AND IN MOZAMBIQUE AS WELL AND 1566 01:16:14,880 --> 01:16:16,360 WORE TRYING TO FIGURE OUT WHAT 1567 01:16:16,360 --> 01:16:19,960 DOES IT MEAN TO BE PCR POSITIVE 1568 01:16:19,960 --> 01:16:22,000 IN THIS DETECTION METHOD. 1569 01:16:22,000 --> 01:16:26,160 WHAT IS THE DIAGNOSTIC 1570 01:16:26,160 --> 01:16:36,120 PERFORMANCE AND HOW LONG DO YOU 1571 01:16:36,120 --> 01:16:37,600 HAVE TO SAMPLE AN INDIVIDUAL AND 1572 01:16:37,600 --> 01:16:39,880 WHAT'S THE PROTOCOL TO MAKE 1573 01:16:39,880 --> 01:16:40,080 THIS. 1574 01:16:40,080 --> 01:16:42,160 AND THEN LATER ON IT WOULD BE TO 1575 01:16:42,160 --> 01:16:45,560 SEE IF ONE IS ABLE TO ASSOCIATE 1576 01:16:45,560 --> 01:16:47,520 WITH ACTIVE TB IN THE HOUSEHOLD 1577 01:16:47,520 --> 01:16:49,240 BECAUSE IF IT WORKS, IT WOULD BE 1578 01:16:49,240 --> 01:16:51,640 A VERY SIMPLE WAY THAT YOU COULD 1579 01:16:51,640 --> 01:16:53,400 JUST, ANYONE COULD MANAGE A 1580 01:16:53,400 --> 01:16:53,880 THOR. 1581 01:16:53,880 --> 01:16:55,800 AND THE PROOF OF THAT IS THAT 1582 01:16:55,800 --> 01:16:57,800 WE'VE DONE THIS PRELIMINARY IN A 1583 01:16:57,800 --> 01:16:58,880 BRAZILIAN PRISON WHERE WE HANDED 1584 01:16:58,880 --> 01:17:01,120 OVER THE DEVICE TO INMATES AND 1585 01:17:01,120 --> 01:17:02,880 THEY WERE ABLE TO SAMPLE 1586 01:17:02,880 --> 01:17:03,440 THEMSELVES. 1587 01:17:03,440 --> 01:17:05,520 SO IF IT WORKS IN A BRAZILIAN 1588 01:17:05,520 --> 01:17:07,160 PRISON, IT WILL WORK ANYMORE AND 1589 01:17:07,160 --> 01:17:11,320 IT'S KIND OF THE RATIONALE BUT 1590 01:17:11,320 --> 01:17:12,680 IT'S EARLY DAYS SO THIS IS WHAT 1591 01:17:12,680 --> 01:17:15,320 IS ON GOING. 1592 01:17:15,320 --> 01:17:17,400 SO, WHAT ABOUT AIR SAMPLING TO 1593 01:17:17,400 --> 01:17:20,760 STUDY THE INFECTION BIOLOGY SO 1594 01:17:20,760 --> 01:17:29,160 THIS IS VERY TRICKY AND AND IN 1595 01:17:29,160 --> 01:17:34,200 LET'S SAY THE INFECTION 1596 01:17:34,200 --> 01:17:42,760 TRANSMISSION AND WE KNOW THAT TB 1597 01:17:42,760 --> 01:17:44,080 IS AN AIRBORN DISEASE AND WE 1598 01:17:44,080 --> 01:17:47,240 KNOW VERY LITTLE ABOUT THIS PART 1599 01:17:47,240 --> 01:17:49,200 AND SO YOU CAN FIND OF SPLIT 1600 01:17:49,200 --> 01:17:49,800 THIS UP. 1601 01:17:49,800 --> 01:17:52,920 I MEAN, YOU CAN SPLIT IT UP INTO 1602 01:17:52,920 --> 01:17:55,640 HOW DOES THE DOUG SURVIVE IN THE 1603 01:17:55,640 --> 01:17:57,320 AEROSOL AND THAT IS IMPORTANT 1604 01:17:57,320 --> 01:17:59,000 FOR INFECTION PREVENTION AND HOW 1605 01:17:59,000 --> 01:18:00,720 LONG IF I COUGH AND I HAVE TB 1606 01:18:00,720 --> 01:18:02,320 AND I LEAVE THIS ALMOST FOR HOW 1607 01:18:02,320 --> 01:18:03,800 LONG IS THAT BUG GOING TO BE 1608 01:18:03,800 --> 01:18:05,840 REMAINING IN THE AIR AND BE A 1609 01:18:05,840 --> 01:18:09,840 RISK FOR TRANSMISSION SO IT'S A 1610 01:18:09,840 --> 01:18:10,440 KEY QUESTION. 1611 01:18:10,440 --> 01:18:12,640 ALSO, YOU KNOW, IN WHAT DOES IT 1612 01:18:12,640 --> 01:18:13,040 MEAN? 1613 01:18:13,040 --> 01:18:15,000 THAT AGING IN THE AEROSOL, HOW 1614 01:18:15,000 --> 01:18:16,520 DOES IT IMPACT THE INFECTION 1615 01:18:16,520 --> 01:18:18,320 EVENT IN THE TARGET CELLS AND 1616 01:18:18,320 --> 01:18:22,120 THE MACROPHAGE AND OF COURSE 1617 01:18:22,120 --> 01:18:25,880 IMMUNE RESPONSE, I AM AN 1618 01:18:25,880 --> 01:18:26,720 IMMUNOLOGIST AND I WOULD LIKE TO 1619 01:18:26,720 --> 01:18:31,360 SEE HOW THE ARROW S AEROSOL PROG 1620 01:18:31,360 --> 01:18:39,000 AND THERE ARE QUESTIONS WITH THE 1621 01:18:39,000 --> 01:18:41,120 AEROSOL AND WHAT'S THE PARTICLE 1622 01:18:41,120 --> 01:18:43,080 SIZE BECAUSE IF YOU JUST DOUBLED 1623 01:18:43,080 --> 01:18:45,240 THE DIAMETER OF THE PARTICLE YOU 1624 01:18:45,240 --> 01:18:47,440 HAVE INCREASED THE HAVE 10 TIMES 1625 01:18:47,440 --> 01:18:49,680 SO THAT CAN HAVE A MAJOR IMPACT 1626 01:18:49,680 --> 01:18:52,400 ON MAKING IT MORE COMFY FOR THE 1627 01:18:52,400 --> 01:18:54,920 BUG AND TO TRAVEL IN THE AIR AND 1628 01:18:54,920 --> 01:18:57,080 IT CAN ALSO MEAN A MUCH HIGHER 1629 01:18:57,080 --> 01:18:58,880 PATHOGEN PAY LOAD AND THAT WOULD 1630 01:18:58,880 --> 01:19:02,000 IMPACT ON THE ABILITY TO INFECT. 1631 01:19:02,000 --> 01:19:04,960 AND SO TO TRY TO INVESTIGATE 1632 01:19:04,960 --> 01:19:06,960 THIS REQUIRES MORE THAN JUST AIR 1633 01:19:06,960 --> 01:19:08,400 SAMPLING THERE AND IT'S MORE 1634 01:19:08,400 --> 01:19:11,600 LIKE AIR SAMPLING IS A COMPONENT 1635 01:19:11,600 --> 01:19:13,440 OF A WHOLE SET OF TOOLS AND 1636 01:19:13,440 --> 01:19:15,320 GADGETS THAT WE'VE JUST SET UP 1637 01:19:15,320 --> 01:19:20,040 IN OUR BSL3 AT KAROLINSKA SO 1638 01:19:20,040 --> 01:19:22,560 WE -- IT'S CRAZY JUST LOOKING AT 1639 01:19:22,560 --> 01:19:29,320 THE PICTURE. 1640 01:19:29,320 --> 01:19:30,440 IT'S AN AIRTIGHT GLOVE BOX 1641 01:19:30,440 --> 01:19:32,560 INSIDE AN AIR FIGHT FLEXIBLE 1642 01:19:32,560 --> 01:19:34,200 CANOPY AND WE CAN GAS THE HELL 1643 01:19:34,200 --> 01:19:36,160 OUT OF EVERYTHING AND DISINFECT 1644 01:19:36,160 --> 01:19:38,640 AND HELP A FILTER IT ALL-OUT SO 1645 01:19:38,640 --> 01:19:44,040 MAKE SURE THAT NOTHING GETS OUT 1646 01:19:44,040 --> 01:19:45,800 AND IN THIS GLOVE BOX HERE WE'RE 1647 01:19:45,800 --> 01:19:56,080 USING THE NEGOTIAT NUMBER YOU LT 1648 01:19:56,080 --> 01:20:05,360 HAS A 1649 01:20:05,360 --> 01:20:08,760 IT HAS LIVE BASIL EYE SO WE'RE 1650 01:20:08,760 --> 01:20:11,760 USING A TAKE IT IN THIS BOX AND 1651 01:20:11,760 --> 01:20:14,440 THEN WE CAN AGE THE AEROSOL IN 1652 01:20:14,440 --> 01:20:16,400 THE BOX AND WE COLLECT THEM ON 1653 01:20:16,400 --> 01:20:21,080 SOMETHING CALLED CORYOLIS SO 1654 01:20:21,080 --> 01:20:22,840 THIS IS A COMMERCIAL HIGH-VOLUME 1655 01:20:22,840 --> 01:20:27,080 AIR SAMPLER AND WOVE MADE SOME 1656 01:20:27,080 --> 01:20:28,480 MODIFICATIONS TO MAKE IT BIO 1657 01:20:28,480 --> 01:20:32,680 SAFE FOR USE IN BSL3 AND THE WAY 1658 01:20:32,680 --> 01:20:36,400 THAT IT WORKS IS IT SUCKS 1659 01:20:36,400 --> 01:20:39,120 PARTICLES INTO THIS HEADPIECE 1660 01:20:39,120 --> 01:20:43,920 THROUGH A CORY OWE LIS EFFECT 1661 01:20:43,920 --> 01:20:45,400 AND THEY GET STUCK IN THAT 1662 01:20:45,400 --> 01:20:46,240 CHAMPAGNE CONE AND IT'S LIQUID 1663 01:20:46,240 --> 01:20:48,120 AND YOU CAN ANALYZE THE 1664 01:20:48,120 --> 01:20:49,640 PARTICLES SO IT'S A NICE 1665 01:20:49,640 --> 01:20:50,160 EXTRACTION PROCESS. 1666 01:20:50,160 --> 01:20:52,800 WE'VE USED THE SET UP AND IN 1667 01:20:52,800 --> 01:20:53,840 PRELIMINARY EXPERIMENTS I'M 1668 01:20:53,840 --> 01:20:59,600 GOING TO SHOW YOU USING BCG, WE 1669 01:20:59,600 --> 01:21:01,160 HAVE AR SOLLIZED BCG AND 1670 01:21:01,160 --> 01:21:05,480 COLLECTED THEM ON THE CORY OWE 1671 01:21:05,480 --> 01:21:15,520 LIS AND 1672 01:21:15,520 --> 01:21:16,680 THIS SPRAY FACTOR IT'S NOT 1673 01:21:16,680 --> 01:21:18,840 REALLY IMPORTANT IT'S JUST 1674 01:21:18,840 --> 01:21:21,760 REALLY -- IT'S A MATHEMATICAL 1675 01:21:21,760 --> 01:21:24,720 KIND OF DATA CRUNCHING FOR YOU 1676 01:21:24,720 --> 01:21:27,800 TO REPORT THE AMOUNT OF CFUs 1677 01:21:27,800 --> 01:21:29,360 THAT YOU'VE EXTRACTED FROM THE 1678 01:21:29,360 --> 01:21:33,080 AIR RELATIVE TO THE AMOUNT THAT 1679 01:21:33,080 --> 01:21:35,600 WAS IN THE COLUMN SO IT'S DATA 1680 01:21:35,600 --> 01:21:38,360 CRUNCHING BUT IT'S A MEASUREMENT 1681 01:21:38,360 --> 01:21:40,720 OF VIABLE BUGS, THE VIABLE 1682 01:21:40,720 --> 01:21:41,720 FRACTIONION AND OVER TIME THE 1683 01:21:41,720 --> 01:21:43,280 SPRAY FACTOR IS GOING DOWN AND 1684 01:21:43,280 --> 01:21:51,360 IT MEANS THE C RECOVERY GOES DO. 1685 01:21:51,360 --> 01:21:54,600 IF YOU TAKE THE BUGS THAT WERE 1686 01:21:54,600 --> 01:21:57,200 AT THIS EIGHT-MINUTE AGING, 1687 01:21:57,200 --> 01:21:58,920 EARLY, AND YOU COMPARE THEM TO 1688 01:21:58,920 --> 01:22:00,720 BUGS THAT COME STRAIGHT OUT OF 1689 01:22:00,720 --> 01:22:03,440 BROTH AND YOU CAN ADD THEM TO 1690 01:22:03,440 --> 01:22:07,280 BONE MARROW MAX, IT SEEMS THAT 1691 01:22:07,280 --> 01:22:09,160 THE BUGS THAT ARE COMING FROM 1692 01:22:09,160 --> 01:22:13,200 THE AIR ARE HAVING A HARD TIME 1693 01:22:13,200 --> 01:22:15,120 ESTABLISHING THE INFECTION IN 1694 01:22:15,120 --> 01:22:20,000 THE MACROPHAGE AND THIS IS EARLY 1695 01:22:20,000 --> 01:22:20,280 DAYS. 1696 01:22:20,280 --> 01:22:22,360 AND SO WE'RE IN THE PROCESS OF 1697 01:22:22,360 --> 01:22:26,160 REPEATING THIS WITH TB NOW AND 1698 01:22:26,160 --> 01:22:29,040 THEN SO WE HAVE A COLLABORATION 1699 01:22:29,040 --> 01:22:30,400 WITH CHAD ROY AT TO YOU LANE 1700 01:22:30,400 --> 01:22:36,840 UNIVERSITY AND HE IS LIKE THE 1701 01:22:36,840 --> 01:22:46,200 KING. 1702 01:22:46,200 --> 01:22:49,560 HE USED THE COLD BERG DRUM THAT 1703 01:22:49,560 --> 01:22:54,120 KEEPS AEROSOLS, BUGS IN THE 1704 01:22:54,120 --> 01:22:55,760 AEROSOLS STATE FOR AS LONG AS 1705 01:22:55,760 --> 01:22:57,560 YOU WANT PRETTY MUCH WHAT HE HAS 1706 01:22:57,560 --> 01:23:08,040 DONE HERE IS COMPARED IT SEEMS 1707 01:23:10,640 --> 01:23:11,480 THAT THE BUGS GOING DOWN IN RISK 1708 01:23:11,480 --> 01:23:14,400 IN TWO AND ONE THEY SEEM TO 1709 01:23:14,400 --> 01:23:17,280 SURVIVE LESS WELL IN AEROSOL 1710 01:23:17,280 --> 01:23:19,400 COMPARED TO TB AND IN THIS CASE 1711 01:23:19,400 --> 01:23:25,080 THE CDC 1551 WHICH IS A 1712 01:23:25,080 --> 01:23:25,960 REPRESENTATIVE OUTBREAKS STRAINS 1713 01:23:25,960 --> 01:23:27,320 AND THAT IS COMMERCIALLY 1714 01:23:27,320 --> 01:23:30,080 AVAILABLE AND SO, WHAT WE WANT 1715 01:23:30,080 --> 01:23:32,000 TO DO NOW IS TOGETHER WITH CHAD 1716 01:23:32,000 --> 01:23:35,400 AND TOGETHER WITH OUR COLLEAGUE 1717 01:23:35,400 --> 01:23:37,520 AT STELLEN BASH, WE WANTED TO 1718 01:23:37,520 --> 01:23:48,080 INVESTIGATE WHAT THIS MEANS WITH 1719 01:23:48,640 --> 01:23:50,640 IS THERE THE ABILITY OF A STRAIN 1720 01:23:50,640 --> 01:23:52,000 THAT IS SUCCESSFUL WITHIN A 1721 01:23:52,000 --> 01:23:55,520 GIVEN COMMUNITY AND A GIVEN 1722 01:23:55,520 --> 01:23:56,800 ENVIRONMENT BECAUSE IT'S MORE 1723 01:23:56,800 --> 01:23:59,720 FIT AND IT'S ADAPTED TO THE 1724 01:23:59,720 --> 01:24:10,240 AEROSOL TRANSPORT PROCESS AND 1725 01:24:22,280 --> 01:24:24,800 YOU CAN ADD THIS TO MACROPHAGES 1726 01:24:24,800 --> 01:24:27,840 AFTER AEROSOL AGING AND SEE WHAT 1727 01:24:27,840 --> 01:24:29,640 WE GET OUT IN THE END. 1728 01:24:29,640 --> 01:24:32,440 AND THAT IS WHAT I WANTED TO 1729 01:24:32,440 --> 01:24:34,480 SHARE WITH YOU GUYS TODAY SO 1730 01:24:34,480 --> 01:24:37,520 THIS IS US AT OUR NEW BUILDING 1731 01:24:37,520 --> 01:24:39,200 AND WE'RE IN THE NINTH FLOOR AND 1732 01:24:39,200 --> 01:24:41,360 I'M AFRAID OF HEIGHTS BUT WE 1733 01:24:41,360 --> 01:24:44,400 HAVE TO BE ON THE TOP BECAUSE 1734 01:24:44,400 --> 01:24:46,520 WHERE THE BSL3 SO IT'S NICE I 1735 01:24:46,520 --> 01:24:49,920 HAVE A BSL3 BY MY OFFICE AND ALL 1736 01:24:49,920 --> 01:24:51,040 THE COMPLAINTS FROM ALL THE 1737 01:24:51,040 --> 01:24:53,040 USERS IS NOT SO NICE AND I TAKE 1738 01:24:53,040 --> 01:24:55,480 THAT AS PART OF A JOB BECAUSE 1739 01:24:55,480 --> 01:24:59,520 THERE'S TREMENDOUS OPPORTUNITIES 1740 01:24:59,520 --> 01:25:03,200 AND THE WORK I SHOWED YOU IS 1741 01:25:03,200 --> 01:25:07,320 DONE BY IN THE LAB BY NUNO 1742 01:25:07,320 --> 01:25:10,560 RUFINO DE SOUSA, A STUDENT FROM 1743 01:25:10,560 --> 01:25:10,960 PORTUGAL. 1744 01:25:10,960 --> 01:25:15,160 THANK YOU, VERY MUCH. 1745 01:25:15,160 --> 01:25:15,600 [APPLAUSE] 1746 01:25:15,600 --> 01:25:17,640 THAT WAS WONDERFUL. 1747 01:25:17,640 --> 01:25:19,320 I DON'T HAVE MUCH OF A QUESTION 1748 01:25:19,320 --> 01:25:22,400 BUT MORE LIKE A COMMENT SO I 1749 01:25:22,400 --> 01:25:28,000 HAVE COLLEAGUES BACK AT RUTGERS 1750 01:25:28,000 --> 01:25:30,320 AND THEY'VE BEEN LOOKING AT HIGH 1751 01:25:30,320 --> 01:25:32,760 TRANSMISSION AND LOW 1752 01:25:32,760 --> 01:25:35,120 TRANSMISSION HOUSEHOLDS ISOLATES 1753 01:25:35,120 --> 01:25:36,480 AND IT SEEMS LIKE I'M NOT SURE 1754 01:25:36,480 --> 01:25:38,160 IF THEY FIGURED OUT WHETHER 1755 01:25:38,160 --> 01:25:43,720 THEY'RE AGAIGONEOWE TYPICALLY DT 1756 01:25:43,720 --> 01:25:47,160 SEEMS LIKE IT'S INTERESTING AND 1757 01:25:47,160 --> 01:25:49,480 THE HIGH TRANSMISSION STRAINS 1758 01:25:49,480 --> 01:25:51,880 SEEM TO INDUCE ACTUALLY LOWER 1759 01:25:51,880 --> 01:25:55,040 BUG COUNTS IN THE LONG AND THE 1760 01:25:55,040 --> 01:26:05,880 G -- SOTHEN THERE'S THIS PROPULF 1761 01:26:09,360 --> 01:26:14,280 THESE BASILII WHERE THE LOW 1762 01:26:14,280 --> 01:26:15,360 TRANSMISSION STRAINS THEY'RE 1763 01:26:15,360 --> 01:26:17,400 HIGHER IN THE LUNG BUT THEY'RE 1764 01:26:17,400 --> 01:26:20,400 ENCASED IN MORE LIKE A TH1 1765 01:26:20,400 --> 01:26:21,600 GRANULOMA SO I THOUGHT IT WOULD 1766 01:26:21,600 --> 01:26:23,400 BE SO COOL, RIGHT, IF YOU CAN 1767 01:26:23,400 --> 01:26:28,600 AGAIN --IF THEY FIGURE OUT A CN 1768 01:26:28,600 --> 01:26:31,560 IF YOU COULD SAMPLE RIGHT FROM 1769 01:26:31,560 --> 01:26:36,280 THE AND FROM THE AIR AIR 1770 01:26:36,280 --> 01:26:38,720 SAMPLING OF WHICH TYPES OF BASIL 1771 01:26:38,720 --> 01:26:42,720 EYE ARE GETTING HIGHLY 1772 01:26:42,720 --> 01:26:52,960 TRANSMITTED,. 1773 01:26:55,200 --> 01:26:58,480 >> IT'S A GREAT POINT. 1774 01:26:58,480 --> 01:27:01,400 SO, THE COOL THING ABOUT THIS 1775 01:27:01,400 --> 01:27:03,360 STELLEN BASH STRAINS WE ARE 1776 01:27:03,360 --> 01:27:06,720 BASICALLY PICKING IN GRANT 1777 01:27:06,720 --> 01:27:07,920 FREEZERS THEY'VE BEEN SEQUENCES 1778 01:27:07,920 --> 01:27:11,280 AND THEY FOLLOWED UP THESE TWO 1779 01:27:11,280 --> 01:27:15,120 COMMUNITIES IN THE WESTERN CAPE 1780 01:27:15,120 --> 01:27:18,440 THIS IS ROB WARRENS STUFF AND SO 1781 01:27:18,440 --> 01:27:20,320 THEY'VE BEEN SEQUENCED SO WE 1782 01:27:20,320 --> 01:27:22,200 WILL HAVE THAT INFORMATION AND 1783 01:27:22,200 --> 01:27:23,520 THERE'S MANY ASPECT THAT'S 1784 01:27:23,520 --> 01:27:25,320 YOU'VE POINTED AT THERE THAT I 1785 01:27:25,320 --> 01:27:26,360 MEAN THERE'S DIFFERENT WAYS TO 1786 01:27:26,360 --> 01:27:27,280 LOOK AT THIS. 1787 01:27:27,280 --> 01:27:28,600 OTHER THING THE FIELD IS 1788 01:27:28,600 --> 01:27:39,120 INVESTIGATING VERY MUCH IS WE 1789 01:28:17,200 --> 01:28:18,400 HAVEN'T PULLED DOWN ENOUGH BUGS 1790 01:28:18,400 --> 01:28:22,200 TO BE ABLE TO DO GENE EXPRESSION 1791 01:28:22,200 --> 01:28:24,920 ANALYSIS BECAUSE IT'S VERY FEW 1792 01:28:24,920 --> 01:28:26,320 BUGS HERE SO THAT WOULD BE A WAY 1793 01:28:26,320 --> 01:28:30,760 TO ADDRESS THAT FURTHER AND. 1794 01:28:30,760 --> 01:28:32,680 >> WONDERING ABOUT TWO SORT OF 1795 01:28:32,680 --> 01:28:36,080 RELATED USE WITH THAT THOR SAM 1796 01:28:36,080 --> 01:28:37,320 PLEASURE YOU SHOWED A NICE 1797 01:28:37,320 --> 01:28:47,840 PICTURE OF IT PULLING SMOKE IN 1798 01:28:58,320 --> 01:28:59,960 SO, I ALSO THE RELATIONSHIP 1799 01:28:59,960 --> 01:29:01,920 BETWEEN HOW FAR AWAY YOU CAN 1800 01:29:01,920 --> 01:29:05,560 PULL PARTICLES AND THE PARTICLE 1801 01:29:05,560 --> 01:29:07,240 SIZE SO DO YOU SAMPLE DIFFERENT 1802 01:29:07,240 --> 01:29:09,720 SIZE PARTICLES AND DIFFERENT 1803 01:29:09,720 --> 01:29:11,040 DEFICIENCIES. 1804 01:29:11,040 --> 01:29:17,960 >> YEAH, SO THIS IS THE PART OF 1805 01:29:17,960 --> 01:29:20,000 THE TRY TO UNDERSTAND THE 1806 01:29:20,000 --> 01:29:24,040 SPECIFICATIONS OF THE DEVOICE 1807 01:29:24,040 --> 01:29:27,320 VOICE SO BECAUSE IT'S AN OPEN 1808 01:29:27,320 --> 01:29:30,320 DEVICE SO WE CAN'T MEASURE THE 1809 01:29:30,320 --> 01:29:31,440 FLOW RATE WHICH SAY MEASUREMENT 1810 01:29:31,440 --> 01:29:35,120 OF MANY OF THESE AIR SAMPLERS SO 1811 01:29:35,120 --> 01:29:37,440 CONSIDER SOMETIMES LIKE A BIG 1812 01:29:37,440 --> 01:29:38,640 VACUUM CLEANER AND IT WOULD 1813 01:29:38,640 --> 01:29:40,040 SOMETIMES YOU CAN ADAPT THE 1814 01:29:40,040 --> 01:29:41,760 FILTER TO THE VACUUM CLEANER AND 1815 01:29:41,760 --> 01:29:43,600 YOU TURN IT ON AND YOU KNOW IT'S 1816 01:29:43,600 --> 01:29:45,440 GOING TO -- THE FLOW RATE OF THE 1817 01:29:45,440 --> 01:29:48,000 VACUUM CLEANER IS 2,000-LITER 1818 01:29:48,000 --> 01:29:49,360 AND THE VOLUME OF THE ROOM SO 1819 01:29:49,360 --> 01:29:51,240 YOU HAVE AN IDEA HOW LONG DO I 1820 01:29:51,240 --> 01:30:01,720 NEED TO SAMPLE IT'S AN OPEN 1821 01:30:03,320 --> 01:30:07,760 DEVICE SO WE WE KNOW THERE'S NO 1822 01:30:07,760 --> 01:30:08,800 AIR FILTRATION AND THERE'S NO 1823 01:30:08,800 --> 01:30:10,160 AIR FLOW OTHER THAN THAT 1824 01:30:10,160 --> 01:30:11,800 GENERATE BID THE DEVICE AND IT 1825 01:30:11,800 --> 01:30:13,160 COMES TO YOUR OTHER POINT OF HOW 1826 01:30:13,160 --> 01:30:15,560 FAR AWAY YOU CAN BE SO THE 1827 01:30:15,560 --> 01:30:19,120 DEVICE ITSELF, THE SAMPLING 1828 01:30:19,120 --> 01:30:22,440 PROCESS DOES GENERATE AN AIR 1829 01:30:22,440 --> 01:30:24,640 FLOW OF SEVERAL LITERS PER 1830 01:30:24,640 --> 01:30:26,720 MINUTE SO IT'S THAN IT WILL ONLY 1831 01:30:26,720 --> 01:30:31,080 SAMPLE MATERIALS WHICH IS 1832 01:30:31,080 --> 01:30:35,160 PRESENT BUT IF YOU ARE COUGHING 1833 01:30:35,160 --> 01:30:37,120 IT WILL BE MUCH HIGHER THAN YOU 1834 01:30:37,120 --> 01:30:38,760 PICK UP FROM SOMEONE FURTHER 1835 01:30:38,760 --> 01:30:40,320 AWAY BUT WE'LL HAVE TO DETERMINE 1836 01:30:40,320 --> 01:30:44,040 THAT BY SEQUENCING THE PATIENT'S 1837 01:30:44,040 --> 01:30:47,600 BUG IF WE GET IT FROM THE COUGH. 1838 01:30:47,600 --> 01:30:48,280 CERTAINLY HOW MANY THORS WOULD 1839 01:30:48,280 --> 01:30:50,320 YOU NEED TO SAMPLE THIS ROOM? 1840 01:30:50,320 --> 01:30:51,120 IS THE QUESTION. 1841 01:30:51,120 --> 01:30:55,240 WE KNOW ONE THOR FOR 1842 01:30:55,240 --> 01:30:59,800 10,000 LITERS IS OUR ROUGH 1843 01:30:59,800 --> 01:31:00,240 ESTIMATE. 1844 01:31:00,240 --> 01:31:01,880 ANOTHER CAVEAT IS THAT IT'S A 1845 01:31:01,880 --> 01:31:04,040 GOOD CAVEAT BUT BAD FOR THE 1846 01:31:04,040 --> 01:31:06,800 SCIENCES THE ELECTROSTATIC 1847 01:31:06,800 --> 01:31:08,960 SAMPLING KILLS TB AS PART OF THE 1848 01:31:08,960 --> 01:31:12,040 COLLECTION PROCESS SO IT'S ALSO 1849 01:31:12,040 --> 01:31:14,400 A FILTRATION DEVICE STERILIZING 1850 01:31:14,400 --> 01:31:15,280 DEVICE AT THE SAME TIME AS IT 1851 01:31:15,280 --> 01:31:16,960 COLLECTS WHICH IS GOOD. 1852 01:31:16,960 --> 01:31:18,320 >> IT'S GOOD FOR COMPLIANCE. 1853 01:31:18,320 --> 01:31:19,160 >> IT'S VERY GOOD. 1854 01:31:19,160 --> 01:31:20,440 BECAUSE OTHERWISE YOU ARE 1855 01:31:20,440 --> 01:31:22,840 CONCENTRATING TB INTO THIS 1856 01:31:22,840 --> 01:31:23,840 TINY -- IT WOULD BE DANGEROUS. 1857 01:31:23,840 --> 01:31:28,520 WE KNOW IT'S STERILIZING AND SO 1858 01:31:28,520 --> 01:31:33,120 YEAH WHERE WAS I. 1859 01:31:33,120 --> 01:31:34,720 >> IT SOUNDS LIKE THE VOLUME 1860 01:31:34,720 --> 01:31:38,880 ISSUE IS IT'S A GREAT SAMPLE FOR 1861 01:31:38,880 --> 01:31:39,640 A HOUSEHOLD. 1862 01:31:39,640 --> 01:31:40,800 YOU ARE NOT GOING FOR A FOOTBALL 1863 01:31:40,800 --> 01:31:41,040 STADIUM. 1864 01:31:41,040 --> 01:31:43,840 >> WE'RE NOT GOING FOR THAT, NO. 1865 01:31:43,840 --> 01:31:44,720 IT WILL BE SOMETHING YOU CAN 1866 01:31:44,720 --> 01:31:46,440 TAKE WITH YOU, RIGHT SO YOU CAN 1867 01:31:46,440 --> 01:31:48,760 HAVE MANY OF THESE SO IT CAN BE 1868 01:31:48,760 --> 01:31:50,160 THE SMOKE DEVICE TYPE OF THING 1869 01:31:50,160 --> 01:31:53,720 IN A PRISON CELL WHERE THE 1870 01:31:53,720 --> 01:31:55,240 INMATE DOES THE SAMPLING AND 1871 01:31:55,240 --> 01:31:57,040 HANDS OFF THE BULLET OR IT COULD 1872 01:31:57,040 --> 01:31:59,200 BE WHAT YOU GO INTO THE VILLAGE 1873 01:31:59,200 --> 01:32:00,720 AND ASK PEOPLE TO COUGH ON TO 1874 01:32:00,720 --> 01:32:02,000 THIS AND THEY CAN EITHER SHIP 1875 01:32:02,000 --> 01:32:05,520 THE BULLET OR YOU WASH THE 1876 01:32:05,520 --> 01:32:11,080 BULLET AT HOME SO IT'S THAT TYPE 1877 01:32:11,080 --> 01:32:15,160 OF -- YEAH. 1878 01:32:15,160 --> 01:32:25,520 [OFF MIC] [OFF MIC] 1879 01:32:48,080 --> 01:32:49,680 YES, SO I HAVE TOLD MANY PEOPLE 1880 01:32:49,680 --> 01:32:52,320 HERE AND THE PANDEMIC HAS REALLY 1881 01:32:52,320 --> 01:32:54,240 BEEN HORRIBLE AND ESPECIALLY IN 1882 01:32:54,240 --> 01:32:55,960 SWEDEN BUT THERE'S THE POSITIVE 1883 01:32:55,960 --> 01:32:57,920 SIDE OF THE HORRIBLE SITUATION 1884 01:32:57,920 --> 01:33:00,000 THAT IS IT HAS BEEN VERY GOOD 1885 01:33:00,000 --> 01:33:02,240 FOR INFECTIOUS DISEASE RESEARCH 1886 01:33:02,240 --> 01:33:03,600 AND WHAT SPILLS OVER IN TB SO 1887 01:33:03,600 --> 01:33:07,720 YES WE'VE DONE A LOT OF WORK 1888 01:33:07,720 --> 01:33:11,040 WITH COVID AND ACTUALLY WE'RE 1889 01:33:11,040 --> 01:33:12,480 USING THOR TO SAMPLE COVID AND 1890 01:33:12,480 --> 01:33:18,240 THIS WAS DONE IN (INAUDIBLE) SO 1891 01:33:18,240 --> 01:33:20,360 WE DIDN'T HAVE ETHICAL TO GET 1892 01:33:20,360 --> 01:33:21,360 PEM TO COUGH ON TO THE DEVICE 1893 01:33:21,360 --> 01:33:23,760 BUT WE SAMPLED THE ROOM AND ROOM 1894 01:33:23,760 --> 01:33:26,440 AIR OF PATIENTS AND WE TOOK 1895 01:33:26,440 --> 01:33:28,920 SURFACE SWABS AND WE ACTUALLY SO 1896 01:33:28,920 --> 01:33:32,960 WE'RE THE FIRST GROUP TO TO 1897 01:33:32,960 --> 01:33:36,760 RECOVER PFUs FROM AIR, COVID 1898 01:33:36,760 --> 01:33:38,200 PFUs FROM AIR SO THERE'S A LOT 1899 01:33:38,200 --> 01:33:41,640 OF RNA DETECTION OF AIR FROM 1900 01:33:41,640 --> 01:33:43,720 COVID AND PATIENT WARDS AND ALSO 1901 01:33:43,720 --> 01:33:45,640 ON THIS WALLS AND SURFACES AND 1902 01:33:45,640 --> 01:33:48,320 IN SURFACES THAT CAN'T BE 1903 01:33:48,320 --> 01:33:50,440 TOUCHED WHICH SUGGEST THAT THEY 1904 01:33:50,440 --> 01:33:51,800 MUST HAVE FLOWN, TRAVELED 1905 01:33:51,800 --> 01:33:53,400 THROUGH AIR STREAMS THERE AND SO 1906 01:33:53,400 --> 01:33:55,240 WE ACTUALLY USING THOR WHICH IS 1907 01:33:55,240 --> 01:33:57,080 SURPRISING BECAUSE I JUST SAID 1908 01:33:57,080 --> 01:33:58,680 IT STERILIZES BUT IN THIS CASE 1909 01:33:58,680 --> 01:34:03,160 WE WERE ABLE TO ACTUALLY REGROW 1910 01:34:03,160 --> 01:34:05,480 PFUs IN CELLS SO IF YOU 1911 01:34:05,480 --> 01:34:07,480 ACTUALLY DO THE EXPERIMENT INVET 1912 01:34:07,480 --> 01:34:14,960 ROW AND YOU PUT VIRUS ON TO THE 1913 01:34:14,960 --> 01:34:25,080 VICE. 1914 01:34:33,040 --> 01:34:34,160 THE AIR FILTRATION WAS VERY LOW 1915 01:34:34,160 --> 01:34:36,120 SO IT WAS 2.4 AIR CHANGES PER 1916 01:34:36,120 --> 01:34:41,120 HOUR SO VERY, VERY LOW AND SO I 1917 01:34:41,120 --> 01:34:43,960 WILL NOT ANSWER -- FELIX WILL 1918 01:34:43,960 --> 01:34:45,440 ANSWER A BUT I WON'T ANSWER A 1919 01:34:45,440 --> 01:34:48,520 QUESTION ABOUT FACE MASKS 1920 01:34:48,520 --> 01:34:50,920 BECAUSE I IF THERE WAS ANYONE 1921 01:34:50,920 --> 01:34:52,000 WITH A FACE MASK QUESTION I 1922 01:34:52,000 --> 01:34:55,240 WON'T ANSWER THAT BUT I WILL SAY 1923 01:34:55,240 --> 01:34:58,840 SO AIR FILTRATION IS THE KEY 1924 01:34:58,840 --> 01:35:07,440 THING FOR PREVENTING AIRBORN 1925 01:35:07,440 --> 01:35:07,760 TRANSMISSION. 1926 01:35:07,760 --> 01:35:10,840 SARS IN THE I WON'T MAKE A 1927 01:35:10,840 --> 01:35:12,440 STATEMENT ABOUT FACE MASKS BUT I 1928 01:35:12,440 --> 01:35:18,040 WILL SAY AIR FILTRATION IS 1929 01:35:18,040 --> 01:35:18,320 IMPORTANT. 1930 01:35:18,320 --> 01:35:22,120 I CAN HAVE ONE MADE FOR YOU NO 1931 01:35:22,120 --> 01:35:22,360 PROBLEM. 1932 01:35:22,360 --> 01:35:24,000 >> THAT'S REALLY GREAT. 1933 01:35:24,000 --> 01:35:25,520 THAT'S FUN. 1934 01:35:25,520 --> 01:35:31,000 IT'S A SUGGESTION RATHER THAN A 1935 01:35:31,000 --> 01:35:31,280 QUESTION. 1936 01:35:31,280 --> 01:35:32,560 THEY TAKE TIME AND IT'S A SLOW 1937 01:35:32,560 --> 01:35:34,480 PROCESS IF YOU MOVE ON TO 1938 01:35:34,480 --> 01:35:38,280 MOLECULAR SENSORS, DETECTION OF 1939 01:35:38,280 --> 01:35:41,560 TB IT WOULD BE GOLDEN THAT'S 1940 01:35:41,560 --> 01:35:43,240 WONDERFUL. 1941 01:35:43,240 --> 01:35:45,920 >> THANK YOU. 1942 01:35:45,920 --> 01:35:46,360 ALL RIGHT. 1943 01:35:46,360 --> 01:35:52,560 [APPLAUSE] 1944 01:35:52,560 --> 01:35:55,680 SO OUR NEXT SPEAKER IS CHUCK 1945 01:35:55,680 --> 01:35:57,240 SCANGA FROM UNIVERSITY OF 1946 01:35:57,240 --> 01:35:59,120 PITTSBURG SO HE IS ONE OF THE 1947 01:35:59,120 --> 01:36:04,080 THREE MUSKETEERS. 1948 01:36:04,080 --> 01:36:05,760 >> THANK YOU, CARL. 1949 01:36:05,760 --> 01:36:07,760 THANK YOU ESPECIALLY TO DRAGANA 1950 01:36:07,760 --> 01:36:08,960 FOR BOG THE OPPORTUNITY TO SPEAK 1951 01:36:08,960 --> 01:36:10,720 TODAY AND ALSO FOR ORGANIZING 1952 01:36:10,720 --> 01:36:13,800 THIS ENTIRE SYMPOSIUM. 1953 01:36:13,800 --> 01:36:15,840 AS CARL MENTIONED I'M ONE OF THE 1954 01:36:15,840 --> 01:36:18,880 ORIGINAL TB MUSKETEERS, CARL, 1955 01:36:18,880 --> 01:36:22,200 DAMIAN AND I SPENT A LOT OF TIME 1956 01:36:22,200 --> 01:36:24,520 SETTING UP THE BSL3 AND IT 1957 01:36:24,520 --> 01:36:27,320 ALLOWED ME TO DO WORK IN KNOCK 1958 01:36:27,320 --> 01:36:32,040 OUT MICE AND THE WORK THAT FEE 1959 01:36:32,040 --> 01:36:34,280 LEX MENTIONED YESTERDAY AND 1960 01:36:34,280 --> 01:36:36,480 AFTER OUR BSL3 GOT UP AND 1961 01:36:36,480 --> 01:36:38,160 RUNNING I PICKED UP A STUDY THAT 1962 01:36:38,160 --> 01:36:40,680 HAD BEEN STARTED IN THE LAB BY 1963 01:36:40,680 --> 01:36:43,600 MARCO SHEET OWE USING HIV 1964 01:36:43,600 --> 01:36:46,840 TRANSGENIC MICE TO LOOK AT CO 1965 01:36:46,840 --> 01:36:48,520 INFECTION AND I EXTENDED THAT 1966 01:36:48,520 --> 01:36:55,040 WORK INTO MTB AND THAT'S A -- 1967 01:36:55,040 --> 01:36:57,440 THAT CO INFECTION WORK IS 1968 01:36:57,440 --> 01:36:58,680 SOMETHING THIS CONTINUES IN MY 1969 01:36:58,680 --> 01:37:01,280 OWN LAB TODAY SO FOR THIS 1970 01:37:01,280 --> 01:37:12,040 AUDIENAUDIENCE IDON'T NEED TO GL 1971 01:37:12,040 --> 01:37:15,880 HEALTH THREAT AND NEEDLESS TO 1972 01:37:15,880 --> 01:37:23,880 SAY IT'S I USE IT COMING FROM 1973 01:37:23,880 --> 01:37:25,640 RUSSIA AND THIS IS A STUDY THAT 1974 01:37:25,640 --> 01:37:27,680 STARTED WITH A COLLABORATION 1975 01:37:27,680 --> 01:37:29,120 WITH SHELBY OWE GONER ABOUT 1976 01:37:29,120 --> 01:37:34,880 EIGHT YEARS AGO AND WE USED 1977 01:37:34,880 --> 01:37:36,560 THESE MACAQUES THEY'VE BEEN USED 1978 01:37:36,560 --> 01:37:39,920 TO STUDY HIV USING SIV AS A 1979 01:37:39,920 --> 01:37:41,520 GARROW GET AND THEY HAVEN'T BEEN 1980 01:37:41,520 --> 01:37:44,480 USED MUCH TO STUDY TB AND SALLY 1981 01:37:44,480 --> 01:37:49,200 SHARP PUBLISHED THE FIRST PAPER 1982 01:37:49,200 --> 01:37:50,600 IN 2017 JUST AS WE WERE GETTING 1983 01:37:50,600 --> 01:37:55,080 STARTED AND THE REASON WE USED 1984 01:37:55,080 --> 01:37:58,720 THEM IS THE MACAQUES COME FROM 1985 01:37:58,720 --> 01:38:03,200 THIS TINY ISOLATED ISLAND OF 1986 01:38:03,200 --> 01:38:04,720 MAURITIAS AND THEY STARTED WITH 1987 01:38:04,720 --> 01:38:07,440 A FOUNDER POPULATION OF JUST 12 1988 01:38:07,440 --> 01:38:10,800 ANIMALS AND THIS IS GENETIC 1989 01:38:10,800 --> 01:38:13,120 BOTTLENECK RESULTED IN A LIMITED 1990 01:38:13,120 --> 01:38:17,320 NUMBER OF MHC HAB LOW TYPES AND 1991 01:38:17,320 --> 01:38:27,840 IT'S TH HAPPEN LOW TYPES. 1992 01:38:51,280 --> 01:38:53,920 WHEN YOU LOOK AT THE PROGRESSION 1993 01:38:53,920 --> 01:38:55,920 OF TB IN THESE TWO SPECIES, YOU 1994 01:38:55,920 --> 01:38:59,000 CAN SEE THERE'S FIRST THERE'S A 1995 01:38:59,000 --> 01:39:00,640 SPECTRUM OF SUSCEPTIBLE WITHIN 1996 01:39:00,640 --> 01:39:02,400 EACH OF THE SPECIES BUT IN 1997 01:39:02,400 --> 01:39:04,800 GENERAL, THE CHINESE MACAQUES 1998 01:39:04,800 --> 01:39:06,560 TEND TO BE MORE RESISTANT AND 1999 01:39:06,560 --> 01:39:12,120 THEY EXHIBIT LESS PATHOLOGY THAN 2000 01:39:12,120 --> 01:39:14,800 DO THE RECESS AND THEY HAVE 2001 01:39:14,800 --> 01:39:15,840 LOWER BACK TER Y'ALL ROADS 2002 01:39:15,840 --> 01:39:19,720 COMPARED TO THE RHESUS AND WE 2003 01:39:19,720 --> 01:39:24,880 USE PET IMAGING AND REUSE FDG AS 2004 01:39:24,880 --> 01:39:26,880 A PROBE FOR A NON SPECIFIC PROBE 2005 01:39:26,880 --> 01:39:28,200 FOR IN FROM MISSION AND IT 2006 01:39:28,200 --> 01:39:39,880 LIGHTSFOR --THEY ARE MUCH CLOSES 2007 01:39:59,160 --> 01:40:02,400 AND SO SHELBY AND I STARTED THIS 2008 01:40:02,400 --> 01:40:03,720 PROJECT QUITE A FEW YEARS AGO 2009 01:40:03,720 --> 01:40:05,320 AND THE FIRST QUESTION WE ASKED 2010 01:40:05,320 --> 01:40:08,520 IS DOES PREEXISTING SIV 2011 01:40:08,520 --> 01:40:10,080 INFECTION AFFECT TB PROGRESSION 2012 01:40:10,080 --> 01:40:16,440 AND TO DO THIS STUDY WE INFECTED 2013 01:40:16,440 --> 01:40:19,720 SOME ANIMALS WITH 2014 01:40:19,720 --> 01:40:21,840 3,000TDI50 AND WE EFFECT THEM 2015 01:40:21,840 --> 01:40:23,600 INTER RECTAL' AND SIX MONTHS 2016 01:40:23,600 --> 01:40:25,160 LATER, WE CO EFFECT THESE 2017 01:40:25,160 --> 01:40:28,040 ANIMALS WITH LOW DOSE OF 2018 01:40:28,040 --> 01:40:29,800 TUBERCULOSIS ANDE USE THE 2019 01:40:29,800 --> 01:40:33,040 STRAIN AND WE DELIVER IT BY 2020 01:40:33,040 --> 01:40:34,200 DELIVERY AND WE FOLLOWED THOSE 2021 01:40:34,200 --> 01:40:36,960 ANIMALS AND WE COMPARED THE TB 2022 01:40:36,960 --> 01:40:39,000 PROGRESSION IN THOSE CO EFFECTED 2023 01:40:39,000 --> 01:40:43,280 ANIMALS TO ANIMALS INFECTED WITH 2024 01:40:43,280 --> 01:40:46,800 MTB ALONE AND THE CO EFFECTED 2025 01:40:46,800 --> 01:40:48,720 ANIMALS EXHIBITED A LOSS OF CD4 2026 01:40:48,720 --> 01:40:51,360 CELLS AS A RESULT OF THE SIV 2027 01:40:51,360 --> 01:40:53,000 INFECTION AND THEY INTENDED TO 2028 01:40:53,000 --> 01:40:57,840 HAVE MORE TB DISEASE AND HIGHER 2029 01:40:57,840 --> 01:41:00,280 BACTERIAL BURDEN. 2030 01:41:00,280 --> 01:41:03,080 AND GIVEN THAT TB IS RESPONSIBLE 2031 01:41:03,080 --> 01:41:05,080 FOR SO MANY DEATHS IN PEOPLE 2032 01:41:05,080 --> 01:41:07,280 LIVING WITH HIV AND IT REALLY 2033 01:41:07,280 --> 01:41:08,680 BEGS TO QUESTION IS THERE A WAY 2034 01:41:08,680 --> 01:41:11,320 THAT WE CAN PROJECT THESE HIV 2035 01:41:11,320 --> 01:41:12,480 POSITIVE INDIVIDUALS FROM TB? 2036 01:41:12,480 --> 01:41:14,640 OF COURSE, THE SIMPLEST WAY IS 2037 01:41:14,640 --> 01:41:19,080 WITH A VACCINE AND IN DEED 2038 01:41:19,080 --> 01:41:23,120 THERE'S A VACCINE FOR 2039 01:41:23,120 --> 01:41:26,040 TUBERCULOSIS WHICH IS A LIFE 2040 01:41:26,040 --> 01:41:28,400 ATTENUATED STRAIN BCG IS ONE OF 2041 01:41:28,400 --> 01:41:30,080 THE MOST WIDELY USED VACCINES IN 2042 01:41:30,080 --> 01:41:31,880 THE WORLD AND ONE OF THE LEAST 2043 01:41:31,880 --> 01:41:34,680 EFFECTIVE AND IT IS BEEN AROUND 2044 01:41:34,680 --> 01:41:37,280 FOR 100 YEARS WHEN IT WAS FIRST 2045 01:41:37,280 --> 01:41:41,000 DEVELOPED BY CALMETTE-GUERIN AND 2046 01:41:41,000 --> 01:41:42,920 IT'S GIVEN SHORTLY AFTERBIRTH 2047 01:41:42,920 --> 01:41:44,920 AND THE DOSE IS FIVE TIMES 10 TO 2048 01:41:44,920 --> 01:41:47,680 THE FIFTH CFU AND IT'S GIVEN 2049 01:41:47,680 --> 01:41:51,520 INTRA BERMALLY AND IT DOES 2050 01:41:51,520 --> 01:41:56,560 PROTECT AGAINST CHILDHOOD TB AND 2051 01:41:56,560 --> 01:42:00,280 AS THEY GROW UP IT IS POOR 2052 01:42:00,280 --> 01:42:02,920 PROTECTION AGAINST ADULT 2053 01:42:02,920 --> 01:42:04,880 PULMONARY TB. 2054 01:42:04,880 --> 01:42:09,200 WE SEE THIS IN MACAQUES. 2055 01:42:09,200 --> 01:42:11,000 THIS IS WORK WE DID HERE AT THE 2056 01:42:11,000 --> 01:42:12,560 VACCINE RESEARCH CENTER AND YOU 2057 01:42:12,560 --> 01:42:16,480 CAN SEE IN THE SUSCEPTIBLE MA 2058 01:42:16,480 --> 01:42:18,400 CONTACT MODEL IT GIVES YOU ONE 2059 01:42:18,400 --> 01:42:24,680 LOG OF PROTECTION IN TERMS OF 2060 01:42:24,680 --> 01:42:35,200 CFU AND MACAQUES BY CHANGING THE 2061 01:42:48,280 --> 01:42:49,760 DOSE OR ROUTE WE COULD GET 2062 01:42:49,760 --> 01:42:52,200 BETTER PROTECTION. 2063 01:42:52,200 --> 01:42:56,400 AND IN THIS STUDY, HE INCREASED 2064 01:42:56,400 --> 01:42:58,000 BY 100 FOLD THE INTRA DETERMINAL 2065 01:42:58,000 --> 01:43:02,360 DOSE OF BCG IN MACAQUES AND 2066 01:43:02,360 --> 01:43:04,840 DELIVERED HIGH DOSE BCG 2067 01:43:04,840 --> 01:43:15,240 INTRAVENOUSLY AND HE DID 2068 01:43:18,520 --> 01:43:20,880 INCLUDED ANIMALS VACCINATED BY 2069 01:43:20,880 --> 01:43:23,720 THE AEROSOL ROUTE AND BOB AND 2070 01:43:23,720 --> 01:43:27,040 HIS TEAM FOLLOWED THE 2071 01:43:27,040 --> 01:43:28,360 DEVELOPMENT AND THE AIRWAY 2072 01:43:28,360 --> 01:43:30,760 RESPONSES USING ABL AND FLOW 2073 01:43:30,760 --> 01:43:32,240 CYTOMETRY TO LOOK AT CELLS AND 2074 01:43:32,240 --> 01:43:38,160 REALLY IT WAS ONLY THE 2075 01:43:38,160 --> 01:43:39,400 INTRAVENOUS ROUTE THAT WAS AWAY 2076 01:43:39,400 --> 01:43:42,600 FROM THE TYPICAL LVO OR 2077 01:43:42,600 --> 01:43:44,480 MACROPHAGES THAT ARE MOST 2078 01:43:44,480 --> 01:43:49,800 PREVALENT IN BAL TO THIS T-CELL 2079 01:43:49,800 --> 01:43:52,080 PROMINENT PHENOTYPE AND THAT IS 2080 01:43:52,080 --> 01:43:55,720 MAINTAINED FOR MANY, MANY WEEKS 2081 01:43:55,720 --> 01:43:57,200 AND MONTHS AFTER VACCINATION. 2082 01:43:57,200 --> 01:43:59,600 ONLY IN THE INTRAVENOUSLY 2083 01:43:59,600 --> 01:44:02,520 VACCINATED ANIMALS AND THEY SENT 2084 01:44:02,520 --> 01:44:04,640 THOSE ANIMALS TO RTB GROUP AT 2085 01:44:04,640 --> 01:44:07,160 PIT LED BY JOANNE FLYNN AND WE 2086 01:44:07,160 --> 01:44:11,280 CHALLENGED THOSE ANIMALS AND YOU 2087 01:44:11,280 --> 01:44:15,080 CAN SEE THAT THE ANIMALS 2088 01:44:15,080 --> 01:44:16,840 VACCINATED INTRAVENOUSLY 90% 2089 01:44:16,840 --> 01:44:21,040 WERE PROTECTED FROM M 2090 01:44:21,040 --> 01:44:21,360 TUBERCULOSIS. 2091 01:44:21,360 --> 01:44:22,640 IN FACT, SIX OUT OF THE 10 2092 01:44:22,640 --> 01:44:24,600 ANIMALS IN THIS GROUP EXHIBITED 2093 01:44:24,600 --> 01:44:25,920 STERILIZING IMMUNITY AND IN 2094 01:44:25,920 --> 01:44:27,280 OTHER WORDS, WE COULD NOT 2095 01:44:27,280 --> 01:44:28,920 CULTURAL ANY MICRO BACTERIAL 2096 01:44:28,920 --> 01:44:31,120 FROM THOSE ANIMALS AT THE TIME 2097 01:44:31,120 --> 01:44:34,440 OF NECROPSY SO THIS WAS REALLY 2098 01:44:34,440 --> 01:44:44,800 DRAMATIC PROTECTION. 2099 01:44:57,800 --> 01:45:02,160 IT'S CHALLENGES WITH NTB AND 2100 01:45:02,160 --> 01:45:03,480 NECROPSY 12 WEEKS LATER. 2101 01:45:03,480 --> 01:45:04,880 THE SECOND GROUP OF ANIMALS, 2102 01:45:04,880 --> 01:45:08,600 THESE ARE SIV NAIVE ANIMALS 2103 01:45:08,600 --> 01:45:11,640 VACCINATED WITH HIGH DOSE 2104 01:45:11,640 --> 01:45:13,160 INTRAVENOUS BCG AND SEVERAL 2105 01:45:13,160 --> 01:45:19,000 MONTHS LATER CHALLENGED AGAIN 2106 01:45:19,000 --> 01:45:20,000 WITH M TUBERCULOSIS. 2107 01:45:20,000 --> 01:45:22,560 AND ONE GROUP OF ANIMALS WAS 2108 01:45:22,560 --> 01:45:25,200 INFECTED WITH SIV AGAIN, WE USED 2109 01:45:25,200 --> 01:45:28,040 THE MACK 239 STRAIN GIVEN 2110 01:45:28,040 --> 01:45:29,440 ININTEREST RECTAL' AND FOLLOWED 2111 01:45:29,440 --> 01:45:31,600 THESE ANIMALS AND FOLLOWED VIRAL 2112 01:45:31,600 --> 01:45:42,240 LOADS IN THESE ANIMALS AND FIVES 2113 01:45:54,600 --> 01:45:56,320 LATER WE VACCINATED THEM WITH A 2114 01:45:56,320 --> 01:45:59,440 HIGH DOSE OF BCG INTRAVENOUSLY 2115 01:45:59,440 --> 01:46:01,040 AND THEN CHALLENGES THEM SEVERAL 2116 01:46:01,040 --> 01:46:02,920 MONTHS LATER WITH M 2117 01:46:02,920 --> 01:46:03,280 TUBERCULOSIS. 2118 01:46:03,280 --> 01:46:06,920 NOW MY BIG FEAR WAS IN THESE 2119 01:46:06,920 --> 01:46:09,000 IMMUNO DEFICIENT ANIMALS SIV 2120 01:46:09,000 --> 01:46:10,920 POSITIVE ANIMALS, THIS HIGH DOSE 2121 01:46:10,920 --> 01:46:16,240 LIVE BCG INJECTIO INJECTED INTOD 2122 01:46:16,240 --> 01:46:17,760 STREAM AND KILL THESE MONKEYS 2123 01:46:17,760 --> 01:46:18,960 AND THAT WAS MY BIGGEST FEAR AND 2124 01:46:18,960 --> 01:46:20,680 BECAUSE OF THAT I DECIDED TO 2125 01:46:20,680 --> 01:46:25,240 TREAT THE ANIMALS WITH TO KILL 2126 01:46:25,240 --> 01:46:28,960 THE BCG THROW TO FOUR WEEKS 2127 01:46:28,960 --> 01:46:31,520 AFTER VACCINATION. 2128 01:46:31,520 --> 01:46:35,120 AND JUST TO KEEP THAT CONSTANT 2129 01:46:35,120 --> 01:46:36,560 AND ALL THE GROUPS, ALL THE 2130 01:46:36,560 --> 01:46:38,000 ANIMALS REGARDLESS OF WHETHER 2131 01:46:38,000 --> 01:46:39,720 THEY'RE VACCINATED, RECEIVED 2132 01:46:39,720 --> 01:46:43,120 THIS SAME HRA REGIMENT WHICH WE 2133 01:46:43,120 --> 01:46:44,800 STOPPED ONE MONTH BEFORE 2134 01:46:44,800 --> 01:46:46,920 CHALLENGE SO THAT THE DRUGS WERE 2135 01:46:46,920 --> 01:46:48,680 NOT PRESENT WHEN WE ACTUALLY DID 2136 01:46:48,680 --> 01:46:55,200 THE CHALLENGE. 2137 01:46:55,200 --> 01:46:57,560 THE FIRST QUESTION IS IT SAFE? 2138 01:46:57,560 --> 01:46:59,880 THEY WERE NEGATIVE IN THE BLOOD 2139 01:46:59,880 --> 01:47:03,080 CULTURE AND WE CAN'T GO OUT BCG 2140 01:47:03,080 --> 01:47:04,200 TWO WEEKS AFTER VACCINATION AND 2141 01:47:04,200 --> 01:47:05,920 THEY DIDN'T EXHIBIT ANY CLINICAL 2142 01:47:05,920 --> 01:47:08,840 SCIENCE OF BCG DISEASE AND THEY 2143 01:47:08,840 --> 01:47:11,880 HAD NO NORMAL ESRs SO JUST 2144 01:47:11,880 --> 01:47:14,320 BASED ON THOSE KIND OF CURSORY 2145 01:47:14,320 --> 01:47:16,760 FINDINGS, IVBCG DOES APPEAR TO 2146 01:47:16,760 --> 01:47:19,920 BE SAFE IN SIV AND THE CAVEAT 2147 01:47:19,920 --> 01:47:21,120 THOUGH IS THAT AT LEAST WHEN 2148 01:47:21,120 --> 01:47:23,480 THEY WERE TREATED WITH ANTI BCG 2149 01:47:23,480 --> 01:47:25,600 DRUGS, STARTING THREE TO FOUR 2150 01:47:25,600 --> 01:47:27,640 WEEKS AFTER VACCINATION. 2151 01:47:27,640 --> 01:47:31,280 SO THE NEXT QUESTION BECAME WHAT 2152 01:47:31,280 --> 01:47:34,880 EFFECT DOES THAT BCG HAVE ON SIV 2153 01:47:34,880 --> 01:47:37,640 SO AGAIN WE UPON INFECTION, YOU 2154 01:47:37,640 --> 01:47:41,320 SEE ALL THE ANIMALS EXHIBIT THIS 2155 01:47:41,320 --> 01:47:51,880 SPIKE IN VI REEMIA THAT IS THEN 2156 01:47:57,800 --> 01:47:59,960 THEY HAVE A SPIKE IN VIREMIA AND 2157 01:47:59,960 --> 01:48:01,480 BACK UNDER CONTROL AND ALL OF 2158 01:48:01,480 --> 01:48:04,800 THESE ANIMALS REESTABLISHED 2159 01:48:04,800 --> 01:48:12,800 THEIR ORIGINAL VIRAL BASE LINES. 2160 01:48:12,800 --> 01:48:17,760 WHAT ABOUT IMMUNO. 2161 01:48:17,760 --> 01:48:24,880 JUST LIKE THE MACAQUES WE SAW IN 2162 01:48:24,880 --> 01:48:30,280 SIV NAIVE MACAQUES IV BCG HAD A 2163 01:48:30,280 --> 01:48:33,800 SHIFT FROM MACROPHAGE DOMINATED 2164 01:48:33,800 --> 01:48:37,000 BAL CELLS TO ONE DOMINATED BY T 2165 01:48:37,000 --> 01:48:39,400 CELLS AND THAT WAS MAINTAINED 2166 01:48:39,400 --> 01:48:44,480 FOR MANY WEEKS AFTER 2167 01:48:44,480 --> 01:48:44,800 VACCINATION. 