1 00:00:06,920 --> 00:00:07,280 >>WELCOME. 2 00:00:07,280 --> 00:00:10,680 I'M CATHERINE LAW, DIRECTOR OF 3 00:00:10,680 --> 00:00:13,120 COMMUNICATIONS AT THE NATIONAL 4 00:00:13,120 --> 00:00:13,680 CENTER FOR COMPLEMENTARY AND 5 00:00:13,680 --> 00:00:14,720 INTEGRATIVE HEALTH (OR 6 00:00:14,720 --> 00:00:18,800 N-C-C-I-H), AT THE NATIONAL 7 00:00:18,800 --> 00:00:19,680 INSTITUTES OF HEALTH. 8 00:00:19,680 --> 00:00:21,080 THANK YOU FOR JOINING US FOR 9 00:00:21,080 --> 00:00:22,720 EXPANDING TRANSLATIONALLY 10 00:00:22,720 --> 00:00:23,240 RELEVANT CHEMICAL SPACE: 11 00:00:23,240 --> 00:00:26,000 INSIGHTS INTO NATURAL PRODUCT 12 00:00:26,000 --> 00:00:27,720 RESOURCES, TECHNOLOGIES, AND 13 00:00:27,720 --> 00:00:29,520 MECHANISMS, THE FIRST OF A 14 00:00:29,520 --> 00:00:30,960 TWO-PART WEBINAR SERIES. 15 00:00:30,960 --> 00:00:33,040 FIRST, I WANT TO TAKE A FEW 16 00:00:33,040 --> 00:00:34,120 MOMENTS TO ACKNOWLEDGE THE MANY 17 00:00:34,120 --> 00:00:36,400 PEOPLE THAT BROUGHT THIS WEBINAR 18 00:00:36,400 --> 00:00:37,000 TO FRUITION, INCLUDING, FIRST 19 00:00:37,000 --> 00:00:38,400 AND FOREMOST, DR. EMMELINE 20 00:00:38,400 --> 00:00:40,400 EDWARDS, DIRECTOR OF OUR 21 00:00:40,400 --> 00:00:42,520 DIVISION OF EXTRAMURAL RESEARCH 22 00:00:42,520 --> 00:00:43,720 WHO CHAMPIONED THIS WEBINAR; DR. 23 00:00:43,720 --> 00:00:46,160 CRAIG HOPP, DEPUTY DIRECTOR OF 24 00:00:46,160 --> 00:00:50,960 OUR DIVISION OF EXTRAMURAL 25 00:00:50,960 --> 00:00:51,520 RESEARCH; DR. PATRICK STILL, 26 00:00:51,520 --> 00:00:53,120 PROGRAM DIRECTOR IN OUR BASIC 27 00:00:53,120 --> 00:00:54,720 AND MECHANISTIC RESEARCH BRANCH; 28 00:00:54,720 --> 00:00:55,320 AND DR. WEN CHEN, CHIEF OF OUR 29 00:00:55,320 --> 00:00:57,280 BASIC AND MECHANISTIC RESEARCH 30 00:00:57,280 --> 00:00:58,880 BRANCH, AS WELL AS MANY 31 00:00:58,880 --> 00:01:00,600 COLLEAGUES WHO PLANNED THE 32 00:01:00,600 --> 00:01:03,000 LOGISTICS AND PROMOTION OF THIS 33 00:01:03,000 --> 00:01:04,960 EVENT INCLUDING MS. IRENE LIU, 34 00:01:04,960 --> 00:01:06,360 MS. ANITA MCRAE-WILLIAMS, MS. 35 00:01:06,360 --> 00:01:08,040 SAHAR FAKHRUDDIN, MS. AILEEN 36 00:01:08,040 --> 00:01:08,680 AMADOR, AND MANY OTHERS WORKING 37 00:01:08,680 --> 00:01:12,880 BEHIND THE SCENES. 38 00:01:12,880 --> 00:01:21,880 BEFORE WE BEGIN, A FEW LOGISTICS 39 00:01:21,880 --> 00:01:22,600 FOR TODAY'S MEETING. 40 00:01:22,600 --> 00:01:23,240 FOR OUR NIH VIDEOCAST VIEWERS, 41 00:01:23,240 --> 00:01:24,480 YOU ARE WELCOME TO SUBMIT 42 00:01:24,480 --> 00:01:26,760 QUESTIONS AT ANY TIME USING THE 43 00:01:26,760 --> 00:01:28,400 VIDEOCAST FEEDBACK FORM; THE 44 00:01:28,400 --> 00:01:29,520 LINK FOR THE FORM SHOULD BE 45 00:01:29,520 --> 00:01:36,360 LOCATED BELOW YOUR SCREEN FOR 46 00:01:36,360 --> 00:01:36,880 VIEWING THE LIVESTREAM. 47 00:01:36,880 --> 00:01:40,400 WE WILL TRY TO GET TO AS MANY 48 00:01:40,400 --> 00:01:44,320 QUESTIONS AS POSSIBLE DURING 49 00:01:44,320 --> 00:01:44,880 QUESTION AND ANSWER PERIODS. 50 00:01:44,880 --> 00:01:47,800 WE'LL SHARE IT WITH OUR PLANNING 51 00:01:47,800 --> 00:01:49,160 TEAM. 52 00:01:49,160 --> 00:01:50,680 FINALLY, THIS EVENT IS BEING 53 00:01:50,680 --> 00:01:53,040 RECORDED AND WILL BE ARCHIVED ON 54 00:01:53,040 --> 00:01:53,840 THE NIH VIDEOCAST WEBSITE FOR 55 00:01:53,840 --> 00:01:56,840 FUTURE VIEWING. 56 00:01:56,840 --> 00:01:58,840 WITH THOSE REMINDERS COVERED, I 57 00:01:58,840 --> 00:02:04,400 AM NOW PLEASED TO INTRODUCE DR. 58 00:02:04,400 --> 00:02:06,240 DAVID SHURTLEFF, DEPUTY DIRECTOR 59 00:02:06,240 --> 00:02:08,160 OF NCCIH, WHO WILL SHARE A FEW 60 00:02:08,160 --> 00:02:10,640 WORDS OF WELCOME BEFORE HANDING 61 00:02:10,640 --> 00:02:13,560 THINGS OFF TO DR. PATRICK STILL. 62 00:02:13,560 --> 00:02:16,240 WHO WILL COVER WHAT WE'RE GOING 63 00:02:16,240 --> 00:02:19,200 TO GET INTO TODAY AND DR. DAVID 64 00:02:19,200 --> 00:02:21,640 SHURLEFF WILL HAND THINGS OFF TO 65 00:02:21,640 --> 00:02:21,960 DR. STILLS. 66 00:02:21,960 --> 00:02:23,200 SO DAVID, PLEASE TAKE IT AWAY. 67 00:02:23,200 --> 00:02:24,080 >>THANK YOU, CATHERINE AND 68 00:02:24,080 --> 00:02:27,280 THANK YOU FOR BEING HERE AND 69 00:02:27,280 --> 00:02:30,120 WELCOME TO OUR -- PARTICIPANTS 70 00:02:30,120 --> 00:02:32,120 HERE IN ZOOM AND ON THE 71 00:02:32,120 --> 00:02:32,400 VIDEOCAST. 72 00:02:32,400 --> 00:02:35,320 IT'S AN EXCITING TIME TO BE IN 73 00:02:35,320 --> 00:02:35,720 NATURAL PRODUCTS. 74 00:02:35,720 --> 00:02:40,760 AN AREA WHICH WE HAVE FOSTERED 75 00:02:40,760 --> 00:02:41,320 SINCE THE BEGINNING. 76 00:02:41,320 --> 00:02:42,920 WE SUPPORTED NATURAL PRODUCTS 77 00:02:42,920 --> 00:02:45,680 FOR OUR ENTIRE HISTORY NOW OVER 78 00:02:45,680 --> 00:02:47,600 20 YEARS IN SUPPORTING RESEARCH 79 00:02:47,600 --> 00:02:49,520 ACROSS THE CONTINUUM FROM IN 80 00:02:49,520 --> 00:02:55,680 VITRO, IN-VIVO, CLINICAL TRIALS 81 00:02:55,680 --> 00:02:57,920 RESEARCH AND ENGAGED WITH OUR 82 00:02:57,920 --> 00:03:00,320 COLLEAGUES ACROSS THE NIH IN 83 00:03:00,320 --> 00:03:01,680 AREAS OF SHARED INTEREST, FOR 84 00:03:01,680 --> 00:03:04,640 EXAMPLE, OUR INTEREST IN 85 00:03:04,640 --> 00:03:05,360 CANNABINOID RESEARCH, NATURAL 86 00:03:05,360 --> 00:03:11,320 PRODUCTS AND PAIN, NUTRITION FOR 87 00:03:11,320 --> 00:03:13,640 PREDICTION HEALTH, A STUDY WE 88 00:03:13,640 --> 00:03:16,320 HOPE TO LAUNCH HERE AT NIH, AND 89 00:03:16,320 --> 00:03:23,920 THE LIST GOES ON AND ON. 90 00:03:23,920 --> 00:03:26,120 TO QUOTE WAYNE GRETZKY, WHEN HE 91 00:03:26,120 --> 00:03:28,600 WAS ASKED ABOUT HIS SUCCESS, HE 92 00:03:28,600 --> 00:03:29,720 WOULD SAY, HE SKATES TO WHERE 93 00:03:29,720 --> 00:03:30,920 THE PUCK IS GOING TO BE AND NOT 94 00:03:30,920 --> 00:03:32,720 WHERE IT HAS BEEN. 95 00:03:32,720 --> 00:03:36,680 AND I FAKE THAT AS -- TAKE THAT 96 00:03:36,680 --> 00:03:39,560 AS THIS SEMINAR IS SKATING TO 97 00:03:39,560 --> 00:03:41,720 WHERE THE PUCK WILL BE HERE AT 98 00:03:41,720 --> 00:03:43,520 NCCIH AND AT THE NIH AT LARGE. 99 00:03:43,520 --> 00:03:44,320 WE WANT TO KNOW AND SUPPORT 100 00:03:44,320 --> 00:03:46,320 WHERE THE NATURAL PRODUCTS 101 00:03:46,320 --> 00:03:47,200 RESEARCH IS GOING AND HOW IT CAN 102 00:03:47,200 --> 00:03:50,560 BEST CAPITALIZE ON CUTTING-EDGE 103 00:03:50,560 --> 00:03:52,920 TECHNOLOGIES AND METHODOLOGIES. 104 00:03:52,920 --> 00:03:55,240 AND I'M VERY EXCITED TO SAY AND 105 00:03:55,240 --> 00:03:58,840 TO HEAR FROM AND LOOK FORWARD TO 106 00:03:58,840 --> 00:04:00,400 THIS SYMPOSIUM FROM OUR ESTEEMED 107 00:04:00,400 --> 00:04:02,640 EXPERTS TODAY WHO WILL HIGHLIGHT 108 00:04:02,640 --> 00:04:04,400 SOME OF THE RESOURCES CURRENTLY 109 00:04:04,400 --> 00:04:05,800 IN DEVELOPMENT, THE CUTTING-EDGE 110 00:04:05,800 --> 00:04:07,840 APPROACHES THAT CAN REALLY SERVE 111 00:04:07,840 --> 00:04:09,680 THE BROADER NATURAL PRODUCTS 112 00:04:09,680 --> 00:04:10,280 RESEARCH COMMUNITIES. 113 00:04:10,280 --> 00:04:12,360 I'M VERY GRATEFUL FOR THIS 114 00:04:12,360 --> 00:04:13,520 SEMINAR AND LOOK FORWARD TO THE 115 00:04:13,520 --> 00:04:14,160 MANY TALKS TODAY. 116 00:04:14,160 --> 00:04:16,160 AND WITH THAT, I'LL TURN IT OVER 117 00:04:16,160 --> 00:04:19,920 TO PATRICK FOR A FEW WORDS. 118 00:04:19,920 --> 00:04:23,960 PATRICK? 119 00:04:23,960 --> 00:04:24,680 >>THANK YOU VERY MUCH, AND GOOD 120 00:04:24,680 --> 00:04:24,960 AFTERNOON. 121 00:04:24,960 --> 00:04:26,120 I'M PATRICK STILL, A PROGRAM 122 00:04:26,120 --> 00:04:28,800 DIRECTOR AT NCCIH IN THE BASIC 123 00:04:28,800 --> 00:04:31,760 AND MECHANISTIC RESEARCH BRANCH. 124 00:04:31,760 --> 00:04:34,400 A MANAGE A PORTFOLIO THAT SPANS 125 00:04:34,400 --> 00:04:42,040 THE NCCIH PRIORITIES IN 126 00:04:42,040 --> 00:04:42,640 TRANSLATIONAL AND 127 00:04:42,640 --> 00:04:46,240 CLINICAL APPLICATIONS OF NATURAL 128 00:04:46,240 --> 00:04:46,920 PRODUCTS. 129 00:04:46,920 --> 00:04:48,400 I WOULD LIKE TO WELCOME EVERYONE 130 00:04:48,400 --> 00:04:49,000 TO THIS FIRST OF TWO EXCITING 131 00:04:49,000 --> 00:04:50,960 WEBINARS! 132 00:04:50,960 --> 00:04:52,920 TO PARAPHRASE A PASSAGE FROM 133 00:04:52,920 --> 00:04:53,960 DRS. NEWMAN AND CRAGG'S 134 00:04:53,960 --> 00:04:54,760 COMPREHENSIVE REVIEWS ON 135 00:04:54,760 --> 00:04:56,160 "NATURAL PRODUCTS AS SOURCES OF 136 00:04:56,160 --> 00:04:58,560 NEW DRUGS," THAT MANY OF YOU ARE 137 00:04:58,560 --> 00:05:03,400 FAMILIAR WITH, [QUOTE] "THAT 138 00:05:03,400 --> 00:05:04,000 NATURE IN ONE GUISE OR ANOTHER 139 00:05:04,000 --> 00:05:04,600 HAS CONTINUED TO INFLUENCE THE 140 00:05:04,600 --> 00:05:06,680 DESIGN OF FDA APPROVED DRUGS, 141 00:05:06,680 --> 00:05:08,640 MANY OF WHICH ARE BASED ON 142 00:05:08,640 --> 00:05:10,560 NATURAL PRODUCT SCAFFOLDS, 143 00:05:10,560 --> 00:05:15,840 REALLY SETS THE TONE FOR THE 144 00:05:15,840 --> 00:05:16,320 TOPIC OF THIS WEBINAR." 145 00:05:16,320 --> 00:05:18,480 ADVANCES IN AUTOMATED SYNTHETIC 146 00:05:18,480 --> 00:05:19,080 CHEMISTRY, HIGH- THROUGHPUT 147 00:05:19,080 --> 00:05:20,080 BIOLOGY, ARTIFICIAL INTELLIGENCE 148 00:05:20,080 --> 00:05:24,440 TECHNOLOGIES, AND INCREASING 149 00:05:24,440 --> 00:05:24,960 ACCESS TO SEQUENCE DATA TO 150 00:05:24,960 --> 00:05:26,600 ASSESS WITH VARIOUS 151 00:05:26,600 --> 00:05:28,760 BIOINFORMATIC TOOLS, THE 152 00:05:28,760 --> 00:05:30,560 BIOSYNTHETIC POTENTIAL OF A 153 00:05:30,560 --> 00:05:32,360 SOURCE ORGANISM FOR TARGETED 154 00:05:32,360 --> 00:05:33,200 DISCOVERY OF NEW NATURAL 155 00:05:33,200 --> 00:05:35,040 PRODUCTS, IS INDEED EXPANDING 156 00:05:35,040 --> 00:05:35,920 TRANSLATIONALLY RELEVANT 157 00:05:35,920 --> 00:05:41,840 CHEMICAL SPACE. 158 00:05:41,840 --> 00:05:44,240 THIS TWO-PART WEBINAR WILL START 159 00:05:44,240 --> 00:05:44,720 TODAY WITH FOUNDATIONAL 160 00:05:44,720 --> 00:05:48,400 RESOURCES AND TECHNOLOGIES THAT 161 00:05:48,400 --> 00:05:50,360 ENABLE DISCOVERY OF NATURAL 162 00:05:50,360 --> 00:05:52,680 PRODUCTS. 163 00:05:52,680 --> 00:05:54,720 AND IN PART 2, PICK UP WITH 164 00:05:54,720 --> 00:05:57,720 ADDITIONAL TECHNOLOGIES SPECIFIC 165 00:05:57,720 --> 00:05:59,520 TO STRUCTURE ELUCIDATION AND 166 00:05:59,520 --> 00:06:02,840 APPLICATIONS OF THOSE 167 00:06:02,840 --> 00:06:05,000 TECHNOLOGIES. 168 00:06:05,000 --> 00:06:05,560 DURING EACH WEBINAR, WE'RE 169 00:06:05,560 --> 00:06:06,480 JOINED BY NIH PARTNERS WHO WILL 170 00:06:06,480 --> 00:06:08,120 SHARE THEIR PERSPECTIVES ON 171 00:06:08,120 --> 00:06:08,880 WEBINAR THEMES AND NATURAL 172 00:06:08,880 --> 00:06:11,120 PRODUCTS RESEARCH IN THE CONTEXT 173 00:06:11,120 --> 00:06:11,680 OF THEIR INSTITUTE OR CENTER 174 00:06:11,680 --> 00:06:15,280 PRIORITIES. 175 00:06:15,280 --> 00:06:15,880 I WOULD NOW LIKE TO INTRODUCE 176 00:06:15,880 --> 00:06:18,040 OUR THREE SPEAKERS FOR TODAY'S 177 00:06:18,040 --> 00:06:19,240 WEBINAR, WHO WILL GIVE THEIR 178 00:06:19,240 --> 00:06:22,560 PRESENTATIONS FOLLOWED BY Q&A 179 00:06:22,560 --> 00:06:23,440 SESSION. 180 00:06:23,440 --> 00:06:25,400 FIRST IS DR. BARRY O'KEEFE, 181 00:06:25,400 --> 00:06:27,200 CHIEF, NATURAL PRODUCTS BRANCH, 182 00:06:27,200 --> 00:06:29,240 DIVISION OF CANCER TREATMENT AND 183 00:06:29,240 --> 00:06:31,120 DIAGNOSIS AT THE NATIONAL CANCER 184 00:06:31,120 --> 00:06:32,640 INSTITUTE, WHO WILL DISCUSS 185 00:06:32,640 --> 00:06:34,960 DISCOVERY AND DEVELOPMENT OF 186 00:06:34,960 --> 00:06:38,560 NATURAL PRODUCTS AND THE NCI 187 00:06:38,560 --> 00:06:39,760 NATURAL PRODUCT COLLECTION; 188 00:06:39,760 --> 00:06:41,480 FOLLOWING DR. O'KEEFE'S TALK 189 00:06:41,480 --> 00:06:43,480 WILL BE DR. ROGER LININGTON, 190 00:06:43,480 --> 00:06:44,720 PROFESSOR AND CANADA RESEARCH 191 00:06:44,720 --> 00:06:46,160 CHAIR IN HIGH-THROUGHPUT 192 00:06:46,160 --> 00:06:48,840 SCREENING AND NATURAL PRODUCTS 193 00:06:48,840 --> 00:06:50,040 DISCOVERY AT SIMON FRASER 194 00:06:50,040 --> 00:06:51,240 UNIVERSITY WHO WILL PRESENT ON 195 00:06:51,240 --> 00:06:52,880 HIGH-THROUGHPUT FUNCTIONAL 196 00:06:52,880 --> 00:06:58,040 ANNOTATION OF NATURAL PRODUCTS 197 00:06:58,040 --> 00:06:58,560 USING INTEGRATED ACTIVITY 198 00:06:58,560 --> 00:06:59,080 PROFILING; WHICH WILL BE 199 00:06:59,080 --> 00:07:01,320 FOLLOWED BY OUR THIRD SPEAKER, 200 00:07:01,320 --> 00:07:02,960 DR. MANDË HOLFORD, ASSOCIATE 201 00:07:02,960 --> 00:07:04,920 PROFESSOR IN DEPARTMENT OF 202 00:07:04,920 --> 00:07:07,160 CHEMISTRY AND BIOCHEMISTRY AT 203 00:07:07,160 --> 00:07:08,960 THE CITY UNIVERSITY OF NEW YORK 204 00:07:08,960 --> 00:07:10,120 AND RESEARCH ASSOCIATE AT THE 205 00:07:10,120 --> 00:07:12,360 SACKLER INSTITUTE FOR 206 00:07:12,360 --> 00:07:15,600 COMPARATIVE GENOMICS, AMERICAN 207 00:07:15,600 --> 00:07:16,680 MUSEUM OF NATURAL HISTORY, WHO 208 00:07:16,680 --> 00:07:19,240 WILL FOCUS ON DEVELOPING MODELS 209 00:07:19,240 --> 00:07:20,320 FOR CHARACTERIZING VENOM-BASED 210 00:07:20,320 --> 00:07:23,680 MARINE NATURAL PRODUCTS. 211 00:07:23,680 --> 00:07:26,000 WITH THIS, I'D LIKE TO WELCOME 212 00:07:26,000 --> 00:07:26,640 OUR SPEAKERS AND THANK EVERYONE 213 00:07:26,640 --> 00:07:29,840 IN THE AUDIENCE FOR JOINING THIS 214 00:07:29,840 --> 00:07:32,400 WEBINAR TODAY, AND I WILL TURN 215 00:07:32,400 --> 00:07:33,040 THINGS OVER TO DR. BARRY O'KEEFE 216 00:07:33,040 --> 00:07:37,640 FOR HIS PRESENTATION. 217 00:07:37,640 --> 00:07:40,120 >>THANK YOU, PATRICK AND THANK 218 00:07:40,120 --> 00:07:41,560 EVERYBODY FOR THIS REALLY 219 00:07:41,560 --> 00:07:42,920 OUTSTANDING MENU. 220 00:07:42,920 --> 00:07:46,000 I THINK THIS IS A GREAT IDEA, 221 00:07:46,000 --> 00:07:47,480 EXPANDING TRANSLATIONAL AND 222 00:07:47,480 --> 00:07:49,800 CHEMICAL SPACE, A FANTASTIC 223 00:07:49,800 --> 00:07:50,360 THEME FOR EVERYTHING. 224 00:07:50,360 --> 00:07:53,400 LET ME SHARE MY SLIDES AND I 225 00:07:53,400 --> 00:07:58,480 WILL START THINGS OFF. 226 00:07:58,480 --> 00:08:00,440 HOPEFULLY YOU CAN SEE THESE NOW. 227 00:08:00,440 --> 00:08:03,280 SO TODAY I WOULD LIKE TO TALK A 228 00:08:03,280 --> 00:08:04,640 LITTLE BIT ABOUT WHAT WE'RE 229 00:08:04,640 --> 00:08:06,520 DOING AT THE NATIONAL CANCER 230 00:08:06,520 --> 00:08:07,040 INSTITUTE IN THE NATURAL 231 00:08:07,040 --> 00:08:08,440 PRODUCTS BRANCH TO TRY AND 232 00:08:08,440 --> 00:08:10,720 EXPAND CHEMICALLY-RELEVANT 233 00:08:10,720 --> 00:08:13,080 NATURAL PRODUCT SPACE FOR 234 00:08:13,080 --> 00:08:13,320 EVERYONE. 235 00:08:13,320 --> 00:08:15,840 A LITTLE BACKGROUND. 236 00:08:15,840 --> 00:08:16,920 THESE ARE COMPOUNDS THAT ARE 237 00:08:16,920 --> 00:08:19,240 PROBABLY USED EVERY DAY IN 238 00:08:19,240 --> 00:08:21,800 THOUSANDS AND THOUSANDS OF 239 00:08:21,800 --> 00:08:22,600 PLACES AROUND THE WORLD. 240 00:08:22,600 --> 00:08:23,720 AND MANY OF YOU PROBABLY USED 241 00:08:23,720 --> 00:08:26,200 MANY OF THESE OVER THE YEARS. 242 00:08:26,200 --> 00:08:29,640 BUT NOT AS MANY PEOPLE OUT IN 243 00:08:29,640 --> 00:08:30,240 THE BIDE WORLD KNOW THAT THESE 244 00:08:30,240 --> 00:08:32,440 ARE THE SOURCE ORGANISMS FOR ALL 245 00:08:32,440 --> 00:08:33,000 THESE AGENTS. 246 00:08:33,000 --> 00:08:36,440 AND THAT THERE IS A HISTORY OF 247 00:08:36,440 --> 00:08:38,480 PHARMACEUTICAL UTILITY FOR 248 00:08:38,480 --> 00:08:42,520 NATURAL PRODUCTS. 249 00:08:42,520 --> 00:08:43,400 AND IT AFFECTS US EVERY DAY AND 250 00:08:43,400 --> 00:08:45,320 THERE IS STILL A LOT MORE THAT 251 00:08:45,320 --> 00:08:47,360 CAN BE DONE. 252 00:08:47,360 --> 00:08:52,720 SO FOR EXAMPLE, I BELIEVE MY 253 00:08:52,720 --> 00:08:54,320 PREDECESSORS, DOCTORS NEW MAN 254 00:08:54,320 --> 00:08:55,280 AND CRAIG, HAVE REPORTED A 255 00:08:55,280 --> 00:08:58,560 VARIETY OF STATISTICS FOR THE 256 00:08:58,560 --> 00:08:59,200 PERCENT OF NEW SMALL MOLECULE 257 00:08:59,200 --> 00:09:02,680 DRUGS FROM NATURAL PRODUCT 258 00:09:02,680 --> 00:09:03,000 SCAFFOLDER. 259 00:09:03,000 --> 00:09:05,240 IN PARTICULAR I USE MORE 260 00:09:05,240 --> 00:09:06,920 CONSERVATIVE ANALYSIS OF THEIRS, 261 00:09:06,920 --> 00:09:08,520 BUT IT IS SAFE TO SAY THAT AT 262 00:09:08,520 --> 00:09:11,600 LEAST 25% OF ALL NEW SMALL 263 00:09:11,600 --> 00:09:13,480 MOLECULE DRUGS APPROVED BY THE 264 00:09:13,480 --> 00:09:16,600 FDA ARE BASED ON NATURAL PRODUCT 265 00:09:16,600 --> 00:09:16,880 SCAFFOLDS. 266 00:09:16,880 --> 00:09:18,400 WHICH IS THE SIGNIFICANT PART OF 267 00:09:18,400 --> 00:09:21,400 THE DRUGS WE USE EVERY DAY. 268 00:09:21,400 --> 00:09:24,160 BUT AT THE NCI WHEN WE TOOK A 269 00:09:24,160 --> 00:09:25,960 LOOK AT IT INTERNALLY WITH 270 00:09:25,960 --> 00:09:26,760 ANOTHER REVIEW THAT WAS 271 00:09:26,760 --> 00:09:29,280 PUBLISHED BY MY COLLEAGUE, BRICE 272 00:09:29,280 --> 00:09:31,520 WILSON, NATURAL PRODUCTS REPORT 273 00:09:31,520 --> 00:09:34,200 IN 2020, IF WE LOOK AT THE 274 00:09:34,200 --> 00:09:36,600 NUMBER OF PAPERS THAT ARE IN 275 00:09:36,600 --> 00:09:38,600 PUBMED BASED ON HIGH-THROUGHPUT 276 00:09:38,600 --> 00:09:40,680 SCREENS, THE MAJOR WAY A LOT OF 277 00:09:40,680 --> 00:09:41,720 DRUGS ARE STILL DISCOVERED 278 00:09:41,720 --> 00:09:44,960 TODAY, WE SEE THESE IN GEE 279 00:09:44,960 --> 00:09:47,480 METRIC PROGRESSION HERE IN 280 00:09:47,480 --> 00:09:50,240 PAPERS COMING OUT AND TOPS OFF 281 00:09:50,240 --> 00:09:52,800 HERE SOMEWHERE AROUND IN THE 282 00:09:52,800 --> 00:09:53,320 2010s. 283 00:09:53,320 --> 00:09:54,760 BUT WHAT WE SEE WITH NATURAL 284 00:09:54,760 --> 00:09:56,000 PRODUCTS, THE NUMBER OF THOSE 285 00:09:56,000 --> 00:09:58,160 SHOWN IN BLUE, VERY SMALL 286 00:09:58,160 --> 00:09:59,400 PERCENT OF ALL THE 287 00:09:59,400 --> 00:10:01,680 HIGH-THROUGHPUT SCREENS ACTUALLY 288 00:10:01,680 --> 00:10:04,800 INCLUDE NATURAL PRODUCT SAMPLES. 289 00:10:04,800 --> 00:10:05,360 NOW THIS MAKES US NATURAL 290 00:10:05,360 --> 00:10:06,880 PRODUCT REACHERS FEEL GOOD 291 00:10:06,880 --> 00:10:09,240 BECAUSE IF YOU'RE GETTING 25% OF 292 00:10:09,240 --> 00:10:10,680 DRUGS FROM WHAT LOOKS TO BE ONE 293 00:10:10,680 --> 00:10:13,920 OR 2% OF THE SCREENS, THAT'S A 294 00:10:13,920 --> 00:10:15,280 PRETTY GOOD RETURN ON 295 00:10:15,280 --> 00:10:15,560 INVESTMENT. 296 00:10:15,560 --> 00:10:17,480 BUT FROM THE NCI'S PERSPECTIVE, 297 00:10:17,480 --> 00:10:20,720 WHAT IF WE COULD INCREASE THIS 298 00:10:20,720 --> 00:10:21,960 PERCENT? 299 00:10:21,960 --> 00:10:23,000 WHAT DO WE NEED TO DO TO GET 300 00:10:23,000 --> 00:10:24,720 MORE PEOPLE SCREENING, INCLUDING 301 00:10:24,720 --> 00:10:26,120 NATURAL PRODUCT SAMPLES IN THOSE 302 00:10:26,120 --> 00:10:28,440 SCREENS SO WE CAN IMPROVE ON 303 00:10:28,440 --> 00:10:31,000 THAT 25%? 304 00:10:31,000 --> 00:10:33,360 AND SO, THERE IS SOME REASONS 305 00:10:33,360 --> 00:10:34,880 WHY PEOPLE HAVEN'T INCLUDED 306 00:10:34,880 --> 00:10:35,400 THESE IN SCREENS. 307 00:10:35,400 --> 00:10:40,680 FOR EXAMPLE, THIS IS AN IMAGE OF 308 00:10:40,680 --> 00:10:41,040 CRUDE EXTRACTS. 309 00:10:41,040 --> 00:10:42,000 THEY POTENTIALLY COULD BE VERY 310 00:10:42,000 --> 00:10:44,160 DIFFICULT TO SCREEN IN THEIR 311 00:10:44,160 --> 00:10:44,440 CRUDE FORM. 312 00:10:44,440 --> 00:10:46,720 THEY CONTAIN NUMEROUS COMPOUNDS 313 00:10:46,720 --> 00:10:47,880 AT DIFFERENT CONCENTRATIONS. 314 00:10:47,880 --> 00:10:51,080 THE PURIFICATION AND STRUCTURAL 315 00:10:51,080 --> 00:10:51,960 ELUCIDATION OF THE ACTIVE 316 00:10:51,960 --> 00:10:53,360 MOLECULES FROM THESE CAN TAKE A 317 00:10:53,360 --> 00:10:55,800 LONG TIME AND DIDN'T REALLY MESH 318 00:10:55,800 --> 00:10:56,320 WELL WITH HIGH-THROUGHPUT 319 00:10:56,320 --> 00:10:58,120 SCREENING WHERE PEOPLE ARE DOING 320 00:10:58,120 --> 00:10:59,480 HUNDREDS OF THOUSANDS OF SAMPLES 321 00:10:59,480 --> 00:11:01,960 A DAY IN SOME CASES. 322 00:11:01,960 --> 00:11:04,760 AND SO OVERALL, THIS RESULTED IN 323 00:11:04,760 --> 00:11:05,440 A SLOW PROCESS THAT INCREASED 324 00:11:05,440 --> 00:11:08,520 THE OVERALL COST NOT JUST FOR 325 00:11:08,520 --> 00:11:09,840 CHEMISTRY, BUT FOR THE 326 00:11:09,840 --> 00:11:10,480 HIGH-THROUGHPUT SCREENING 327 00:11:10,480 --> 00:11:12,400 ITSELF, KEEPING THE CELLS ALIVE, 328 00:11:12,400 --> 00:11:16,280 KEEPING THE ASSAYS RUNNING FOR 329 00:11:16,280 --> 00:11:16,800 LONGER PERIODS OF TIME. 330 00:11:16,800 --> 00:11:18,120 AND SO, WE FELT THE NEED TO 331 00:11:18,120 --> 00:11:20,800 ADDRESS THESE CHALLENGES TO 332 00:11:20,800 --> 00:11:24,000 EFFICIENTLY ACCESS THIS UNIQUE 333 00:11:24,000 --> 00:11:24,560 CHEMICAL DIVERSITY IN THESE 334 00:11:24,560 --> 00:11:24,840 EXTRACTS. 335 00:11:24,840 --> 00:11:26,600 AND YOU MIGHT WONDER WHY DOES 336 00:11:26,600 --> 00:11:28,160 THE NCI CARE ABOUT THIS? 337 00:11:28,160 --> 00:11:30,120 WE HAVE A RATHER LARGE 338 00:11:30,120 --> 00:11:33,560 REPOSITORY OF NATURAL PRODUCT 339 00:11:33,560 --> 00:11:34,200 CRUDE EXTRACTS THAT NUMBER OVER 340 00:11:34,200 --> 00:11:35,960 200,000. 341 00:11:35,960 --> 00:11:36,560 WHAT YOU'RE SEEING HERE IS THE 342 00:11:36,560 --> 00:11:38,760 BREAKDOWN ON THE RIGHT-HAND SIDE 343 00:11:38,760 --> 00:11:42,600 OF PLANTS, MARINE ORGANISMS AND 344 00:11:42,600 --> 00:11:46,280 MICROBIAL SOURCES THAT WERE IN 345 00:11:46,280 --> 00:11:47,000 THIS REPOSITORY, AND ON THE 346 00:11:47,000 --> 00:11:48,880 LEFT, YOU SEE A MAP OF WHERE 347 00:11:48,880 --> 00:11:50,120 THESE HAVE BEEN COLLECTED AROUND 348 00:11:50,120 --> 00:11:51,920 THE WORLD. 349 00:11:51,920 --> 00:11:54,640 THE SIZES OF THE HEXAGON ARE 350 00:11:54,640 --> 00:11:55,480 INDICATIVE OF THE SIZE OF THE 351 00:11:55,480 --> 00:11:57,360 COLLECTION IN THOSE AREAS AND 352 00:11:57,360 --> 00:11:59,120 THE COLORS ARE INDICATIVE OF 353 00:11:59,120 --> 00:12:00,400 WHETHER THEY ARE PLANTS IN 354 00:12:00,400 --> 00:12:03,000 GREEN, MARINE ORGANISMS IN BLUE 355 00:12:03,000 --> 00:12:07,400 OR IN MICROBIAL COLLECTIONS IN 356 00:12:07,400 --> 00:12:07,640 BROWN. 357 00:12:07,640 --> 00:12:09,320 SO WE HAVE A BIG COLLECTION OF 358 00:12:09,320 --> 00:12:12,080 NATURAL PRODUCT EXTRACTS AT THE 359 00:12:12,080 --> 00:12:13,600 NCI ABOUT YOU NOBODY WANTED TO 360 00:12:13,600 --> 00:12:14,040 SCREEN THEM. 361 00:12:14,040 --> 00:12:16,400 SO, WHAT ARE WE GOING TO DO? 362 00:12:16,400 --> 00:12:18,440 WE WERE ABLE TO CONVINCE TWO 363 00:12:18,440 --> 00:12:20,000 DIFFERENT DIVISIONS OF THE NCI, 364 00:12:20,000 --> 00:12:22,480 DIVISION OF CANCER TREATMENT AND 365 00:12:22,480 --> 00:12:24,160 DIAGNOSIS AND THE CENTER FOR 366 00:12:24,160 --> 00:12:24,800 CANCER RESEARCH, TO WORK 367 00:12:24,800 --> 00:12:26,280 TOGETHER AND SET UP THE NCI 368 00:12:26,280 --> 00:12:28,080 PROGRAM FOR NATURAL PRODUCT 369 00:12:28,080 --> 00:12:32,200 DISCOVERY WHICH IS DESIGNED TO 370 00:12:32,200 --> 00:12:32,680 FACILITATE INTRAPURE AND 371 00:12:32,680 --> 00:12:33,920 EXTRAMURAL RESEARCH AND ADDRESS 372 00:12:33,920 --> 00:12:36,440 CURRENT CHALLENGES IN NATURAL 373 00:12:36,440 --> 00:12:37,360 PRODUCT DISCOVERY. 374 00:12:37,360 --> 00:12:39,200 THIS HAS BEEN FUNDED BY THE 375 00:12:39,200 --> 00:12:40,520 CANCER MOONSHOT PROGRAM. 376 00:12:40,520 --> 00:12:43,120 THESE ARE THE SPECIFIC AIMS OF 377 00:12:43,120 --> 00:12:43,520 THAT PROGRAM. 378 00:12:43,520 --> 00:12:45,480 WE NEEDED TO CREATE NEW 379 00:12:45,480 --> 00:12:48,920 TECHNOLOGIES, TO CREATE A PRE 380 00:12:48,920 --> 00:12:50,120 FRACTIONATEY LIBRARY MORE 381 00:12:50,120 --> 00:12:52,720 AMENABLE TO HIGH-THROUGHPUT 382 00:12:52,720 --> 00:12:54,560 SCREENING. 383 00:12:54,560 --> 00:12:56,360 INCREASE SCREENING FOR CULTURAL 384 00:12:56,360 --> 00:12:56,720 MICROORGANISMS. 385 00:12:56,720 --> 00:12:58,760 PROVIDE THAT LIBRARY TOW 386 00:12:58,760 --> 00:13:00,320 SCREENING CENTERS WORLDWIDE AND 387 00:13:00,320 --> 00:13:00,720 THEN ENCOURAGE THE 388 00:13:00,720 --> 00:13:03,120 HIGH-THROUGHPUT SCREENING, 389 00:13:03,120 --> 00:13:04,440 SUPPORT THOSE RESEARCHERS, 390 00:13:04,440 --> 00:13:05,160 PROVIDE FASTER ANALYTICAL 391 00:13:05,160 --> 00:13:07,320 RESOURCES AND THEN PULL 392 00:13:07,320 --> 00:13:07,920 EVERYTHING TOGETHER AS MUCH AS 393 00:13:07,920 --> 00:13:11,320 POSSIBLE IN A DATABASE AND MAKE 394 00:13:11,320 --> 00:13:13,360 AS MUCH OF THAT AS PUBLIC AS IT 395 00:13:13,360 --> 00:13:17,520 IS JUST A VIABLE AND ACCEPTABLE 396 00:13:17,520 --> 00:13:18,360 TO OUR COLLABORATORS WHO ALLOWED 397 00:13:18,360 --> 00:13:19,040 THESE COLLECTIONS TO TAKE PLACE 398 00:13:19,040 --> 00:13:19,920 IN THEIR HOST COUNTRIES. 399 00:13:19,920 --> 00:13:22,800 SO, THE FIRST ISSUE WAS TO PRE 400 00:13:22,800 --> 00:13:23,320 FRACTIONATE THE LIBRARY. 401 00:13:23,320 --> 00:13:24,600 THE GOAL IS EVENTUALLY TO CREATE 402 00:13:24,600 --> 00:13:27,480 A LIBRARY OF OVER A MILLION 403 00:13:27,480 --> 00:13:28,800 SEMI--PURE NATURAL PRODUCT 404 00:13:28,800 --> 00:13:29,040 FRACTIONS. 405 00:13:29,040 --> 00:13:30,640 AND TO SUPPLY THIS TO 406 00:13:30,640 --> 00:13:32,960 RESEARCHERS FOR FREE FOR 407 00:13:32,960 --> 00:13:34,440 SCREENING AGAINST ALL DISEASE 408 00:13:34,440 --> 00:13:37,160 TARGETS, NOT JUST CANCER. 409 00:13:37,160 --> 00:13:40,200 THIS REQUIRED A LOT OF METHOD 410 00:13:40,200 --> 00:13:40,480 DEVELOPMENT. 411 00:13:40,480 --> 00:13:43,160 WE ENDED UP PURIFYING THESE 412 00:13:43,160 --> 00:13:44,400 COMPOUNDS BASED ON PO LATERY. 413 00:13:44,400 --> 00:13:47,800 WE NEEDED TO OPTIMIZE FOR MASK, 414 00:13:47,800 --> 00:13:48,920 COMPOUND SEPARATION, BIOLOGICAL 415 00:13:48,920 --> 00:13:49,160 ACTIVITY. 416 00:13:49,160 --> 00:13:51,560 WE HAD TO BE ABLE TO PRODUCE IF 417 00:13:51,560 --> 00:13:54,600 ABOUT 150,000 FRACTIONS PER YEAR 418 00:13:54,600 --> 00:13:55,160 AND TO DO SO WITH SUFFICIENT 419 00:13:55,160 --> 00:13:57,880 MASS TO SUPPORT AT LEAST 20 420 00:13:57,880 --> 00:13:59,200 SCREENING PROGRAMS A YEAR FOR A 421 00:13:59,200 --> 00:13:59,440 DECADE. 422 00:13:59,440 --> 00:14:01,280 AND THEN WE HAD TO HAVE 423 00:14:01,280 --> 00:14:03,040 AUTOMATED ACCESS TO THESE 424 00:14:03,040 --> 00:14:04,800 FRACTIONS ONCE THEY WERE 425 00:14:04,800 --> 00:14:05,440 PRODUCED. 426 00:14:05,440 --> 00:14:06,480 SO THERE WAS A LOT OF EFFORT 427 00:14:06,480 --> 00:14:07,360 THAT WENT INTO THIS. 428 00:14:07,360 --> 00:14:08,600 I'M NOT GOING TO GO INTO ALL 429 00:14:08,600 --> 00:14:12,240 THIS DETAIL AND THIS HAS ALL 430 00:14:12,240 --> 00:14:13,040 BEEN AUTOMATED NOW. 431 00:14:13,040 --> 00:14:15,520 WE WORKED WITH A LOT OF 432 00:14:15,520 --> 00:14:16,600 DIFFERENT VENDORS FOR EQUIPMENT 433 00:14:16,600 --> 00:14:18,800 TO BE ABLE TO PRE FRACTIONATE 434 00:14:18,800 --> 00:14:21,560 EXTRACTS IN A HIGH-THROUGHPUT 435 00:14:21,560 --> 00:14:21,760 MANNER. 436 00:14:21,760 --> 00:14:23,840 THIS DATA JUST SHOWS A LITTLE 437 00:14:23,840 --> 00:14:27,120 BIT OF THE REPRODUCIBILITY OF 438 00:14:27,120 --> 00:14:28,640 THAT PROCESS. 439 00:14:28,640 --> 00:14:31,640 THIS IS A GRAPH THAT SHOWS MASS 440 00:14:31,640 --> 00:14:33,880 OF 88 EXTRACTS FRACTIONATED INTO 441 00:14:33,880 --> 00:14:35,840 7 FRACTIONS EACH RESULTING IN 442 00:14:35,840 --> 00:14:38,240 OVER 600 INDIVIDUAL FRACTIONS 443 00:14:38,240 --> 00:14:39,440 AND THIS JUST SHOWS THAT IF WE 444 00:14:39,440 --> 00:14:42,400 RAN THE SAME EXACT DATA, THE 445 00:14:42,400 --> 00:14:43,840 SAME PROCESS MONTHS LATER THAT 446 00:14:43,840 --> 00:14:45,840 THE MASSES IN EACH FRACTION WERE 447 00:14:45,840 --> 00:14:47,320 HIGHLY REPRODUCIBLE. 448 00:14:47,320 --> 00:14:50,680 SO THE CHEMISTRY, WE BELIEVE, IN 449 00:14:50,680 --> 00:14:52,280 EACH FRACTION IS HIGHLY 450 00:14:52,280 --> 00:14:52,720 REPRODUCIBLE. 451 00:14:52,720 --> 00:14:54,040 DOWN BELOW YOU'RE SEEING THE 452 00:14:54,040 --> 00:14:54,840 SAME THING. 453 00:14:54,840 --> 00:14:57,440 THIS TIME WE ARE USING ACTIVITY 454 00:14:57,440 --> 00:15:00,800 ANALYSIS AND LOOKING AT THE MEAN 455 00:15:00,800 --> 00:15:01,960 GI50 AND AGAIN, YOU SEE THINGS 456 00:15:01,960 --> 00:15:05,000 ARE GENERALLY HIGHLY 457 00:15:05,000 --> 00:15:05,640 REPRODUCIBLE, A LITTLE BIT MORE 458 00:15:05,640 --> 00:15:07,720 PLAY WITH AN ACTIVITY ASSAY AND 459 00:15:07,720 --> 00:15:12,160 THE MEAN POINT OF A SIGMOID. 460 00:15:12,160 --> 00:15:13,320 BUT STILL, VERY GOOD DATA 461 00:15:13,320 --> 00:15:13,560 OVERALL. 462 00:15:13,560 --> 00:15:15,640 TO GET TO THE POINT OF HOW MANY 463 00:15:15,640 --> 00:15:17,440 COMPOUNDS ARE IN EACH FRACTION, 464 00:15:17,440 --> 00:15:19,320 WE USED A VARIETY OF WAYS TO 465 00:15:19,320 --> 00:15:22,320 ANALYZE THEM. 466 00:15:22,320 --> 00:15:22,960 ELSD, MASS SPEC, AND IN GENERAL, 467 00:15:22,960 --> 00:15:25,920 WE GO WITH THE TOTAL MASS SPEC 468 00:15:25,920 --> 00:15:28,360 AS THE NUMBER OF POTENTIAL 469 00:15:28,360 --> 00:15:28,920 COMPOUNDS IN EACH INDIVIDUAL 470 00:15:28,920 --> 00:15:33,080 FRACTION AND SO YOU CAN SEE HERE 471 00:15:33,080 --> 00:15:35,400 BY FRACTION 1, 2, 3, 4, 5, 6, 7, 472 00:15:35,400 --> 00:15:36,960 HOW MANY COMPOUNDS MIGHT BE IN 473 00:15:36,960 --> 00:15:37,160 EACH. 474 00:15:37,160 --> 00:15:41,240 ON AVERAGE 20-25 COMPOUNDS PER 475 00:15:41,240 --> 00:15:41,520 FRACTION. 476 00:15:41,520 --> 00:15:44,040 SO, WHERE ARE WE NOW ON THIS 477 00:15:44,040 --> 00:15:44,440 PROCESS? 478 00:15:44,440 --> 00:15:50,320 WE HAVE MADE ABOUT 580 THOUSAND. 479 00:15:50,320 --> 00:15:54,480 YOU CAN SEE THIS AUTOMATED 480 00:15:54,480 --> 00:15:56,160 FRACTIONATION TAKING PLACE. 481 00:15:56,160 --> 00:15:57,760 WE HAVE RELEASED OVER A HALF 482 00:15:57,760 --> 00:15:58,520 MILLION TO THE PUBLIC. 483 00:15:58,520 --> 00:16:01,960 WE PLATED OUT 25 MILLION WELLS 484 00:16:01,960 --> 00:16:03,000 OF THESE. 485 00:16:03,000 --> 00:16:04,920 THEY ARE STORED, READY TO SHIP. 486 00:16:04,920 --> 00:16:06,320 WE HAVE SHIPPED ABOUT 5 MILLION 487 00:16:06,320 --> 00:16:06,960 OF THESE SO FAR. 488 00:16:06,960 --> 00:16:08,520 INCLUDING ABOUT TWO MILLION JUST 489 00:16:08,520 --> 00:16:10,160 LAST YEAR. 490 00:16:10,160 --> 00:16:12,080 WE HAVE INITIAL PUBLICATIONS IF 491 00:16:12,080 --> 00:16:13,000 PEOPLE ARE INTERESTED IN HOW 492 00:16:13,000 --> 00:16:16,120 THIS LIBRARY WAS CREATED. 493 00:16:16,120 --> 00:16:19,040 AND THE METHODS AND THE CHEMICAL 494 00:16:19,040 --> 00:16:20,880 BIOLOGY BACK IN 2018, AND AS USE 495 00:16:20,880 --> 00:16:23,240 FOR SCREENING, HOW TO DAP ASSAYS 496 00:16:23,240 --> 00:16:24,640 FOR NATURAL PRODUCT SCREENING, 497 00:16:24,640 --> 00:16:26,880 WE PUBLISHED IN 2020 IN NATURAL 498 00:16:26,880 --> 00:16:27,720 PRODUCT REPORTS. 499 00:16:27,720 --> 00:16:31,480 WE HAVE SEEN A LOT OF OTHER 500 00:16:31,480 --> 00:16:33,080 GROUPS ADAPT AND ADOPT THESE 501 00:16:33,080 --> 00:16:35,560 METHODS FOR THEIR OWN USES, BOTH 502 00:16:35,560 --> 00:16:38,400 IN THE UNITED STATES AND AROUND 503 00:16:38,400 --> 00:16:40,800 THE WORLD, SOUTH AFRICA AND 504 00:16:40,800 --> 00:16:41,760 BRAZIL, SWEDEN, AS WELL AS 505 00:16:41,760 --> 00:16:42,320 SEVERAL STATES IN THE UNITED 506 00:16:42,320 --> 00:16:42,560 STATES. 507 00:16:42,560 --> 00:16:45,600 AND FINALLY THIS IS A SHOUT OUT 508 00:16:45,600 --> 00:16:45,880 TO MANDY. 