2168 01:48:44,800 --> 01:48:47,400 AND QUITE SURPRISINGLY TO ME WE 2169 01:48:47,400 --> 01:48:50,080 SAW THAT SAME AFFECT HERE IN THE 2170 01:48:50,080 --> 01:48:54,880 SIV POSITIVE ANIMALS AND AGAIN, 2171 01:48:54,880 --> 01:48:57,720 EVEN IN ANIMALS INFECTED WITH 2172 01:48:57,720 --> 01:49:01,600 SIV, IVBCG STILL ILLICITTED THIS 2173 01:49:01,600 --> 01:49:03,160 DRAMATIC INCREASE IN THE 2174 01:49:03,160 --> 01:49:10,400 PREPORTION OF T CELLS IN THE 2175 01:49:10,400 --> 01:49:16,840 BAL. 2176 01:49:16,840 --> 01:49:19,120 IT WAS T CONTROLS SHOWN IN THE 2177 01:49:19,120 --> 01:49:24,480 BAL AND THIS IS BUSY LIED BUT 2178 01:49:24,480 --> 01:49:32,920 THE THIN LINES AND WHETHER OR 2179 01:49:32,920 --> 01:49:39,320 NOT THEY HAD PREEXISTING SIV 2180 01:49:39,320 --> 01:49:40,800 INFECTION YOU SEE THE INCREASE 2181 01:49:40,800 --> 01:49:43,760 IN THE LUNG AND THESE T CELLS 2182 01:49:43,760 --> 01:49:45,680 THAT COME INTO THE LUNG WERE 2183 01:49:45,680 --> 01:49:49,200 ACTUALLY PRIME TO MICRO BACTERIA 2184 01:49:49,200 --> 01:49:51,760 AN THROW AGAINST SO YOU SEE THIS 2185 01:49:51,760 --> 01:49:53,960 SHOWING CD4 MEMORY CELLS THAT 2186 01:49:53,960 --> 01:49:57,280 ARE RESPONDING BY MAKING 2187 01:49:57,280 --> 01:50:02,360 CYTOKINES IN RESPONSE TO PPD 2188 01:50:02,360 --> 01:50:12,600 RESTIMULATION. 2189 01:50:15,320 --> 01:50:17,880 YOU CAN SEE WHETHER THEY HAVE 2190 01:50:17,880 --> 01:50:24,760 SERVE OR NOT FOLLOWING MTB 2191 01:50:24,760 --> 01:50:25,600 CHALLENGE. 2192 01:50:25,600 --> 01:50:27,560 IN THE SIV AND VACCINATIONED AND 2193 01:50:27,560 --> 01:50:29,760 WE SAW COMPLETE PROTECTION FROM 2194 01:50:29,760 --> 01:50:40,280 DISEASE IN ALL OF THE ANIMALS. 2195 01:50:50,400 --> 01:50:54,280 WE SAW THAT IVBCG ELICITED 2196 01:50:54,280 --> 01:50:55,680 STRIKING PROTECTION IN THE 2197 01:50:55,680 --> 01:50:58,200 MAJORITY OF ANIMALS THIS SEVEN 2198 01:50:58,200 --> 01:51:00,720 OUT OF THE 10 ANIMALS THEY 2199 01:51:00,720 --> 01:51:02,800 REALLY HAD NO DISEASE VISIBLE BY 2200 01:51:02,800 --> 01:51:08,680 PET CT AND ONE ANIMAL WAS 2201 01:51:08,680 --> 01:51:12,360 PARTIALLY PROTECT AND TWO 2202 01:51:12,360 --> 01:51:15,320 ANIMALS THAT WERE VACCINE AND WE 2203 01:51:15,320 --> 01:51:20,560 CAN QUANTIFY THIS PROTECTION BY 2204 01:51:20,560 --> 01:51:23,880 MEASURING THE TOTAL FDG 2205 01:51:23,880 --> 01:51:26,120 ACCUMULATION AND YOU CAN SEE 2206 01:51:26,120 --> 01:51:29,120 THAT IDBCG ANIMALS, WHETHER 2207 01:51:29,120 --> 01:51:30,680 THEY'RE INFECTED AND WHETHER 2208 01:51:30,680 --> 01:51:41,240 THEY'RE INFECTED OR NOT AND AND 2209 01:52:03,840 --> 01:52:05,480 THEY HAVE STERILIZING IMMUNITY 2210 01:52:05,480 --> 01:52:07,200 TO A MTB CHALLENGE AND SEVEN OUT 2211 01:52:07,200 --> 01:52:10,440 OF THE 10 ANIMALS SIV POSITIVE 2212 01:52:10,440 --> 01:52:13,320 ANIMALS WERE SIMILARLY STERILE 2213 01:52:13,320 --> 01:52:15,480 AFTER CHALLENGE. 2214 01:52:15,480 --> 01:52:17,160 AND ONE ANIMAL IS PARTIALLY 2215 01:52:17,160 --> 01:52:20,480 PROTECTED AND TWO ANIMALS WERE 2216 01:52:20,480 --> 01:52:20,840 NOT. 2217 01:52:20,840 --> 01:52:23,000 AND I THINK ONE OF THE MOST 2218 01:52:23,000 --> 01:52:24,840 DRAMATIC FINDINGS FROM THIS 2219 01:52:24,840 --> 01:52:28,160 STUDY WHEN WE DID PBMC ALLEY 2220 01:52:28,160 --> 01:52:30,960 SPOTS, AFTER INFECTION AND 2221 01:52:30,960 --> 01:52:33,040 RESTIMULATED THE CELLS WITH 2222 01:52:33,040 --> 01:52:36,440 MTB-SPECIFIC ANTIGENS SO WHICH 2223 01:52:36,440 --> 01:52:38,800 ARE PRESENT ONLY IN MTB NOT 2224 01:52:38,800 --> 01:52:43,480 PRESENT IN BCG AND AS EXPECTED 2225 01:52:43,480 --> 01:52:45,600 BEFORE MTB CHALLENGE AND YOU 2226 01:52:45,600 --> 01:52:47,240 DON'T SEE ANY RESPONSES IN ANY 2227 01:52:47,240 --> 01:52:51,000 OF THE ANIMALS AND IN THE 2228 01:52:51,000 --> 01:52:53,800 UNVACCINATED ANIMALS, AFTER MTB 2229 01:52:53,800 --> 01:52:55,720 CHALLENGE, YOU SEE THE NICE 2230 01:52:55,720 --> 01:52:57,720 INTERFERON GAMMA RESPONSES IN 2231 01:52:57,720 --> 01:53:01,560 THE PBMCs IN RESPONSE TO THESE 2232 01:53:01,560 --> 01:53:05,000 MTB-SPECIFIC ANTIGENS AND QUITE 2233 01:53:05,000 --> 01:53:07,600 STRIKINGLY IN THE VACCINATED 2234 01:53:07,600 --> 01:53:11,240 ANIMALS, EVEN AFTER MTV AND YOU 2235 01:53:11,240 --> 01:53:17,480 DID SEE RESPONSE AND IT SUGGESTS 2236 01:53:17,480 --> 01:53:19,880 THAT THE VACCINATED ANIMALS AND 2237 01:53:19,880 --> 01:53:21,440 ELIMINATING CLEARING THE 2238 01:53:21,440 --> 01:53:23,680 BACTERIA BEFORE AND ADAPTIVE AND 2239 01:53:23,680 --> 01:53:27,840 IS EVEN GENERATED AND THAT IS 2240 01:53:27,840 --> 01:53:30,680 QUITE INTRIGUING AND AMAZING SO 2241 01:53:30,680 --> 01:53:41,800 THE CONCLUSION 0 CON IT PROTECTV 2242 01:53:55,160 --> 01:53:57,840 NAIVE AND CONFERRED PROTECTION 2243 01:53:57,840 --> 01:54:04,640 IN 80% OF THE SIV POSITIVE AND 2244 01:54:04,640 --> 01:54:14,040 SO THOSE STUDIES CHRONICALLY 2245 01:54:14,040 --> 01:54:16,800 EFFECTED WITH SIV AND IT REALLY 2246 01:54:16,800 --> 01:54:19,640 OPENS UP SOME EXCITING POTENTIAL 2247 01:54:19,640 --> 01:54:23,280 FOR EFFECTIVE VACCINES IN THIS 2248 01:54:23,280 --> 01:54:26,800 REALLY SIS SUSCEPTIBLE 2249 01:54:26,800 --> 01:54:27,120 POPULATION. 2250 01:54:27,120 --> 01:54:31,720 SO WITH THAT LET ME ACKNOWLEDGE 2251 01:54:31,720 --> 01:54:42,160 LOB, TRISHA, WITHIN THE TB 2252 01:54:46,680 --> 01:54:48,920 RESEARCH GROUP AT PIT LED BY 2253 01:54:48,920 --> 01:54:49,880 JOANNE FLYNN WHO I KNOW MANY OF 2254 01:54:49,880 --> 01:55:00,280 YOU KNOW WELL AND THIS. 2255 01:56:57,120 --> 01:57:02,840 >> WE MIGHT BE ABLE TO USE 2256 01:57:02,840 --> 01:57:04,200 MUTANT OR SOMETHING LIKE THAT TO 2257 01:57:04,200 --> 01:57:07,400 BE A MUCH SAFER VACCINE BECAUSE 2258 01:57:07,400 --> 01:57:10,280 GIVING HIGH DOSE IVBCD IN HIV 2259 01:57:10,280 --> 01:57:11,600 POSITIVE PEOPLE PROBABLY IS HIGH 2260 01:57:11,600 --> 01:57:14,080 BAR TO CLEAR BUT THESE DATA 2261 01:57:14,080 --> 01:57:15,480 CERTAINLY SUGGEST THAT WE COULD 2262 01:57:15,480 --> 01:57:18,840 USE A SAFER VARIANT OF BCG. 2263 01:57:18,840 --> 01:57:21,080 >> DEAD BUGS DOESN'T GET SAFER. 2264 01:57:21,080 --> 01:57:23,320 >> DEAD BUGS SOMETHING LIKE THAT 2265 01:57:23,320 --> 01:57:25,120 AND DEFINITELY THINGS THAT WE'RE 2266 01:57:25,120 --> 01:57:26,840 LOOKING AT. 2267 01:57:26,840 --> 01:57:27,800 >> COOL. 2268 01:57:27,800 --> 01:57:29,360 >> CONGRATULATIONS ON THAT 2269 01:57:29,360 --> 01:57:31,640 REALLY IMPORTANT RESULT. 2270 01:57:31,640 --> 01:57:34,600 WHY DO THE CELLS GO TO THE LUNG 2271 01:57:34,600 --> 01:57:35,600 IF THE VACCINATION? 2272 01:57:35,600 --> 01:57:38,440 WHAT'S THE IMMUNO PHENOTYPE AND 2273 01:57:38,440 --> 01:57:39,480 FUNCTIONALITY OF THE T CELLS 2274 01:57:39,480 --> 01:57:42,040 LONG BEFORE INFECTION AND CAN 2275 01:57:42,040 --> 01:57:46,000 YOU GIVE BCG INTRAVENOUSLY TO 2276 01:57:46,000 --> 01:57:47,320 TREAT ESTABLISHED TB INFECTION? 2277 01:57:47,320 --> 01:57:49,600 >> ALL GOOD QUESTIONS, WE'VE NOT 2278 01:57:49,600 --> 01:57:53,880 DONE THE USE OF BCGIVBCG AS A 2279 01:57:53,880 --> 01:57:55,160 THERAPEUTIC AND CERTAINLY THAT'S 2280 01:57:55,160 --> 01:57:56,640 SOMETHING THAT COULD BE 2281 01:57:56,640 --> 01:57:58,440 INVESTIGATED AND WHY ARE THE 2282 01:57:58,440 --> 01:57:59,960 CELLS TO THE LUNG AND WHAT ARE 2283 01:57:59,960 --> 01:58:01,120 THEY DOING WHEN THEY GET THERE 2284 01:58:01,120 --> 01:58:02,560 IS A QUESTION THAT WE'RE 2285 01:58:02,560 --> 01:58:03,760 ACTIVELY LOOKING AT NOW AND 2286 01:58:03,760 --> 01:58:06,960 WE'RE USING A LOT OF SINGLE CELL 2287 01:58:06,960 --> 01:58:09,080 RNC SEEK TO MORE FULLY 2288 01:58:09,080 --> 01:58:10,160 CHARACTERIZE THE CELL 2289 01:58:10,160 --> 01:58:12,200 POPULATIONS SO I HOPE TO HAVE 2290 01:58:12,200 --> 01:58:13,600 SOME BETTER ANSWERS FOR YOU 2291 01:58:13,600 --> 01:58:19,520 WITHIN THE NEXT YEAR. 2292 01:58:19,520 --> 01:58:21,200 >> I WAS VERY STRIKING AT THE 2293 01:58:21,200 --> 01:58:23,720 END WHEN YOU SUGGESTED THAT YOU 2294 01:58:23,720 --> 01:58:26,640 COULDN'T FIND THE SPECIFIC T 2295 01:58:26,640 --> 01:58:29,320 CELLS IN THE BLOOD BECAUSE I 2296 01:58:29,320 --> 01:58:30,920 THINK WE WERE ALL THINKING 2297 01:58:30,920 --> 01:58:32,080 THAT'S WHAT YOU WERE GOING TO 2298 01:58:32,080 --> 01:58:32,480 FIND. 2299 01:58:32,480 --> 01:58:34,120 WHAT IS THE MECHANISM? 2300 01:58:34,120 --> 01:58:35,840 WHAT DO YOU THINK IS GOING ON? 2301 01:58:35,840 --> 01:58:40,240 >> THE MECHANISM IS A REALLY, 2302 01:58:40,240 --> 01:58:42,640 REALLY IMPORTANT QUESTION AND SO 2303 01:58:42,640 --> 01:58:44,160 WE'RE TRYING IDENTIFY THE 2304 01:58:44,160 --> 01:58:49,920 MECHANISM AND LOOK FOR COR 2305 01:58:49,920 --> 01:58:50,200 IMMUNITY. 2306 01:58:50,200 --> 01:58:52,000 I KNOW STUDIES WITH BOB SEEDER 2307 01:58:52,000 --> 01:58:54,280 AND JOANNE FLYNN HAS SHOWN AN 2308 01:58:54,280 --> 01:58:56,680 NIH NAIVE ANIMALS AND PRETEXT IS 2309 01:58:56,680 --> 01:59:00,160 ASSOCIATED WITH IGM AND IT'S 2310 01:59:00,160 --> 01:59:03,360 ASSOCIATED WITH AN INFLUX OF T 2311 01:59:03,360 --> 01:59:04,720 RESIDENT MEMBER RE CELLS AND 2312 01:59:04,720 --> 01:59:06,800 THESE ARE ALL ASSOCIATIONS WHERE 2313 01:59:06,800 --> 01:59:11,120 CURRENTLY DOING STUDIES TO KIND 2314 01:59:11,120 --> 01:59:13,000 OF MORE FIRMLY HAVE MECHANISM 2315 01:59:13,000 --> 01:59:13,480 PROTECTION. 2316 01:59:13,480 --> 01:59:15,200 >> YOU ARE NOT ARGUING IT'S NOT 2317 01:59:15,200 --> 01:59:16,440 T CELLS YOU ARE ARGUING THEY 2318 01:59:16,440 --> 01:59:17,920 MIGHT NOT BE IN THE BLOOD. 2319 01:59:17,920 --> 01:59:18,320 >> THAT'S RIGHT. 2320 01:59:18,320 --> 01:59:20,440 >> THEY MIGHT BE IN THE LUNG. 2321 01:59:20,440 --> 01:59:20,800 >> ABSOLUTELY. 2322 01:59:20,800 --> 01:59:27,520 >> IS IT ETHICALLY FEASIBLE TO 2323 01:59:27,520 --> 01:59:30,400 SPLIN HE CAN TOM EYES THESE NON 2324 01:59:30,400 --> 01:59:31,040 PRAIRIE HUMAN IT'S A. 2325 01:59:31,040 --> 01:59:36,800 PRACTICE. 2326 01:59:36,800 --> 01:59:42,960 >> DO YOU AT THIS NOTICE THE 2327 01:59:42,960 --> 01:59:43,200 SPLEEN. 2328 01:59:43,200 --> 01:59:47,480 >> THEY DEVELOP A SPLEENAMOGLIA 2329 01:59:47,480 --> 01:59:51,360 AND I THINK IT'S THE IDEA. 2330 01:59:51,360 --> 01:59:52,640 PRIOR TO INFECTION. 2331 01:59:52,640 --> 01:59:57,080 >> THANK YOU. 2332 01:59:57,080 --> 02:00:07,520 >> WAS THAT RELATED IN THE 2333 02:00:08,120 --> 02:00:08,320 MACAQUES? 2334 02:00:08,320 --> 02:00:12,440 >> YEAH, THE ANIMALS THIS 2335 02:00:12,440 --> 02:00:14,680 UNPROTECTED BY IVBCG HAD ONE 2336 02:00:14,680 --> 02:00:17,040 THING IN COMMON, THEY WERE POOR 2337 02:00:17,040 --> 02:00:19,720 VIRAL CONTROLLER NUMBER ONE AND 2338 02:00:19,720 --> 02:00:22,120 NUMBER TWO, THEY INTENDED TO 2339 02:00:22,120 --> 02:00:32,680 HAVE FEWER -- A MORE DRAMATIC 2340 02:00:36,480 --> 02:00:37,360 CD4 DEPLETION. 2341 02:00:37,360 --> 02:00:41,280 WE KNOW THAT WITH ART THERAPY 2342 02:00:41,280 --> 02:00:42,520 THOSE THINGS ARE CORRECTED SO I 2343 02:00:42,520 --> 02:00:45,880 THINK CERTAINLY IN HIV CONTEXT 2344 02:00:45,880 --> 02:00:48,040 ART WOULD BE A REALLY IMPORTANT 2345 02:00:48,040 --> 02:00:54,280 COMPONENT OF THIS. 2346 02:00:54,280 --> 02:01:04,120 [OFF MIC] 2347 02:01:04,120 --> 02:01:04,240 THE 2348 02:01:08,160 --> 02:01:18,280 [OFF MIC] 2349 02:01:24,160 --> 02:01:25,800 >> ABSOLUTELY, IT'S A REALLY 2350 02:01:25,800 --> 02:01:27,000 GOOD QUESTION, IT'S TRUE THAT 2351 02:01:27,000 --> 02:01:29,800 THE AEROSOL DELIVERED BCG JUST 2352 02:01:29,800 --> 02:01:30,840 DOESN'T PROTECT WELL. 2353 02:01:30,840 --> 02:01:31,800 OF COURSE IT'S GET TO GO THE 2354 02:01:31,800 --> 02:01:33,680 LUNG BY A DIFFERENT MECHANISM, 2355 02:01:33,680 --> 02:01:36,560 RIGHT, IT'S COMING IN FROM THE 2356 02:01:36,560 --> 02:01:38,480 AIRWAYS RATHER THAN SOME PLACE 2357 02:01:38,480 --> 02:01:42,280 ELSE AND THE IMMUNE CELLS ARE 2358 02:01:42,280 --> 02:01:47,880 ENTERING THE LUNG PRANK FROM THE 2359 02:01:47,880 --> 02:01:48,520 VAAS CUE LATOUR. 2360 02:01:48,520 --> 02:01:50,320 IF WE CAN TEASE OUT THE 2361 02:01:50,320 --> 02:01:51,480 DIFFERENCES BETWEEN THOSE TWO 2362 02:01:51,480 --> 02:01:54,760 ROUTES I THINK IT WOULD BE 2363 02:01:54,760 --> 02:01:55,440 REALLY CONSTRUCTIVE. 2364 02:01:55,440 --> 02:02:05,640 [OFF MIC] 2365 02:02:08,280 --> 02:02:12,000 >> I WAS REALLY HAPPY TO 2366 02:02:12,000 --> 02:02:13,040 RECAPITULATE THE FINDINGS 2367 02:02:13,040 --> 02:02:15,240 BETWEEN JOB AND JOANNE IN A 2368 02:02:15,240 --> 02:02:17,160 MODEL RATHER THAN REHSUS VERY 2369 02:02:17,160 --> 02:02:17,360 GOOD. 2370 02:02:17,360 --> 02:02:18,200 >> THANK YOU, ALL. 2371 02:02:18,200 --> 02:02:23,920 [APPLAUSE] 2372 02:02:23,920 --> 02:02:25,400 >> WE'RE GOING TO CHANGE THE 2373 02:02:25,400 --> 02:02:29,680 TOPIC NOW SO OUR NEXT SPEAKER IS 2374 02:02:29,680 --> 02:02:32,320 DIEGO COSTA FROM UNIVERSITY OF 2375 02:02:32,320 --> 02:02:33,840 SAO PAULO. 2376 02:02:42,840 --> 02:02:45,200 >> I WOULD LIKE TO SAY IT'S A 2377 02:02:45,200 --> 02:02:46,840 HUGE HONOR TO BE HERE PRESENTING 2378 02:02:46,840 --> 02:02:49,120 MY WORK AND ALSO TO THANK 2379 02:02:49,120 --> 02:02:53,520 DRAGANA AND DAN FOR MAKING THIS 2380 02:02:53,520 --> 02:03:04,040 BOTH ABLE SO I'M GOING TO SHOW 2381 02:03:04,480 --> 02:03:05,440 YOU THE DEVELOPMENT OF THE WORK 2382 02:03:05,440 --> 02:03:08,120 I'VE DONE AS A TIME AS A TRAINEE 2383 02:03:08,120 --> 02:03:09,320 FOR ESTABLISHING THE RESEARCH 2384 02:03:09,320 --> 02:03:10,480 PROGRAM THAT I'M START TO GO 2385 02:03:10,480 --> 02:03:15,120 DEVELOP IN BRAZIL RIGHT NOW. 2386 02:03:15,120 --> 02:03:16,440 I HAVE WORKED WITH ALAN AND I 2387 02:03:16,440 --> 02:03:17,520 CONTINUE TO DO THAT AND I'M 2388 02:03:17,520 --> 02:03:20,440 GOING TO SHOW YOU DATA FOR TB 2389 02:03:20,440 --> 02:03:25,360 AND TARGETING HOMEOSTASIS AND 2390 02:03:25,360 --> 02:03:27,680 LUNG INFLAMMATION SO IT WAS 2391 02:03:27,680 --> 02:03:28,640 INTRODUCED HERE A MAJOR 2392 02:03:28,640 --> 02:03:29,920 PUBLIC-HEALTH PROBLEM AROUND THE 2393 02:03:29,920 --> 02:03:33,640 WORLD AND SO JUST LAST YEAR, 2394 02:03:33,640 --> 02:03:34,200 AROUND 10 MILLION PEOPLE HAD 2395 02:03:34,200 --> 02:03:35,960 BEEN INFECTED AND HALF MILLION 2396 02:03:35,960 --> 02:03:38,200 OF THOSE PEOPLE WITH DRUG 2397 02:03:38,200 --> 02:03:40,320 RESISTANT BAGS AND 1.5 MILLION 2398 02:03:40,320 --> 02:03:43,000 PEOPLE DIED FROM THE DISEASE AND 2399 02:03:43,000 --> 02:03:44,440 SO WHY DID WE CONTINUE TO BE 2400 02:03:44,440 --> 02:03:46,000 SUCH A MAJOR PROBLEM IF THERE'S 2401 02:03:46,000 --> 02:03:49,520 A VACCINE FOR IT AND A TREATMENT 2402 02:03:49,520 --> 02:03:51,760 AND THE VACCINE IS NOT THAT 2403 02:03:51,760 --> 02:03:56,080 EFFECTIVE IN CONTAINING 2404 02:03:56,080 --> 02:03:57,920 PREVENTING TUBERCULOSIS AND THE 2405 02:03:57,920 --> 02:03:59,800 TREATMENT, THE REGULAR 2406 02:03:59,800 --> 02:04:01,720 TREATMENT, THE DIRECT TREATMENT 2407 02:04:01,720 --> 02:04:04,680 SHORT COURSE LASTS FOR SIX 2408 02:04:04,680 --> 02:04:05,840 MONTHS WHERE FOUR DIFFERENT 2409 02:04:05,840 --> 02:04:09,080 DRUGS ARE ADMINISTERED SO THE 2410 02:04:09,080 --> 02:04:10,280 PATIENTS PRESENT SEVERAL SIDE 2411 02:04:10,280 --> 02:04:13,280 EFFECTS AND A LOT OF THEM DO NOT 2412 02:04:13,280 --> 02:04:17,640 COMPLY WITH THE FULL TREATMENT 2413 02:04:17,640 --> 02:04:19,600 IN THAT FAVORS THE RELAPSE FOR 2414 02:04:19,600 --> 02:04:20,600 THE DISEASE AND SELECTION OF 2415 02:04:20,600 --> 02:04:25,320 DRUG ROW RESISTANT TREATMENT SOS 2416 02:04:25,320 --> 02:04:27,960 AN URGENT NEED THAT ELIMINATED 2417 02:04:27,960 --> 02:04:29,320 THE TREATMENT FOR RAPIDLY AND 2418 02:04:29,320 --> 02:04:33,000 ALSO THEY DO NOT RELY ON 2419 02:04:33,000 --> 02:04:37,440 ANTIBIOTICS AND IN THAT SENSE, 2420 02:04:37,440 --> 02:04:39,960 WE COME TO THE THERAPY AS A 2421 02:04:39,960 --> 02:04:40,960 STRATEGY BECAUSE THEY TARGET 2422 02:04:40,960 --> 02:04:42,880 HOST BIOLOGICAL FACTORS THAT CAN 2423 02:04:42,880 --> 02:04:49,480 FAVOR THE DISEASE DEVELOPMENT 2424 02:04:49,480 --> 02:04:52,600 AND AND HOW DOES HOST IMMUNITY 2425 02:04:52,600 --> 02:04:54,680 AND WORK AND IT'S A BACTERIAL 2426 02:04:54,680 --> 02:04:56,080 THAT IS TRANCE MUTED THROUGH THE 2427 02:04:56,080 --> 02:04:58,840 AIR SO IT EFFECTS MAINLY THE 2428 02:04:58,840 --> 02:05:00,880 LUNGS AND IN THE LUNGS, IT'S 2429 02:05:00,880 --> 02:05:10,840 FIRST ENCOUNTERING THEY ARE THE 2430 02:05:10,840 --> 02:05:17,520 MAIN CELLS BY TB AND TB HAS 2431 02:05:17,520 --> 02:05:21,840 DELAND THEYARE PART ANT CYTOKINE 2432 02:05:21,840 --> 02:05:23,320 HOST COULD CONTAIN THE DISEASE 2433 02:05:23,320 --> 02:05:25,920 AND THESE MACROPHAGES WILL PHAGO 2434 02:05:25,920 --> 02:05:29,680 SIGHT THOSE BACTERIA AND PHAGO 2435 02:05:29,680 --> 02:05:31,960 SOME WILL OCCUR AND THE FUSION 2436 02:05:31,960 --> 02:05:34,080 AND THIS CAN LEAD TO THE 2437 02:05:34,080 --> 02:05:35,400 BACTERIA AND IF THEY'RE NOT 2438 02:05:35,400 --> 02:05:38,280 KILLED AND LATER ON AND TH1 2439 02:05:38,280 --> 02:05:41,200 IMMUNITY WILL KICK IN WITH THE 2440 02:05:41,200 --> 02:05:42,320 PREDICTION AND IT'S IMPORTANT 2441 02:05:42,320 --> 02:05:46,360 FOR ACTIVATING THE EXPRESSION OF 2442 02:05:46,360 --> 02:05:53,680 INOS AND OX SA DAZING MACROPHAGE 2443 02:05:53,680 --> 02:05:57,320 AND THEY'RE HARMFUL BUT EVEN SO, 2444 02:05:57,320 --> 02:05:59,720 ALL ALONG THE EVOLUTION, THE CO 2445 02:05:59,720 --> 02:06:02,280 EVOLUTION WITH THE HUMAN SPECIES 2446 02:06:02,280 --> 02:06:04,400 AND THERE ARE WAYS TO SUBVERT 2447 02:06:04,400 --> 02:06:06,840 THIS IMMUNO RESPONSE AND IT CAN 2448 02:06:06,840 --> 02:06:11,120 SURVIVE THIS STRETCH FROM THE 2449 02:06:11,120 --> 02:06:15,320 MACROPHAGE ONE OF THE THINGS IS 2450 02:06:15,320 --> 02:06:18,560 THEY CAN TRIGGER A MASSIVE 2451 02:06:18,560 --> 02:06:20,360 PRODUCTION, ESCAPE THIS TRIGGERS 2452 02:06:20,360 --> 02:06:26,600 A MASSIVE PREDICTION AND WHEN A 2453 02:06:26,600 --> 02:06:29,640 CHRONIC DEVELOP WE CAN HAVE A 2454 02:06:29,640 --> 02:06:31,440 PROTECTIVE CYTOKINES AND LEAD TO 2455 02:06:31,440 --> 02:06:34,320 GO A MASSIVE PREDICTION AND THIS 2456 02:06:34,320 --> 02:06:37,080 WILL END UP TRIGGERING CELL 2457 02:06:37,080 --> 02:06:40,840 DEATH OF THE MACROPHAGES BECAUSE 2458 02:06:40,840 --> 02:06:43,000 THEY WILL TRIGGER TISSUE DAMAGE 2459 02:06:43,000 --> 02:06:49,680 AND THE BACTERIA AND SO THE THEY 2460 02:06:49,680 --> 02:06:51,760 SHOW DESTRUCTION IS WELL 2461 02:06:51,760 --> 02:06:53,200 CHARACTERIZED IN THE GRANULOMA 2462 02:06:53,200 --> 02:06:58,160 SO THEY HAVE A MASSIVE CASE OF 2463 02:06:58,160 --> 02:06:59,600 NECROSIS WHICH WILL LEAD TO THE 2464 02:06:59,600 --> 02:07:02,520 FORMATION OF THIS CAVITIES AND 2465 02:07:02,520 --> 02:07:05,120 THIS CAN HELP TO SPREAD BACTERIA 2466 02:07:05,120 --> 02:07:09,080 TO TRANSMIT THE BACTERIA SO 2467 02:07:09,080 --> 02:07:11,000 CONSIDERING THAT THE IMMUNE 2468 02:07:11,000 --> 02:07:12,680 RESPONSE IS IMPORTANT TO CONTAIN 2469 02:07:12,680 --> 02:07:14,880 THE BACTERIA AND ALSO TRIGGER 2470 02:07:14,880 --> 02:07:16,640 TISSUE DESTRUCTION THE MAIN 2471 02:07:16,640 --> 02:07:18,720 STRATEGIES FOR DEVELOPMENT OF 2472 02:07:18,720 --> 02:07:20,720 HOST DISTRICTED THERAPIST FOR TB 2473 02:07:20,720 --> 02:07:22,680 RELY ON INCREASING THIS IMMUNITY 2474 02:07:22,680 --> 02:07:24,560 SO WE CAN GET RID OF THE 2475 02:07:24,560 --> 02:07:26,960 BACTERIA MORE EASILY OR USE 2476 02:07:26,960 --> 02:07:28,640 ANTIINFLAMMATORY STRATEGIES SO 2477 02:07:28,640 --> 02:07:32,360 WE CAN CALM DOWN THIS 2478 02:07:32,360 --> 02:07:33,920 INFLAMMATORY RESPONSE PRESERVING 2479 02:07:33,920 --> 02:07:39,080 TISSUE AND DISRUPT GRANULOMA SO 2480 02:07:39,080 --> 02:07:40,040 THEY PENETRATE INTO THE CORE 2481 02:07:40,040 --> 02:07:42,720 WHERE THE EFFECTED CELLS ARE. 2482 02:07:42,720 --> 02:07:44,840 SO, WHEN I WAS IN THE LAB, WE 2483 02:07:44,840 --> 02:07:48,280 WERE TRYING TO TARGET FOR HOST 2484 02:07:48,280 --> 02:07:51,200 DIRECTED THERAPIES SO HO1 IS 2485 02:07:51,200 --> 02:07:54,280 ANEN TIME THAT CATALYZES THE 2486 02:07:54,280 --> 02:08:02,120 DEROGATION AND RELEASING AMOUNTS 2487 02:08:02,120 --> 02:08:03,000 OF CARBON MONOXIDE AND BILLY VER 2488 02:08:03,000 --> 02:08:04,920 DIN AND IT WAS A STUDY THAT WAS 2489 02:08:04,920 --> 02:08:06,760 DEVELOPED BY BRUNO WHEN HE WAS 2490 02:08:06,760 --> 02:08:16,960 IN THE LAB. 2491 02:08:23,280 --> 02:08:26,280 THIS IS HUMANS SUCCESSFUL 2492 02:08:26,280 --> 02:08:28,080 TREATMENT CURSE THERE'S A 2493 02:08:28,080 --> 02:08:29,640 EXPRESSION OF HO-1. 2494 02:08:29,640 --> 02:08:32,040 IT'S A GOOD BIOMARKER BUT WE 2495 02:08:32,040 --> 02:08:35,160 WERE INTERESTED IN THE ROLE OF 2496 02:08:35,160 --> 02:08:39,320 IT AND WE USED THESE INHIBITOR 2497 02:08:39,320 --> 02:08:43,280 OF HO-1 THAT IS ALSO CALLED 2498 02:08:43,280 --> 02:08:46,800 LIPIDS YOU CAN SEE HERE IT'S AN 2499 02:08:46,800 --> 02:08:50,520 MOLECULE OF HEME AND INSTEAD OF 2500 02:08:50,520 --> 02:08:54,720 RAILRRIN FROM THE SO WHEN WE IND 2501 02:08:54,720 --> 02:08:57,600 THE MICE WITH A LOW DOSE OF TB 2502 02:08:57,600 --> 02:08:59,600 AND WAITED FOR THE INFECTION TO 2503 02:08:59,600 --> 02:09:04,240 ROW ESTAREESTABLISH AND ONLY TWS 2504 02:09:04,240 --> 02:09:06,240 OF TREATMENT LED TO A MASSIVE 2505 02:09:06,240 --> 02:09:08,560 REDUCTION OF THE BACTERIAL LOAD 2506 02:09:08,560 --> 02:09:09,880 IN THE LUNGS AND NOT JUST THAT 2507 02:09:09,880 --> 02:09:12,040 WHEN YOU COMBINE THIS WITH THE 2508 02:09:12,040 --> 02:09:17,360 REAGAN ANTIBIOTICS AND WE FOLLOE 2509 02:09:17,360 --> 02:09:18,600 MICE IN THE LONG-TERM YOU CAN 2510 02:09:18,600 --> 02:09:24,280 SEE IN THE GROWN L GREEN LINE AS 2511 02:09:24,280 --> 02:09:26,240 COMPARED TO THE RED LINE THAT 2512 02:09:26,240 --> 02:09:27,760 ANTIBIOTICS ALONE SO IN FOUR 2513 02:09:27,760 --> 02:09:29,320 MONTHS IT COULD CLEAR THE 2514 02:09:29,320 --> 02:09:30,720 BACTERIA FROM THE LUNGS AND 2515 02:09:30,720 --> 02:09:34,520 TREATED ONLY WITH ANTIBIOTICS IT 2516 02:09:34,520 --> 02:09:36,600 SAKES SIX MONTHS SO WE SAVE TWO 2517 02:09:36,600 --> 02:09:37,280 MONTHS OF TREATMENT. 2518 02:09:37,280 --> 02:09:40,000 ONE INTERESTING THING THAT WE 2519 02:09:40,000 --> 02:09:41,720 FOUND WHEN WE STARTED TO TREAT 2520 02:09:41,720 --> 02:09:44,080 THESE MICE FROM DAY ZERO IS THAT 2521 02:09:44,080 --> 02:09:45,800 DURING THIS FIRST THREE WEEKS, 2522 02:09:45,800 --> 02:09:48,080 WE HAD NO CHANGE IN BACTERIAL 2523 02:09:48,080 --> 02:09:48,280 LOAD. 2524 02:09:48,280 --> 02:09:51,440 YOU COULD ONLY WORK LATER ON SO 2525 02:09:51,440 --> 02:09:53,440 THEM IF WE HAVE SIX WEEKS POST 2526 02:09:53,440 --> 02:09:55,000 INFECTION WE COULD FIND THE 2527 02:09:55,000 --> 02:09:56,960 BACTERIA LOAD REDUCTION AND ONE 2528 02:09:56,960 --> 02:09:58,680 THING THAT IS VERY CLAR TERRIZED 2529 02:09:58,680 --> 02:10:00,680 ALREADY IN TB IS IN THE THIRD 2530 02:10:00,680 --> 02:10:03,840 WEEK OF INFECTION, IT'S WHEN THE 2531 02:10:03,840 --> 02:10:05,440 T-CELL RESPONSE KICKS IN SO HERE 2532 02:10:05,440 --> 02:10:09,200 WE HAVE THIS MASSIVE INCREASE IN 2533 02:10:09,200 --> 02:10:11,920 PRODUCTION AND WE CAN SEE THE 2534 02:10:11,920 --> 02:10:13,560 EXPRESSION SO WE WANTED TO KNOW 2535 02:10:13,560 --> 02:10:17,880 IF THESE EFFECT WOULD BE THE T 2536 02:10:17,880 --> 02:10:20,120 CELLS SO AND THEY'RE KNOCK OFF 2537 02:10:20,120 --> 02:10:22,120 MICE AND TREATED THEM AND WE CAN 2538 02:10:22,120 --> 02:10:32,680 SEE HERE A NICE REDUCTION AND WE 2539 02:10:38,440 --> 02:10:41,800 HAVE NO REDUCTION IN GAMMA AND 2540 02:10:41,800 --> 02:10:43,920 SO THIS SHOWS THAT THE BACTERIAL 2541 02:10:43,920 --> 02:10:48,360 LOAD RESULTING FROM THE HO-1 IS 2542 02:10:48,360 --> 02:10:52,240 THE IMMUNE RESPONSE AND MORE 2543 02:10:52,240 --> 02:10:55,320 SPECIFICALLY IN THE REDEX OF 2544 02:10:55,320 --> 02:10:57,720 EXPRESSION OF IONS SO WE ALSO 2545 02:10:57,720 --> 02:10:59,960 MADE A NICE CHARACTERIZATION OF 2546 02:10:59,960 --> 02:11:01,880 WHICH CELLS EXPRESSED HO1 IN THE 2547 02:11:01,880 --> 02:11:03,480 LONG INFECTED MICE AND I'M NOT 2548 02:11:03,480 --> 02:11:04,920 SHOWING THE DATA HERE BECAUSE OF 2549 02:11:04,920 --> 02:11:07,320 LACK OF TIME BUT BASICALLY WE 2550 02:11:07,320 --> 02:11:09,200 FOUND THAT THIS CELLS WHERE WE 2551 02:11:09,200 --> 02:11:11,760 HAD THE LARGEST INCREASE IN HO1 2552 02:11:11,760 --> 02:11:13,720 EXPRESSION WERE INFLAMMATORY 2553 02:11:13,720 --> 02:11:15,000 MACROPHAGES THAT WERE RECRUITED 2554 02:11:15,000 --> 02:11:18,240 FOR MONOCYTES AND THE LUNGS SO, 2555 02:11:18,240 --> 02:11:21,520 WE USED AN IN VITRO MODEL OF THE 2556 02:11:21,520 --> 02:11:23,520 MACROPHAGES TO ANALYZE WHAT WERE 2557 02:11:23,520 --> 02:11:30,520 THE MECHANISMS BEHIND THIS 2558 02:11:30,520 --> 02:11:32,400 INQUIZ ITS EFFECT WE WERE SERVE 2559 02:11:32,400 --> 02:11:42,880 WHAT IS WE BROUGHT THE AND AS 2560 02:12:02,480 --> 02:12:06,680 EXPECTED, WE SEE JUST MEASURING 2561 02:12:06,680 --> 02:12:08,360 THE EXPRESSION AND IT'S TREATED 2562 02:12:08,360 --> 02:12:10,200 WITH GAMMA IN THE PRESENCE OR 2563 02:12:10,200 --> 02:12:12,800 ABSENCE OF THE INHIBITOR, BLOCK 2564 02:12:12,800 --> 02:12:15,080 H1 WE HAVE AN INCREASED 2565 02:12:15,080 --> 02:12:18,520 EXPRESSION OF FOLLOWED BY THE 2566 02:12:18,520 --> 02:12:26,440 INCREASED PRODUCTION AND SO IN 2567 02:12:26,440 --> 02:12:29,560 THE BLOCK HO-1 THEY HAVE 2568 02:12:29,560 --> 02:12:31,120 ENHANCED EXPRESSION IN RESPONSE 2569 02:12:31,120 --> 02:12:36,120 TO GAMMA ACTIVATION AND SO SINCE 2570 02:12:36,120 --> 02:12:40,960 HO-1, WORKS BY DEGRADING HIM, 2571 02:12:40,960 --> 02:12:42,240 RELEASING CARBON MONOXIDE IN WE 2572 02:12:42,240 --> 02:12:46,280 WERE INTERESTED IN SEEING WHICH 2573 02:12:46,280 --> 02:12:47,880 OF THESE PRODUCTS WOULD BE SO WE 2574 02:12:47,880 --> 02:12:49,560 REPEATED THE SAME APPROACH AS WE 2575 02:12:49,560 --> 02:12:52,760 CAN SEE HERE WE HAVE GAMMA AND 2576 02:12:52,760 --> 02:12:54,400 THE EFFECT WITH GAMMA PLUS 2577 02:12:54,400 --> 02:12:58,400 INHIBITOR AND WE GAVE BACK 2578 02:12:58,400 --> 02:12:59,160 CARBON MONOXIDE OR IRON AND AS 2579 02:12:59,160 --> 02:13:02,200 YOU CAN SEE HERE, CARBON 2580 02:13:02,200 --> 02:13:04,000 MONOXIDE MAY BE THAT RESULT IN 2581 02:13:04,000 --> 02:13:09,240 ANY CHANGE AND BILIVERDIN AND WE 2582 02:13:09,240 --> 02:13:15,760 REVERSED THE EFFECT AND SO THEY 2583 02:13:15,760 --> 02:13:19,000 WERE ACTIVATED WITH GAMMA IN THE 2584 02:13:19,000 --> 02:13:21,000 PRESENCE AND THE INHIBITOR AS 2585 02:13:21,000 --> 02:13:22,720 YOU CAN SEE HERE, THIS INCREASE 2586 02:13:22,720 --> 02:13:24,920 THE EXPRESSION IN THE PRESENCE 2587 02:13:24,920 --> 02:13:28,320 OF H-01 INHIBITOR IS REVERTED IF 2588 02:13:28,320 --> 02:13:30,520 WE HAD IRON BACK TO THE CELLS 2589 02:13:30,520 --> 02:13:32,200 AND WHEN WE DO THE OPPOSITE 2590 02:13:32,200 --> 02:13:34,880 APPROACH WE WILL INCUBATE THE 2591 02:13:34,880 --> 02:13:36,520 CELLS AND WE HAVE A MASSIVE 2592 02:13:36,520 --> 02:13:38,800 INCREASE IN THE EXPRESSION OF 2593 02:13:38,800 --> 02:13:40,680 THE VIRUS SO THIS SHOWS US THAT 2594 02:13:40,680 --> 02:13:43,440 THE IRON THAT IS BEING RELEASED 2595 02:13:43,440 --> 02:13:46,480 BY ACTIVITY ACTUALLY IMPAIRS 2596 02:13:46,480 --> 02:13:50,880 THAT EXPRESSION RESULTING FROM 2597 02:13:50,880 --> 02:13:52,560 IS THE EFFECTIVE TEE OF THE 2598 02:13:52,560 --> 02:13:55,080 EFFECTED MACROPHAGES AND SO WITH 2599 02:13:55,080 --> 02:13:57,960 THESE WE WANTED TO FINALLY PROVE 2600 02:13:57,960 --> 02:14:03,120 THAT IN FACT THE TREATMENT WITH 2601 02:14:03,120 --> 02:14:07,320 H-O1 THE IRON LEVELS OF THE CELL 2602 02:14:07,320 --> 02:14:14,840 SO WE DID WITH DEBATED CELLS 2603 02:14:14,840 --> 02:14:17,280 RESULTING A REDUCTION IN THE 2604 02:14:17,280 --> 02:14:19,720 INTER CELL LEVELS AND IN VIVO AS 2605 02:14:19,720 --> 02:14:23,120 WELL WE ISOLATED LUNGS FROM 2606 02:14:23,120 --> 02:14:24,800 TREATED MICE OR SMMP TREATED 2607 02:14:24,800 --> 02:14:31,320 MICE WE CAN SEE HERE THIS BROWN 2608 02:14:31,320 --> 02:14:33,120 SPOTS WHERE SUSTAINED AND SO WE 2609 02:14:33,120 --> 02:14:38,080 SEE A LOT OF IRON IN THE LUNG OF 2610 02:14:38,080 --> 02:14:41,360 ANIMALS INFECTED WITH TB BUT NOT 2611 02:14:41,360 --> 02:14:42,840 TREAT SOD THERE'S IRON 2612 02:14:42,840 --> 02:14:53,400 COMBINATION IN CELLS AND WE HAVE 2613 02:14:54,080 --> 02:15:03,880 A DECREASING AND INFECTED ITSELF 2614 02:15:03,880 --> 02:15:08,280 AND WE SET UP THE IDEA OF HOW 2615 02:15:08,280 --> 02:15:12,200 THE MODULATION OF HOMEOSTASIS 2616 02:15:12,200 --> 02:15:13,960 CAN BE MAUD LATING THE RESPONSE 2617 02:15:13,960 --> 02:15:19,360 OF MACROPHAGES AND CAN THIS BE 2618 02:15:19,360 --> 02:15:20,600 TARGETED FOR THE DEVELOPMENT OF 2619 02:15:20,600 --> 02:15:23,000 NEW THERAPY SO WITH THAT, I 2620 02:15:23,000 --> 02:15:25,920 WROTE A GRANT APPLICATION FOR IN 2621 02:15:25,920 --> 02:15:29,040 BRAZIL AND SO I GOT THIS CALLED 2622 02:15:29,040 --> 02:15:30,240 YOUNG INVESTIGATOR GRANT AND I 2623 02:15:30,240 --> 02:15:32,720 WAS ABLE TO MOVE BACK TO BRAZIL 2624 02:15:32,720 --> 02:15:36,160 MORE SPECIFICALLY I WENT BACK TO 2625 02:15:36,160 --> 02:15:37,960 SAO PAULO AND MORE SPECIFICALLY 2626 02:15:37,960 --> 02:15:41,120 I WENT BACK TO WHERE I DID MY 2627 02:15:41,120 --> 02:15:42,920 PH.D IN UNIVERSITY OF SAO PAULO 2628 02:15:42,920 --> 02:15:46,720 SO HERE IS A PICTURE. 2629 02:15:46,720 --> 02:15:51,040 HERE IS A PICTURE OF THE MEDICAL 2630 02:15:51,040 --> 02:15:52,920 SCHOOL IN THE UNIVERSITY OF SAO 2631 02:15:52,920 --> 02:15:54,600 PAULO AND THIS IS A BEAUTIFUL 2632 02:15:54,600 --> 02:15:56,000 PICTURE OF THIS BUILDING HERE 2633 02:15:56,000 --> 02:16:01,920 THAT IS WHERE THE BASIC SIGNS 2634 02:16:01,920 --> 02:16:02,880 LABS ARE LOCATED BECAUSE HERE IS 2635 02:16:02,880 --> 02:16:03,840 THE HOSPITAL. 2636 02:16:03,840 --> 02:16:07,040 OUR LAB IS IN THIS BUILDING AND 2637 02:16:07,040 --> 02:16:10,360 THERE ARE JOINED ABOUT THE GROUP 2638 02:16:10,360 --> 02:16:11,920 AND MY GROUP WITH THEY WERE 2639 02:16:11,920 --> 02:16:13,400 PATIO OF THAT BUILDING AND WE 2640 02:16:13,400 --> 02:16:18,520 HAVE A NICE CAFETERIA HERE SO 2641 02:16:18,520 --> 02:16:21,600 SHE HELPED ME TO SET UP THIS 2642 02:16:21,600 --> 02:16:24,840 PROGRAM THERE AND HER HELP WAS 2643 02:16:24,840 --> 02:16:26,200 CRITICAL FOR ME TO BE ABLE TO 2644 02:16:26,200 --> 02:16:27,600 DEVELOP IT THERE AND ACTUALLY 2645 02:16:27,600 --> 02:16:30,280 I'M START TO GO DEVELOP IT AND 2646 02:16:30,280 --> 02:16:32,040 HERE I HAVE A PICTURE OF MY OWN 2647 02:16:32,040 --> 02:16:33,560 GROUP SO THOSE ARE MY STUDENTS 2648 02:16:33,560 --> 02:16:36,520 WITH ME AND THE INTEREST O 2649 02:16:36,520 --> 02:16:38,280 ENTRANCE OF THAT BUILDING AND AS 2650 02:16:38,280 --> 02:16:39,080 I MENTIONED TO YOU I'M 2651 02:16:39,080 --> 02:16:43,280 INTERESTED IN HOW IRON CAN BE 2652 02:16:43,280 --> 02:16:44,560 MODULATING THIS I'M UNION 2653 02:16:44,560 --> 02:16:46,840 RESPONSE TO TB SO PARTICULARLY 2654 02:16:46,840 --> 02:16:49,120 IN MACROPHAGES, WHICH ARE THE 2655 02:16:49,120 --> 02:16:52,880 CELLS AFFECTED BY TB WE WANT TO 2656 02:16:52,880 --> 02:16:55,560 ADDRESS HOW IRON METABOLISM IS 2657 02:16:55,560 --> 02:16:58,360 WORKING IN TB INFECTION SO 2658 02:16:58,360 --> 02:16:59,800 MACROPHAGES CAN AK PAIR IRON 2659 02:16:59,800 --> 02:17:02,560 THROUGH MULTIPLE WAYS SO 2660 02:17:02,560 --> 02:17:04,040 ESPECIALLY BY RED BLOOD CELLS 2661 02:17:04,040 --> 02:17:08,880 AND THEY CAN ALSO DEGRADE HEMO 2662 02:17:08,880 --> 02:17:11,520 PROTEINS AND GET HEMOGLOBIN FROM 2663 02:17:11,520 --> 02:17:14,160 THE CIRCULATION AND THIS IRON 2664 02:17:14,160 --> 02:17:16,840 AND ALSO ACQUIRE IRON DIRECT 2665 02:17:16,840 --> 02:17:17,760 LIEU THROUGH OTHER TRANSMITTERS 2666 02:17:17,760 --> 02:17:19,920 BUT THEY CAN ONLY GET RID OF 2667 02:17:19,920 --> 02:17:23,440 IRON BY THESE TRANSPORTERS HERE 2668 02:17:23,440 --> 02:17:26,040 THAT IS FERRO FOR TIN. 2669 02:17:26,040 --> 02:17:28,040 WE GOT INTERESTED IN THE 2670 02:17:28,040 --> 02:17:29,000 MODULATION BECAUSE THE 2671 02:17:29,000 --> 02:17:34,000 REGULATION OF THE EXPRESSION OF 2672 02:17:34,000 --> 02:17:44,280 FER OWE FOR TIN. 2673 02:17:58,960 --> 02:18:01,680 THE PRODUCED BY IRON AND THE SER 2674 02:18:01,680 --> 02:18:03,360 OWN BUT IT CAN BE PRODUCED BY 2675 02:18:03,360 --> 02:18:05,400 MACROPHAGES IN RESPONSE TO 2676 02:18:05,400 --> 02:18:08,600 INFLAMMATORY SUCH AS IL-11, IL-6 2677 02:18:08,600 --> 02:18:14,320 AND RECEPTORS 4 SO THESE HAVE 2678 02:18:14,320 --> 02:18:15,600 PRODUCTION WE WILL FERROPORTIN 2679 02:18:15,600 --> 02:18:17,640 AND ON THE OTHER SIDE TRYING 2680 02:18:17,640 --> 02:18:19,800 ORING OF RECEPTORS 2 CAN LEAD TO 2681 02:18:19,800 --> 02:18:25,440 DOWN REGULATION OF FERROPORTIN 2682 02:18:25,440 --> 02:18:28,320 TRANSLATION SO THESE ARE ALL 2683 02:18:28,320 --> 02:18:29,560 ACTIVATED AND WE ARE INTERESTING 2684 02:18:29,560 --> 02:18:32,120 KNOW THE ROLE OF FERROPORTIN 2685 02:18:32,120 --> 02:18:33,880 DURING THE TB INFECTION AND HOW 2686 02:18:33,880 --> 02:18:36,000 DOES IT WORK IN THE MODULATION 2687 02:18:36,000 --> 02:18:38,200 OF HOMEOSTASIS AND MODULATION IN 2688 02:18:38,200 --> 02:18:39,200 IMMUNE RESPONSE SO THIS IS A 2689 02:18:39,200 --> 02:18:40,440 WORK IN PROGRESS AND I'M GOING 2690 02:18:40,440 --> 02:18:41,880 TO SHOW YOU SOME VERY 2691 02:18:41,880 --> 02:18:45,200 PRELIMINARY DETAILS THAT I'M 2692 02:18:45,200 --> 02:18:47,280 START TO GO GET IN THE LAB WITH 2693 02:18:47,280 --> 02:18:48,000 MY STUDENTS. 2694 02:18:48,000 --> 02:18:49,440 MY MASTER STUDENT IS WORKING ON 2695 02:18:49,440 --> 02:18:53,120 THIS PROJECT SO SHE JUST 2696 02:18:53,120 --> 02:18:56,080 MEASURED H-01 EXPRESSION AND AS 2697 02:18:56,080 --> 02:18:58,560 YOU CAN SEE HERE WHY H-01 GOES 2698 02:18:58,560 --> 02:19:02,760 UP AND FERROPORTIN GOES DOWN SO 2699 02:19:02,760 --> 02:19:04,120 THIS IS FLAVORING THE LUNGS SO 2700 02:19:04,120 --> 02:19:07,240 INTERESTINGLY, THIS IS THE 2701 02:19:07,240 --> 02:19:10,360 EXPRESSION OF HELP SEW DIN AND 2702 02:19:10,360 --> 02:19:12,840 IT GOES DOWN SO THE DOWN 2703 02:19:12,840 --> 02:19:14,240 REGULATION OF FERROPORTIN IN THE 2704 02:19:14,240 --> 02:19:19,120 CELLS MAY NOT BE RELATED TO 2705 02:19:19,120 --> 02:19:22,120 HEPSODINE ITSELF BUT AS WELL AS 2706 02:19:22,120 --> 02:19:25,600 TALL 1 AND 6 ARE BEING WITH ON 2707 02:19:25,600 --> 02:19:27,920 GOING INFECTION SO WE BELIEVE 2708 02:19:27,920 --> 02:19:30,160 THAT MAYBE THIS DOWN REGULATION 2709 02:19:30,160 --> 02:19:38,040 IS MEDIATED BY REACC RETO BE ANE 2710 02:19:38,040 --> 02:19:40,360 DID MODEL OF INFECTION IN 2711 02:19:40,360 --> 02:19:42,120 MACROPHAGES SO WE ASKED THE 2712 02:19:42,120 --> 02:19:45,400 COMPANY TO SYNTHESIZE AND TEST 2713 02:19:45,400 --> 02:19:47,600 IT IF IT WAS REALLY WORKING TO 2714 02:19:47,600 --> 02:19:51,000 DOWN REGULATE FARRO PORTIN 2715 02:19:51,000 --> 02:19:53,000 THERE'S A DOWN REGULATION IN THE 2716 02:19:53,000 --> 02:19:55,120 FIRST OF THIS BONE MARROW DRIVE 2717 02:19:55,120 --> 02:19:57,600 AND WHEN I SEE EFFECTED THOSE 2718 02:19:57,600 --> 02:20:00,000 CELLS WITH TB AND TREATED THEM 2719 02:20:00,000 --> 02:20:07,400 WITH GAMMA OR HEPCIDIN IT DID 2720 02:20:07,400 --> 02:20:09,520 ARE NOT HAVE A CHANGE IN THED 2721 02:20:09,520 --> 02:20:11,560 CELLS AND INTER FUR AN GAMMA WE 2722 02:20:11,560 --> 02:20:14,320 SEE A NICE REDUCTION BUT PUT 2723 02:20:14,320 --> 02:20:18,160 HELP SEDIN HERE AND IT WILL DOWN 2724 02:20:18,160 --> 02:20:28,640 REGULATE IT AND IT'S A WORK IN 2725 02:20:36,680 --> 02:20:37,680 PROGRESS AND WE HAVE ESTABLISHED 2726 02:20:37,680 --> 02:20:39,000 A COLLABORATION WITH DAVID 2727 02:20:39,000 --> 02:20:42,720 FRASIER FROM AUSTRALIA AND GET 2728 02:20:42,720 --> 02:20:45,080 THIS IN MICE AND WORE BREEDING 2729 02:20:45,080 --> 02:20:48,840 THEM WITH SOME PRETTY EXPRESSING 2730 02:20:48,840 --> 02:20:50,360 STRAINS TO KNOCK OUT IT 2731 02:20:50,360 --> 02:20:54,520 SPECIFICALLY IN THE MIO LLOYD 2732 02:20:54,520 --> 02:20:56,000 CELLS AND WEREN'T ABLE BECAUSE 2733 02:20:56,000 --> 02:20:57,680 WE FOUND THAT THESE ONES WERE 2734 02:20:57,680 --> 02:21:00,920 NOT VIABLE IF WE CROSSED THEM 2735 02:21:00,920 --> 02:21:04,440 WITH CSFR1 AND LET'S SEE WHAT 2736 02:21:04,440 --> 02:21:05,520 HAPPENS SO MA PRONE A IS DOING 2737 02:21:05,520 --> 02:21:08,840 HER FIRST INFECTION THIS WEEK. 2738 02:21:08,840 --> 02:21:10,320 LET'S SEE WHAT WE HAVE FROM 2739 02:21:10,320 --> 02:21:10,760 THAT. 2740 02:21:10,760 --> 02:21:14,160 AND ALSO, WE'RE INTERESTED IN 2741 02:21:14,160 --> 02:21:16,400 SEEING HOW IS IT MODULATING 2742 02:21:16,400 --> 02:21:20,080 THESE AND IN PARTICULAR, WE ARE 2743 02:21:20,080 --> 02:21:22,520 INTERESTED IN SEEING YOU HOW 2744 02:21:22,520 --> 02:21:27,000 THEY CAN MODULATE THE EXPRESSION 2745 02:21:27,000 --> 02:21:32,640 OF HIGH POX AND HI F-1 AND HI 2746 02:21:32,640 --> 02:21:43,000 F-2 AND WHY IS THAT? 2747 02:21:49,120 --> 02:21:57,560 AND DEGRADING THE HIF OF THE 2748 02:21:57,560 --> 02:21:58,960 MOLECULES AND IT TURNS OUT THAT 2749 02:21:58,960 --> 02:22:03,960 IT ALSO UTILIZES IRON TO THIS 2750 02:22:03,960 --> 02:22:14,600 AND FO HIF-1 WHEN IRON DEPLETION 2751 02:22:15,800 --> 02:22:17,440 OCCURS IT CAN MIGRATE TO THE 2752 02:22:17,440 --> 02:22:20,560 NUCLEUS AND INDUCE THE SUB 2753 02:22:20,560 --> 02:22:22,520 DESCRIPTION OF SEVERAL GENES 2754 02:22:22,520 --> 02:22:24,840 ASSOCIATED WITH METABOLISM OF 2755 02:22:24,840 --> 02:22:26,200 GLUCOSE AND A LOT OF CYTOKINES 2756 02:22:26,200 --> 02:22:28,600 THAT ARE IMPORTANT FOR IT AND ON 2757 02:22:28,600 --> 02:22:33,760 THE OTHER HAND, THE MODULATION 2758 02:22:33,760 --> 02:22:35,800 OF IRON WORKS ON THE OPPOSITE 2759 02:22:35,800 --> 02:22:38,920 DIRECTION AND THAT WORKS BECAUSE 2760 02:22:38,920 --> 02:22:40,360 THAT HAPPENS LIKE THIS BECAUSE 2761 02:22:40,360 --> 02:22:42,160 OF THIS IRON RESPONSIVE ELEMENT 2762 02:22:42,160 --> 02:22:45,600 AND THIS IS A MOTIVE PRESENT ON 2763 02:22:45,600 --> 02:22:50,120 THE MANAGERRER RNA MOLECULE SO 2764 02:22:50,120 --> 02:22:51,520 WHEN WE HAVE THE INTERACTION OF 2765 02:22:51,520 --> 02:22:53,560 THESE PROTEINS THAT THE IRON 2766 02:22:53,560 --> 02:22:54,920 REGULATORY PROTEIN WITH THESE 2767 02:22:54,920 --> 02:22:57,080 IRON RESPONSIVE ELEMENTS AND 2768 02:22:57,080 --> 02:23:01,280 WHEN THE IRON CONCENTRATION OF 2769 02:23:01,280 --> 02:23:03,400 THE CELLS AND LOW THEY HAVE A 2770 02:23:03,400 --> 02:23:05,880 CONFIRMATION, THEY HAVE A HIGH 2771 02:23:05,880 --> 02:23:06,920 AFFINITY FOR THE IRON SO THEY'RE 2772 02:23:06,920 --> 02:23:09,320 GOING TO MIND AND THROUGH THE 2773 02:23:09,320 --> 02:23:12,840 PRESENT IN HIF-2 AND BLOCK ITS 2774 02:23:12,840 --> 02:23:14,080 TRANSLATION AND WHEN IRON 2775 02:23:14,080 --> 02:23:15,040 ACCUMULATES INSIDE THE CELLS, 2776 02:23:15,040 --> 02:23:18,920 IT'S GOING TO BIND TO THIS IRP 2777 02:23:18,920 --> 02:23:20,480 AND ALTERS ITS CONFIRMATION AND 2778 02:23:20,480 --> 02:23:22,680 LOSES ITS AFFINITY AND RELEASES 2779 02:23:22,680 --> 02:23:24,920 THE MRNA AND THEN WE HAVE AN 2780 02:23:24,920 --> 02:23:27,920 INCREASE IN THE EXPRESSION OF 2781 02:23:27,920 --> 02:23:29,800 HIF-2 SO WHEN IRON IS HIGH 2782 02:23:29,800 --> 02:23:31,520 INSIDE CELLS WE HAVE A DEM 2783 02:23:31,520 --> 02:23:34,760 INAUGURATION OF HIF-1 ALPHA AND 2784 02:23:34,760 --> 02:23:36,920 HIF-2 ALPHA AND WHAT HAPPENS IS 2785 02:23:36,920 --> 02:23:39,440 HIF-1 ALPHA IS ASSOCIATED WITH 2786 02:23:39,440 --> 02:23:41,320 M1 MACROPHAGES WHERE WE HAVE 2787 02:23:41,320 --> 02:23:44,000 INFECTION OF EFFECT AND BETA 2788 02:23:44,000 --> 02:23:46,040 PRODUCTION AND ALL IMPORTANT FOR 2789 02:23:46,040 --> 02:23:49,240 CONTAINING TB REPLICATION AND 2790 02:23:49,240 --> 02:23:51,280 THEY ASSOCIATED WITH MACROPHAGES 2791 02:23:51,280 --> 02:23:56,400 AND IT'S AN IMPORTANT INDUCER OF 2792 02:23:56,400 --> 02:23:59,520 RGNA1 WHICH FACILITATES 2793 02:23:59,520 --> 02:24:00,920 REPLICATION AND MACROPHAGES SO 2794 02:24:00,920 --> 02:24:02,520 WE'RE INTERESTED IN ESPECIALLY 2795 02:24:02,520 --> 02:24:07,280 IN ASSESSING WHAT IS THE ROLE OF 2796 02:24:07,280 --> 02:24:11,560 THIS ALPHA PATHWAY IN INFECTION 2797 02:24:11,560 --> 02:24:13,560 AND ESPECIALLY FIGURING OUT HOW 2798 02:24:13,560 --> 02:24:15,400 THE MODULATION OF THESE IRON 2799 02:24:15,400 --> 02:24:18,280 LEVELS INSIDE THE CELLS CAN BE 2800 02:24:18,280 --> 02:24:19,440 REGULATING THESE PATHWAYS SO 2801 02:24:19,440 --> 02:24:22,280 THIS IS OUR WORK THAT IS BEING 2802 02:24:22,280 --> 02:24:23,200 DEVELOPED BY A PH.D STUDENT IN 2803 02:24:23,200 --> 02:24:26,160 MY LAB AND SO THIS IS ALSO SOME 2804 02:24:26,160 --> 02:24:28,800 VERY PRELIMINARY DATA USING BONE 2805 02:24:28,800 --> 02:24:30,880 MARROW MACROPHAGES TREATED WITH 2806 02:24:30,880 --> 02:24:35,400 ANY INHIBITOR WE DO SEE A 2807 02:24:35,400 --> 02:24:36,720 REDUCTION AND WHEN WE TRICK THEM 2808 02:24:36,720 --> 02:24:38,760 WITH GAMMA HERE IS THE REDUCTION 2809 02:24:38,760 --> 02:24:43,040 AND WE PUT GAMMA PLUS THE 2810 02:24:43,040 --> 02:24:49,600 INHIBITOR WE HAVE THIS OF THE 2811 02:24:49,600 --> 02:24:51,200 ACTIVITIES OF THIS MACROPHAGES 2812 02:24:51,200 --> 02:24:58,120 AND WE ALSO USE THIS H37RVN TO 2813 02:24:58,120 --> 02:25:01,760 BE EXPRESSING SO WE COULD SEE IF 2814 02:25:01,760 --> 02:25:04,760 INVIVO THE INFECTION WOULD 2815 02:25:04,760 --> 02:25:15,240 TRIGGER THE INFECTION SO WE 2816 02:25:18,320 --> 02:25:19,800 COMPARED TO THE NON EFFECTED 2817 02:25:19,800 --> 02:25:22,200 CELLS SO WITH THAT, WE WANTED TO 2818 02:25:22,200 --> 02:25:26,360 START A SESSION THE ROLE DURING 2819 02:25:26,360 --> 02:25:29,640 MTB INFECTION AND WE USE IT 2820 02:25:29,640 --> 02:25:31,880 MODEL OF A LOW DOSE AND TREATED 2821 02:25:31,880 --> 02:25:36,280 WITH AN INHIBITOR OF HIF-2 ALPHA 2822 02:25:36,280 --> 02:25:38,960 AND THE MOUSE HAVE A LOWER 2823 02:25:38,960 --> 02:25:42,920 BACTERIAL LOAD IN THE LUNGS SO 2824 02:25:42,920 --> 02:25:51,160 WE GOT THIS AND WHAT WE GOT IS N 2825 02:25:51,160 --> 02:25:53,120 EFFECT THE MICE WERE CONDITIONED 2826 02:25:53,120 --> 02:25:56,360 KNOCK OUT MICE WITH LOW OR HIGH 2827 02:25:56,360 --> 02:25:59,720 DOSE OF BOTH OF THEM AND WE HAVE 2828 02:25:59,720 --> 02:26:03,000 A LOWER BACTERIAL LOAD WITH MORE 2829 02:26:03,000 --> 02:26:04,600 EVIDENCE IN HIGH DOSE SO 2830 02:26:04,600 --> 02:26:05,800 EVERYTHING POINTS OUT TO THE 2831 02:26:05,800 --> 02:26:09,040 FACT THAT HIF-2 ALPHA IS 2832 02:26:09,040 --> 02:26:10,480 DETRIMENTAL FOR THE CONTROL OF 2833 02:26:10,480 --> 02:26:11,520 BACTERIAL INFECTION AND WE 2834 02:26:11,520 --> 02:26:14,560 BELIEVE THIS IS BEING MODULATED 2835 02:26:14,560 --> 02:26:16,320 BY THE CHANGES IN IRON LEVELS 2836 02:26:16,320 --> 02:26:18,040 INSIDE THE CELLS AND IN RESPONSE 2837 02:26:18,040 --> 02:26:23,160 TO OTHER INFLAMMATORY SO, THAT 2838 02:26:23,160 --> 02:26:25,000 IS ONE PROJECT AND THIS IS 2839 02:26:25,000 --> 02:26:27,120 ANOTHER PROJECT THAT WE ARE 2840 02:26:27,120 --> 02:26:28,640 CARRYING ON IN OUR LABORATORY 2841 02:26:28,640 --> 02:26:30,600 AND THIS IS IMPORTANT FOR ME TO 2842 02:26:30,600 --> 02:26:35,160 SAY THAT IT'S BEING DEVELOPED IN 2843 02:26:35,160 --> 02:26:40,880 COLLABORATION WITH Dr. CARLA 2844 02:26:40,880 --> 02:26:42,040 ROTH LYNN AND HERE AGAIN CAN BE 2845 02:26:42,040 --> 02:26:44,920 PRESENT BECAUSE I REMEMBER FIRST 2846 02:26:44,920 --> 02:26:46,920 OF ALL, CARLA IS AN EXPERT IN 2847 02:26:46,920 --> 02:26:48,760 THE FIELD OF RECEPTORS RIGHT SO 2848 02:26:48,760 --> 02:26:52,000 THESE RECEPTORS THEY RECOGNIZE 2849 02:26:52,000 --> 02:26:55,560 IN THE MEMBRANES OF CELLS AND 2850 02:26:55,560 --> 02:26:59,000 THEY BRIDGE WITH THESE LIE GANTZ 2851 02:26:59,000 --> 02:27:00,360 TO PRO MOT THE CELLS AND PHAGO 2852 02:27:00,360 --> 02:27:09,080 TIE SEW SIS IS CALLED OF CELLS 2853 02:27:09,080 --> 02:27:19,560 AND ALSO I SAID THIS PATHWAY 2854 02:27:20,720 --> 02:27:22,840 MUST BE VERY IMPORTANT FOR THE 2855 02:27:22,840 --> 02:27:23,920 REGULATION OF IMMUNE RESPONSES 2856 02:27:23,920 --> 02:27:26,160 IN TB AND WE MAY HAVE NICE 2857 02:27:26,160 --> 02:27:29,160 TARGETS HERE TO TRY TO DEVELOP 2858 02:27:29,160 --> 02:27:31,640 NEW STRETCHES, YOU KNOW, WE 2859 02:27:31,640 --> 02:27:33,800 SHOULD GET MICE WITH HER AND SEE 2860 02:27:33,800 --> 02:27:35,360 AND SHE SAID TOTALLY, LET'S TALK 2861 02:27:35,360 --> 02:27:37,160 WITH HER, SHE'S A VERY NICE 2862 02:27:37,160 --> 02:27:39,480 PERSON AND ALAN INTRODUCED ME TO 2863 02:27:39,480 --> 02:27:41,280 CARLA SO I KNEW HER AND GOT TO 2864 02:27:41,280 --> 02:27:43,560 KNOW HER AND ACTUALLY SHE SENT 2865 02:27:43,560 --> 02:27:45,120 THE MICE TO ME AND WE ARE 2866 02:27:45,120 --> 02:27:46,440 DEVELOPING THIS PROJECT RIGHT 2867 02:27:46,440 --> 02:27:48,080 NOW AND SO THIS IS SOME RESULTS 2868 02:27:48,080 --> 02:27:49,640 THAT I'M GOING TO SHOW YOU TOO, 2869 02:27:49,640 --> 02:27:50,920 THESE ARE VERY PRELIMINARY AND 2870 02:27:50,920 --> 02:27:52,440 BEING DEVELOPED BY THIS STUDENT 2871 02:27:52,440 --> 02:27:54,920 OF MINE ANDREA, HE IS A MASTERS 2872 02:27:54,920 --> 02:28:00,000 STUDENT AND HE IS SHOWN THAT THE 2873 02:28:00,000 --> 02:28:02,840 EXPRESSION OF AXL IN MACROPHAGES 2874 02:28:02,840 --> 02:28:04,800 IN RESPONSE TO INFECTION THIS IS 2875 02:28:04,800 --> 02:28:06,400 24 AND 48 HOURS AS YOU CAN SEE 2876 02:28:06,400 --> 02:28:09,480 HERE AND HE ALSO FOUND THAT IN 2877 02:28:09,480 --> 02:28:11,080 VIVO, IN MICE INFECTED WITH A 2878 02:28:11,080 --> 02:28:13,040 HIGH DOSE, WE STARTED WITH A 2879 02:28:13,040 --> 02:28:14,720 HIGH DOSE BECAUSE WE WANTED TO 2880 02:28:14,720 --> 02:28:17,880 SEE HOW IT COMMODE YOU LATE THE 2881 02:28:17,880 --> 02:28:20,000 LESIONS IN THIS MICE AND THE 2882 02:28:20,000 --> 02:28:20,720 SIGNIFICANT INCREASE IN IF YOU 2883 02:28:20,720 --> 02:28:23,680 ARE MACROPHAGES BUT IF YOU ARE 2884 02:28:23,680 --> 02:28:24,960 MACROPHAGES ARE ALREADY 2885 02:28:24,960 --> 02:28:27,280 EXPRESSING A LOT OF AXL SINCE 2886 02:28:27,280 --> 02:28:29,560 THE BEGINNING AND IT'S LITTLE TO 2887 02:28:29,560 --> 02:28:31,440 DECREASE BUZZ IN PARTICULARLY IN 2888 02:28:31,440 --> 02:28:34,760 THIS CD11B POSITIVE CELLS AS YOU 2889 02:28:34,760 --> 02:28:37,120 CAN SEE IT'S REDISTRICTED AND 2890 02:28:37,120 --> 02:28:39,200 IT'S POSITIVE EVENTS AND WE HAVE 2891 02:28:39,200 --> 02:28:41,360 A MAJOR INCREASE IN THE 2892 02:28:41,360 --> 02:28:44,000 EXPRESSION OF AXL THAT AT THE 2893 02:28:44,000 --> 02:28:46,200 SAME TIME IN THE LONG OF THESE 2894 02:28:46,200 --> 02:28:47,600 ANIMALS WE HAVE A MAJOR INCREASE 2895 02:28:47,600 --> 02:28:50,520 IN THE PREDICTION OF THE LAG ANT 2896 02:28:50,520 --> 02:28:54,440 SO WE HAVE TWO OPTIONS, FIRST, 2897 02:28:54,440 --> 02:28:58,840 IF WE AXL CAN BE DOWN MODULATING 2898 02:28:58,840 --> 02:29:00,800 AND IF YOU COULD BLOCK IT WE CAN 2899 02:29:00,800 --> 02:29:02,360 MAKE IT BETTER OR ON THE OTHER 2900 02:29:02,360 --> 02:29:07,080 SIDE, IT'S THERE TO MODULATE IT 2901 02:29:07,080 --> 02:29:08,680 AND IF YOU BLOCK IT IT WILL BE 2902 02:29:08,680 --> 02:29:08,920 BAD. 2903 02:29:08,920 --> 02:29:11,760 TO START ADDRESSING THESE WE 2904 02:29:11,760 --> 02:29:13,280 EFFECTED MICE WITH A HIGH DOSE 2905 02:29:13,280 --> 02:29:17,320 OF TB AND TREATED THEM WITH A 2906 02:29:17,320 --> 02:29:19,440 CONTROL OR AN INHIBITOR AND THIS 2907 02:29:19,440 --> 02:29:22,440 IS A DRUG THAT HAS BEEN USED IN 2908 02:29:22,440 --> 02:29:24,000 CLINICAL TRIALS FOR CANCER SO 2909 02:29:24,000 --> 02:29:25,840 THE GOOD THINGS HERE IS IT CAN 2910 02:29:25,840 --> 02:29:28,080 BE REPRE POSED. 2911 02:29:28,080 --> 02:29:30,720 AND WHAT I FOUND IS THAT WE HAD 2912 02:29:30,720 --> 02:29:33,560 TO SPEED OUR EXPERIMENT BECAUSE 2913 02:29:33,560 --> 02:29:35,200 BY DAY 25 THE MICE TREATED WITH 2914 02:29:35,200 --> 02:29:37,360 THE AXL INHIBITOR WERE STARTING 2915 02:29:37,360 --> 02:29:38,080 TO DIE. 2916 02:29:38,080 --> 02:29:44,760 AND WHEN WE EUTHANIZED THESE 2917 02:29:44,760 --> 02:29:45,520 MICERS THERE WAS NO CHANGE IN 2918 02:29:45,520 --> 02:29:47,480 THE LUNGS OF THE MICE AND THE 2919 02:29:47,480 --> 02:29:49,880 MICE TREATED WITH THE INHIBITORY 2920 02:29:49,880 --> 02:29:54,640 THEY HAD MILE OWE CELLS AND IN 2921 02:29:54,640 --> 02:29:56,400 PARTICULAR, NEUTROPHILS SO WE 2922 02:29:56,400 --> 02:30:02,800 HAD THE KNOCK OUT MICE IN THE 2923 02:30:02,800 --> 02:30:11,440 LAB AND AGAIN, NO CHANGE IN WHEE 2924 02:30:11,440 --> 02:30:13,400 HAVE THEM THREE WEEKS POST 2925 02:30:13,400 --> 02:30:17,040 INFECTION BUT THEY HAVE WAY MORE 2926 02:30:17,040 --> 02:30:18,800 SPECIALTY IN THE LUNGS AND WHEN 2927 02:30:18,800 --> 02:30:22,240 WE MEASURED THE CD4 AND CD8 BY 2928 02:30:22,240 --> 02:30:25,720 ACTIVATING THE CD4 CELLS WITH 2929 02:30:25,720 --> 02:30:27,720 PEPTIDES AND SPECIFIC PEPTIDES 2930 02:30:27,720 --> 02:30:30,200 WE SEE HERE THAT CD4s 2931 02:30:30,200 --> 02:30:33,120 EXPRESSWAY MORE GAMMA AND TNF 2932 02:30:33,120 --> 02:30:35,680 ALPHA AND THIS IS THE KNOCK OUTS 2933 02:30:35,680 --> 02:30:37,840 MICE AND CD8 CELLS WHEN 2934 02:30:37,840 --> 02:30:41,560 ACTIVATED WITH SPECIFIC PEPTIDES 2935 02:30:41,560 --> 02:30:47,800 AS WELL THEY ARE HIGHER AND THE 2936 02:30:47,800 --> 02:30:49,600 MAJOR PHENOTYPE IS THAT HUGE 2937 02:30:49,600 --> 02:30:50,560 INCREASING IN THE LUNGS OF THESE 2938 02:30:50,560 --> 02:31:00,120 MICE SO YOU CAN SEE HERE. 2939 02:31:00,120 --> 02:31:02,360 ASSOCIATED WITH THAT, IT'S KNOWN 2940 02:31:02,360 --> 02:31:02,880 TO BE DID HE TELL INTEREST 2941 02:31:02,880 --> 02:31:14,360 DETRIMENTAL AND YOU CANSEE BY TD 2942 02:31:17,480 --> 02:31:19,560 THERE'S MORE KNOCK OUT MICE AS 2943 02:31:19,560 --> 02:31:23,320 WELL AS MORE KNOW TOE SIS AND AS 2944 02:31:23,320 --> 02:31:27,240 YOU CAN SEE BY THE GRAPH SO 2945 02:31:27,240 --> 02:31:28,920 WE'RE CONTINUING TO WORK ON THAT 2946 02:31:28,920 --> 02:31:32,960 TO ACTUALLY ASSESS WHICH ARE THE 2947 02:31:32,960 --> 02:31:36,480 MECHANISMS INVOLVED IN THIS 2948 02:31:36,480 --> 02:31:38,360 HIGHER INFLAMMATION AND IF NETS 2949 02:31:38,360 --> 02:31:39,880 ARE REALLY CONTRIBUTING TO THE 2950 02:31:39,880 --> 02:31:41,760 DAMAGE TO THE LUNGS OF THESE 2951 02:31:41,760 --> 02:31:47,160 MICE AND WITH THAT WE EXPECT TO 2952 02:31:47,160 --> 02:31:48,360 PINPOINT SPECIFIC MEDIATORS WE 2953 02:31:48,360 --> 02:31:51,040 CAN TARGET TO DEVELOP NEW STRAT 2954 02:31:51,040 --> 02:31:54,320 GOES FOR TREATING THESE MICE 2955 02:31:54,320 --> 02:31:55,040 WITH THAT, THESE ARE VERY 2956 02:31:55,040 --> 02:31:55,560 PRELIMINARY DATA THAT I'M 2957 02:31:55,560 --> 02:31:57,800 SHOWING HERE THAT I'M STILL 2958 02:31:57,800 --> 02:31:59,240 START TO GO DEVELOP IN BRAZIL. 2959 02:31:59,240 --> 02:32:02,160 I WOULD LIKE TO THANK ALL THE 2960 02:32:02,160 --> 02:32:03,520 LAB MEMBERS AND MY LAB MEMBERS 2961 02:32:03,520 --> 02:32:08,880 FOR THEIR SUPPORT AND WITHOUT 2962 02:32:08,880 --> 02:32:10,920 WHICH I WOULD NOT START THIS AND 2963 02:32:10,920 --> 02:32:12,280 ALAN SHER AND THE LAB MEMBERS 2964 02:32:12,280 --> 02:32:16,480 AND BRUNO AND THEY HAVE ALWAYS 2965 02:32:16,480 --> 02:32:22,440 PARTICIPATED A LOT IN THE 2966 02:32:22,440 --> 02:32:24,720 DEVELOPMENT IN THIS PROJECT AND 2967 02:32:24,720 --> 02:32:26,960 ALAN AS EVERYBODY HERE ALREADY 2968 02:32:26,960 --> 02:32:28,320 MENTIONED HIS SUPPORT WAS 2969 02:32:28,320 --> 02:32:31,120 CRITICAL FOR ME AND IT SEEMS 2970 02:32:31,120 --> 02:32:33,400 LIKE I CAME TO THE NIH UNTIL I 2971 02:32:33,400 --> 02:32:34,640 LEFT IT WAS CRITICAL FOR ME TO 2972 02:32:34,640 --> 02:32:37,080 CHANGE MY WAY OF THINKING 2973 02:32:37,080 --> 02:32:41,360 SCIENCE AND ALAN IS VERY 2974 02:32:41,360 --> 02:32:43,040 CRITICAL ATTENTION OF MAKING YOU 2975 02:32:43,040 --> 02:32:44,720 LEARN STUFF AND ESPECIALLY 2976 02:32:44,720 --> 02:32:47,960 TEACHING YOU HOW TO WRITE. 2977 02:32:47,960 --> 02:32:51,000 SO ALONG THE HOT SEATS I HAD TO 2978 02:32:51,000 --> 02:32:54,120 WRITE PAPERS OR EVERYTHING, I 2979 02:32:54,120 --> 02:32:55,920 THINK MY ENGLISH SKILLS AND 2980 02:32:55,920 --> 02:33:00,240 WRITING SKILLS IMPROVED 2981 02:33:00,240 --> 02:33:02,720 EXPONENTIALLY SO AS I SAID, 2982 02:33:02,720 --> 02:33:06,600 ALAN'S TOUCH TO FACILITATE OUR 2983 02:33:06,600 --> 02:33:07,640 COLLABORATIONS WITH OTHER PEOPLE 2984 02:33:07,640 --> 02:33:09,240 IN THE FIELD AS WELL AND THEY 2985 02:33:09,240 --> 02:33:11,640 HAVE BEEN VERY IMPORTANT AND HIS 2986 02:33:11,640 --> 02:33:12,680 COLLABORATION HAS BEEN AND 2987 02:33:12,680 --> 02:33:13,560 CONTINUES TO BE VERY IMPORTANT 2988 02:33:13,560 --> 02:33:15,840 FOR THE DEVELOPMENT OF THIS WORK 2989 02:33:15,840 --> 02:33:18,920 AND I EXPECT THAT YOU CONTINUE 2990 02:33:18,920 --> 02:33:21,840 TO HAVE YOUR SUPPORT AND BE ABLE 2991 02:33:21,840 --> 02:33:23,400 TO CHAT WITH HIM WITH THE 2992 02:33:23,400 --> 02:33:25,280 RESULTS HAVING HIS INPUT AND 2993 02:33:25,280 --> 02:33:26,880 EVERYTHING BECAUSE I KNOW THAT'S 2994 02:33:26,880 --> 02:33:30,920 "REAL LIFE" CCRITICAL FORT DEVEE 2995 02:33:30,920 --> 02:33:31,120 WORK. 2996 02:33:31,120 --> 02:33:32,560 THANK YOU, EVERYBODY. 2997 02:33:32,560 --> 02:33:37,960 [APPLAUSE] 2998 02:33:37,960 --> 02:33:42,040 >> SO MANY FASCINATING 2999 02:33:42,040 --> 02:33:42,400 OBSERVATIONS. 3000 02:33:42,400 --> 02:33:44,400 I GUESS I'LL START FROM THE LAST 3001 02:33:44,400 --> 02:33:45,200 SECTION. 3002 02:33:45,200 --> 02:33:46,600 SO IN THE ACTION I WILL KNOCK 3003 02:33:46,600 --> 02:33:55,280 OUT MICE, DO YOU HAVE A DEFECT 3004 02:33:55,280 --> 02:34:05,800 IN NITRIC OXIDE WE ALSO TRIED TO 3005 02:34:16,600 --> 02:34:18,920 SEE IF THERE'S A DIFFERENCE IN 3006 02:34:18,920 --> 02:34:20,320 THE AXLE POSITIVE AND NEGATIVE 3007 02:34:20,320 --> 02:34:24,080 CELLS REGARDING THE INS 3008 02:34:24,080 --> 02:34:26,600 EXPRESSION AND WE FOUND THAT 3009 02:34:26,600 --> 02:34:37,080 POSITIVE CELLS ARE DOING AND 3010 02:35:07,000 --> 02:35:08,200 SPECIFICALLY THAT IS HAPPENING 3011 02:35:08,200 --> 02:35:16,360 AND OR IF IT'S JUST MORE AND 3012 02:35:16,360 --> 02:35:18,520 MORE CYTOKINES OR IF THERE'S A 3013 02:35:18,520 --> 02:35:20,640 ROW FOR AXL IN MODULATE 3014 02:35:20,640 --> 02:35:24,880 SOMETHING KIND OF SPECIFIC 3015 02:35:24,880 --> 02:35:27,840 NECROSIS TYPE OF DEATH OR SO 3016 02:35:27,840 --> 02:35:30,840 WE'RE STARTING TO INVESTIGATE 3017 02:35:30,840 --> 02:35:32,640 THAT NOW BUT I THINK THE MOST 3018 02:35:32,640 --> 02:35:34,120 LOGICAL THING TO THINK BY NOW IS 3019 02:35:34,120 --> 02:35:38,200 THAT IT'S A FAILURE TO CLEAR 3020 02:35:38,200 --> 02:35:38,480 CELLS. 3021 02:35:38,480 --> 02:35:42,480 DO YOU KNOW IF IT'S CELL 3022 02:35:42,480 --> 02:35:43,720 AUTONOMOUS? 3023 02:35:43,720 --> 02:35:47,160 >> MEANING YOU KNOW, IF YOU MADE 3024 02:35:47,160 --> 02:35:49,440 A CHIMER IT ONLY OCCURS? 3025 02:35:49,440 --> 02:35:50,840 >> SO I DON'T REALLY KNOW MANY 3026 02:35:50,840 --> 02:35:51,920 OF THAT'S ANOTHER THING WE'RE 3027 02:35:51,920 --> 02:35:52,800 TRYING TO SEE. 3028 02:35:52,800 --> 02:35:58,400 WE ACTUALLY GOT THE AXL FLUXED 3029 02:35:58,400 --> 02:35:59,880 MICE THAT WE'RE BREEDING WITH 3030 02:35:59,880 --> 02:36:07,480 SOME LINES SO WE WILL TROY TO 3031 02:36:07,480 --> 02:36:08,680 DELETE CELLS AND THE MAIN WOULD 3032 02:36:08,680 --> 02:36:13,360 BE THE MACROPHAGES. 3033 02:36:13,360 --> 02:36:16,120 >> I AM ASSUMING THAT THE TRYING 3034 02:36:16,120 --> 02:36:22,520 TO PROTECT THIS CELL FROM THE 3035 02:36:22,520 --> 02:36:33,040 RIGHT INDUCTION AND SO -- IT'S 3036 02:37:08,000 --> 02:37:14,800 HANIN ZOABI HYOU CAN COMPLETE T. 3037 02:37:14,800 --> 02:37:16,280 >> YES. 3038 02:37:16,280 --> 02:37:16,600 DEFINITELY. 3039 02:37:16,600 --> 02:37:19,320 THANK YOU FOR THE EXCELLENT 3040 02:37:19,320 --> 02:37:19,720 TALK. 3041 02:37:19,720 --> 02:37:22,200 BOTH THE MACROPHAGE AND THE BUG 3042 02:37:22,200 --> 02:37:23,520 NEED IRON AND I COULDN'T QUITE 3043 02:37:23,520 --> 02:37:25,440 TELL WHETHER YOU DISTINGUISHED 3044 02:37:25,440 --> 02:37:29,480 BETWEEN THE REQUIREMENT OF 3045 02:37:29,480 --> 02:37:30,600 EITHER OF THE BUG FOR IRON IN 3046 02:37:30,600 --> 02:37:31,240 YOUR SYSTEM? 3047 02:37:31,240 --> 02:37:34,920 >> RIGHT. 3048 02:37:34,920 --> 02:37:36,920 YEAH, SO, THAT'S THE PROBLEM OF 3049 02:37:36,920 --> 02:37:38,680 MISSING WITH IRON METABOLISM AS 3050 02:37:38,680 --> 02:37:39,720 A WHOLE, RIGHT. 3051 02:37:39,720 --> 02:37:43,400 SO IRON IS CRITICAL FOR PART OF 3052 02:37:43,400 --> 02:37:46,840 GROWTH AND BUT TB SPECIFICALLY 3053 02:37:46,840 --> 02:37:49,160 IS A LITTLE BIT MORE RESISTANCE 3054 02:37:49,160 --> 02:37:51,680 TO IRON DEPRIVATION THAN OTHER 3055 02:37:51,680 --> 02:37:52,920 SPECIES OF MICRO BACTERIA FOR 3056 02:37:52,920 --> 02:37:54,720 EXAMPLE AND MICRO BACTERIA IS 3057 02:37:54,720 --> 02:37:57,040 VERY, VERY SUSCEPTIBLE AND IF 3058 02:37:57,040 --> 02:38:00,480 YOU EFFECT MICE LA LACK IT WILL 3059 02:38:00,480 --> 02:38:05,680 PUT IRON INSIDE THE PHAGO SOME, 3060 02:38:05,680 --> 02:38:06,880 THE MICE PROSECUTE GOING TO BE 3061 02:38:06,880 --> 02:38:08,760 RESISTANT TO AVIAN BUT NOT TO 3062 02:38:08,760 --> 02:38:14,000 MTV FOR EXAMPLE. 3063 02:38:14,000 --> 02:38:16,840 AND DEFINITELY IT'S A TWO-HEADED 3064 02:38:16,840 --> 02:38:17,040 SWORD. 3065 02:38:17,040 --> 02:38:19,080 IF I LIMIT IRON I'LL BE STARVING 3066 02:38:19,080 --> 02:38:23,280 THE BUGS AND I MAY BE I'M ALSO 3067 02:38:23,280 --> 02:38:25,280 GOING TO BE MAKING THE 3068 02:38:25,280 --> 02:38:28,120 MACROPHAGES WORK BETTER SO THEN 3069 02:38:28,120 --> 02:38:30,840 THERE'S ANOTHER POINT SO IN 3070 02:38:30,840 --> 02:38:34,520 STUDYING THE EYE OWN HOMEOSTASIS 3071 02:38:34,520 --> 02:38:39,440 ITSELF, IT'S TRICKY FOR US TO 3072 02:38:39,440 --> 02:38:40,600 DEAL, THIS IS GOING TO CAUSE 3073 02:38:40,600 --> 02:38:41,480 OTHERS PROBLEMS, RIGHT. 3074 02:38:41,480 --> 02:38:44,880 THIS IS GOING TO CAUSE ANEMIA 3075 02:38:44,880 --> 02:38:49,680 AND SEVERAL OTHER STUFF OR LET'S 3076 02:38:49,680 --> 02:38:51,120 INDUCE A LOT OF -- IT WILL MESS 3077 02:38:51,120 --> 02:38:53,680 UP WITH THE WHOLE BODY OUR 3078 02:38:53,680 --> 02:38:54,840 HOMEOSTASIS SYSTEM AND THE POINT 3079 02:38:54,840 --> 02:38:58,680 YOU ARE USED TO ACTUALLY FIND 3080 02:38:58,680 --> 02:39:03,400 WHICH ARE THE MODULATING THIS 3081 02:39:03,400 --> 02:39:06,560 AND STRETCH THE TARGET THEN AND 3082 02:39:06,560 --> 02:39:07,760 FOR EXAMPLE, IF TOO OFTEN IT'S A 3083 02:39:07,760 --> 02:39:10,440 GO AHEAD ONE, BECAUSE ALSO WE 3084 02:39:10,440 --> 02:39:12,240 HAVE THESE THAT HAVE BEEN USED 3085 02:39:12,240 --> 02:39:13,480 ALREADY IN CANCER TREATMENT AND 3086 02:39:13,480 --> 02:39:17,040 IT CAN BE EASILY REPO POSED FOR 3087 02:39:17,040 --> 02:39:19,600 TB SO WE'RE TRYING TO THINK AND 3088 02:39:19,600 --> 02:39:21,640 IDENTIFY THAT CAN BE TARGETED. 3089 02:39:21,640 --> 02:39:23,240 IF YOU REAL WITH IRON ALONE, 3090 02:39:23,240 --> 02:39:24,680 IT'S GOING TO BE A MESS, I 3091 02:39:24,680 --> 02:39:25,200 GUESS. 3092 02:39:25,200 --> 02:39:27,000 >> SO IT SOUNDS LIKE YOU ARE NOT 3093 02:39:27,000 --> 02:39:30,480 ENTHUSIASTIC ABOUT DEVELOPING 3094 02:39:30,480 --> 02:39:34,320 SNPP9 AS A CLINICAL AGENT. 3095 02:39:34,320 --> 02:39:35,640 >> WE HAVE COLLABORATION THAT 3096 02:39:35,640 --> 02:39:40,000 PEOPLE HAVE BEEN TRYING TO -- 3097 02:39:40,000 --> 02:39:47,800 OUR INHIBITORS OF H-O01 AND THEY 3098 02:39:47,800 --> 02:39:49,400 CAN'T USE IT FOR A LONG TIME AND 3099 02:39:49,400 --> 02:39:51,880 IT HAS TO BE SHORT TERM. 3100 02:39:51,880 --> 02:39:55,000 >> ONE LAST QUESTION, THERE'S 3101 02:39:55,000 --> 02:39:56,520 IRON DEFICIENCY IN THE THIRD 3102 02:39:56,520 --> 02:39:58,080 WORLD, IS THERE ANY DATA 3103 02:39:58,080 --> 02:39:59,760 ASSOCIATING BETTER OUTCOMES IN 3104 02:39:59,760 --> 02:40:01,360 TB PATIENTS THAT ARE IRON 3105 02:40:01,360 --> 02:40:01,640 DEFICIENT? 3106 02:40:01,640 --> 02:40:03,760 >> YES, SO IT VARIES A LOT. 3107 02:40:03,760 --> 02:40:05,760 THERE ARE SOME VERY OLD PAPERS 3108 02:40:05,760 --> 02:40:08,400 THAT ALREADY SHOW IN THE 1800S 3109 02:40:08,400 --> 02:40:10,880 THAT PATIENTS THAT HAVE BEEN 3110 02:40:10,880 --> 02:40:12,080 SUPPLEMENTED WITH IRON WOULD 3111 02:40:12,080 --> 02:40:14,360 HAVE A WORSENING OF THE HE HAVE 3112 02:40:14,360 --> 02:40:16,040 EFFECTS OR IT WOULD FAVOR THE 3113 02:40:16,040 --> 02:40:17,120 DISSEMINATION BECAUSE MAINLY YOU 3114 02:40:17,120 --> 02:40:19,680 HAVE THESE RETENTION OF IRON IN 3115 02:40:19,680 --> 02:40:21,680 THE LIVER AND IN THE SPLEEN, SO 3116 02:40:21,680 --> 02:40:24,760 IT FAVORS THE DISSEMINATION OF 3117 02:40:24,760 --> 02:40:25,560 BACTERIA. 3118 02:40:25,560 --> 02:40:26,480 THERE ARE NOT SO MANY NEW 3119 02:40:26,480 --> 02:40:28,560 STUDIES ON THIS CASE THEY'RE 3120 02:40:28,560 --> 02:40:32,520 MAJORLY OLD STUDIES. 3121 02:40:32,520 --> 02:40:34,200 >> I AM BUILDING ON PHIL'S 3122 02:40:34,200 --> 02:40:37,000 QUESTIONS ABOUT IRON REGULATION. 3123 02:40:37,000 --> 02:40:38,320 IT'S ALSO THOUGHT TO PLAY A ROLE 3124 02:40:38,320 --> 02:40:41,000 IN THE OBESITY EPIDEMIC IN NASH 3125 02:40:41,000 --> 02:40:43,120 WITH HELP SIDE AND I THINK 3126 02:40:43,120 --> 02:40:49,960 LEVELS DECROWS CREASING AND LEAO 3127 02:40:49,960 --> 02:40:51,280 HIGH GROW SIS SO I'M CURIOUS 3128 02:40:51,280 --> 02:40:53,200 WHAT IS THE CORRELATION SORRY 3129 02:40:53,200 --> 02:40:56,120 CONNECTION BETWEEN OBESITY AND 3130 02:40:56,120 --> 02:40:57,600 NASH AND SEVERITY OF TB? 3131 02:40:57,600 --> 02:41:00,120 >> IS THAT KNOWN? 3132 02:41:00,120 --> 02:41:02,360 >> I KNOW LIKE THERE ARE SOME 3133 02:41:02,360 --> 02:41:05,400 DATA SHOWING THAT OBESITY IS A 3134 02:41:05,400 --> 02:41:10,280 RISK FACTOR FOR TB, RIGHT. 3135 02:41:10,280 --> 02:41:12,720 SO ACTUALLY WE JUST SUBMIT AID 3136 02:41:12,720 --> 02:41:15,480 PAPER IN AN EXPERIMENTAL MODEL 3137 02:41:15,480 --> 02:41:20,960 WHERE WE FEED HIGH-FAT DIE ITS 3138 02:41:20,960 --> 02:41:29,400 FOR THESE HIGHS IT'S NOT SO BAD 3139 02:41:29,400 --> 02:41:33,440 FOR BACK ROLE AND IT TRIGGERED 3140 02:41:33,440 --> 02:41:35,360 BECAUSE OF THESE LIP ITS AND 3141 02:41:35,360 --> 02:41:38,560 THERE'S GOING TO TRIGGER INFLAM 3142 02:41:38,560 --> 02:41:41,840 OWE SOMEONE'S AND IT MAKES IT 3143 02:41:41,840 --> 02:41:44,080 WORSE SO FOR OBESITY IT'S BA% 3144 02:41:44,080 --> 02:41:45,800 úFOR TB BUT MAINLY BECAUSE OF 3145 02:41:45,800 --> 02:41:48,200 THESE HIGH INFLAMMATION THAT IS 3146 02:41:48,200 --> 02:41:48,920 GENERATED. 3147 02:41:48,920 --> 02:41:49,120 >> COOL. 3148 02:41:49,120 --> 02:41:49,400 NICE WORK. 3149 02:41:49,400 --> 02:41:51,520 >> THANK YOU. 3150 02:41:51,520 --> 02:41:51,680 >> 3151 02:41:51,680 --> 02:41:57,040 [APPLAUSE] 3152 02:41:57,040 --> 02:42:07,240 [OFF MIC] 3153 02:42:30,680 --> 02:42:32,800 >> IT'S ALWAYS TREATED BY 3154 02:42:32,800 --> 02:42:33,280 ANTIBIOTICS. 3155 02:42:33,280 --> 02:42:33,600 >> THANK YOU. 3156 02:42:33,600 --> 02:42:34,600 >> ALL RIGHT. 3157 02:42:34,600 --> 02:42:40,200 SO NEXT SPEAKER IS NICOLAS 3158 02:42:40,200 --> 02:42:44,720 RITEAU HE IS FROM FRANCE AND 3159 02:42:44,720 --> 02:42:45,080 PLEASE. 3160 02:42:45,080 --> 02:42:47,040 >> THANK YOU, VERY MUCH. 3161 02:42:47,040 --> 02:42:49,920 FIRST I'D LIKE TO THANK DRAGANA, 3162 02:42:49,920 --> 02:42:52,040 LIKE ALL THE OTHERS, FOR 3163 02:42:52,040 --> 02:42:54,520 ORGANIZING THIS REALLY NICE 3164 02:42:54,520 --> 02:42:56,480 SYMPOSIUM SO I WAS A POSTDOC IN 3165 02:42:56,480 --> 02:43:00,000 ALAN'S LAB FROM 2012 TO 2017 AND 3166 02:43:00,000 --> 02:43:01,120 SOME OF THE PEOPLE I KNEW IN THE 3167 02:43:01,120 --> 02:43:03,000 LAB AND IT'S A GREAT OCCASION 3168 02:43:03,000 --> 02:43:04,720 AND IN ANY CASE TO MEET A LOT OF 3169 02:43:04,720 --> 02:43:06,400 PEOPLE AND IN FRANCE SO ONCE 3170 02:43:06,400 --> 02:43:08,040 AGAIN THANK YOU VERY MUCH. 3171 02:43:08,040 --> 02:43:10,560 SO, DURING MY TIME AT ALAN'S LAB 3172 02:43:10,560 --> 02:43:16,120 I WORK MAINLY ON CONTEXT OF 3173 02:43:16,120 --> 02:43:17,520 VACCINES AND NOW WHAT I'M GOING 3174 02:43:17,520 --> 02:43:21,120 TO PRESENT TO YOU IS MORE 3175 02:43:21,120 --> 02:43:22,720 STEROID INFLAMMATION AND MODEL 3176 02:43:22,720 --> 02:43:28,200 IN THE CONTEXT OF THE ROLE OF 3177 02:43:28,200 --> 02:43:34,760 STING IN THIS DAY SO I'M SENIOR 3178 02:43:34,760 --> 02:43:39,720 SCIENTIST IN FRANCE AND SO IN 3179 02:43:39,720 --> 02:43:42,000 ADDITION TO THE CLASSICAL MODEL 3180 02:43:42,000 --> 02:43:46,920 OF INNATE IMMUNITY, AND FIRST 3181 02:43:46,920 --> 02:43:51,160 DESCRIBED BY JANEWAY WE HAVE 3182 02:43:51,160 --> 02:43:53,560 PATHOGEN RECOGNITION AND 3183 02:43:53,560 --> 02:43:57,200 RECEPTORS AND THAT ARE GOING TO 3184 02:43:57,200 --> 02:43:59,200 DRIVE IMMUNO ACTIVATION AND 3185 02:43:59,200 --> 02:44:03,920 REGULATION AND MATT SINGER IN 3186 02:44:03,920 --> 02:44:14,320 ABOUT 28 YEARS AGO SAID. 3187 02:47:24,200 --> 02:47:29,360 >> AND ATP AND THROUGH RECEPTIVE 3188 02:47:29,360 --> 02:47:31,560 2X7 BUT WE'RE NOW IN LINE WITH 3189 02:47:31,560 --> 02:47:38,560 THE RECENTLY WE TRIED TO SENSING 3190 02:47:38,560 --> 02:47:42,200 AND AND ESPECIALLY THE STING 3191 02:47:42,200 --> 02:47:44,680 PATHWAY SO THIS IS BRIEFLY 3192 02:47:44,680 --> 02:47:49,640 MENTIONED YESTERDAY BY JASMINE 3193 02:47:49,640 --> 02:47:51,160 AND THIS STING WAS FIRST 3194 02:47:51,160 --> 02:47:53,680 DESCRIBED IN 2008 AND THE 3195 02:47:53,680 --> 02:48:04,200 CONTEXT OF INFECTION AND SO THIS 3196 02:48:06,840 --> 02:48:10,200 BINDS TO FORMED THEY GO THE IN 3197 02:48:10,200 --> 02:48:20,800 THTHTHE CYTOPLASM AND. 3198 02:49:50,880 --> 02:49:58,560 >> SO YOU CAN OTHER AND OR AND 3199 02:49:58,560 --> 02:50:06,600 DEPENDING ON HOW LONG AND YOU 3200 02:50:06,600 --> 02:50:08,160 ENVIRONMENT AND SIGNAL AND WHERE 3201 02:50:08,160 --> 02:50:18,560 YOU WANT TO TREAT AND. 3202 02:51:27,960 --> 02:51:31,800 >> YOU CAN SEE THERE ARE MANY 3203 02:51:31,800 --> 02:51:35,200 CELLS EXPRESSING STING AND IT IS 3204 02:51:35,200 --> 02:51:40,080 EXPOSED BY MANY DIFFERENT CELL 3205 02:51:40,080 --> 02:51:42,280 TYPES AND SO AT FIRST WE SAW 3206 02:51:42,280 --> 02:51:45,480 THAT IF WE WOULD REMOVE STING, 3207 02:51:45,480 --> 02:51:47,400 WE WOULD HAVE LESS PATHOLOGY AND 3208 02:51:47,400 --> 02:51:52,360 IT'S WHAT WE HAVE SEEN WHEN WE 3209 02:51:52,360 --> 02:51:56,160 REMOVED INNATE MEDIATORS AND 3210 02:51:56,160 --> 02:51:58,480 PROTEINS THAT ARE IN PATHWAYS 3211 02:51:58,480 --> 02:52:03,880 SUCH AS THE INFLAMOSOME AND WE 3212 02:52:03,880 --> 02:52:06,200 HAD A DECREASED PATHOLOGY AND 3213 02:52:06,200 --> 02:52:07,960 EVERYTHING IS BY HOST IF YOU 3214 02:52:07,960 --> 02:52:09,240 REMOVED ONE OF THE PATHWAYS YOU 3215 02:52:09,240 --> 02:52:11,720 HAVE LESS INFLAMMATORY AND 3216 02:52:11,720 --> 02:52:14,560 FIBROSIS AND WE GOT REALLY 3217 02:52:14,560 --> 02:52:16,880 EXCITED WHEN WE REMOVED STINGS 3218 02:52:16,880 --> 02:52:18,520 AND WE USED STING KNOCK OUT 3219 02:52:18,520 --> 02:52:21,440 ANIMALS WE HAD AN INCREASE IN 3220 02:52:21,440 --> 02:52:22,920 THE CLINICAL SCORE OF THE 3221 02:52:22,920 --> 02:52:29,680 ANIMALS AND INCREASED WEIGHT 3222 02:52:29,680 --> 02:52:40,320 LOSS AND THE AND AND IN THE LUND 3223 02:54:42,800 --> 02:54:44,280 THEY'RE FREQUENT AND THEIR 3224 02:54:44,280 --> 02:54:46,160 PHENOTYPE IS ALTERED AND SO WE 3225 02:54:46,160 --> 02:54:50,000 LOOK AT DIFFERENT MARKERS AND WE 3226 02:54:50,000 --> 02:54:55,200 WERE ABLE TO SHOW THAT THE IMAGE 3227 02:54:55,200 --> 02:54:56,520 CLASS 2 EXPRESSION OF 3228 02:54:56,520 --> 02:54:57,640 NEUTROPHILS IS DECREASED 3229 02:54:57,640 --> 02:55:00,280 COMPARED TO THE WILD TYPE 3230 02:55:00,280 --> 02:55:01,640 NEUTROPHILS SO WE DO KNOW 3231 02:55:01,640 --> 02:55:06,080 EXACTLY WHAT IT MEANS BUT WE CAN 3232 02:55:06,080 --> 02:55:09,880 SOMEHOW BE RELATED WITHOUT IT AW 3233 02:55:09,880 --> 02:55:14,080 AN INCREASE THIS TYPE OF 3234 02:55:14,080 --> 02:55:16,920 EXPRESSION IN COMPARED TO THE 3235 02:55:16,920 --> 02:55:19,000 WILD TYPES AND THIS CAN BE 3236 02:55:19,000 --> 02:55:21,600 LINKED MAYBE TO INCREASED 3237 02:55:21,600 --> 02:55:22,920 EXPRESSION AND THEY'RE PAPERS 3238 02:55:22,920 --> 02:55:29,200 SHOWINTHAT THEY'RE CONNECTIONS 3239 02:55:29,200 --> 02:55:39,680 BETWEEN WHERE THE INDUCTION OF 3240 02:55:53,400 --> 02:56:03,840 TYPE ONE INTER NEURONS AND A FEW 3241 02:57:05,080 --> 02:57:08,240 PAPERS SHOWED IT'S HAPPENING IN 3242 02:57:08,240 --> 02:57:14,440 OTHER COULD BE TEXT THAT IT'S 3243 02:57:14,440 --> 02:57:17,200 REALLY IMPORTANT ALSO BECAUSE 3244 02:57:17,200 --> 02:57:23,440 TH17 CELLS AND I17 IS A DRIVER 3245 02:57:23,440 --> 02:57:27,120 OF THIS MODEL AND IT'S A PAPER 3246 02:57:27,120 --> 02:57:28,560 THAT TOM WYNN PUBLISHED ABOUT 10 3247 02:57:28,560 --> 02:57:32,800 YEARS AGO SHOWING THAT IL-17 IS 3248 02:57:32,800 --> 02:57:35,080 IMPORTANT TO DRIVE PATHOLOGY BUT 3249 02:57:35,080 --> 02:57:36,400 HERE WE DIDN'T SEE ANY 3250 02:57:36,400 --> 02:57:38,120 DIFFERENCE COMPARING WILD TYPE 3251 02:57:38,120 --> 02:57:41,040 MICE AND KNOCK OUT ANIMALS AND 3252 02:57:41,040 --> 02:57:42,240 TREATED WITH ROW HIGH SINCE SO 3253 02:57:42,240 --> 02:57:46,080 IT'S REPRESENTATIVE AND CD4 3254 02:57:46,080 --> 02:57:49,800 POSITIVE T CELLS IN THE LUNGS OF 3255 02:57:49,800 --> 02:57:56,720 SALINE CONTRA MICE SO ALMOST NO 3256 02:57:56,720 --> 02:58:01,040 IL-17 AND AFTER THERE'S AN 3257 02:58:01,040 --> 02:58:02,920 INDUCTION OF IL-17 PROGRESS 3258 02:58:02,920 --> 02:58:05,440 CELLS BUT NO DIFFERENCE 3259 02:58:05,440 --> 02:58:06,600 COMPARING WILD TYPE AND STING 3260 02:58:06,600 --> 02:58:10,640 KNOCK OUT ANIMALS AS QUANTIFY 3261 02:58:10,640 --> 02:58:12,920 HERE BY IL-17 POSITIVE CELLS OR 3262 02:58:12,920 --> 02:58:15,480 THE TOTAL NUMBERS OF THESE CELLS 3263 02:58:15,480 --> 02:58:17,960 AND SO THEN WE MOVED AND WE ARE 3264 02:58:17,960 --> 02:58:19,920 NOW REALLY INTERESTED IN TYPE 3 3265 02:58:19,920 --> 02:58:24,040 INTER NEURONS OR IL28 AND 29 AND 3266 02:58:24,040 --> 02:58:26,560 THEY ARE AT LEAST NOW MORE THAN 3267 02:58:26,560 --> 02:58:28,240 THAT FIVE OR SIX MORE PAPERS 3268 02:58:28,240 --> 02:58:33,320 SHOWING YOU CAN HAVE TYPE 3 3269 02:58:33,320 --> 02:58:34,760 INDUCTION DOWNSTREAM OF STING SO 3270 02:58:34,760 --> 02:58:38,640 IT'S LESS KNOWN THAT THEY ARE 3271 02:58:38,640 --> 02:58:42,640 DISCOVERED IN 2003 AND THEY ARE 3272 02:58:42,640 --> 02:58:46,240 FOUR INTERFERON IN HUMANS ONLY 3273 02:58:46,240 --> 02:58:51,640 TWO IN MICE AND THEY ARE REALLY 3274 02:58:51,640 --> 02:58:54,280 ABUNDANT AND IN TRACT AND THEY 3275 02:58:54,280 --> 02:58:58,000 SHARE A UNIQUE RECEPTORS AND 3276 02:58:58,000 --> 02:59:01,320 WITH ONE CHAIN OF THE I L-10 3277 02:59:01,320 --> 02:59:02,600 RECEPTORS AND THIS SIGNALING 3278 02:59:02,600 --> 02:59:04,640 DOWNSTREAM IS VERY SIMILAR TO 3279 02:59:04,640 --> 02:59:08,760 THAT OF TYPE 1 NEURONS AND THEY 3280 02:59:08,760 --> 02:59:11,800 CANNOT INDUCE THE SAME ISGs SO 3281 02:59:11,800 --> 02:59:14,800 IT SOUNDS EXPRESSING AND THE 3282 02:59:14,800 --> 02:59:19,280 EVERYTHING AROUND REALLY THE 3283 02:59:19,280 --> 02:59:23,000 ACTUAL DEFERS AND IT'S BEEN MANY 3284 02:59:23,000 --> 02:59:26,800 STUDY AND IDEA IS WHEN YOU HAVE 3285 02:59:26,800 --> 02:59:29,360 AND BY MOSTLY THE CELLS AND THEN 3286 02:59:29,360 --> 02:59:31,000 IF IT'S EFFECTIVE, YOU WOULD 3287 02:59:31,000 --> 02:59:35,920 HAVE LESS TYPE 1 INDUCTION AND 3288 02:59:35,920 --> 02:59:38,000 PATHOLOGY SO THESE ARE THE 3289 02:59:38,000 --> 02:59:39,160 PRELIMINARY DATA BUT WE WERE 3290 02:59:39,160 --> 02:59:43,000 ABLE TO SHOW THAT THERE IS AN 3291 02:59:43,000 --> 02:59:45,040 INDUCTION OF I28 IN THE LONG OF 3292 02:59:45,040 --> 02:59:50,040 WILD TYPE MICE TREATED WITH A 3293 02:59:50,040 --> 02:59:52,800 PARTIAL REDUCTION WHEN WE LOOKED 3294 02:59:52,800 --> 02:59:56,000 IN ANIMALS AND THE CASE IN THE 3295 02:59:56,000 --> 02:59:57,280 TYPE 1 KNOCK OUT ANIMALS AND 3296 02:59:57,280 --> 03:00:03,520 IT'S SHOWN HERE BY WESTERN BLOCK 3297 03:00:03,520 --> 03:00:05,080 AND THERE'S LESS EXPRESSION IN 3298 03:00:05,080 --> 03:00:08,720 THE KNOCK OUT AS COMPARED TO THE 3299 03:00:08,720 --> 03:00:10,560 WILD TYPES. 3300 03:00:10,560 --> 03:00:13,120 SO THAT'S OUR WORK HYPOTHESIS AT 3301 03:00:13,120 --> 03:00:16,520 LEAST IN LINE WITH TYPE 3 3302 03:00:16,520 --> 03:00:18,040 INTERFERON WHICH DOWNSTREAM OF 3303 03:00:18,040 --> 03:00:21,200 STING THIS WITH BIND TO 3304 03:00:21,200 --> 03:00:22,760 SELECTIVELY EXPRESS RECEPTORS ON 3305 03:00:22,760 --> 03:00:26,160 THE CELLS ON NEUTRAL AND THIS 3306 03:00:26,160 --> 03:00:31,680 CAN SOMEHOW RETURN AND AND EVENT 3307 03:00:31,680 --> 03:00:34,720 LOW THE FIBROSIS AND WE ALSO 3308 03:00:34,720 --> 03:00:38,680 KNOW WE ARE INTERESTED IN LOOK 3309 03:00:38,680 --> 03:00:42,800 AT A SO I DIDN'T SHOW YOU 3310 03:00:42,800 --> 03:00:44,760 DOWNSTREAM BUT IT'S INVOLVED IN 3311 03:00:44,760 --> 03:00:45,920 MANY DIFFERENT PROCESSES 3312 03:00:45,920 --> 03:00:49,000 DEPENDING ON THE CELL TYPES AND 3313 03:00:49,000 --> 03:00:51,360 CONTEXT AND I HAVE THREE 3314 03:00:51,360 --> 03:00:53,760 ACTIVATION AND MENTIONED BUT 3315 03:00:53,760 --> 03:00:55,240 ALSO MORE CELL DEATH ESPECIALLY 3316 03:00:55,240 --> 03:01:05,840 IN AUTO PATH GEE AND ALSO, WE DD 3317 03:01:10,280 --> 03:01:13,520 THE EXPRESSION LEVEL AND AND 3318 03:01:13,520 --> 03:01:17,960 IT'S REALLY HARD AND PATHWAY AND 3319 03:01:17,960 --> 03:01:22,640 WHAT WE SEE HERE IS WE HAVE 3320 03:01:22,640 --> 03:01:25,560 INDUCTION OF THIS AUTOPHAGY IN 3321 03:01:25,560 --> 03:01:30,080 THE WILD TYPE MICE TREATED WITH 3322 03:01:30,080 --> 03:01:32,080 NOT THE CASE IN SING ANIMALS BUT 3323 03:01:32,080 --> 03:01:34,520 WE ALSO HAVE A STRONG INDUCTION 3324 03:01:34,520 --> 03:01:37,000 OF P62 IN WILD TYPE MICE THAT 3325 03:01:37,000 --> 03:01:40,000 WOULD INDICATE MORE LIKE 3326 03:01:40,000 --> 03:01:44,800 DECREASED OR LIKE A BLOCKED SO 3327 03:01:44,800 --> 03:01:47,400 IT'S NOT COMPLETELY CLEAR HOW 3328 03:01:47,400 --> 03:01:49,560 THIS HAPPENS BUT IMPORTANTLY 3329 03:01:49,560 --> 03:01:52,120 THIS IS ALSO CRITICALLY 3330 03:01:52,120 --> 03:01:53,320 DECREASING IN ANIMALS SO THERE'S 3331 03:01:53,320 --> 03:01:54,760 SOMETHING THAT WE WOULD LIKE TO 3332 03:01:54,760 --> 03:02:00,040 PURSUE AND SEE WHETHER THIS 3333 03:02:00,040 --> 03:02:02,400 PATHWAY CAN BE WHAT IS DRIVING 3334 03:02:02,400 --> 03:02:05,000 THE PROTECTION OF DOWNSTREAM OF 3335 03:02:05,000 --> 03:02:08,800 STING AND THIS IS RELEVANT IN 3336 03:02:08,800 --> 03:02:11,200 THE TEAM IT'S BEEN SLOAN THAT IT 3337 03:02:11,200 --> 03:02:16,600 PROTEINS ARE DECREASED IN 3338 03:02:16,600 --> 03:02:19,920 PATIENTS AND THAT FEARS AND 3339 03:02:19,920 --> 03:02:22,720 DEROGATION IN MOUSE AND SURVIVAL 3340 03:02:22,720 --> 03:02:28,360 AND WHEN IT'S LINK THE TO CELL 3341 03:02:28,360 --> 03:02:30,520 SIGNIFICANCE AND EFFICIENT MICE 3342 03:02:30,520 --> 03:02:36,320 AND THEN PEOPLE HAVE SHOWED THAT 3343 03:02:36,320 --> 03:02:39,120 THIS MICE DID I PLAY INCREASED 3344 03:02:39,120 --> 03:02:42,400 FIBROSIS AND SO, THIS AND MY 3345 03:02:42,400 --> 03:02:44,840 LAST DATA SLIDE AND WE ARE NOW 3346 03:02:44,840 --> 03:02:51,400 ALSO TRYING TO SEE WHETHER WE 3347 03:02:51,400 --> 03:02:52,480 CAN ACT RATE IS STING SO WE'RE 3348 03:02:52,480 --> 03:02:56,720 USING THIS REALLY STRONG 3349 03:02:56,720 --> 03:03:02,520 IMPORTANT AND IN THIS PARTICULAR 3350 03:03:02,520 --> 03:03:06,880 EXPERIMENT, ONE SINGLE 3351 03:03:06,880 --> 03:03:10,080 ADMINISTRATION OF DIABZ7 WAS 3352 03:03:10,080 --> 03:03:14,000 ENOUGH TO REDUCE FIBROSIS WITH 3353 03:03:14,000 --> 03:03:17,480 THE SCORE AND ALSO, THE COLOGIN 3354 03:03:17,480 --> 03:03:18,240 CONTENT SO IT'S SOMETHING THAT 3355 03:03:18,240 --> 03:03:20,400 WE ARE REALLY INTERESTED IN AND 3356 03:03:20,400 --> 03:03:22,320 WE'RE GOING TO PURSUE SO THE 3357 03:03:22,320 --> 03:03:27,040 GENERAL IDEA IS THAT IT'S KNOWN 3358 03:03:27,040 --> 03:03:29,680 TO CREATE A LOT OF CELL THERE'S 3359 03:03:29,680 --> 03:03:34,280 NOT IN DNA DAMAGE AND DNA 3360 03:03:34,280 --> 03:03:37,160 RELEASE AND SO THIS WOULD NEED 3361 03:03:37,160 --> 03:03:41,040 TO AN INCREASE OF MIGHT TOE AND 3362 03:03:41,040 --> 03:03:44,520 IN THE PLUS UM ACTIVATING AND 3363 03:03:44,520 --> 03:03:48,760 THE OTHER SENSORS AND THE 3364 03:03:48,760 --> 03:03:49,880 INDUCTION THAT COULD BE 3365 03:03:49,880 --> 03:03:53,520 BENEFICIAL AND ALSO STING CAN BE 3366 03:03:53,520 --> 03:03:54,880 PART OF THIS PROCESS AND WE HAVE 3367 03:03:54,880 --> 03:03:55,960 A COUPLE OF QUESTIONS THAT WE 3368 03:03:55,960 --> 03:03:58,600 ARE TRYING TO ADDRESS AT THE 3369 03:03:58,600 --> 03:04:07,800 MOMENT AND THE TYPE OF ACID AND 3370 03:04:07,800 --> 03:04:10,640 AND MAYBE SOME OF THEM ARE 3371 03:04:10,640 --> 03:04:13,080 INTERESTING TO LOOK AT AND ALSO 3372 03:04:13,080 --> 03:04:14,600 I WOULD GAIN ACCESS TO THE SITE 3373 03:04:14,600 --> 03:04:16,400 AND IT'S SOMETHING REALLY 3374 03:04:16,400 --> 03:04:17,800 IMPORTANT IN THE FIELD BECAUSE 3375 03:04:17,800 --> 03:04:22,600 YOU HAVE CELLS AND DNA FLOATING 3376 03:04:22,600 --> 03:04:24,240 AROUND, HOW CAN IT COME TO THE 3377 03:04:24,240 --> 03:04:27,160 SO IT'S NOT SOMETHING THAT WELL 3378 03:04:27,160 --> 03:04:30,560 ASK THERE'S A BIG BLACK BOX HERE 3379 03:04:30,560 --> 03:04:39,840 AND AND ALSO, IF WE CAN ACTIVATE 3380 03:04:39,840 --> 03:04:42,120 STING AND SEE IF CAN BE 3381 03:04:42,120 --> 03:04:42,760 BENEFICIAL OF THE FIBROSIS AS 3382 03:04:42,760 --> 03:04:47,800 WELL AS THE EFFECT OF TYPE 3 3383 03:04:47,800 --> 03:04:52,520 INTERFERON AND THE AUTO IF GEE 3384 03:04:52,520 --> 03:04:53,880 AND SO THESE ARE THE PEOPLE IN 3385 03:04:53,880 --> 03:04:58,160 MY LAB THAT ARE LED BY ISABEL 3386 03:04:58,160 --> 03:05:01,040 AND THE DIRECTORS OF I KNOW ALAN 3387 03:05:01,040 --> 03:05:07,280 KNOW THEM REALLY WELL AND I USED 3388 03:05:07,280 --> 03:05:08,800 TO WORK WITH TB FOR MANY YEARS 3389 03:05:08,800 --> 03:05:14,160 AND HOW I GOT TO KNOW ALAN AT 3390 03:05:14,160 --> 03:05:16,200 FIRST AND I'D LIKE TO SHARE A 3391 03:05:16,200 --> 03:05:17,560 FEW PICTURES SO I TOOK WHEN I 3392 03:05:17,560 --> 03:05:21,440 WAS A POSTDOC AND LIKE MANY 3393 03:05:21,440 --> 03:05:25,040 OTHERS, I THINK IT HOTSEAT IS 3394 03:05:25,040 --> 03:05:26,400 SOMETHING THAT SOME WOULD CALL 3395 03:05:26,400 --> 03:05:35,000 IT PAINFUL AND YOU TOOK MANY 3396 03:05:35,000 --> 03:05:36,880 TIME AT EVERY OCCASION IT WAS 3397 03:05:36,880 --> 03:05:43,160 LIKE A 15-LINE ABSTRACT IT WOULD 3398 03:05:43,160 --> 03:05:48,880 TAKE ONE AFTERNOON TO GO SO I 3399 03:05:48,880 --> 03:05:51,240 WAS ABLE TO SPEAK TO HIM A 3400 03:05:51,240 --> 03:05:54,640 COUPLE OF TIMES DURING THE 3401 03:05:54,640 --> 03:05:55,640 HOTSEAT SO I DON'T HAVE ALL OF 3402 03:05:55,640 --> 03:05:56,440 THE PEOPLE THAT WERE AROUND BUT 3403 03:05:56,440 --> 03:05:59,880 I GOT MANY OF THEM SO KEN AND 3404 03:05:59,880 --> 03:06:02,600 TOSH, PH.D STUDENT IN THE LAB 3405 03:06:02,600 --> 03:06:04,240 AND I ALREADY SHOWED THIS 3406 03:06:04,240 --> 03:06:07,480 PICTURE SO THIS WAS THE NATURE 3407 03:06:07,480 --> 03:06:10,880 PAPER AND IN PROGRESS TOO AND 3408 03:06:10,880 --> 03:06:15,120 DRAG AN SA, NO EXCEPTION. 