509 00:16:45,880 --> 00:16:48,200 WE ARE THIS YEAR, WORKING ON A 510 00:16:48,200 --> 00:16:51,880 NEW MARINE ACHUOUS, PRE 511 00:16:51,880 --> 00:16:52,320 FRACTIONATED LIBRARY 512 00:16:52,320 --> 00:16:54,480 PARTICULARLY RICH IN 513 00:16:54,480 --> 00:16:55,080 BIOTHERAPEUTICS, SMALL PEPTIDES 514 00:16:55,080 --> 00:16:57,960 AND PROTEINS FOUND IN THESE 515 00:16:57,960 --> 00:16:58,600 MARINE INVERTEBRATES THAT ARE 516 00:16:58,600 --> 00:17:01,800 THE BASIS OF THE NCI CRUDE 517 00:17:01,800 --> 00:17:02,200 FRACTION LIBRARY. 518 00:17:02,200 --> 00:17:04,280 WE HOPE TO MAKE THOSE AVAILABLE 519 00:17:04,280 --> 00:17:06,600 NEXT YEAR MAYBE A LIBRARY OF UP 520 00:17:06,600 --> 00:17:08,720 TO 100,000 FRACTIONS 521 00:17:08,720 --> 00:17:10,320 SPECIFICALLY ENHANCED FOR 522 00:17:10,320 --> 00:17:11,640 POTENTIAL PROTEINS AND PEPTIDES 523 00:17:11,640 --> 00:17:14,600 AND BIOTHERAPEUTICS. 524 00:17:14,600 --> 00:17:16,800 WE ALSO SAID THAT WE WOULD WORK 525 00:17:16,800 --> 00:17:18,240 ON CONSULTERABLE ORGANISMS. 526 00:17:18,240 --> 00:17:19,280 WE SET UP A PARTNERSHIP WITH THE 527 00:17:19,280 --> 00:17:21,720 UNIVERSITY OF OKLAHOMA, CITIZEN 528 00:17:21,720 --> 00:17:25,040 SCIENCE PROGRAM AND WHO HELPED 529 00:17:25,040 --> 00:17:27,200 US IN WORKING WITH US TO COLLECT 530 00:17:27,200 --> 00:17:30,400 A VARIETY OF SOIL FURNY FROM 531 00:17:30,400 --> 00:17:32,760 AROUND THE U.S. AND -- FUNGI -- 532 00:17:32,760 --> 00:17:35,520 AND HE PROVIDED 4000 A YEAR TO 533 00:17:35,520 --> 00:17:36,600 THE NCI. 534 00:17:36,600 --> 00:17:38,520 WHAT YOU SEE IS A MAP OF THE 535 00:17:38,520 --> 00:17:40,040 UNITED STATES SHOWING WHERE 536 00:17:40,040 --> 00:17:41,320 THOSE COLLECTIONS TOOK PLACE ALL 537 00:17:41,320 --> 00:17:43,560 OVER THE COUNTRY. 538 00:17:43,560 --> 00:17:45,320 WE SET UP A NEW FIRM ENITATION 539 00:17:45,320 --> 00:17:46,560 FACILITY AND NEW METHODS HERE AT 540 00:17:46,560 --> 00:17:48,400 THE NCI IN FREDRICK. 541 00:17:48,400 --> 00:17:52,520 YOU CAN SEE A TAXINOMIC 542 00:17:52,520 --> 00:17:56,200 BREAKDOWN OF SOME OF THE SOIL 543 00:17:56,200 --> 00:17:56,640 FUNGI INCLUDED IN THIS 544 00:17:56,640 --> 00:17:58,240 COLLECTION AND WE ARE GETTING 545 00:17:58,240 --> 00:18:00,440 READY TO SUBMIT A PAPER SOON ON 546 00:18:00,440 --> 00:18:01,480 SOME OF THE PILOT WORK THAT WE 547 00:18:01,480 --> 00:18:02,680 HAVE DONE ON THIS. 548 00:18:02,680 --> 00:18:04,400 JUST TO GIVE YOU A LITTLE TASTE, 549 00:18:04,400 --> 00:18:06,600 THIS IS SOME OF THE COMPOUNDS 550 00:18:06,600 --> 00:18:07,920 THAT WERE ISOLATED IN A RANDOM 551 00:18:07,920 --> 00:18:10,080 SELECTION OF A VARIETY OF THESE 552 00:18:10,080 --> 00:18:11,120 SOIL FUNGI FROM AROUND THE 553 00:18:11,120 --> 00:18:11,480 UNITED STATES. 554 00:18:11,480 --> 00:18:13,720 AND WE ARE SEEING A SIGNIFICANT 555 00:18:13,720 --> 00:18:15,560 AMOUNT OF CHEMICAL DIVERSITY IN 556 00:18:15,560 --> 00:18:15,800 THESE. 557 00:18:15,800 --> 00:18:19,120 WE PLAN TO NOT ONLY MAKE 558 00:18:19,120 --> 00:18:20,080 FRACTIONS AVAILABLE FROM THESE 559 00:18:20,080 --> 00:18:23,880 SOURCE ORGANISMS BUT ALSO THE 560 00:18:23,880 --> 00:18:25,880 SOURCE ORGANISMS THEMSELVES 561 00:18:25,880 --> 00:18:27,000 COULD BE AVAILABLE TO 562 00:18:27,000 --> 00:18:27,840 RESEARCHERS AROUND THE WORLD TO 563 00:18:27,840 --> 00:18:30,440 ENABLE RESEARCH WE COULDN'T EACH 564 00:18:30,440 --> 00:18:32,400 CONCEIVE OF AT THE NCI TO DO 565 00:18:32,400 --> 00:18:32,840 WITH THEM. 566 00:18:32,840 --> 00:18:34,920 SO WE HAVE HAD A PRETTY GOOD 567 00:18:34,920 --> 00:18:36,520 UPTAKE IN PEOPLE INTERESTED IN 568 00:18:36,520 --> 00:18:39,480 GETTING THE FRACTION LIBRARY. 569 00:18:39,480 --> 00:18:40,080 THIS SHOWS WHO HAS REQUESTED 570 00:18:40,080 --> 00:18:42,120 THESE AND COMPLETED MTAs. 571 00:18:42,120 --> 00:18:44,160 WE HAVE COMPLETED ABOUT ONE MTA 572 00:18:44,160 --> 00:18:46,800 A MONTH TO GET THESE LIBRARIES 573 00:18:46,800 --> 00:18:48,800 IN THEIR HANDS. 574 00:18:48,800 --> 00:18:51,400 IF YOUR UNIVERSITY OR RESEARCH 575 00:18:51,400 --> 00:18:53,200 ORGANIZATION ISN'T ON THIS LIST, 576 00:18:53,200 --> 00:18:53,560 CONTACT US. 577 00:18:53,560 --> 00:18:56,400 WE'D LOVE TO BE ABLE TO SEND YOU 578 00:18:56,400 --> 00:18:57,000 SAMPLES AND HAVE YOU SCREEN 579 00:18:57,000 --> 00:18:57,200 THEM. 580 00:18:57,200 --> 00:18:57,880 I'M GOING TO GO ON A LITTLE BIT 581 00:18:57,880 --> 00:19:00,840 MORE DETAIL ON SOME OF OUR U.S. 582 00:19:00,840 --> 00:19:04,640 GOVERNMENT PARTNERS. 583 00:19:04,640 --> 00:19:06,800 NCCIH IN PARTICULAR IS BOTH 584 00:19:06,800 --> 00:19:08,200 ISSUED A GRANT FOR GLOBAL 585 00:19:08,200 --> 00:19:10,600 NATURAL PRODUCT DATABASE, HUGELY 586 00:19:10,600 --> 00:19:12,760 IMPORTANT OVERALL BUT ALSO 587 00:19:12,760 --> 00:19:16,400 FUNDING NPNPD HEAL INITIATIVE OR 588 00:19:16,400 --> 00:19:21,840 HELPING END ADDICTION LONG TERM, 589 00:19:21,840 --> 00:19:22,640 INITIATIVE EFFORTS AND IGNITE 590 00:19:22,640 --> 00:19:23,040 SCREENING GRANTS. 591 00:19:23,040 --> 00:19:23,600 AND I'LL SAY A LITTLE BIT OF 592 00:19:23,600 --> 00:19:24,320 THOSE AT THE END HERE AS WE HAVE 593 00:19:24,320 --> 00:19:25,640 JUST AN EXAMPLE. 594 00:19:25,640 --> 00:19:30,400 WE ALSO SEE PARTNERSHIPS WITH 595 00:19:30,400 --> 00:19:31,160 NIAID THE DEPARTMENT OF DEFENSE, 596 00:19:31,160 --> 00:19:35,000 NCATS AND NOAA, THE NCI, 597 00:19:35,000 --> 00:19:36,000 DIVISION OF CANCER CHEMO 598 00:19:36,000 --> 00:19:37,280 PREVENTION RECENTLY INITIATED A 599 00:19:37,280 --> 00:19:37,760 GRANT PROGRAM. 600 00:19:37,760 --> 00:19:40,440 I THINK IT WILL BE UP AND GOING 601 00:19:40,440 --> 00:19:41,880 THIS COMING FISCAL YEAR TO 602 00:19:41,880 --> 00:19:42,920 ENCOURAGE ASSAY DEVELOPMENT 603 00:19:42,920 --> 00:19:44,520 SCREENING OF NATURAL PRODUCT 604 00:19:44,520 --> 00:19:47,280 SAMPLES AGAINST CHEMO PREVENTION 605 00:19:47,280 --> 00:19:47,840 TARGETS. 606 00:19:47,840 --> 00:19:48,960 AND JUST LAST WEEK I WAS 607 00:19:48,960 --> 00:19:50,880 CONTACTED BY THE NATIONAL 608 00:19:50,880 --> 00:19:52,320 INSTITUTE OF AGING. 609 00:19:52,320 --> 00:19:53,640 PERHAPS WE'LL HAVE ANOTHER 610 00:19:53,640 --> 00:19:54,760 PERSON TO ADD ON THIS WILLS AND 611 00:19:54,760 --> 00:19:55,760 I'LL HAVE TO DECREASE THE SIZE 612 00:19:55,760 --> 00:19:58,640 OF THE FONT AT THAT THE POINT. 613 00:19:58,640 --> 00:19:59,720 SO, IF ALL OF THESE PEOPLE ARE 614 00:19:59,720 --> 00:20:02,000 GOING TO GET THESE SAMPLES, ONE 615 00:20:02,000 --> 00:20:04,440 OF THE ISSUES IS HOW TO GET TO 616 00:20:04,440 --> 00:20:06,760 THE STRUCTURAL ELUCIDATION OF A 617 00:20:06,760 --> 00:20:09,760 ACTIVE COMPOUND FROM A PRE 618 00:20:09,760 --> 00:20:10,280 FRACTIONATED SAMPLE. 619 00:20:10,280 --> 00:20:13,120 SO WE SET UP A HIGHLY AUTOMATED 620 00:20:13,120 --> 00:20:15,920 SECOND STAGE PURIFICATION SYSTEM 621 00:20:15,920 --> 00:20:17,480 WHERE SOMEONE COULD SEND US A 622 00:20:17,480 --> 00:20:20,720 HIT LIST OF 500,000 AND WITHIN 623 00:20:20,720 --> 00:20:22,720 TWO WEEKS WE WOULD FRACTIONATE 624 00:20:22,720 --> 00:20:24,760 ALL 500 OF THOSE ACTIVE 625 00:20:24,760 --> 00:20:26,400 FRACTIONS INTO 22 SUB FRACTIONS 626 00:20:26,400 --> 00:20:29,280 AND PROVIDE THEM APPROXIMATELY 627 00:20:29,280 --> 00:20:31,480 11,000 FRACTIONS BACK WITHIN TWO 628 00:20:31,480 --> 00:20:32,400 WEEKS FOR THEM TO SCREEN. 629 00:20:32,400 --> 00:20:34,440 THAT WAY THEIR ASSAY IS UP AND 630 00:20:34,440 --> 00:20:34,680 RUNNING. 631 00:20:34,680 --> 00:20:36,240 THE EFFICIENCY IS MUCH BETTER 632 00:20:36,240 --> 00:20:39,200 OVERALL IN THEIR LABORATORY AND 633 00:20:39,200 --> 00:20:39,600 OURS. 634 00:20:39,600 --> 00:20:40,840 SO THIS AT THIS POINT IS WHERE 635 00:20:40,840 --> 00:20:46,120 WE COLLECT NMR, MASS SPEC AND IR 636 00:20:46,120 --> 00:20:46,640 DATA. 637 00:20:46,640 --> 00:20:47,200 IT GENERATION CHEMICAL 638 00:20:47,200 --> 00:20:48,840 INFORMATION ON THE IDENTITY OF 639 00:20:48,840 --> 00:20:49,960 THESE COMPOUNDS AND REDUCES THE 640 00:20:49,960 --> 00:20:50,920 COST TO SCREENING AND 641 00:20:50,920 --> 00:20:53,680 IMPORTANTLY, WE ARE DOING THIS 642 00:20:53,680 --> 00:20:55,800 WITH ONLY ONE MILLIGRAM OF A 643 00:20:55,800 --> 00:20:57,320 FRACTION DERIVED FROM 250 644 00:20:57,320 --> 00:20:58,640 FRACTIONS OF A CRUDE EXTRACT. 645 00:20:58,640 --> 00:21:02,160 WE ARE CONSERVING THE EXTRACTS 646 00:21:02,160 --> 00:21:04,840 THEMSELVES WHICH IS VITALLY 647 00:21:04,840 --> 00:21:05,120 IMPORTANT. 648 00:21:05,120 --> 00:21:06,960 SO FAR, WE HAVE DONE PROBABLY 649 00:21:06,960 --> 00:21:10,280 65,000 OF THESE WITH RESEARCH 650 00:21:10,280 --> 00:21:10,520 GROUPS. 651 00:21:10,520 --> 00:21:11,760 THIS IS JUST A PIE CHART SHOWING 652 00:21:11,760 --> 00:21:13,800 A VARIETIY OF ASSAYS AND GROUPS 653 00:21:13,800 --> 00:21:15,480 WE WORKED WITH AND HOW MANY 654 00:21:15,480 --> 00:21:17,560 SAMPLES WE SCREENED AND WORKED 655 00:21:17,560 --> 00:21:19,120 THROUGH PROCESS FOR SECOND STAGE 656 00:21:19,120 --> 00:21:20,440 PURIFICATION. 657 00:21:20,440 --> 00:21:23,680 IMPORTANTLY, ACROSS ALL OF THESE 658 00:21:23,680 --> 00:21:24,720 ASSAYS AND MORE AT THIS POINT, 659 00:21:24,720 --> 00:21:27,080 AFTER THIS STAGE OF 660 00:21:27,080 --> 00:21:28,160 PURIFICATION, 22 SUBFRACTIONS, 661 00:21:28,160 --> 00:21:31,600 ABOUT 70% OF ACTIVE COMPOUND 662 00:21:31,600 --> 00:21:32,560 CLASSES CAN BE DETERMINED 663 00:21:32,560 --> 00:21:35,480 WITHOUT ANY FURTHER 664 00:21:35,480 --> 00:21:35,800 PURIFICATION. 665 00:21:35,800 --> 00:21:37,160 SO SOMEONE SENDS US A HIT LIST 666 00:21:37,160 --> 00:21:39,880 OF 500 THINGS, WE CAN LIKELY 667 00:21:39,880 --> 00:21:40,960 IDENTIFY WHAT IS RESPONSIBLE FOR 668 00:21:40,960 --> 00:21:43,680 THE ACTIVITY AND ABOUT 300, 325 669 00:21:43,680 --> 00:21:47,600 OF THOSE WITHOUT ANY FURTHER 670 00:21:47,600 --> 00:21:47,960 PURIFICATION. 671 00:21:47,960 --> 00:21:49,640 AND SO OVERALL, WE HAVE SET UP 672 00:21:49,640 --> 00:21:51,160 METHODS AND AGAIN IN 673 00:21:51,160 --> 00:21:52,360 HIGH-THROUGHPUT MANNER SO THIS 674 00:21:52,360 --> 00:21:53,840 REQUIRES SIGNIFICANTLY LESS 675 00:21:53,840 --> 00:21:54,560 CHEMIST TIME. 676 00:21:54,560 --> 00:21:56,720 MOST OF THESE PROJECTS CAN BE 677 00:21:56,720 --> 00:21:58,760 DONE WITH A COUPLE OF POCKETS. 678 00:21:58,760 --> 00:22:00,800 AND FINALLY, AND IMPORTANTLY, 679 00:22:00,800 --> 00:22:02,480 ABOUT 80% OF THE TIME WHEN WE 680 00:22:02,480 --> 00:22:05,880 SEE AN ACTIVE FRACTION, WE DO 681 00:22:05,880 --> 00:22:06,720 NOT SEE THE CRUDE EXTRACT 682 00:22:06,720 --> 00:22:10,400 TESTING ACTIVE IN THE SAME ASSAY 683 00:22:10,400 --> 00:22:10,920 TESTED IN THE SAME 684 00:22:10,920 --> 00:22:11,240 CONCENTRATION. 685 00:22:11,240 --> 00:22:12,560 WE PLAYED OUT THE SAMPLE WITH 686 00:22:12,560 --> 00:22:14,520 THE FRACTION SO PEOPLE CAN TEST 687 00:22:14,520 --> 00:22:15,720 IT SIMULTANEOUSLY AND THE 688 00:22:15,720 --> 00:22:17,800 MAJORITY OF THE TIME, 4-5 TIMES, 689 00:22:17,800 --> 00:22:20,600 WHEN WE SEE ACTIVITY IN A 690 00:22:20,600 --> 00:22:21,200 FRACTION, THAT CRUDE EXTRACT 691 00:22:21,200 --> 00:22:22,600 WOULD NOT HAVE BEEN SEEN AS 692 00:22:22,600 --> 00:22:23,680 ACTIVE INDICATING WE ARE FINDING 693 00:22:23,680 --> 00:22:25,840 A LOT OF NEW CHEMICAL DIVERSITY 694 00:22:25,840 --> 00:22:29,080 THAT MIGHT HAVE BEEN HIDDEN 695 00:22:29,080 --> 00:22:30,000 BEFORE. 696 00:22:30,000 --> 00:22:30,960 AGAIN, THE METHODS AND HOW WE DO 697 00:22:30,960 --> 00:22:35,840 THIS IS ALL PUBLISHED BACK IN 698 00:22:35,840 --> 00:22:36,120 2020. 699 00:22:36,120 --> 00:22:39,960 IT WAS PUBLISHED IN ACS CHEMICAL 700 00:22:39,960 --> 00:22:40,200 BIOLOGY. 701 00:22:40,200 --> 00:22:40,840 TO GET AN IDEA, ARE WE GETTING 702 00:22:40,840 --> 00:22:43,960 TO MOLECULES THAT CAN TRANSLATE 703 00:22:43,960 --> 00:22:44,120 TOO? 704 00:22:44,120 --> 00:22:46,240 THAT'S PART OF WHAT THIS SEMINAR 705 00:22:46,240 --> 00:22:47,320 IS ABOUT TODAY. 706 00:22:47,320 --> 00:22:48,400 AND WHAT WE DID IS TOOK A LOOK 707 00:22:48,400 --> 00:22:50,080 AT THE COMPOUNDS THAT CAME 708 00:22:50,080 --> 00:22:53,320 THROUGH A PILOT PROGRAM OR 709 00:22:53,320 --> 00:22:55,040 COMPOUNDS IN RED AND COMPARING 710 00:22:55,040 --> 00:22:57,280 THEM TO APPROVED NATURAL PRODUCT 711 00:22:57,280 --> 00:23:00,080 DRUGS FROM 19 EIGHTY ONE-2010. 712 00:23:00,080 --> 00:23:05,800 YOU CAN SEE HERE IF WE'RE LOOK 713 00:23:05,800 --> 00:23:06,360 AGO - 1981 -- LOOKING AT A 714 00:23:06,360 --> 00:23:07,480 VARIETY OF PARAMETERS ON 715 00:23:07,480 --> 00:23:08,000 COMPOUNDS. 716 00:23:08,000 --> 00:23:10,720 THIS IS PRINCIPLE COMPONENT 717 00:23:10,720 --> 00:23:12,120 ANALYSIS, THE THREE TOP 718 00:23:12,120 --> 00:23:14,360 PRINCIPLE COMPONENTS RESPONSIBLE 719 00:23:14,360 --> 00:23:15,920 FOR ABOUT 75% OF THE 720 00:23:15,920 --> 00:23:17,360 DIFFERENTIAL OF THESE COMPOUNDS 721 00:23:17,360 --> 00:23:18,760 AND THESE ARE BASICALLY SO YOU 722 00:23:18,760 --> 00:23:23,200 KNOW, MOLECULAR WEIGHT, AND SP3 723 00:23:23,200 --> 00:23:23,440 CAR BOBS. 724 00:23:23,440 --> 00:23:26,240 YOU CAN SEE HERE A VERY GOOD 725 00:23:26,240 --> 00:23:27,680 OVERLAP OF THE NPNPD COMPOUNDS 726 00:23:27,680 --> 00:23:28,920 WITH THE DRUGS THAT HAVE BEEN 727 00:23:28,920 --> 00:23:30,000 APPROVED INDICATING WE ARE 728 00:23:30,000 --> 00:23:34,240 GETTING TO MOLECULES THAT ARE 729 00:23:34,240 --> 00:23:34,560 TRANSLATABLE. 730 00:23:34,560 --> 00:23:36,120 FINALLY, WE ALSO HAVE DATA 731 00:23:36,120 --> 00:23:38,320 SYSTEMS TO HANDLE ALL OF THIS. 732 00:23:38,320 --> 00:23:40,200 IT'S SECURE AND WEB ACCESSIBLE. 733 00:23:40,200 --> 00:23:41,800 WE CAN TRACK ALL OF OUR 734 00:23:41,800 --> 00:23:42,320 PROJECTS. 735 00:23:42,320 --> 00:23:45,520 WE MONITOR FRACTION PRODUCTION, 736 00:23:45,520 --> 00:23:47,240 384 WELL PLATE PRODUCTION. 737 00:23:47,240 --> 00:23:55,080 WE HAVE INDIVIDUAL COLLABORA 738 00:23:55,080 --> 00:23:55,600 COLLABORATORS, MONITOR OUR 739 00:23:55,600 --> 00:23:56,160 INTERACTIONS WITH OUR 740 00:23:56,160 --> 00:23:58,360 COLLABORATORS TO TRACK PROGRESS 741 00:23:58,360 --> 00:23:59,840 AND MAKE SURE WE ARE NOT BEING 742 00:23:59,840 --> 00:24:01,440 SLOW ON ANYTHING FROM EVERYTHING 743 00:24:01,440 --> 00:24:04,240 THEY GET. 744 00:24:04,240 --> 00:24:04,840 WE CAN ALSO VISUALIZE AND HAVE 745 00:24:04,840 --> 00:24:05,320 DATA ON THE GEOGRAPHIC 746 00:24:05,320 --> 00:24:05,640 INFORMATION. 747 00:24:05,640 --> 00:24:07,640 WE HAVE ANNOTATION ON ALL OF 748 00:24:07,640 --> 00:24:08,360 THESE SAMPLES BACK TO THE 749 00:24:08,360 --> 00:24:12,440 PHOTOGRAPH AS SHOWN HERE OF THE 750 00:24:12,440 --> 00:24:15,920 SOURCE ORGANISM, GPS COORDINATES 751 00:24:15,920 --> 00:24:16,840 AND KEEP TRACK OF ALL THE 752 00:24:16,840 --> 00:24:18,520 CHEMISTRY BEING GENERATE FRIDAY 753 00:24:18,520 --> 00:24:19,000 THIS TOO. 754 00:24:19,000 --> 00:24:21,360 AS PEOPLE COME BACK TO US WITH 755 00:24:21,360 --> 00:24:22,440 HIT LISTS AND WE DO THIS AGAIN, 756 00:24:22,440 --> 00:24:25,960 THIS BUILDS A VIRTUAL CYCLE 757 00:24:25,960 --> 00:24:26,560 WHEREBY PREVIOUS RESEARCH DONE 758 00:24:26,560 --> 00:24:28,000 ON THIS HELPS TO INCREASE THE 759 00:24:28,000 --> 00:24:29,760 EFFICIENCY OF FUTURE RESEARCHERS 760 00:24:29,760 --> 00:24:32,400 USING THESE CHEMICAL LIBRARIES. 761 00:24:32,400 --> 00:24:35,200 SO FINALLY I WANT TO JUST TALK 762 00:24:35,200 --> 00:24:38,400 QUICKLY FOR MY LAST SLIDE HERE, 763 00:24:38,400 --> 00:24:40,280 NPNPD COLLABORATIONS ON THE HEAL 764 00:24:40,280 --> 00:24:43,400 INITIATIVE WITH NCCIH AND NCATS 765 00:24:43,400 --> 00:24:45,800 AND IN THIS EXAMPLE, TARGETS 766 00:24:45,800 --> 00:24:48,120 ASSOCIATED WITH PAIN ARE WHAT IS 767 00:24:48,120 --> 00:24:50,000 INDICATIVE OF THE ASSAYS AND THE 768 00:24:50,000 --> 00:24:52,120 FUNDING THAT IS GOING INTO THIS. 769 00:24:52,120 --> 00:24:56,400 SO, THESE ARE FUNDED THROUGH AN 770 00:24:56,400 --> 00:24:57,960 NCCIH NOsY. 771 00:24:57,960 --> 00:24:59,560 IT IS PERFORMED AT NCATS AND 772 00:24:59,560 --> 00:25:03,800 IDENTIFIES COMPOUNDS, SENDS THEM 773 00:25:03,800 --> 00:25:05,000 INTO LABS. 774 00:25:05,000 --> 00:25:05,600 TWO INITIAL SCREENS HAVE BEEN 775 00:25:05,600 --> 00:25:10,760 COMPLETED ON THESE TWO RECEPTORS 776 00:25:10,760 --> 00:25:18,080 A GAL AN IN AND/OR FAN RECEPTOR. 777 00:25:18,080 --> 00:25:18,560 COLLABORATORSA -- ORPHAN 778 00:25:18,560 --> 00:25:19,520 RECEPTOR. 779 00:25:19,520 --> 00:25:23,160 AND THEY HAVE ALREADY SCREENED 780 00:25:23,160 --> 00:25:26,040 150,000 FRACTIONS AND GOT BACK 781 00:25:26,040 --> 00:25:27,480 11,000 SUBFRACTIONS WITHIN TWO 782 00:25:27,480 --> 00:25:27,800 WEEKS. 783 00:25:27,800 --> 00:25:30,600 AND SO FAR WE HAVE ISOLATED TWO 784 00:25:30,600 --> 00:25:34,640 COMPOUND CLASSES OF PARTICULAR 785 00:25:34,640 --> 00:25:35,640 INTEREST WHICH MIGHT BE 786 00:25:35,640 --> 00:25:38,640 TRANSLATABLE FURTHER DOWN THE 787 00:25:38,640 --> 00:25:39,880 ROAD AS WE PASS THESE BACK TO 788 00:25:39,880 --> 00:25:42,320 THE RESEARCHERS AT MOUNT SINAI 789 00:25:42,320 --> 00:25:44,600 AND NIDA AND SEE HOW WILL THEY 790 00:25:44,600 --> 00:25:45,720 WORKED IN THEIR SYSTEMS. 791 00:25:45,720 --> 00:25:47,560 AND I WOULD LIKE TO ACKNOWLEDGE 792 00:25:47,560 --> 00:25:49,440 EVERYTHING WHO HAS DONE SO MUCH 793 00:25:49,440 --> 00:25:51,400 WORK TO MAKE ALL OF THIS 794 00:25:51,400 --> 00:25:53,680 POSSIBLE I SHOWED YOU TODAY AND 795 00:25:53,680 --> 00:25:55,120 THE NATURAL PRODUCT SUPPORT 796 00:25:55,120 --> 00:25:57,680 GROUP AND THE NATURAL PRODUCT 797 00:25:57,680 --> 00:26:01,080 BRANCH AND OUR COLLABORATORS. 798 00:26:01,080 --> 00:26:09,600 AND THANK YOU ALL FOR YOUR 799 00:26:09,600 --> 00:26:16,160 ATTENTION. 800 00:26:16,160 --> 00:26:17,560 >>THANK YOU. 801 00:26:17,560 --> 00:26:20,920 WE WILL HAVE A Q&A SESSION 802 00:26:20,920 --> 00:26:28,400 FOLLOWING ALL THE TALKS. 803 00:26:28,400 --> 00:26:31,880 AND NOW DR. ROGER LININGTON HAS 804 00:26:31,880 --> 00:26:32,200 OUR NEXT TALK. 805 00:26:32,200 --> 00:26:33,320 >>THANK YOU VERY MUCH. 806 00:26:33,320 --> 00:26:37,400 I'M JUST GETTING SET UP HERE. 807 00:26:37,400 --> 00:26:40,360 SO I'M GOING TO TELL YOU ABOUT 808 00:26:40,360 --> 00:26:40,880 HIGH-THROUGHPUT FUNCTIONAL 809 00:26:40,880 --> 00:26:43,760 ANNOTATION OF NATURAL PRODUCTS 810 00:26:43,760 --> 00:26:44,440 USING INTEGRATED ACTIVITY 811 00:26:44,440 --> 00:26:45,040 PROFILING. 812 00:26:45,040 --> 00:26:47,760 THIS IS REPRESENTATIVE PROJECT 813 00:26:47,760 --> 00:26:48,440 FROM THE HIGH FAN PROGRAM, ONE 814 00:26:48,440 --> 00:26:54,200 OF THE U41 PROJECTS SUPPORTED BY 815 00:26:54,200 --> 00:26:55,960 NCCIH AND UNDER CARBON PROGRAM. 816 00:26:55,960 --> 00:26:58,920 SO I THINK THE INTRODUCTORY 817 00:26:58,920 --> 00:27:01,760 TITLE IS A VERY TELLING REMINDER 818 00:27:01,760 --> 00:27:04,720 OF THE RICHNESS AND COMPLEXITY 819 00:27:04,720 --> 00:27:06,320 OF NATURAL PRODUCTS CHEMISTRY. 820 00:27:06,320 --> 00:27:06,920 AND NICELY HIGHLIGHTS SOME OF 821 00:27:06,920 --> 00:27:09,280 THE CHALLENGES WHICH FACE 822 00:27:09,280 --> 00:27:11,120 NATURAL PRODUCTS IN THE 21ST 823 00:27:11,120 --> 00:27:12,760 CENTURY IN TERMS OF DISCOVERY 824 00:27:12,760 --> 00:27:14,720 AND DEVELOPMENT. 825 00:27:14,720 --> 00:27:15,840 IN PARTICULAR, I THINK IT'S 826 00:27:15,840 --> 00:27:17,720 CLEAR IF YOU TAKE ANY ORGANISM 827 00:27:17,720 --> 00:27:20,320 OR SET OF ORGANISMS AND HERE I 828 00:27:20,320 --> 00:27:23,440 GIVE A MACRO ORGANISM AS AN 829 00:27:23,440 --> 00:27:26,400 EXAMPLE BUT THIS COULD BE 830 00:27:26,400 --> 00:27:29,640 BOTANICAL SAMPLES, BONDS, MARINE 831 00:27:29,640 --> 00:27:29,960 INVERTEBRATES. 832 00:27:29,960 --> 00:27:36,320 WE HAVE A LOT OF VERY POWERFUL 833 00:27:36,320 --> 00:27:37,120 PROFILING TECHNOLOGIES. 834 00:27:37,120 --> 00:27:40,400 AND THIS MIGHT BE GENOME 835 00:27:40,400 --> 00:27:42,520 SEQUENCING OR BY CHROME GRAPHIC 836 00:27:42,520 --> 00:27:44,360 METHODS, LCMS BEING POPULAR. 837 00:27:44,360 --> 00:27:46,040 I WOULD ARGUE THAT IT'S STILL 838 00:27:46,040 --> 00:27:47,040 VERY DIFFICULT AT THIS STAGE TO 839 00:27:47,040 --> 00:27:49,480 BE CONFIDENT ABOUT THE CHEMICAL 840 00:27:49,480 --> 00:27:56,200 COMPOSITION OF ANY SINGLE SAMPLE 841 00:27:56,200 --> 00:27:58,920 LET ALONE LARGE LIBRARIES OF 842 00:27:58,920 --> 00:27:59,160 SAMPLES. 843 00:27:59,160 --> 00:28:01,040 IF YOU DON'T KNOW WHAT YOU HAVE, 844 00:28:01,040 --> 00:28:02,480 IT'S DIFFICULT TO UNDERSTAND 845 00:28:02,480 --> 00:28:05,160 WHAT YOU SHOULD DO WITH THOSE 846 00:28:05,160 --> 00:28:06,280 MATERIALS. 847 00:28:06,280 --> 00:28:09,800 HOWEVER, I WOULD ALSO ARGUE THAT 848 00:28:09,800 --> 00:28:11,280 TECHNOLOGIES IN THIS AREA ARE 849 00:28:11,280 --> 00:28:12,520 REVOLVING VERY QUICKLY. 850 00:28:12,520 --> 00:28:13,960 AND I THINK WE WILL COME TO A 851 00:28:13,960 --> 00:28:16,560 POINT AS A FIELD IN THE NEAR 852 00:28:16,560 --> 00:28:18,480 FUTURE WHERE THESE QUESTIONS 853 00:28:18,480 --> 00:28:19,560 ABOUT COMPOSITION MEANING HOW 854 00:28:19,560 --> 00:28:21,400 MANY MOLECULES ARE IN THE SAMPLE 855 00:28:21,400 --> 00:28:23,720 AND HOW THEY ARE DISTRIBUTED 856 00:28:23,720 --> 00:28:25,720 BETWEEN SAMPLES AND THEN ALSO 857 00:28:25,720 --> 00:28:28,480 IDENTIFICATION, SO WHAT ARE THE 858 00:28:28,480 --> 00:28:29,040 STRUCTURES? 859 00:28:29,040 --> 00:28:30,640 PERHAPS THE CLASS SPACE LEVEL 860 00:28:30,640 --> 00:28:31,960 AND ULTIMATELY AT THE FULL 861 00:28:31,960 --> 00:28:32,440 STRUCTURAL LEVEL. 862 00:28:32,440 --> 00:28:35,680 THESE QUESTIONS ARE THE SUBJECT 863 00:28:35,680 --> 00:28:37,920 OF INTENSE RESEARCH IN THE 864 00:28:37,920 --> 00:28:39,280 INFORMATICS AND TECHNOLOGY SPACE 865 00:28:39,280 --> 00:28:40,120 IN NATURAL PRODUCTS. 866 00:28:40,120 --> 00:28:42,720 I THINK WE ARE ALREADY SEEING A 867 00:28:42,720 --> 00:28:43,760 NUMBER OF PLATFORMS WHICH HAVE 868 00:28:43,760 --> 00:28:46,120 BEEN HELPFUL IN TRYING TO SOLVE 869 00:28:46,120 --> 00:28:49,160 THESE ISSUES AND MORE ARE ON THE 870 00:28:49,160 --> 00:28:50,440 WAY. 871 00:28:50,440 --> 00:28:52,280 SO THIS CONCEPT THAT 872 00:28:52,280 --> 00:28:53,120 COMPOSITIONAL QUESTIONS WILL 873 00:28:53,120 --> 00:28:54,760 START TO BE ANSWERED GIVES US AN 874 00:28:54,760 --> 00:28:55,640 OPPORTUNITY AS A FIELD TO 875 00:28:55,640 --> 00:28:57,520 APPROACH THE WAY WE DISCOVER 876 00:28:57,520 --> 00:28:59,600 NATURAL PRODUCTS REALLY QUITE 877 00:28:59,600 --> 00:29:02,040 RADICALLY DIFFERENTLY THAN THE 878 00:29:02,040 --> 00:29:03,040 WAY WE DO TODAY. 879 00:29:03,040 --> 00:29:07,040 IF WE LOOK AT A TYPICAL CARTOON 880 00:29:07,040 --> 00:29:10,000 WORK FLOW OF WHAT MOST NATURAL 881 00:29:10,000 --> 00:29:11,320 PRODUCT PROGRAMS LOOK LIKE, IN 882 00:29:11,320 --> 00:29:13,640 GENERAL, ONE STARTS WITH SOME 883 00:29:13,640 --> 00:29:15,120 SOURCE OF NATURAL PRODUCTS 884 00:29:15,120 --> 00:29:18,440 DIVERSITY WHICH GETS CONVERTED 885 00:29:18,440 --> 00:29:19,080 TO EXTRACT LIBRARIES AS 886 00:29:19,080 --> 00:29:21,760 DESCRIBED. 887 00:29:21,760 --> 00:29:23,520 AND THEN THOSE LIBRARIES ARE 888 00:29:23,520 --> 00:29:25,680 SUBJECT JECTED TO CHROME GRAPHIC 889 00:29:25,680 --> 00:29:27,800 INVESTIGATION AND ALSO SOME 890 00:29:27,800 --> 00:29:29,160 ELEMENT OF BIOLOGICAL STUDY. 891 00:29:29,160 --> 00:29:31,640 AND HERE BIOLOGICAL STUDY IS 892 00:29:31,640 --> 00:29:32,120 LOOSELY DEFINED. 893 00:29:32,120 --> 00:29:35,080 SO I SHOWED HERE A CELL-BASED 894 00:29:35,080 --> 00:29:37,560 ASSAY AND TOXICITY READ OUT BUT 895 00:29:37,560 --> 00:29:39,040 THAT COULD BE A BEHAVIORAL AS A 896 00:29:39,040 --> 00:29:40,920 OR CHEMICAL ECOLOGY AS A. 897 00:29:40,920 --> 00:29:43,080 BUT SOME SORT OF FUNCTIONAL 898 00:29:43,080 --> 00:29:43,400 ASSESSMENT. 899 00:29:43,400 --> 00:29:44,880 AND THEN THERE IS ALWAYS ONCE 900 00:29:44,880 --> 00:29:47,840 THOSE TWO STAGES ARE COMPLETE, A 901 00:29:47,840 --> 00:29:48,520 STEP WHERE ONE NEEDS TO 902 00:29:48,520 --> 00:29:50,760 INTEGRATE THE INFORMATION FROM 903 00:29:50,760 --> 00:29:52,360 THOSE TWO DIFFERENT EXPERIMENTS 904 00:29:52,360 --> 00:29:53,680 IN ORDER TO CONNECT CHEMO TYPES 905 00:29:53,680 --> 00:29:56,120 AND PHENOTYPES AND TO RECOGNIZE 906 00:29:56,120 --> 00:29:58,640 WHICH MOLECULES ARE RELEVANT FOR 907 00:29:58,640 --> 00:30:00,040 THE PROPERTY OR BEHAVIOR WE ARE 908 00:30:00,040 --> 00:30:01,120 LOOKING FOR. 909 00:30:01,120 --> 00:30:03,480 AND THEN LASTLY, ONE HAS TO MAKE 910 00:30:03,480 --> 00:30:05,600 DECISIONS ABOUT WHICH OF THESE 911 00:30:05,600 --> 00:30:06,200 PRODUCTS TO FOCUS ATTENTION ON 912 00:30:06,200 --> 00:30:11,000 AND WHERE TO INVEST THE 913 00:30:11,000 --> 00:30:11,640 LABOR-INTENSIVE EFFORT IN 914 00:30:11,640 --> 00:30:16,840 MATERIAL STUDIES, ET CETERA. 915 00:30:16,840 --> 00:30:17,480 SO WE DEVELOPED A LOT OF TOOLS 916 00:30:17,480 --> 00:30:19,440 AND TECHNOLOGIES WHICH TRY TO 917 00:30:19,440 --> 00:30:20,640 ASSIST IN THESE VARIOUS AREAS. 918 00:30:20,640 --> 00:30:22,080 SOME OF THESE THINGS ARE ALREADY 919 00:30:22,080 --> 00:30:24,080 PUBLISHED. 920 00:30:24,080 --> 00:30:24,720 SOME YOU WILL SEE COMING OUT IN 921 00:30:24,720 --> 00:30:26,960 THE NEXT 12 MONTHS. 922 00:30:26,960 --> 00:30:28,080 ESSENTIALLY WE AND MANY OTHERS 923 00:30:28,080 --> 00:30:32,400 IN THE FIELD OF INFORMATICS 924 00:30:32,400 --> 00:30:33,880 RELATED NATURAL PRODUCTS TRYING 925 00:30:33,880 --> 00:30:35,640 TO DEVELOP METHODOLOGIES THAT 926 00:30:35,640 --> 00:30:39,120 WILL LOWER THE VARIOUS ENTRY AND 927 00:30:39,120 --> 00:30:39,760 IMPROVED QUALITY AND SPEC IN ALL 928 00:30:39,760 --> 00:30:40,240 THESE DIFFERENT AREAS. 929 00:30:40,240 --> 00:30:41,920 I THINK IT'S OPENING UP AN 930 00:30:41,920 --> 00:30:42,440 OPPORTUNITY TO DO NATURAL 931 00:30:42,440 --> 00:30:46,000 PRODUCTS DISCOVERY ON SCALE TO 932 00:30:46,000 --> 00:30:48,840 MOVE FROM A SCENARIO WHERE 933 00:30:48,840 --> 00:30:50,280 PERHAPS ONE STUDENT MIGHT STUDY 934 00:30:50,280 --> 00:30:53,680 ONE OR A FEW SAMPLES AT A TIME 935 00:30:53,680 --> 00:30:55,840 OR PROJECTS ARE SAMPLE-BASED TO 936 00:30:55,840 --> 00:30:57,120 A SITUATION WHERE PROJECTS ARE 937 00:30:57,120 --> 00:30:59,080 REALLY LIVELY BASED AND THE 938 00:30:59,080 --> 00:31:01,120 NATURAL PRODUCTS CATCHES UP WITH 939 00:31:01,120 --> 00:31:02,040 SOME OF THE OTHER 940 00:31:02,040 --> 00:31:03,040 HIGH-THROUGHPUT METHODOLOGIES 941 00:31:03,040 --> 00:31:05,720 WHICH ARE COMMON IN SMALL 942 00:31:05,720 --> 00:31:07,240 MOLECULE LIBRARIES AND SYNTHETIC 943 00:31:07,240 --> 00:31:08,440 CHEMISTRY LIBRARIES. 944 00:31:08,440 --> 00:31:10,280 AND I THINK ALONG WITH THIS 945 00:31:10,280 --> 00:31:12,800 COMES HIGHER QUALITY HARDWARE 946 00:31:12,800 --> 00:31:16,440 AND MASS SPECTROMETRY, GREATER 947 00:31:16,440 --> 00:31:18,000 ACCESS IN THE ACADEMIC 948 00:31:18,000 --> 00:31:18,560 ENVIRONMENT, HIGH-THROUGHPUT 949 00:31:18,560 --> 00:31:20,160 SCREENING TOOLS AND 950 00:31:20,160 --> 00:31:20,880 TECHNOLOGIES. 951 00:31:20,880 --> 00:31:22,960 SO OBVIOUSLY I DON'T HAVE TIME 952 00:31:22,960 --> 00:31:24,440 TO TELL YOU ABOUT ALL THE TOOLS 953 00:31:24,440 --> 00:31:25,400 IN 15 MINUTES. 954 00:31:25,400 --> 00:31:27,800 I'M JUST GOING TO FOLK ON ONE. 955 00:31:27,800 --> 00:31:30,440 THAT'S THIS TOOL HERE, NP 956 00:31:30,440 --> 00:31:30,680 ANALYST. 957 00:31:30,680 --> 00:31:32,320 WHAT NP ANALYST DOES IS IT 958 00:31:32,320 --> 00:31:34,280 OFFERS AN OPPORTUNITY TO 959 00:31:34,280 --> 00:31:37,040 INTEGRATE DATA FROM THESE TWO 960 00:31:37,040 --> 00:31:39,920 PARALLEL STAGES OF DISCOVERY. 961 00:31:39,920 --> 00:31:43,920 SO IT WILL TAKE DATA FROM 962 00:31:43,920 --> 00:31:45,440 UNTARGETED METABOLOMICS ANALYSIS 963 00:31:45,440 --> 00:31:48,200 OF LIBRARIES AND PAIR THAT WITH 964 00:31:48,200 --> 00:31:49,800 RESULTS FROM HIGH-THROUGHPUT 965 00:31:49,800 --> 00:31:51,160 SCREENING OR OTHER BIOLOGICAL 966 00:31:51,160 --> 00:31:52,760 CHARACTERIZATION IN ORDER TO 967 00:31:52,760 --> 00:31:54,520 PRIORITIZE AND HIGHLIGHT 968 00:31:54,520 --> 00:31:55,720 MOLECULES WITH THE HIGHEST VALUE 969 00:31:55,720 --> 00:31:57,760 FOR DOWNSTREAM ISOLATION. 970 00:31:57,760 --> 00:32:01,280 AND THIS IS A STEP WHICH IS 971 00:32:01,280 --> 00:32:02,000 HISTORICALLY BEING QUITE 972 00:32:02,000 --> 00:32:03,120 DIFFICULT TO DO. 973 00:32:03,120 --> 00:32:06,000 IT'S DIFFICULT TO DO MANUALLY 974 00:32:06,000 --> 00:32:08,400 AND IT'S BEING CHALLENGING TO DO 975 00:32:08,400 --> 00:32:08,960 COMPUTATIONALLY. 976 00:32:08,960 --> 00:32:10,960 SO, IF WE LOOK BRIEFLY AT EACH 977 00:32:10,960 --> 00:32:12,680 OF THESE TWO TYPES OF UP PUT 978 00:32:12,680 --> 00:32:14,880 DATA, THE FIRST IS UNTARGETED 979 00:32:14,880 --> 00:32:17,080 METABOLOMICS DATA. 980 00:32:17,080 --> 00:32:19,200 AND IT REMAINS VERY COMPLICATED 981 00:32:19,200 --> 00:32:20,920 DATA TYPE TO HANDLE. 982 00:32:20,920 --> 00:32:23,640 SO THIS IS HIGH RESOLUTION MASS 983 00:32:23,640 --> 00:32:24,240 SPEC TROM TERON THE LEFT. 984 00:32:24,240 --> 00:32:26,840 THIS MACHINE GENERATES ON THE 985 00:32:26,840 --> 00:32:29,760 ORDER OF 5 GIGABYTES OF RAW DATA 986 00:32:29,760 --> 00:32:30,000 AN HOUR. 987 00:32:30,000 --> 00:32:33,000 AND THE DATA ON THE RIGHT GIVE 988 00:32:33,000 --> 00:32:34,440 SOME IDEA THE DATA POINT 989 00:32:34,440 --> 00:32:35,680 COMPLEXITY OF THAT DATASET MIGHT 990 00:32:35,680 --> 00:32:36,440 LOOK LIKE. 991 00:32:36,440 --> 00:32:38,720 AND OF COURSE, AT THE BEGINNING 992 00:32:38,720 --> 00:32:40,520 WHEN THE EXPERIMENT IS FINISHED, 993 00:32:40,520 --> 00:32:43,560 THOSE MASS SPECTROMETRY DATA ARE 994 00:32:43,560 --> 00:32:46,080 ALL VERY POORLY STRUCTURED. 995 00:32:46,080 --> 00:32:47,000 A LARGE NUMBER OF INDIVIDUAL 996 00:32:47,000 --> 00:32:49,000 DISTANCE TELL YOU ABOUT THE MASS 997 00:32:49,000 --> 00:32:50,880 SPECTRA OF THE MASS SAMPLE AT 998 00:32:50,880 --> 00:32:52,360 ANY PARTICULAR TIME POINT BUT 999 00:32:52,360 --> 00:32:54,400 DON'T NECESSARILY TELL YOU ABOUT 1000 00:32:54,400 --> 00:32:54,680 COMPOSITION. 1001 00:32:54,680 --> 00:32:58,480 SO THERE ARE A LOT OF CHALLENGES 1002 00:32:58,480 --> 00:32:59,120 INVOLVED IN DATA PROCESSING AND 1003 00:32:59,120 --> 00:32:59,440 DATA ANALYSIS. 1004 00:32:59,440 --> 00:33:00,160 LOTS OF DIFFERENT WAYS ONE CAN 1005 00:33:00,160 --> 00:33:02,000 DO THAT AND AT THE MOMENT THERE 1006 00:33:02,000 --> 00:33:05,000 IS RELATIVELY LOW CONSENSUS 1007 00:33:05,000 --> 00:33:06,640 AMONG THE NATURAL PRODUCTS 1008 00:33:06,640 --> 00:33:06,880 COMMUNITY. 1009 00:33:06,880 --> 00:33:09,080 SO THIS IS ONE CHALLENGE. 1010 00:33:09,080 --> 00:33:11,320 THE ONLY THING I WOULD NOTE HERE 1011 00:33:11,320 --> 00:33:13,720 IS OF COURSE, NOT ALL OF THESE 1012 00:33:13,720 --> 00:33:17,160 DATA POINTS CORRESPOND TO UNIQUE 1013 00:33:17,160 --> 00:33:18,480 MOLECULES IN THE SAMPLE. 1014 00:33:18,480 --> 00:33:21,680 ONE MOLECULE CAN GENERATE MANY 1015 00:33:21,680 --> 00:33:22,760 DIFFERENT MASS SPEC FEATURES BE 1016 00:33:22,760 --> 00:33:25,240 IT THROUGH FRAGMENTATION, THE 1017 00:33:25,240 --> 00:33:27,400 FORMATION OF DIFFERENT ADDUCTS 1018 00:33:27,400 --> 00:33:29,200 OR DIFFERENT CHARGE STATES, 1019 00:33:29,200 --> 00:33:29,440 ET CETERA. 1020 00:33:29,440 --> 00:33:33,280 AND SO THERE WAS A LEVEL OF 1021 00:33:33,280 --> 00:33:34,240 COMPLEXITY HERE WHICH GOES 1022 00:33:34,240 --> 00:33:35,880 BEYOND THE COMPLEXITY OF THE 1023 00:33:35,880 --> 00:33:37,120 CHEMISTRY AND THE SAMPLE ITSELF. 