3409 03:06:15,120 --> 03:06:17,680 HOTSEAT IS NOT ONLY FOR FELLOWS 3410 03:06:17,680 --> 03:06:18,920 IT'S EVERYBODY HAD TO GO THERE 3411 03:06:18,920 --> 03:06:24,440 SO THIS IS WHEN IN DRAGANA SAME 3412 03:06:24,440 --> 03:06:31,000 SO YOU CAN -- YEAH. 3413 03:06:31,000 --> 03:06:31,560 JACKIE. 3414 03:06:31,560 --> 03:06:32,000 YEAH. 3415 03:06:32,000 --> 03:06:34,640 IT'S THE ONLY ONE WHERE HE IS 3416 03:06:34,640 --> 03:06:36,120 SITTING AND WRITING SO I DON'T 3417 03:06:36,120 --> 03:06:37,760 KNOW WHAT WAS GOING ON HERE BUT 3418 03:06:37,760 --> 03:06:40,880 SEE THE KIND OF SURPRISE BECAUSE 3419 03:06:40,880 --> 03:06:43,280 IT WAS NOT UP ANDIST LEAVING. 3420 03:06:43,280 --> 03:06:44,680 WHAT ARE WE DOING? 3421 03:06:44,680 --> 03:06:46,400 I'M HAPPY I DID IT AND IT'S THE 3422 03:06:46,400 --> 03:06:51,040 ONE I TOOK IN (INAUDIBLE). 3423 03:06:51,040 --> 03:06:54,200 A FEW YEARS AGO AND SO ALTHOUGH 3424 03:06:54,200 --> 03:06:56,880 I'M FRENCH I'M NOT BRAZILIAN, MY 3425 03:06:56,880 --> 03:07:00,000 WIFE IS BRAZILIAN AND IT WAS MY 3426 03:07:00,000 --> 03:07:01,240 GREAT PLEASURE TO BE SURROUNDED 3427 03:07:01,240 --> 03:07:03,200 BY SO MANY BRAZILIAN PEOPLE AND 3428 03:07:03,200 --> 03:07:05,400 BE ADOPTED BY THEM SO I'M REALLY 3429 03:07:05,400 --> 03:07:09,720 GRATEFUL THAT I'VE BEEN IN THIS 3430 03:07:09,720 --> 03:07:12,880 ENVIRONMENT AND OF COURSE, MANY 3431 03:07:12,880 --> 03:07:16,320 OTHER PEOPLE ALYSE, THAT WE'RE 3432 03:07:16,320 --> 03:07:19,560 PART OF THE COMMUNITY AND THE 3433 03:07:19,560 --> 03:07:22,040 CHILDREN OF ALAN AT THE TIME I 3434 03:07:22,040 --> 03:07:24,360 WAS THERE AND WE ALSO REALLY 3435 03:07:24,360 --> 03:07:25,720 GRATEFUL THAT WE HAVE BEEN 3436 03:07:25,720 --> 03:07:29,160 INVITED AND WONDERFUL BARBECUES 3437 03:07:29,160 --> 03:07:31,120 AND ALSO THANKSGIVING PARTIES 3438 03:07:31,120 --> 03:07:37,720 WITH ALAN AND STEPHANIE AND I'VE 3439 03:07:37,720 --> 03:07:39,600 ALSO KNOWN IN FACT WITH MANY 3440 03:07:39,600 --> 03:07:40,800 GOOD FRIENDS IN DIFFERENT LABS 3441 03:07:40,800 --> 03:07:44,040 SO THAT IS ALAN AND YOU KNOW HIM 3442 03:07:44,040 --> 03:07:45,800 SO LIKE YESTERDAY, THERE WERE 3443 03:07:45,800 --> 03:07:47,800 TWO OTHER FRENCH PEOPLE IN THIS 3444 03:07:47,800 --> 03:07:49,600 ROOM, AT LEAST TWO AND ALAN 3445 03:07:49,600 --> 03:07:52,280 WANTED TO MACK SURE THAT I WOULD 3446 03:07:52,280 --> 03:07:54,240 INTERACT AND GET TO KNOW THEM SO 3447 03:07:54,240 --> 03:07:57,840 OH YOU DON'T KNOW, COME! 3448 03:07:57,840 --> 03:07:59,840 SO NOW I KNOW ISABEL AND DANIEL 3449 03:07:59,840 --> 03:08:02,160 BUT IT'S SOMETHING THAT ALAN 3450 03:08:02,160 --> 03:08:03,680 WOULD DO WITH EVERYBODY. 3451 03:08:03,680 --> 03:08:05,000 IT'S NOTHING SPECIAL. 3452 03:08:05,000 --> 03:08:07,320 IT IS A PICTURE, A BLURRY ONE, 3453 03:08:07,320 --> 03:08:11,640 FROM THE TYPE INTERFERON 3454 03:08:11,640 --> 03:08:13,280 KEYSTONE MEETING AND JUST TO SAY 3455 03:08:13,280 --> 03:08:17,080 IN ADDITION TO BE A GREAT 3456 03:08:17,080 --> 03:08:18,960 MENTOR, AND TO BE AND I'M 3457 03:08:18,960 --> 03:08:20,360 GRATEFUL HE HIRED ME HE IS A 3458 03:08:20,360 --> 03:08:21,680 GREAT HUMAN BEING AND I'M HAPPY 3459 03:08:21,680 --> 03:08:22,480 TO BE HERE TODAY. 3460 03:08:22,480 --> 03:08:26,640 THANK YOU, VERY MUCH. 3461 03:08:26,640 --> 03:08:33,720 [APPLAUSE] 3462 03:08:33,720 --> 03:08:35,080 >> DO YOU WANT TO ASK A 3463 03:08:35,080 --> 03:08:35,360 QUESTION? 3464 03:08:35,360 --> 03:08:40,240 >> SO, OK. 3465 03:08:40,240 --> 03:08:42,960 >> SO NUR ANALYSIS OF THE 3466 03:08:42,960 --> 03:08:45,320 INCREASE DISEASE IN THE ABSENCE 3467 03:08:45,320 --> 03:08:46,000 OF STING THE NEWT TRA FILL 3468 03:08:46,000 --> 03:08:48,240 RESPONSE WAS DRAMATIC AND 3469 03:08:48,240 --> 03:08:49,040 SUSTAINED SO I'M CURIOUS ABOUT 3470 03:08:49,040 --> 03:08:50,560 HOW YOU ARE FOLLOWING UP ON THAT 3471 03:08:50,560 --> 03:08:54,280 AND THAT THE INCREASE CURE ARE 3472 03:08:54,280 --> 03:08:57,280 YOU CERTAIN THAT WAS SAT A SOL I 3473 03:08:57,280 --> 03:09:03,400 CAN OR MIG MIGHT OW -- THERE'S W 3474 03:09:03,400 --> 03:09:05,280 APPRECIATION IT'S INCREASE NORTH 3475 03:09:05,280 --> 03:09:06,600 VARIOUS CELL TYPES SO A CHANGE 3476 03:09:06,600 --> 03:09:08,920 IN THE METABOLIC CHANGE OF THE 3477 03:09:08,920 --> 03:09:10,120 CELLS AND IT'S INTERESTING 3478 03:09:10,120 --> 03:09:13,680 BECAUSE SYNTHESIZES SUBSTRATES 3479 03:09:13,680 --> 03:09:16,120 THAT CAN INCREASE FIBERROSIS. 3480 03:09:16,120 --> 03:09:17,240 >> THAT'S A GOOD POINT. 3481 03:09:17,240 --> 03:09:18,680 WE DID IT BY FLOW. 3482 03:09:18,680 --> 03:09:20,120 SO I DON'T KNOW WHETHER IT WAS 3483 03:09:20,120 --> 03:09:24,240 FROM THE MITO IS IT'S SOMETHING. 3484 03:09:24,240 --> 03:09:25,240 >> IT WOULD BE INTERESTING TO DO 3485 03:09:25,240 --> 03:09:26,880 A WHOLE MORE SINGLE CELL 3486 03:09:26,880 --> 03:09:29,360 ANALYSIS OF THAT BECAUSE THERE 3487 03:09:29,360 --> 03:09:31,840 IS A LOT OF INTEREST TO THE CD9 3488 03:09:31,840 --> 03:09:33,240 POSITIVE SCAR ASSOCIATED MAX AND 3489 03:09:33,240 --> 03:09:34,640 THEY'RE THOUGHT TO BE PROFANE 3490 03:09:34,640 --> 03:09:37,280 ROT TICK SO THERE'S A NEWT TRA 3491 03:09:37,280 --> 03:09:37,920 FILL PART OF THAT. 3492 03:09:37,920 --> 03:09:39,680 >> YEAH, YEAH. 3493 03:09:39,680 --> 03:09:42,480 >> IT'S SOMETHING THAT WE ARE 3494 03:09:42,480 --> 03:09:44,720 REALLY SURPRISED WITH AND REALLY 3495 03:09:44,720 --> 03:09:46,120 INTERESTED BUT I DON'T KNOW 3496 03:09:46,120 --> 03:09:48,440 WHETHER IT'S THEY'RE JUST IF 3497 03:09:48,440 --> 03:09:50,720 IT'S ALSO LIKE COMING OF THE 3498 03:09:50,720 --> 03:09:52,800 PERSIST AND HOW MUCH IT'S 3499 03:09:52,800 --> 03:09:54,240 RELATED TO OTHER THINGS THAT ARE 3500 03:09:54,240 --> 03:09:57,320 GOING ON AND THAT LEAD TO THIS 3501 03:09:57,320 --> 03:09:58,840 PERSISTENCE OR REALLY THEY'RE 3502 03:09:58,840 --> 03:10:00,640 PARTICIPATING IN THE DISEASE SO 3503 03:10:00,640 --> 03:10:02,560 IT'S SOMETHING THAT I DON'T 3504 03:10:02,560 --> 03:10:02,760 KNOW. 3505 03:10:02,760 --> 03:10:05,000 >> AND YOUR SNAPSHOT OF IL-17 3506 03:10:05,000 --> 03:10:07,480 DID YOU LOOK A SINGLE TIME 3507 03:10:07,480 --> 03:10:07,720 POINT. 3508 03:10:07,720 --> 03:10:09,880 >> I DID TWO TIME POINTS SO IT'S 3509 03:10:09,880 --> 03:10:11,680 THE 8 AND I ALSO HAVE A LATER 3510 03:10:11,680 --> 03:10:13,560 TIME POINT AND IT WAS NO 3511 03:10:13,560 --> 03:10:13,880 DIFFERENCE. 3512 03:10:13,880 --> 03:10:16,680 >> THANK YOU. 3513 03:10:16,680 --> 03:10:20,640 >> I'LL ASK THE LAST REQUEST 3514 03:10:20,640 --> 03:10:21,000 QUESTION. 3515 03:10:21,000 --> 03:10:24,400 SO HOW DO YOU THINK THE ROLE OF 3516 03:10:24,400 --> 03:10:25,960 TYPE 3 INTERFERON REGULATING 3517 03:10:25,960 --> 03:10:27,000 NEUTROPHIL RESPONSE IN THIS 3518 03:10:27,000 --> 03:10:27,200 MODEL? 3519 03:10:27,200 --> 03:10:29,000 >> IN THIS MODEL I DON'T KNOW 3520 03:10:29,000 --> 03:10:33,200 BUT IT'S BEEN SHOWN IN TWO OTHER 3521 03:10:33,200 --> 03:10:37,000 MODELS AND ONE PAPER SHOWED THAT 3522 03:10:37,000 --> 03:10:40,080 IL-28 CAN LIMIT THE NEUTRAL 3523 03:10:40,080 --> 03:10:42,480 MIGRATION SO THE SKIN AND THE 3524 03:10:42,480 --> 03:10:44,800 OTHER ONE SAID THAT IN THE GUT 3525 03:10:44,800 --> 03:10:46,200 IT'S NOT THE CASE AT ALL. 3526 03:10:46,200 --> 03:10:49,320 IT DOESN'T CHANGE BUT IT'S 3527 03:10:49,320 --> 03:10:51,160 EFFECTIVE FUNCTION OF NEWT TREE 3528 03:10:51,160 --> 03:10:54,200 FILLS THAT ARE EFFECTED WITH 3529 03:10:54,200 --> 03:10:57,000 LESS WHEN YOU HAVE IL-28 SO IT'S 3530 03:10:57,000 --> 03:10:58,160 NOT SURE WHAT IT'S DOING. 3531 03:10:58,160 --> 03:11:00,520 I THINK IT HAS MULTIPLE ROLES. 3532 03:11:00,520 --> 03:11:01,440 >> ALL RIGHT. 3533 03:11:01,440 --> 03:11:01,840 THANK YOU. 3534 03:11:01,840 --> 03:11:05,840 >> THANK YOU. 3535 03:11:05,840 --> 03:11:16,600 >[OFF MIC]>> IN THE MOUSE YOU HS 3536 03:11:18,760 --> 03:11:19,320 PATHOLOGY. 3537 03:11:19,320 --> 03:11:23,000 WITH THE GR1 AT LEAST. 3538 03:11:23,000 --> 03:11:27,440 [APPLAUSE] 3539 03:11:27,440 --> 03:11:37,960 >> SO, LAST SPEAKER AND KEVIN 3540 03:11:41,000 --> 03:11:44,680 SCHENDEROV. 3541 03:11:46,760 --> 03:11:48,120 DRAGON A, THANK YOU FOR IN 3542 03:11:48,120 --> 03:11:49,000 INVITING ME TO SPEAK. 3543 03:11:49,000 --> 03:11:51,760 IT'S REALLY A GREAT HONOR TO BE 3544 03:11:51,760 --> 03:11:53,960 HERE WITH SO MANY LUMINARIES 3545 03:11:53,960 --> 03:11:56,960 FROM WITHIN LPD OUTSIDE LPD 3546 03:11:56,960 --> 03:11:59,360 STANDING AT THIS PODIUM IT'S 3547 03:11:59,360 --> 03:12:00,560 INCREDIBLE TO BE HERE AND SO 3548 03:12:00,560 --> 03:12:02,600 GRATEFUL TO BE INVITED. 3549 03:12:02,600 --> 03:12:04,880 YOU KNOW, TONY PUT THIS AS A 3550 03:12:04,880 --> 03:12:07,680 FAMILY REUNION AND I ACTUALLY, 3551 03:12:07,680 --> 03:12:09,120 YESTERDAY AND THIS MORNING I WAS 3552 03:12:09,120 --> 03:12:10,360 THINKING THE EX ACTS SAME 3553 03:12:10,360 --> 03:12:11,680 PHRASING THIS REALLY DOES FEEL 3554 03:12:11,680 --> 03:12:14,160 LIKE COMING HOME TO A FAMILY TO 3555 03:12:14,160 --> 03:12:16,280 BE AMONG AWFUL YOU AND IT'S SO 3556 03:12:16,280 --> 03:12:20,120 GRATEFUL TO SEE EVERYONE HORNING 3557 03:12:20,120 --> 03:12:21,480 ALAN AND USUALLY ALAN IS NOT THE 3558 03:12:21,480 --> 03:12:24,320 CENTER OF ATTENTION BECAUSE AS 3559 03:12:24,320 --> 03:12:26,920 ALAN'S TRAINEE, I HAVE FELT AND 3560 03:12:26,920 --> 03:12:28,400 I KNOW SO MANY OTHERS HAVE SAID 3561 03:12:28,400 --> 03:12:29,960 THE SAME THING THAT HE ALWAYS 3562 03:12:29,960 --> 03:12:31,920 PUT US FRONT AND CENTER AND THAT 3563 03:12:31,920 --> 03:12:34,120 HE WAS ALWAYS SUPPORTING US AND 3564 03:12:34,120 --> 03:12:38,880 HELPING US AND INTERROG INTRODUO 3565 03:12:38,880 --> 03:12:39,920 OTHERS EVEN YESTERDAY AT 3566 03:12:39,920 --> 03:12:42,480 RECEPTION, ALAN'S HONOR, HE WAS 3567 03:12:42,480 --> 03:12:43,800 INTRODUCING US TO OTHER PEOPLE 3568 03:12:43,800 --> 03:12:46,440 SO I KNOW THAT THIS IS PROBABLY 3569 03:12:46,440 --> 03:12:48,120 COUNTER TO YOUR NATURAL AN BUT 3570 03:12:48,120 --> 03:12:50,880 I'M GLAD WE'RE TAKING THE TIME 3571 03:12:50,880 --> 03:12:52,240 TO REALLY TALK ABOUT EVERYTHING 3572 03:12:52,240 --> 03:12:53,880 THAT YOU'VE DONE FOR ALL OF US 3573 03:12:53,880 --> 03:12:56,280 AND THIS IS OF COURSE FROM LAST 3574 03:12:56,280 --> 03:12:59,200 NIGHT AND AS CARL MENTIONED, I 3575 03:12:59,200 --> 03:13:02,720 WAS A GRAD STUDENT WITH ALAN 3576 03:13:02,720 --> 03:13:04,600 FROM '07 TO 2012 I CAME TO HIM 3577 03:13:04,600 --> 03:13:06,960 BEING INTERESTED IN WORKING ON 3578 03:13:06,960 --> 03:13:08,800 TH17 CELLS AND HE GRACIOUSLY 3579 03:13:08,800 --> 03:13:13,920 TOOK ME ON AND EVEN THOUGH HE 3580 03:13:13,920 --> 03:13:15,880 WAS BASICALLY WITH PTDOCS OR 3581 03:13:15,880 --> 03:13:19,240 MUCH MORE EXPERIENCED THAN I WAS 3582 03:13:19,240 --> 03:13:21,200 AT THE TIME IN THE LAB AND HE 3583 03:13:21,200 --> 03:13:23,080 WAS WILLING TO HUMOR ME AND 3584 03:13:23,080 --> 03:13:25,960 TRAIN ME AND TEACH ME SO MUCH 3585 03:13:25,960 --> 03:13:28,080 ABOUT SCIENCE AND HOW TO CRAFT 3586 03:13:28,080 --> 03:13:30,440 EXPERIMENT AND HOW TO WRITE 3587 03:13:30,440 --> 03:13:31,920 PAPERS AND EVEN AFTER I LEFT THE 3588 03:13:31,920 --> 03:13:35,160 LAB, HE HAS BEEN SO SUPPORTIVE I 3589 03:13:35,160 --> 03:13:36,800 WENT TO HOP TINS FOR MEDICINE 3590 03:13:36,800 --> 03:13:39,160 SCHOOL, ALAN CAME TO MY 3591 03:13:39,160 --> 03:13:40,560 GRADUATION AND SINCE THEN I'M 3592 03:13:40,560 --> 03:13:42,320 BACK IN THE RESEARCH WORLD AS 3593 03:13:42,320 --> 03:13:48,920 SAY FELLOW AND PULL LYNN ARY 3594 03:13:48,920 --> 03:13:50,280 CRITICAL AIR AND I'M APPLYING 3595 03:13:50,280 --> 03:13:53,320 FOR A GRANT AND RECENTLY AND 3596 03:13:53,320 --> 03:13:55,120 VERY HELPFULLY SUGGESTED THAT I 3597 03:13:55,120 --> 03:13:58,880 SPEAK TO EDMONTON PEARCE WHEN 3598 03:13:58,880 --> 03:13:59,480 EDMONTON PEARCE CAME AND MY 3599 03:13:59,480 --> 03:14:00,760 CURRENT MENTOR IS LEAVING 3600 03:14:00,760 --> 03:14:04,320 HOPKINS AND ED IS GRACIOUSLY 3601 03:14:04,320 --> 03:14:06,160 TAKING ME ON SO ALAN HAS BEEN 3602 03:14:06,160 --> 03:14:08,160 HELPING ME EVERYWHERE ALONG THE 3603 03:14:08,160 --> 03:14:10,600 WAY WHEN I WAS IN HIS LAB TO 3604 03:14:10,600 --> 03:14:13,000 CURRENTLY AND MY WIFE AND I HAD 3605 03:14:13,000 --> 03:14:15,680 A SON 16 MONTHS AGO NOW AND ALAN 3606 03:14:15,680 --> 03:14:18,120 ALSO IS THERE AT HIS PANDEMIC 3607 03:14:18,120 --> 03:14:19,840 ZOOM BIRTHDAY PARTY AND 3608 03:14:19,840 --> 03:14:22,480 GRACIOUSLY PUTTING UP WITH THE 3609 03:14:22,480 --> 03:14:23,720 BIBBY SHARK VIDEO THAT WE WERE 3610 03:14:23,720 --> 03:14:25,600 WATCHING AND SO ALAN HAS BEEN SO 3611 03:14:25,600 --> 03:14:27,600 MUCH MORE THAN JUST A COLLEAGUE 3612 03:14:27,600 --> 03:14:32,600 AND A MENTOR AND YOU HAVE BEEN 3613 03:14:32,600 --> 03:14:33,840 REALLY A FRIEND TO US AND THANK 3614 03:14:33,840 --> 03:14:35,520 YOU SO MUCH, ALAN. 3615 03:14:35,520 --> 03:14:38,800 GETTING TO THE SCIENTIFIC PART 3616 03:14:38,800 --> 03:14:40,320 I'M GOING TO TALK ABOUT WORK 3617 03:14:40,320 --> 03:14:44,360 RELATED TO ACUTE RESPIRATORY 3618 03:14:44,360 --> 03:14:47,600 DISTRESS SYSTEM SO I'M DOING 3619 03:14:47,600 --> 03:14:49,360 TRAINING SO I SPENT IN THE 3620 03:14:49,360 --> 03:14:50,600 ICUs AND THIS IS A CONDITION 3621 03:14:50,600 --> 03:14:52,320 WE TREAT REGULARLY AND 3622 03:14:52,320 --> 03:14:53,560 ESPECIALLY RECENTLY WITH THE 3623 03:14:53,560 --> 03:14:59,240 COVID PANDEMIC AND SO ARDS IS 3624 03:14:59,240 --> 03:15:01,880 DISEASES CALLED IN L AS AN 3625 03:15:01,880 --> 03:15:03,480 ACRONYM WAS FIRST DESCRIBED IN 3626 03:15:03,480 --> 03:15:05,760 1967 IN THE STUDY IN THE LAND 3627 03:15:05,760 --> 03:15:08,160 SET IN A DOZEN PATIENTS WITH 3628 03:15:08,160 --> 03:15:09,720 RESPIRATORY FAILURE FOR VARIOUS 3629 03:15:09,720 --> 03:15:11,560 REASONS AND SINCE THEN WE'VE 3630 03:15:11,560 --> 03:15:13,600 REALIZED THAT AIRDS CAN OCCUR 3631 03:15:13,600 --> 03:15:16,240 DUE TO DIRECTOR INDIRECT LUNG 3632 03:15:16,240 --> 03:15:18,160 INJURY FOR ANY NUMBER OF CAUSES 3633 03:15:18,160 --> 03:15:19,760 THAT EFFECT ABOUT 200,000 3634 03:15:19,760 --> 03:15:22,600 INDIVIDUALS IN THE U.S. AND A 3635 03:15:22,600 --> 03:15:24,160 FEW MILLION WORLDWIDE EACH YEAR 3636 03:15:24,160 --> 03:15:25,600 AND UNFORTUNATELY WE'RE TERRIBLE 3637 03:15:25,600 --> 03:15:26,920 AT TREATING IT. 3638 03:15:26,920 --> 03:15:29,400 WE REALLY HAVE VERY HIGH 3639 03:15:29,400 --> 03:15:32,800 MORTALITY DESPITE BEST ICU CARE 3640 03:15:32,800 --> 03:15:36,880 30% TO 40% OF ERS DIE OF MULTI 3641 03:15:36,880 --> 03:15:38,600 ORGAN FAILURE PRIMARILY AND JUST 3642 03:15:38,600 --> 03:15:40,680 TO GIVE AN IDEA OF WHAT IT LOOKS 3643 03:15:40,680 --> 03:15:43,520 LIKE, THIS IS A NORMAL X-RAY. 3644 03:15:43,520 --> 03:15:44,960 THE LUNGS LOOK DARK AND YOU DO 3645 03:15:44,960 --> 03:15:47,120 HAVE TO BE A PULL MINUTOLOGIST 3646 03:15:47,120 --> 03:15:51,040 TO SEE THE LUNGS LOOK WHITE AND 3647 03:15:51,040 --> 03:15:54,320 SO REALLY DIFFUSED LUNG INJURY 3648 03:15:54,320 --> 03:15:56,680 AND I ALLUDED TO MANY DIFFERENT 3649 03:15:56,680 --> 03:15:58,680 CLAUSES BUT JUST TO SPECIFY A 3650 03:15:58,680 --> 03:16:01,000 FEW OF THEM IN TERMS OF DIRECT 3651 03:16:01,000 --> 03:16:03,480 LUNG ENTRY AND PNEUMONIA AND 3652 03:16:03,480 --> 03:16:07,680 SEVERE COVID-19 LEADING TO 3653 03:16:07,680 --> 03:16:10,560 PNEUMONIA AND AS SIRRATION AND 3654 03:16:10,560 --> 03:16:13,040 TRAUMA TO THE CHEST AND NEAR 3655 03:16:13,040 --> 03:16:18,320 DROWNING AND ALSO INDIRECT LUNG 3656 03:16:18,320 --> 03:16:20,080 INJURY AND NON NA MOAN KA CAN 3657 03:16:20,080 --> 03:16:28,240 CAUSE ARDS IN ADDITION TO NA 3658 03:16:28,240 --> 03:16:30,200 KNOWNIA AND THEY CAN CAUSE ARDS 3659 03:16:30,200 --> 03:16:34,000 AND REALLY ARE CARE FOR ARDS IS 3660 03:16:34,000 --> 03:16:37,760 SUPPORTIVE SO PEOPLE HAVE 3661 03:16:37,760 --> 03:16:39,040 SIGNIFICANT HIGH POXEMIA, LOW 3662 03:16:39,040 --> 03:16:40,360 LEVELS OF OXYGEN SO WE PUT THEM 3663 03:16:40,360 --> 03:16:42,520 ON VENTILATORS AND BREATHING 3664 03:16:42,520 --> 03:16:44,920 MACHINES TO HELP SUPPORT AND WE 3665 03:16:44,920 --> 03:16:47,080 HAVE LEARNED THAT YOU HAVE TO 3666 03:16:47,080 --> 03:16:48,840 USE A VENTILATOR IN A SPECIFIC 3667 03:16:48,840 --> 03:16:49,160 WAY. 3668 03:16:49,160 --> 03:16:50,920 WE CALL IT LUNG PROTECTIVE 3669 03:16:50,920 --> 03:16:52,240 VENTILATION AND LOW TITLE 3670 03:16:52,240 --> 03:16:54,440 VOLUMES TO REDUCE TRAUMA FROM 3671 03:16:54,440 --> 03:16:56,680 PRESSURE AND OVER DIS TENSION OF 3672 03:16:56,680 --> 03:16:58,400 THE LUNGS AND WE'VE ALSO FOUND 3673 03:16:58,400 --> 03:17:00,720 THAT CERTAIN PATIENTS BENEFIT 3674 03:17:00,720 --> 03:17:02,720 FROM PRONING, TURNING THEM ON 3675 03:17:02,720 --> 03:17:03,960 THEIR BELLY NOW THAT I HAVE A 3676 03:17:03,960 --> 03:17:07,240 KID I CALL IT TUMMY TIME AND WE 3677 03:17:07,240 --> 03:17:08,480 LEARNED YOU HAVE TO BE CAREFUL 3678 03:17:08,480 --> 03:17:10,960 OF THE A FLUID YOU GIVE THESE 3679 03:17:10,960 --> 03:17:12,480 PATIENTS BUT THERE'S NO 3680 03:17:12,480 --> 03:17:15,680 PHARMACOLOGICAL THERAPY FOR 3681 03:17:15,680 --> 03:17:16,000 ARDS. 3682 03:17:16,000 --> 03:17:17,680 WE DO KNOW PATH OWE 3683 03:17:17,680 --> 03:17:21,240 PHYSIOLOGICALLY THAT ARDS IS 3684 03:17:21,240 --> 03:17:23,160 HIGHLY INFLAMMATORY SO THIS IS A 3685 03:17:23,160 --> 03:17:24,640 FIGURE SUMMARIZING WHAT WE KNOW 3686 03:17:24,640 --> 03:17:26,960 BUT IN THE INITIAL PHASE OF 3687 03:17:26,960 --> 03:17:29,800 ARDS, YOU GET ACTIVATION OF A 3688 03:17:29,800 --> 03:17:32,240 LOT OF THE INNATE IMMUNE CELLS 3689 03:17:32,240 --> 03:17:34,760 THAT WE ALL KNOW AND LOVE AND 3690 03:17:34,760 --> 03:17:38,080 THEY USE LOTS OF LOAN CYTOKINES, 3691 03:17:38,080 --> 03:17:40,080 REACTIVE OXYGEN PEE SEIZE AND 3692 03:17:40,080 --> 03:17:43,440 YOU GET LOTS OF BARRIER INJURY 3693 03:17:43,440 --> 03:17:46,120 TO THE BARRIERS AND MORE CELLS 3694 03:17:46,120 --> 03:17:49,080 COME IN FLUID COMES IN AND THE 3695 03:17:49,080 --> 03:17:51,240 VLI ARE FLOODED THAT WHY THE 3696 03:17:51,240 --> 03:17:54,480 LUNG IS WHITE AS I SHOWED YOU ON 3697 03:17:54,480 --> 03:17:55,160 THAT X-RAY. 3698 03:17:55,160 --> 03:17:59,320 IF MANY PATIENTS, IF YOU SUPPORT 3699 03:17:59,320 --> 03:18:00,720 THEM, THEN OVER TIME THEY WILL 3700 03:18:00,720 --> 03:18:02,640 HEAL AND THIS WILL ROW SOLVE 3701 03:18:02,640 --> 03:18:04,640 THERE'S A SHIFT IN THE 3702 03:18:04,640 --> 03:18:06,200 PHENOTYPES OF THE MACROPHAGES IN 3703 03:18:06,200 --> 03:18:08,480 THE LUNG AND THEY BECOME MORE 3704 03:18:08,480 --> 03:18:10,720 PRO RESOLUTION RATHER THAN PRO 3705 03:18:10,720 --> 03:18:12,200 INFLAMMATORY AND YOU HAVE A DROP 3706 03:18:12,200 --> 03:18:17,040 IN THE PRODUCTION OF CYTOKINES 3707 03:18:17,040 --> 03:18:22,520 AND BASICALLY THESE PRONE 3708 03:18:22,520 --> 03:18:25,320 INFLAMMATORY STIMULI RESOLVE AND 3709 03:18:25,320 --> 03:18:27,280 THERE'S HEALING AND 3710 03:18:27,280 --> 03:18:29,080 UNFORTUNATELY AS I SAID, 30% TO 3711 03:18:29,080 --> 03:18:32,200 40% OF PATIENTS DOES NOT HAPPEN 3712 03:18:32,200 --> 03:18:34,280 AND EVEN IN PEOPLE WHO DO HEAL A 3713 03:18:34,280 --> 03:18:37,920 LOT OF THEM HEAL IN A 3714 03:18:37,920 --> 03:18:41,520 DIS-REGULATED FIE BROTT TICK WAY 3715 03:18:41,520 --> 03:18:44,560 AND HAVE ARDS, EVEN IF PATIENTS 3716 03:18:44,560 --> 03:18:47,400 SURVIVE THEY CAN HAVE MORBIDITY 3717 03:18:47,400 --> 03:18:49,680 LATER ON. 3718 03:18:49,680 --> 03:18:51,040 PEOPLE HAVE TRIED KNOWING THIS 3719 03:18:51,040 --> 03:18:54,320 PATH OF PHYSIOLOGY VARIOUS 3720 03:18:54,320 --> 03:18:56,560 INFLAMMATORY THERAPIES AND 3721 03:18:56,560 --> 03:18:58,360 UNFORTUNATELY, THEY HAVE LARGELY 3722 03:18:58,360 --> 03:18:59,480 BEEN FAILURES SO STEROIDS 3723 03:18:59,480 --> 03:19:03,040 HAVEN'T WORKED OUTSIDE OF 3724 03:19:03,040 --> 03:19:07,040 COVID-19 AND ANTI-GMCSF, ALL OF 3725 03:19:07,040 --> 03:19:09,720 THESE HAVE BEEN FAILED CLINICAL 3726 03:19:09,720 --> 03:19:13,360 TRIALS AND SO THE THOUGHT BEHIND 3727 03:19:13,360 --> 03:19:15,600 THE WORK THAT I DID, I STARTED 3728 03:19:15,600 --> 03:19:19,160 THIS WITH JOHNATHAN POWELL AND 3729 03:19:19,160 --> 03:19:21,200 MAUREEN HORTON AT HOPKINS AND 3730 03:19:21,200 --> 03:19:22,880 WE'LL CONTINUE ED PEARCE IS 3731 03:19:22,880 --> 03:19:23,920 MAYBE WE'RE NOT TARGETING 3732 03:19:23,920 --> 03:19:26,280 INFLAMMATION THE RIGHT WAY SO 3733 03:19:26,280 --> 03:19:28,400 WE'RE INTERESTED IN IMMUNO 3734 03:19:28,400 --> 03:19:30,840 METABOLISM AND PEOPLE HAVE 3735 03:19:30,840 --> 03:19:33,520 REALIZED THAT THERE ARE PROFOUND 3736 03:19:33,520 --> 03:19:35,800 METABOLIC SHIFTS GOING ON IN 3737 03:19:35,800 --> 03:19:37,240 IMMUNE CELLS THAT'S AIR 3738 03:19:37,240 --> 03:19:39,560 ACTIVATED DEPENDING ON HOW YOU 3739 03:19:39,560 --> 03:19:41,160 ACTIVATE THEM AND THOSE 3740 03:19:41,160 --> 03:19:42,400 METABOLIC CHANGES ARE VERY 3741 03:19:42,400 --> 03:19:44,720 IMPORTANT FOR THEIR FUNCTION. 3742 03:19:44,720 --> 03:19:46,880 SO, WE HYPOTHESIZED THAT MAYBE 3743 03:19:46,880 --> 03:19:49,040 BY UNDERSTANDING SOME OF THE 3744 03:19:49,040 --> 03:19:51,360 METABOLIC CHANGES HAPPENING IN 3745 03:19:51,360 --> 03:19:53,160 ARDS, WE CAN FIND SOME 3746 03:19:53,160 --> 03:19:55,080 DIS-REGULATED METABOLIC PATHWAYS 3747 03:19:55,080 --> 03:19:58,120 SO THAT MAYBE WE CAN TARGET TO 3748 03:19:58,120 --> 03:20:01,160 TROY TO PROMOTE BETTER RECOVER 3749 03:20:01,160 --> 03:20:04,480 ROW FROM LUNG INJURY AND REDUCED 3750 03:20:04,480 --> 03:20:05,640 DETRIMENTAL INFLAMMATION SO OUR 3751 03:20:05,640 --> 03:20:07,920 APPROACH WAS TO SET UP MODELS OF 3752 03:20:07,920 --> 03:20:10,240 LUNG INJURY BECAUSE WE WANTED TO 3753 03:20:10,240 --> 03:20:11,120 FIND PATHWAYS THAT OCCURRED IN 3754 03:20:11,120 --> 03:20:12,480 MORE THAN ONE MODEL AND WE 3755 03:20:12,480 --> 03:20:14,840 DIDN'T WANT TO JUST FIND ONE 3756 03:20:14,840 --> 03:20:17,240 MODEL SPECIFIC PATHWAY AND SO WE 3757 03:20:17,240 --> 03:20:18,600 SET UP A FEW DIFFERENT MODELS 3758 03:20:18,600 --> 03:20:22,960 AND USING METABALOMICS, WE 3759 03:20:22,960 --> 03:20:25,240 MEASURED LEVELS OF A FEW HUNDRED 3760 03:20:25,240 --> 03:20:26,600 METABOLITES IN THE LUNGS OF 3761 03:20:26,600 --> 03:20:28,960 INJURED VERSUS UNINJURED MICE 3762 03:20:28,960 --> 03:20:30,800 AND SO JUST TO QUICKLY TELL YOU 3763 03:20:30,800 --> 03:20:36,120 THE MODELS WE USED, ONE IS A 3764 03:20:36,120 --> 03:20:46,600 BACTERIA MA KNOWNIA AND AND 3765 03:21:01,840 --> 03:21:12,000 EARLY ON AND. 3766 03:21:38,320 --> 03:21:44,440 >> TO MA LAB LOAM I CAN AND IN 3767 03:21:44,440 --> 03:21:49,320 RED AND THESE AND DIFFERENT 3768 03:21:49,320 --> 03:21:52,120 BETWEEN THE DAMAGE LUNGS VERSUS 3769 03:21:52,120 --> 03:21:55,400 THE NAIVE MICE SO THIS IS IN THE 3770 03:21:55,400 --> 03:21:57,560 MODEL AND SO YOU CAN SEE MANY 3771 03:21:57,560 --> 03:21:59,480 METABOLITES ARE CHANGING AND IF 3772 03:21:59,480 --> 03:22:02,160 YOU DO A PRINCIPLE COMPONENT 3773 03:22:02,160 --> 03:22:03,560 ANALYSIS WE CAN SEE THE MICE 3774 03:22:03,560 --> 03:22:05,560 REALLY DO CLUSTER BASED ON THEIR 3775 03:22:05,560 --> 03:22:08,280 STATUS SO THESE ARE THE NAIVE 3776 03:22:08,280 --> 03:22:10,840 MICE AND THE INFECTED MICE AT 3777 03:22:10,840 --> 03:22:11,640 DIFFERENT TIME POINTS AND THE 3778 03:22:11,640 --> 03:22:17,520 MICE AR RESOLVING THE RESOLUTIOO 3779 03:22:17,520 --> 03:22:19,280 THEY GO BACK TO THE NAIVE MICE. 3780 03:22:19,280 --> 03:22:20,760 THIS IS A HEAT MAP SHOWING IS 3781 03:22:20,760 --> 03:22:24,720 THAT MANY OF THE METABOLITES WE 3782 03:22:24,720 --> 03:22:27,160 LOOK AT START OFF HIGH IN THE 3783 03:22:27,160 --> 03:22:28,960 NAIVE MICE SO EACH A IS A MOUSE 3784 03:22:28,960 --> 03:22:31,000 AND THE RED ARE NAIVE SO THEY 3785 03:22:31,000 --> 03:22:33,160 START OFF HIGH AND NAIVE AND 3786 03:22:33,160 --> 03:22:35,280 DROVE DURING INJURY AND START TO 3787 03:22:35,280 --> 03:22:38,200 RECOVER DURING LATER TIME POINTS 3788 03:22:38,200 --> 03:22:41,480 AND THEN ALSO, SOME METABOLITES 3789 03:22:41,480 --> 03:22:43,960 START LOW AND GO UP DURING LUNG 3790 03:22:43,960 --> 03:22:45,320 INJURY AND THEN START TO COME 3791 03:22:45,320 --> 03:22:47,440 BACK DOWN SO, THERE ARE BOTH 3792 03:22:47,440 --> 03:22:50,160 PATTERNS THAT WE SEE AND OF 3793 03:22:50,160 --> 03:22:51,560 COURSE, IT'S HARD LOOKING AT 3794 03:22:51,560 --> 03:22:53,120 LISTS OF THESE SO ONE THING WE 3795 03:22:53,120 --> 03:22:55,080 DID WAS LOOK AT PATHWAY ANALYSIS 3796 03:22:55,080 --> 03:22:56,920 AND YOU CAN SEE VARIOUS 3797 03:22:56,920 --> 03:23:00,080 METABOLICS PATHWAYS THAT ARE 3798 03:23:00,080 --> 03:23:03,200 CHANGING DURING LUNG INJURY WITH 3799 03:23:03,200 --> 03:23:07,000 STREP NOW MANY OWE AND YOU SEE 3800 03:23:07,000 --> 03:23:09,560 NUCLEOTIDE METABOLISM, AMINO 3801 03:23:09,560 --> 03:23:13,000 ACID, TCA CYCLE, ET CETERA. 3802 03:23:13,000 --> 03:23:14,360 WE BECAME INTERESTED IN TWO 3803 03:23:14,360 --> 03:23:19,400 SPECIFIC METABOLITES, MIO AND WE 3804 03:23:19,400 --> 03:23:22,160 SAW THAT ACROSS THE THREE LUNG 3805 03:23:22,160 --> 03:23:24,520 INJURY MODELS THEY HAD SIMILAR 3806 03:23:24,520 --> 03:23:28,960 CONNETICS SO IN ALL THREE 3807 03:23:28,960 --> 03:23:30,360 MODELS, BOTH WOULD DROP DURING 3808 03:23:30,360 --> 03:23:34,400 ACUTE LUNG INJURY AND THEN AS 3809 03:23:34,400 --> 03:23:35,960 YOU LOOK LATER THEY START TO 3810 03:23:35,960 --> 03:23:39,080 COME BACK UP. 3811 03:23:39,080 --> 03:23:45,280 SO, MANY OF YOU MAY KNOW 3812 03:23:45,280 --> 03:23:50,160 GLUTATHIONE IS A TRY PEP SIDE 3813 03:23:50,160 --> 03:23:54,040 AND REACTS WITH FRO RADICALS AND 3814 03:23:54,040 --> 03:23:56,120 THOSE CHANGE IT FROM A REDUCED 3815 03:23:56,120 --> 03:24:00,320 FORM TO SAY OXIDIZED FORM AND 3816 03:24:00,320 --> 03:24:02,000 INTERESTINGLY FOR A LONG TIME 3817 03:24:02,000 --> 03:24:04,320 ACTUALLY, PEOPLE HAD SHOWN THAT 3818 03:24:04,320 --> 03:24:14,920 THE LEVELS OF GLUTE A THIGH ON O 3819 03:24:17,560 --> 03:24:19,120 IT'S A LITTLE CHALLENGING TO 3820 03:24:19,120 --> 03:24:23,160 ACTUALLY USE THIS AS A TREATMENT 3821 03:24:23,160 --> 03:24:31,080 THOUGH BECAUSE IT'S NOT 3822 03:24:31,080 --> 03:24:33,080 INEFFICIENT WAY TO INCREASE SO 3823 03:24:33,080 --> 03:24:34,320 PEOPLE HAVE TRIED ALTERNATIVES 3824 03:24:34,320 --> 03:24:37,280 AND SO THERE WAS ACTUALLY A 3825 03:24:37,280 --> 03:24:42,040 COUPLE OF TRIALS IN PEOPLE USING 3826 03:24:42,040 --> 03:24:44,720 SISTINE KNACK WHICH IS PROVIDING 3827 03:24:44,720 --> 03:24:47,120 SISTINE IT'S AN AMINO ACID SO 3828 03:24:47,120 --> 03:24:54,800 IT'S THOUGHT IT WILL HELP 3829 03:24:54,800 --> 03:24:56,080 INCREASE IN OTHER COMPOUND WE 3830 03:24:56,080 --> 03:25:02,240 WERE INTERESTED IN IS IT'S A HAS 3831 03:25:02,240 --> 03:25:04,600 BETTER BIO AVAILABILITY AND CELL 3832 03:25:04,600 --> 03:25:05,720 PERMEABILITY AND ACTUALLY CAN 3833 03:25:05,720 --> 03:25:07,760 GET INTO CELLS AND IS CONVERTED 3834 03:25:07,760 --> 03:25:15,720 INTO REDUCED GLUTATHIONE AND THE 3835 03:25:15,720 --> 03:25:18,880 OTHER IS A SUGAR ALCOHOL THAT IS 3836 03:25:18,880 --> 03:25:21,800 A PRECURSOR USED IN INTRA 3837 03:25:21,800 --> 03:25:26,600 CELLULAR SIGNALING LIKE THE KAI 3838 03:25:26,600 --> 03:25:29,240 A NAS PATHWAY SO IT'S A PRE 3839 03:25:29,240 --> 03:25:31,840 CURSER OF A COMPONENT AND SUR 3840 03:25:31,840 --> 03:25:33,520 FALK TIN IS IMPORTANT FOR THE 3841 03:25:33,520 --> 03:25:35,360 LUNG AND TO REDUCE SURFACE 3842 03:25:35,360 --> 03:25:38,320 FUNCTION AND IT HAS A REGULATORY 3843 03:25:38,320 --> 03:25:41,360 ROLE AND IT'S BEEN SHOWN TO HELP 3844 03:25:41,360 --> 03:25:44,400 WITH INSULIN RESISTANCE AND ALSO 3845 03:25:44,400 --> 03:25:46,600 MOST RELEVANT TO WHAT WE SAW 3846 03:25:46,600 --> 03:25:49,560 WITH GLUTATHIONE IT HAS A ROLE 3847 03:25:49,560 --> 03:25:55,240 IN REDOX BALANCE. 3848 03:25:55,240 --> 03:25:57,560 IT CAN HELP WITH THE PHOSPHATE 3849 03:25:57,560 --> 03:26:00,800 PATHWAY SO WE ASKED A RELATIVELY 3850 03:26:00,800 --> 03:26:03,240 SIMPLE QUESTION SINCE THE MIO 3851 03:26:03,240 --> 03:26:06,000 INOS OWE TOLL AND LEVELS ARE LOW 3852 03:26:06,000 --> 03:26:13,560 IN THE MICE WITH ACUTE LUNG 3853 03:26:13,560 --> 03:26:23,720 INJURY, 3854 03:26:25,880 --> 03:26:29,760 WE TREATED MICE WITH EITHER JUST 3855 03:26:29,760 --> 03:26:34,600 CONTROL WATER OR MIO MONTHS 3856 03:26:34,600 --> 03:26:36,560 INTOLL OR KNACK AND IT DIDN'T 3857 03:26:36,560 --> 03:26:39,560 WORK IN THE HUMAN TRIALS AND 3858 03:26:39,560 --> 03:26:41,080 DAILY BY PUT THESE COMPOUNDS IN 3859 03:26:41,080 --> 03:26:42,200 THEIR DRINKING WATER SO THEY 3860 03:26:42,200 --> 03:26:43,840 WERE EXPOSED TO THEM 3861 03:26:43,840 --> 03:26:45,240 CONTINUOUSLY DURING THAT TIME AS 3862 03:26:45,240 --> 03:26:47,440 WELL AND WE WERE EXCITED TO SEE 3863 03:26:47,440 --> 03:26:50,920 THAT WE DID SEE A REDUCTION IN 3864 03:26:50,920 --> 03:26:55,760 MORTALITY FROM STREP NUMO AND 3865 03:26:55,760 --> 03:26:56,880 INTERESTINGLY DIDN'T SEE ANY 3866 03:26:56,880 --> 03:27:02,080 REDUCTION MORTALITY WITH KNACK 3867 03:27:02,080 --> 03:27:03,600 SO THIS WE HAVE TO SEE WHETHER 3868 03:27:03,600 --> 03:27:05,840 THIS HAS ANY RELEVANCE TO ANY 3869 03:27:05,840 --> 03:27:06,960 MODELS OF LUNG INJURY BUT WE 3870 03:27:06,960 --> 03:27:08,560 WERE EXCITED TO SEE THIS AT 3871 03:27:08,560 --> 03:27:12,760 LEAST IN ONE MODEL. 3872 03:27:12,760 --> 03:27:14,480 AND WE'RE WORKING ON 3873 03:27:14,480 --> 03:27:15,280 MECHANISTICALLY SEEING WHAT IS 3874 03:27:15,280 --> 03:27:16,680 GOING ON BUT ONE THING WE HAVE 3875 03:27:16,680 --> 03:27:19,080 SEEN IS REDUCED BACTERIAL LOADS 3876 03:27:19,080 --> 03:27:21,480 SO FASTER BACTERIAL CLEAR NOT IN 3877 03:27:21,480 --> 03:27:28,320 ANCE IN THEBAL AND IN DAY FIVE R 3878 03:27:28,320 --> 03:27:29,760 INFECTION SO IT SEEMS THAT 3879 03:27:29,760 --> 03:27:32,480 TREATING THE MICE WITH THESE 3880 03:27:32,480 --> 03:27:34,800 COMPOUNDS DOES SPEED UP 3881 03:27:34,800 --> 03:27:36,120 BACTERIAL CLEARANCE SO OF 3882 03:27:36,120 --> 03:27:37,440 COURSE, WE'RE WONDERING WHETHER 3883 03:27:37,440 --> 03:27:39,600 THIS IS AN ALL RELEVANT TO 3884 03:27:39,600 --> 03:27:41,600 PEOPLE SO THIS MIGHT JUST BE A 3885 03:27:41,600 --> 03:27:44,200 PHENOMENON OF MICE SO TO GET AT 3886 03:27:44,200 --> 03:27:47,000 THIS, WE'VE DONE SOME 3887 03:27:47,000 --> 03:27:49,800 METABOLOMICS IN HUMANS SO IN OUR 3888 03:27:49,800 --> 03:27:51,520 ICUs OF COURSE, ESPECIALLY 3889 03:27:51,520 --> 03:27:52,600 EARLY IN THE PANDEMIC WE HAD A 3890 03:27:52,600 --> 03:27:56,320 LOT OF COVID-19 PATIENTS AND 3891 03:27:56,320 --> 03:27:57,800 SOME OF THEIR FAMILIES CONSENTED 3892 03:27:57,800 --> 03:28:05,200 FOR US TO DO NON LAVAGE WHERE WE 3893 03:28:05,200 --> 03:28:10,200 PUT A SUCTION CATHETER DOWN IN 3894 03:28:10,200 --> 03:28:11,200 THE TRACK Y'ALL TUBES AND PULLED 3895 03:28:11,200 --> 03:28:15,760 IT BACK AND WITH OUR 3896 03:28:15,760 --> 03:28:26,240 COLLABORATORS WE'VE DONE -- 3897 03:28:30,240 --> 03:28:32,120 COMPARED TO PATIENTS UNDER 3898 03:28:32,120 --> 03:28:33,320 ANESTHESIAIA FOR ELECTIVE 3899 03:28:33,320 --> 03:28:34,600 SURGERY AND AGREED TO LET US DO 3900 03:28:34,600 --> 03:28:36,920 THE SAME PROCEDURE, COMPARED TO 3901 03:28:36,920 --> 03:28:37,920 THESE HEALTHY CONTROLS, THE 3902 03:28:37,920 --> 03:28:40,760 COVID PATIENTS WITH ARDS HAVE 3903 03:28:40,760 --> 03:28:45,160 LOWER LEVELS OF MIO INOS TOLL 3904 03:28:45,160 --> 03:28:46,880 AND OF COURSE WAS EXCITING SINCE 3905 03:28:46,880 --> 03:28:48,400 THAT CORRELATED WITH WHAT WE SAW 3906 03:28:48,400 --> 03:28:50,440 IN THE MOUSE MODELS. 3907 03:28:50,440 --> 03:28:55,200 SO, TO CONCLUDE, WE'VE SEEN THAT 3908 03:28:55,200 --> 03:28:58,560 THERE ARE SOME METABOLICS SHARED 3909 03:28:58,560 --> 03:29:00,040 BETWEEN VARIOUS LUNG INJURY 3910 03:29:00,040 --> 03:29:02,200 MODELS AND BOTH DIRECT AND 3911 03:29:02,200 --> 03:29:05,960 INDIRECT LUNG INJURY AND IT 3912 03:29:05,960 --> 03:29:06,920 SEEMS THAT THEY ARE INDEPENDENT 3913 03:29:06,920 --> 03:29:14,160 OF THE EXACT MECHANISM OF INJURY 3914 03:29:14,160 --> 03:29:24,680 AND SO WE'RE HOPING THAT THIS 3915 03:29:35,920 --> 03:29:41,720 ACTUALLY IS RELEVANT TO HUMAN 3916 03:29:41,720 --> 03:29:43,360 ARDS AND LOOKING AT OTHER LUNG 3917 03:29:43,360 --> 03:29:51,800 INJURY MODEL AND MODEL THAT NICO 3918 03:29:51,800 --> 03:29:55,000 SHOWED LOOKING MORE AT MECHANISM 3919 03:29:55,000 --> 03:29:56,320 AND WHAT THEY'RE DOING AND ALSO 3920 03:29:56,320 --> 03:29:58,400 ALL THE DATA I'VE SHOWN YOU IS 3921 03:29:58,400 --> 03:29:59,840 LOOKING AT WHOLE LUNG AND WE'RE 3922 03:29:59,840 --> 03:30:00,880 INTERESTED IN UNDERSTANDING 3923 03:30:00,880 --> 03:30:02,840 WHETHER THESE METABOLICS CHANGES 3924 03:30:02,840 --> 03:30:06,760 ARE HAPPENING IN THE IMMUNE OR 3925 03:30:06,760 --> 03:30:13,560 NON IMMUNE AND AND METABOLOMICS 3926 03:30:13,560 --> 03:30:15,560 ON THOSE SO INTERESTED IN 3927 03:30:15,560 --> 03:30:19,040 LOOKING AT REGULATION OF GONE 3928 03:30:19,040 --> 03:30:20,960 EXPRESSION METABOLIC ENZYMES AND 3929 03:30:20,960 --> 03:30:22,200 SEEING IF THEY'RE CHANGING 3930 03:30:22,200 --> 03:30:24,280 WHETHER IT UNDERLIES THE 3931 03:30:24,280 --> 03:30:26,240 METABOLITE CHANGES WE'RE SEEING 3932 03:30:26,240 --> 03:30:29,480 AND LOOKING AT METABOLIC FLUX 3933 03:30:29,480 --> 03:30:31,920 THROUGH THESE PATHWAYS AND 3934 03:30:31,920 --> 03:30:33,560 LOOKING AT NON COVID-19 ARDS 3935 03:30:33,560 --> 03:30:35,560 PATIENTS TO SEE WHETHER THIS IS 3936 03:30:35,560 --> 03:30:37,560 RELEVANT TO DISEASES OTHER THAN 3937 03:30:37,560 --> 03:30:40,840 COVID-19 SO A LOT OF WORK TO DO 3938 03:30:40,840 --> 03:30:43,000 SO WE HAVE SO FAR SO, I WANT TO 3939 03:30:43,000 --> 03:30:45,320 THANK MY ADVISERS AND AS I 3940 03:30:45,320 --> 03:30:47,080 MENTIONED I STARTED THIS WORK 3941 03:30:47,080 --> 03:30:53,800 WITH MAUREEN AND JOHNATHAN AND 3942 03:30:53,800 --> 03:30:56,920 ED IS GOING TO TAKE ME ON AS 3943 03:30:56,920 --> 03:30:58,200 JOHNATHAN AND MAUREEN HAVE LEFT 3944 03:30:58,200 --> 03:31:00,120 AND WE HAVE A LOT OF HELP FROM 3945 03:31:00,120 --> 03:31:02,600 PEOPLE AT MAUREEN'S LAB AND LEON 3946 03:31:02,600 --> 03:31:05,840 AND ED IS REALLY THE KEY 3947 03:31:05,840 --> 03:31:07,720 METABOLOMICS COLLABORATOR AND WE 3948 03:31:07,720 --> 03:31:09,520 HAD A LOT OF HELP AND SO THANK 3949 03:31:09,520 --> 03:31:12,520 YOU GUYS SO MUCH FOR YOUR 3950 03:31:12,520 --> 03:31:13,680 ATTENTION AND LOVE TO TAKE ANY 3951 03:31:13,680 --> 03:31:14,720 QUESTIONS. 3952 03:31:14,720 --> 03:31:20,440 [APPLAUSE] 3953 03:31:20,440 --> 03:31:22,160 >> TERRIFIC TALK. 3954 03:31:22,160 --> 03:31:22,880 THANK YOU. 3955 03:31:22,880 --> 03:31:24,720 YOU KNOW, MORE OF A COMMENT THAN 3956 03:31:24,720 --> 03:31:26,160 ANYTHING ELSE. 3957 03:31:26,160 --> 03:31:29,200 GIVEN THE HUGE AMOUNT OF 3958 03:31:29,200 --> 03:31:31,000 LITERATURE ON OXIDATE TIVE 3959 03:31:31,000 --> 03:31:32,440 STRESS, AND THE FACT THAT 3960 03:31:32,440 --> 03:31:33,600 CLINICAL TRIALS BASICALLY HE 3961 03:31:33,600 --> 03:31:35,000 HAVE ALWAYS FAILED, 3962 03:31:35,000 --> 03:31:37,280 , IF YOU LOCK AT THAT LITERATURE 3963 03:31:37,280 --> 03:31:38,880 THE THING THAT IS MOST A PARENT 3964 03:31:38,880 --> 03:31:41,400 IS AS PEOPLE MOVE 3965 03:31:41,400 --> 03:31:42,480 TRANSLATIONALLY COMPLETE LACK OF 3966 03:31:42,480 --> 03:31:44,800 ATTENTION TO PKPD RELATIONSHIPS 3967 03:31:44,800 --> 03:31:46,680 AND SO AS YOU F. THIS GOES 3968 03:31:46,680 --> 03:31:48,080 FORWARD AS YOU DO THIS I THINK 3969 03:31:48,080 --> 03:31:49,840 IT'S THE CRITICAL THING WHEN YOU 3970 03:31:49,840 --> 03:31:51,280 START THINKING TRANSLATIONALLY 3971 03:31:51,280 --> 03:31:53,360 AND BECAUSE THAT LITERATURE IS 3972 03:31:53,360 --> 03:31:55,520 JUST RIFE WITH DISAPPOINTMENT 3973 03:31:55,520 --> 03:31:57,760 AND RIFE WITH POOR TRANSLATION. 3974 03:31:57,760 --> 03:32:03,200 >> THAT'S A GREAT POINT, THANK 3975 03:32:03,200 --> 03:32:04,920 YOU. 3976 03:32:12,600 --> 03:32:13,120 >>LET'S START WHERE WHERE 3977 03:32:13,120 --> 03:32:14,680 STOPPED BEFORE LUNCH SO WE'LL 3978 03:32:14,680 --> 03:32:21,600 JUST FINISH THE LAST SECTION AND 3979 03:32:21,600 --> 03:32:23,080 WE MENTION SEVERAL TIMES IN THIS 3980 03:32:23,080 --> 03:32:25,440 MEETING, ALAN'S LAB ALWAYS HAS A 3981 03:32:25,440 --> 03:32:27,200 LOT OF BRAZILIANS SO I THINK 3982 03:32:27,200 --> 03:32:31,960 THIS IS INGREDIENT FOR BRAZILIAN 3983 03:32:31,960 --> 03:32:34,040 SCIENTISTS EVEN ENRICHED IN THE 3984 03:32:34,040 --> 03:32:38,080 TV PROGRAMS OR FIVE OR SIX 3985 03:32:38,080 --> 03:32:42,280 BRAZILIANS AND SIX OR SEVEN OR 3986 03:32:42,280 --> 03:32:52,800 10 YEARS AND SHE SPENT SIX YEARS 3987 03:32:58,480 --> 03:33:08,960 AND IN TUCSON AND ALL RIGHT -- I 3988 03:33:11,080 --> 03:33:20,720 HOPE EVERYBODY IS WELL FED. 3989 03:33:20,720 --> 03:33:26,360 SO, I WANT TODAY REALLY EXPRESS 3990 03:33:26,360 --> 03:33:27,320 MY GRATEFULNESS TO BE HERE AND 3991 03:33:27,320 --> 03:33:30,360 I'M REALLY GRATEFUL, NOT ONLY TO 3992 03:33:30,360 --> 03:33:33,280 BE HERE NOW BUT GRATEFUL BY ALL 3993 03:33:33,280 --> 03:33:37,360 THE TIME THAT I SPENT IN THE 3994 03:33:37,360 --> 03:33:47,760 IMMUNO BIOLOGY SECTION. 3995 03:33:50,360 --> 03:33:52,960 NOW I'M BACK IN BRAZIL AND I SET 3996 03:33:52,960 --> 03:33:55,520 UP MY SHOP SOUTH OF BRAZIL 3997 03:33:55,520 --> 03:33:59,520 ALTHOUGH AS A BIT COLD SO ALAN 3998 03:33:59,520 --> 03:34:02,720 VISITS THERE BUT TAKES A WHILE 3999 03:34:02,720 --> 03:34:06,000 BECAUSE HE REALLY, REALLY LIKES 4000 03:34:06,000 --> 03:34:08,160 THE NORTHEAST PART OF BRAZIL AND 4001 03:34:08,160 --> 03:34:11,840 THAT IS HIS FAVORITE AND LOOK AT 4002 03:34:11,840 --> 03:34:12,080 THAT. 4003 03:34:12,080 --> 03:34:17,880 THAT WAS NATAL AND SO LOOK AT 4004 03:34:17,880 --> 03:34:20,400 HIS FACE AND HIS SMILE. 4005 03:34:20,400 --> 03:34:22,320 HE IS RELAXED THERE. 4006 03:34:22,320 --> 03:34:24,160 HE IS ALWAYS LIKE THAT WHEN HE 4007 03:34:24,160 --> 03:34:30,680 IS IN NORTHEAST, I CAN TELL YOU. 4008 03:34:30,680 --> 03:34:32,080 I AM GOING TO READ SOMETHING 4009 03:34:32,080 --> 03:34:35,960 THAT I WROTE SO I DON'T -- I 4010 03:34:35,960 --> 03:34:40,040 DON'T MISS ANYTHING THAT I WANT 4011 03:34:40,040 --> 03:34:41,160 TO SAY. 4012 03:34:41,160 --> 03:34:45,280 ALAN, FIRST EVER ALL, I LOVE 4013 03:34:45,280 --> 03:34:45,600 YOU. 4014 03:34:45,600 --> 03:34:50,160 I LOVE YOU GATO, A LOT. 4015 03:34:50,160 --> 03:34:51,640 SERIOUSLY, 22 YEARS AGO, HOW CAN 4016 03:34:51,640 --> 03:34:53,040 I NOT LOVE THIS GUY. 4017 03:34:53,040 --> 03:34:56,120 22 YEARS AGO, ALAN TAKES A RIDE 4018 03:34:56,120 --> 03:35:01,760 WITH ME BECAUSE MY FORMER 4019 03:35:01,760 --> 03:35:06,120 PROFESSORS GINA BA HAW ASKED ME 4020 03:35:06,120 --> 03:35:11,160 TO TAKE ALAN, STEPHANIE AND BOB 4021 03:35:11,160 --> 03:35:13,920 COFFMAN TO SHOW THEM A GOOD 4022 03:35:13,920 --> 03:35:14,360 TIME. 4023 03:35:14,360 --> 03:35:17,680 OF COURSE, THAT'S WHAT I DID. 4024 03:35:17,680 --> 03:35:22,480 SO, WE WENT TO PILLOW RIO AND 4025 03:35:22,480 --> 03:35:26,400 ALISON AND LAURA WAS ALSO THERE 4026 03:35:26,400 --> 03:35:30,120 SO WE WENT AND DID A LOT OF 4027 03:35:30,120 --> 03:35:32,960 DANCING AND SALVADOR IF YOU ARE 4028 03:35:32,960 --> 03:35:35,760 NOT FAMILIAR WITH THE AREA. 4029 03:35:35,760 --> 03:35:41,600 A LOT OF CYPERONIAS. 4030 03:35:41,600 --> 03:35:43,440 IT WAS AN OLD CAR AND I FELT 4031 03:35:43,440 --> 03:35:47,520 REALLY RESPONSIBLE FOR THESE 4032 03:35:47,520 --> 03:35:49,040 GUYS, I BECAUSE NOTHING COULD 4033 03:35:49,040 --> 03:35:50,640 HAPPEN LIKE AN ACCIDENT OR 4034 03:35:50,640 --> 03:35:52,320 ANYTHING SO IT WAS KIND OF A 4035 03:35:52,320 --> 03:35:56,280 VERY BIG RESPONSIBILITY. 4036 03:35:56,280 --> 03:35:58,800 SO, I DID MY JOB, I DELIVERED 4037 03:35:58,800 --> 03:36:01,280 THEM VERY HAPPY TO THE HOTEL. 4038 03:36:01,280 --> 03:36:04,880 SO THE NEXT DAY, ALAN ASKED ME 4039 03:36:04,880 --> 03:36:08,040 WHAT I WANT TO DO AFTER MEDICAL 4040 03:36:08,040 --> 03:36:11,360 SCHOOL AND I SAID, I WANT TO DO 4041 03:36:11,360 --> 03:36:14,640 RESEARCH AND HE SAID, I LIKED 4042 03:36:14,640 --> 03:36:15,680 YOU. 4043 03:36:15,680 --> 03:36:17,760 I WANT TO WORK ON A MECHANISM 4044 03:36:17,760 --> 03:36:20,600 FOR YOU TO COME TO THE IMMUNO 4045 03:36:20,600 --> 03:36:24,360 BIOLOGY SE SECTION AND WORK WITS 4046 03:36:24,360 --> 03:36:26,600 SO IT WAS MY DREAMT AND I FELT 4047 03:36:26,600 --> 03:36:29,680 REALLY, REALLY HAPPY ABOUT IT. 4048 03:36:29,680 --> 03:36:31,960 SO I GUESS ALAN SAW SOMETHING IN 4049 03:36:31,960 --> 03:36:36,160 ME THAT I WAS NOT EVEN SEEING 4050 03:36:36,160 --> 03:36:36,880 BACK THEN. 4051 03:36:36,880 --> 03:36:42,720 SO I ARRIVED HERE IN 2001 AND IT 4052 03:36:42,720 --> 03:36:44,760 WAS A VERY COLD WINTER BUT 4053 03:36:44,760 --> 03:36:47,840 COMING FROM BRAZIL BUT I WAS 4054 03:36:47,840 --> 03:36:51,200 STAYING AT CHIEFERS PLACE, REST 4055 03:36:51,200 --> 03:36:54,560 IN PEACE, AND HE INTRODUCED ME 4056 03:36:54,560 --> 03:37:01,280 TO A LOT OF THE THINGS, EVEN THE 4057 03:37:01,280 --> 03:37:03,680 CHIEFERENI WHICH IS A WAY TO 4058 03:37:03,680 --> 03:37:05,720 MAKE HYPER INIA. 4059 03:37:05,720 --> 03:37:08,440 I LOVE THIS RIGHT AWAY. 4060 03:37:08,440 --> 03:37:11,920 I MET THESE GUYS ARE THE THREE 4061 03:37:11,920 --> 03:37:14,200 MUSKETEERS AND I REMEMBER THEM 4062 03:37:14,200 --> 03:37:17,640 IN IT TOOK ME LIKE IN THE HAND 4063 03:37:17,640 --> 03:37:19,600 AND GAVE ME A TOUR AT THE NIH, 4064 03:37:19,600 --> 03:37:23,560 WE CAME TO FAS BACK THEN WE HAD 4065 03:37:23,560 --> 03:37:26,240 TO SHOW THE IAP66 FORM BUT NOW 4066 03:37:26,240 --> 03:37:27,760 THEY CHANGED TO HOLD THE NUMBERS 4067 03:37:27,760 --> 03:37:32,480 SO IT WAS REALLY FUN. 4068 03:37:32,480 --> 03:37:35,880 AND THAT WAS -- 4069 03:37:35,880 --> 03:37:45,080 [LAUGHTER] 4070 03:37:45,080 --> 03:37:48,960 SO I HAVE LEARNED ANYTHING FOR 4071 03:37:48,960 --> 03:37:49,520 YOU. 4072 03:37:49,520 --> 03:37:53,360 CHOW CHUCK, DAMIAN AND ALSO I 4073 03:37:53,360 --> 03:37:55,200 WORKED A LITTLE BIT AND I 4074 03:37:55,200 --> 03:37:58,200 LEARNED A LOT EVEN THOUGH I 4075 03:37:58,200 --> 03:38:00,120 DON'T THINK I'M A TOXO PERSON 4076 03:38:00,120 --> 03:38:01,840 BUT I LEARNED A LOT FROM THE 4077 03:38:01,840 --> 03:38:05,480 MEETINGS AND WITH DRAGANA, 4078 03:38:05,480 --> 03:38:07,120 ROMINA AND JULIO BACK THEN. 4079 03:38:07,120 --> 03:38:09,800 AFTERWARDS, I WORKED WITH TWO 4080 03:38:09,800 --> 03:38:13,320 CRUISE IN THE LAB AND HOW TO PAG 4081 03:38:13,320 --> 03:38:23,880 STUDENT AND HE CAME SO HE WORKED 4082 03:38:23,880 --> 03:38:24,640 HARD EARL ON. 4083 03:38:24,640 --> 03:38:29,880 SO HERE, I DID SOME PADDING AND 4084 03:38:29,880 --> 03:38:32,880 I DID A LOT OF THE BARBECUE FOR 4085 03:38:32,880 --> 03:38:37,200 ALAN AND I DID A LOT OF LAB 4086 03:38:37,200 --> 03:38:37,640 ENTERTAINMENT. 4087 03:38:37,640 --> 03:38:40,120 AND I CAN TELL YOU FROM MY 4088 03:38:40,120 --> 03:38:42,960 HEART, I LIKED THAT EACH ONE OF 4089 03:38:42,960 --> 03:38:48,120 YOU CAN FEEL MY LOVE AND MY HUG 4090 03:38:48,120 --> 03:38:49,520 FOR THE SPECIAL TREATMENT I 4091 03:38:49,520 --> 03:38:53,840 RECEIVED TO HEAR AND ACTUALLY, 4092 03:38:53,840 --> 03:38:55,760 IT WAS VERY IMPORTANT FOR ME NOT 4093 03:38:55,760 --> 03:38:57,920 ONLY AS A SCIENTIST BUT AS A 4094 03:38:57,920 --> 03:39:07,360 SCIENTIST BUT AS A HUMAN BEING. 4095 03:39:07,360 --> 03:39:09,040 ALAN, I NEVER TOLD YOU GUYS I 4096 03:39:09,040 --> 03:39:10,320 WON THE LOTTERY HERE BUT 4097 03:39:10,320 --> 03:39:16,240 SOMETHING WAY, WAY BETTER THAN 4098 03:39:16,240 --> 03:39:17,440 MONEY, NEW SISTERS AND BROTHERS 4099 03:39:17,440 --> 03:39:20,320 CAME INTO MY LIFE WHICH I STILL 4100 03:39:20,320 --> 03:39:22,720 HAVE TODAY SO MY STUDENTS, 4101 03:39:22,720 --> 03:39:25,520 FORMER STUDENTS IN THE LAB, THEY 4102 03:39:25,520 --> 03:39:26,440 CAME TO CHUCK'S LAB AND THEY 4103 03:39:26,440 --> 03:39:33,720 EVEN WENT TO AUSTRALIA AND 4104 03:39:33,720 --> 03:39:37,400 ACROSS GROUP AND THEY DID A LOT 4105 03:39:37,400 --> 03:39:41,400 OF COURSES WITH BIO FORMAT TICKS 4106 03:39:41,400 --> 03:39:45,320 SO I'M TRYING TO GIVE BACK TO 4107 03:39:45,320 --> 03:39:48,680 THE PLANET WHAT YOU TAUGHT ME. 4108 03:39:48,680 --> 03:39:53,880 AND THANK YOU VERY MUCH FOR THE 4109 03:39:53,880 --> 03:39:55,280 OPPORTUNITY. 4110 03:39:55,280 --> 03:40:04,560 SO, JUST THAT'S ALAN I WAS A 4111 03:40:04,560 --> 03:40:08,880 VISITING PROFESSOR IN 2017 AND I 4112 03:40:08,880 --> 03:40:10,960 ALWAYS COME HERE AND ALAN WOULD 4113 03:40:10,960 --> 03:40:13,440 ALWAYS TAKE ME AND DRAGANA AND 4114 03:40:13,440 --> 03:40:15,040 EVERYBODY WAS, I WAS VERY HAPPY 4115 03:40:15,040 --> 03:40:17,240 AND I FELT REALLY AT HOME AND 4116 03:40:17,240 --> 03:40:20,080 THAT DRAGANA, MAYBE I CAN DO 4117 03:40:20,080 --> 03:40:21,160 THIS ALL ON HERE. 4118 03:40:21,160 --> 03:40:22,960 THERE'S A SOUND THERE WE CANNOT 4119 03:40:22,960 --> 03:40:24,440 HEAR SO HE IS MAKING A COFFEE 4120 03:40:24,440 --> 03:40:27,320 AND HE IS LIKE, OH, I GOT TO DIG 4121 03:40:27,320 --> 03:40:29,840 UP THIS OLD PICTURE OF ME ON MY 4122 03:40:29,840 --> 03:40:31,360 SURF BOARD BECAUSE I WAS DOING 4123 03:40:31,360 --> 03:40:34,840 SUFFERING BACK THEN SO, I DON'T 4124 03:40:34,840 --> 03:40:37,440 THINK THAT'S THE PICTURE BECAUSE 4125 03:40:37,440 --> 03:40:40,400 THE SKIN COLOR DOESN'T MATCH BUT 4126 03:40:40,400 --> 03:40:42,280 IT COULD BE YOU I STILL WAIT ON 4127 03:40:42,280 --> 03:40:44,200 THAT PICTURE. 4128 03:40:44,200 --> 03:40:52,880 OF COURSE, THE ONE TO ONE 4129 03:40:52,880 --> 03:40:54,800 HOTSEAT WRITING THE PAPER AND I 4130 03:40:54,800 --> 03:40:56,160 HAD MY CURLY BIG HAIR DURING MY 4131 03:40:56,160 --> 03:40:57,400 SA BAD CAL. 4132 03:40:57,400 --> 03:41:06,240 I CAME HERE AND WORKED ON THE 4133 03:41:06,240 --> 03:41:16,400 HOTSEAT. 4134 03:41:18,160 --> 03:41:19,240 I TOOK OUT THE ADDRESS BUT I 4135 03:41:19,240 --> 03:41:20,640 KNOW YOU ARE INVITING PEOPLE SO 4136 03:41:20,640 --> 03:41:22,120 YOU CAN REMOVE IT AND PEOPLE CAN 4137 03:41:22,120 --> 03:41:24,040 SEE THE ADDRESS OVER HERE. 4138 03:41:24,040 --> 03:41:28,080 SO, AND THAT IS ALAN'S 4139 03:41:28,080 --> 03:41:28,480 INVITATION. 4140 03:41:28,480 --> 03:41:31,320 HE LIKED THE LITTLE WORD DOCK 4141 03:41:31,320 --> 03:41:34,280 GUYS AND I THINK THAT WAS BEFORE 4142 03:41:34,280 --> 03:41:36,840 THE PANDEMIC SO YOU SEE ALSO 4143 03:41:36,840 --> 03:41:41,360 DIEGO HERE, EDUARDO, THAT IS 4144 03:41:41,360 --> 03:41:45,680 PEDRO AND THAT IS -- WHAT'S HIS 4145 03:41:45,680 --> 03:41:46,120 NAME. 4146 03:41:46,120 --> 03:41:50,440 AND THAT IS ALSO -- WHAT'S HIS 4147 03:41:50,440 --> 03:41:54,040 NAME? 4148 03:41:54,040 --> 03:41:57,040 SO, I DIDN'T BRING ANY DATA. 4149 03:41:57,040 --> 03:42:02,480 I WANT TO SHOW YOU WHAT I HELPED 4150 03:42:02,480 --> 03:42:05,080 PEOPLE AT MY UNIVERSITY. 4151 03:42:05,080 --> 03:42:10,840 SO WE WORKED ON THIS NEW HERE 4152 03:42:10,840 --> 03:42:15,640 AND THAT IS MY RIDE I USED TO DO 4153 03:42:15,640 --> 03:42:18,960 EVERYDAY DURING THE PANDEMIC AND 4154 03:42:18,960 --> 03:42:20,720 HERE THAT'S OUR IF STYLE THAT 4155 03:42:20,720 --> 03:42:22,360 I'M GOING TO BE RESPONSIBLE IN 4156 03:42:22,360 --> 03:42:31,640 THAT INSTITUTION NOW. 4157 03:42:31,640 --> 03:42:33,360 DEDICATING TO OUR BRAZIL VERSION 4158 03:42:33,360 --> 03:42:35,760 OF THE LAB OF IMMUNO BIOLOGY 4159 03:42:35,760 --> 03:42:39,280 THAT'S NOT OF COURSE STOPPING 4160 03:42:39,280 --> 03:42:42,920 HERE AND IT'S DAVID SACKS PUT IT 4161 03:42:42,920 --> 03:42:45,560 REALLY NICELY BEFORE. 4162 03:42:45,560 --> 03:42:50,200 SO, IN THIS 13 AND 14 YEARS A 4163 03:42:50,200 --> 03:42:57,320 LOT OF PEOPLE STUDENT HE'D IN 4164 03:42:57,320 --> 03:43:02,680 THE LABS ABLE TO CREATE THREE 4165 03:43:02,680 --> 03:43:13,200 P.I.s AND EVERYTHING THAT ALAN 4166 03:43:56,880 --> 03:43:59,560 CAUGHT ME AND AS I PROMISED, 4167 03:43:59,560 --> 03:44:03,920 THAT'S ISABELLA MY DAUGHTER AND 4168 03:44:03,920 --> 03:44:06,760 WE USED TO GO SURFING TOGETHER 4169 03:44:06,760 --> 03:44:10,840 AND OVER HERE AND SHE WAS LITTLE 4170 03:44:10,840 --> 03:44:15,680 SHE STARTED PAINTING AND NOW 4171 03:44:15,680 --> 03:44:19,200 SHE'S GRILL AND SHE'S BECOMING 4172 03:44:19,200 --> 03:44:20,960 AN ARTIST WITH THE WATER 4173 03:44:20,960 --> 03:44:23,000 PAINTING THAT SHE'S DOING A LOT 4174 03:44:23,000 --> 03:44:26,160 NOW AND ALAN IS ALWAYS ASKING 4175 03:44:26,160 --> 03:44:27,480 HOW IS SHE. 4176 03:44:27,480 --> 03:44:30,520 SHE'S NOW 14-YEARS-OLD SO NOW 4177 03:44:30,520 --> 03:44:33,240 THAT SHE'S GOT HER MOTHER'S 4178 03:44:33,240 --> 03:44:37,040 LOOKS, I GUESS, BEAUTIFUL. 4179 03:44:37,040 --> 03:44:37,800 AND THAT IT. 4180 03:44:37,800 --> 03:44:38,400 THANK YOU, VERY MUCH. 4181 03:44:38,400 --> 03:44:48,840 [APPLAUSE] 4182 03:44:48,840 --> 03:44:50,280 I FORGOT TO TELL YOU GUYS, I WAS 4183 03:44:50,280 --> 03:44:53,640 GOING TO DID A GEORGE YO PLAY SO 4184 03:44:53,640 --> 03:44:57,120 HE INVITED YOU TO GO TO HIS 4185 03:44:57,120 --> 03:44:58,080 HOUSE IN ITALY. 4186 03:44:58,080 --> 03:45:00,160 THAT'S NOT AS BEAUTIFUL AS ITALY 4187 03:45:00,160 --> 03:45:03,560 HOUSE BUT YOU CAN COME TO MY 4188 03:45:03,560 --> 03:45:03,800 HOUSE. 4189 03:45:03,800 --> 03:45:04,840 IT'S AVAILABLE TO YOU TOO. 4190 03:45:04,840 --> 03:45:07,400 THANK YOU. 4191 03:45:07,400 --> 03:45:17,640 [APPLAUSE] 4192 03:45:46,560 --> 03:45:49,240 >> GOOD AFTERNOON, EVERYONE, I'M 4193 03:45:49,240 --> 03:45:50,640 FROM THE NATIONAL CANCER 4194 03:45:50,640 --> 03:45:52,840 INSTITUTE AND TOGETHER WITH 4195 03:45:52,840 --> 03:45:55,760 NIKKI AT NIDCR I'M CHAIRING THE 4196 03:45:55,760 --> 03:46:02,920 NIH FDA CYTOKINE CENTER GROUP 4197 03:46:02,920 --> 03:46:13,000 AND. 4198 03:46:13,640 --> 03:46:15,640 >> IT'S AN 800-MEMBER STRONG 4199 03:46:15,640 --> 03:46:17,200 COMMUNITY OF SCIENTISTS AT NIH 4200 03:46:17,200 --> 03:46:19,840 AND FDA INTERESTED IN SIGN 4201 03:46:19,840 --> 03:46:21,520 CYTOKINE BIOLOGY AND WE DO TWO 4202 03:46:21,520 --> 03:46:23,880 OR THREE MINI SYMPOSIUMS ON 4203 03:46:23,880 --> 03:46:25,320 CYTOKINE RESEARCH EVERY YEAR AND 4204 03:46:25,320 --> 03:46:27,680 WE WATER ANNUAL BEST PAPER IN 4205 03:46:27,680 --> 03:46:38,800 SIGHT OWEICYTOKINE AND WE HAVE R 4206 03:46:47,400 --> 03:46:50,080 WINNER FROM MIKE AND THE REASON 4207 03:46:50,080 --> 03:46:52,200 WHY WE ARE HERE ACTUALLY IS 4208 03:46:52,200 --> 03:46:55,840 BECAUSE NIH CIG HAS FINISHED 4209 03:46:55,840 --> 03:46:57,560 TELEVISION 1992 AND HAS BEEN CO 4210 03:46:57,560 --> 03:46:59,760 FOUNDED, IT'S ACTUALLY A 4211 03:46:59,760 --> 03:47:01,000 BRAINCHILD OF ALAN, WHO 4212 03:47:01,000 --> 03:47:02,080 ORGANIZED AT IT AT THAT TIME AND 4213 03:47:02,080 --> 03:47:03,480 HAS BEEN STILL RUNNING IT ON TO 4214 03:47:03,480 --> 03:47:07,680 THIS TIME TOGETHER WITH US AND 4215 03:47:07,680 --> 03:47:11,840 SO IN 2017 THE CIG CELEBRATED 4216 03:47:11,840 --> 03:47:13,760 ITS 25th ANNIVERSARY AND I 4217 03:47:13,760 --> 03:47:16,560 REMEMBER IT WAS A COMMITTEE IN 4218 03:47:16,560 --> 03:47:17,880 GEORGE YO'S LAB AT BUILDING 37 4219 03:47:17,880 --> 03:47:18,840 AND WE WERE THINKING ABOUT HOW 4220 03:47:18,840 --> 03:47:23,000 TO ORGANIZE IT AND MAKE A POSTER 4221 03:47:23,000 --> 03:47:33,400 FOR IT AND ALAN SAID I 4222 03:47:38,200 --> 03:47:39,480 THINK WE SHOULD HAVE A BALLOON? 4223 03:47:39,480 --> 03:47:43,520 I SAID YOU WANT A BALLOON FOR A 4224 03:47:43,520 --> 03:47:43,760 POSTER. 4225 03:47:43,760 --> 03:47:46,120 I WANT A BALLOON WITH THIS ONE 4226 03:47:46,120 --> 03:47:48,560 HERE AND I SAID, YOU WANT A 4227 03:47:48,560 --> 03:47:50,120 CONGRATULATIONS BALLOON, NO, I 4228 03:47:50,120 --> 03:47:53,040 WANT MANY BALLOONS. 4229 03:47:53,040 --> 03:47:54,840 SO, I WAS ASKING ALAN S. THAT 4230 03:47:54,840 --> 03:47:55,320 ENOUGH? 4231 03:47:55,320 --> 03:47:56,920 YEAH BUT THEN IT NEEDS TO BE 4232 03:47:56,920 --> 03:47:58,520 CONNECTED TO THE NIH AND I 4233 03:47:58,520 --> 03:48:01,480 REALLY HAD NO IDEA WHAT IS GOING 4234 03:48:01,480 --> 03:48:03,240 ABOUT AND LISTENING TO ALL THE 4235 03:48:03,240 --> 03:48:04,760 TALKS, ALAN HAS AN ALREADY AND 4236 03:48:04,760 --> 03:48:07,400 HE LIKES TO DRAG IT OUT AND THEN 4237 03:48:07,400 --> 03:48:09,480 AFTER TALKING WITH ALAN, I 4238 03:48:09,480 --> 03:48:10,960 FINALLY FOUND OUT WHAT HE 4239 03:48:10,960 --> 03:48:11,280 WANTED. 4240 03:48:11,280 --> 03:48:12,920 AND HE WANTED, HE GOT 4241 03:48:12,920 --> 03:48:14,520 INSPIRATION FROM HIS FAVORITE 4242 03:48:14,520 --> 03:48:17,040 MOVIE WHICH IS THIS -- AND WHAT 4243 03:48:17,040 --> 03:48:18,960 HE WANTED IS HAVING A LOT OF 4244 03:48:18,960 --> 03:48:21,160 BALLOONS AND LIFTING UP A HOUSE 4245 03:48:21,160 --> 03:48:22,520 WHICH IS THE NIH. 4246 03:48:22,520 --> 03:48:24,600 SO, WE ENDED UP WITH THIS 4247 03:48:24,600 --> 03:48:24,960 POSTER. 4248 03:48:24,960 --> 03:48:27,280 AND AS WE CAN SEE, IT'S THE 4249 03:48:27,280 --> 03:48:29,320 BALLOON AND ALAN WAS HAPPY AND 4250 03:48:29,320 --> 03:48:31,400 HE WAS LIFTING THE NIH THAT WAS 4251 03:48:31,400 --> 03:48:33,240 ALSO GOOD AND THEN HE SAYS NOW 4252 03:48:33,240 --> 03:48:36,440 LET'S ALL DECIDE TO TEST COVERED 4253 03:48:36,440 --> 03:48:38,720 BY NIH INVESTIGATORS WHO ARE AT 4254 03:48:38,720 --> 03:48:39,680 THE NIH. 4255 03:48:39,680 --> 03:48:40,600 SO IT WAS GREAT. 4256 03:48:40,600 --> 03:48:43,560 I THINK IN HINDSIGHT WE WERE 4257 03:48:43,560 --> 03:48:47,120 WRONG BECAUSE THE SCIENCE AT NIH 4258 03:48:47,120 --> 03:48:48,560 IS LIFTED BY THE PEOPLE WHO DO 4259 03:48:48,560 --> 03:48:51,160 THE SCIENCE AND IN HAD I THINK 4260 03:48:51,160 --> 03:48:53,920 THERE'S A BIG BALLOON WHICH IS 4261 03:48:53,920 --> 03:48:55,360 MISSING WHICH IS ALAN AND THIS 4262 03:48:55,360 --> 03:48:57,800 IS JUST CELEBRATING THAT HE 4263 03:48:57,800 --> 03:48:59,600 REALLY HAS WON THIS ALL TOGETHER 4264 03:48:59,600 --> 03:49:02,400 TO CYTOKINE FOR THE LAST 30 4265 03:49:02,400 --> 03:49:04,200 YEARS AND AS YOU CAN REMEMBER, 4266 03:49:04,200 --> 03:49:06,320 THIS YEAR IT'S GOING TO BE A 4267 03:49:06,320 --> 03:49:09,280 30th ANNIVERSARY OF THE THE 4268 03:49:09,280 --> 03:49:11,560 NIH FDA CYTOKINE INTEREST GROUP 4269 03:49:11,560 --> 03:49:13,920 AND ALAN HAS A LOT OF FREE TIME 4270 03:49:13,920 --> 03:49:14,120 NOW -- 4271 03:49:14,120 --> 03:49:14,520 [LAUGHTER] 4272 03:49:14,520 --> 03:49:18,000 >> I HOPE IT'S GOING TO HELP US 4273 03:49:18,000 --> 03:49:19,520 TO ORGANIZE AND I'M NOT SURE 4274 03:49:19,520 --> 03:49:21,480 WHAT MOVIES HE IS WATCHING BUT 4275 03:49:21,480 --> 03:49:23,680 AT LEAST WE'LL HAVE DECIDE ABOUT 4276 03:49:23,680 --> 03:49:26,000 WHAT THE POSTER LOOKS LIKE SO 4277 03:49:26,000 --> 03:49:27,720 WITH THAT, I'LL GIVE IT TO 4278 03:49:27,720 --> 03:49:29,040 KAREN. 4279 03:49:29,040 --> 03:49:32,480 [APPLAUSE] 4280 03:49:32,480 --> 03:49:34,400 THANK YOU SO I'M KAREN I'M FROM 4281 03:49:34,400 --> 03:49:37,720 THE CENTER FOR BUY LOGICS OF THE 4282 03:49:37,720 --> 03:49:40,320 FD A AND CONTINUING THE THEME OF 4283 03:49:40,320 --> 03:49:42,640 INTEREST GROUPS REPRESENTATION 4284 03:49:42,640 --> 03:49:43,960 I'M HAPPEN TO BE THE CURRENT 4285 03:49:43,960 --> 03:49:46,480 CHAIR OF THE IMMUNOLOGY INTEREST 4286 03:49:46,480 --> 03:49:50,880 GROUP OF WHICH ALAN HAS BEEN A 4287 03:49:50,880 --> 03:49:52,520 SUPPORTER EVERY MANY, MANY 4288 03:49:52,520 --> 03:49:52,720 YEARS. 4289 03:49:52,720 --> 03:49:55,280 I HAVE TO DIVERT AND BLOW 4290 03:49:55,280 --> 03:49:58,120 DRAGANA FIVE MINUTES TO ALSO 4291 03:49:58,120 --> 03:49:59,760 ACKNOWLEDGE THAT I THINK I'M A 4292 03:49:59,760 --> 03:50:01,760 REPRESENTATIVE OF ONE OF THE' 4293 03:50:01,760 --> 03:50:02,800 NUMEROUS ABLE PEOPLE OUT THERE 4294 03:50:02,800 --> 03:50:13,440 BEYOND THE IMMEDIATE TRAINEES WR 4295 03:50:17,640 --> 03:50:19,040 I WAS YOUNGER AND STUPIDER THAN 4296 03:50:19,040 --> 03:50:20,720 I AM NOW, ALAN WENT OUT OF HIS 4297 03:50:20,720 --> 03:50:22,840 WAY TO TAKE AN INTEREST IN ME 4298 03:50:22,840 --> 03:50:24,480 AND MY CAREER AND MY SCIENCE AND 4299 03:50:24,480 --> 03:50:27,240 FOR MANY YEARS, HE HAS BEEN A 4300 03:50:27,240 --> 03:50:30,200 SOUNDING BOARD, A SOURCE OF 4301 03:50:30,200 --> 03:50:32,000 WONDERFUL IN A SCIENTIFIC 4302 03:50:32,000 --> 03:50:33,560 INSPIRATION, PERSONAL SUPPORT 4303 03:50:33,560 --> 03:50:36,480 AND ADVISE, I AM STANDING IN MY 4304 03:50:36,480 --> 03:50:37,960 CURRENT JOB ALMOST ENTIRELY 4305 03:50:37,960 --> 03:50:41,040 BECAUSE OF A PIECE OF SAGE 4306 03:50:41,040 --> 03:50:43,040 ADVICE HE GAVE ME WHEN I WAS 4307 03:50:43,040 --> 03:50:44,680 CONSIDERING THIS RELATIVELY NEW 4308 03:50:44,680 --> 03:50:46,720 POSITION FOR ME AND WHICH I 4309 03:50:46,720 --> 03:50:53,880 CANNOT REMEET A PUBLIC MEETING. 4310 03:50:53,880 --> 03:50:55,480 THANK YOU SO MUCH FOR IN 4311 03:50:55,480 --> 03:50:56,920 CONCLUDING ME AND MY LAB AND 4312 03:50:56,920 --> 03:50:58,880 EVERYTHING THAT IS HAPPENED OVER 4313 03:50:58,880 --> 03:51:01,320 THE LAST MANY, MANY YEARS. 4314 03:51:01,320 --> 03:51:02,800 YOU KNOW, WE HAVE ALL TALKED 4315 03:51:02,800 --> 03:51:04,160 THROUGHOUT THE LAST TWO DAYS 4316 03:51:04,160 --> 03:51:06,120 ABOUT ALAN'S BUILDING OF 4317 03:51:06,120 --> 03:51:07,120 COMMUNITIES EVERYWHERE WITHIN 4318 03:51:07,120 --> 03:51:08,960 THE LPD, OF COURSE BUT THROUGH 4319 03:51:08,960 --> 03:51:12,080 OUT THE SCIENCE WORLD AND SO THE 4320 03:51:12,080 --> 03:51:14,240 REST OF MY TASK IS TO RECOGNIZE 4321 03:51:14,240 --> 03:51:19,360 HIS ROLE IN FORMAL COMMUNITY 4322 03:51:19,360 --> 03:51:23,240 BUILDING AND HYUN TOLD US ABOUT 4323 03:51:23,240 --> 03:51:34,480 THTHTHE SIGH COC SIGH CO -- HE D 4324 03:51:35,240 --> 03:51:35,680 THE KNIT BRITS AND THAT 4325 03:51:35,680 --> 03:51:37,320 COMMUNITY TOO IS DRAWING 4326 03:51:37,320 --> 03:51:40,280 TOGETHER PEOPLE WITH COMMON 4327 03:51:40,280 --> 03:51:41,520 INTERESTS IN TUBERCULOSIS AND IT 4328 03:51:41,520 --> 03:51:42,400 IS GOING STRONG. 4329 03:51:42,400 --> 03:51:44,600 ON BEHALF OF ALL OF THOSE NORMAL 4330 03:51:44,600 --> 03:51:46,080 GROUPS THAT YOU HAVE GONE OUT OF 4331 03:51:46,080 --> 03:51:48,720 YOUR WAY TO CREATE AND NURTURE, 4332 03:51:48,720 --> 03:51:50,880 AND TO MOVE ALONG TO THE NEXT 4333 03:51:50,880 --> 03:51:53,520 GENERATION OF PEOPLE, WE HAVE A 4334 03:51:53,520 --> 03:51:55,800 VERY SMALL TOKEN OF APPRECIATION 4335 03:51:55,800 --> 03:51:57,760 WHICH THIS CAN GO TO THE 4336 03:51:57,760 --> 03:51:59,720 BATHROOM AND MOVE DAVID'S MUCH 4337 03:51:59,720 --> 03:52:05,680 BETTER POSTER UP. 4338 03:52:05,680 --> 03:52:15,920 [APPLAUSE] 4339 03:52:40,680 --> 03:52:46,960 [APPLAUSE] 4340 03:52:46,960 --> 03:52:57,200 >> THANK YOU. 4341 03:52:58,840 --> 03:53:03,240 >> HELLO, I'M CATHY ZOON I'M THE 4342 03:53:03,240 --> 03:53:07,600 FORMER SD OF NIAID AND I HAVE A 4343 03:53:07,600 --> 03:53:10,040 DIVISION OF INTRAMURAL RESEARCH 4344 03:53:10,040 --> 03:53:12,760 AND SO I WOULD LIKE TO FIRST OF 4345 03:53:12,760 --> 03:53:23,200 ALL THANK THE ORGANIZERS. 4346 03:53:52,520 --> 03:53:54,080 >> GENEROSITY IN SO MANY WAYS 4347 03:53:54,080 --> 03:53:57,160 AND I'LL ELABORATE ON TWO THINGS 4348 03:53:57,160 --> 03:54:00,080 THAT HAVE GOTTEN SOME ATTENTION 4349 03:54:00,080 --> 03:54:03,080 ALREADY. 4350 03:54:03,080 --> 03:54:05,160 HOPEFULLY WE'LL ADD A FEW MORE 4351 03:54:05,160 --> 03:54:07,040 TIDBITS TO ALAN'S REMARKS OVER 4352 03:54:07,040 --> 03:54:09,040 THE PAST TWO DAYS. 4353 03:54:09,040 --> 03:54:10,240 I'D LIKE TO TALK A LITTLE BIT 4354 03:54:10,240 --> 03:54:13,480 ABOUT ALAN'S LEADERSHIP SKILLS 4355 03:54:13,480 --> 03:54:17,040 AND THEN ALSO HIS MENTORING 4356 03:54:17,040 --> 03:54:25,360 SKILLS AND YOU KNOW, AS A LEADER 4357 03:54:25,360 --> 03:54:26,640 IN ANY ORGANIZATION YOU CAN ONLY 4358 03:54:26,640 --> 03:54:28,160 DO SO MUCH WITHOUT THE SUPPORT 4359 03:54:28,160 --> 03:54:32,600 OF OTHER LEADERS IN YOUR 4360 03:54:32,600 --> 03:54:37,320 ORGANIZATION AND ALAN HAS ALWAYS 4361 03:54:37,320 --> 03:54:39,440 BEEN ONE OF THE FOLKS WHEN I WAS 4362 03:54:39,440 --> 03:54:40,360 SCIENTIFIC DIRECTOR I COULD 4363 03:54:40,360 --> 03:54:41,240 COUNT ON. 4364 03:54:41,240 --> 03:54:44,840 HE WAS ALWAYS THERE AND ASKING 4365 03:54:44,840 --> 03:54:46,920 WHAT HE COULD DO TO HELP. 4366 03:54:46,920 --> 03:54:51,440 SOMETIMES IT WASN'T HELP BUT -- 4367 03:54:51,440 --> 03:54:54,920 ME WAS THERE AND YOU KNOW, I 4368 03:54:54,920 --> 03:54:58,920 HAVE TO SAY ALAN, AND THIS IS 4369 03:54:58,920 --> 03:55:00,560 PARTICULARLY INTERESTING BECAUSE 4370 03:55:00,560 --> 03:55:03,560 ALAN DOES ALWAYS SMILE, ALWAYS 4371 03:55:03,560 --> 03:55:03,800 SMILES. 4372 03:55:03,800 --> 03:55:07,880 BUT ALAN ALSO WORRIES ALL THE 4373 03:55:07,880 --> 03:55:10,920 TIME. 4374 03:55:10,920 --> 03:55:15,360 AND YOU KNOW, NO ONE BROUGHT 4375 03:55:15,360 --> 03:55:16,400 THAT UP. 4376 03:55:16,400 --> 03:55:17,920 ALAN, YOU WOULD COME INTO MY 4377 03:55:17,920 --> 03:55:19,200 OFFICE AND YOU WOULD HAVE A 4378 03:55:19,200 --> 03:55:21,000 SMILE AND YOU WOULD SAY WELL, 4379 03:55:21,000 --> 03:55:23,880 I'M CONCERNED ABOUT THIS AND I'M 4380 03:55:23,880 --> 03:55:25,720 CONCERNED ABOUT THAT AND WE 4381 03:55:25,720 --> 03:55:28,480 WOULD TALK FOR ANOTHER HOUR AND 4382 03:55:28,480 --> 03:55:31,720 FINALLY WE WOULD GET TO THE 4383 03:55:31,720 --> 03:55:38,320 NITTY GRITTY OF THE PROBLEM AND 4384 03:55:38,320 --> 03:55:40,600 I APPRECIATED THAT BECAUSE YOU 4385 03:55:40,600 --> 03:55:43,160 EXPANDED MY HORIZONS AND WHAT TO 4386 03:55:43,160 --> 03:55:43,800 THINK ABOUT AS WELL AS MAKE SURE 4387 03:55:43,800 --> 03:55:45,880 I DIDN'T OVERLOOK ANYTHING AND 4388 03:55:45,880 --> 03:55:48,640 WE ALL RECOGNIZE ALAN'S GREAT 4389 03:55:48,640 --> 03:55:49,600 SCIENTIFIC ACHIEVEMENTS AND I 4390 03:55:49,600 --> 03:55:59,960 HAVE TO SAY, SINKEL BSE THE 4391 03:55:59,960 --> 03:56:02,160 LABORATORY HAD OUTSTANDING 4392 03:56:02,160 --> 03:56:03,320 REVIEW AND PROBABLY THAT I 4393 03:56:03,320 --> 03:56:05,720 SHOULDN'T SAY THAT BECAUSE IT'S 4394 03:56:05,720 --> 03:56:06,960 PROBABLY CONFIDENTIAL 4395 03:56:06,960 --> 03:56:11,640 INFORMATION BUT TOO BAD AND HE 4396 03:56:11,640 --> 03:56:15,720 DID A MARVEL US JOB PREPARING 4397 03:56:15,720 --> 03:56:20,760 HIS FOLKS FOR THE BSCs, ALWAYS 4398 03:56:20,760 --> 03:56:22,280 OUTSTANDING PRESENTATIONS AND HE 4399 03:56:22,280 --> 03:56:23,920 WENT OVER EACH AND EVERY ONE OF 4400 03:56:23,920 --> 03:56:25,640 YOUR SLIDES AND MADE SURE IT WAS 4401 03:56:25,640 --> 03:56:30,920 ALL PERFECT AND I BELIEVE IT HAD 4402 03:56:30,920 --> 03:56:36,560 A GREAT CONTRIBUTION TO THE 4403 03:56:36,560 --> 03:56:38,840 SUCCESS OF LPD AND WHEN WE HAD 4404 03:56:38,840 --> 03:56:40,400 NEW INITIATIVES AND I COULD SAY 4405 03:56:40,400 --> 03:56:43,640 FOR SURE, THERE WAS A TIME AT 4406 03:56:43,640 --> 03:56:46,440 NIH WHEN ACTUALLY WE DIDN'T HAVE 4407 03:56:46,440 --> 03:56:49,240 AN INCREASE IN OUR BUDGET WE 4408 03:56:49,240 --> 03:56:51,200 ACTUALLY HAD A RELATIVE DECREASE 4409 03:56:51,200 --> 03:56:53,120 IN OUR BUDGET AND IT WAS GOING 4410 03:56:53,120 --> 03:56:58,240 TO BE PRETTY TRAUMATIC FOR THE 4411 03:56:58,240 --> 03:56:59,880 INTRAMURAL RESEARCH DIVISION SO 4412 03:56:59,880 --> 03:57:01,880 WE GOT TOGETHER TO COME UP WITH 4413 03:57:01,880 --> 03:57:04,120 SOME IDEAS AND ONE OF THEM WAS 4414 03:57:04,120 --> 03:57:09,560 TO MAKE SURE THAT WE PRESERVED 4415 03:57:09,560 --> 03:57:11,200 THE RESOURCES FOR OUR TENURE 4416 03:57:11,200 --> 03:57:13,880 TRACKS AND ALAN WAS A BIG 4417 03:57:13,880 --> 03:57:15,440 SUPPORTER OF THAT TO REALLY MAKE 4418 03:57:15,440 --> 03:57:19,360 SURE OUR YOUNG PEOPLE COULD DO 4419 03:57:19,360 --> 03:57:21,800 THEIR RESEARCH AND BE ABLE TO 4420 03:57:21,800 --> 03:57:22,920 MOVE ON. 4421 03:57:22,920 --> 03:57:26,720 SOME OF THE OLDER FOLKS WERE NOT 4422 03:57:26,720 --> 03:57:28,040 ENAMOR WITH THAT BUT THEY 4423 03:57:28,040 --> 03:57:37,640 UNDERSTAND THE IMPORTANCE OF ITG 4424 03:57:37,640 --> 03:57:39,440 TO ALL OF THAT. 4425 03:57:39,440 --> 03:57:47,800 I ALSO WANT TO SAY THAT YOU 4426 03:57:47,800 --> 03:57:49,080 KNOW, TOM WYNN IS HERE BUT WHEN 4427 03:57:49,080 --> 03:57:52,160 I LEFT NIH I WENT TO BE ON THE 4428 03:57:52,160 --> 03:57:54,600 BOARD OF THE INTERNATIONAL 4429 03:57:54,600 --> 03:57:56,160 BIOMEDICAL RESEARCH ALLIANCE AND 4430 03:57:56,160 --> 03:57:58,480 THAT IS A NON-PROFIT 4431 03:57:58,480 --> 03:58:00,600 ORGANIZATION WHICH HELPS SUPPORT 4432 03:58:00,600 --> 03:58:04,520 THE NIH OXFORD, CAMBRIDGE 4433 03:58:04,520 --> 03:58:06,320 SCHOLARS PROGRAM AND TOM, WHO 4434 03:58:06,320 --> 03:58:11,040 WAS LEADING THE PRO VERSE 4435 03:58:11,040 --> 03:58:13,080 MICHAEL LENARD OWE AND TOM WYNN 4436 03:58:13,080 --> 03:58:15,080 AND TOM HAD AN OFFER HE COULDN'T 4437 03:58:15,080 --> 03:58:19,000 REFUSE TO GO TO PFIZER SO ALAN 4438 03:58:19,000 --> 03:58:20,840 STEPPED IN TAKING ON THE 4439 03:58:20,840 --> 03:58:22,360 LEADERSHIP ROLE THERE AND I HAVE 4440 03:58:22,360 --> 03:58:24,360 TO SAY ALAN, WITH THE HELP OF 4441 03:58:24,360 --> 03:58:26,440 CHRISTIE PORTER, WHO IS NOW YOUR 4442 03:58:26,440 --> 03:58:29,200 RIGHT HAND PERSON, YOU'VE DONE 4443 03:58:29,200 --> 03:58:32,480 AN OUTSTANDING JOB IN HELPING 4444 03:58:32,480 --> 03:58:35,520 THIS PROGRAM TO GROW AND 4445 03:58:35,520 --> 03:58:37,760 CONTINUE TO BENEFIT ALL OUR 4446 03:58:37,760 --> 03:58:39,240 GRADUATE STUDENTS WHO ARE 4447 03:58:39,240 --> 03:58:41,480 INVOLVED IN THAT PROGRAM SO, 4448 03:58:41,480 --> 03:58:44,480 THANK YOU AND I HAVE EVERY 4449 03:58:44,480 --> 03:58:45,360 CONFIDENCE THAT YOU ARE GOING TO 4450 03:58:45,360 --> 03:58:48,640 BE CONTINUING TO HAVE A ROLE IN 4451 03:58:48,640 --> 03:58:51,880 THAT PROGRAM AND HELPING MENTOR 4452 03:58:51,880 --> 03:58:53,320 THOSE STUDENTS BECAUSE THEY 4453 03:58:53,320 --> 03:58:56,520 REALLY LOCK FORWARD TO ALL YOUR 4454 03:58:56,520 --> 03:58:57,120 SAGE ADVICE. 4455 03:58:57,120 --> 03:58:59,000 WELL WITH MENTORING, SO MANY 4456 03:58:59,000 --> 03:59:01,000 PEOPLE HAVE TALKED ABOUT ALAN 4457 03:59:01,000 --> 03:59:03,640 AND HIS MENTORING SKILLS. 4458 03:59:03,640 --> 03:59:04,480 HE EVEN MEN FORWARD TO ME SO 4459 03:59:04,480 --> 03:59:09,720 THANK YOU, ALAN. 4460 03:59:09,720 --> 03:59:11,760 FOR PEOPLE WHO DON'T KNOW, ALAN 4461 03:59:11,760 --> 03:59:17,480 IS SO GENEROUS WITH HIS TIME AND 4462 03:59:17,480 --> 03:59:25,200 WE HAVE COMMUNITY AND 4463 03:59:25,200 --> 03:59:26,960 PREPARATION FOR THEIR TENURE AS 4464 03:59:26,960 --> 03:59:30,680 WELL AS FOR THEIR BSCs AND HE 4465 03:59:30,680 --> 03:59:32,160 WAS ALWAYS THERE GIVING THEM ADD 4466 03:59:32,160 --> 03:59:33,640 VOICE FOR ALL THE COMMITTEES HE 4467 03:59:33,640 --> 03:59:35,880 WAS ON SO ALAN, YOU'VE DONE SUCH 4468 03:59:35,880 --> 03:59:42,040 A GREAT SERVICE TO ALL. 4469 03:59:42,040 --> 03:59:45,680 AND JUST A NOTE. 4470 03:59:45,680 --> 03:59:49,160 WHEN I RETIRED, IT WAS ALWAYS A 4471 03:59:49,160 --> 03:59:49,600 PUSH-PULL. 4472 03:59:49,600 --> 03:59:51,840 YOU NEVER KNOW WHAT THE RIGHT 4473 03:59:51,840 --> 03:59:54,160 TIME IS IT TO -- NOT EVEN RETIRE 4474 03:59:54,160 --> 03:59:56,280 RETIRE BUT EVEN TO STEP AWAY 4475 03:59:56,280 --> 03:59:59,680 FROM THE BENCH I WOULD SAY AND 4476 03:59:59,680 --> 04:00:03,560 SO ALAN, I KNOW YOU HAVE COME TO 4477 04:00:03,560 --> 04:00:05,760 THE FORK IN THE ROAD AND AS YOGI 4478 04:00:05,760 --> 04:00:11,560 BAR A SAYS, TAKE IT. 4479 04:00:11,560 --> 04:00:13,000 AND I THINK TAKE SOME TIME NOW 4480 04:00:13,000 --> 04:00:15,320 TO DO THE THINGS YOU LOVE AND 4481 04:00:15,320 --> 04:00:20,640 BEING WITH YOUR FAMILY AND BEING 4482 04:00:20,640 --> 04:00:24,320 WITH VISITING THE CHILDREN AND 4483 04:00:24,320 --> 04:00:25,280 GRANDCHILDREN AND TRAVEL AND 4484 04:00:25,280 --> 04:00:26,480 DOING THE THINGS YOU LOVE AND I 4485 04:00:26,480 --> 04:00:28,560 WILL BE HERE TO MENTOR HERE ON 4486 04:00:28,560 --> 04:00:32,160 HOW TO RETIRE. 4487 04:00:32,160 --> 04:00:36,160 [LAUGHTER] 4488 04:00:36,160 --> 04:00:41,800 AND SO, YOU ARE DEVOTED AND WILL 4489 04:00:41,800 --> 04:00:49,240 WANT SCIENTIFICALLY BECAUSE IT'S 4490 04:00:49,240 --> 04:00:51,120 INAND I CAN NEVER GUARANTEE SO I 4491 04:00:51,120 --> 04:00:52,600 WANT TO CLOSE IN SAY IN THE 4492 04:00:52,600 --> 04:00:57,720 WORDS OF ALBERT EINSTEIN. 4493 04:00:57,720 --> 04:00:59,320 KEEP YOUR BALANCE ON A BICYCLE 4494 04:00:59,320 --> 04:01:01,160 YOU MUST KEEP MOVING AND ALAN, 4495 04:01:01,160 --> 04:01:02,720 I'LL BE THERE FOR YOU AND IT'S 4496 04:01:02,720 --> 04:01:06,240 BEEN WONDERFUL WORKING WITH YOU 4497 04:01:06,240 --> 04:01:08,200 AND WARM REGARDS ON YOUR NEXT 4498 04:01:08,200 --> 04:01:18,920 STEPS IN YO YO JOURNEY. 4499 04:01:19,480 --> 04:01:27,760 THANK YOU. 4500 04:01:27,760 --> 04:01:31,840 >> THANK YOU, VERY MUCH. 4501 04:01:31,840 --> 04:01:32,640 THANK YOU FOR STICKING AROUND 4502 04:01:32,640 --> 04:01:34,040 FOR THE LAST SCIENTIFIC SESSION 4503 04:01:34,040 --> 04:01:37,520 OF THE AFTERNOON AND BEFORE I 4504 04:01:37,520 --> 04:01:39,760 START, I'LL JUST MAKE A COUPLE 4505 04:01:39,760 --> 04:01:41,160 OF QUICK COMMENTS. 4506 04:01:41,160 --> 04:01:42,960 I THINK OVERWHELMING MAJORITY OF 4507 04:01:42,960 --> 04:01:45,520 THE PEOPLE IN THE ROOM ARE 4508 04:01:45,520 --> 04:01:48,280 ALAN'S SCIENTIFIC GRANDCHILDREN 4509 04:01:48,280 --> 04:01:52,400 AND CHILDREN AND I FALL IN THE 4510 04:01:52,400 --> 04:01:54,280 CATEGORY OF NEPHEW OR FIRST 4511 04:01:54,280 --> 04:01:58,080 COUSIN ONCE REMOVED AND I SAY 4512 04:01:58,080 --> 04:02:00,320 THAT BECAUSE IT TURNS OUT 4513 04:02:00,320 --> 04:02:04,640 THATTAL ANNE AND CRITICAL ROLE 4514 04:02:04,640 --> 04:02:14,560 TO PLAY AND IF AND HAD ANY 4515 04:02:14,560 --> 04:02:15,600 RESEARCH JOB WITH WITH A 4516 04:02:15,600 --> 04:02:18,560 COLLEAGUE OFFALLANCE WHO SORT OF 4517 04:02:18,560 --> 04:02:23,840 ALLUDED TO BY AND THERE WERE 4518 04:02:23,840 --> 04:02:28,640 THREE PH.D STUDENTS AT THE IN 4519 04:02:28,640 --> 04:02:29,520 SAN DIEGO AND ALL TOGETHER AND 4520 04:02:29,520 --> 04:02:35,400 MADE A DECISION TO DITCH BASIC 4521 04:02:35,400 --> 04:02:45,960 IMMUNOLOGY AND MOVE TO NEGLEC 4522 04:02:55,000 --> 04:02:55,200 NEGLECTED. 4523 04:02:55,200 --> 04:02:57,360 >> WHILE I WAS THERE I WENT TO 4524 04:02:57,360 --> 04:03:00,280 HARVARD WHERE ALAN AND ANTHONY 4525 04:03:00,280 --> 04:03:03,120 BUTTERWORTH WERE SHARING A 4526 04:03:03,120 --> 04:03:06,520 CUBICAL AND AND I MET HIM AND I 4527 04:03:06,520 --> 04:03:10,600 WAS ABLE TO PARLAY THAT 4528 04:03:10,600 --> 04:03:17,280 INTERACTION AND INTO A AFTER THE 4529 04:03:17,280 --> 04:03:20,120 FIRST YEARS OF MEDICAL SCHOOL 4530 04:03:20,120 --> 04:03:29,000 AND KENYA AND IT WAS THAT 4531 04:03:29,000 --> 04:03:33,840 EXPERIENCE THAT FIELD WORK AND 4532 04:03:33,840 --> 04:03:37,760 DISEASE AND WANTED TO DO AND SO 4533 04:03:37,760 --> 04:03:41,600 FOR THAT, INDIRECTLY, ALAN 4534 04:03:41,600 --> 04:03:48,120 REALLY WAS ALREADY AN INFLUENCE 4535 04:03:48,120 --> 04:03:58,640 AND FOR THE PROGRAM AND AND IN 4536 04:04:01,000 --> 04:04:05,720 1982 AND PRIVILEGE TO WORK 4537 04:04:05,720 --> 04:04:13,320 ALONGSIDE AND AND CAREER AND WE 4538 04:04:13,320 --> 04:04:22,240 WERE COMBATING ARMS AND FIGHTING 4539 04:04:22,240 --> 04:04:27,200 OFF THE ONSLAUGHT AND OF MALARIA 4540 04:04:27,200 --> 04:04:33,840 AND MAKING BEGINNING FOR AND 4541 04:04:33,840 --> 04:04:38,000 RESEARCH AND FOR THE PAST 20 SO 4542 04:04:38,000 --> 04:04:42,440 YEARS AS SORT OF A PARTNER IN 4543 04:04:42,440 --> 04:04:45,920 AND HELPING TO OVERSEE THE 4544 04:04:45,920 --> 04:04:47,880 OPPORTUNITY AND I VALUE EVERY 4545 04:04:47,880 --> 04:04:58,160 MINUTE AND ALAN WAS AND SO THANK 4546 04:04:58,160 --> 04:04:58,320 YOU. 4547 04:04:58,320 --> 04:05:04,600 [APPLAUSE] 4548 04:05:04,600 --> 04:05:06,680 WE'RE GOING TO THE PROGRAM AND 4549 04:05:06,680 --> 04:05:17,120 IT'S ED PEARCE, IS THAT -- 4550 04:05:21,280 --> 04:05:23,160 >> THANK YOU FOR GIVING ME AN 4551 04:05:23,160 --> 04:05:24,560 OPPORTUNITY TO SAY A FEW WORDS 4552 04:05:24,560 --> 04:05:27,240 ABOUT ALAN. 4553 04:05:27,240 --> 04:05:31,520 I THINK AS YOU GET OLDER, I HAVE 4554 04:05:31,520 --> 04:05:33,120 REALIZED THE IMPORTANCE THESE 4555 04:05:33,120 --> 04:05:34,640 EVENTS AND SUE GET TO SAY THINGS 4556 04:05:34,640 --> 04:05:36,120 THAT YOU MIGHT NOT SAY TO OTHER 4557 04:05:36,120 --> 04:05:37,720 PEOPLE AND YOU SAY THEM PUBLICLY 4558 04:05:37,720 --> 04:05:39,320 AND I DON'T KNOW WHY THAT'S 4559 04:05:39,320 --> 04:05:44,840 EASIER BUT PERHAPS IT IS. 4560 04:05:44,840 --> 04:05:46,600 ANYWAY, I'M -- I WAS GOING TO 4561 04:05:46,600 --> 04:05:49,640 SAY EXACTLY WHAT TOM SAID ABOUT 4562 04:05:49,640 --> 04:05:53,720 ALAN BEING ONE OF THROW THREE 4563 04:05:53,720 --> 04:05:55,600 MUSKETEERS WHO WERE BASIC 4564 04:05:55,600 --> 04:05:57,560 IMMUNOLOGISTS WHO TURNED TO 4565 04:05:57,560 --> 04:06:00,000 WORKING -- WHO DECIDED 4566 04:06:00,000 --> 04:06:01,880 IDEALISTICKLY TO WORK ON 4567 04:06:01,880 --> 04:06:04,160 NEGLECTED TROPICAL DISEASES AND 4568 04:06:04,160 --> 04:06:05,240 THAT USE MADE AN IMPRESSION ON 4569 04:06:05,240 --> 04:06:08,800 ME AND I GOT TO MEAT PAUL AND 4570 04:06:08,800 --> 04:06:10,440 DONATO THE OTHER TWO GUYS THAT 4571 04:06:10,440 --> 04:06:15,480 WERE ALAN'S FRIENDS AND THEY 4572 04:06:15,480 --> 04:06:19,160 MADE AN IMPRESSION ON ME AS 4573 04:06:19,160 --> 04:06:20,040 WELL. 4574 04:06:20,040 --> 04:06:30,560 SO, THE THING THAT ALAN LOVES 4575 04:06:34,160 --> 04:06:35,520 SCIENCE AND HE IS INTERESTED IN 4576 04:06:35,520 --> 04:06:36,480 EVERY SCIENTIFIC QUESTION AND 4577 04:06:36,480 --> 04:06:37,560 ONE OF THE FANTASTIC THINGS 4578 04:06:37,560 --> 04:06:39,760 ABOUT ALAN IS HIS ENTHUSIASM AND 4579 04:06:39,760 --> 04:06:41,920 AS A TRAINEE IN HIS LAB, YOU 4580 04:06:41,920 --> 04:06:44,120 COME UP WITH AN IDEA AND HE 4581 04:06:44,120 --> 04:06:46,160 WOULD ALWAYS PUT A POSITIVE SPIN 4582 04:06:46,160 --> 04:06:47,520 ON IT AND TRY AND MAKE IT GO 4583 04:06:47,520 --> 04:06:49,560 FORWARD AND SEE THE GOOD SIDE OF 4584 04:06:49,560 --> 04:06:51,280 IT AND YOU KNOW, BE SUPPORTIVE 4585 04:06:51,280 --> 04:06:53,560 AS YOU TRIED TO MAKE SOMETHING 4586 04:06:53,560 --> 04:06:55,000 COME OF THAT IDEA THAT YOU'VE 4587 04:06:55,000 --> 04:06:59,000 HAD AND THAT WAS AND INVALUABLE 4588 04:06:59,000 --> 04:07:00,440 AND SUCCEED AS WELL AS ALAN DID 4589 04:07:00,440 --> 04:07:03,480 AND THAT IS SOMETHING THAT WAS 4590 04:07:03,480 --> 04:07:05,480 REALLY AND WHEN I WAS IN HIS LAB 4591 04:07:05,480 --> 04:07:08,520 AND IT'S SOMETHING THAT I REALLY 4592 04:07:08,520 --> 04:07:09,120 APPRECIATE. 4593 04:07:09,120 --> 04:07:13,320 SO A POINT THAT WAS MADE, MAYBE 4594 04:07:13,320 --> 04:07:14,600 IT WAS IT'S SOMETHING WE'LL ALL 4595 04:07:14,600 --> 04:07:18,080 AWARE OF HOW PROLIFIC AND IT'S 4596 04:07:18,080 --> 04:07:22,200 PUBLISHED AND OVER 500 PAPERS 4597 04:07:22,200 --> 04:07:24,560 AND IT'S A TESTAMENT TO HIS WORK 4598 04:07:24,560 --> 04:07:26,040 OATH I CAN AND ALAN WORKS 4599 04:07:26,040 --> 04:07:27,400 REALLY, REALLY HARD AND IT'S 4600 04:07:27,400 --> 04:07:30,520 SOMETHING I RECOGNIZED AS WELL 4601 04:07:30,520 --> 04:07:32,600 AND YOU KNOW THAT IS AN AMAZING 4602 04:07:32,600 --> 04:07:38,080 ROLE MODEL IN THAT RECORD. 4603 04:07:38,080 --> 04:07:40,320 SO, WHEN I THINK ABOUT MY TIME 4604 04:07:40,320 --> 04:07:43,120 IN ALAN'S LAB IT CERTAINLY IS 4605 04:07:43,120 --> 04:07:45,280 THE TIME WHEN I LEARNED TO BE A 4606 04:07:45,280 --> 04:07:45,920 SCIENTIST. 4607 04:07:45,920 --> 04:07:47,480 ALAN TAUGHT ME HOW TO BE A 4608 04:07:47,480 --> 04:07:49,320 SCIENTIST AND THROUGH HIS 4609 04:07:49,320 --> 04:07:50,200 ENTHUSIASM AND THROUGH TAKING 4610 04:07:50,200 --> 04:07:52,280 THE TIME TO SIT DOWN AND TALK TO 4611 04:07:52,280 --> 04:07:53,880 ME AND THE EXPERIMENTS I WAS 4612 04:07:53,880 --> 04:07:55,400 DOING AND HOW I SHOULD INTERPRET 4613 04:07:55,400 --> 04:07:56,920 THE DATA AND WHAT WE SHOULD SEE 4614 04:07:56,920 --> 04:07:57,800 IN IT. 4615 04:07:57,800 --> 04:07:58,920 HE TAUGHT ME HOW TO WRITE. 