1024 00:33:37,120 --> 00:33:39,200 BUT IF WE THINK ABOUT THE 1025 00:33:39,200 --> 00:33:40,680 PROJECT FROM A NATURAL PRODUCTS 1026 00:33:40,680 --> 00:33:43,760 DISCOVERY PERSPECTIVE, THEN 1027 00:33:43,760 --> 00:33:44,680 REALLY EVERY EXPERIMENT BOILS 1028 00:33:44,680 --> 00:33:45,280 DOWN TO THIS SIMPLE GRAPHIC. 1029 00:33:45,280 --> 00:33:50,960 ON THE LEFT WE HAVE A COMPOUND 1030 00:33:50,960 --> 00:33:52,040 CHROME ATOGRAM AND ON THE RIGHT 1031 00:33:52,040 --> 00:33:54,640 WE HAVE SOME BIOLOGICAL 1032 00:33:54,640 --> 00:33:55,040 FINGERPRINT. 1033 00:33:55,040 --> 00:34:00,000 I'LL COME BACK TO THE BIOLOGICAL 1034 00:34:00,000 --> 00:34:01,680 BARCODE WE HAVE HERE IN JUST A 1035 00:34:01,680 --> 00:34:01,920 SECOND. 1036 00:34:01,920 --> 00:34:04,400 AND IF WE THINK ABOUT THE 1037 00:34:04,400 --> 00:34:06,600 WORKLOAD, WHAT WE WANT TO KNOW 1038 00:34:06,600 --> 00:34:08,200 ABOUT ANY OF THESE. 1039 00:34:08,200 --> 00:34:09,400 WE TAKE ONE AS AN EXAMPLE, WE 1040 00:34:09,400 --> 00:34:11,280 WANT TO KNOW THE ANSWERS TO TWO 1041 00:34:11,280 --> 00:34:11,560 QUESTIONS. 1042 00:34:11,560 --> 00:34:14,480 WE WOULD LIKE TO KNOW IS THIS 1043 00:34:14,480 --> 00:34:16,520 METABOLITE PREDICTED TO BE 1044 00:34:16,520 --> 00:34:16,760 BIOACTIVE? 1045 00:34:16,760 --> 00:34:18,440 AND IF SO, IS IT CORRELATED WITH 1046 00:34:18,440 --> 00:34:21,600 A PARTICULAR PHENOTYPE OR 1047 00:34:21,600 --> 00:34:22,120 BIOLOGICAL FINGERPRINT? 1048 00:34:22,120 --> 00:34:22,880 BUT WE WANT TO KNOW THAT 1049 00:34:22,880 --> 00:34:26,040 INFORMATION NOT JUST FOR A 1050 00:34:26,040 --> 00:34:27,520 SINGLE MOLECULE IN THE SAMPLE 1051 00:34:27,520 --> 00:34:29,720 BUT RATHER WE WOULD LIKE TO KNOW 1052 00:34:29,720 --> 00:34:30,360 THAT INFORMATION COMPREHENSIVELY 1053 00:34:30,360 --> 00:34:32,360 FOR ALL THE MOLECULES IN THE 1054 00:34:32,360 --> 00:34:33,040 SAMPLE. 1055 00:34:33,040 --> 00:34:35,120 AND I THINK THIS SHIFT TOWARDS 1056 00:34:35,120 --> 00:34:36,240 DATA-CENTRIC APPROACHES TO 1057 00:34:36,240 --> 00:34:37,960 NATURAL PRODUCTS GIVES THE FIELD 1058 00:34:37,960 --> 00:34:40,320 THE OPPORTUNITY TO DO THESE 1059 00:34:40,320 --> 00:34:42,000 KINDS OF THINGS IN WHICH 1060 00:34:42,000 --> 00:34:43,400 PREVIOUSLY HAVE BEEN 1061 00:34:43,400 --> 00:34:44,440 FUNCTIONALLY IMPOSSIBLE TO DO. 1062 00:34:44,440 --> 00:34:46,280 REQUEST WE THINK ABOUT 1063 00:34:46,280 --> 00:34:47,880 BIOLOGICAL FINGERPRINTS AND WHAT 1064 00:34:47,880 --> 00:34:48,480 THAT MEANS, THERE ARE LOTS OF 1065 00:34:48,480 --> 00:34:50,160 WAYS IN WHICH ONE CAN DEFINE 1066 00:34:50,160 --> 00:34:50,680 BIOLOGICAL FINGERPRINTS. 1067 00:34:50,680 --> 00:34:51,720 IT COULD BE AS SIMPLE AS A 1068 00:34:51,720 --> 00:34:54,000 SINGLE READ OUT. 1069 00:34:54,000 --> 00:34:56,400 IT COULD BE A LIVE READ OUT FROM 1070 00:34:56,400 --> 00:34:56,960 A SINGLE CELL LINE. 1071 00:34:56,960 --> 00:34:59,520 A NUMBER OF TECHNOLOGIES ARE 1072 00:34:59,520 --> 00:35:02,480 COMING ON LINE AND AVAILABLE. 1073 00:35:02,480 --> 00:35:04,920 TWO THAT I PARTICULARLY AM 1074 00:35:04,920 --> 00:35:05,240 INTERESTED IN. 1075 00:35:05,240 --> 00:35:06,480 CELL PAINTING IS ONE. 1076 00:35:06,480 --> 00:35:09,040 THIS IS AN IMAGE-BASED SCREENING 1077 00:35:09,040 --> 00:35:10,840 METHODOLOGY THAT LOOKS AT 1078 00:35:10,840 --> 00:35:14,480 HUNDREDS OF SIZE AND SHAPE 1079 00:35:14,480 --> 00:35:15,200 PARAMETER TERS AT THE INDIVIDUAL 1080 00:35:15,200 --> 00:35:17,560 CELL LEVEL FOR CELLS UNDER DRUG 1081 00:35:17,560 --> 00:35:18,880 TREATMENT AND COMPARES THOSE TO 1082 00:35:18,880 --> 00:35:23,320 CELLS THAT ARE NOT UNDER DRUG 1083 00:35:23,320 --> 00:35:23,960 TREATMENT AND THEN USES GUILT BY 1084 00:35:23,960 --> 00:35:24,640 ASSOCIATION MECHANISM TO RELATE 1085 00:35:24,640 --> 00:35:27,200 THE SIZE AND SHAPE VARIATIONS OF 1086 00:35:27,200 --> 00:35:28,960 CELLS UNDER DRUG PRESSURE FROM 1087 00:35:28,960 --> 00:35:30,200 KNOWN DRUGS TO THE SIZE AND 1088 00:35:30,200 --> 00:35:33,400 SHAPE VARIATIONS FOR CELLS UNDER 1089 00:35:33,400 --> 00:35:35,080 DRUG PRESSURE WITH EXPERIMENTAL 1090 00:35:35,080 --> 00:35:37,320 DRUGS OR TEST EXTRACTS LIKE 1091 00:35:37,320 --> 00:35:37,720 NATURAL PRODUCTS. 1092 00:35:37,720 --> 00:35:40,520 IT'S A WAY OF DEVELOPING AN 1093 00:35:40,520 --> 00:35:43,480 UNBIASED PLATFORM FOR MAKING 1094 00:35:43,480 --> 00:35:44,640 MECHANISTIC PROTECTIONS ABOUT 1095 00:35:44,640 --> 00:35:45,560 ANY SEGMENT SAMPLE. 1096 00:35:45,560 --> 00:35:51,080 SO THIS IS ONE CELL LINE. 1097 00:35:51,080 --> 00:35:53,120 ALTERNATIVELY, LAB AUTOMATION 1098 00:35:53,120 --> 00:35:54,760 TECHNOLOGIES MEAN WE CAN RUN 1099 00:35:54,760 --> 00:35:57,840 STRAIGHTFORWARD ASSAYS SUCH AS 1100 00:35:57,840 --> 00:35:59,920 ANTIMICROBIAL ASSAYS. 1101 00:35:59,920 --> 00:36:01,240 NOW ON VERY HIGH-THROUGHPUT. 1102 00:36:01,240 --> 00:36:02,840 IT'S NOT UNREASONABLE FOR A 1103 00:36:02,840 --> 00:36:05,040 SINGLE RESEARCH GROUP TO RUN A 1104 00:36:05,040 --> 00:36:05,360 SET LIKE THIS. 1105 00:36:05,360 --> 00:36:08,600 ON THE RIGHT WE HAVE BIOMELT 1106 00:36:08,600 --> 00:36:11,600 RICK PANEL AND MICROBIAL PANEL 1107 00:36:11,600 --> 00:36:12,400 BASED IN MY LAB AND HERE WE TAKE 1108 00:36:12,400 --> 00:36:15,240 A SET OF 20 DIFFERENT PATHOGENS 1109 00:36:15,240 --> 00:36:17,000 AND SCREEN THE NATURAL PRODUCTS 1110 00:36:17,000 --> 00:36:17,720 LIBRARY AGAINST EVERY MEMBER IN 1111 00:36:17,720 --> 00:36:19,840 THIS SET AND LOOK AT THE PROFILE 1112 00:36:19,840 --> 00:36:21,480 OF ACTIVITY OF EACH NATURAL 1113 00:36:21,480 --> 00:36:23,280 PRODUCTS EXTRACT ACROSS THE FULL 1114 00:36:23,280 --> 00:36:24,800 SET OF PATHOGENS IN THE LIBRARY. 1115 00:36:24,800 --> 00:36:26,280 AND IN THIS WAY, YOU'RE LOOKING 1116 00:36:26,280 --> 00:36:28,080 AT THE SPECTRUM OF ACTIVITY OF 1117 00:36:28,080 --> 00:36:30,160 THE NATURAL PRODUCT AGAINST A 1118 00:36:30,160 --> 00:36:32,560 BROAD PANEL OF DIFFERENT 1119 00:36:32,560 --> 00:36:33,320 STRAINS, RATHER THAN JUST 1120 00:36:33,320 --> 00:36:35,320 LOOKING AT LIVE DATA RESULTS 1121 00:36:35,320 --> 00:36:36,040 AGAINST A SINGLE STRAIN. 1122 00:36:36,040 --> 00:36:37,960 IN BOTH CASES, WHAT COMES FROM 1123 00:36:37,960 --> 00:36:46,520 THIS IS AN ABILITY TO GROUP -- 1124 00:36:46,520 --> 00:36:46,960 BASED ON SIGNATURES. 1125 00:36:46,960 --> 00:36:49,040 IF WE IMAGINE WE RUN CELL 1126 00:36:49,040 --> 00:36:50,280 PAINTING ANALYSIS ON THREE 1127 00:36:50,280 --> 00:36:51,720 DIFFERENT SAMPLES, PERHAPS THOSE 1128 00:36:51,720 --> 00:36:54,040 THREE SAMPLES GIVE US BIOLOGICAL 1129 00:36:54,040 --> 00:36:55,160 FINGERPRINTS LIKE THIS WHICH ARE 1130 00:36:55,160 --> 00:36:58,080 ALL VERY SIMILAR TO ONE ANOTHER. 1131 00:36:58,080 --> 00:37:00,080 YET IF WE LOOK AT THE 1132 00:37:00,080 --> 00:37:02,680 METABOLOMICS DATA, HERE WE HAVE 1133 00:37:02,680 --> 00:37:07,360 ON THE LEFT THE CARTOON OF THEIR 1134 00:37:07,360 --> 00:37:07,720 HBLCMS PROFILES. 1135 00:37:07,720 --> 00:37:10,000 THERE IS NO OBVIOUS CORRELATION 1136 00:37:10,000 --> 00:37:12,400 BETWEEN THESE THREE PROFILES. 1137 00:37:12,400 --> 00:37:14,680 AND YET, IF WE ASK WHETHER OR 1138 00:37:14,680 --> 00:37:17,080 NOT THERE ARE ANY MOLECULES 1139 00:37:17,080 --> 00:37:21,360 WHICH ARE COMMON TO THIS THRE 1140 00:37:21,360 --> 00:37:22,040 THREE-SET OF CHROMOGRAMS, WE 1141 00:37:22,040 --> 00:37:24,680 FIND THERE ARE TWO MOLECULES 1142 00:37:24,680 --> 00:37:26,200 HERE COMMON TO ALL THREE CASES 1143 00:37:26,200 --> 00:37:27,720 AND SO ONE TESTABLE HYPOTHESIS 1144 00:37:27,720 --> 00:37:29,800 IS THAT ONE OR BOTH OF THESE 1145 00:37:29,800 --> 00:37:32,480 MOLECULES ARE RESPONSIBLE FOR 1146 00:37:32,480 --> 00:37:33,880 THE PHENOTYPE. 1147 00:37:33,880 --> 00:37:36,280 AND SO REALLY THAT PROCESS OF 1148 00:37:36,280 --> 00:37:38,760 TAKING LARGE UNSTRUCTURED 1149 00:37:38,760 --> 00:37:40,200 METABOLOMICS DATASETS, PAIRING 1150 00:37:40,200 --> 00:37:42,240 THEM WITH BIOLOGICAL PROFILING 1151 00:37:42,240 --> 00:37:45,120 DATA FROM PROFILING SCREEN OF 1152 00:37:45,120 --> 00:37:48,360 CHOICE AND STILLING THOSE 1153 00:37:48,360 --> 00:37:50,240 INFORMATION DOWN TO MOLECULES 1154 00:37:50,240 --> 00:37:51,160 FOR FEATURE IDENTIFICATION, THAT 1155 00:37:51,160 --> 00:37:54,520 IS REALLY AT THE HEART OF THIS 1156 00:37:54,520 --> 00:37:55,160 PLATFORM WHICH I WOULD LIKE TO 1157 00:37:55,160 --> 00:37:58,720 TELL YOU A LITTLE BIT MORE 1158 00:37:58,720 --> 00:37:59,560 ABOUT. 1159 00:37:59,560 --> 00:38:01,200 SO NP ANALYST WAS RELEASED EARLY 1160 00:38:01,200 --> 00:38:03,080 LAST YEAR. 1161 00:38:03,080 --> 00:38:06,640 AN OPEN-SOURCE COMPLETELY FREE 1162 00:38:06,640 --> 00:38:06,880 PLATFORM. 1163 00:38:06,880 --> 00:38:11,800 IT HAS A -- MASS SPEC PLATFORM 1164 00:38:11,800 --> 00:38:12,120 INDEPENDENT. 1165 00:38:12,120 --> 00:38:15,080 IT'S ALSO LARGELY BIOASSAY 1166 00:38:15,080 --> 00:38:16,560 INDEPENDENT SO YOU CAN USE 1167 00:38:16,560 --> 00:38:18,640 BIOASSAYS WITH READ OUTS OF MOST 1168 00:38:18,640 --> 00:38:23,440 TYPES YOU MIGHT ENCOUNTER LIVE, 1169 00:38:23,440 --> 00:38:24,160 DEAD, ET CETERA. 1170 00:38:24,160 --> 00:38:25,840 IT HAS BOTH ONLINE WEB SERVER 1171 00:38:25,840 --> 00:38:30,440 WHICH YOU CAN ACCESS HERE AS 1172 00:38:30,440 --> 00:38:33,440 WELL AS A LOCAL VERSION IF YOU 1173 00:38:33,440 --> 00:38:34,480 WOULD RATHER RUN IT ON YOUR 1174 00:38:34,480 --> 00:38:36,400 LOCAL MACHINE AND NOT PUT YOUR 1175 00:38:36,400 --> 00:38:38,360 DATA ON OUR WEB SERVER. 1176 00:38:38,360 --> 00:38:40,080 AND IT HAS A SUPPORT NETWORK SO 1177 00:38:40,080 --> 00:38:44,120 YOU CAN ASK QUESTIONS AND GET 1178 00:38:44,120 --> 00:38:44,320 HELP. 1179 00:38:44,320 --> 00:38:45,640 REALLY THE SYSTEM WORKS IN FOUR 1180 00:38:45,640 --> 00:38:45,840 WAYS. 1181 00:38:45,840 --> 00:38:48,400 IT HAS A STAGE FOR UP LOADING 1182 00:38:48,400 --> 00:38:48,760 YOUR DATA. 1183 00:38:48,760 --> 00:38:51,000 WE DO A NUMBER EVER DATA 1184 00:38:51,000 --> 00:38:52,400 VALIDATION, QUALITY CONTROL 1185 00:38:52,400 --> 00:38:53,560 CHECKS TO MAKE SURE THE DATASET 1186 00:38:53,560 --> 00:38:55,000 YOU HAVE UP LOADED IS 1187 00:38:55,000 --> 00:38:57,800 APPROPRIATE FOR ANALYSIS AND TRY 1188 00:38:57,800 --> 00:39:00,000 AND GIVE FEEDBACK IN CASES WHERE 1189 00:39:00,000 --> 00:39:00,440 THERE ARE PROBLEMS. 1190 00:39:00,440 --> 00:39:01,320 THEN WE PERFORM THE CORE 1191 00:39:01,320 --> 00:39:03,800 ACTIVITY MAPPING, WHICH MAKES 1192 00:39:03,800 --> 00:39:04,640 PREDICTIONS ABOUT WHICH NATURAL 1193 00:39:04,640 --> 00:39:07,440 PRODUCTS ARE RELEVANT TO THE 1194 00:39:07,440 --> 00:39:08,240 OBSERVED ACTIVITIES AND THEN WE 1195 00:39:08,240 --> 00:39:10,400 HAVE ON LOAN DATA VISUALIZATION 1196 00:39:10,400 --> 00:39:11,960 TOOLS TO HELP INTERPRET THE DATA 1197 00:39:11,960 --> 00:39:15,680 AT THE END. 1198 00:39:15,680 --> 00:39:16,280 SO, WHAT I WOULD LIKE TO DO IN 1199 00:39:16,280 --> 00:39:20,120 THE NEXT FEW SLIDES IS JUST 1200 00:39:20,120 --> 00:39:21,040 EXPLAIN A LITTLE BIT ABOUT HOW 1201 00:39:21,040 --> 00:39:22,160 THIS PLATFORM WORKS UNDER THE 1202 00:39:22,160 --> 00:39:24,320 HOOD AND HOW IT MIGHT BE APPLIED 1203 00:39:24,320 --> 00:39:27,320 TO NATURAL PRODUCTS DISCOVERY 1204 00:39:27,320 --> 00:39:28,400 PROGRAMS BUT HOPEFULLY ARE 1205 00:39:28,400 --> 00:39:29,640 RELEVANT TO MANY OF YOU HERE IN 1206 00:39:29,640 --> 00:39:31,000 THE AUDIENCE. 1207 00:39:31,000 --> 00:39:33,360 SO IF WE START BY THINKING ABOUT 1208 00:39:33,360 --> 00:39:35,920 A SET OF SAMPLES, SO HERE WE 1209 00:39:35,920 --> 00:39:38,200 HAVE JUST NINE SAMPLES IN OUR 1210 00:39:38,200 --> 00:39:38,840 CARTOON VIEW. 1211 00:39:38,840 --> 00:39:41,480 IF WE SCREEN THOSE IN SOME 1212 00:39:41,480 --> 00:39:42,960 PROFILING ASSAY, AGAIN THIS 1213 00:39:42,960 --> 00:39:46,040 COULD BE ANYTHING. 1214 00:39:46,040 --> 00:39:47,440 THIS COULD BE EACH COLUMN IS 1215 00:39:47,440 --> 00:39:48,720 DIFFERENT BIOASSAY READ OUT. 1216 00:39:48,720 --> 00:39:50,360 THESE COULD BE DIFFERENT SIZE 1217 00:39:50,360 --> 00:39:51,640 AND SHAPE FEATURES FROM IMAGE 1218 00:39:51,640 --> 00:39:54,120 BASED SCREENING. 1219 00:39:54,120 --> 00:39:54,720 THEY COULD BE THE RESPONSES OF 1220 00:39:54,720 --> 00:39:55,880 DIFFERENT ORGANISMS PERHAPS A 1221 00:39:55,880 --> 00:40:01,400 PANEL OF DIFFERENT TYPES OF ORG 1222 00:40:01,400 --> 00:40:01,640 NITION. 1223 00:40:01,640 --> 00:40:02,520 OR THEY COULD BE DIFFERENT 1224 00:40:02,520 --> 00:40:04,800 RESISTANT MUTANTS OF THE SAME 1225 00:40:04,800 --> 00:40:05,560 ORGANISM OR SOMETHING LIKE THIS. 1226 00:40:05,560 --> 00:40:07,480 IN ANY CASE, HERE WE HAVE A SORT 1227 00:40:07,480 --> 00:40:09,840 OF HEAT MAP WHICH SHOWS THE 1228 00:40:09,840 --> 00:40:11,320 RELATIVE EFFICACY OF EACH SAMPLE 1229 00:40:11,320 --> 00:40:12,520 IN EACH OF THE READ OUTS AND 1230 00:40:12,520 --> 00:40:14,440 THEN WE COMPARE THIS WITH 1231 00:40:14,440 --> 00:40:16,040 METABOLOMICS DATA AND THEN IN 1232 00:40:16,040 --> 00:40:18,640 THIS CASE, THE ROWS -- EACH ROW 1233 00:40:18,640 --> 00:40:20,640 IS A SAMPLE AND IN THIS CASE, 1234 00:40:20,640 --> 00:40:23,720 THE COLUMNS ARE INDIVIDUAL MASS 1235 00:40:23,720 --> 00:40:24,080 SPEC FEATURES. 1236 00:40:24,080 --> 00:40:27,720 SO EACH COLUMN IS A SINGLE MASS 1237 00:40:27,720 --> 00:40:29,200 SPEC FEATURE FROM YOUR RUN AND 1238 00:40:29,200 --> 00:40:32,000 THE GRAY AND WHITE DENOTES 1239 00:40:32,000 --> 00:40:32,600 WHETHER THAT MASS SPEC FEATURE 1240 00:40:32,600 --> 00:40:35,240 IS PRESENT IN THAT SAMPLE OR 1241 00:40:35,240 --> 00:40:36,400 NOT. 1242 00:40:36,400 --> 00:40:40,520 SO YOU CAN MANAGE THIN MASS SPEC 1243 00:40:40,520 --> 00:40:41,560 FEATURE IS HIGHLY PREVALENT IN 1244 00:40:41,560 --> 00:40:42,600 ALL CASE WHERE IS IT'S THIS ONE 1245 00:40:42,600 --> 00:40:45,520 NEXT DOOR IS ONLY PRESENT IN A 1246 00:40:45,520 --> 00:40:45,840 SINGLE SAMPLE. 1247 00:40:45,840 --> 00:40:47,720 SO IF WE LOOK AT THESE DATA, IN 1248 00:40:47,720 --> 00:40:49,080 THE PAST, IT WILL BE LEFT TO 1249 00:40:49,080 --> 00:40:52,680 STUDENTS OR RESEARCHERS TO TRY 1250 00:40:52,680 --> 00:40:54,840 AND EMPIRICALLY DRAW 1251 00:40:54,840 --> 00:40:56,120 CONNECTIVITY BETWEEN PRESENCE OR 1252 00:40:56,120 --> 00:40:57,440 ABSENCE OF PARTICULAR PHENOTYPES 1253 00:40:57,440 --> 00:41:00,680 AND PRESENCE OR ABSENCE OF 1254 00:41:00,680 --> 00:41:02,280 CHEMISTRY WHICH MIGHT BE WORTH 1255 00:41:02,280 --> 00:41:02,640 ISOLATING. 1256 00:41:02,640 --> 00:41:06,320 THIS IS WHERE WE ENDED UP WITH 1257 00:41:06,320 --> 00:41:11,000 REPETITIVE BIOASS I GUIDED 1258 00:41:11,000 --> 00:41:12,400 FRACTIONATION METHODOLOGY. 1259 00:41:12,400 --> 00:41:15,520 BUT IF WE EXTRACT OR LOOK AT THE 1260 00:41:15,520 --> 00:41:17,520 DATA CAREFULLY, WE FIND THAT 1261 00:41:17,520 --> 00:41:20,040 FOUR OF THESE SAMPLES GIVE US 1262 00:41:20,040 --> 00:41:20,640 FINGERPRINTS WHICH ARE VERY, 1263 00:41:20,640 --> 00:41:21,360 VERY SIMILAR. 1264 00:41:21,360 --> 00:41:22,480 AND IF WE EXTRACT JUST THESE 1265 00:41:22,480 --> 00:41:26,840 ROWS OF THE DATASET, AND WE CAN 1266 00:41:26,840 --> 00:41:29,040 SEE THAT IF WE LOOK AT THE 1267 00:41:29,040 --> 00:41:31,640 METABOLOMICS DATA FOR THESE FOUR 1268 00:41:31,640 --> 00:41:33,360 SAMPLES, THERE ARE TWO SAMPLES 1269 00:41:33,360 --> 00:41:33,640 HERE. 1270 00:41:33,640 --> 00:41:35,880 THIS ONE OUTLINED IN RED AND 1271 00:41:35,880 --> 00:41:37,960 THIS ONE OUTLINED IN GREEN THAT 1272 00:41:37,960 --> 00:41:39,880 ARE PRESENT IN ALL FOUR CASES. 