4616 04:07:58,920 --> 04:08:00,200 THE STORY THAT EVERYBODY HAS HAD 4617 04:08:00,200 --> 04:08:01,800 ABOUT BEING IN THE HOTSEAT, I 4618 04:08:01,800 --> 04:08:07,440 WAS IN THE HOTSEAT MANY, MANY 4619 04:08:07,440 --> 04:08:12,680 TIMES AND IT'S AMAZING WE WERE 4620 04:08:12,680 --> 04:08:16,720 DOING IT IN A LONGHAND ON A 4621 04:08:16,720 --> 04:08:19,440 YELLOW PAD AND HE WOULD WE 4622 04:08:19,440 --> 04:08:20,640 REWRITE IT AND IT'S HARD TO 4623 04:08:20,640 --> 04:08:22,240 THINK THAT'S THE WAY WE DID IT. 4624 04:08:22,240 --> 04:08:23,640 THAT'S HOW I LEARNED TO WRITE 4625 04:08:23,640 --> 04:08:24,960 AND IT'S INVALUABLE. 4626 04:08:24,960 --> 04:08:26,480 AS A SCIENTIST, IF YOU CAN'T 4627 04:08:26,480 --> 04:08:29,960 WRITE YOU ARE DONE. 4628 04:08:29,960 --> 04:08:31,440 SO, HE NOT ONLY TAUGHT ME HOW TO 4629 04:08:31,440 --> 04:08:33,200 BE A SCIENTIST AND HOW TO WRITE 4630 04:08:33,200 --> 04:08:34,720 BUT HE TAUGHT ME OTHER THING. 4631 04:08:34,720 --> 04:08:35,920 HE TOOK ME SAILING ONCE AND 4632 04:08:35,920 --> 04:08:46,440 TRIED TO TEACH ME HOW TO SAIL. 4633 04:09:44,200 --> 04:09:45,720 >> THAT SPEAKS TO ALAN'S 4634 04:09:45,720 --> 04:09:46,680 CONNECTIONS AND HE IS CONNECTED 4635 04:09:46,680 --> 04:09:48,600 TO SO MANY PEOPLE AND OBVIOUSLY 4636 04:09:48,600 --> 04:09:52,680 THE EMPHASIS TODAY IS ON 4637 04:09:52,680 --> 04:09:54,040 IMMUNOLOGISTS AND HE IS WIDELY 4638 04:09:54,040 --> 04:09:56,400 RESPECTED AND CONNECTED IN THE 4639 04:09:56,400 --> 04:09:58,480 IMMUNOLOGY FIELD AND HE IS AND 4640 04:09:58,480 --> 04:10:01,800 HE IS CONNECTED TO HARDCORE 4641 04:10:01,800 --> 04:10:03,360 PATHTOLOGISTS AND THAT'S ANOTHER 4642 04:10:03,360 --> 04:10:06,640 THING AND HE IS MEETING THESE 4643 04:10:06,640 --> 04:10:07,840 FANTASTIC WHO COME THROUGH AND 4644 04:10:07,840 --> 04:10:09,000 VISIT AND ALL SORTS OF PEOPLE 4645 04:10:09,000 --> 04:10:10,320 WERE COMING THROUGH AND VISITING 4646 04:10:10,320 --> 04:10:11,680 IN THE LAB ALL THE TIME AND HE 4647 04:10:11,680 --> 04:10:13,760 WOULD GO OUT OF HIS TO INTRODUCE 4648 04:10:13,760 --> 04:10:16,720 US AND I GOT TO KNOW PAUL 4649 04:10:16,720 --> 04:10:18,280 ENGLAND AND JOHN HOPKINS WHO WAS 4650 04:10:18,280 --> 04:10:19,760 ONE OF THE PEOPLE THAT WORKED 4651 04:10:19,760 --> 04:10:22,280 OUT HOW GPI ANCHORS ARE 4652 04:10:22,280 --> 04:10:23,840 CONSTRUCTED AND INSIDE A CELL 4653 04:10:23,840 --> 04:10:26,440 AND I GOT TO MEET A OCC WANG 4654 04:10:26,440 --> 04:10:37,320 FROM UCSF WHO DISCOVE INEVER MEC 4655 04:10:43,240 --> 04:10:45,680 TIN AND ALAN IS THE CENTER OF 4656 04:10:45,680 --> 04:10:47,840 THIS SCIENTIST OF PEOPLE THAT 4657 04:10:47,840 --> 04:10:49,680 I'M A PART OF AND THIS IS 4658 04:10:49,680 --> 04:10:50,800 FANTASTIC BECAUSE IT OPENS THE 4659 04:10:50,800 --> 04:10:55,000 DOOR TO US ALL GOING TO EACH 4660 04:10:55,000 --> 04:10:58,320 OTHER AND I FEEL LIKE AND THAT'S 4661 04:10:58,320 --> 04:11:08,880 BECAUSE OF ALAN AND THAT AND THE 4662 04:11:13,760 --> 04:11:15,920 WAY HE CAN BEHAVE AS A 4663 04:11:15,920 --> 04:11:17,040 CHEERLEADER AND TO BE HONEST 4664 04:11:17,040 --> 04:11:22,880 WITH YOU, IT'S PRETTY 4665 04:11:22,880 --> 04:11:23,840 INTOXICATING WHEN HE IS WORKING 4666 04:11:23,840 --> 04:11:27,960 WITH YOU TO GET THAT PAPER 4667 04:11:27,960 --> 04:11:38,480 TOGETHER AND AND IT WAS BETTER 4668 04:11:39,480 --> 04:11:45,840 WHEN HE WAS THINKING ABOUT MY 4669 04:11:45,840 --> 04:11:49,320 WORLD TO WORK HARD AND HE DID 4670 04:11:49,320 --> 04:11:59,840 THAT IN A GREAT WAY AND AND THE 4671 04:12:00,640 --> 04:12:04,200 WAY HE TALKED ABOUT MICHAEL AND 4672 04:12:04,200 --> 04:12:05,560 MICHAEL GOOD WAS MANY OF YOU MAY 4673 04:12:05,560 --> 04:12:07,920 KNOW AND HE ENDED UP AND BEING 4674 04:12:07,920 --> 04:12:10,720 CURE IMR AND HE REALLY IS A GOOD 4675 04:12:10,720 --> 04:12:12,640 SCIENTIST AND WHEN ALAN WERE 4676 04:12:12,640 --> 04:12:15,200 TALK TO US ABOUT MICHAEL GOOD HE 4677 04:12:15,200 --> 04:12:17,400 WAS A PARADIGM OF VIRTUE AND 4678 04:12:17,400 --> 04:12:23,760 THIS IS HOW YOU GET AND MICHAEL. 4679 04:12:23,760 --> 04:12:24,600 GOOD. 4680 04:12:24,600 --> 04:12:26,640 MICHAEL EXCELLENCE AND SO I JUST 4681 04:12:26,640 --> 04:12:28,920 THINK ABOUT IT AND I NEVER THINK 4682 04:12:28,920 --> 04:12:31,960 OF MICHAEL GOOD WITHOUT THINKING 4683 04:12:31,960 --> 04:12:33,480 ABOUT HIM AS MICHAEL EXCELLENT. 4684 04:12:33,480 --> 04:12:37,320 THANK YOU, ALAN, IT'S BEEN MY 4685 04:12:37,320 --> 04:12:38,720 PRIVILEGE TO BE HERE TODAY. 4686 04:12:38,720 --> 04:12:39,480 THANK YOU. 4687 04:12:39,480 --> 04:12:42,440 AND SO MOVING ON FROM THERE, I 4688 04:12:42,440 --> 04:12:45,240 HAVE THE PRIVILEGE ALSO OF 4689 04:12:45,240 --> 04:12:48,280 INTRODUCE PAUL BRINDLEY, MY OLD 4690 04:12:48,280 --> 04:12:50,160 COM PADRES FROM ALAN'S LAB AND 4691 04:12:50,160 --> 04:12:52,880 WE SPENT A LOT OF TIME TOGETHER 4692 04:12:52,880 --> 04:12:54,080 AND I'M LOOKING FORWARD TO 4693 04:12:54,080 --> 04:12:56,960 HEARING WHAT YOU HAVE TO SAY, 4694 04:12:56,960 --> 04:12:57,400 PAUL. 4695 04:12:57,400 --> 04:13:05,000 [APPLAUSE] 4696 04:13:05,000 --> 04:13:07,480 >> THANK YOU, ED. 4697 04:13:07,480 --> 04:13:09,120 AND THANK YOU TO DRAGANA AND THE 4698 04:13:09,120 --> 04:13:11,760 OTHER FOLKS WHO INVITED ME INTO 4699 04:13:11,760 --> 04:13:17,040 PUTTING ON THIS WONDERFUL 4700 04:13:17,040 --> 04:13:19,040 SYMPOSIUM. 4701 04:13:19,040 --> 04:13:21,800 OK. 4702 04:13:21,800 --> 04:13:24,200 SO, DRAGANA ASKED ME OR I SAID I 4703 04:13:24,200 --> 04:13:26,720 COULD TALK ABOUT SOMETHING TO DO 4704 04:13:26,720 --> 04:13:29,800 WITH GENOMES AND RELATED FLUKES 4705 04:13:29,800 --> 04:13:36,240 SO I WANT TO MAKE A FEW SIMILAR 4706 04:13:36,240 --> 04:13:39,640 REMARKS TO THAT PROFESSOR PEARCE 4707 04:13:39,640 --> 04:13:41,320 AND OTHERS WHO HAVE MADE TODAY 4708 04:13:41,320 --> 04:13:45,240 BECAUSE I ALSO WAS A POSTDOC IN 4709 04:13:45,240 --> 04:13:48,120 ALAN'S LAB AND SO I'M GOING TO 4710 04:13:48,120 --> 04:13:49,680 TALK ABOUT THE SCIENTIFIC 4711 04:13:49,680 --> 04:13:50,440 ASPECTS A LITTLE BIT FURTHER ON 4712 04:13:50,440 --> 04:13:52,600 AND I'M GOING TO CONSUME TOO 4713 04:13:52,600 --> 04:13:54,280 MUCH TIME AND I'VE BEEN OFFERED 4714 04:13:54,280 --> 04:13:57,040 LESS BUT I WANT TO MAKE A COUPLE 4715 04:13:57,040 --> 04:14:00,680 OF PERSONAL REMARKS. 4716 04:14:00,680 --> 04:14:02,560 SO, THAT IS THE INTERVAL WHEN I 4717 04:14:02,560 --> 04:14:07,840 WAS IN ALAN'S LAB IN 1985 TO 4718 04:14:07,840 --> 04:14:10,040 1991 AND WHERE AS ALAN MIGHT 4719 04:14:10,040 --> 04:14:11,880 HAVE KNOWN Dr. MICHAEL 4720 04:14:11,880 --> 04:14:13,240 EXCELLENT HE DIDN'T KNOW ME AND 4721 04:14:13,240 --> 04:14:15,120 EVEN THOUGH MICHAEL AND I KNEW 4722 04:14:15,120 --> 04:14:17,280 EACH OTHER AND WE WERE BOTH FROM 4723 04:14:17,280 --> 04:14:19,720 AUSTRALIA I WANT TO TELL YOU HOW 4724 04:14:19,720 --> 04:14:22,240 I CAME TO A ARRIVE HERE SO, I 4725 04:14:22,240 --> 04:14:26,520 JUST FINISHED MY PH.D DEGREE AT 4726 04:14:26,520 --> 04:14:27,880 AN INSTITUTE ALAN NEVER HEARD OF 4727 04:14:27,880 --> 04:14:32,560 AND THE DOCTOR GOOD WAS ALSO A 4728 04:14:32,560 --> 04:14:38,800 GRADUATE AND SO I WROTE A LETTER 4729 04:14:38,800 --> 04:14:40,840 AND PUT IT A LETTER IN A BOTTLE 4730 04:14:40,840 --> 04:14:42,840 THAT I TOSSED INTO THE PACIFIC 4731 04:14:42,840 --> 04:14:44,480 OCEAN AND I FORGOT ABOUT IT AND 4732 04:14:44,480 --> 04:14:46,240 I HAD WRITTEN THIS LETTER TO THE 4733 04:14:46,240 --> 04:14:48,400 DIRECTOR OF NIAID WHICH I TAKE 4734 04:14:48,400 --> 04:14:51,120 IT OUT WAS PART OF THE NIH AND 4735 04:14:51,120 --> 04:14:53,840 SOMETIMES LATER, I RECEIVED A 4736 04:14:53,840 --> 04:14:59,760 LETTER BACK IN THE MAIL AND AND 4737 04:14:59,760 --> 04:15:04,240 I SAVED AND HOW LONG AND AND I 4738 04:15:04,240 --> 04:15:12,600 OPENED IT UP AND IT JUST ALLUDE 4739 04:15:12,600 --> 04:15:16,160 TODAY AND AND SEVERAL PAGES OF 4740 04:15:16,160 --> 04:15:17,560 THE CURSE TOMORROW EXPLAINED WHO 4741 04:15:17,560 --> 04:15:19,440 HE WAS AND THAT MY LETTER HAD 4742 04:15:19,440 --> 04:15:23,360 BEEN RECEIVED BY THE NIAID AND 4743 04:15:23,360 --> 04:15:26,800 IT MOVED Dr. GALAN'S OFFICE 4744 04:15:26,800 --> 04:15:29,680 AND HE TALKED TO Dr. FRANKLIN 4745 04:15:29,680 --> 04:15:32,920 THE CHIEF OF THE LPD AND SOMEHOW 4746 04:15:32,920 --> 04:15:34,920 Dr. NEVER DECIDED THAT I MIGHT 4747 04:15:34,920 --> 04:15:36,880 BE A PERSON WHO COULD HELP HIM 4748 04:15:36,880 --> 04:15:38,520 OUT BECAUSE THIS GUY BRINDLEY 4749 04:15:38,520 --> 04:15:41,040 CLAIMED HE KNEW SOMETHING ABOUT 4750 04:15:41,040 --> 04:15:43,200 WORMS IN HIS DOCTORATE AND Dr. 4751 04:15:43,200 --> 04:15:45,040 NEVER HAD AN INTEREST IN WORMS 4752 04:15:45,040 --> 04:15:50,040 BUT HE TALKED TO ALLEN AND SAID, 4753 04:15:50,040 --> 04:15:52,560 YOU'VE BEEN BADGERING ME FOR A 4754 04:15:52,560 --> 04:15:54,720 POSTDOC BUDGET SALARY AND HE 4755 04:15:54,720 --> 04:15:55,680 SAID I'VE GOT AN INTEREST IN 4756 04:15:55,680 --> 04:15:57,200 THIS LETTER THAT Dr. GALLON 4757 04:15:57,200 --> 04:15:59,000 HAS PASSED ON TO ME AND WE 4758 04:15:59,000 --> 04:16:01,600 BETTER DO SOMETHING ABOUT IT BUT 4759 04:16:01,600 --> 04:16:03,360 I WILL TAKE HIM ON IF YOU WILL 4760 04:16:03,360 --> 04:16:04,920 TAKE HIM ON TOO. 4761 04:16:04,920 --> 04:16:06,440 I THINK IT'S HOW THE STORY WENT 4762 04:16:06,440 --> 04:16:08,280 AND SO ALAN EXPLAINED TO ME IN 4763 04:16:08,280 --> 04:16:10,840 THIS LETTER ON THE YELLOW NOTE 4764 04:16:10,840 --> 04:16:12,200 PAD THAT YES, THAT I'M 4765 04:16:12,200 --> 04:16:13,640 INTERESTED IN HIRING ME BUT I 4766 04:16:13,640 --> 04:16:15,760 WOULD HAVE TO WORK PRETTY HARD, 4767 04:16:15,760 --> 04:16:20,200 12 HOURS FOR Dr. NEVER EACH 4768 04:16:20,200 --> 04:16:22,080 DAY AND 12 HOURS FOR Dr. SHER. 4769 04:16:22,080 --> 04:16:28,480 THE UP REPO SHORT OF THAT, SO A 4770 04:16:28,480 --> 04:16:30,600 LITTLE WHILE LATER, AFTER IF I 4771 04:16:30,600 --> 04:16:32,600 SAT IN THE HOTSEAT WITH ALAN WE 4772 04:16:32,600 --> 04:16:36,720 MANAGED TO PUBLISH THIS PAPER 4773 04:16:36,720 --> 04:16:39,680 AND THIS PAPER DEALT WITH 4774 04:16:39,680 --> 04:16:44,360 EXPOSURE OF MICE TO THE 4775 04:16:44,360 --> 04:16:50,320 ANTI- PARASITIC DRUG AND 4776 04:16:50,320 --> 04:16:53,840 OTHERWISE MY SURFACE THAT Dr. 4777 04:16:53,840 --> 04:16:57,840 HALL BY OTHER ANTIGENS WERE 4778 04:16:57,840 --> 04:17:00,440 EXPOSED TO SERUM ANTIBODIES AND 4779 04:17:00,440 --> 04:17:02,680 SOON THE MICE WERE EXPELLED SO 4780 04:17:02,680 --> 04:17:11,000 THE LINKAGE WAS THERE THAT 4781 04:17:11,000 --> 04:17:13,320 EFFICACY OF THIS DRUG HAD AN 4782 04:17:13,320 --> 04:17:15,160 IMMUNE DEPENDEN SEE COMPONENT 4783 04:17:15,160 --> 04:17:16,640 AND THE OTHER THING I WOULD LIKE 4784 04:17:16,640 --> 04:17:19,040 TO SAY ABOUT THIS PAPER AS PROUD 4785 04:17:19,040 --> 04:17:22,360 OF IT I WAS, THE DAY THE LETTER 4786 04:17:22,360 --> 04:17:26,680 FROM THE JOURNAL OF IMMUNOLOGY 4787 04:17:26,680 --> 04:17:29,840 SAID IT WAS ACCEPTED WE WERE 4788 04:17:29,840 --> 04:17:32,240 FEELING CHUFFED AND ANOTHER 4789 04:17:32,240 --> 04:17:35,520 LETTER APPEARED ON MY DESK AND 4790 04:17:35,520 --> 04:17:37,080 THIS LETTER EXPLAINED THAT THEY 4791 04:17:37,080 --> 04:17:40,680 MADE A TERRIBLE MISTAKE. 4792 04:17:40,680 --> 04:17:42,480 AND THAT THERE WAS A CLERICAL 4793 04:17:42,480 --> 04:17:44,320 ERROR AND ACTUALLY THE PAPER 4794 04:17:44,320 --> 04:17:45,280 HADN'T BEEN ACCEPTED AND THEY 4795 04:17:45,280 --> 04:17:47,640 WERE WITH DRUG THEIR OFFER OF 4796 04:17:47,640 --> 04:17:50,760 ACCEPTANCE AND YOU WOULD HAVE TO 4797 04:17:50,760 --> 04:17:54,840 TROY SOMEWHERE ELSE BUT Dr. 4798 04:17:54,840 --> 04:17:58,520 CHIEFER WAS RESPONSIBLE FOR 4799 04:17:58,520 --> 04:17:58,720 THAT. 4800 04:17:58,720 --> 04:18:02,000 THAT WAS MY THE LAB IN IMMUNO 4801 04:18:02,000 --> 04:18:06,160 BIOLOGY AND IMMUNE SERUM AND 4802 04:18:06,160 --> 04:18:07,880 ALAN PROBABLY PRESENTLY DECIDED 4803 04:18:07,880 --> 04:18:10,160 THAT THIS GUY BRIND LIKE UNLIKE 4804 04:18:10,160 --> 04:18:11,480 Dr. EXCELLENT, KNEW NOTHING 4805 04:18:11,480 --> 04:18:13,480 ABOUT IMMUNOLOGY AND THAT'S THE 4806 04:18:13,480 --> 04:18:15,920 LAST I WORKED ON ANYTHING IMMUNE 4807 04:18:15,920 --> 04:18:18,720 LOGICAL SO ALAN SUGGESTED I WORK 4808 04:18:18,720 --> 04:18:25,440 ON THE WORM THEMSELVES OR THEIR 4809 04:18:25,440 --> 04:18:26,760 GENOMES, I'M GOING TO SHOW THE 4810 04:18:26,760 --> 04:18:28,800 WORK I DID TO ALAN'S ADVICE TO 4811 04:18:28,800 --> 04:18:31,880 STICK TO THE PARASITE. 4812 04:18:31,880 --> 04:18:35,360 SOME FOLKS MENTION Dr. GEORGE 4813 04:18:35,360 --> 04:18:37,520 YAP INDICATED THAT IF YOU HAD A 4814 04:18:37,520 --> 04:18:39,200 FORK IN THE ROAD AND Dr. SHER 4815 04:18:39,200 --> 04:18:42,280 SAID YOU CAN WORK ON TOXO YOU 4816 04:18:42,280 --> 04:18:42,920 WOULD SOON BELIEVE YOUR CAREER 4817 04:18:42,920 --> 04:18:45,360 WAS DEAD ENDED IF YOU WORK ON 4818 04:18:45,360 --> 04:18:49,560 SISTER SO YOU BETTER WORK ON 4819 04:18:49,560 --> 04:18:50,520 TOXOPLASMOSIS AND HE DIDN'T 4820 04:18:50,520 --> 04:18:52,760 OFFER ME THAT ADVICE, I DIDN'T 4821 04:18:52,760 --> 04:18:54,520 GET THE OFFER SEW SAID YOU WORK 4822 04:18:54,520 --> 04:18:57,400 ON SHISTER SEEMS. 4823 04:18:57,400 --> 04:19:02,000 SO ANYWAY, THE PROBLEM WITH S 4824 04:19:02,000 --> 04:19:03,840 THEY'RE GENETICALLY NOT VERY 4825 04:19:03,840 --> 04:19:05,360 ATTRACT ABLE AND THEY'RE WORK TO 4826 04:19:05,360 --> 04:19:07,960 WORK ON AND THEY'RE UNLIKE 4827 04:19:07,960 --> 04:19:10,080 SINGLE CELL PATHOGENS THEY HAVE 4828 04:19:10,080 --> 04:19:13,280 A COMPLEX GENOME AND THEY SEX 4829 04:19:13,280 --> 04:19:14,680 I'LLLY REPRODUCE AND THEY HAVE A 4830 04:19:14,680 --> 04:19:16,200 COMPLEX LIFE CYCLE AND SOME OF 4831 04:19:16,200 --> 04:19:19,080 THEM ARE MORE COMPLEX AND THEY 4832 04:19:19,080 --> 04:19:21,000 HAVE A SMELL INVOLVED. 4833 04:19:21,000 --> 04:19:22,000 SO IN SUBSEQUENT YEARS, YOU 4834 04:19:22,000 --> 04:19:24,560 KNOW, IN A PARTICULAR SINCE THE 4835 04:19:24,560 --> 04:19:26,480 CRISPR REVOLUTION AND THE NOBEL 4836 04:19:26,480 --> 04:19:29,960 PRIZE TO RELATED TO THAT, PEOPLE 4837 04:19:29,960 --> 04:19:33,840 NOW HAVE ADAPTED CRISPR GENE 4838 04:19:33,840 --> 04:19:35,600 NOAM ETIQUETTING AND WE'VE BEEN 4839 04:19:35,600 --> 04:19:37,200 INVOLVED IN THAT OURSELVES AND 4840 04:19:37,200 --> 04:19:38,720 I'LL MENTION THAT AND WHAT WE 4841 04:19:38,720 --> 04:19:49,280 REALLY WOULD LIKE TO DO IS IT'S 4842 04:19:54,440 --> 04:19:56,040 A CHARGE BUT IT'S WHAT WE DO IN 4843 04:19:56,040 --> 04:19:59,040 SOME RELATED WORMS NOWADAYS. 4844 04:19:59,040 --> 04:20:02,160 TO GET INTO CRISPR EDITING, A 4845 04:20:02,160 --> 04:20:03,560 COUPLE OF YEARS A. I CAME BECOME 4846 04:20:03,560 --> 04:20:05,560 TO SEE ALAN AND DRAGANA JUST 4847 04:20:05,560 --> 04:20:06,960 BEFORE THE COVID AND I WAS A 4848 04:20:06,960 --> 04:20:11,000 WAIVER THEIR PAPER FROM THE 4849 04:20:11,000 --> 04:20:12,800 MIDDLE, WELL ABOUT 2009 AND I 4850 04:20:12,800 --> 04:20:13,920 QUICK WILL HE CHECKED PUBMED 4851 04:20:13,920 --> 04:20:17,720 TODAY AND AMONG THOSE 500 PAPERS 4852 04:20:17,720 --> 04:20:19,440 THAT ALAN PUBLISHED THIS WAS THE 4853 04:20:19,440 --> 04:20:21,920 LAST ONE THAT HAD THE NAME OF 4854 04:20:21,920 --> 04:20:27,240 SHER AND SCHISTOME IN THE SEARCH 4855 04:20:27,240 --> 04:20:28,080 THAT I PICKED UP. 4856 04:20:28,080 --> 04:20:33,480 I WAS AWARE THAT THE EGG OF THE 4857 04:20:33,480 --> 04:20:35,680 SCHISTOSOME WAS RESPONSIBLE FOR 4858 04:20:35,680 --> 04:20:37,200 THE DISEASE AND SO WE DECIDED IN 4859 04:20:37,200 --> 04:20:41,320 MY LAB, PARTICULARLY WITH 4860 04:20:41,320 --> 04:20:42,640 HOTSHOT YOUNG ASSISTANT 4861 04:20:42,640 --> 04:20:44,000 PROFESSOR WHO WORKED WITH ME 4862 04:20:44,000 --> 04:20:46,880 THAT WE WOULD EDIT SOMETHING AND 4863 04:20:46,880 --> 04:20:48,360 GET A PHENOTYPE AND WE KNEW THE 4864 04:20:48,360 --> 04:20:50,840 EGGS HAD A PHENOTYPE OF THE 4865 04:20:50,840 --> 04:20:56,040 GRANULOMA AND THE TH2 SHIFT AND 4866 04:20:56,040 --> 04:21:00,880 SO WHAT COULD WE EDIT IN A EGG 4867 04:21:00,880 --> 04:21:02,560 AND THERE WAS THIS PEOPLE AND 4868 04:21:02,560 --> 04:21:04,720 THEY PUBLISHED SIMILAR PAPERS 4869 04:21:04,720 --> 04:21:12,920 THAT THE EGG SECRETS A OMEGA 1 4870 04:21:12,920 --> 04:21:14,200 PROBABLY NAMED DISCOVERED LONG 4871 04:21:14,200 --> 04:21:16,360 BEFORE BY DAVID DUNN AS WELL. 4872 04:21:16,360 --> 04:21:18,200 THE OMEGA STANDARD FOR THE 4873 04:21:18,200 --> 04:21:20,480 FRACTION FROM THE CROW MATGRAM 4874 04:21:20,480 --> 04:21:22,240 SO WE'RE ABLE TO LOOK AT THE 4875 04:21:22,240 --> 04:21:22,800 GENOME. 4876 04:21:22,800 --> 04:21:24,440 THE GENOME IS IN GOOD SHAPE 4877 04:21:24,440 --> 04:21:25,800 NOWADAYS BUT NOT TOTALLY 4878 04:21:25,800 --> 04:21:27,440 COMPLETE. 4879 04:21:27,440 --> 04:21:28,680 UNFORTUNATELY THIS PARTICULAR 4880 04:21:28,680 --> 04:21:30,200 ENZYME HAS THREE GENES BUT 4881 04:21:30,200 --> 04:21:31,680 THEY'RE ALL SIMILAR AND I WANT 4882 04:21:31,680 --> 04:21:32,800 TO POINT OUT WHAT IS SOMETHING 4883 04:21:32,800 --> 04:21:34,840 ON THE BOTTOM OF THE PANEL 4884 04:21:34,840 --> 04:21:35,120 THERE. 4885 04:21:35,120 --> 04:21:36,880 DON'T WORRY ABOUT THE GENE 4886 04:21:36,880 --> 04:21:37,320 STRUCTURE. 4887 04:21:37,320 --> 04:21:40,080 THAT PARTICULAR ENZYME HAS A 4888 04:21:40,080 --> 04:21:41,520 VERY SPECIFIC DEVELOPMENTAL 4889 04:21:41,520 --> 04:21:43,600 EXPRESSION AND IT'S ONLY 4890 04:21:43,600 --> 04:21:48,640 EXPRESSED IN THE EXPRESSION 4891 04:21:48,640 --> 04:21:50,720 LEVELS OF THE TRANSCRIPT AT 4892 04:21:50,720 --> 04:21:53,000 VARIOUS STAGES OF THE LIFE CYCLE 4893 04:21:53,000 --> 04:21:54,400 OF THE THREE DIFFERENT GENES. 4894 04:21:54,400 --> 04:21:57,520 ONLY SEEN WITHIN THE EGG AND THE 4895 04:21:57,520 --> 04:21:58,520 EGG PROBABLY TAKES SEVEN DAYS TO 4896 04:21:58,520 --> 04:22:00,080 DEVELOP WHEN THE FEMALE LAYS IT 4897 04:22:00,080 --> 04:22:02,560 UNTIL IT COULD REACH THE BELL 4898 04:22:02,560 --> 04:22:03,560 AND ONLY EXPRESSED? 4899 04:22:03,560 --> 04:22:05,560 THE LAST THREE OUR FOUR DAYS OF 4900 04:22:05,560 --> 04:22:08,200 THAT SO IN THE MATURE EGG SO WE 4901 04:22:08,200 --> 04:22:15,280 DECIDED TO TRY AND EDIT THAT 4902 04:22:15,280 --> 04:22:17,960 THIS THE UP SHOT OF WHAT WE SAW 4903 04:22:17,960 --> 04:22:20,360 THAT ON THE LEFT HAND PANEL WE 4904 04:22:20,360 --> 04:22:21,840 CAN GET A REDUCTION THAT WE CAN 4905 04:22:21,840 --> 04:22:24,240 MEASURE IF WE TOOK RNA FROM THE 4906 04:22:24,240 --> 04:22:26,400 EGGS AND WE DELIVERED IT AND WE 4907 04:22:26,400 --> 04:22:30,240 ALSO CAN DELIVER BY THE VIRUS 4908 04:22:30,240 --> 04:22:32,880 AND IT'S INFECTIOUS THOUGH OR 4909 04:22:32,880 --> 04:22:43,400 OTHER RETRO AND SO AND I DON'T 4910 04:23:21,240 --> 04:23:26,440 WANT TO SHOW YOU THE EDITING PAD 4911 04:23:26,440 --> 04:23:30,600 ENTER AND A SMALL PERCENTAGE OF 4912 04:23:30,600 --> 04:23:32,800 THE GENOMES SO WE TAKE 10,000 4913 04:23:32,800 --> 04:23:37,000 EGGS AND EDIT THEM AND RECOVER 4914 04:23:37,000 --> 04:23:47,520 THE FEW DAYS AND, I WANT TO TALK 4915 04:23:59,040 --> 04:24:00,520 ABOUT JUST AS I FINISH UP ON 4916 04:24:00,520 --> 04:24:02,480 THIS RUN RIGHT NOW. 4917 04:24:02,480 --> 04:24:05,920 BUT THOSE MANIPULATED EGGS IF WE 4918 04:24:05,920 --> 04:24:08,160 PUT THEM INTO LUNG GRANULOMA 4919 04:24:08,160 --> 04:24:10,440 WHEN YOU LOOK AT THESE 10 DAYS 4920 04:24:10,440 --> 04:24:13,240 LATER IN THE MOUSE, THAT IS THE 4921 04:24:13,240 --> 04:24:15,680 VOLUME OF THE GRANULOMA 4922 04:24:15,680 --> 04:24:16,440 SURROUNDING THE EGG. 4923 04:24:16,440 --> 04:24:18,440 THE EGG IS RIGHT THERE. 4924 04:24:18,440 --> 04:24:21,240 THE GENOME EGGS IS JUST 4925 04:24:21,240 --> 04:24:23,800 GOBSMACKEDDINGLY ABSENT AND THE 4926 04:24:23,800 --> 04:24:29,640 SIZE OF THE GRANULOMA AND ROB 4927 04:24:29,640 --> 04:24:32,760 THOMPSON WHO WORKED FOR TOM WYNN 4928 04:24:32,760 --> 04:24:33,800 HELPED US SCAN THOSE AND HE LET 4929 04:24:33,800 --> 04:24:37,720 US USE BUT THIS IS JUST THE 4930 04:24:37,720 --> 04:24:39,880 VOLUME AND THE AMOUNT OF VOLUME 4931 04:24:39,880 --> 04:24:42,760 TO AND THAT IS THE EDITING CAN 4932 04:24:42,760 --> 04:24:45,680 DO ON THIS PARTICULAR ENZYME AND 4933 04:24:45,680 --> 04:24:47,240 IT WAS CURIOUS WHEN WE SAW THAT 4934 04:24:47,240 --> 04:24:50,240 BECAUSE WE GOT THIS 100% 4935 04:24:50,240 --> 04:24:51,680 REDUCTION IN TRANSCRIPT LEVEL 4936 04:24:51,680 --> 04:24:54,360 AND AT LEAST 50% REDUCTION IN 4937 04:24:54,360 --> 04:24:56,960 THE RNA ACTIVITY AND AT THE 4938 04:24:56,960 --> 04:24:58,520 GENOME LEVEL A SMALL PERCENTAGE 4939 04:24:58,520 --> 04:25:00,480 WERE EDITED AND WHY IS THAT 4940 04:25:00,480 --> 04:25:01,720 BECAUSE THIS IS THE STAGE, THE 4941 04:25:01,720 --> 04:25:03,640 EGG STAGE IS WHAT WE EDITED AND 4942 04:25:03,640 --> 04:25:05,360 THIS IS NOT OUR WORK THIS IS 4943 04:25:05,360 --> 04:25:07,280 FROM THE LITERATURE AND THE EGG 4944 04:25:07,280 --> 04:25:08,320 ITSELF WHEN IT'S DEVELOPED AND 4945 04:25:08,320 --> 04:25:10,440 YOU CAN SEE THE SILLIA ON THE 4946 04:25:10,440 --> 04:25:11,640 OUTSIDE OF THIS WITHIN THE EGG 4947 04:25:11,640 --> 04:25:13,840 SHELL IN THE MOUSE LIVER, THIS 4948 04:25:13,840 --> 04:25:14,200 EXAMPLE. 4949 04:25:14,200 --> 04:25:17,560 AND THERE'S ACTUALLY SOME TISSUE 4950 04:25:17,560 --> 04:25:21,200 JUST INSIDE THE INNER COAT OF 4951 04:25:21,200 --> 04:25:22,680 THE EGG AND IN AN ENVELOPE WHICH 4952 04:25:22,680 --> 04:25:24,680 IS ANOTHER THING WHEN TISSUE 4953 04:25:24,680 --> 04:25:29,080 GROWS OUT AS THE EGG DEVELOPS DD 4954 04:25:29,080 --> 04:25:30,880 IT'S THE ONLY PLACE IN THIS 4955 04:25:30,880 --> 04:25:32,520 ORGANISM WHERE OMEGA IS 4956 04:25:32,520 --> 04:25:36,520 EXPRESSED AND WHEN WE INTRODUCE 4957 04:25:36,520 --> 04:25:38,800 THOSE EGGS IN CRISPR IN THOSE 4958 04:25:38,800 --> 04:25:40,920 EGGS CLEARLY JUST PHYSICAL LIE 4959 04:25:40,920 --> 04:25:44,360 WE ONLY REACH THAT TISSUE SO 4960 04:25:44,360 --> 04:25:47,120 VERY WE KNOCKED OUT THIS 4961 04:25:47,120 --> 04:25:48,400 VACCINES OF PHENOTYPE AND WE 4962 04:25:48,400 --> 04:25:53,000 CHOSE AN INTEREST GENE TO SO IT 4963 04:25:53,000 --> 04:25:53,840 HAPPENED THERE. 4964 04:25:53,840 --> 04:25:57,480 I MENTIONED THAT THE SISTER 4965 04:25:57,480 --> 04:25:59,640 SEEMS ARE DIFFERENTLY AND TO 4966 04:25:59,640 --> 04:26:01,480 MANIPULATE SO YOU CAN WELL 4967 04:26:01,480 --> 04:26:02,040 MARRIAGE OTHER PEOPLE ARE 4968 04:26:02,040 --> 04:26:03,680 INTERESTED IN THIS GERM LINE 4969 04:26:03,680 --> 04:26:06,320 EDITING AND THAT WAS AN EXAMPLE 4970 04:26:06,320 --> 04:26:08,360 OF TISSUE EDITING DONE NOW FOR 4971 04:26:08,360 --> 04:26:11,920 THE TREATMENT OF HUMAN 4972 04:26:11,920 --> 04:26:12,800 HEMOGLOBIN FOR INSTANCE. 4973 04:26:12,800 --> 04:26:14,560 AND WE WOULD LIKE TO GERM LINE 4974 04:26:14,560 --> 04:26:16,960 AND CHANGE THE ORGANISM AND TURN 4975 04:26:16,960 --> 04:26:18,640 IT BLUE OR GROWN TO MAKE THE 4976 04:26:18,640 --> 04:26:19,880 COVER EVER A MAGAZINE OR 4977 04:26:19,880 --> 04:26:22,920 SOMETHING BUT TO GET IT TO GERM 4978 04:26:22,920 --> 04:26:25,040 LINE AND THE GERM LINE IS A 4979 04:26:25,040 --> 04:26:26,600 VALUABLE IN A NUMBER OF WINDOWS 4980 04:26:26,600 --> 04:26:28,600 IN THE DEVELOPMENTAL CYCLE BUT 4981 04:26:28,600 --> 04:26:30,320 IT'S AVAILABLE AS SOON AS THE 4982 04:26:30,320 --> 04:26:40,880 EGGS LAY BECAUSE THEY'RE THAT IS 4983 04:27:02,880 --> 04:27:04,400 WHAT HAPPENS IN THE LIVER WHERE 4984 04:27:04,400 --> 04:27:07,000 THEY'RE TRAPPED SO WE WANTED TO 4985 04:27:07,000 --> 04:27:10,720 LAY CRISPR MATER MATERIAL AND TS 4986 04:27:10,720 --> 04:27:14,880 OUR PLAN SO WE DECIDE THAT 4987 04:27:14,880 --> 04:27:17,480 BEFORE CRISPR BY VIRAL INFECTION 4988 04:27:17,480 --> 04:27:20,600 OF EGGS AND MAKE GERM LINE WORMS 4989 04:27:20,600 --> 04:27:22,520 AND WE PUBLISHED THIS A FEW 4990 04:27:22,520 --> 04:27:24,000 YEARS AGO AND I WENT GO THROUGH 4991 04:27:24,000 --> 04:27:28,240 THE PATENT BUT THESE THE GENE 4992 04:27:28,240 --> 04:27:30,520 HERE WE CAN FIND IT IN THE F-1 4993 04:27:30,520 --> 04:27:33,040 AND THE DIFFICULTY IS THAT THAT 4994 04:27:33,040 --> 04:27:34,240 IS A SINGLE SEX. 4995 04:27:34,240 --> 04:27:35,800 IT'S HOW THE MALE OR FEMALE AND 4996 04:27:35,800 --> 04:27:39,840 THAT'S WHAT WE GOT AND WE MADE A 4997 04:27:39,840 --> 04:27:45,320 NUMBER OF AND WE CAN TRANSIT AND 4998 04:27:45,320 --> 04:27:49,520 GOWN THE GENERATIONS AND AND THE 4999 04:27:49,520 --> 04:27:51,960 REPORTED SOON WAS SOONLY 5000 04:27:51,960 --> 04:27:54,480 ACTIVATED WHEN USED RETRO VIRUS 5001 04:27:54,480 --> 04:27:56,640 AND THIS INVOLVED AND THEY'RE 5002 04:27:56,640 --> 04:28:01,480 OFTEN DEPENDING ON THE LAND AND 5003 04:28:01,480 --> 04:28:03,120 NONE THE LESS I WANT TO TRY TO 5004 04:28:03,120 --> 04:28:10,560 TELL YOU THAT WE CAN MAKE AND WE 5005 04:28:10,560 --> 04:28:13,800 CROSS THEM AND IT WILL BE IN 5006 04:28:13,800 --> 04:28:15,240 CONTAIN THE TRANCE GENE AT THIS 5007 04:28:15,240 --> 04:28:17,320 LOCUS AND THEN IT WILL BE PASSED 5008 04:28:17,320 --> 04:28:19,920 DOWN THE LINE AND IN VERY RECENT 5009 04:28:19,920 --> 04:28:22,600 TIMES THESE DATA ARE UNPUBLISHED 5010 04:28:22,600 --> 04:28:24,360 AND WE ACTUALLY IDENTIFIED WHAT 5011 04:28:24,360 --> 04:28:27,160 WE CONSIDERED GENOME SAFE 5012 04:28:27,160 --> 04:28:30,000 HARBORS IN THE GENOME SAYING TO 5013 04:28:30,000 --> 04:28:31,560 THE ROSE 26 SIDE AND OTHERS THAT 5014 04:28:31,560 --> 04:28:33,800 ARE USED IN HUMAN GENE THERAPY 5015 04:28:33,800 --> 04:28:36,360 OR MOUSE MODELS OF HUMAN GENE 5016 04:28:36,360 --> 04:28:39,840 THERAPY AND SO WITH A NUMBER OF 5017 04:28:39,840 --> 04:28:42,360 MANIPULATIONS AND GRUNT WE CAN 5018 04:28:42,360 --> 04:28:44,560 DELIVER CRISPR REPORTED TRANCE 5019 04:28:44,560 --> 04:28:48,120 AGAINST WE WANT TO PUNE NA TIVE 5020 04:28:48,120 --> 04:28:50,480 SAFE HARBOR SO IF WE LOCK TO THE 5021 04:28:50,480 --> 04:28:59,000 EGG IT WAS FLORES ANTS WE CAN GO 5022 04:28:59,000 --> 04:29:09,520 70% OF THE EGGS WILL BE DARPHA 5023 04:29:16,120 --> 04:29:17,200 CONTACTED US AND CALLED ABOUT 5024 04:29:17,200 --> 04:29:19,000 THE BIO SYSTEM AND I WON'T GO 5025 04:29:19,000 --> 04:29:21,680 INTO THIS AND I WILL PROBABLY BE 5026 04:29:21,680 --> 04:29:23,680 BREAKING SOME CONFIDENCE WITHIN 5027 04:29:23,680 --> 04:29:26,080 AND I'LL BE ARRESTED BUT, 5028 04:29:26,080 --> 04:29:27,520 THEY'RE INTERESTED IN CHANGING 5029 04:29:27,520 --> 04:29:30,640 THE MICROBE OF SOLDIERS AND 5030 04:29:30,640 --> 04:29:32,480 MEDICAL FIRST RESPONDERS BY A 5031 04:29:32,480 --> 04:29:34,760 NUMBER OF WAYS THEY SAID COULD A 5032 04:29:34,760 --> 04:29:37,880 MACRO BUY OT I CAN ORGANISM LIKE 5033 04:29:37,880 --> 04:29:44,280 A SCHISTOSOMES OR A HOOK WORM BE 5034 04:29:44,280 --> 04:29:54,800 SOLVED AND AND IT'S MUCH MORE 5035 04:29:55,800 --> 04:30:00,600 GENETICALLY ATTRACT ABLE. 5036 04:30:00,600 --> 04:30:04,080 AND IT'S DIFFICULT PROJECTS AND 5037 04:30:04,080 --> 04:30:08,000 SOUTHEAST ASIA IN THE RIVER 5038 04:30:08,000 --> 04:30:18,520 DELTA AND THEY'RE A CURSE AND. 5039 04:31:05,920 --> 04:31:14,840 >> THE FISH THE LARVA AND AND 5040 04:31:14,840 --> 04:31:20,880 ARRIVES IN THE UPPER SMALL 5041 04:31:20,880 --> 04:31:23,640 INTESTINE AND LIVES IN THE TRACT 5042 04:31:23,640 --> 04:31:32,600 AND IT'S A HUMAN AND RELATIVELY 5043 04:31:32,600 --> 04:31:34,240 RESEARCH IN MEDICAL SCHOOL IN 5044 04:31:34,240 --> 04:31:35,280 NORTHEAST THAILAND AND YOU CAN 5045 04:31:35,280 --> 04:31:38,360 SEE A COUPLE OF THE FLUKES ARE 5046 04:31:38,360 --> 04:31:40,680 JUST POPPED OUT AND SEVERED WILD 5047 04:31:40,680 --> 04:31:42,080 AND THIS TISSUE WAS SECTION BY 5048 04:31:42,080 --> 04:31:44,160 THE PATHOLOGIST IN THE LAB OF A 5049 04:31:44,160 --> 04:31:51,320 COLLEAGUE OF MINE AND THE TUMOR 5050 04:31:51,320 --> 04:31:53,120 THE SURGEON WAS ADDRESS WHAT IS 5051 04:31:53,120 --> 04:31:56,600 THIS SECTION IS UP IN THE TOP 5052 04:31:56,600 --> 04:31:59,240 CORNER AND IT'S A DIRE DISMAL 5053 04:31:59,240 --> 04:32:03,080 PROGNOSIS AND MOST OF THE PEOPLE 5054 04:32:03,080 --> 04:32:08,920 WOULD BE AND DEAD AFTER THE 5055 04:32:08,920 --> 04:32:09,160 DIAGNOSIS. 5056 04:32:09,160 --> 04:32:11,160 THE WORMS LIVE IN THE BILE DUCT 5057 04:32:11,160 --> 04:32:15,560 AND LONG LIST LIKE SCHIS. 5058 04:32:15,560 --> 04:32:18,320 >> Toni-Marie: AND THEY EAT IN 5059 04:32:18,320 --> 04:32:21,360 THE BIO DUCT IN THIS TISSUE HERE 5060 04:32:21,360 --> 04:32:23,800 AND THIS IS EXPERIMENT FROM OUR 5061 04:32:23,800 --> 04:32:27,920 GROUP WHERE WE JUST CULTURE 5062 04:32:27,920 --> 04:32:31,640 HUMAN CHOLANGIOCYTES AND YOU CAN 5063 04:32:31,640 --> 04:32:33,440 SEE THE VEHICLES ARE UPTAKEN BY 5064 04:32:33,440 --> 04:32:40,960 THE CHOLANGIOCYTES AND WE GEE 5065 04:32:40,960 --> 04:32:42,400 OWN EDIT THIS FLUTE AND AFTER WE 5066 04:32:42,400 --> 04:32:45,280 MA LIP NATURED THE LAVA 5067 04:32:45,280 --> 04:32:46,960 INFECTING THE HAMSTERS AND YOU 5068 04:32:46,960 --> 04:32:49,720 LOCK AT EXPERIMENTALLY INFECTED 5069 04:32:49,720 --> 04:32:54,440 WITH A FLU AND RIGHT THERE THIS 5070 04:32:54,440 --> 04:33:01,120 ALREADY HYPO PLASIC LINING IS 5071 04:33:01,120 --> 04:33:02,680 SEVERAL CELLS THICK IN NATURE 5072 04:33:02,680 --> 04:33:05,840 IT'S ONE CELL THICK HOWEVER, THE 5073 04:33:05,840 --> 04:33:07,440 PLACE WE HAD THIS GENOME IN 5074 04:33:07,440 --> 04:33:12,200 CODES OF GROWTH FACTOR KNOWN AS 5075 04:33:12,200 --> 04:33:14,800 GRAN YOU LYNN AND IN THE ABSENCE 5076 04:33:14,800 --> 04:33:18,680 OF GRANYOU, LYNN THERE'S NO 5077 04:33:18,680 --> 04:33:19,280 PROLIFERATION OF THE TRACT AND 5078 04:33:19,280 --> 04:33:21,720 THAT IS THE CELL THAT IS SELL OF 5079 04:33:21,720 --> 04:33:24,160 ORIGIN OF THIS LIVER CANCER AND 5080 04:33:24,160 --> 04:33:25,640 WE HAD BEEN PLAYING AROUND WITH 5081 04:33:25,640 --> 04:33:27,320 A GROWTH FACTOR AND I DON'T HAVE 5082 04:33:27,320 --> 04:33:29,800 TIME TO TELL YOU ABOUT IT. 5083 04:33:29,800 --> 04:33:31,440 WE COULD GET RID OF SOME OF THE 5084 04:33:31,440 --> 04:33:33,520 DISEASE AND SO, CHANGE TRACK A 5085 04:33:33,520 --> 04:33:35,560 LITTLE BIT, THIS IS NOT MY WORK 5086 04:33:35,560 --> 04:33:40,360 BUT WORK BY CONCORD UNIVERSITY. 5087 04:33:40,360 --> 04:33:42,280 THE GEE OWN SEQUENCED CARCINOMA 5088 04:33:42,280 --> 04:33:43,800 FROM HUMANS AND IN THAT PART OF 5089 04:33:43,800 --> 04:33:54,320 THE WORLD SO LIVER FLUKE IT'S A 5090 04:34:05,560 --> 04:34:07,600 GREAT ON CARCINOGEN AND WHEN 5091 04:34:07,600 --> 04:34:14,600 THEY PROFILED THE GENETIC 5092 04:34:14,600 --> 04:34:21,080 CHANGES, ON THE FEWTATION THAT'S 5093 04:34:21,080 --> 04:34:25,200 PROGRESSIVE IN VERSUS NON LIVER 5094 04:34:25,200 --> 04:34:27,520 FLUKE AND IT MIGHT TURN BORING I 5095 04:34:27,520 --> 04:34:33,000 WANT TO POINT OUT THAT TP5 3 IS 5096 04:34:33,000 --> 04:34:35,840 SEEN AND THIS IS A CHRONIC 5097 04:34:35,840 --> 04:34:37,280 INFECTION SO WE'RE IN A GENERAL 5098 04:34:37,280 --> 04:34:41,880 WAY THIS IS A CHRONIC INFECTION 5099 04:34:41,880 --> 04:34:43,240 ASSOCIATED MALIGNANCY AND SO 5100 04:34:43,240 --> 04:34:44,520 BACK TO MY STORY. 5101 04:34:44,520 --> 04:34:48,840 SO WOAD LIKE TO MODEL THAT. 5102 04:34:48,840 --> 04:34:51,240 IF WE INFECT A HAMSTER IN THE 5103 04:34:51,240 --> 04:34:52,600 LAB AND THESE WORMS ARE WILD 5104 04:34:52,600 --> 04:34:53,800 ANIMALS AND THESE ARE NOT 5105 04:34:53,800 --> 04:34:55,120 MAINTAINED IN THE LAB. 5106 04:34:55,120 --> 04:34:57,640 THE COLLEAGUES HAVE TO GO TO THE 5107 04:34:57,640 --> 04:34:59,320 MARKET OR HAVE SOMEONE FISH TO 5108 04:34:59,320 --> 04:35:01,040 FIND THESE SO WE ONLY GET THE 5109 04:35:01,040 --> 04:35:02,840 WORMS FROM THE WILD. 5110 04:35:02,840 --> 04:35:05,960 AND THEN YOU INFECT THE LAB 5111 04:35:05,960 --> 04:35:07,560 RODENTS OR WHATEVER HAMSTER AND 5112 04:35:07,560 --> 04:35:08,840 YOU DO AROUND EXPERIMENT IN THE 5113 04:35:08,840 --> 04:35:10,760 LIFE OF A HAMSTER IN THE LABS A 5114 04:35:10,760 --> 04:35:12,720 YEAR OR SO, THE TUMOR DOESN'T 5115 04:35:12,720 --> 04:35:14,600 DEVELOP AND IT DOESN'T DEVELOP 5116 04:35:14,600 --> 04:35:16,040 UNTIL THE MID DECADES OF LIFE IN 5117 04:35:16,040 --> 04:35:19,600 PEOPLE BUT IT WAS WELL-KNOWN FOR 5118 04:35:19,600 --> 04:35:21,560 30 OR 40 YEARS, PARTICULARLY 5119 04:35:21,560 --> 04:35:23,760 FROM PEOPLE AT THE UNIVERSITY IN 5120 04:35:23,760 --> 04:35:26,560 BANGKOK, THAT THEY COULD INDUCE 5121 04:35:26,560 --> 04:35:33,280 A MODEL OF COL ANGIE OWE C CARCA 5122 04:35:33,280 --> 04:35:35,240 BY ADDING IT RELEVANT BECAUSE 5123 04:35:35,240 --> 04:35:37,640 THE DIET OF THE PEOPLE IN 5124 04:35:37,640 --> 04:35:48,160 NORTHEAST THAILAND IS RICH CAN 5125 04:35:56,880 --> 04:36:00,480 YOU INDUCE IN A FEW MONTHS SO 5126 04:36:00,480 --> 04:36:01,880 DURING COVID WE TRIED TO DID 5127 04:36:01,880 --> 04:36:03,400 THAT EXPERIMENT AND WE HAD TO 5128 04:36:03,400 --> 04:36:05,800 GUESS WHICH OF THESE LEVELS SO 5129 04:36:05,800 --> 04:36:06,800 WE ACTUALLY DIALED RIGHT UP AND 5130 04:36:06,800 --> 04:36:10,160 WE USED 100 NUCKS AND 12.5 PARTS 5131 04:36:10,160 --> 04:36:12,160 PER MILLION AND WE INFECTED A 5132 04:36:12,160 --> 04:36:13,280 NUMBER OF HAMSTERS AND VERY 5133 04:36:13,280 --> 04:36:15,360 BRIEFLY TO FINISH UP, WHEN WE 5134 04:36:15,360 --> 04:36:17,640 DID THAT, AND I ONLY JUST PLEASE 5135 04:36:17,640 --> 04:36:20,760 LOOK AT THE TWO LEFT HAND BARS 5136 04:36:20,760 --> 04:36:22,280 THERE, THE PUNCH LINE IS THIS 5137 04:36:22,280 --> 04:36:24,840 AND THIS IS UNDER REVIEW AT 5138 04:36:24,840 --> 04:36:26,960 PRESENT PEER ROW VIEW BUT IT'S 5139 04:36:26,960 --> 04:36:28,640 IN YOU WANT TO LOOK AT IT AND 5140 04:36:28,640 --> 04:36:33,200 ALL THE HAMSTERS GOT CARCINOMA 5141 04:36:33,200 --> 04:36:35,600 BUT THERE WAS SIGNIFICANTLY LESS 5142 04:36:35,600 --> 04:36:37,680 DISEASE AND LESS MARKET DISEASE 5143 04:36:37,680 --> 04:36:39,800 WHEN WE KNOCKED OUT GRANULE LAR 5144 04:36:39,800 --> 04:36:46,480 AND INFECTED LIVER FLOCKS SO FL. 5145 04:36:46,480 --> 04:36:48,240 IT'S OVER LEVEL FLEW BUT WE 5146 04:36:48,240 --> 04:36:52,120 LOOKED AT MANY OF THE KIND OF 5147 04:36:52,120 --> 04:36:54,440 HALLMARKS OF CANCER THINGS, 5148 04:36:54,440 --> 04:36:56,840 CANCER EXPERTS LOOK AT INCLUDING 5149 04:36:56,840 --> 04:36:58,120 PROLIFERATION AND THERE'S A LOT 5150 04:36:58,120 --> 04:37:02,040 MORE PROLIFERATION OF THE SITES 5151 04:37:02,040 --> 04:37:04,160 AND IN THE CONTROLS VERSUS THE 5152 04:37:04,160 --> 04:37:06,320 ONES THAT WHERE IT'S KNOCKED OUT 5153 04:37:06,320 --> 04:37:09,880 OR KNOCKED DOWN AND I THINK LET 5154 04:37:09,880 --> 04:37:18,520 ME SEE, YEAH, AND P53 THIS IS 5155 04:37:18,520 --> 04:37:20,640 LESS OF MUTANT P53 THAN IN THE 5156 04:37:20,640 --> 04:37:22,440 CONTROLS SO, I THINK I'M 5157 04:37:22,440 --> 04:37:26,480 FINISHING UP NOW IS CRISPR 5158 04:37:26,480 --> 04:37:28,080 EDITING IS ACTION TIVE IN LIVER 5159 04:37:28,080 --> 04:37:28,960 FLOCKS AS SOME OF THE THINGS YOU 5160 04:37:28,960 --> 04:37:34,520 CAN DO WITH IT SUCH AS REPAIR 5161 04:37:34,520 --> 04:37:36,000 AND IN TERMS OF THE TWO EXAMPLES 5162 04:37:36,000 --> 04:37:39,480 OF SHOWED YOU, WE IN 5163 04:37:39,480 --> 04:37:41,680 SCHISTOSOMES WE KNOCKED OUT THE 5164 04:37:41,680 --> 04:37:44,720 MEGA RESPONSIBLE FOR THE TH2 AS 5165 04:37:44,720 --> 04:37:46,880 AN EXAMPLE AND WE'RE TRYING TO 5166 04:37:46,880 --> 04:37:48,760 DERIVE A LINE BUT IT MAY BE A 5167 04:37:48,760 --> 04:37:50,360 LETHAL MUTATION AND I SHOWED YOU 5168 04:37:50,360 --> 04:37:52,160 THAT WE CAN GET SIMILAR THINGS 5169 04:37:52,160 --> 04:37:54,440 TO WORK IN LIVER FLUKES SO WE 5170 04:37:54,440 --> 04:37:56,320 THINK FUNCTIONAL GENOMICS IS 5171 04:37:56,320 --> 04:37:58,400 ACCESSIBLE FOR PARA SID I CAN 5172 04:37:58,400 --> 04:38:07,240 ELEMENTS FOR THE MAJOR AND HOPEY 5173 04:38:07,240 --> 04:38:07,760 IT'S LOWER. 5174 04:38:07,760 --> 04:38:10,160 THESE ARE THE FOLKS I'VE 5175 04:38:10,160 --> 04:38:10,560 COLLABORATED. 5176 04:38:10,560 --> 04:38:13,840 JUST TOO MANY PEOPLE TO GO INTO. 5177 04:38:13,840 --> 04:38:16,760 I WILL MENTION MY COLLEAGUES IN 5178 04:38:16,760 --> 04:38:18,240 CON CANE UNIVERSITY AND JAMES 5179 04:38:18,240 --> 04:38:18,920 COOK UNIVERSITY. 5180 04:38:18,920 --> 04:38:21,320 I WANT TO FINISH UP WITH THIS 5181 04:38:21,320 --> 04:38:22,840 SLIDE BECAUSE BLACK AND WHITE, 5182 04:38:22,840 --> 04:38:24,600 ALL WE COULD AFFORD IN THE PAPER 5183 04:38:24,600 --> 04:38:30,880 WAS A BLACK AND WHITE 5184 04:38:30,880 --> 04:38:31,800 PHOTOGRAPH. 5185 04:38:31,800 --> 04:38:35,360 I NOW HAVE A COLOR CAMERA AND I 5186 04:38:35,360 --> 04:38:37,240 STILL COME DOWNTOWN HERE AND 5187 04:38:37,240 --> 04:38:40,080 TAKE ELLEN'S SAGE ADVICE ABOUT 5188 04:38:40,080 --> 04:38:42,080 OMEGA AND OTHER THINGS AND IT'S 5189 04:38:42,080 --> 04:38:43,880 USUALLY IN AN IRISH BAR SO THANK 5190 04:38:43,880 --> 04:38:48,960 YOU, VERY MUCH, ALAN. 5191 04:38:48,960 --> 04:38:59,160 [APPLAUSE] 5192 04:39:03,680 --> 04:39:07,240 [OFF MIC] 5193 04:39:07,240 --> 04:39:10,600 WE KNOCKED OUT A SECOND GENE 5194 04:39:10,600 --> 04:39:13,600 ENCODING A BAN ON THE WORMS 5195 04:39:13,600 --> 04:39:16,120 DIDN'T SURVIVE. 5196 04:39:16,120 --> 04:39:16,800 THE GRANULAR WORMS ARE 5197 04:39:16,800 --> 04:39:17,760 RECOVERABLE AT THE END OF THE 5198 04:39:17,760 --> 04:39:21,080 SIX MONTH EXPERIMENT AND WE 5199 04:39:21,080 --> 04:39:22,800 DON'T THINK THERE'S FIT BUT IT'S 5200 04:39:22,800 --> 04:39:26,520 TRACT ABLE TO DO THAT KIND OF 5201 04:39:26,520 --> 04:39:33,640 MALIGNANCY ASSOCIATED RODENT 5202 04:39:33,640 --> 04:39:36,480 EXPERIMENT. 5203 04:39:36,480 --> 04:39:38,040 WE CAN LOOK AT MARKERS BUT 5204 04:39:38,040 --> 04:39:39,520 DEFINITELY FIT ENOUGH TO DO THIS 5205 04:39:39,520 --> 04:39:41,400 KIND OF EXPERIMENT. 5206 04:39:41,400 --> 04:39:43,360 WHAT I WOULD SAY ABOUT LIVER 5207 04:39:43,360 --> 04:39:44,920 FLUKE THOUGH, WE DON'T HAVE ANY 5208 04:39:44,920 --> 04:39:46,800 PRE TENSION THAT'S WE COULD MAKE 5209 04:39:46,800 --> 04:39:48,720 A GERM LINE TRANSGENIC ANY TIME 5210 04:39:48,720 --> 04:39:51,880 SOON BUT WE CAN DEFINITELY DO 5211 04:39:51,880 --> 04:39:52,920 THAT WITH (INAUDIBLE) NOW. 5212 04:39:57,960 --> 04:40:05,040 [OFF MIC] 5213 04:40:05,040 --> 04:40:11,480 >> OH, BECAUSE THE -- 5214 04:40:11,480 --> 04:40:16,040 NO, THE BLOCK IS, WELL, THE 5215 04:40:16,040 --> 04:40:17,720 BLOCK IS HUMAN GET AROUND ABLE 5216 04:40:17,720 --> 04:40:19,480 WITH MY POOR EXAMPLE OF ENGLISH. 