1273 00:41:39,880 --> 00:41:41,080 AND SO ONE HYPOTHESIS IS, ONE OF 1274 00:41:41,080 --> 00:41:42,960 THESE TWO IS RESPONSIBLE FOR THE 1275 00:41:42,960 --> 00:41:43,960 BIOLOGICAL ACTIVITY. 1276 00:41:43,960 --> 00:41:47,040 BUT IF WE LOOK BACKWARDS AT THE 1277 00:41:47,040 --> 00:41:48,040 ORIGINAL DATASET, WE FIND THIS 1278 00:41:48,040 --> 00:41:50,040 SAMPLE HIGHLIGHTED IN RED 1279 00:41:50,040 --> 00:41:50,840 ALTHOUGH IT IS PRESENT IN ALL 1280 00:41:50,840 --> 00:41:52,800 THE SAMPLES WHICH HAVE THIS 1281 00:41:52,800 --> 00:41:54,280 PHENOTYPE, IT IS ALSO PRESENT IN 1282 00:41:54,280 --> 00:41:55,520 QUITE A FEW SAMPLES WHICH DID 1283 00:41:55,520 --> 00:41:57,480 NOT HAVE THAT PHENOTYPE. 1284 00:41:57,480 --> 00:41:59,480 THE PROBABILITY THAT THIS 1285 00:41:59,480 --> 00:42:02,480 PARTICULAR FEATURE IS THE DRIVER 1286 00:42:02,480 --> 00:42:03,560 OF THIS PARTICULAR BIOLOGICAL 1287 00:42:03,560 --> 00:42:05,080 PROFILE IS LOW. 1288 00:42:05,080 --> 00:42:07,080 BY CONTRAST, IN THE SECOND 1289 00:42:07,080 --> 00:42:08,440 EXAMPLE, IT'S PRESENT IN EVERY 1290 00:42:08,440 --> 00:42:09,880 CASE WHERE THIS PHENOTYPE IS 1291 00:42:09,880 --> 00:42:11,800 OBSERVED AND ONLY PRESENT IN 1292 00:42:11,800 --> 00:42:12,680 MOST CASES. 1293 00:42:12,680 --> 00:42:14,800 SO THAT WOULD BE HIGH PRIORITY. 1294 00:42:14,800 --> 00:42:20,520 SO REALLY NP ANALYST JOB IS TO 1295 00:42:20,520 --> 00:42:22,880 PRIORITIZE THOSE WHICH ARE 1296 00:42:22,880 --> 00:42:23,160 RELEVANT. 1297 00:42:23,160 --> 00:42:23,960 THE IMPORTANT THING ABOUT THIS, 1298 00:42:23,960 --> 00:42:24,840 THIS STEPS AWAY FROM THE MORE 1299 00:42:24,840 --> 00:42:28,240 TRADITIONAL MODEL WHERE MA TAB 1300 00:42:28,240 --> 00:42:29,480 LIGHTS WERE STUDIED BECAUSE THEY 1301 00:42:29,480 --> 00:42:32,440 HAD GOOD CHROMATIC PROPERTIES OR 1302 00:42:32,440 --> 00:42:34,560 THEY WERE A REASONABLE TITER OR 1303 00:42:34,560 --> 00:42:37,080 IN SOME OTHER WAY SORT OF 1304 00:42:37,080 --> 00:42:39,280 PRIORITIZED AFTER THE RAW DATA 1305 00:42:39,280 --> 00:42:39,920 BY HUMAN OPERATORS. 1306 00:42:39,920 --> 00:42:41,920 AND IN THIS CASE, REALLY WE ARE 1307 00:42:41,920 --> 00:42:44,400 ASKING ONLY ABOUT THE 1308 00:42:44,400 --> 00:42:45,560 STATISTICAL RELEVANCE FOR EACH 1309 00:42:45,560 --> 00:42:48,520 FEATURE AND IN TURN, THAT COULD 1310 00:42:48,520 --> 00:42:50,200 HIGHLIGHT THE NEXT GENERATION 1311 00:42:50,200 --> 00:42:51,480 DATA IN THE NATURAL PRODUCTS 1312 00:42:51,480 --> 00:42:52,240 PHASE. 1313 00:42:52,240 --> 00:42:54,000 SO IF WE THINK ABOUT HOW TO 1314 00:42:54,000 --> 00:42:56,400 SCORE THESE, WE WANT TO HAVE TWO 1315 00:42:56,400 --> 00:42:56,640 THINGS. 1316 00:42:56,640 --> 00:42:57,960 WE'D LIKE TO KNOW HOW STRONG IS 1317 00:42:57,960 --> 00:43:00,240 THE PHENOTYPE AND HOW CONSISTENT 1318 00:43:00,240 --> 00:43:01,600 IS IT? 1319 00:43:01,600 --> 00:43:03,280 SO IN TERMS OF STRICT OF THE 1320 00:43:03,280 --> 00:43:05,720 PHENOTYPE F WE PICK ONE OF THESE 1321 00:43:05,720 --> 00:43:06,960 FEATURES AND EXTRACT THE 1322 00:43:06,960 --> 00:43:10,280 BIOASSAY DATA FOR THE SAMPLES 1323 00:43:10,280 --> 00:43:11,120 THIS FEATURE IS N WE GET A 1324 00:43:11,120 --> 00:43:14,120 REDUCED TABLE LIKE THIS. 1325 00:43:14,120 --> 00:43:14,720 YOU CAN SEE IF WE LOOK AT ANY 1326 00:43:14,720 --> 00:43:15,560 PARTICULAR BIOASSAY READ OUT 1327 00:43:15,560 --> 00:43:17,440 WHICH IS EACH OF THESE COLUMNS, 1328 00:43:17,440 --> 00:43:19,800 THE CONSISTENCY IS VERY POOR. 1329 00:43:19,800 --> 00:43:22,040 SO IF WE AVERAGE THE BIOASSAY 1330 00:43:22,040 --> 00:43:25,840 SCORES DOWN EACH COLUMN, WE FIND 1331 00:43:25,840 --> 00:43:27,120 THAT AVERAGE FRIENDSHIP IS WEAK. 1332 00:43:27,120 --> 00:43:30,120 IF WE TAKE OUR OTHER CANDIDATE 1333 00:43:30,120 --> 00:43:30,960 MOLECULE AND EXTRACT THOSE ROWS, 1334 00:43:30,960 --> 00:43:32,880 BECAUSE OF THE CONSISTENCY IN 1335 00:43:32,880 --> 00:43:34,040 EACH COLUMN IS HIGH, WE AVERAGE 1336 00:43:34,040 --> 00:43:37,640 THOSE VALUES FOR CONSISTENCY IN 1337 00:43:37,640 --> 00:43:38,360 THE AVERAGE FINGERPRINT SOURCE 1338 00:43:38,360 --> 00:43:38,680 IS VERY HIGH. 1339 00:43:38,680 --> 00:43:41,120 THIS IS A WAY TO MEASURE THE 1340 00:43:41,120 --> 00:43:42,640 STRENGTH OF THE ACTIVITY IN EACH 1341 00:43:42,640 --> 00:43:47,800 OF YOUR READ OUTS AND THAT TELLS 1342 00:43:47,800 --> 00:43:49,000 YOU SOMETHING ABOUT THE POWER OF 1343 00:43:49,000 --> 00:43:49,960 THE SYSTEM. 1344 00:43:49,960 --> 00:43:52,320 AND THEN THE OTHER QUESTION IS, 1345 00:43:52,320 --> 00:43:55,240 HOW CONSISTENT IS THIS READ OUT? 1346 00:43:55,240 --> 00:43:58,160 AND WE COMPARE THE FINGERPRINTS 1347 00:43:58,160 --> 00:43:58,800 AGAIN TO ONE ANOTHER. 1348 00:43:58,800 --> 00:44:01,000 SO ESSENTIALLY WE LOOK AT ALL 1349 00:44:01,000 --> 00:44:03,240 THE SAMPLES OF THAT PARTICULAR 1350 00:44:03,240 --> 00:44:05,200 METABOLITE IS IN. 1351 00:44:05,200 --> 00:44:07,120 WE COMPARE THEM AGAINST 1352 00:44:07,120 --> 00:44:08,920 THEMSELVES AND IN THIS CASE, YOU 1353 00:44:08,920 --> 00:44:10,160 CAN SEE BECAUSE OF THE 1354 00:44:10,160 --> 00:44:12,320 CONSISTENCY IS QUITE LOW, MANY 1355 00:44:12,320 --> 00:44:17,000 OF THE COMPARATIVE VALUES ARE 1356 00:44:17,000 --> 00:44:23,200 QUITE LOW. 1357 00:44:23,200 --> 00:44:26,240 SO WE CAN TAKE THE AVERAGE OF 1358 00:44:26,240 --> 00:44:27,760 THESE VALUES AND USE THAT AS AN 1359 00:44:27,760 --> 00:44:28,280 INDEPENDENT PHENOTYPIC 1360 00:44:28,280 --> 00:44:30,800 INDEPENDENT SCORE AND THEN SAY 1361 00:44:30,800 --> 00:44:34,880 SOMETHING ABOUT THE RELATIVE 1362 00:44:34,880 --> 00:44:36,400 CONSISTENCY. 1363 00:44:36,400 --> 00:44:37,440 >>I THINK YOU HAVE ABOUT A 1364 00:44:37,440 --> 00:44:38,200 MINUTE LEFT. 1365 00:44:38,200 --> 00:44:38,560 >>OKAY. 1366 00:44:38,560 --> 00:44:40,960 WE ARE JUST WRAPPING UP SO IT 1367 00:44:40,960 --> 00:44:42,680 WILL BE FINE. 1368 00:44:42,680 --> 00:44:43,840 >>THANK YOU. 1369 00:44:43,840 --> 00:44:46,600 >>SO, IF WE GIVE ONE EXAMPLE 1370 00:44:46,600 --> 00:44:50,320 HERE, WE TOOK 154 MARINE 1371 00:44:50,320 --> 00:44:52,560 BACTERIA AND TURNED THEM INTO 1372 00:44:52,560 --> 00:44:55,520 925 PRE FRACTIONS AND RAN THAT 1373 00:44:55,520 --> 00:44:58,760 IN TRIPLICATE ON THE MASS SPEC 1374 00:44:58,760 --> 00:45:09,280 TROM TERFOR UNDER 2800 SAMPLES. 1375 00:45:17,480 --> 00:45:20,280 IF WE LOOK QUICKLY AS ONE 1376 00:45:20,280 --> 00:45:22,560 EXAMPLE HERE, WE FIND IN THIS 1377 00:45:22,560 --> 00:45:24,760 CASE, MANY OF THE SAMPLES, MANY 1378 00:45:24,760 --> 00:45:25,840 OF THE SQUARES ARE ALL CONNECTED 1379 00:45:25,840 --> 00:45:29,040 BY A SINGLE MASS SPEC FEATURE. 1380 00:45:29,040 --> 00:45:31,960 IF WE LOOK AT THE CHROME 1381 00:45:31,960 --> 00:45:33,520 ATOGRAM, TOP IS THE RAW AND THE 1382 00:45:33,520 --> 00:45:35,920 BOTTOM IS THE EXTRACTED FOR THIS 1383 00:45:35,920 --> 00:45:37,600 FEATURE, WE FIND THAT FEATURE 1384 00:45:37,600 --> 00:45:40,400 ALTHOUGH LARGELY OBSCURED IN THE 1385 00:45:40,400 --> 00:45:42,440 ORIGINAL IS EASY TO IDENTIFY 1386 00:45:42,440 --> 00:45:43,200 HERE. 1387 00:45:43,200 --> 00:45:44,000 AND IF WE THEN LOOK AT WHAT THAT 1388 00:45:44,000 --> 00:45:46,800 CHEMISTRY IS, WE CAN YUSILA LATE 1389 00:45:46,800 --> 00:45:51,520 THOSE MATERIALS AND SOLVE THESE 1390 00:45:51,520 --> 00:45:53,600 STRUCTURES. 1391 00:45:53,600 --> 00:45:55,040 SO THE TAKE HOME MESSAGE IS 1392 00:45:55,040 --> 00:45:56,560 INFORMATICS AND TECHNOLOGY 1393 00:45:56,560 --> 00:45:57,680 APPROACHES ARE INFLUENCING 1394 00:45:57,680 --> 00:46:00,680 HEAVILY THE WAY RESEARCH GROUPS 1395 00:46:00,680 --> 00:46:01,640 DEVELOP NATURAL PRODUCTS 1396 00:46:01,640 --> 00:46:08,360 DISCOVERY AND THAT WE AND OTHERS 1397 00:46:08,360 --> 00:46:11,000 IN THIS AREA ARE REVISING THOSE 1398 00:46:11,000 --> 00:46:11,360 PLATFORMS. 1399 00:46:11,360 --> 00:46:12,640 IT'S BRINGING A WHOLE NEW WORLD 1400 00:46:12,640 --> 00:46:20,040 OF DISCOVERY TO THE FIELD. 1401 00:46:20,040 --> 00:46:22,160 THE LAST THING I SHOULD DO IS 1402 00:46:22,160 --> 00:46:22,760 THANK THE COLLABORATORS. 1403 00:46:22,760 --> 00:46:24,600 THE FOLKS FROM MY LAB WHO 1404 00:46:24,600 --> 00:46:25,160 DEVELOPED A NUMBER OF THESE 1405 00:46:25,160 --> 00:46:26,640 TOOLS AND THE FUNDING AGENCIES 1406 00:46:26,640 --> 00:46:29,040 FOR THEIR SUPPORT AND YOU HAVE 1407 00:46:29,040 --> 00:46:32,920 TO ASK QUESTIONS IN THE Q&A. 1408 00:46:32,920 --> 00:46:33,880 >>THANK YOU VERY MUCH FOR YOUR 1409 00:46:33,880 --> 00:46:35,120 PRESENTATION. 1410 00:46:35,120 --> 00:46:36,760 VERY VALUABLE INSIGHTS INTO 1411 00:46:36,760 --> 00:46:41,320 INTEGRATING BIOLOGICAL SCREENING 1412 00:46:41,320 --> 00:46:42,480 AND MASS SPECTRO METRIC DATA. 1413 00:46:42,480 --> 00:46:44,200 WE'LL GIVE THE FLOOR NOW TO OUR 1414 00:46:44,200 --> 00:46:45,760 NEXT AND FINAL SPEAKER BEFORE 1415 00:46:45,760 --> 00:46:48,400 OUR Q&A CISION AND THAT IS 1416 00:46:48,400 --> 00:46:50,960 DR. MANDE HOLFORD. 1417 00:46:50,960 --> 00:46:51,360 >>HI, EVERYONE. 1418 00:46:51,360 --> 00:46:52,560 THANK YOU FOR JOINING US TODAY. 1419 00:46:52,560 --> 00:46:54,640 THANK YOU TO CRAIG AND PATRICK 1420 00:46:54,640 --> 00:46:57,040 FOR THE INVITATION TO PRESENT 1421 00:46:57,040 --> 00:46:58,040 AND SHARE OUR WORK. 1422 00:46:58,040 --> 00:47:00,600 I WANT TO TELL YOU, AND THEY 1423 00:47:00,600 --> 00:47:02,280 PROBABLY DIDN'T PLAN IT THIS 1424 00:47:02,280 --> 00:47:06,240 WAY, BUT IT'S VERY GOOD ORDERING 1425 00:47:06,240 --> 00:47:09,800 OF HAVING US SPEAK IN THE ORDER 1426 00:47:09,800 --> 00:47:11,600 WE DID BARRY FOLLOWED BY ROGER 1427 00:47:11,600 --> 00:47:12,280 AND THEN MYSELF. 1428 00:47:12,280 --> 00:47:14,480 AND WE REALLY ARE TALKING ABOUT 1429 00:47:14,480 --> 00:47:16,880 WHERE WE WANT TO GO WITH NATURAL 1430 00:47:16,880 --> 00:47:18,640 PRODUCTS DEVELOPMENT IN MY TALK. 1431 00:47:18,640 --> 00:47:20,360 SO SEEING WHERE THE HOCKEY PUCK 1432 00:47:20,360 --> 00:47:22,120 IS GOING TO BE INSTEAD OF WHERE 1433 00:47:22,120 --> 00:47:23,080 IT IS. 1434 00:47:23,080 --> 00:47:24,640 SO WE'RE GOING TO TALK ABOUT 1435 00:47:24,640 --> 00:47:27,400 DEVELOPING MODELS FOR 1436 00:47:27,400 --> 00:47:27,920 CHARACTERIZING VENOM BASED 1437 00:47:27,920 --> 00:47:28,440 MARINE NATURAL PRODUCTS. 1438 00:47:28,440 --> 00:47:33,680 AND I WANT TO START OFF WITH 1439 00:47:33,680 --> 00:47:35,480 THIS QUOTE, PROGRESS IN SCIENCE 1440 00:47:35,480 --> 00:47:39,840 DEPENDS MOSTLY ON NEW 1441 00:47:39,840 --> 00:47:40,480 TECHNIQUES, NEW DISCOVERIES AND 1442 00:47:40,480 --> 00:47:40,720 NEW IDEAS. 1443 00:47:40,720 --> 00:47:41,680 PROBABLY IN THAT PARTICULAR 1444 00:47:41,680 --> 00:47:42,040 ORDER. 1445 00:47:42,040 --> 00:47:44,880 AND SO, I THINK WE ARE AT THIS 1446 00:47:44,880 --> 00:47:45,400 MOMENT WHERE TECHNOLOGICAL 1447 00:47:45,400 --> 00:47:47,280 INNOVATIONS ARE MEETING THE 1448 00:47:47,280 --> 00:47:48,600 SCIENTIFIC COMPLEXITY AS 1449 00:47:48,600 --> 00:47:52,400 WITNESSED OR EVIDENCED BY HUBBLE 1450 00:47:52,400 --> 00:47:54,600 VERSUS JWST IMAGE. 1451 00:47:54,600 --> 00:47:58,040 WE ARE IN RAY PLACE WHERE FOR 1452 00:47:58,040 --> 00:48:00,160 NATURAL PRODUCTS, PARTICULARLY 1453 00:48:00,160 --> 00:48:01,680 VENOM-BASED, THERE ARE TWO 1454 00:48:01,680 --> 00:48:03,040 TECHNOLOGICAL THINGS THAT NEED 1455 00:48:03,040 --> 00:48:05,400 TO HAPPEN FOR US TO ADVANCE HOW 1456 00:48:05,400 --> 00:48:06,960 WE DISCOVER AND CHARACTERIZE 1457 00:48:06,960 --> 00:48:08,200 NATURAL PRODUCTS FROM THESE 1458 00:48:08,200 --> 00:48:09,080 VENOMOUS ORGANISMS. 1459 00:48:09,080 --> 00:48:11,560 ONE IS TO CONSTRUCT A VENOM'S 1460 00:48:11,560 --> 00:48:12,760 KNOWLEDGE BASE, AND I'LL TALK 1461 00:48:12,760 --> 00:48:13,760 ABOUT THIS SOME MORE, AND THE 1462 00:48:13,760 --> 00:48:15,320 OTHER IS TO DEVELOP MODEL 1463 00:48:15,320 --> 00:48:18,200 SYSTEMS FOR CHARACTERIZING VENOM 1464 00:48:18,200 --> 00:48:18,760 GENETIC REGULATION AND 1465 00:48:18,760 --> 00:48:19,040 EXPRESSION. 1466 00:48:19,040 --> 00:48:21,120 AND I'LL TALK ABOUT THIS IN TWO 1467 00:48:21,120 --> 00:48:23,000 PLACES WHERE I'D LIKE MY LAB TO 1468 00:48:23,000 --> 00:48:23,160 GO. 1469 00:48:23,160 --> 00:48:26,240 AND THAT IS LOOKING AT THE VENOM 1470 00:48:26,240 --> 00:48:28,400 GLANCED IN DEVELOPING ORGANOIDS 1471 00:48:28,400 --> 00:48:32,600 FROM CONES, AND SNAILS AND 1472 00:48:32,600 --> 00:48:33,400 LOOKING AT SEF LOW PODS AND 1473 00:48:33,400 --> 00:48:37,080 BEING ABLE TO DO GENOME EDITING 1474 00:48:37,080 --> 00:48:40,840 OF THE EMBRYONIC STAGE OF THESE 1475 00:48:40,840 --> 00:48:42,720 ANIMALS IN ORDER TORD DEVELOP 1476 00:48:42,720 --> 00:48:43,720 TRANSGENIC VENOMOUS ORGANISMS. 1477 00:48:43,720 --> 00:48:45,320 SO THE POWER OF GENOME 1478 00:48:45,320 --> 00:48:47,120 SEQUENCING HAS REALLY CHANGED 1479 00:48:47,120 --> 00:48:49,720 THE WAY THAT WE DO SCIENCE 1480 00:48:49,720 --> 00:48:50,280 EVERYWHERE. 1481 00:48:50,280 --> 00:48:51,880 EVERY SINGLE THING FROM NATURAL 1482 00:48:51,880 --> 00:48:53,840 PRODUCT CHEMIST TO THE 1483 00:48:53,840 --> 00:48:55,840 TRADITIONAL BIOLOGISTS IN THE 1484 00:48:55,840 --> 00:48:56,760 TURN OF THE CENTURY IN 2000, 1485 00:48:56,760 --> 00:48:58,120 WHEN THEY SOLVED THE HUMAN 1486 00:48:58,120 --> 00:49:00,000 GENOME OR STARTED TO SOLVE IT, 1487 00:49:00,000 --> 00:49:02,920 IT LED TO NOW ALL OF THESE 1488 00:49:02,920 --> 00:49:04,960 INCREASES WE SEE IN PRECISION 1489 00:49:04,960 --> 00:49:05,200 HEALTH. 1490 00:49:05,200 --> 00:49:07,760 IN A SINGULAR WAY A RECENT 1491 00:49:07,760 --> 00:49:09,680 PROJECT WAS DESCRIBED WHERE THEY 1492 00:49:09,680 --> 00:49:12,440 HOPED TO SEQUENCE ALL EUKARYOTIC 1493 00:49:12,440 --> 00:49:14,000 LIFE ON EARTH FOR THE POTENTIAL 1494 00:49:14,000 --> 00:49:15,680 OF TRYING TO SUSTAIN AND FURTHER 1495 00:49:15,680 --> 00:49:17,400 FUTURE LIFE. 1496 00:49:17,400 --> 00:49:18,680 AND SO AFTER CENTURIES OF DOING 1497 00:49:18,680 --> 00:49:23,240 SORT OF REDUCTIONIST AND SILOED 1498 00:49:23,240 --> 00:49:24,440 KINDS OF RESEARCH, THIS QUOTE IS 1499 00:49:24,440 --> 00:49:27,840 VERY PERTINENT IN OUR TASK IS TO 1500 00:49:27,840 --> 00:49:28,640 RESYNTHESIZE BIOLOGY, PUT 1501 00:49:28,640 --> 00:49:30,400 ORGANISMS BACK INTO THE ITS 1502 00:49:30,400 --> 00:49:31,360 ENVIRONMENT AND CONNECT AGAIN TO 1503 00:49:31,360 --> 00:49:32,400 EVOLUTIONARY PAST AND LET US 1504 00:49:32,400 --> 00:49:34,520 FEEL THAT COMPLEX FLOW THAT IS 1505 00:49:34,520 --> 00:49:36,400 ORGANISM, EVOLUTION AND 1506 00:49:36,400 --> 00:49:37,600 ENVIRONMENT UNITED. 1507 00:49:37,600 --> 00:49:39,760 SO I THINK THERE IS NO BETTER 1508 00:49:39,760 --> 00:49:41,800 EXAMPLE OF THAT COMPLEX FLOW OF 1509 00:49:41,800 --> 00:49:45,080 ORGANISM EVOLUTION AND 1510 00:49:45,080 --> 00:49:46,480 ENVIRONMENT THAN VENOM. 1511 00:49:46,480 --> 00:49:48,160 SO VENOM AND VENOMOUS ANIMALS. 1512 00:49:48,160 --> 00:49:50,120 WHEN MOST PEOPLE THINK OF THESE 1513 00:49:50,120 --> 00:49:51,760 THINGS THEY THINK OF AGENTS OF 1514 00:49:51,760 --> 00:49:52,160 FEAR. 1515 00:49:52,160 --> 00:49:54,720 I THINK OF THEM AS AGENTS OF 1516 00:49:54,720 --> 00:49:56,400 CHANGE AND INNOVATION AS NATURE 1517 00:49:56,400 --> 00:49:57,440 HAS SHOWN THEM. 1518 00:49:57,440 --> 00:50:02,760 MY LAB IS FOCUSED ON SNAILS AND 1519 00:50:02,760 --> 00:50:05,120 THEY USE VENOM AS A MEANS THE 1520 00:50:05,120 --> 00:50:06,800 WAY NATURE USED IT TO TRANSFORM 1521 00:50:06,800 --> 00:50:11,280 A PHYSICAL WARFARE INTO A 1522 00:50:11,280 --> 00:50:12,000 BIOCHEMICAL ONE. 1523 00:50:12,000 --> 00:50:12,920 THIS SNAIL IS UNDER THE SAND T 1524 00:50:12,920 --> 00:50:17,280 WILL INJECT VENOM INTO THE FISH, 1525 00:50:17,280 --> 00:50:17,840 THE PREY, AND THEN IT WILL 1526 00:50:17,840 --> 00:50:18,320 SWALLOW THE PREY WHOLE. 