5217 04:40:19,480 --> 04:40:21,800 IF YOU DON'T HAVE OMEGA, YOU 5218 04:40:21,800 --> 04:40:24,080 WON'T GET A GRANULOMA AND THE 5219 04:40:24,080 --> 04:40:28,440 GRANULOMA IS NEEDED FOR THE 5220 04:40:28,440 --> 04:40:32,120 TRANSIT ACROSS THE BALL WALL. 5221 04:40:32,120 --> 04:40:36,440 WE PRESUME WE WOULD RECOVER EGGS 5222 04:40:36,440 --> 04:40:38,400 FROM THE LIVER, THERE WOULDN'T 5223 04:40:38,400 --> 04:40:44,200 BE A GRANULOMA AND THEY VERY 5224 04:40:44,200 --> 04:40:54,480 WELL MAY HATCH. 5225 04:41:12,760 --> 04:41:13,000 THANK YOU. 5226 04:41:13,000 --> 04:41:17,680 >> THE NEXT SPEAKER IS Dr. 5227 04:41:17,680 --> 04:41:19,800 P'NG LOKE. 5228 04:41:19,800 --> 04:41:22,280 NIAID WAS LUCKY ENOUGH TO 5229 04:41:22,280 --> 04:41:24,160 RECRUIT HIM RECENTLY AND WHO IS 5230 04:41:24,160 --> 04:41:33,960 TALK TO TALK ABOUT HETEROGENEITY 5231 04:41:33,960 --> 04:41:44,160 MACROPHAGES. 5232 04:41:45,960 --> 04:41:49,800 >> WELL, FIRST OF ALL IT'S 5233 04:41:49,800 --> 04:41:52,200 REALLY SUCH A PLEASURE AND HONOR 5234 04:41:52,200 --> 04:41:58,400 TO BE SPEAKING AT ALAN AND IT IS 5235 04:41:58,400 --> 04:42:00,800 DRAG AM A FOR PUTTING TOGETHER 5236 04:42:00,800 --> 04:42:05,520 THIS AMAMAZING EVENT. 5237 04:42:05,520 --> 04:42:06,840 LONG BIFF METAL AN I WAS READING 5238 04:42:06,840 --> 04:42:17,320 HIS PAPER SO I AM ABOUT THE 5239 04:42:19,720 --> 04:42:21,560 CELLS THAT WOULD HAVE MAJOR 5240 04:42:21,560 --> 04:42:23,160 EFFECTS ON THE WAY THAT I 5241 04:42:23,160 --> 04:42:27,360 THOUGHT ABOUT PARASITE IMMUNE 5242 04:42:27,360 --> 04:42:34,000 RESPONSES SO AND I USE IT A LOT 5243 04:42:34,000 --> 04:42:36,000 IN MY PRESENTATION AND IT WAS 5244 04:42:36,000 --> 04:42:39,080 ALREADY THERE IN THIS ORIGINAL 5245 04:42:39,080 --> 04:42:39,480 REVIEW ARTICLE. 5246 04:42:39,480 --> 04:42:41,120 AND YOU KNOW, DURING THE COST OF 5247 04:42:41,120 --> 04:42:45,840 THE LAST FEW DAYS, WE'VE HEARD A 5248 04:42:45,840 --> 04:42:56,080 LOT ABOUT THE TCH AND HE PASSED 5249 04:42:56,080 --> 04:42:58,920 AND TALKING ABOUT THE ASPECTS OF 5250 04:42:58,920 --> 04:43:02,560 IMMUNE RESPONSE AND THE 5251 04:43:02,560 --> 04:43:06,080 CONTRIBUTION AND I DON'T HAVE 5252 04:43:06,080 --> 04:43:13,400 ALAN AND UNDERSTANDING AND AND 5253 04:43:13,400 --> 04:43:21,840 LONG BEFORE HE WORKED ON THE TB 5254 04:43:21,840 --> 04:43:24,880 GRANULOMA AND IT WAS A KEY COM 5255 04:43:24,880 --> 04:43:35,360 PHONE AROUND OF THE PARK IN 5256 04:43:52,120 --> 04:43:55,000 SOMEONE THEY GET STUCK IN THE 5257 04:43:55,000 --> 04:43:56,480 LIVER AND CAUSE THESE GRANULOMA 5258 04:43:56,480 --> 04:44:00,840 TO FORM AND IN DEED THE 5259 04:44:00,840 --> 04:44:02,560 GRANULOMA IS THE PASSAGE FOR THE 5260 04:44:02,560 --> 04:44:05,360 INTESTINE AND THIS CAME OUT 5261 04:44:05,360 --> 04:44:06,840 YESTERDAY THAT I OFTEN THINK OF 5262 04:44:06,840 --> 04:44:11,440 THIS AS BEING A GOOD MODEL FOR 5263 04:44:11,440 --> 04:44:15,240 TUMOR METASTASIS AND TUMORS HAVE 5264 04:44:15,240 --> 04:44:17,680 GRANULOMA STRUCTURE THAT MIGRATE 5265 04:44:17,680 --> 04:44:19,920 THROUGH DIFFERENT TISSUE WALLS 5266 04:44:19,920 --> 04:44:23,120 AND AS WE HEARD FROM BOB COFFMAN 5267 04:44:23,120 --> 04:44:26,520 EARLIER THERE WAS A REMARKABLE 5268 04:44:26,520 --> 04:44:28,880 PERIOD OF WORK FROM ED PEARCE 5269 04:44:28,880 --> 04:44:34,960 AND TOM AND ALAN TO REALLY 5270 04:44:34,960 --> 04:44:45,480 DESCRIBE THE FUNCTION OF AND IL4 5271 04:44:46,240 --> 04:44:51,120 AND IL5 AND IL-12 INTERFERON 5272 04:44:51,120 --> 04:44:53,480 GAMMA AND THE ROLE OF ALL THESE 5273 04:44:53,480 --> 04:45:00,600 CYTOKINES AND FUNCTION OF THESE 5274 04:45:00,600 --> 04:45:11,080 CYTO TO INITIATE THIS ENTIRE 5275 04:45:12,800 --> 04:45:15,600 CASCADE AND I THINK THE WORK 5276 04:45:15,600 --> 04:45:17,320 THAT ALAN'S GROUP HAS DONE ON 5277 04:45:17,320 --> 04:45:19,760 ALL THESE CYTOKINES ARE 5278 04:45:19,760 --> 04:45:23,080 INCREASINGLY IMPORTANT IN OUR 5279 04:45:23,080 --> 04:45:25,760 UNDERSTANDING OF THE ROLE OF THE 5280 04:45:25,760 --> 04:45:27,880 TYPE 2 IMMUNE RESPONSE AND 5281 04:45:27,880 --> 04:45:30,720 MAINTAINING TISSUE HOMEOSTASIS 5282 04:45:30,720 --> 04:45:31,960 AND IT BECOMES MORE AND MORE 5283 04:45:31,960 --> 04:45:34,080 CLEAR THAT OVER THE LAST, FROM 5284 04:45:34,080 --> 04:45:35,400 WORK OVER THE LAST FEW YEARS 5285 04:45:35,400 --> 04:45:36,960 THAT THIS TYPE 2 RESPONSE IS 5286 04:45:36,960 --> 04:45:42,360 VERY IMPORTANT FOR THE PROCESSES 5287 04:45:42,360 --> 04:45:43,200 OF WOUND REPAIR AND WOUND 5288 04:45:43,200 --> 04:45:47,200 HEALING AND TISSUE REPAIR AND 5289 04:45:47,200 --> 04:45:49,600 ALSO, ADD A POST TISSUE AND 5290 04:45:49,600 --> 04:45:51,280 METABOLISM AND I USED TO BE IN 5291 04:45:51,280 --> 04:45:52,720 THE CAMP THAT BELIEVED THE TYPE 5292 04:45:52,720 --> 04:45:57,280 2 IMMUNE RESPONSE EVOLVED TO 5293 04:45:57,280 --> 04:46:05,560 PROTECT US FROM HELL MINUTE 5294 04:46:05,560 --> 04:46:12,000 INFECTIONS TO MAINTAIN AND WAS 5295 04:46:12,000 --> 04:46:19,200 CO OPTED BY THE IMMUNE SYSTEM 5296 04:46:19,200 --> 04:46:25,440 AND THE SAME PROCESS OF WOUND 5297 04:46:25,440 --> 04:46:28,440 HEALING AND TISSUE REPAIR AND 5298 04:46:28,440 --> 04:46:30,720 VERY IMPORTANT ALSO IN 5299 04:46:30,720 --> 04:46:34,240 RESISTANCE AND TOLERANCE 5300 04:46:34,240 --> 04:46:35,920 MECHANISMS TO HELMINTH 5301 04:46:35,920 --> 04:46:39,480 INFECTIONS SO FOR ME PERSONALLY 5302 04:46:39,480 --> 04:46:43,920 AND I THINK MY INTEREST START 5303 04:46:43,920 --> 04:46:49,120 TODAY OVER HAL THAT WAS DONE AND 5304 04:46:49,120 --> 04:46:51,200 DEACTIVATED AND MAKE ROW PAGES 5305 04:46:51,200 --> 04:46:55,640 AND THIS CONCEPT I THINK THAT 5306 04:46:55,640 --> 04:47:00,120 AND AND THE TEEN SIGHT AND HE 5307 04:47:00,120 --> 04:47:02,720 DIFFERENT PHONY TYPE AND 5308 04:47:02,720 --> 04:47:04,120 ACTIVATION AND NOW WELL 5309 04:47:04,120 --> 04:47:05,320 SEPTEMBER AND BY EVERYONE AND 5310 04:47:05,320 --> 04:47:12,720 IT'S CLEAR THAT THE THESE 5311 04:47:12,720 --> 04:47:20,360 ALTERNATIVE MACROPHAGES AND WITH 5312 04:47:20,360 --> 04:47:26,560 HIGH CONCENTRATIONS O THEY'RE NT 5313 04:47:26,560 --> 04:47:27,440 REPRESENTATIVE PERHAPS OF WHAT 5314 04:47:27,440 --> 04:47:32,760 IS FOUND IN THE TISSUE AND IT'S 5315 04:47:32,760 --> 04:47:34,440 CLEAR SEEK EXPERIMENTS AND 5316 04:47:34,440 --> 04:47:37,600 MACROPHAGES IN THE TISSUE AND 5317 04:47:37,600 --> 04:47:41,880 FALL MORE DIFFERENT ACTIVATIONS 5318 04:47:41,880 --> 04:47:52,440 STATES OF WHICH AND THE OTHER IS 5319 04:47:57,680 --> 04:48:00,240 THESE ARE ACTIVATION STATES SO 5320 04:48:00,240 --> 04:48:01,760 MACROPHAGES ARE MUCH MORE 5321 04:48:01,760 --> 04:48:05,000 PLASTIC CELL TYPES AND THE 5322 04:48:05,000 --> 04:48:08,960 TRANSCRIPTION FACTORS ARE MORE 5323 04:48:08,960 --> 04:48:10,880 SNAPS DEPEND AND LINEAGE 5324 04:48:10,880 --> 04:48:12,640 DEPENDING AND THAT YOU CAN GET 5325 04:48:12,640 --> 04:48:18,040 WITH T CELLS. 5326 04:48:18,040 --> 04:48:20,720 MY INTEREST IN THESE 5327 04:48:20,720 --> 04:48:22,360 ALTERNATIVELY ACTIVATED 5328 04:48:22,360 --> 04:48:25,920 MACROPHAGES STARTED WHEN I WAS A 5329 04:48:25,920 --> 04:48:27,600 PH.D STUDENT AND AND IT'S 5330 04:48:27,600 --> 04:48:30,200 ANOTHER FAVORITE ORGANISM OF THE 5331 04:48:30,200 --> 04:48:33,800 LPD AND ALTHOUGH I THINK TOM 5332 04:48:33,800 --> 04:48:35,640 THOUGHT THESE EXPERIMENTS WHERE 5333 04:48:35,640 --> 04:48:38,800 WE IMPLANTED THESE PARASITES 5334 04:48:38,800 --> 04:48:41,680 INTO THE PERITONEAL CAVITY WAS 5335 04:48:41,680 --> 04:48:45,720 NOT PHYSIOLOGICAL BUT NONE THE 5336 04:48:45,720 --> 04:48:47,400 LESS, WHILE I WAS PH.D STUDENT 5337 04:48:47,400 --> 04:48:51,720 IN JUDY ALLEN'S LAB, WE FOUND 5338 04:48:51,720 --> 04:48:57,720 THAT THEY INDUCE ACCUMULATIONS 5339 04:48:57,720 --> 04:48:59,320 AND THEY HAD A DISTINCT 5340 04:48:59,320 --> 04:49:00,960 PHENOTYPE OF BEING ABLE TO 5341 04:49:00,960 --> 04:49:03,440 SUPPRESS T-CELL PROLIFERATION 5342 04:49:03,440 --> 04:49:05,480 AND EXPRESS THESE GENES THAT AT 5343 04:49:05,480 --> 04:49:07,280 A TIME THE FUNCTION OF WHICH WAS 5344 04:49:07,280 --> 04:49:09,960 VERY MUCH UNCHARACTERIZED AND 5345 04:49:09,960 --> 04:49:11,880 HAS BECOME REALLY USEFUL MARKERS 5346 04:49:11,880 --> 04:49:17,760 FORT PRESENCE OF IL-4 ACTIVATED 5347 04:49:17,760 --> 04:49:19,080 MACROPHAGES OVER THE LAST FOUR 5348 04:49:19,080 --> 04:49:23,360 YEARS AND WE KNOW FROM THE WORK 5349 04:49:23,360 --> 04:49:25,080 OF TOM WYNN THAT JUDY ALLEN'S 5350 04:49:25,080 --> 04:49:29,520 LAB HAS CONTINUED TO WORK ON THE 5351 04:49:29,520 --> 04:49:30,520 CHITON ACE LIKE MOLECULES AND 5352 04:49:30,520 --> 04:49:32,640 ANOTHER TRAINEE IN JUDY ALAN'S 5353 04:49:32,640 --> 04:49:35,480 LAB HAS CONTINUED TO WORK ON ALL 5354 04:49:35,480 --> 04:49:37,960 OF THESE MOLECULES PLAY VERY 5355 04:49:37,960 --> 04:49:39,400 IMPORTANT ROLES IN IMMUNE 5356 04:49:39,400 --> 04:49:40,800 REGULATION AND IMMUNE REGULATION 5357 04:49:40,800 --> 04:49:44,600 IS A VERY IMPORTANT FUNCTION OF 5358 04:49:44,600 --> 04:49:47,040 THESE ALTERNATIVE ACTIVATED 5359 04:49:47,040 --> 04:49:49,440 MACROPHAGES AND NOW, I WENT AND 5360 04:49:49,440 --> 04:49:52,480 DID MY POSTDOC TO BAL WORK IN 5361 04:49:52,480 --> 04:49:55,560 JIM WALL SON'S LAB AT BERKELEY 5362 04:49:55,560 --> 04:50:00,200 SO I SEARCHED AWAY AND STARTED 5363 04:50:00,200 --> 04:50:02,600 TO WORK ON MOLECULES AND ONE OF 5364 04:50:02,600 --> 04:50:07,000 THE THINGS I FOUND AT THE TIME 5365 04:50:07,000 --> 04:50:10,800 WAS IF YOU PAR TENILLEAL 5366 04:50:10,800 --> 04:50:13,400 MACROPHAGES IF YOU HAVE IL-4 OR 5367 04:50:13,400 --> 04:50:16,680 TH-2 CELLS THEY WOULD UP 5368 04:50:16,680 --> 04:50:20,440 REGULATE SPECIFICALLY THE PDL2 5369 04:50:20,440 --> 04:50:24,480 SO THE TH1 CELLS AND THE TH2 5370 04:50:24,480 --> 04:50:27,240 CELLS UP REGULATED PDL2 BUT THE 5371 04:50:27,240 --> 04:50:28,680 THING THAT BOTHERED ME ABOUT THE 5372 04:50:28,680 --> 04:50:33,120 WORK THAT WE DID AT THE TIME WAS 5373 04:50:33,120 --> 04:50:36,760 NO HARD I LOOKED THEY WERE 5374 04:50:36,760 --> 04:50:39,240 INDUCED NEVER UP REGULATED PDL2 5375 04:50:39,240 --> 04:50:40,920 AND THIS IS SOMETHING THAT 5376 04:50:40,920 --> 04:50:42,720 REALLY BOTHERED ME AT A TIME AND 5377 04:50:42,720 --> 04:50:44,920 DIDN'T MAKE IT INTO THE 5378 04:50:44,920 --> 04:50:48,680 MANUSCRIPT OR THE PAPER, AND IT 5379 04:50:48,680 --> 04:50:52,120 WAS REALLY ONLY MANY, MANY YEARS 5380 04:50:52,120 --> 04:50:52,960 LATER THAT I UNDERSTAND WHY THIS 5381 04:50:52,960 --> 04:50:56,440 WAS THE CASE AND IT COMES BACK 5382 04:50:56,440 --> 04:50:58,760 TO SOME OF THE SUBJECT THAT 5383 04:50:58,760 --> 04:51:00,800 FELIX WAS TALKING ABOUT THAT WE 5384 04:51:00,800 --> 04:51:04,120 KNOW NOW THAT TISSUE MACROPHAGES 5385 04:51:04,120 --> 04:51:06,320 COMES FROM DIFFERENT ORIGINS AND 5386 04:51:06,320 --> 04:51:08,040 YOU HAVE INFLAMMATORY 5387 04:51:08,040 --> 04:51:09,800 MACROPHAGES THAT ARE DERIVED 5388 04:51:09,800 --> 04:51:12,360 FROM MONOCYTES AND YOU ALSO HAVE 5389 04:51:12,360 --> 04:51:14,960 TISSUE RESIDENT MACROPHAGES 5390 04:51:14,960 --> 04:51:17,000 DERIVED FROM EMBRYONIC PRE 5391 04:51:17,000 --> 04:51:19,080 CURSERS THAT CAN PROLIFERATE AND 5392 04:51:19,080 --> 04:51:21,840 SELF-RENEW WITHIN THE TISSUES 5393 04:51:21,840 --> 04:51:25,200 AND IT TURNS OUT THAT DEPENDING 5394 04:51:25,200 --> 04:51:29,160 ON THE TYPE OF PARASITE, HELMET 5395 04:51:29,160 --> 04:51:30,720 PARASITE YOU ARE LOOKING AT YOU 5396 04:51:30,720 --> 04:51:32,640 CAN GET ACCUMULATION OF 5397 04:51:32,640 --> 04:51:34,400 ALTERNATIVELY ACTIVATED 5398 04:51:34,400 --> 04:51:36,840 MACROPHAGES THAT COME FROM 5399 04:51:36,840 --> 04:51:39,880 DIFFERENT ORIGINS AND SO I HAD 5400 04:51:39,880 --> 04:51:44,240 THIS FUN VISIT TO EDINBURGH AIR 5401 04:51:44,240 --> 04:51:46,920 STARTED MY LAB AT NY YOU AND 5402 04:51:46,920 --> 04:51:48,320 JUDY AND RICK INVITED ME BACK TO 5403 04:51:48,320 --> 04:51:50,080 GIVE A SEMINAR AND I WAS 5404 04:51:50,080 --> 04:51:54,920 CHATTING WITH JUDY AND I WAS 5405 04:51:54,920 --> 04:51:57,560 SAYING, OH, I KNOW WHERE THESE 5406 04:51:57,560 --> 04:51:59,120 ALTERNATIVE MACRO RATE ISED COME 5407 04:51:59,120 --> 04:52:00,720 FROM MAN OWE SIGHTS AND JUDY 5408 04:52:00,720 --> 04:52:04,960 ALAN WAS LIKE NO, NO, NO, THESE 5409 04:52:04,960 --> 04:52:07,440 COME FROM PROLIFERATING TISSUE 5410 04:52:07,440 --> 04:52:09,880 AND MACROPHAGES AND WHAT IT 5411 04:52:09,880 --> 04:52:20,320 TURNED OUT AND SO WE AND 5412 04:52:27,520 --> 04:52:32,640 ALONGSIDE, WE KNOW THAT IT 5413 04:52:32,640 --> 04:52:37,880 INDUCES THE ACCUMULATION OF 5414 04:52:37,880 --> 04:52:39,840 TISSUE RESIDENT ALTERNATIVELY 5415 04:52:39,840 --> 04:52:41,560 ACTIVATED MACROPHAGES THAT ARE 5416 04:52:41,560 --> 04:52:43,680 DERIVED FROM FETAL PRE CURSERS 5417 04:52:43,680 --> 04:52:45,040 WHEREAS, IN OUR LAB, AT THE 5418 04:52:45,040 --> 04:52:51,080 TIME, WE WERE STUDYING THE SHIR 5419 04:52:51,080 --> 04:52:54,560 SOMA AND THE MACROPHAGES YOU GET 5420 04:52:54,560 --> 04:52:57,840 AROUND THE ARE DERIVED FROM 5421 04:52:57,840 --> 04:53:02,240 MONOCYTES AND PHENOTYPICALLY 5422 04:53:02,240 --> 04:53:08,520 THEY CAN ALTERNATIVE MACROPHAGES 5423 04:53:08,520 --> 04:53:10,560 DO NOT EXPRESS AND THEY CANNOT 5424 04:53:10,560 --> 04:53:12,920 UP REGULATE PDL2 AND THEY 5425 04:53:12,920 --> 04:53:16,040 EXPRESS HIGH LEVELS OF F-4 08 5426 04:53:16,040 --> 04:53:18,320 AND UNCOUPLING PROTEIN UCP1 AND 5427 04:53:18,320 --> 04:53:19,920 THE FUNCTION OF WHICH WE STILL 5428 04:53:19,920 --> 04:53:23,440 DON'T FULLY UNDERSTAND AND SO 5429 04:53:23,440 --> 04:53:25,520 THIS ENDS UP BEING A VERY NICE 5430 04:53:25,520 --> 04:53:27,800 MODEL BECAUSE DEPENDING ON WHICH 5431 04:53:27,800 --> 04:53:29,360 LINEAGE OF MACROPHAGES YOU ARE 5432 04:53:29,360 --> 04:53:33,120 INTERESTED IN STUDYING, YOU CAN 5433 04:53:33,120 --> 04:53:37,440 USE DIFFERENT HELMET PARASITES 5434 04:53:37,440 --> 04:53:39,200 FOR THE DEVELOPMENTAL BIOLOGY 5435 04:53:39,200 --> 04:53:42,040 AND ONE OF THE REASONS I HAD 5436 04:53:42,040 --> 04:53:52,560 READ UP ON ALL OF THE WORK IN 5437 04:54:02,200 --> 04:54:10,000 AND THE CELLS WERE INVITE RALLYE 5438 04:54:10,000 --> 04:54:12,520 GRANULOMA AND THE PRODUCTION OF 5439 04:54:12,520 --> 04:54:21,120 IL-4 AND IT ALSO BECAME CLEAR TE 5440 04:54:21,120 --> 04:54:22,760 IL-4 WERE ACTING ON THE 5441 04:54:22,760 --> 04:54:25,120 MACROPHAGES IN ORDER TO HAVE THE 5442 04:54:25,120 --> 04:54:30,040 PROPER GRANULOMA AND SO THEY 5443 04:54:30,040 --> 04:54:32,840 WERE ESSENTIAL FOR HOST SURVIVAL 5444 04:54:32,840 --> 04:54:36,160 AND WERE INCORPORATED INTO THESE 5445 04:54:36,160 --> 04:54:39,040 GRANULOMA INDUCED BY THE TYPE 2 5446 04:54:39,040 --> 04:54:39,720 CYTOKINE. 5447 04:54:39,720 --> 04:54:42,760 WHEN WE STARTED THIS EXPERIMENT, 5448 04:54:42,760 --> 04:54:44,680 THERE WAS A QUESTION OF WHETHER 5449 04:54:44,680 --> 04:54:47,280 THESE MACROPHAGES WERE DERIVED 5450 04:54:47,280 --> 04:54:56,240 FROM LY60 HIGH OR HIGH MONOCYTES 5451 04:54:56,240 --> 04:54:59,120 AND IT WAS CLEAR FROM A POSTDOC 5452 04:54:59,120 --> 04:55:01,840 IN MY LAB, ESPECIALLY TRUE 5453 04:55:01,840 --> 04:55:05,600 MONOCYTE TRANSFER EXPERIMENTS IT 5454 04:55:05,600 --> 04:55:08,040 WAS THE LY60 HIGH MONOCYTES THAT 5455 04:55:08,040 --> 04:55:12,720 WERE THE SOURCE OF THESE 5456 04:55:12,720 --> 04:55:17,480 GRANULOMA MACROPHAGES AND THIS 5457 04:55:17,480 --> 04:55:19,640 WAS AROUND THE SAME TIME I WORK 5458 04:55:19,640 --> 04:55:23,360 FROM ED PEARCE'S LAB AND ALSO 5459 04:55:23,360 --> 04:55:24,600 PAUL CUBES' LAB AND IT ALL 5460 04:55:24,600 --> 04:55:26,880 POINTED TO THE DIRECTION OF THE 5461 04:55:26,880 --> 04:55:29,160 LY6C HIGH MONOCYTES AS BEING THE 5462 04:55:29,160 --> 04:55:32,800 PRIMARY SOURCE OF THE 5463 04:55:32,800 --> 04:55:34,720 ALTERNATIVELY ACTIVATED 5464 04:55:34,720 --> 04:55:35,840 MACROPHAGES AND WHAT WAS 5465 04:55:35,840 --> 04:55:37,200 INTERESTING THOUGH IS THAT AS 5466 04:55:37,200 --> 04:55:40,400 THE LY60 HIGH MONOCYTES 5467 04:55:40,400 --> 04:55:42,560 ENCOUNTER THIS INFLAMED TISSUE 5468 04:55:42,560 --> 04:55:45,120 THEY WOULD DOWN REGULATE 5469 04:55:45,120 --> 04:55:47,320 EXPRESSION OF AND ADOPT PET 5470 04:55:47,320 --> 04:55:49,600 TROLLING BEHAVIOR THAT WAS 5471 04:55:49,600 --> 04:55:51,440 REMINISCENT OF THE LOW MONOCYTE 5472 04:55:51,440 --> 04:55:53,240 POPULATION BEFORE UP REGULATING 5473 04:55:53,240 --> 04:55:57,680 EXPRESSIONS OF PDL2 AND WE 5474 04:55:57,680 --> 04:56:00,560 HYPOTHESIZED THIS IS A IMPORTANT 5475 04:56:00,560 --> 04:56:03,120 PART OF ROW MODELING PROCESS TO 5476 04:56:03,120 --> 04:56:08,320 REMOVE THE EGGS OUT OF THE BLOOD 5477 04:56:08,320 --> 04:56:09,280 VESSELS. 5478 04:56:09,280 --> 04:56:11,400 OF COURSE, BEING IMMUNOLOGY, 5479 04:56:11,400 --> 04:56:13,480 THINGS GET MORE AND MORE 5480 04:56:13,480 --> 04:56:14,880 COMPLICATED AND ONE OF THE 5481 04:56:14,880 --> 04:56:17,800 THINGS THAT TASHA IN THE LAB AT 5482 04:56:17,800 --> 04:56:28,280 THE TIME WAS THINKING AND WHAT 5483 04:56:32,800 --> 04:56:35,560 TASHA REALIZED WAS THAT THIS 5484 04:56:35,560 --> 04:56:37,080 INFLAMMATORY MACROPHAGES, WHEN 5485 04:56:37,080 --> 04:56:39,280 THEY SPENT ENOUGH TIME IN THE 5486 04:56:39,280 --> 04:56:42,280 TISSUES, BEGIN TO ADOPT THE 5487 04:56:42,280 --> 04:56:43,520 PROPERTIES OF THE TISSUE 5488 04:56:43,520 --> 04:56:46,520 RESIDENT MACROPHAGES AND IN THE 5489 04:56:46,520 --> 04:56:47,960 GRANULOMA, ONE COULD SEE THAT AS 5490 04:56:47,960 --> 04:56:53,920 THE GRANULOMA MATURE, THE 5491 04:56:53,920 --> 04:56:59,200 MACROPHAGES AROUND THE FOR FRINS 5492 04:56:59,200 --> 04:57:03,240 ADOPT PROPERTIES OF THE TISSUE 5493 04:57:03,240 --> 04:57:10,240 RESIDENT AND AND AT THE SAME 5494 04:57:10,240 --> 04:57:13,320 TIME, WAS STUDY THE 5495 04:57:13,320 --> 04:57:23,800 VITAMIN A ON THE THERE WAS A 5496 04:57:27,600 --> 04:57:29,640 FAILURE FOR THESE INFLAMMATORY 5497 04:57:29,640 --> 04:57:31,400 MACROPHAGES TO CONVERT INTO THIS 5498 04:57:31,400 --> 04:57:41,840 TISSUE RESIDENT PHENOTYPE. 5499 04:57:44,080 --> 04:57:49,960 AND IN DEED, IN VITAMIN A MICE 5500 04:57:49,960 --> 04:58:01,240 THEY CONDUCT SOPPED T -- LEADINC 5501 04:58:13,440 --> 04:58:20,000 PHONY TYPES TO ONE OF THE AND IS 5502 04:58:20,000 --> 04:58:30,440 THAT AND AT NYU ONE OF MY 5503 04:58:48,640 --> 04:58:51,000 COLLEAGUES AND DARWIN AND 5504 04:58:51,000 --> 04:59:00,160 POINTED OUT TO ME SOME WORK AND 5505 04:59:00,160 --> 04:59:03,120 WHAT WAS REMARKABLE ABOUT THIS 5506 04:59:03,120 --> 04:59:08,000 EPIDEMIOLOGICAL STUDY WAS THAT 5507 04:59:08,000 --> 04:59:10,000 THEY FOUND THAT BASELINE VITAMIN 5508 04:59:10,000 --> 04:59:12,920 A DEFICIENCY WAS ACTUALLY 5509 04:59:12,920 --> 04:59:16,280 ASSOCIATED WITH A 10 FOLD 5510 04:59:16,280 --> 04:59:18,200 INCREASE RISK OF TUBERCULOSIS 5511 04:59:18,200 --> 04:59:23,120 DISEASE AND SO IT'S POSSIBLE 5512 04:59:23,120 --> 04:59:24,920 THAT THIS CONVERSION PROCESS TO 5513 04:59:24,920 --> 04:59:27,400 TISSUE RESIDENT MACROPHAGES HEY 5514 04:59:27,400 --> 04:59:31,560 BE IMPORTANT FOR A WIDE RANGE OF 5515 04:59:31,560 --> 04:59:34,720 INFECTIOUS DISEASES AND 5516 04:59:34,720 --> 04:59:36,000 ESPECIALLY SITUATIONS WHERE YOU 5517 04:59:36,000 --> 04:59:40,800 GET FORMATION OF GRANULOMA. 5518 04:59:40,800 --> 04:59:43,640 NOW, BEING IMMUNOLOGY, THINGS 5519 04:59:43,640 --> 04:59:48,520 GET EVEN MORE COMPLICATED. 5520 04:59:48,520 --> 04:59:52,720 BECAUSE AS WE SHOWN WHAT WE 5521 04:59:52,720 --> 04:59:57,240 REALIZE AND LATER EVENT AND 5522 04:59:57,240 --> 04:59:58,720 SUBSEQUENT THAT IN ADDITION 5523 04:59:58,720 --> 05:00:02,040 VITAMIN A DEFICIENCY AND 5524 05:00:02,040 --> 05:00:08,680 REGULATE THIS CONVERSION AND 5525 05:00:08,680 --> 05:00:13,800 MACROPHAGES PHENOTYPE IN 5526 05:00:13,800 --> 05:00:14,440 DIFFERENT INBRED STRAINS OF MICE 5527 05:00:14,440 --> 05:00:16,480 AND THE RATE OF A CONVERSION TO 5528 05:00:16,480 --> 05:00:20,520 A TISSUE RESIDENT MACROPHAGES IS 5529 05:00:20,520 --> 05:00:22,680 DIFFERENT AND EVEN BETWEEN 5530 05:00:22,680 --> 05:00:24,560 DIFFERENT SEXES OF MICE AND IS 5531 05:00:24,560 --> 05:00:31,080 THIS REALLY THE WORK 5532 05:00:31,080 --> 05:00:37,240 FROM JUDY AND AND THEY STRUGGLE 5533 05:00:37,240 --> 05:00:42,560 THAT MALE MICE MORE RAPIDLY 5534 05:00:42,560 --> 05:00:45,080 CONVERTED BON MARROW MACROPHAGES 5535 05:00:45,080 --> 05:00:48,600 INTO TISSUE RESIDENT MACROPHAGES 5536 05:00:48,600 --> 05:00:55,720 THAN FEMALE MICE SO IN THE CASEF 5537 05:00:55,720 --> 05:00:59,400 JUDY ALAN'S LAB I WANTED TO SHOW 5538 05:00:59,400 --> 05:01:00,680 YOU THIS PARTICULAR PIECE OF 5539 05:01:00,680 --> 05:01:04,320 DATA FROM THEIR LAB WHERE THEY 5540 05:01:04,320 --> 05:01:05,440 SHOWED THAT THERE IS A BIG 5541 05:01:05,440 --> 05:01:07,760 DIFFERENCE BETWEEN THE BLACK SIX 5542 05:01:07,760 --> 05:01:15,560 MOUSE AND THE C MICE WHERE AND 5543 05:01:15,560 --> 05:01:18,720 THE EXPANSION OF THE TISSUE 5544 05:01:18,720 --> 05:01:20,720 MACROPHAGES DURING THE INFECTION 5545 05:01:20,720 --> 05:01:23,400 PRIMARILY THESE LARGE PARROT 5546 05:01:23,400 --> 05:01:24,120 TENILLE MACROPHAGES AND THERE'S 5547 05:01:24,120 --> 05:01:26,920 SOME EXPANSIONS OF THE MONOCYTE 5548 05:01:26,920 --> 05:01:29,880 DERIVED MACROPHAGES BUT IN THE C 5549 05:01:29,880 --> 05:01:33,440 MICE, THERE'S MUCH LESS 5550 05:01:33,440 --> 05:01:36,600 ACCUMULATION OF THE TISSUE 5551 05:01:36,600 --> 05:01:39,120 RESIDENT AND MACROPHAGES AND 5552 05:01:39,120 --> 05:01:42,640 THEY HAVE NOW DONE EXPERIMENTS 5553 05:01:42,640 --> 05:01:45,240 TO INDICATE THAT INFLAMMATORY 5554 05:01:45,240 --> 05:01:49,920 MACROPHAGES GET STUCK IN THE 5555 05:01:49,920 --> 05:01:52,000 MICE INTO A TISSUE RESIDENT 5556 05:01:52,000 --> 05:01:53,680 MACROPHAGES AND THIS IS 5557 05:01:53,680 --> 05:01:57,920 INTERESTING IN THE CONTEXT OF 5558 05:01:57,920 --> 05:01:59,480 INFECTION AND JUDY THINKS THIS 5559 05:01:59,480 --> 05:02:01,800 MIGHT BE RELATED TO THE 5560 05:02:01,800 --> 05:02:03,680 DIFFERENCE IN SUSCEPTIBLE 5561 05:02:03,680 --> 05:02:11,120 BECAUSE UNLIKE THE INTESTINAL 5562 05:02:11,120 --> 05:02:21,640 AND AND COMING BACK AND IN ABOVE 5563 05:02:26,000 --> 05:02:28,200 SEA MICE AND THERE'S LESS 5564 05:02:28,200 --> 05:02:31,240 CONVERSION OF THE MONOCYTE DRIVE 5565 05:02:31,240 --> 05:02:34,920 MACROPHAGES INTO THE TISSUE AND 5566 05:02:34,920 --> 05:02:36,360 YOU ALSO ZIZI GREATER 5567 05:02:36,360 --> 05:02:41,680 ACCUMULATION OF PDL2 POSITIVE 5568 05:02:41,680 --> 05:02:43,480 MACROPHAGES WHICH PREVIOUSLY NOT 5569 05:02:43,480 --> 05:02:46,400 SEEN IN THIS C57 BLACK SIX MICE 5570 05:02:46,400 --> 05:02:52,480 SO THIS MADE UP BEGIN TO REALIZE 5571 05:02:52,480 --> 05:02:54,760 AND AND BIOLOGY AND 5572 05:02:54,760 --> 05:02:57,800 DIFFERENTIATION IS BASED ON WORK 5573 05:02:57,800 --> 05:03:01,400 AND ALL THE LINEAGE TRACKING 5574 05:03:01,400 --> 05:03:03,800 SYSTEMS AND ALL THE LABS HAVE 5575 05:03:03,800 --> 05:03:06,880 UTILIZED BASED ON THE BLACK SIX 5576 05:03:06,880 --> 05:03:13,080 SYSTEM, SO NOT ONLY IS 5577 05:03:13,080 --> 05:03:14,680 DEVELOPMENTAL BIOLOGY 5578 05:03:14,680 --> 05:03:17,520 POTENTIALLY EFFECTED AND BY THE 5579 05:03:17,520 --> 05:03:19,840 GENETIC BACKGROUND OF THE MICE 5580 05:03:19,840 --> 05:03:26,840 AND CHRIS GLASS HAS DONE AND 5581 05:03:26,840 --> 05:03:29,160 THEY MADE BONE MARROW 5582 05:03:29,160 --> 05:03:30,840 MACROPHAGES FROM FIVE DIFFERENT 5583 05:03:30,840 --> 05:03:33,840 STRAINS OF MICE AND STIMULATED 5584 05:03:33,840 --> 05:03:37,920 THEM WITH IL-4 TO LOOK AT HOW 5585 05:03:37,920 --> 05:03:40,640 THESE GENETIC BACKGROUND OF THE 5586 05:03:40,640 --> 05:03:43,760 BONE MARROW MACROPHAGES AND IN 5587 05:03:43,760 --> 05:03:46,680 VITRO SETTING AND IT WOULD 5588 05:03:46,680 --> 05:03:48,240 EFFECT THE TRANSCRIPTIONAL 5589 05:03:48,240 --> 05:03:58,720 RESPONSE TO IL4 AND ONLY 27 5590 05:04:00,640 --> 05:04:11,040 GENES AND MACROPHAGES AND SO 5591 05:04:12,360 --> 05:04:16,040 THERE'S A HIGHLY STRAIN SPECIFIC 5592 05:04:16,040 --> 05:04:18,080 TRANSCRIPTIONAL RESPONSE TO IL-4 5593 05:04:18,080 --> 05:04:21,880 AND MEDIATED SIGNALING AND SO I 5594 05:04:21,880 --> 05:04:24,240 COME FROM A SELL EYE LAR 5595 05:04:24,240 --> 05:04:25,600 IMMUNOLOGY BACKGROUND AND IT WAS 5596 05:04:25,600 --> 05:04:30,280 REALLY A POSTDOC IN THE LAB 5597 05:04:30,280 --> 05:04:32,360 MAYSON TANG WHO KIND OF BROUGHT 5598 05:04:32,360 --> 05:04:34,280 US DOWN BIT ROAD OF 5599 05:04:34,280 --> 05:04:36,160 TRANSCRIPTIONAL REGULATIONS AND 5600 05:04:36,160 --> 05:04:39,800 I'M SURE THAT ALAN AND ALL THE 5601 05:04:39,800 --> 05:04:43,240 OTHER PEOPLE HERE HAVE 5602 05:04:43,240 --> 05:04:44,320 APPRECIATED WHEN THEY HAD A 5603 05:04:44,320 --> 05:04:54,840 TRAINEES THAT TAKEN DOWN A AND 5604 05:04:56,400 --> 05:04:58,480 BROUGHT THE IDEAS OF 5605 05:04:58,480 --> 05:04:59,760 TRANSCRIPTIONAL REGULATION TO A 5606 05:04:59,760 --> 05:05:01,920 LAB AND ONE OF THE THINGS THAT 5607 05:05:01,920 --> 05:05:04,640 SHE FOUND WAS THAT IN DEED, YOU 5608 05:05:04,640 --> 05:05:08,280 KNOW, IN THE PAR TA KNEAL CAVITY 5609 05:05:08,280 --> 05:05:10,560 THAT WAS CONSISTENT WITH THE 5610 05:05:10,560 --> 05:05:20,160 WORK THAT JUDY AND WE HAVE THIS 5611 05:05:20,160 --> 05:05:24,040 VERY LARGE THOSE STRINGS AND AND 5612 05:05:24,040 --> 05:05:27,960 ACTIVATION AND THIS WORK IS 5613 05:05:27,960 --> 05:05:29,480 BEING CONTINUED IN OUR LAB HERE 5614 05:05:29,480 --> 05:05:32,640 AT NYU, AT NIH. 5615 05:05:32,640 --> 05:05:33,040 [LAUGHTER] 5616 05:05:33,040 --> 05:05:36,760 I SAID THAT, I'VE BEEN USING NYU 5617 05:05:36,760 --> 05:05:41,080 FOR SO MANY WORDS IT'S HARD TO 5618 05:05:41,080 --> 05:05:41,360 TRANSITION. 5619 05:05:41,360 --> 05:05:49,000 AND SO THIS IS A VERY SIMPLE SIL 5620 05:05:49,000 --> 05:05:59,520 AND THE COMPLICATED HELM AND THE 5621 05:06:00,640 --> 05:06:04,440 MACROPHAGES FOR IN THIS CASE 5622 05:06:04,440 --> 05:06:05,920 RNA-SEQ AND WHAT IS REALLY 5623 05:06:05,920 --> 05:06:10,520 INTERESTING HERE IS THAT THE IS 5624 05:06:10,520 --> 05:06:14,960 THE STRAIN OF MICE IS ACTUAL 5625 05:06:14,960 --> 05:06:16,280 WILL HE EXPLAINS 61% OF THE 5626 05:06:16,280 --> 05:06:20,920 VARIANTS WHEREAS THE EFFECTS OF 5627 05:06:20,920 --> 05:06:23,360 IL-4 IS 34% OF THE VARIANTS 5628 05:06:23,360 --> 05:06:25,200 INDICATING THAT THE STRING 5629 05:06:25,200 --> 05:06:26,480 SPECIFIC EFFECTS ARE GREATER 5630 05:06:26,480 --> 05:06:28,320 THAN THE EFFECTS OF THIS 5631 05:06:28,320 --> 05:06:29,840 STIMULATION ITSELF AND WHAT 5632 05:06:29,840 --> 05:06:31,400 WE'VE ALSO BEEN REALLY 5633 05:06:31,400 --> 05:06:33,240 INTERESTED IN IS THAT DESPITE 5634 05:06:33,240 --> 05:06:39,800 THE FACT THAT WE THINK OF C MICE 5635 05:06:39,800 --> 05:06:41,920 AS BEG MORE TH-2 BOY AS WHEN IT 5636 05:06:41,920 --> 05:06:44,040 COMES TO THE MACROPHAGES 5637 05:06:44,040 --> 05:06:45,800 TRANSCRIPTIONAL RESPONSES TO 5638 05:06:45,800 --> 05:06:50,840 THIS IL-4IP TREATMENT, IT IS THE 5639 05:06:50,840 --> 05:06:52,680 BLACK SIX MACROPHAGES THAT ARE 5640 05:06:52,680 --> 05:06:56,120 MORE RESPONSIVE IN TERMS OF 5641 05:06:56,120 --> 05:06:57,240 TRANSCRIPTIONAL CHANGES IN 5642 05:06:57,240 --> 05:07:00,720 RESPONSE TO IL-4 AND JUST AS WAS 5643 05:07:00,720 --> 05:07:02,360 SHOWN IN CHRIS GOSSE'S WORK 5644 05:07:02,360 --> 05:07:04,480 THAT'S ACTUALLY QUITE A SMALL 5645 05:07:04,480 --> 05:07:07,760 OVERLAP IN TERMS OF THE GENES 5646 05:07:07,760 --> 05:07:11,840 THAT ARE INDUCED IN BOTH OF THE 5647 05:07:11,840 --> 05:07:22,360 BLACK 6 AND C MICE SO SHE'S BEEN 5648 05:07:26,520 --> 05:07:27,840 USING THESE DIFFERENT DENOAM I 5649 05:07:27,840 --> 05:07:29,400 CAN APPROACHES TO UNDERSTAND THE 5650 05:07:29,400 --> 05:07:31,120 DIFFERENCE THIS IS THIS 5651 05:07:31,120 --> 05:07:32,240 TRANSCRIPTIONAL REGULATION 5652 05:07:32,240 --> 05:07:37,600 RESPONSE TO IL4 IN THE BLACK SIX 5653 05:07:37,600 --> 05:07:39,160 MACROPHAGES. 5654 05:07:39,160 --> 05:07:44,800 SO I JUST WANT TO SUMMARIZE SOME 5655 05:07:44,800 --> 05:07:46,280 OF THE OBSERVATIONS SHE'S MADE 5656 05:07:46,280 --> 05:07:47,720 THAT ESSENTIALLY AS I SAID THE 5657 05:07:47,720 --> 05:07:51,040 BLACK SIX MACROPHAGES ARE MORE 5658 05:07:51,040 --> 05:07:53,280 RESPONSIVE TO IL-4 STIMULATION 5659 05:07:53,280 --> 05:07:55,520 AND IT DOES SEEM TO BE 5660 05:07:55,520 --> 05:07:56,960 ENRICHMENT FOR THE ACTIVITIES OF 5661 05:07:56,960 --> 05:08:01,800 THE PU1 AND NF FACTORS WHEREAS 5662 05:08:01,800 --> 05:08:05,800 IN THE MICE WE SEE MORE 5663 05:08:05,800 --> 05:08:08,880 ENRICHMENT IN THE AP1 FAMILY OF 5664 05:08:08,880 --> 05:08:10,440 TRANSCRIPTION FACTORS AND FOR 5665 05:08:10,440 --> 05:08:13,160 THE BLACK SIX GENES, THERE ARE 5666 05:08:13,160 --> 05:08:15,040 INDUCED BY IL4 THEY'RE 5667 05:08:15,040 --> 05:08:17,520 ASSOCIATED WITH SUPER ENHANCERS 5668 05:08:17,520 --> 05:08:18,880 WHICH MIGHT EXPLAIN WHY THEY ARE 5669 05:08:18,880 --> 05:08:22,920 MORE RESPONSIVE TO I L-4 5670 05:08:22,920 --> 05:08:24,160 STIMULATION AND THE SEA MICE IN 5671 05:08:24,160 --> 05:08:34,680 THE SINGLE CELL RNA-SEQ THOSE 5672 05:08:37,120 --> 05:08:39,600 HETEROGENEITY AND HOW IT MIGHT 5673 05:08:39,600 --> 05:08:43,800 APPEAR TO BE LESS 5674 05:08:43,800 --> 05:08:44,720 TRANSCRIPTIONALLY RESPONSIVE AND 5675 05:08:44,720 --> 05:08:48,360 HOWEVER WHAT WE WERE HOPING TO 5676 05:08:48,360 --> 05:08:54,240 DO IS MAP THE 5677 05:08:54,240 --> 05:08:57,040 DIFFERENCES IN THE CHROMATIN 5678 05:08:57,040 --> 05:08:59,320 DIFFERENCES WITH SPECIFIC 5679 05:08:59,320 --> 05:09:01,480 SEQUENCE IN THOSE SITES AND IN 5680 05:09:01,480 --> 05:09:04,240 THIS ESSENCE WE WOULD LIKE TO GO 5681 05:09:04,240 --> 05:09:09,160 IN AND DID CRISPR REGIONS RIGHT 5682 05:09:09,160 --> 05:09:13,360 AND WE WOULD FIND WE WOULD FIND 5683 05:09:13,360 --> 05:09:18,080 THE REGION IN THE GATA6 LOCUS 5684 05:09:18,080 --> 05:09:25,920 THAT WOULD THE LEVEL THAT 5685 05:09:25,920 --> 05:09:36,360 DIFFERENTER BETWEEN THE NOT 5686 05:09:41,440 --> 05:09:43,160 ASSOCIATED WITH DIFFERENCES IN 5687 05:09:43,160 --> 05:09:44,440 SEQUENCE IN THOSE PARTICULAR 5688 05:09:44,440 --> 05:09:46,280 REGIONS AND SO THERE IS 5689 05:09:46,280 --> 05:09:50,320 CERTAINLY STILL A LOT MORE WE 5690 05:09:50,320 --> 05:09:52,480 DON'T UNDERSTAND ABOUT WHY YOU 5691 05:09:52,480 --> 05:09:55,960 HAVE THESE STRAIN-SPECIFIC 5692 05:09:55,960 --> 05:09:59,600 DIFFERENCES IN EPIGENETIC AND AS 5693 05:09:59,600 --> 05:10:00,720 WELL AS TRANSCRIPTIONAL 5694 05:10:00,720 --> 05:10:06,400 RESPONSES TO IL-4 AND BUT WE 5695 05:10:06,400 --> 05:10:09,640 COULD GOING BACK TO THE MODEL 5696 05:10:09,640 --> 05:10:16,520 AND I CONTINUE TO HAVING 5697 05:10:16,520 --> 05:10:17,760 BRAZILIAN POSTDOCS IN THE LAB 5698 05:10:17,760 --> 05:10:20,760 AND A NEW POSTDOC FROM BRAZIL IN 5699 05:10:20,760 --> 05:10:25,800 THE LAB AND SHE HAS DONE 5700 05:10:25,800 --> 05:10:27,600 EXPERIMENTS WHERE WE ARE LOOKING 5701 05:10:27,600 --> 05:10:30,680 AT GOING BACK TO IN BRED STRAINS 5702 05:10:30,680 --> 05:10:33,360 OF MICE AND THIS IS THE GOING 5703 05:10:33,360 --> 05:10:37,720 BACK TO THE ROOTS OF PARASITE 5704 05:10:37,720 --> 05:10:41,560 IMMUNOLOGY AND THE BLACK 6 MICE 5705 05:10:41,560 --> 05:10:47,240 AND DIFFERENCES IN THE RESPONSES 5706 05:10:47,240 --> 05:10:49,440 AND WHAT CAMILLA HAS FOUND IS 5707 05:10:49,440 --> 05:10:51,600 THAT IN SOME OF THIS IS 5708 05:10:51,600 --> 05:10:52,640 REPEATING WORK THAT HAD BEEN 5709 05:10:52,640 --> 05:10:55,480 DONE IN THE 1980s AND 1990s 5710 05:10:55,480 --> 05:11:00,040 THAT THE DIFFERENCES IN 5711 05:11:00,040 --> 05:11:04,080 SUSCEPTIBLITY BETWEEN DIFFERENT 5712 05:11:04,080 --> 05:11:06,200 INBRED STRAINS OF MICE SO SCHISO 5713 05:11:06,200 --> 05:11:08,680 INFECTION AND WHAT IS 5714 05:11:08,680 --> 05:11:13,600 INTERESTING IS THAT SP LE 5715 05:11:13,600 --> 05:11:14,560 NOMEGALY THAT IS POORLY 5716 05:11:14,560 --> 05:11:18,240 UNDERSTAND IN THE CONTEXT OF 5717 05:11:18,240 --> 05:11:22,640 SCHISTO INFECTION AND AN 5718 05:11:22,640 --> 05:11:26,040 INDICATION OF EXTRA (INAUDIBLE) 5719 05:11:26,040 --> 05:11:28,520 IS MUCH GREATER IN THE STRAINS 5720 05:11:28,520 --> 05:11:31,800 OF MICE AND PARASITE INFECTION 5721 05:11:31,800 --> 05:11:38,160 AND IN DEED THIS IS NOT ACTUALLY 5722 05:11:38,160 --> 05:11:40,960 REFLECTED IN NECESSARILY IN THE 5723 05:11:40,960 --> 05:11:46,920 LIVER AND IN THE LIVER SHOWN BY 5724 05:11:46,920 --> 05:11:50,520 MIGGAL GROUP SUFFERED MUCH 5725 05:11:50,520 --> 05:11:52,400 GREATER AND SOMEHOW THEY 5726 05:11:52,400 --> 05:12:02,880 SURVIVED AND SEA MICE AND IT 5727 05:12:08,680 --> 05:12:09,640 REPRESENTS THE WORK I'VE BEEN 5728 05:12:09,640 --> 05:12:20,160 TRYING TO PURSUE AND IT REFLECTS 5729 05:12:20,840 --> 05:12:24,320 HOW HOW INFECTIONS DELIVER IN 5730 05:12:24,320 --> 05:12:27,400 TERMS OF PATHOGENESIS BECAUSE 5731 05:12:27,400 --> 05:12:30,680 PEOPLE AND IN AN ENDEMIC 5732 05:12:30,680 --> 05:12:36,280 SITUATION, MOST PEOPLE ARE 5733 05:12:36,280 --> 05:12:38,480 ASYMPTOMATIC FROM THE HELMINTH 5734 05:12:38,480 --> 05:12:39,600 INFECTION AND PEOPLE THAT 5735 05:12:39,600 --> 05:12:43,000 DEVELOP PATHOLOGY FALL ON THE 5736 05:12:43,000 --> 05:12:43,840 EXTREMES AND EITHER THEY ARE 5737 05:12:43,840 --> 05:12:46,040 SUPER INFECTED OR THEY SUFFER 5738 05:12:46,040 --> 05:12:47,760 FROM IMMUNO PATHOLOGY AND THIS 5739 05:12:47,760 --> 05:12:53,640 KIND OF DISTRIBUTION IS COMMON 5740 05:12:53,640 --> 05:13:04,200 AMONG ALL AND THIS KIND OF ENTER 5741 05:13:07,120 --> 05:13:08,800 INDIVIDUAL VARIATION IN IMMUNE 5742 05:13:08,800 --> 05:13:10,440 RESPONSES BETWEEN PEOPLE AND 5743 05:13:10,440 --> 05:13:20,840 SOMETHING THAT I THINK AND THEY 5744 05:13:20,840 --> 05:13:22,120 HAVE TAKEN REDUCTIONIST 5745 05:13:22,120 --> 05:13:23,680 APPROACHES OVER THE LAST FEW 5746 05:13:23,680 --> 05:13:26,960 DECADES TO TRY AND UNDERSTAND 5747 05:13:26,960 --> 05:13:29,400 SPECIFIC CELLULAR AND MOLECULAR 5748 05:13:29,400 --> 05:13:30,960 MECHANISMS BUT WHEN WE WANT TO 5749 05:13:30,960 --> 05:13:32,840 TRY AND UNDERSTAND VARIATIONS IN 5750 05:13:32,840 --> 05:13:35,080 IMMUNE RESPONSES WE MIGHT HAVE 5751 05:13:35,080 --> 05:13:37,760 TO TURN TOWARDS TOOLS THAT 5752 05:13:37,760 --> 05:13:40,120 ECOLOGISTS AND COMPUTATIONAL 5753 05:13:40,120 --> 05:13:42,080 BIOLOGIST USE TO MEASURE THE 5754 05:13:42,080 --> 05:13:45,440 EFFECT SIZES AND OF THE 5755 05:13:45,440 --> 05:13:47,960 DIFFERENT COMPONENTS AND OF 5756 05:13:47,960 --> 05:13:49,600 COURSE, IT'S GOING TO BE A 5757 05:13:49,600 --> 05:13:52,040 COMBINATION OF GENETIC AND 5758 05:13:52,040 --> 05:13:53,520 ENVIRONMENTAL FACTORS THAT 5759 05:13:53,520 --> 05:13:55,760 DETERMINE THIS INTER INDIVIDUAL 5760 05:13:55,760 --> 05:14:00,320 VARIATION BUT HOW THIS GENETIC 5761 05:14:00,320 --> 05:14:10,840 AND IT'S A KEY THAT FAULT IN THE 5762 05:14:21,160 --> 05:14:23,640 GENOME IN OFTEN FOUND THAT WILL 5763 05:14:23,640 --> 05:14:27,240 BE THE LARGEST CONTRIBUTORS TO 5764 05:14:27,240 --> 05:14:30,680 THE INDIVIDUAL VARIATION AND IN 5765 05:14:30,680 --> 05:14:33,200 SOME WAYS THE MICE ACTUALLY A 5766 05:14:33,200 --> 05:14:35,640 GOOD MODEL FOR THAT BECAUSE ONE 5767 05:14:35,640 --> 05:14:38,440 CAN TRACK, ONE CAN ESSENTIALLY 5768 05:14:38,440 --> 05:14:41,280 AND AS FORM YOU MUTATION ALANAL 5769 05:14:41,280 --> 05:14:44,480 SIS AND TO STUDY SEQUENCE 5770 05:14:44,480 --> 05:14:47,000 VARIANTS THAT FALL INTO THESE 5771 05:14:47,000 --> 05:14:53,080 NON CODING REGIONS. 5772 05:14:53,080 --> 05:14:57,480 SO, I FEEL -- SO THIS WORK OF 5773 05:14:57,480 --> 05:15:03,920 COURSE HAS BEEN DONE BY -- THIS 5774 05:15:03,920 --> 05:15:06,400 IS THE FIRST COHORT OF PEOPLE IN 5775 05:15:06,400 --> 05:15:10,160 THE LAB AND OF THIS COHORT, 5776 05:15:10,160 --> 05:15:12,320 TASHA, MICHAEL AND THAT IS AN 5777 05:15:12,320 --> 05:15:14,680 PLAYED CRITICAL ROLES IN OUR 5778 05:15:14,680 --> 05:15:17,960 STUDY ON MACROPHAGES BIOLOGY 5779 05:15:17,960 --> 05:15:21,040 THAT WAS ALWAYS BEEN A CLOSE 5780 05:15:21,040 --> 05:15:23,080 COLLABORATION WITH JUDY ALLEN 5781 05:15:23,080 --> 05:15:25,160 AND HER GROUP BECAUSE NOW IN THE 5782 05:15:25,160 --> 05:15:26,760 UNIVERSITY OF MANCHESTER AND 5783 05:15:26,760 --> 05:15:31,640 THIS WAS THE SECOND COHORT OF 5784 05:15:31,640 --> 05:15:35,680 PEOPLE IN MY LAB AND IT WAS AN 5785 05:15:35,680 --> 05:15:38,600 NYU JUST BECAUSE WE JOINED THE 5786 05:15:38,600 --> 05:15:42,880 NIH AND I'M REALLY EXTREMELY 5787 05:15:42,880 --> 05:15:47,320 EXCITED TO BE HERE AND WE NOW 5788 05:15:47,320 --> 05:15:51,600 HAVE A GREAT DEAL OF PEOPLE AND 5789 05:15:51,600 --> 05:15:56,000 I WANT TO REALLY THANK ALAN FOR 5790 05:15:56,000 --> 05:15:58,840 EVEN I THINK SEVERAL YEARS 5791 05:15:58,840 --> 05:16:00,600 BEFORE THE POSITION WAS 5792 05:16:00,600 --> 05:16:04,440 OFFICIALLY OPENED, IT WAS 5793 05:16:04,440 --> 05:16:07,920 ALREAENCOURAGING ME TO THINK ABT 5794 05:16:07,920 --> 05:16:18,440 THE POSSIBILITY OF AND THIS AND 5795 05:16:21,000 --> 05:16:25,400 AND MUCH LATER AND MOST OF YOU 5796 05:16:25,400 --> 05:16:30,240 BECAUSE HE WAS HE WAS A LEGEND 5797 05:16:30,240 --> 05:16:32,600 AND WHEN I MET HIM IN-PERSON AND 5798 05:16:32,600 --> 05:16:36,480 HE REALLY DIDN'T FIT WITH MY 5799 05:16:36,480 --> 05:16:38,320 INITIAL CONCEPTIONS OF THIS 5800 05:16:38,320 --> 05:16:43,480 LEGEND OF THE FIELD AND AND I 5801 05:16:43,480 --> 05:16:44,880 THINK THAT THE THING THAT HASN'T 5802 05:16:44,880 --> 05:16:46,800 BEEN MENTIONED BECAUSE 5803 05:16:46,800 --> 05:16:48,200 EVERYTHING HAS ALMOST EVERYTHING 5804 05:16:48,200 --> 05:16:56,000 HAS ALREADY BEEN SAID, I HAD THE 5805 05:16:56,000 --> 05:17:01,160 PRIVILEGE OF ORGANIZING THE 5806 05:17:01,160 --> 05:17:06,000 IMMUNOLOGY MODULE FOR THE PARA 5807 05:17:06,000 --> 05:17:11,080 SITTISM COURSE AND AND THIS IS A 5808 05:17:11,080 --> 05:17:13,480 LONG HISTORY AND WE INVITED ALAN 5809 05:17:13,480 --> 05:17:15,600 TO GIVE THE PRODUCTION TO 5810 05:17:15,600 --> 05:17:25,600 IMMUNOLOGY COSTS AND I WOULD SAY 5811 05:17:25,600 --> 05:17:29,680 80% OF STUDENTS ON THIS CAUSE 5812 05:17:29,680 --> 05:17:40,200 ARE BASIC AND YOU CAN SEE THE 5813 05:17:41,560 --> 05:17:44,920 EYES LIGHT UP AS HE EXPLAINS TO 5814 05:17:44,920 --> 05:17:46,840 THEM EXPANSION AND THEY'VE NEVER 5815 05:17:46,840 --> 05:17:49,000 THOUGHT ABOUT THAT WHOLE PROCESS 5816 05:17:49,000 --> 05:17:50,800 BEFORE AND SO ALAN IN ADDITION 5817 05:17:50,800 --> 05:17:52,640 TO ALL THE THE THINGS THAT YOU 5818 05:17:52,640 --> 05:17:55,400 GUYS HAVE SAID IS ALSO A 5819 05:17:55,400 --> 05:18:02,000 REMARKABLE TEACHER AND OF OF NEW 5820 05:18:02,000 --> 05:18:04,080 COMMERCE TO IMMUNOLOGY AND I 5821 05:18:04,080 --> 05:18:08,120 THINK IT'S REALLY A PRIVILEGE TO 5822 05:18:08,120 --> 05:18:09,880 NOW HAVE YOU AS A COLLEAGUE AND 5823 05:18:09,880 --> 05:18:11,480 OF COURSE HE IS DONE ALL THE 5824 05:18:11,480 --> 05:18:13,600 THINGS YOU HAVE SAID AND HE HAS 5825 05:18:13,600 --> 05:18:17,320 INTRODUCED ME TO EVERYONE IN THE 5826 05:18:17,320 --> 05:18:18,960 NIH, AND CONNECTED ME TO BASED 5827 05:18:18,960 --> 05:18:24,440 ON THE SCIENCE, YOU KNOW I THINK 5828 05:18:24,440 --> 05:18:25,840 THAT'S THE AMAZING FEATURE OF 5829 05:18:25,840 --> 05:18:28,360 ALAN IS HE IS ABLE TO IDENTIFY 5830 05:18:28,360 --> 05:18:30,760 THE RIGHT FIT OF PEOPLE BASED ON 5831 05:18:30,760 --> 05:18:32,400 THE WORK THAT THEY'RE DOING SO 5832 05:18:32,400 --> 05:18:36,440 KIND OF BRING THEM TOGETHER AND 5833 05:18:36,440 --> 05:18:41,360 SO WITH THAT, THANK YOU, ALAN 5834 05:18:41,360 --> 05:18:44,520 FOR ADOPTING ME INTO THE KIND OF 5835 05:18:44,520 --> 05:18:45,640 LPD/NIH FAMILY. 5836 05:18:45,640 --> 05:18:54,320 [APPLAUSE] 5837 05:18:54,320 --> 05:18:57,600 >> SO, THANK YOU AND VERY 5838 05:18:57,600 --> 05:18:57,920 INTERESTING. 5839 05:18:57,920 --> 05:19:00,200 I WANTED TO ASK ABOUT TWO OTHER 5840 05:19:00,200 --> 05:19:02,000 GENETIC DIFFERENCES BETWEEN 5841 05:19:02,000 --> 05:19:06,840 VALVE C AND 6 THAT MIGHT PLAY A 5842 05:19:06,840 --> 05:19:07,040 ROLE. 5843 05:19:07,040 --> 05:19:09,360 ONE IS THAT B6 EXPRESSES HIGHER 5844 05:19:09,360 --> 05:19:11,960 LEVELS OF ONE CHAIN OF THE IL-12 5845 05:19:11,960 --> 05:19:14,560 RECEPTORS WHICH MAKES B6 MORE 5846 05:19:14,560 --> 05:19:16,960 RESPONSIVE TO IL12 OF COURSE 5847 05:19:16,960 --> 05:19:19,360 LEADING TO INTERFERING GAMMA 5848 05:19:19,360 --> 05:19:19,880 PRODUCTION. 5849 05:19:19,880 --> 05:19:22,480 AND THE OTHER IS DIFFERENCES IN 5850 05:19:22,480 --> 05:19:26,520 THE NK LOCUS THAT WAYNE HAS 5851 05:19:26,520 --> 05:19:28,760 STUDIED EXTENSIVELY BETWEEN THE 5852 05:19:28,760 --> 05:19:32,560 TWO STRAINS WITH REKUM BENT 5853 05:19:32,560 --> 05:19:34,880 STRAINS THAT ARE PART OF ONE 5854 05:19:34,880 --> 05:19:36,160 STRAIN AND PART OF THE LOCUS 5855 05:19:36,160 --> 05:19:38,400 FROM ANOTHER STRAIN AND THAT 5856 05:19:38,400 --> 05:19:43,400 INFECT THINGS LIKE THE MCMV 5857 05:19:43,400 --> 05:19:46,080 INFECTION AND OF COURSE NK CELLS 5858 05:19:46,080 --> 05:19:48,280 MAKE ANOTHER GAMMA INTERFERON 5859 05:19:48,280 --> 05:19:50,120 CELLS SO THAT'S A LOT OF COM 5860 05:19:50,120 --> 05:19:52,560 ANALITY AND YOU FOCUSED ON IL-4 5861 05:19:52,560 --> 05:19:55,200 BUT I WONDER IF THOSE GENETIC 5862 05:19:55,200 --> 05:19:56,280 DIFFERENCES MIGHT PLAY A ROLE 5863 05:19:56,280 --> 05:19:56,560 HERE? 5864 05:19:56,560 --> 05:19:58,480 >> I THINK IT'S VERY IMPORTANT 5865 05:19:58,480 --> 05:19:59,920 POINT THAT HAS BEEN POINTED OUT 5866 05:19:59,920 --> 05:20:03,040 TO ME BY DRAGANA AND DAVID SACKS 5867 05:20:03,040 --> 05:20:07,760 IS THAT THE DIFFICULTY IN 5868 05:20:07,760 --> 05:20:09,120 SEPARATING THE ENVIRONMENT FROM 5869 05:20:09,120 --> 05:20:14,840 THE CELL INTRINSIC EFFECTS OF 5870 05:20:14,840 --> 05:20:16,920 THE MACROPHAGES THEMSELVES SO WE 5871 05:20:16,920 --> 05:20:20,760 PLAN TO TRY AND ADDRESS THIS 5872 05:20:20,760 --> 05:20:24,560 QUESTION AND WHETHER THE 5873 05:20:24,560 --> 05:20:27,320 ENVIRONMENT AND THE TISSUE 5874 05:20:27,320 --> 05:20:28,520 ENVIRONMENT AND AND THE 5875 05:20:28,520 --> 05:20:30,080 COMPETITION OF THE IMMUNE CELLS 5876 05:20:30,080 --> 05:20:33,920 AND ALTHOUGH I GUESS, THE CASE 5877 05:20:33,920 --> 05:20:40,360 AND ADDRESS THAT AND TRUE USING, 5878 05:20:40,360 --> 05:20:50,480 DOING A. 5879 05:20:59,880 --> 05:21:01,680 >> GREAT TALK. 5880 05:21:01,680 --> 05:21:06,120 SO M. WHAT RELATED TO THE 5881 05:21:06,120 --> 05:21:07,440 COMMENTS (INAUDIBLE) DUE TO 5882 05:21:07,440 --> 05:21:09,760 OTHER CELLS AND THE VARIATION 5883 05:21:09,760 --> 05:21:11,560 CAUSED THE BEHAVIOR OF OTHER 5884 05:21:11,560 --> 05:21:14,160 CELLS AND I THINK DIRECTLY THE 5885 05:21:14,160 --> 05:21:15,560 MACROPHAGES BUT WHEN YOU THINK 5886 05:21:15,560 --> 05:21:18,680 ABOUT IT ALL THOSE PROBABLY 5887 05:21:18,680 --> 05:21:21,280 WOULD BE SOMEWHAT MARKETED GREN 5888 05:21:21,280 --> 05:21:22,720 ET TICK LEVEL SO HAVE YOU 5889 05:21:22,720 --> 05:21:27,400 ACTUALLY TRIED TO LOOK AT BEFORE 5890 05:21:27,400 --> 05:21:31,200 OURS AND THERE'S AND IT'S THAT 5891 05:21:31,200 --> 05:21:33,560 WERE PRONE THEM TO BE MORE AND 5892 05:21:33,560 --> 05:21:41,320 AS I SAID BEFORE AND STIMULATION 5893 05:21:41,320 --> 05:21:44,720 AND AND IT'S SOME OF THE WORK 5894 05:21:44,720 --> 05:21:48,680 THAT MING HAS BEEN DOING AND WE 5895 05:21:48,680 --> 05:21:54,360 LOOKED AT. 5896 05:21:54,360 --> 05:21:57,520 EXIST EXAMINING DIFFERENCES AND 5897 05:21:57,520 --> 05:22:00,240 EPI GENETIC LEVEL AND WHAT IS 5898 05:22:00,240 --> 05:22:08,120 INTERESTING AND THE RESPONSE TO 5899 05:22:08,120 --> 05:22:09,200 I-L4 BETWEEN TWO DIFFERENT 5900 05:22:09,200 --> 05:22:15,400 STRAINS OF MICE AND INDUCED CROW 5901 05:22:15,400 --> 05:22:19,080 A TIN CHANGES AND AND WHAT IS 5902 05:22:19,080 --> 05:22:23,160 AND THE REGENTS THAT ARE AND 5903 05:22:23,160 --> 05:22:24,320 STATUS AND THOSE TEND TO FALL IN 5904 05:22:24,320 --> 05:22:32,840 THE NON CODING REGIONS AND THE 5905 05:22:32,840 --> 05:22:39,160 NAIVE SO THE NAIVE CON AND AND 5906 05:22:39,160 --> 05:22:41,280 PROMOTE REGIONS AND SO THERE IS 5907 05:22:41,280 --> 05:22:43,040 LESS OF THOSE DIFFERENCES BUT 5908 05:22:43,040 --> 05:22:48,400 THEY'RE INDUCED CHANGES TEND TO 5909 05:22:48,400 --> 05:22:58,840 BE AND AND IN BETWEEN THE 5910 05:22:59,080 --> 05:22:59,880 STRAINS AND SO -- 5911 05:22:59,880 --> 05:23:02,200 >> IS IT FAIR TO SAY THAT THOSE 5912 05:23:02,200 --> 05:23:03,840 FUNCTIONING MOSTLY IMPORTANTLY 5913 05:23:03,840 --> 05:23:08,200 THE GENES AND ACTUALLY VERY 5914 05:23:08,200 --> 05:23:10,480 CONSERVED WHERE LESS IMPORTANT 5915 05:23:10,480 --> 05:23:14,160 GONE MAY REPRESENTING AND 5916 05:23:14,160 --> 05:23:15,880 INDUCING MAY NOT BE FUNCTIONING 5917 05:23:15,880 --> 05:23:19,720 AND CAN YOU ACTUALLY A GOOD 5918 05:23:19,720 --> 05:23:22,920 EXAMPLE THAT DEMONSTRATES AND 5919 05:23:22,920 --> 05:23:23,520 FUNCTIONALITY. 5920 05:23:23,520 --> 05:23:26,000 >> THAT'S A GREAT POINT AND IN 5921 05:23:26,000 --> 05:23:30,560 FACT, I WAS TALKING TO JUDY 5922 05:23:30,560 --> 05:23:35,040 ALLEN ABOUT THAT AND I WAS 5923 05:23:35,040 --> 05:23:38,360 SPECULATING SO THAT HUMANS, THE 5924 05:23:38,360 --> 05:23:40,240 LONG BEEN KNOWN THAT 5925 05:23:40,240 --> 05:23:43,360 ALTERNATIVELY ACTIVATED GENES IN 5926 05:23:43,360 --> 05:23:45,480 MICE ARE NOT REFLECTIVE IN 5927 05:23:45,480 --> 05:23:49,240 HUMANS, RIGHT AND SO ONE OF THE 5928 05:23:49,240 --> 05:23:50,280 HYPOTHESIS WAS MAYBE IT'S 5929 05:23:50,280 --> 05:23:55,120 BECAUSE WE'RE STARTING BLACK SIX 5930 05:23:55,120 --> 05:23:56,640 MICE AND MAYBE WE NEED TO LOOK 5931 05:23:56,640 --> 05:23:59,800 AT THE CONSERVED GENES THAT ARE 5932 05:23:59,800 --> 05:24:03,960 CONSERVED AND ALTHOUGH AND THEY 5933 05:24:03,960 --> 05:24:06,080 PHASE AND THOSE ARE HIGHLY 5934 05:24:06,080 --> 05:24:08,160 CONSERVATIVE OF BEING INDUCED 5935 05:24:08,160 --> 05:24:09,480 AND WHERE THOSE ARE THE ONES 5936 05:24:09,480 --> 05:24:18,200 THAT ACTUALLY AND AND IT MIGHT 5937 05:24:18,200 --> 05:24:21,880 BE SPECIFIC CORE KIND OF EFFECTS 5938 05:24:21,880 --> 05:24:24,800 THAT ARE PULLING. 5939 05:24:24,800 --> 05:24:27,920 >> THAT'S BEAUTIFUL AS ALWAYS. 5940 05:24:27,920 --> 05:24:32,120 A REMARE DIFFERENCE IS 5941 05:24:32,120 --> 05:24:34,480 BETWEEN NAIVE BOB C AND B6 5942 05:24:34,480 --> 05:24:41,000 MACROPHAGES BEGGING TO QUESTION 5943 05:24:41,000 --> 05:24:45,760 IF YOU AND AND MACROPHAGES AND 5944 05:24:45,760 --> 05:24:47,320 STRAINED CROSS TO CHAIN 5945 05:24:47,320 --> 05:24:49,040 DEFICIENT MICE AND TO ELIMINATE 5946 05:24:49,040 --> 05:24:52,520 THE FACTS OF INNATELY AND T 5947 05:24:52,520 --> 05:24:57,480 CELLS PRIMING IN IDEALLY EVEN 5948 05:24:57,480 --> 05:24:58,080 DERIVED TO GERM FREE ENVIRONMENT 5949 05:24:58,080 --> 05:24:59,240 WHAT DO YOU THINK WOULD BE THE 5950 05:24:59,240 --> 05:24:59,600 DIFFERENCES? 5951 05:24:59,600 --> 05:25:01,080 WOULD IT BE REDUCED? 5952 05:25:01,080 --> 05:25:05,560 >> I MEAN, YEAH, THAT'S AGAIN A 5953 05:25:05,560 --> 05:25:07,400 GREAT IDEA TO TRY AND REMOVE AS 5954 05:25:07,400 --> 05:25:11,560 MUCH AS POSSIBLE THE 5955 05:25:11,560 --> 05:25:14,600 CONTRIBUTIONS OF THE OTHER CELL 5956 05:25:14,600 --> 05:25:21,760 TYPES AND INTO THE SYSTEM. 5957 05:25:21,760 --> 05:25:23,040 THE GROUP HAS LOOKED AT THAT 5958 05:25:23,040 --> 05:25:26,080 FROM THE PERSPECTIVE OF BONE 5959 05:25:26,080 --> 05:25:27,800 MARROW MACROPHAGES AND WE KNOW 5960 05:25:27,800 --> 05:25:30,680 THAT TISSUE AND MACROPHAGES ARE 5961 05:25:30,680 --> 05:25:32,920 NOT THE SAME AS BONE MARROW 5962 05:25:32,920 --> 05:25:34,440 MACROPHAGES SO THAT'S A GREAT 5963 05:25:34,440 --> 05:25:35,040 IDEA. 5964 05:25:35,040 --> 05:25:36,720 >> BONE MARROW MACROPHAGES THE 5965 05:25:36,720 --> 05:25:39,280 HEAVY INFLUENCES AND JASMINE 5966 05:25:39,280 --> 05:25:41,280 SHOWED BEAUTIFULLY AND IT'S A 5967 05:25:41,280 --> 05:25:41,800 WAY TO START. 5968 05:25:41,800 --> 05:25:42,720 >> YEAH. 5969 05:25:42,720 --> 05:25:42,920 YEAH. 5970 05:25:42,920 --> 05:25:45,600 >> GOOD. 5971 05:25:45,600 --> 05:25:46,120 >> THANK YOU. 5972 05:25:46,120 --> 05:25:56,080 [APPLAUSE] 5973 05:25:56,080 --> 05:26:00,200 >> WE'RE GOING TO TURN THIS OVER 5974 05:26:00,200 --> 05:26:02,040 TO TOM WYNN WHO IS GOING TO HAVE 5975 05:26:02,040 --> 05:26:04,160 TO PENT ULTIMATE REMARKS. 5976 05:26:04,160 --> 05:26:06,520 >> I SEE THE BIG BOSS IS HERE, 5977 05:26:06,520 --> 05:26:08,000 HI, STEVE. 5978 05:26:08,000 --> 05:26:11,400 SO I PROBABLY DON'T HAVE AS MUCH 5979 05:26:11,400 --> 05:26:12,960 TIME AS I THINK OF THE THANK YOU 5980 05:26:12,960 --> 05:26:15,240 FOR ORGANIZING IT'S BEEN A 5981 05:26:15,240 --> 05:26:18,640 REALLY FUN TWO DAYS AND MY 5982 05:26:18,640 --> 05:26:20,320 CAREER AT NIH STARTED 31 YEARS 5983 05:26:20,320 --> 05:26:22,360 AGO AND I SPENT 26 YEARS HERE 5984 05:26:22,360 --> 05:26:23,440 BEFORE DECIDING TO LEAVE ABOUT 5985 05:26:23,440 --> 05:26:25,160 FIVE YEARS AGO AND IT WAS A VERY 5986 05:26:25,160 --> 05:26:25,880 HARD DECISION. 5987 05:26:25,880 --> 05:26:27,720 IT WAS A JOY TO WORK WITH ALAN 5988 05:26:27,720 --> 05:26:31,200 FOR SO MANY YEARS. 5989 05:26:31,200 --> 05:26:32,640 AND IT WAS A GREAT CHOICE TO 5990 05:26:32,640 --> 05:26:34,040 COME HERE AND I WAS DECIDING 5991 05:26:34,040 --> 05:26:36,040 BETWEEN HIS LABORATORY AND 5992 05:26:36,040 --> 05:26:36,920 ROBERT MAUD LYNN WHO WORKED ON 5993 05:26:36,920 --> 05:26:42,280 HELP RA SEE AND TB AND THE TH2 5994 05:26:42,280 --> 05:26:52,800 AND RICHARD AND THERE'S A LOT OF 5995 05:26:59,360 --> 05:27:02,960 FUNNY STORIES I WANT TO SHARE. 5996 05:27:02,960 --> 05:27:07,680 AND IT'S GREAT TO SEE LPD AND 5997 05:27:07,680 --> 05:27:18,200 AND INFECTION MORE THAN I STILL 5998 05:27:35,200 --> 05:27:36,600 HAVEN'T FOUND IT AND I KNOW IT'S 5999 05:27:36,600 --> 05:27:37,840 OUT THERE SOMEWHERE. 6000 05:27:37,840 --> 05:27:38,840 DAVID SACKS FOR LETTING ME SIT 6001 05:27:38,840 --> 05:27:41,080 IN HIS LAB WHEN I FIRST CAME. 6002 05:27:41,080 --> 05:27:42,480 ALAN'S LAB WAS OVERFLOWING WITH 6003 05:27:42,480 --> 05:27:44,000 PEOPLE NOT SURPRISINGLY AND 6004 05:27:44,000 --> 05:27:45,520 DAVID LET ME SIT IN HIS 6005 05:27:45,520 --> 05:27:47,000 LABORATORY AND I SAT IN THE AREA 6006 05:27:47,000 --> 05:27:51,040 WHERE THEY KILLED THE MICE AND 6007 05:27:51,040 --> 05:27:52,440 THAT WAS AN INTERESTING 6008 05:27:52,440 --> 05:27:53,760 EXPERIENCE AND SO I WAS SITTING 6009 05:27:53,760 --> 05:27:57,240 RIGHT BEHIND HIS REALLY AWFUL 6010 05:27:57,240 --> 05:28:03,400 OFFICE AND I STILL HAVE AND SO 6011 05:28:03,400 --> 05:28:04,120 THANK YOU AND THANK YOU. 6012 05:28:04,120 --> 05:28:06,880 WE HAD A LOT OF THIS AND A LOT 6013 05:28:06,880 --> 05:28:10,800 OF PEOPLE TOUCHED ON THE AMAZING 6014 05:28:10,800 --> 05:28:12,960 EDUCATION AND CAREER AND I'M 6015 05:28:12,960 --> 05:28:14,080 GOING BACK FURTHER BACK TO 6016 05:28:14,080 --> 05:28:17,080 COLLEGE AND THIS IS MY FIRST 6017 05:28:17,080 --> 05:28:21,840 CONNECTION FOR ALLEN AND AND 6018 05:28:21,840 --> 05:28:23,600 ALAN WOULDN'T TO OBSERVER LAND 6019 05:28:23,600 --> 05:28:27,560 AND FANCY AND ELITE LIBERAL ARTS 6020 05:28:27,560 --> 05:28:32,240 COLLEGE AND BEAUTIFUL COLLEGE 6021 05:28:32,240 --> 05:28:33,880 AND NEAR CLEVELAND AND SOME OF 6022 05:28:33,880 --> 05:28:35,720 YOU DO REALIZE AND CORRECT ME IF 6023 05:28:35,720 --> 05:28:37,000 I'M WRONG BUT YOU WERE AN 6024 05:28:37,000 --> 05:28:38,600 ENGLISH MAJOR. 6025 05:28:38,600 --> 05:28:40,160 >> WHAT IS IT? 6026 05:28:40,160 --> 05:28:44,000 >> CLASSICS. 6027 05:28:44,000 --> 05:28:44,520 BUT OK CLASSICS. 6028 05:28:44,520 --> 05:28:46,040 HE IS A GOOD WRITER BECAUSE OF 6029 05:28:46,040 --> 05:28:47,720 HIS EDUCATION AT THE SCHOOL I 6030 05:28:47,720 --> 05:28:48,040 THINK. 6031 05:28:48,040 --> 05:28:51,080 THERE WAS A REAL FOCUS ON 6032 05:28:51,080 --> 05:28:51,440 WRITING. 6033 05:28:51,440 --> 05:28:54,480 AND WE'VE ALL TALKED ABOUT THAT 6034 05:28:54,480 --> 05:28:56,280 TODAY HOWEN INFLUENTIAL THAT'S 6035 05:28:56,280 --> 05:29:00,880 BEEN AND AS WE MOW WE MOVED ONTO 6036 05:29:00,880 --> 05:29:02,680 THE MILL HILL, ASSIST APARTMENT 6037 05:29:02,680 --> 05:29:04,560 PROFESSOR AT HARVARD AND THE NIH 6038 05:29:04,560 --> 05:29:07,680 AND THIS IS WHAT WE'RE LEFT 6039 05:29:07,680 --> 05:29:08,280 WITH. 6040 05:29:08,280 --> 05:29:09,800 ALAN WAS ALWAYS A LOT OF FUN AND 6041 05:29:09,800 --> 05:29:11,320 HE WAS NOT ONLY A GREAT MENTOR 6042 05:29:11,320 --> 05:29:13,480 BUT HE WAS A REALLY FUN MENTOR 6043 05:29:13,480 --> 05:29:15,640 TO WORK WITH AND WE'VE GONE 6044 05:29:15,640 --> 05:29:16,840 THROUGH ALL OF THIS AND THE 6045 05:29:16,840 --> 05:29:18,240 HISTORY AND I THOUGHT I WOULD 6046 05:29:18,240 --> 05:29:22,480 TURN IT BACK ON ALL OF YOU 6047 05:29:22,480 --> 05:29:24,080 BECAUSE THIS IS WHAT ALAN CARES 6048 05:29:24,080 --> 05:29:25,160 ABOUT THE MOST. 6049 05:29:25,160 --> 05:29:27,040 I'M GLAD WE'RE ABLE TO DO THIS 6050 05:29:27,040 --> 05:29:28,800 NOW BEFORE YOU ARE 100-YEARS-OLD 6051 05:29:28,800 --> 05:29:31,000 AND WE'RE CELEBRATING YOUR 6052 05:29:31,000 --> 05:29:32,240 100th BIRTHDAY SO YOU STILL 6053 05:29:32,240 --> 05:29:33,760 REMEMBER WHO WE ARE. 6054 05:29:33,760 --> 05:29:35,560 AND SO IT'S GREAT YOU CAN BE 6055 05:29:35,560 --> 05:29:42,800 HERE AND CELEBRATE AND PUBLISH 6056 05:29:42,800 --> 05:29:44,520 SEMINOLE PAPERS AND WE'VE TALKED 6057 05:29:44,520 --> 05:29:47,280 ABOUT THE EARLY WORK WITH PHIL 6058 05:29:47,280 --> 05:29:52,160 SCOTT AND MOB MAUDELYNN AND IT'S 6059 05:29:52,160 --> 05:29:55,000 AN AMAZING AND AND ALAN AGAIN, A 6060 05:29:55,000 --> 05:29:56,920 LOT OF AND I THINK THIS IS ALAN, 6061 05:29:56,920 --> 05:29:59,600 ROB THOMPSON SENT ME THESE 6062 05:29:59,600 --> 05:30:00,400 PHOTOGRAPHS AND I THINK THAT'S 6063 05:30:00,400 --> 05:30:01,440 ALAN ON THE LEFT. 6064 05:30:01,440 --> 05:30:11,320 HE REALLY LIKED HALLOWEEN AND HE 6065 05:30:11,320 --> 05:30:16,400 LIKED TO I COULD NOT FIND A 6066 05:30:16,400 --> 05:30:26,920 PHOTO OF THAT AND AND BENEFITED 6067 05:30:37,720 --> 05:30:39,560 FROM AMMAN WORKING ON TOXO SO IT 6068 05:30:39,560 --> 05:30:41,280 FREED THAT AREA UP FOR THEM TO 6069 05:30:41,280 --> 05:30:42,920 EXCEL AND BE RECOGNIZED FOR 6070 05:30:42,920 --> 05:30:46,280 THEIR OWN SEMINOLE RESEARCH. 6071 05:30:46,280 --> 05:30:49,720 HE MOVED ON TO TALK AND I'M SURE 6072 05:30:49,720 --> 05:30:53,520 THE HIV EPIDEMIC HAD A LOT TO DO 6073 05:30:53,520 --> 05:30:54,400 WITH THAT PARTICULAR INTEREST 6074 05:30:54,400 --> 05:30:56,040 AND IT'S AN AMAZING GROUP OF 6075 05:30:56,040 --> 05:30:57,120 COLLEAGUES THAT WORKED WITH HIM 6076 05:30:57,120 --> 05:30:58,600 OVER THE YEARS AND SOME OF THE 6077 05:30:58,600 --> 05:30:59,600 NICE PAPERS THAT GROUP PUBLISHED 6078 05:30:59,600 --> 05:31:01,320 AND SOME OF THE MOST CITED 6079 05:31:01,320 --> 05:31:02,520 PAPERS ARE SHOWN HERE AND ONE 6080 05:31:02,520 --> 05:31:06,320 THAT WAS PERSONALLY INSPIRING 6081 05:31:06,320 --> 05:31:16,160 FOR ME AND TO A DIFFERENT WAY 6082 05:31:16,160 --> 05:31:26,640 AND AND IT'S CRITICAL AND I 6083 05:31:36,240 --> 05:31:38,480 THOUGHT THAT WAY IN MY OWN 6084 05:31:38,480 --> 05:31:39,560 RESEARCH FOR MANY YEARS AND IT 6085 05:31:39,560 --> 05:31:43,160 GUIDES THE RESEARCH THAT I DO. 6086 05:31:43,160 --> 05:31:45,360 HE ALSO MOVED ON ANOTHER MAJOR 6087 05:31:45,360 --> 05:31:49,080 AREA AND I HAVE TO SAY A PET 6088 05:31:49,080 --> 05:31:52,160 AREA OF RESEARCH IDENTIFYING THE 6089 05:31:52,160 --> 05:31:57,040 PERSON PARASITE FACTORS THAT 6090 05:31:57,040 --> 05:31:58,600 WERE DRIVING AND WHAT WERE THE 6091 05:31:58,600 --> 05:32:05,000 FACTORS WHAT WERE THE RESPONSE 6092 05:32:05,000 --> 05:32:12,600 AND AND THAT WAS A PROJECT THAT 6093 05:32:12,600 --> 05:32:14,520 ALAN ENJOYED HERE AND HE IS 6094 05:32:14,520 --> 05:32:16,880 STANCING AFTER THE DISCOVERY OF 6095 05:32:16,880 --> 05:32:20,360 PRO FILL AND INTERACTING WITH 6096 05:32:20,360 --> 05:32:22,080 RECEPTORS 11 AND THEN DRAGANA'S 6097 05:32:22,080 --> 05:32:23,920 BEAUTIFUL WORK ON THE OMEGA 1 6098 05:32:23,920 --> 05:32:27,160 THAT WE HEARD ABOUT EARLIER. 6099 05:32:27,160 --> 05:32:29,280 AND A BIG MOVE AGAIN THIS CAME 6100 05:32:29,280 --> 05:32:33,880 AROUND THE TIME WHERE I WAS 6101 05:32:33,880 --> 05:32:36,040 BECOMING A 10-YEAR TRACK 6102 05:32:36,040 --> 05:32:36,840 INVESTIGATOR AND ACTUALLY 6103 05:32:36,840 --> 05:32:38,480 ANOTHER FUNNY STORY IS THAT I 6104 05:32:38,480 --> 05:32:40,280 NEVER REALLY WORKED IN ALAN'S 6105 05:32:40,280 --> 05:32:41,520 LAB WHEN I FIRST CAME. 6106 05:32:41,520 --> 05:32:44,120 I SAT IN DAVID'S LAB AND WE 6107 05:32:44,120 --> 05:32:45,480 ACQUIRED SPACE IN THE SUB 6108 05:32:45,480 --> 05:32:46,920 BASEMENT WHERE THERE ARE NO 6109 05:32:46,920 --> 05:32:49,840 WINDOWS AND BUILDING 4 AND I WAS 6110 05:32:49,840 --> 05:32:52,480 TOWN THERE WITH LENA AND DRAGANA 6111 05:32:52,480 --> 05:32:55,160 AND OUR OWN LITTLE TRIO AND NO 6112 05:32:55,160 --> 05:32:57,080 WINDOWS AND WE WOULD BE THERE 6113 05:32:57,080 --> 05:32:58,560 UNTIL 8:00 AT NIGHT BECAUSE WE 6114 05:32:58,560 --> 05:32:59,880 HAD NO IDEA WHAT TIME IT WAS BUT 6115 05:32:59,880 --> 05:33:01,800 IT WAS A GOOD THING AND IT WAS A 6116 05:33:01,800 --> 05:33:03,200 FUN TIME AND I REMEMBER ONE 6117 05:33:03,200 --> 05:33:05,720 STORY THAT RICARDO COMING DOWN. 6118 05:33:05,720 --> 05:33:07,680 IT WAS A PLACE WHERE WE KILLED 6119 05:33:07,680 --> 05:33:08,720 MICE AND COLLECTED PARASITE 6120 05:33:08,720 --> 05:33:11,880 MATERIALS AND RICARDO COMES DOWN 6121 05:33:11,880 --> 05:33:12,480 COLLECTING MOUSE BRAINS TO GET 6122 05:33:12,480 --> 05:33:13,880 TOXO AND HE IS SITTING RIGHT 6123 05:33:13,880 --> 05:33:14,880 NEXT TO ME. 6124 05:33:14,880 --> 05:33:17,000 I WAS A MOLECULAR BIOLOGIST 6125 05:33:17,000 --> 05:33:19,200 DOING PCR AND RICARDO IS RIGHT 6126 05:33:19,200 --> 05:33:22,520 NEXT TO ME, LAB COAST, GLOVES, 6127 05:33:22,520 --> 05:33:25,160 MASK, EYE FIELD, AND I SAT HERE 6128 05:33:25,160 --> 05:33:28,200 WITH NOTHING AND NOTHING AND 6129 05:33:28,200 --> 05:33:30,000 RICARDO, DO I NEED TO BE WORRIED 6130 05:33:30,000 --> 05:33:30,840 ABOUT THIS. 6131 05:33:30,840 --> 05:33:31,920 TOM, TOM, NO! 6132 05:33:31,920 --> 05:33:35,640 YOU DON'T HAVE TO WORRY. 6133 05:33:35,640 --> 05:33:37,680 SURE ENOUGH, WHEN WE WENT TO THE 6134 05:33:37,680 --> 05:33:39,000 COURSE LATER THAT YEAR ONE OF 6135 05:33:39,000 --> 05:33:41,920 THE STUDIES THAT WE DID WAS TO 6136 05:33:41,920 --> 05:33:44,000 DO A SERUM AS SAY FOR EXPOSURE 6137 05:33:44,000 --> 05:33:46,160 TO AND I WAS THE POSITIVE 6138 05:33:46,160 --> 05:33:49,680 CONTROL AND I WAS SCREAMING AND 6139 05:33:49,680 --> 05:33:54,040 THANK YOU, RICARDO. 6140 05:33:54,040 --> 05:33:55,760 BUT THIS WAS AN AMAZING RESEARCH 6141 05:33:55,760 --> 05:34:00,600 AND I LIKE THE PAPER AND AND BY 6142 05:34:00,600 --> 05:34:04,520 ANNE REALLY AND BEAUTIFUL WORK 6143 05:34:04,520 --> 05:34:06,680 AND THE TV WORK IS CONTINUING IN 6144 05:34:06,680 --> 05:34:08,800 GREAT HANDS HERE AT THE NIH WITH 6145 05:34:08,800 --> 05:34:16,040 CAT AND BEGAN SO T DAN SO IT'S T 6146 05:34:16,040 --> 05:34:17,440 OF CHARACTERS THAT PLAYED A KEY 6147 05:34:17,440 --> 05:34:25,680 ROLE IN THE WORK AND I CAME INTO 6148 05:34:25,680 --> 05:34:27,960 ALAN'S LAB IS A PAPER LOOKING AT 6149 05:34:27,960 --> 05:34:32,360 THE THI AND TH2 DICHOTOMY TO 6150 05:34:32,360 --> 05:34:42,880 JUST TO SOME INFECTION AND IT 6151 05:34:48,240 --> 05:34:50,920 WAS LIKE SO I JUST THOUGHT I WAS 6152 05:34:50,920 --> 05:34:53,120 GOING TO FREE ASSOCIATE WHAT 6153 05:34:53,120 --> 05:34:54,880 WERE THE WORDS I ASSOCIATE WITH 6154 05:34:54,880 --> 05:34:57,160 THAT AND BE RELENTLESS AND ALAN 6155 05:34:57,160 --> 05:34:59,080 WAS RELENTLESS WHEN I DECIDED TO 6156 05:34:59,080 --> 05:35:00,760 COME TO HIS LAB. 6157 05:35:00,760 --> 05:35:03,040 AND IN FACT, WHEN I WAS DECIDING 6158 05:35:03,040 --> 05:35:07,400 BETWEEN BOB AND RICH, HE 6159 05:35:07,400 --> 05:35:10,160 LITERALLY AND HE CALLED AND SHE 6160 05:35:10,160 --> 05:35:11,840 SAID IT'S YOUR NEW BOSS ON THE 6161 05:35:11,840 --> 05:35:13,480 PHONE AND SO HE WAS REALLY 6162 05:35:13,480 --> 05:35:14,680 RELENTLESS ABOUT ME DECIDE TO GO 6163 05:35:14,680 --> 05:35:16,320 COME TO HIS LAB AND I ALWAYS 6164 05:35:16,320 --> 05:35:17,960 APPRECIATED THAT BECAUSE I KNEW 6165 05:35:17,960 --> 05:35:20,560 THAT HE WANTED ME TO COME AND 6166 05:35:20,560 --> 05:35:21,640 THAT MEANT A LOT TO ME AND I 6167 05:35:21,640 --> 05:35:22,920 THINK ABOUT THAT A LOT WHEN I 6168 05:35:22,920 --> 05:35:24,240 WOULD HIRE PEOPLE THAT MAKE IT 6169 05:35:24,240 --> 05:35:27,240 CLEAR THAT YOU ARE REALLY 6170 05:35:27,240 --> 05:35:28,080 WANTING THEM. 6171 05:35:28,080 --> 05:35:30,880 BE SEEN AND WOVE HEARD A LOT 6172 05:35:30,880 --> 05:35:33,400 ABOUT THAT AND GO TO MEETINGS 6173 05:35:33,400 --> 05:35:34,280 AND BRAG ABOUT YOUR WORK AND YOU 6174 05:35:34,280 --> 05:35:36,760 ARE THE CHEERLEADER AND I HAVE 6175 05:35:36,760 --> 05:35:37,600 THAT BELOW. 6176 05:35:37,600 --> 05:35:39,680 ALAN WAS AN AMAZING CHEERLEADER 6177 05:35:39,680 --> 05:35:42,080 AND ED USED THAT WORD AND ALAN 6178 05:35:42,080 --> 05:35:42,960 IS A CHEERLEADER. 6179 05:35:42,960 --> 05:35:45,160 I REMEMBER THE FIRST YEAR IN THE 6180 05:35:45,160 --> 05:35:52,240 LAB, NO ONE KNEW WHICH WAS AND . 6181 05:35:52,240 --> 05:35:53,320 PEOPLE WERE COMING UP TO ME 6182 05:35:53,320 --> 05:35:54,800 SAYING WOW WE LIKE YOUR WORK AND 6183 05:35:54,800 --> 05:35:56,400 I WAS LIKE HOW DO YOU KNOW. 6184 05:35:56,400 --> 05:35:58,000 I HAVE NOT PUBLISHED ANYTHING 6185 05:35:58,000 --> 05:36:02,680 AND ALAN WAS OUT THERE BEING MY 6186 05:36:02,680 --> 05:36:08,120 CHEERLEADER AND BE A STORY 6187 05:36:08,120 --> 05:36:13,560 TELLER AND A FANTASTIC AND 6188 05:36:13,560 --> 05:36:16,360 STRIVING FOR EXCELLENCE AND 6189 05:36:16,360 --> 05:36:18,320 WE'VE HEARD ABOUT TEAMWORK AND 6190 05:36:18,320 --> 05:36:22,440 THANK GOD FOR SARAH HEINE'Y AND 6191 05:36:22,440 --> 05:36:24,160 PAT CASPER SO WE CAN EXCEL AT 6192 05:36:24,160 --> 05:36:26,720 OUR WORK AND OF COURSE 6193 05:36:26,720 --> 05:36:31,160 COLLABORATION BOB COFFMAN AND 6194 05:36:31,160 --> 05:36:33,160 GORGIO AND HE HAD A GREAT 6195 05:36:33,160 --> 05:36:34,760 COLLABORATORS AND THAT ALSO 6196 05:36:34,760 --> 05:36:36,080 ELEVATED THE KIND OF WORK THAT 6197 05:36:36,080 --> 05:36:38,320 HE DID AND HE WAS ALWAYS 6198 05:36:38,320 --> 05:36:40,840 GRACIOUS AND THANKED US AND 6199 05:36:40,840 --> 05:36:49,160 PATIENTS AND NOT SO MUCH. 6200 05:36:49,160 --> 05:36:57,400 AND HE WOULD I'VE LEARNED TO BE 6201 05:36:57,400 --> 05:36:58,400 PATIENT IN MY OWN LIFE. 6202 05:36:58,400 --> 05:37:00,840 HE WAS COURAGEOUS AND LET'S TRY 6203 05:37:00,840 --> 05:37:06,760 WITH THEM AND LET'S SAY AND 6204 05:37:06,760 --> 05:37:08,120 SITTING IN THAT AWFUL SEAT AND 6205 05:37:08,120 --> 05:37:10,800 WE ALL LEARNED A LOT AND HE 6206 05:37:10,800 --> 05:37:11,840 ALWAYS CELEBRATED OUR 6207 05:37:11,840 --> 05:37:13,920 ACCOMPLISHMENTS AND THERE WAS A 6208 05:37:13,920 --> 05:37:17,080 BOTTLE OF CHAMPAGNE AND LOVED 6209 05:37:17,080 --> 05:37:19,040 THAT AND MADE YOU FEEL SPECIAL 6210 05:37:19,040 --> 05:37:23,120 AND LOVED TO PARTY AND ALWAYS 6211 05:37:23,120 --> 05:37:29,720 HAD GREAT PARTIES ALAN CHIEFER 6212 05:37:29,720 --> 05:37:35,920 WAS A PESSIMIST AND WHAT A GREAT 6213 05:37:35,920 --> 05:37:36,320 SITUATION. 6214 05:37:36,320 --> 05:37:37,480 ALAN SAID EVERYTHING IS EXCITING 6215 05:37:37,480 --> 05:37:39,440 AND YOU CAN DO THAT AND I COULD 6216 05:37:39,440 --> 05:37:40,960 TELL ALAN AND SAID YOU CAN DO 6217 05:37:40,960 --> 05:37:43,200 THAT FIVE YEARS AGO HE WOULD GO 6218 05:37:43,200 --> 05:37:45,360 TO HIS COMPLEX FILE SYSTEM AND 6219 05:37:45,360 --> 05:37:47,000 PULL THE PAPER OUT AND SHOW ME 6220 05:37:47,000 --> 05:37:48,520 BUT THERE'S ALWAYS A NEW ANGLE 6221 05:37:48,520 --> 05:37:51,840 ON IT AND SO I HAD TWO GREAT 6222 05:37:51,840 --> 05:37:53,560 MENTORS HERE AND HE WAS A GREAT 6223 05:37:53,560 --> 05:37:57,240 COOK AND I HAD INDIAN DINNERS 6224 05:37:57,240 --> 05:38:00,000 AND HE WAS VERY GOOD AT LAMB AND 6225 05:38:00,000 --> 05:38:02,680 THAT WAS HIS CONTRIBUTION AND 6226 05:38:02,680 --> 05:38:04,200 THE HOTSEAT, THIS IS LIZ WHO 6227 05:38:04,200 --> 05:38:05,920 COULDN'T BE HERE AND SO SHE 6228 05:38:05,920 --> 05:38:07,280 WOULD HAVE LOVED TO HAVE BEEN 6229 05:38:07,280 --> 05:38:09,440 HERE AND WE ALL HATED THIS 6230 05:38:09,440 --> 05:38:10,640 HOTSEAT AND I LEARNED A LOT 6231 05:38:10,640 --> 05:38:12,800 ABOUT WRITING AND I ALSO LEARNED 6232 05:38:12,800 --> 05:38:15,840 A LOT ABOUT WHAT FAVORITE WORDS 6233 05:38:15,840 --> 05:38:18,760 ALAN HAD AND YOU CAN THROW OUT 6234 05:38:18,760 --> 05:38:21,920 HIS FAVORITE WORDS AND I 6235 05:38:21,920 --> 05:38:22,360 REMEMBER NEVERTHELESS. 6236 05:38:22,360 --> 05:38:27,800 HE WAS SO HAPPY IF HE USED IT. 6237 05:38:27,800 --> 05:38:32,840 >> SO WILL YOU, ALAN. 6238 05:38:32,840 --> 05:38:38,800 I IT'S AN IMPACT AND THIS IS A 6239 05:38:38,800 --> 05:38:41,000 REVIEW ABOUT COLLEAGUES ABOUT 6240 05:38:41,000 --> 05:38:43,840 TH1 AND T H2 PARADIGM WHICH 6241 05:38:43,840 --> 05:38:46,000 NEVER DIES AND HOPEFULLY THIS 6242 05:38:46,000 --> 05:38:47,120 WILL ILLUSTRATE WHY IT'S 6243 05:38:47,120 --> 05:38:49,840 IMPORTANT AND ALAN WORKED ON ALL 6244 05:38:49,840 --> 05:38:54,040 OF THESE AND THE FLIP SIDE AND 6245 05:38:54,040 --> 05:38:55,480 TH-2 RESPONSE AND WHEN YOU THINK 6246 05:38:55,480 --> 05:38:57,520 ABOUT OTHER DISEASES THAT ARE 6247 05:38:57,520 --> 05:38:59,560 IMPACTED BY THIS PARADIGM, 6248 05:38:59,560 --> 05:39:03,040 DISEASES THAT I NOW WORK ON, 6249 05:39:03,040 --> 05:39:06,200 PSORIASIS, ARTHRITIS, CROWNS, 6250 05:39:06,200 --> 05:39:08,000 RA, ALL DRIVEN BY WHAT LOOKS 6251 05:39:08,000 --> 05:39:10,320 LIKE A TYPE ONE INFLAMMATORY 6252 05:39:10,320 --> 05:39:11,680 RESPONSE AND THEN ON THE OTHER 6253 05:39:11,680 --> 05:39:13,840 SIDE, THESE DISEASES, FOOD 6254 05:39:13,840 --> 05:39:18,640 ALLERGY, ASTHMA AND DRIVEN BY 6255 05:39:18,640 --> 05:39:20,360 THAT TH2 SIGNATURE AND THERE'S 6256 05:39:20,360 --> 05:39:23,240 SOME DISEASES THAT DON'T FALL 6257 05:39:23,240 --> 05:39:24,160 NEATLY INTO THESE CATEGORIES 6258 05:39:24,160 --> 05:39:26,920 THAT HAVE A MIXED INFLAMMATORY 6259 05:39:26,920 --> 05:39:28,560 RESPONSE AND WHAT IS TRULY 6260 05:39:28,560 --> 05:39:31,240 AMAZING IS THE NUMBER OF NEW 6261 05:39:31,240 --> 05:39:32,720 MEDS THAT ARE BEING MADE AND 6262 05:39:32,720 --> 05:39:34,880 BASED OFF OF THE SITE OWE KEEN 6263 05:39:34,880 --> 05:39:36,080 WORK THAT A LOT OF YOU HAVE DONE 6264 05:39:36,080 --> 05:39:39,640 IN THIS ROOM AND HUMARA IS A 6265 05:39:39,640 --> 05:39:41,000 OTHER BILLION DOLLAR A YEAR 6266 05:39:41,000 --> 05:39:44,520 INDUSTRY CREATING MANY DIFFERENT 6267 05:39:44,520 --> 05:39:47,600 DISEASES, ANTI-IL-6 AND IL-1 AND 6268 05:39:47,600 --> 05:39:52,240 WE THINK ABOUT IL-17, IL-23, 6269 05:39:52,240 --> 05:39:54,800 P-19, IL-12. 6270 05:39:54,800 --> 05:39:56,680 AND MULTI BILLION DOLLARS DRUGS 6271 05:39:56,680 --> 05:39:58,000 AND EVERY YEAR AND TREATING 6272 05:39:58,000 --> 05:40:00,520 THESE DISEASES AND ON THE FLIP 6273 05:40:00,520 --> 05:40:07,360 SIDE, THE TH2 RESPONSE AND 6274 05:40:07,360 --> 05:40:10,680 ANTIBODY IL4 RECEPTORS AND IL5, 6275 05:40:10,680 --> 05:40:14,840 MORE RECENTLY TSLP ARE START TO 6276 05:40:14,840 --> 05:40:17,040 GO TREAT THESE TH2 DISEASE AND 6277 05:40:17,040 --> 05:40:27,560 THE OVER ALL IMPACTS IS IT'S A 6278 05:40:28,120 --> 05:40:29,400 $1 BILLION A YEAR INDUSTRY SO A 6279 05:40:29,400 --> 05:40:33,440 LOT OF THAT CAN COME BACK TO YOU 6280 05:40:33,440 --> 05:40:35,040 AND THE TRAINEES YOU'VE TRAINED 6281 05:40:35,040 --> 05:40:36,720 OVER THE YEARS, I'LL STOP THERE. 6282 05:40:36,720 --> 05:40:36,960 THANK YOU. 6283 05:40:36,960 --> 05:40:47,200 [APPLAUSE] 6284 05:40:49,480 --> 05:40:50,720 >> WE'RE COMING TO THE END SO 6285 05:40:50,720 --> 05:40:56,240 I'M GOING TO TURN IT 6286 05:40:56,240 --> 05:40:57,280 >> THE SCIENTIFIC DIRECTOR OF 6287 05:40:57,280 --> 05:40:59,200 THE DIVISION OF INTRAMURAL 6288 05:40:59,200 --> 05:41:08,120 RESEARCH RIGHT HERE. 6289 05:41:08,120 --> 05:41:12,920 >> ALL RIGHT, ALLAN. 6290 05:41:12,920 --> 05:41:13,240 ALAN. 6291 05:41:13,240 --> 05:41:14,560 TOM, I WAS VERY HAPPY TO HEAR 6292 05:41:14,560 --> 05:41:18,720 YOU TALK ABOUT $100 BILLION 6293 05:41:18,720 --> 05:41:21,000 COMING BACK TO ALAN. 6294 05:41:21,000 --> 05:41:22,200 I WILL HAVE MY PEOPLE TALK TO 6295 05:41:22,200 --> 05:41:22,560 YOUR PEOPLE. 6296 05:41:22,560 --> 05:41:28,560 THANK YOU. 6297 05:41:28,560 --> 05:41:29,840 ALAN, HAVE YOU HAD A CHANCE TO 6298 05:41:29,840 --> 05:41:31,120 STAND UP AND LOOK AT EVERYBODY 6299 05:41:31,120 --> 05:41:32,200 HERE? 6300 05:41:32,200 --> 05:41:32,840 STAND UP. 6301 05:41:32,840 --> 05:41:33,600 JUST STAND UP. 6302 05:41:33,600 --> 05:41:35,560 TAKE A TURN AROUND. 6303 05:41:35,560 --> 05:41:38,840 THIS IS REALLY REMARKABLE. 6304 05:41:38,840 --> 05:41:49,000 [APPLAUSE] 6305 05:41:50,360 --> 05:41:52,280 I MET ALAN ABOUT 33 YEARS AGO IN 6306 05:41:52,280 --> 05:41:55,800 THE BASEMENT OF BUILDING 4, AND 6307 05:41:55,800 --> 05:41:57,080 I SAW THAT PIPETTE TIP. 6308 05:41:57,080 --> 05:42:00,120 I THINK IT WAS THE SAME ONE FOR 6309 05:42:00,120 --> 05:42:00,680 SEVERAL YEARS. 6310 05:42:00,680 --> 05:42:05,640 HE WAS AN ENERGETIC OMNIPRESENT 6311 05:42:05,640 --> 05:42:09,680 GUY, ABSOLUTELY NEVER AT REST. 6312 05:42:09,680 --> 05:42:11,320 THAT POISE THAT YOU CAUGHT 6313 05:42:11,320 --> 05:42:12,880 DANCING, IT HAD TO BE A FREEZE 6314 05:42:12,880 --> 05:42:13,840 FRAME BECAUSE IT DIDN'T HAPPEN 6315 05:42:13,840 --> 05:42:16,320 ANY OTHER TIME. 6316 05:42:16,320 --> 05:42:17,960 SO I HAD A CHANCE OVER THE YEARS 6317 05:42:17,960 --> 05:42:19,760 TO COLLABORATE WITH ALAN TO 6318 05:42:19,760 --> 05:42:23,000 LEARN A LOT FROM HIM, BOTH AS A 6319 05:42:23,000 --> 05:42:25,760 YOUNG PRE-TENURED TRACK, TENURED 6320 05:42:25,760 --> 05:42:28,240 TRACK, AND THEN A MORE USELESS 6321 05:42:28,240 --> 05:42:31,120 INVESTIGATOR. 6322 05:42:31,120 --> 05:42:33,280 AND ALAN HAS ALWAYS BEEN REALLY 6323 05:42:33,280 --> 05:42:34,840 EXTRAORDINARY IN TERMS OF THE 6324 05:42:34,840 --> 05:42:37,800 ABILITY TO GIVE ADVICE, TO GIVE 6325 05:42:37,800 --> 05:42:39,960 ENCOURAGEMENT, AND JUST TO GIVE 6326 05:42:39,960 --> 05:42:41,080 WISDOM. 6327 05:42:41,080 --> 05:42:42,840 ALAN IS A REALLY REMARKABLE GUY. 6328 05:42:42,840 --> 05:42:48,960 AND THIS MORNING, AS I WAS 6329 05:42:48,960 --> 05:42:51,480 THINKING ABOUT THIS, I HAD 6330 05:42:51,480 --> 05:42:52,480 REMEMBERED THAT ALAN HAD GIVEN 6331 05:42:52,480 --> 05:42:53,160 AN ORAL HISTORY. 6332 05:42:53,160 --> 05:42:56,520 I DON'T KNOW IF ANY OF YOU HAVE 6333 05:42:56,520 --> 05:42:57,960 READ HIS OR ANY OF THE ORAL 6334 05:42:57,960 --> 05:42:58,920 HISTORYS THAT HAVE BEEN DONE 6335 05:42:58,920 --> 05:43:00,600 HERE AT THE NIH FOR 6336 05:43:00,600 --> 05:43:00,920 INVESTIGATORS. 6337 05:43:00,920 --> 05:43:02,320 THEY'RE REALLY REMARKABLE. 6338 05:43:02,320 --> 05:43:03,840 AND ALAN'S HISTORY WAS 6339 05:43:03,840 --> 05:43:04,320 WONDERFUL. 6340 05:43:04,320 --> 05:43:05,800 I HAD A GREAT TIME READING THAT. 6341 05:43:05,800 --> 05:43:07,120 I WANTED TO SHARE A COUPLE OF 6342 05:43:07,120 --> 05:43:10,360 QUOTES FROM IT. 6343 05:43:10,360 --> 05:43:11,760 I'M NOT ORIGINAL ENOUGH TO COME 6344 05:43:11,760 --> 05:43:13,440 UP WITH MY OWN, AND THESE, I 6345 05:43:13,440 --> 05:43:15,480 PROMISE, ARE VERBATIM. 6346 05:43:15,480 --> 05:43:16,880 A GOOD LEADER FINDS OUT WHAT 6347 05:43:16,880 --> 05:43:19,880 PEOPLE ARE GOOD AT, AND THEN 6348 05:43:19,880 --> 05:43:22,600 LETS THEM DO THAT THING. 6349 05:43:22,600 --> 05:43:24,320 SEEMS PRETTY STRAIGHTFORWARD. 6350 05:43:24,320 --> 05:43:25,440 NOT MANY PEOPLE ARE ABLE TO DO 6351 05:43:25,440 --> 05:43:25,920 THAT. 6352 05:43:25,920 --> 05:43:27,760 I HEARD ABOUT THE HOT SEAT. 6353 05:43:27,760 --> 05:43:29,160 I READ ABOUT THAT TOO. 6354 05:43:29,160 --> 05:43:32,320 BUT IT IS THAT ABILITY TO TRY 6355 05:43:32,320 --> 05:43:34,400 AND FIGURE OUT, WELL, WHAT IS 6356 05:43:34,400 --> 05:43:35,200 SOMEBODY GOOD AT? 6357 05:43:35,200 --> 05:43:36,400 AND THEN MAKE SURE THAT THEY GET 6358 05:43:36,400 --> 05:43:37,600 A CHANCE TO DO THAT AND PROVIDE 6359 05:43:37,600 --> 05:43:43,240 THAT OPPORTUNITY. 6360 05:43:43,240 --> 05:43:47,080 AS PUN GWAS POINTING OUT, IT'S 6361 05:43:47,080 --> 05:43:48,520 SORT OF BEING CAUGHT IN A 6362 05:43:48,520 --> 05:43:49,720 SPIDER'S WEB BUT RATHER THAN 6363 05:43:49,720 --> 05:43:50,920 THAT SPIDER THAT SUCKS ALL THE 6364 05:43:50,920 --> 05:43:53,520 JUICE OUT, IT'S THE OPPOSITE. 6365 05:43:53,520 --> 05:43:54,960 YOU GET CAUGHT AND THEN HE'S 6366 05:43:54,960 --> 05:43:56,400 LIKE, HERE, COME ON, DO THIS, DO 6367 05:43:56,400 --> 05:43:57,920 THAT, WHAT ARE YOU DOING, DO 6368 05:43:57,920 --> 05:43:58,920 THIS, DO THIS. 6369 05:43:58,920 --> 05:44:03,720 ALAN IS A SPECIAL INVIGORATING 6370 05:44:03,720 --> 05:44:07,000 ENLIVENING SOURCE. 6371 05:44:07,000 --> 05:44:09,000 HE ALSO SAID AS YOU POINTED OUT, 6372 05:44:09,000 --> 05:44:10,200 MY PHILOSOPHY IS SIMPLE. 6373 05:44:10,200 --> 05:44:11,040 I'M A CHEERLEADER. 6374 05:44:11,040 --> 05:44:12,480 AND THERE'S NO QUESTION THAT 6375 05:44:12,480 --> 05:44:13,680 THAT IS -- YOU KNOW, THERE ARE A 6376 05:44:13,680 --> 05:44:15,640 LOT OF PEOPLE WHO ARE CHEER 6377 05:44:15,640 --> 05:44:15,960 LEERS. 6378 05:44:15,960 --> 05:44:17,480 THERE AREN'T A LOT OF PEOPLE WHO 6379 05:44:17,480 --> 05:44:21,240 ARE OUTSTANDING CHEER LEERS. 6380 05:44:21,240 --> 05:44:22,080 LEERED -- 6381 05:44:22,080 --> 05:44:22,640 CHEERLEADERS. 6382 05:44:22,640 --> 05:44:23,520 ALAN REALLY HAS BEEN THAT 6383 05:44:23,520 --> 05:44:24,720 THROUGHOUT THE 33 YEARS THAT 6384 05:44:24,720 --> 05:44:25,160 I'VE KNOWN HIM. 6385 05:44:25,160 --> 05:44:27,560 IN THE LAST FEW YEARS, WE AS AN 6386 05:44:27,560 --> 05:44:29,720 INSTITUTION HAVE BEEN ENORMOUSLY 6387 05:44:29,720 --> 05:44:33,560 BLESSED TO HAVE HIM LEADING THE 6388 05:44:33,560 --> 05:44:34,760 PROGRAM, HELPING TO TAKE YOUNG 6389 05:44:34,760 --> 05:44:36,320 PEOPLE AND PERVERT THEM TO OUR 6390 05:44:36,320 --> 05:44:38,280 WAY OF LIFE. 6391 05:44:38,280 --> 05:44:41,000 [LAUGHTER] 6392 05:44:41,000 --> 05:44:43,080 AND ALAN DIDN'T COME TO THIS BY 6393 05:44:43,080 --> 05:44:43,560 ACCIDENT. 6394 05:44:43,560 --> 05:44:44,600 AND ONE OF THE THINGS THAT YOU 6395 05:44:44,600 --> 05:44:47,360 ALSO LEARN IS THAT ALAN, AS YOU 6396 05:44:47,360 --> 05:44:52,520 ALL KNOW, HE'S BRAVE, HE'S 6397 05:44:52,520 --> 05:44:56,000 INDEPENDENT, ICONICLASTIC, WISE, 6398 05:44:56,000 --> 05:44:59,480 AND THAT WAS SHOWN WHEN HE LEFT 6399 05:44:59,480 --> 05:45:02,680 BASIC IMMUNOLOGY TO GO AFTER, 6400 05:45:02,680 --> 05:45:03,760 EWW, PARASITES. 6401 05:45:03,760 --> 05:45:05,400 TOM, I KNOW WHERE YOUR FOOT IS, 6402 05:45:05,400 --> 05:45:05,920 DON'T WORRY. 6403 05:45:05,920 --> 05:45:10,440 TO GO LOOK AT PARASITOLOGY, AND 6404 05:45:10,440 --> 05:45:11,960 THEN WHEN HE MADE THAT HORRIBLE, 6405 05:45:11,960 --> 05:45:13,040 HORRIBLE BLUNDER TO LEAVE 6406 05:45:13,040 --> 05:45:16,880 HARVARD AND COME HERE. 6407 05:45:16,880 --> 05:45:19,120 MY GOD, WHAT A BACKWATER, YOU 6408 05:45:19,120 --> 05:45:19,520 KNOW? 6409 05:45:19,520 --> 05:45:21,400 WHO GOES THERE EXCEPT TO DIE? 6410 05:45:21,400 --> 05:45:25,840 BUT ALAN KNEW THAT THIS WAS 6411 05:45:25,840 --> 05:45:27,480 SMART, HE KNEW IT WAS TIME TO GO 6412 05:45:27,480 --> 05:45:32,200 INTO SOMETHING NEW, LIKE 6413 05:45:32,200 --> 05:45:32,960 PARASITOLOGY. 6414 05:45:32,960 --> 05:45:34,600 THE IMPACT HE'S HAD ON THESE 6415 05:45:34,600 --> 05:45:36,360 FIELDS AND OUR LIFE AND WORLD IN 6416 05:45:36,360 --> 05:45:37,440 WHICH WE LIVE HAS BEEN 6417 05:45:37,440 --> 05:45:38,200 EXTRAORDINARY. 6418 05:45:38,200 --> 05:45:41,840 SO I JUST WANTED TO CONCLUDE BY 6419 05:45:41,840 --> 05:45:47,400 THANKING ALAN FOR COMMITTING 6420 05:45:47,400 --> 05:45:52,400 THIS EXPERIMENT IN LEAVING THE 6421 05:45:52,400 --> 05:45:55,040 BEATEN PATH AND IN COMING HERE 6422 05:45:55,040 --> 05:45:57,240 AND CARVING OUT NEW AREAS AND 6423 05:45:57,240 --> 05:45:59,080 NEW PARADIGMS, SHARING THEM WITH 6424 05:45:59,080 --> 05:46:01,080 US AND SHARING THEM WITH THE 6425 05:46:01,080 --> 05:46:01,520 WORLD. 6426 05:46:01,520 --> 05:46:03,600 YOU HAVE DONE AN EXTRAORDINARY 6427 05:46:03,600 --> 05:46:06,000 JOB, AND MADE US RICHER AND 6428 05:46:06,000 --> 05:46:07,440 BETTER FOR IT. 6429 05:46:07,440 --> 05:46:10,040 AND I JUST WANT TO EXTEND MY 6430 05:46:10,040 --> 05:46:11,480 PERSONAL AND PROFESSIONAL 6431 05:46:11,480 --> 05:46:13,880 GRATITUDE FOR YOUR SERVICE HERE. 6432 05:46:13,880 --> 05:46:14,760 THANK YOU. 6433 05:46:14,760 --> 05:46:24,960 [APPLAUSE] 6434 05:46:29,240 --> 05:46:31,560 >>SO WITH THIS, THIS CONCLUDES 6435 05:46:31,560 --> 05:46:34,280 THIS INCREDIBLE TWO-DAY 6436 05:46:34,280 --> 05:46:38,040 SYMPOSIUM IN ALAN'S HONOR. 6437 05:46:38,040 --> 05:46:40,560 ONE MORE CHEER FOR REALLY 6438 05:46:40,560 --> 05:46:41,320 PUTTING THIS TOGETHER. 6439 05:46:41,320 --> 05:46:44,160 [APPLAUSE] 6440 05:46:44,160 --> 05:46:48,000 IT WAS ABSOLUTELY -- IT COULD 6441 05:46:48,000 --> 05:46:49,320 NOT HAVE HAPPENED. 6442 05:46:49,320 --> 05:46:50,160 AND I KNOW THIS WON'T BE THE 6443 05:46:50,160 --> 05:46:53,880 LAST TIME WE'RE ALL TOGETHER. 6444 05:46:53,880 --> 05:46:55,640 SO ANYWAY, ENJOY THE REST OF THE 6445 05:46:55,640 --> 05:47:05,880 FESTIVITIES.