1527 00:50:18,320 --> 00:50:19,760 IF THIS IS AN INNOVATION IN 1528 00:50:19,760 --> 00:50:21,400 NATURE, I DON'T KNOW WHAT IS. 1529 00:50:21,400 --> 00:50:23,000 THE REASON THAT THESE SNAILS ARE 1530 00:50:23,000 --> 00:50:24,320 ABLE TO DO THIS IS BECAUSE VENOM 1531 00:50:24,320 --> 00:50:28,360 IS A VERY COMPLEX THING. 1532 00:50:28,360 --> 00:50:29,640 THESE SNAILS PREY ON FISH, WORMS 1533 00:50:29,640 --> 00:50:33,560 AND OTHER MARINE ORGANISMS. 1534 00:50:33,560 --> 00:50:35,840 VENOM HAS BEEN CONVERGENT 1535 00:50:35,840 --> 00:50:37,600 EVOLUTION THROUGHOUT THE TREE OF 1536 00:50:37,600 --> 00:50:38,400 LIFE. 1537 00:50:38,400 --> 00:50:41,280 EVERYWHERE YOU'RE SEEING RED 1538 00:50:41,280 --> 00:50:42,400 INDICATES A VENOMOUS ORGANISM. 1539 00:50:42,400 --> 00:50:44,360 AND VENOM ITSELF IS INTEGRATED 1540 00:50:44,360 --> 00:50:48,240 PROCESS OF SPECIALIZED TISSUES 1541 00:50:48,240 --> 00:50:49,880 USUALLY GLANCED, AND IT'S 1542 00:50:49,880 --> 00:50:53,920 DELIVERED THROUGH ASSOCIATED 1543 00:50:53,920 --> 00:50:54,680 STRUCTURES, FANGS OR HARPOONS 1544 00:50:54,680 --> 00:50:55,520 AND AS THE ULTIMATE PAIRING OF 1545 00:50:55,520 --> 00:50:57,960 THE ORGANISM WITH THE 1546 00:50:57,960 --> 00:50:58,720 ENVIRONMENT, VENOM CAN LINK 1547 00:50:58,720 --> 00:51:01,440 PHENOTYPE AND GENOTYPE BEHAVIORS 1548 00:51:01,440 --> 00:51:04,120 THAT ARE MEASURABLE BECAUSE 1549 00:51:04,120 --> 00:51:04,840 VENOM IS ONCE USED, IT'S USUALLY 1550 00:51:04,840 --> 00:51:06,960 USED IN ECOLOGICAL BEHAVIORS OF 1551 00:51:06,960 --> 00:51:09,240 PREDATION, DEFENSE OR SEXUAL 1552 00:51:09,240 --> 00:51:10,440 COMPETITION. 1553 00:51:10,440 --> 00:51:12,360 AND SO I THINK THAT THIS IS THE 1554 00:51:12,360 --> 00:51:15,280 ULTIMATE TOOL THAT ENABLES US TO 1555 00:51:15,280 --> 00:51:16,520 ASK A SET OF INTEGRATED 1556 00:51:16,520 --> 00:51:20,440 QUESTIONS THAT ARE ALSO 1557 00:51:20,440 --> 00:51:21,280 COMPLEMENTARY. 1558 00:51:21,280 --> 00:51:22,880 TO GIVE YOU A LITTLE BIT MORE ON 1559 00:51:22,880 --> 00:51:23,520 THE MOLECULAR STRUCTURE, THEY 1560 00:51:23,520 --> 00:51:25,160 ARE NOT ONE THING, THEY ARE 1561 00:51:25,160 --> 00:51:26,160 SEVERAL THINGS. 1562 00:51:26,160 --> 00:51:28,120 SO MADE UP OF SMALL MOLECULES, 1563 00:51:28,120 --> 00:51:29,920 PEPTIDES AND PROTEINS. 1564 00:51:29,920 --> 00:51:32,920 WE FOCUS MOSTLY ON THE PEPTIDES. 1565 00:51:32,920 --> 00:51:36,200 PEPTIDES FROM VENOMOUS SNAILS, 1566 00:51:36,200 --> 00:51:36,880 WHICH CAN HAVE -- EACH SNAIL 1567 00:51:36,880 --> 00:51:40,040 VENOM CONTAINS ANYWHERE FROM 250 1568 00:51:40,040 --> 00:51:41,680 UNIQUE PEPTIDES TO MORE. 1569 00:51:41,680 --> 00:51:42,640 NO TWO SNAILS HAVE EXACTLY THE 1570 00:51:42,640 --> 00:51:48,400 SAME PEPTIDE, SO WHETHER INTEROR 1571 00:51:48,400 --> 00:51:48,960 INTRASPECIES, VENOM IS VERY 1572 00:51:48,960 --> 00:51:49,720 SPECIES SPECIFIC. 1573 00:51:49,720 --> 00:51:52,000 SECOND, THEY ATTACK CONSERVED 1574 00:51:52,000 --> 00:51:53,920 PHYSIOLOGICAL TARGETS. 1575 00:51:53,920 --> 00:51:55,720 THEY ARE CUSTER BOMBS WORKING IN 1576 00:51:55,720 --> 00:51:56,680 CONCERTED FASHION. 1577 00:51:56,680 --> 00:51:58,600 THAT'S WHY YOU'RE ABLE TO SEE 1578 00:51:58,600 --> 00:51:59,880 THE SNAIL EAT THE FISH SO VERY 1579 00:51:59,880 --> 00:52:00,480 QUICKLY. 1580 00:52:00,480 --> 00:52:04,600 THAT FISH DOESN'T HAVE A CHANCE. 1581 00:52:04,600 --> 00:52:06,880 THEY GO FOR BLOOD BRAINS AND 1582 00:52:06,880 --> 00:52:08,480 MEMBRANES BECAUSE -- AND THEY DO 1583 00:52:08,480 --> 00:52:09,840 SO IN A RAPID FIRE ACTION. 1584 00:52:09,840 --> 00:52:12,480 SO THE THIRD PART IS THAT THESE 1585 00:52:12,480 --> 00:52:13,720 MOLECULES WORK. 1586 00:52:13,720 --> 00:52:15,600 SO THEY ARE VERY SUCCESSFUL 1587 00:52:15,600 --> 00:52:16,800 MOLECULAR INNOVATION AND VERY 1588 00:52:16,800 --> 00:52:18,320 GOOD AT WHAT THEY DO. 1589 00:52:18,320 --> 00:52:19,840 AND IN TERMS OF VENOM PEPTIDES, 1590 00:52:19,840 --> 00:52:21,320 VERY GOOD AT MANIPULATING 1591 00:52:21,320 --> 00:52:22,640 CELLULAR COMMUNICATION. 1592 00:52:22,640 --> 00:52:26,880 SO OUR JOB AS SCIENTISTS AS 1593 00:52:26,880 --> 00:52:27,520 ROGER AND BARRY WERE POINTING 1594 00:52:27,520 --> 00:52:28,640 OUT IS TO FIGURE OUT HOW THEY 1595 00:52:28,640 --> 00:52:28,880 WORK. 1596 00:52:28,880 --> 00:52:30,680 WE HAVE DONE A LOT OF 1597 00:52:30,680 --> 00:52:31,520 HIGH-THROUGHPUT METHODS TO TRY 1598 00:52:31,520 --> 00:52:33,080 TO FIGURE THAT OUT BUT WE STILL 1599 00:52:33,080 --> 00:52:34,320 DON'T KNOW. 1600 00:52:34,320 --> 00:52:36,320 WE HAVE BEEN SUCCESSFUL IN 1601 00:52:36,320 --> 00:52:38,800 UNDERSTANDING SOME OF HOW VENOM 1602 00:52:38,800 --> 00:52:39,920 PUP TIDES CAN BE TURNED INTO 1603 00:52:39,920 --> 00:52:42,320 THERAPIES FOR TREATING HUMAN 1604 00:52:42,320 --> 00:52:43,280 DISEASE AND DISORDERS. 1605 00:52:43,280 --> 00:52:47,200 HERE YOU SEE SCREENSHOT OF 1606 00:52:47,200 --> 00:52:48,240 SEVERAL PEPTIDES THEMSELVES OR 1607 00:52:48,240 --> 00:52:51,120 COMPOUNDS DERIVED FROM VENOM 1608 00:52:51,120 --> 00:52:51,600 PEPTIDES USED TO TREAT 1609 00:52:51,600 --> 00:52:53,760 EVERYTHING FROM HYPERTENSION TO 1610 00:52:53,760 --> 00:52:55,400 DIABETES TO CHRONIC PAIN. 1611 00:52:55,400 --> 00:52:57,400 AND SO WHAT IS EXCITING IS NOT 1612 00:52:57,400 --> 00:53:00,360 ONLY WE ARE GETTING NEW 1613 00:53:00,360 --> 00:53:00,960 COMPOUNDS FROM THESE VENOMOUS 1614 00:53:00,960 --> 00:53:03,440 ORGANISMS BUT ALSO FINDING NEW 1615 00:53:03,440 --> 00:53:05,560 PATHWAYS IN HOW TO TREAT THESE 1616 00:53:05,560 --> 00:53:06,680 THINGS. 1617 00:53:06,680 --> 00:53:09,400 FOR EXAMPLE, IN THE CONE SNAIL 1618 00:53:09,400 --> 00:53:10,120 DRUG, IT IS USED TO TREAT 1619 00:53:10,120 --> 00:53:12,320 CHRONIC PAIN AND HIV IN CANCER 1620 00:53:12,320 --> 00:53:12,960 PATIENTS BUT IT DOESN'T WORK ON 1621 00:53:12,960 --> 00:53:16,320 OPIOID RECEPTORS T WORKS ON 1622 00:53:16,320 --> 00:53:16,840 ANTI-CALCIUM CHANNEL. 1623 00:53:16,840 --> 00:53:19,520 SO WE HAVE RIGHT NOW THE MEANS 1624 00:53:19,520 --> 00:53:21,080 TO STUDY AND CHARACTERIZE VENOM 1625 00:53:21,080 --> 00:53:23,480 FROM BIOLOGY USING ALL THE TOOLS 1626 00:53:23,480 --> 00:53:26,000 THAT ARE CURRENTLY AVAILABLE, 1627 00:53:26,000 --> 00:53:26,960 PROTEOMICS, GENOMICS, BIOEN 1628 00:53:26,960 --> 00:53:28,200 FORMATTICS AND FUNCTIONAL 1629 00:53:28,200 --> 00:53:28,440 ASSAYS. 1630 00:53:28,440 --> 00:53:30,840 I THINK WE ARE MISSING A VERY 1631 00:53:30,840 --> 00:53:32,000 VALUABLE PIECE OF THE PUZZLE. 1632 00:53:32,000 --> 00:53:35,120 THIS IS WHERE MY VENOM EVOLUTION 1633 00:53:35,120 --> 00:53:38,800 MATHEMATICS COMES IN. 1634 00:53:38,800 --> 00:53:40,040 MANIPULATE THE VENOM ARSENAL WE 1635 00:53:40,040 --> 00:53:41,880 HAVE TO MANIPULATE THE GENES. 1636 00:53:41,880 --> 00:53:44,120 MOST RESEARCH HAVE FOCUSED 1637 00:53:44,120 --> 00:53:46,480 STRICTLY ON THE TOXINS, SMALL 1638 00:53:46,480 --> 00:53:47,040 MOLECULES, PEPTIDES AND THE 1639 00:53:47,040 --> 00:53:47,520 PROTEINS. 1640 00:53:47,520 --> 00:53:49,000 ESPECIALLY IN NATURAL PRODUCTS 1641 00:53:49,000 --> 00:53:49,480 DEVELOPMENT. 1642 00:53:49,480 --> 00:53:50,560 THE PROBLEM WITH THAT IS THAT 1643 00:53:50,560 --> 00:53:54,240 THE TOXINS EVOLVE VERY RAPIDLY. 1644 00:53:54,240 --> 00:53:54,840 THEY HAVE COMPLEX PATTERNS OF 1645 00:53:54,840 --> 00:53:58,200 EXPRESSION AND THEY RECENTLY 1646 00:53:58,200 --> 00:53:58,760 INCORPORATED INTO THE VENOM 1647 00:53:58,760 --> 00:54:00,360 ARSENAL WHICH MEANS THEY ARE 1648 00:54:00,360 --> 00:54:00,840 CRUDE MIXTURES AND VERY 1649 00:54:00,840 --> 00:54:05,240 DIFFICULT TO PURIFY. 1650 00:54:05,240 --> 00:54:05,880 AND SO, I THINK MOST IMPORTANTLY 1651 00:54:05,880 --> 00:54:08,400 WHEN WE FOCUS ONLY ON THE SMALL 1652 00:54:08,400 --> 00:54:08,880 MOLECULES, PEPTIDES AND 1653 00:54:08,880 --> 00:54:11,400 PROTEINS, WE ARE MISSING THAT 1654 00:54:11,400 --> 00:54:14,680 GRAND OPPORTUNITY WHERE WE ARE 1655 00:54:14,680 --> 00:54:15,920 ABLE TO LOOK AT THE COMPLEX 1656 00:54:15,920 --> 00:54:19,560 MIXTURE AT THE GENETIC AND 1657 00:54:19,560 --> 00:54:20,360 ORGANISMAL PHENOTYPIC BIOLOGY. 1658 00:54:20,360 --> 00:54:21,800 SO THE QUESTION THAT IS GOING 1659 00:54:21,800 --> 00:54:24,520 FORWARD IN MY LAB, I WANT TO 1660 00:54:24,520 --> 00:54:27,760 FOCUS ON HOW VENOM GENES 1661 00:54:27,760 --> 00:54:28,320 WEAPONIZE FOR ECOLOGICAL AND 1662 00:54:28,320 --> 00:54:29,800 WHEN WE DEVELOP THEM AS NATURAL 1663 00:54:29,800 --> 00:54:31,720 PRODUCTS, THERAPEUTIC ADVANTAGE. 1664 00:54:31,720 --> 00:54:32,400 IN ORDER TO ADDRESS THAT 1665 00:54:32,400 --> 00:54:34,640 QUESTION, WE HAVE TO LOOK AT NOT 1666 00:54:34,640 --> 00:54:36,400 JUST THE SMALL MALL COOLS, 1667 00:54:36,400 --> 00:54:38,240 PEPTIDES AND PROTEINS, BUT WE 1668 00:54:38,240 --> 00:54:39,480 HAVE TO LOOK AT THE GENE ITSELF. 1669 00:54:39,480 --> 00:54:41,360 SO NOT FOCUSING ON THE FINISHED 1670 00:54:41,360 --> 00:54:43,080 PRODUCTS BUT LOOKING AT THE 1671 00:54:43,080 --> 00:54:45,320 GENE. 1672 00:54:45,320 --> 00:54:47,320 AND SO ALL VENOM PEPTIDES AND 1673 00:54:47,320 --> 00:54:49,040 PROTEINS ARE EXPRESSED AS A 1674 00:54:49,040 --> 00:54:51,520 SINGLE GENE WITH A SIGNAL 1675 00:54:51,520 --> 00:54:53,000 SEQUENCE THAT IS HIGHLY 1676 00:54:53,000 --> 00:54:56,280 CONSERVED AND THEN A MATURE 1677 00:54:56,280 --> 00:54:57,720 PEPTIDE AT THE END THAT BECOMES 1678 00:54:57,720 --> 00:54:59,560 BIOACTIVE TOXIN. 1679 00:54:59,560 --> 00:55:02,400 WHAT IS GREAT IS EACH VENOM GENE 1680 00:55:02,400 --> 00:55:04,640 CAN BE TRADES TO A DISTINCT 1681 00:55:04,640 --> 00:55:04,840 LOCI. 1682 00:55:04,840 --> 00:55:06,400 THAT ENABLES US TO HAVE A LEVEL 1683 00:55:06,400 --> 00:55:08,760 OF GENETIC ATTRACTABILITY THAT 1684 00:55:08,760 --> 00:55:10,440 IS HARDLY SEEN IN MOST OTHER 1685 00:55:10,440 --> 00:55:10,840 TRAITS. 1686 00:55:10,840 --> 00:55:12,480 IF WE ARE ABLE TO DEVELOP TOOLS 1687 00:55:12,480 --> 00:55:14,760 IN WHICH WE HAVE GENETIC 1688 00:55:14,760 --> 00:55:17,080 ATTRACTABLE MODELS, WE ARE ABLE 1689 00:55:17,080 --> 00:55:20,000 TO MANIPULATE A LOT OF HOW THESE 1690 00:55:20,000 --> 00:55:22,280 PROTEINS AND SMALL MOLECULES ARE 1691 00:55:22,280 --> 00:55:26,920 EXPRESSED AND REGULATED. 1692 00:55:26,920 --> 00:55:33,160 AND BECAUSE AGAIN WE ARE ABLE TO 1693 00:55:33,160 --> 00:55:33,760 DO THIS IN A VERY COMPARATIVE 1694 00:55:33,760 --> 00:55:34,360 MANNER WHICH WE CAN LINK AGAIN 1695 00:55:34,360 --> 00:55:34,960 AS I SAID BEFORE, GENOTYPE TO 1696 00:55:34,960 --> 00:55:35,840 PHENOTYPE AND IMPORTANT FOR THIS 1697 00:55:35,840 --> 00:55:38,840 AUDIENCE, WE START TO REALLY 1698 00:55:38,840 --> 00:55:39,600 UNDERSTAND HOW VENOM PEPTIDES 1699 00:55:39,600 --> 00:55:42,000 FUNCTION TO MANIPULATE CELLULAR 1700 00:55:42,000 --> 00:55:42,320 PHYSIOLOGY. 1701 00:55:42,320 --> 00:55:45,160 AND SO TO DO THESE TWO THINGS, I 1702 00:55:45,160 --> 00:55:47,840 THINK WE NEED NUMBER 1, 1703 00:55:47,840 --> 00:55:49,640 KNOWLEDGE BASE FOR THE VENOM 1704 00:55:49,640 --> 00:55:49,920 COMMUNITY. 1705 00:55:49,920 --> 00:55:54,200 SIMILAR TO HOW THE FLY BASE AND 1706 00:55:54,200 --> 00:55:54,840 ZEN BASE DEVELOPED, THEY 1707 00:55:54,840 --> 00:55:55,440 GALVANIZED THE COMMUNITY, SET 1708 00:55:55,440 --> 00:55:59,720 STANDARDS AND PROTOCOL AND ALLOW 1709 00:55:59,720 --> 00:56:00,360 US TO MAKE BIG LEAPSES IN TERMS 1710 00:56:00,360 --> 00:56:01,880 OF IDEAS AND DISCOVERIES. 1711 00:56:01,880 --> 00:56:03,760 WE NEED TO DEVELOP AND CONSTRUCT 1712 00:56:03,760 --> 00:56:04,760 A VENOM'S KNOWLEDGE BASE AND 1713 00:56:04,760 --> 00:56:06,720 BECAUSE I WORK WITH THE MARINE 1714 00:56:06,720 --> 00:56:08,400 ORGANISMS, THE FIRST SHOULD BE 1715 00:56:08,400 --> 00:56:10,280 THE MARINE VENOM BASE BUT IT 1716 00:56:10,280 --> 00:56:12,160 COULD BE IN GENERAL. 1717 00:56:12,160 --> 00:56:14,480 AND WHILE GENOMES FROM HUMANS 1718 00:56:14,480 --> 00:56:16,200 AND OTHER ORGANISMS HAVE BEEN 1719 00:56:16,200 --> 00:56:22,360 AVAILABLE SINCE THE EARLY TWO 1720 00:56:22,360 --> 00:56:26,840 THOUSANDS, THE FIRST GENOME FROM 1721 00:56:26,840 --> 00:56:28,280 CONE SNAILS ONLY CAME OUT TWO 1722 00:56:28,280 --> 00:56:28,520 YEARS AGO. 1723 00:56:28,520 --> 00:56:33,800 AND WE RECENTLY HAVE GENOMES FOR 1724 00:56:33,800 --> 00:56:35,640 OCTOPUS AND THE SQUID WHICH IS 1725 00:56:35,640 --> 00:56:36,400 UNPUBLISHED FROM COLLEAGUES AT 1726 00:56:36,400 --> 00:56:38,480 THE MARINE BIOLOGICAL 1727 00:56:38,480 --> 00:56:38,760 LABORATORY. 1728 00:56:38,760 --> 00:56:41,960 IT'S A VERY NASCENT FIELD WHENY 1729 00:56:41,960 --> 00:56:44,200 WE THINK ABOUT HOW TO LOOK AT 1730 00:56:44,200 --> 00:56:45,000 VENOMS NATURAL PRODUCT 1731 00:56:45,000 --> 00:56:47,640 DEVELOPMENT AT A GENETIC AND 1732 00:56:47,640 --> 00:56:48,800 GENOMIC LEVEL BECAUSE WE DON'T 1733 00:56:48,800 --> 00:56:50,440 HAVE ENOUGH GENOMES TO DO THAT. 1734 00:56:50,440 --> 00:56:51,480 WE NEED MORE. 1735 00:56:51,480 --> 00:56:52,280 TO GIVE YOU AN EXAMPLE OF WHAT 1736 00:56:52,280 --> 00:56:54,800 IS POSSIBLE FROM OUR OWN WORK IN 1737 00:56:54,800 --> 00:56:57,760 OUR APPROACH, WE COMBINE 1738 00:56:57,760 --> 00:57:01,760 PHYLOGENETIC STORY OF HOW THESE 1739 00:57:01,760 --> 00:57:02,560 SNAILS DEVELOPED OVER TIME, 1740 00:57:02,560 --> 00:57:03,920 EVOLVED, WITH THE TRANSCRIPTOMIC 1741 00:57:03,920 --> 00:57:06,040 AND PROTEOMICS DATA TO GIVE US A 1742 00:57:06,040 --> 00:57:11,160 VALIDATED DATABASE OF TOXIN 1743 00:57:11,160 --> 00:57:11,760 SPECIFICS FROM THE SNAILS USING 1744 00:57:11,760 --> 00:57:12,680 THIS INTEGRATED METHOD. 1745 00:57:12,680 --> 00:57:15,320 WE HAVE IDENTIFIED OUR SNAIL 1746 00:57:15,320 --> 00:57:19,120 TOXINS ARE NEW AND DISTINCT FROM 1747 00:57:19,120 --> 00:57:20,840 THE SNAILS SNAIL TOXINS THAT ARE 1748 00:57:20,840 --> 00:57:21,040 KNOWN. 1749 00:57:21,040 --> 00:57:26,240 WE DID THIS WITH CONEIS AND -- 1750 00:57:26,240 --> 00:57:28,200 TWO REPOSITORIES ON THE MARKET 1751 00:57:28,200 --> 00:57:32,480 RIGHT NOW FOR HELPING US TO 1752 00:57:32,480 --> 00:57:33,880 DECIPHER VENOMOUS SEQUENCES. 1753 00:57:33,880 --> 00:57:34,760 BUT WHILE THEY WORK, THEY ARE 1754 00:57:34,760 --> 00:57:37,360 VERY LIMITED IN WHAT THEY CAN 1755 00:57:37,360 --> 00:57:37,520 DO. 1756 00:57:37,520 --> 00:57:40,680 WE WERE ALSO THE FIRST TO THEN 1757 00:57:40,680 --> 00:57:42,640 IDENTIFY ACTIVITY OF THE TOXINS 1758 00:57:42,640 --> 00:57:44,000 AS PERIPHERAL ANALGESIC 1759 00:57:44,000 --> 00:57:46,560 COMPOUNDS USING A WHOLE ANIMAL 1760 00:57:46,560 --> 00:57:47,480 ASSAY AND THEN WE ALSO 1761 00:57:47,480 --> 00:57:50,160 IDENTIFIED THE ACTIVITY OF OUR 1762 00:57:50,160 --> 00:57:51,440 PEPTIDES, ONE OF THE PEPTIDES N 1763 00:57:51,440 --> 00:57:54,080 HELPING TO TARGET DYSREGULATED 1764 00:57:54,080 --> 00:57:57,480 ION CHANNELS IN LIVER CANCER. 1765 00:57:57,480 --> 00:57:59,440 SO OUR VENOM MOLECULE IS SHOWN 1766 00:57:59,440 --> 00:58:01,440 IN GREEN, TESTED AGAINST 1767 00:58:01,440 --> 00:58:03,240 DOXORUBICIN AND THEN NOT TREATED 1768 00:58:03,240 --> 00:58:04,480 IN RED. 1769 00:58:04,480 --> 00:58:06,560 OUR VENOM PEPTIDE IS GOOD AT 1770 00:58:06,560 --> 00:58:08,080 TARGETING LIVER CANCER TUMORS. 1771 00:58:08,080 --> 00:58:12,400 BUT AGAIN, BY FOCUSING MOSTLY ON 1772 00:58:12,400 --> 00:58:14,400 THE PEPTIDES ITSELF, IT HASN'T 1773 00:58:14,400 --> 00:58:16,920 GIVEN US MUCH IN SIGHT AS TO WHY 1774 00:58:16,920 --> 00:58:18,120 THIS PEPTIDE TARGETS THE 1775 00:58:18,120 --> 00:58:19,400 PARTICULAR CHANNEL IT IS IT. 1776 00:58:19,400 --> 00:58:22,120 TO DO THAT, WE REALLY NEED TO 1777 00:58:22,120 --> 00:58:24,720 DEVELOP MODEL SYSTEMS TO 1778 00:58:24,720 --> 00:58:25,640 CHARACTERIZE VENOM GENETIC 1779 00:58:25,640 --> 00:58:26,360 REGULATION AND EXPRESS. 1780 00:58:26,360 --> 00:58:30,680 AND THE SO, THESE MOL ED SYSTEMS 1781 00:58:30,680 --> 00:58:31,560 HAVE BEEN INFLUENTIAL AND 1782 00:58:31,560 --> 00:58:32,160 TRANSFORMATIVE AND CONTINUE TO 1783 00:58:32,160 --> 00:58:33,640 BE TO HELP US FIGURE OUT A LOT 1784 00:58:33,640 --> 00:58:35,880 ABOUT CELLULAR PHYSIOLOGY AND 1785 00:58:35,880 --> 00:58:37,440 ABOUT NATURAL PRODUCTS 1786 00:58:37,440 --> 00:58:37,800 DEVELOPMENT. 1787 00:58:37,800 --> 00:58:40,680 BUT NONE OF THESE ANIMALS ARE 1788 00:58:40,680 --> 00:58:40,920 VENOMOUS. 1789 00:58:40,920 --> 00:58:43,040 SO IN ORDER TO REALLY BE ABLE TO 1790 00:58:43,040 --> 00:58:45,720 MAKE AND MANIPULATE VENOM GENE 1791 00:58:45,720 --> 00:58:47,720 EXPRESSION AND REGULATION, WE 1792 00:58:47,720 --> 00:58:50,200 ARE GOING TO FOCUS ON TWO 1793 00:58:50,200 --> 00:58:52,440 DIFFERENT MODELS. 1794 00:58:52,440 --> 00:58:55,480 ONE IS USING VENOM GLAND 1795 00:58:55,480 --> 00:58:55,760 ORGANOIDS. 1796 00:58:55,760 --> 00:58:57,600 THERE ARE NO INVERTEBRATE 1797 00:58:57,600 --> 00:58:59,280 ORGANOIDS IN EXISTENCE. 1798 00:58:59,280 --> 00:59:00,680 SO IF WE ARE ABLE TO PULL THIS 1799 00:59:00,680 --> 00:59:02,360 OFF, IT WOULD BE PRETTY BIG. 1800 00:59:02,360 --> 00:59:03,880 MOST ORGANIZED COME FROM 1801 00:59:03,880 --> 00:59:05,200 VERTEBRATE SYSTEMS. 1802 00:59:05,200 --> 00:59:08,440 AND SO, THE SECOND THING IS TO 1803 00:59:08,440 --> 00:59:11,560 DO GENETIC -- GENOME-MODIFIED 1804 00:59:11,560 --> 00:59:13,880 VERSIONS OF SEF LOW PODS, 1805 00:59:13,880 --> 00:59:16,840 PARTICULARLY OCTOPUS, SQUIDS AND 1806 00:59:16,840 --> 00:59:17,400 CUDDLE FISH IN COLLABORATION 1807 00:59:17,400 --> 00:59:18,720 WITH THE MARINE BIOLOGICAL 1808 00:59:18,720 --> 00:59:21,040 LABORATORY WHERE WE CAN 1809 00:59:21,040 --> 00:59:24,360 GENETICALLY ALTER AND ENGINEER 1810 00:59:24,360 --> 00:59:25,760 THE SALIVARY GLANDS OF THESE SEF 1811 00:59:25,760 --> 00:59:27,880 LOW PODS IN ORDER TO MAKE A 1812 00:59:27,880 --> 00:59:29,160 TRANSGENIC SEF LOW POD. 1813 00:59:29,160 --> 00:59:30,600 SO FIRST HOWEVER HAVE WE GOTTEN 1814 00:59:30,600 --> 00:59:32,400 ON THE ORGANOIDS? 1815 00:59:32,400 --> 00:59:33,320 ALL ORGANOIDS FOR THE MOST PART 1816 00:59:33,320 --> 00:59:35,480 ARE MADE FROM EPITHELIAL CELLS 1817 00:59:35,480 --> 00:59:36,520 SO OUR FIRST STEP WAS TO 1818 00:59:36,520 --> 00:59:39,240 IDENTIFY DID WE HAVE EPITHELIAL 1819 00:59:39,240 --> 00:59:42,760 CELLS IN THESE VENOM GLANCED? 1820 00:59:42,760 --> 00:59:45,080 WE DO WHEN WE DID 1821 00:59:45,080 --> 00:59:45,680 IMMUNOHISTOCHEMISTRY. 1822 00:59:45,680 --> 00:59:49,200 AND THE SECOND THING IS THE 1823 00:59:49,200 --> 00:59:49,680 GROWTH FRACTORS ARE VERY 1824 00:59:49,680 --> 00:59:50,320 IMPORTANT FOR GROWING ORGANOIDS 1825 00:59:50,320 --> 00:59:53,280 AND MOST OF THEM COME FROM THE 1826 00:59:53,280 --> 00:59:57,080 WHITE SYSTEM, SO WE TOOK OUR 1827 00:59:57,080 --> 00:59:57,680 TRANSCRIPTOME AND SEARCHED TO 1828 00:59:57,680 --> 00:59:59,280 SEE IF THESE INVERTEBRATES HAVE 1829 00:59:59,280 --> 01:00:00,560 SIMILAR GROWTH FACTORS. 1830 01:00:00,560 --> 01:00:02,080 THEY DO. 1831 01:00:02,080 --> 01:00:02,560 HAPPY DAY. 1832 01:00:02,560 --> 01:00:04,720 SO, WE HAVE BEEN ABLE TO 1833 01:00:04,720 --> 01:00:09,200 SUCCESSFULLY CULTURE THESE 1834 01:00:09,200 --> 01:00:11,640 MARINE SNAIL VENOM GLAND CELLS 1835 01:00:11,640 --> 01:00:12,440 FROM TWO SNAILS BUT THEY DON'T 1836 01:00:12,440 --> 01:00:12,840 SURVIVE VERY LONG. 1837 01:00:12,840 --> 01:00:13,240 WE CAN SEE THEM. 1838 01:00:13,240 --> 01:00:15,720 THEY GROW FOR A FEW WEEKS AND 1839 01:00:15,720 --> 01:00:18,360 THEN THEY GET INFECTED AND DIE. 1840 01:00:18,360 --> 01:00:19,120 SO WE ARE CURRENTLY AT THE STAGE 1841 01:00:19,120 --> 01:00:22,760 WHERE WE ARE MESSING WITH OUR 1842 01:00:22,760 --> 01:00:24,160 GROWTH COCKTAIL, MESSING WITH 1843 01:00:24,160 --> 01:00:25,480 OUR DIGESTION METHODS, MESSING 1844 01:00:25,480 --> 01:00:26,600 WITH THE WHOLE THING TO FIGURE 1845 01:00:26,600 --> 01:00:29,080 OUT HOW TO KEEP THEM ALIVE AND 1846 01:00:29,080 --> 01:00:29,720 THEN HOW TO GET THEM TO THE 1847 01:00:29,720 --> 01:00:33,200 POINT WHERE WE CAN ACTUALLY 1848 01:00:33,200 --> 01:00:34,640 CHARACTERIZE WHAT KIND OF VENOM 1849 01:00:34,640 --> 01:00:36,560 IS GROWING IN THE ORGANOID IF AT 1850 01:00:36,560 --> 01:00:36,720 ALL. 1851 01:00:36,720 --> 01:00:39,200 AND THEN LAST SUMMER I SPENT -- 1852 01:00:39,200 --> 01:00:41,440 I WAS A WHITMAN FELLOW AND I 1853 01:00:41,440 --> 01:00:43,240 WILL BE AGAIN THIS SUMMER AT THE 1854 01:00:43,240 --> 01:00:47,920 MARINE BIOLOGICAL INSTITUTE -- 1855 01:00:47,920 --> 01:00:48,680 LABORATORY NEWOODS HOLE. 1856 01:00:48,680 --> 01:00:51,440 AND THERE I LEARNED ABOUT THE 1857 01:00:51,440 --> 01:00:53,920 CULTURE PROGRAM FOR SEF LOW 1858 01:00:53,920 --> 01:00:54,720 PODS, TO ME IS MANNY FROM HEAVEN 1859 01:00:54,720 --> 01:00:57,400 BECAUSE IT HELPS ME TO FIGURE 1860 01:00:57,400 --> 01:00:59,920 OUT HOW TO MAKE VENOM MODEL 1861 01:00:59,920 --> 01:01:03,960 SYSTEMS FROM A COMPLEX ORGANISM. 1862 01:01:03,960 --> 01:01:06,680 SO THERE ARE SYSTEMS GENETICALLY 1863 01:01:06,680 --> 01:01:08,680 TRACTABLE AND ALSO PRODUCE VENOM 1864 01:01:08,680 --> 01:01:11,360 BUT NOTHING FOR MORE COMPLEX 1865 01:01:11,360 --> 01:01:11,600 ORGANISM. 1866 01:01:11,600 --> 01:01:13,480 SO THEY FIGURED OUT WAYS TO GROW 1867 01:01:13,480 --> 01:01:20,480 CERTAIN SPECIES OF SEF LOW PODS 1868 01:01:20,480 --> 01:01:23,160 FROM THE EMBRYONIC STAGE AND 1869 01:01:23,160 --> 01:01:24,360 WILL THEY GROW PRETTY QUICKLY IN 1870 01:01:24,360 --> 01:01:26,000 A MATTER OF 6 WEEKS OR SO AND 1871 01:01:26,000 --> 01:01:30,160 THEN YOU'RE ALLOWED TO DO GENOME 1872 01:01:30,160 --> 01:01:31,960 EDITING AT THE EMBRYONIC STAGE 1873 01:01:31,960 --> 01:01:32,360 OF THESE ANIMALS. 1874 01:01:32,360 --> 01:01:34,560 WHAT WE ARE INTERESTED IN IS 1875 01:01:34,560 --> 01:01:39,160 TRACK TRAING HOW THE SALIVARY 1876 01:01:39,160 --> 01:01:40,360 GLAND THAT HAS THE TOXINS, 1877 01:01:40,360 --> 01:01:41,880 SIMILAR TO THE VENOM GLANCED IN 1878 01:01:41,880 --> 01:01:42,760 SNAILS, HOW THAT GLAND IS 1879 01:01:42,760 --> 01:01:44,640 DEVELOPED, HOW THE GENES THAT 1880 01:01:44,640 --> 01:01:46,600 ARE EXPRESSED IN DIFFERENT AREAS 1881 01:01:46,600 --> 01:01:49,120 OF THE SALIVARY GLAND ARE 1882 01:01:49,120 --> 01:01:49,800 DETERMINED BECAUSE CERTAIN GENES 1883 01:01:49,800 --> 01:01:52,320 ARE EXPRESSING DEFENSIVE VENOM 1884 01:01:52,320 --> 01:01:53,840 AND OTHER VENOMS AND CAN WE 1885 01:01:53,840 --> 01:01:57,200 TWEAK THAT SO WE END UP WITH A 1886 01:01:57,200 --> 01:01:58,280 TRANSGENIC VENOM ANIMAL TO GIVE 1887 01:01:58,280 --> 01:02:00,400 US MORE INFORMATION ABOUT HOW 1888 01:02:00,400 --> 01:02:02,400 THE VENOM PRODUCT ARE MADE. 1889 01:02:02,400 --> 01:02:04,720 SO BASICALLY WE ARE GOING TO DO 1890 01:02:04,720 --> 01:02:06,080 COMPARATIVE GENOMIC AND 1891 01:02:06,080 --> 01:02:07,600 TRANSCRIPTOMIC ANALYSIS OF THESE 1892 01:02:07,600 --> 01:02:08,320 ANIMALS WHICH ARE ALREADY 1893 01:02:08,320 --> 01:02:09,240 AVAILABLE FOR SOME OF EM THIS 1894 01:02:09,240 --> 01:02:11,760 WITH COLLABORATORS AT THE MARINE 1895 01:02:11,760 --> 01:02:12,400 BIOLOGICAL LABORATORY AND THEN 1896 01:02:12,400 --> 01:02:15,560 WE ARE GOING TO PERFORM A SERIES 1897 01:02:15,560 --> 01:02:17,200 OF GLAND DEVELOPMENTAL STUDIES 1898 01:02:17,200 --> 01:02:19,440 TO INVESTIGATE HOW EXACTLY THE 1899 01:02:19,440 --> 01:02:23,480 TOXINS ARE BEING MADE AND 1900 01:02:23,480 --> 01:02:23,760 REGULATED. 1901 01:02:23,760 --> 01:02:26,160 WE STARTED DOING SOME OF THE 1902 01:02:26,160 --> 01:02:28,480 COMPARATIVE GENOMIC WORK LOOKING 1903 01:02:28,480 --> 01:02:31,280 AT THE DOCKSINS FROM THE SEF LOW 1904 01:02:31,280 --> 01:02:34,680 PODS IN PARTICULAR THIS ONE IN 1905 01:02:34,680 --> 01:02:35,560 THE CUDDLE FISH LOOKING AT BOTH 1906 01:02:35,560 --> 01:02:37,880 MALE AND FEMALE ANIMALS. 1907 01:02:37,880 --> 01:02:39,120 WE IDENTIFIED SERIES OF TOXINS 1908 01:02:39,120 --> 01:02:41,960 THAT ARE COMMON TO TOXINS FOUND 1909 01:02:41,960 --> 01:02:43,640 IN SNAKES AND SNAILS AND OTHER 1910 01:02:43,640 --> 01:02:44,000 THINGS. 1911 01:02:44,000 --> 01:02:46,520 SO WHILE IT'S NOT VERY 1912 01:02:46,520 --> 01:02:48,240 WELL-KNOWN THAT SEF LOW POD 1913 01:02:48,240 --> 01:02:49,960 TOXINS EXIST, THEY DO AND THEY 1914 01:02:49,960 --> 01:02:52,320 HAVE SIMILAR THINGS TO WHAT WE 1915 01:02:52,320 --> 01:02:52,680 FIND IN SNAILS. 1916 01:02:52,680 --> 01:02:55,320 AND THEN IN RECENT WORK FROM 1917 01:02:55,320 --> 01:02:58,440 SNAKES, WHERE THEY IDENTIFIED A 1918 01:02:58,440 --> 01:03:02,160 GENE REGULATORY NET FOOTWORK FOR 1919 01:03:02,160 --> 01:03:03,640 TOXIN GENES THAT ARE INVOLVED IN 1920 01:03:03,640 --> 01:03:05,120 PROTEIN MODIFICATION AND 1921 01:03:05,120 --> 01:03:06,160 TRANSPORT, PARTICULARLY THE 1922 01:03:06,160 --> 01:03:12,720 UNFOLDED PROTEIN UPR AND ERAD 1923 01:03:12,720 --> 01:03:13,200 ENDOPLAST MICK RETICK 1924 01:03:13,200 --> 01:03:14,080 LUMASSOCIATEOD BEGREDATION 1925 01:03:14,080 --> 01:03:14,760 PATHWAYS. 1926 01:03:14,760 --> 01:03:16,800 THEY IDENTIFIED A BUNCH OF GENES 1927 01:03:16,800 --> 01:03:18,920 INVOLVED IN MAKING SURE PROTEINS 1928 01:03:18,920 --> 01:03:22,640 AND PEPTIDE FOLD CORRECTLY OR IN 1929 01:03:22,640 --> 01:03:26,160 CASE OF THE PROTEIN DISULFIDE 1930 01:03:26,160 --> 01:03:30,040 STRUCTURES THAT WHICH ALL VENOM 1931 01:03:30,040 --> 01:03:32,720 PEPTIDES HAVE, ARE ABLE TO FORM 1932 01:03:32,720 --> 01:03:33,000 CORRECTLY. 1933 01:03:33,000 --> 01:03:34,440 SO WE ALREADY KNOW CERTAIN 1934 01:03:34,440 --> 01:03:38,000 TARGETS IN THE GENE REGULATORY 1935 01:03:38,000 --> 01:03:40,560 PATHWAY WE'D LIKE TO MANIPULATE 1936 01:03:40,560 --> 01:03:43,200 OR GENETICALLY MODIFY IF WE ARE 1937 01:03:43,200 --> 01:03:47,520 ABLE TO MAKE OUR GENETICALLY SEF 1938 01:03:47,520 --> 01:03:48,400 LOW POD MODELS. 1939 01:03:48,400 --> 01:03:49,960 WE KNOW THAT THOSE PATHWAYS 1940 01:03:49,960 --> 01:03:51,560 USUALLY ARE ACTIVATED IN MOMENTS 1941 01:03:51,560 --> 01:03:54,680 OF STRESS BUT THEY CAN ALSO BE 1942 01:03:54,680 --> 01:03:57,400 ACTIVATED IN DEVELOPMENTAL AND 1943 01:03:57,400 --> 01:04:01,480 CELL SURFACING AND PHYSIOLOGICAL 1944 01:04:01,480 --> 01:04:03,440 TIMES AS WELL. 1945 01:04:03,440 --> 01:04:04,520 SO IN TEAMS OF NON STRESS. 1946 01:04:04,520 --> 01:04:05,880 WE ARE HOPING TO MANIPULATE 1947 01:04:05,880 --> 01:04:08,280 THESE PATHWAYS AND SEE HOW IT 1948 01:04:08,280 --> 01:04:10,200 ALTERS THE EXPRESSION OF THE 1949 01:04:10,200 --> 01:04:14,400 PEPTIDES AND PROTEINS THAT ARE 1950 01:04:14,400 --> 01:04:14,680 INVOLVED. 1951 01:04:14,680 --> 01:04:16,160 I'M AT THE END. 1952 01:04:16,160 --> 01:04:18,720 OUT OF THE SEA AND INTO THE 1953 01:04:18,720 --> 01:04:20,320 WELL, DEVELOPING VENOM MODEL 1954 01:04:20,320 --> 01:04:21,800 SYSTEMS WILL HELP US TO ADDRESS 1955 01:04:21,800 --> 01:04:23,360 THESE THREE BIG QUESTIONS ABOUT 1956 01:04:23,360 --> 01:04:24,560 WHERE WE WOULD LIKE TO GO. 1957 01:04:24,560 --> 01:04:27,360 SO WE STILL DON'T REALLY KNOW 1958 01:04:27,360 --> 01:04:29,520 HOW VENOM PEPTIDES HAVE EVOLVED, 1959 01:04:29,520 --> 01:04:30,640 WHAT DRIVES THE VENOM VARIATION, 1960 01:04:30,640 --> 01:04:34,080 WHY ARE THEIR SO MANY OF THESE 1961 01:04:34,080 --> 01:04:34,760 COMPOUNDS AND HOW DO THEY 1962 01:04:34,760 --> 01:04:35,280 FUNCTION? 1963 01:04:35,280 --> 01:04:37,520 WHY DO THEY TARGET THE MOLECULAR 1964 01:04:37,520 --> 01:04:38,640 TARGETS THEY DO? 1965 01:04:38,640 --> 01:04:40,720 SO WHEN YOU START TO ASK THESE 1966 01:04:40,720 --> 01:04:41,840 QUESTIONS THERE IS A BUNCH OF 1967 01:04:41,840 --> 01:04:44,400 OTHER QUESTIONS THAT ARE NESTED 1968 01:04:44,400 --> 01:04:46,520 AND AS IMPORTANT AND 1969 01:04:46,520 --> 01:04:46,880 COMPLEMENTARY. 1970 01:04:46,880 --> 01:04:48,120 FOR THIS PARTICULAR AUDIENCE, 1971 01:04:48,120 --> 01:04:52,120 THE IDEA OF HOW VENOMS FUNCTION 1972 01:04:52,120 --> 01:04:55,080 IS DOES THE FORM, MEANING IN THE 1973 01:04:55,080 --> 01:04:57,040 TISSUE IN THE SALIVARY GLANDS D 1974 01:04:57,040 --> 01:05:00,560 THAT DICTATE THE FUNCTION? 1975 01:05:00,560 --> 01:05:02,160 ARE THERE SIMILAR MECHANISMS FOR 1976 01:05:02,160 --> 01:05:03,800 THESE TARGETS? 1977 01:05:03,800 --> 01:05:05,600 ION CHANNELS AND RECEPTORS OF 1978 01:05:05,600 --> 01:05:06,960 ALL VARIOUS KINDS AND THEN 1979 01:05:06,960 --> 01:05:09,280 LOOKING'S PHYSIOLOGICAL 1980 01:05:09,280 --> 01:05:10,720 MANIPULATION, SPECIFIC TO THE 1981 01:05:10,720 --> 01:05:11,720 NATURAL PRODUCTS DEVELOPMENT HOW 1982 01:05:11,720 --> 01:05:15,400 CAN WE GET THEM TO IN THESE 1983 01:05:15,400 --> 01:05:20,720 CASES, TARGET THE DYSREGULATIONS 1984 01:05:20,720 --> 01:05:24,880 I ON CHALLENGES VERSUS NORMAL 1985 01:05:24,880 --> 01:05:26,760 CELLS SO I THINK WE ARE AT A 1986 01:05:26,760 --> 01:05:28,520 SWEET SPOT OF WHERE WE HAVE 1987 01:05:28,520 --> 01:05:29,920 TECHNOLOGICAL INNOVATIONS 1988 01:05:29,920 --> 01:05:31,280 MEETING SCIENTIFIC COMIT AND WE 1989 01:05:31,280 --> 01:05:34,240 ARE ABLE TO BE ABLE TO ANSWER 1990 01:05:34,240 --> 01:05:35,720 HOW THE ORGANISM, THE 1991 01:05:35,720 --> 01:05:37,600 ENVIRONMENT AND EVOLUTION PAST 1992 01:05:37,600 --> 01:05:40,880 COME TOGETHER WITH VENOM AND 1993 01:05:40,880 --> 01:05:41,720 VENOMOUS ANTHILLS TO LOOK AT HOW 1994 01:05:41,720 --> 01:05:44,320 TO CHANGE THE IDENTIFICATION AND 1995 01:05:44,320 --> 01:05:45,240 CHARACTERIZATION OF NATURAL 1996 01:05:45,240 --> 01:05:46,440 PRODUCTS DEVELOPMENT SO IT'S NO 1997 01:05:46,440 --> 01:05:48,400 LONGER A HIT-OR-MISS BUT REALLY 1998 01:05:48,400 --> 01:05:49,920 TRYING TO PREDICT AND GUIDE 1999 01:05:49,920 --> 01:05:51,640 WHERE WE GO. 2000 01:05:51,640 --> 01:05:52,480 AND WITH THAT, I'D LIKE TO THANK 2001 01:05:52,480 --> 01:05:54,640 THE LAB MEMBERS, PEOPLE DRIVING 2002 01:05:54,640 --> 01:06:01,920 THIS WORK IS MOSTLY TWO GRAD 2003 01:06:01,920 --> 01:06:02,320 STUDENTS STUDENTS. 2004 01:06:02,320 --> 01:06:03,840 AND I'D ALSO LIKE TO THANK OUR 2005 01:06:03,840 --> 01:06:04,360 COLLABORATORS. 2006 01:06:04,360 --> 01:06:10,360 WE STARTED THE ORGANOID WORK IN 2007 01:06:10,360 --> 01:06:12,320 HAHN'S LAB ANDIGENCE HAS HIS OWN 2008 01:06:12,320 --> 01:06:15,960 LAP IN GERMANY AND AT THE MARINE 2009 01:06:15,960 --> 01:06:18,480 BIOLOGICAL LABORATORY PEOPLE ARE 2010 01:06:18,480 --> 01:06:21,040 WORKING IN THE PROGRAM INCLUDING 2011 01:06:21,040 --> 01:06:22,640 CAYY AND JOSH AND ROGER. 2012 01:06:22,640 --> 01:06:26,280 WE STARTED WORKING WITH THEM AND 2013 01:06:26,280 --> 01:06:29,480 RICHARD'S LAB LEADING THE CUDDLE 2014 01:06:29,480 --> 01:06:30,400 FISH BRIGADE. 2015 01:06:30,400 --> 01:06:32,480 WITH THAT, I THANK YOU AND I ASK 2016 01:06:32,480 --> 01:06:38,200 YOU FOR ANY QUESTIONS. 2017 01:06:38,200 --> 01:06:39,920 >>THANK YOU ALL FOR THOSE 2018 01:06:39,920 --> 01:06:40,880 WONDERFUL TALKS. 2019 01:06:40,880 --> 01:06:42,160 WE DO HAVE A LOT OF QUESTIONS 2020 01:06:42,160 --> 01:06:42,480 COMING IN. 2021 01:06:42,480 --> 01:06:44,120 WE HAVE ABOUT 600 PEOPLE ON 2022 01:06:44,120 --> 01:06:44,320 LINE. 2023 01:06:44,320 --> 01:06:46,480 SO YOU CAN IMAGINE WE ARE 2024 01:06:46,480 --> 01:06:47,040 GETTING A LARGE VOLUME AND 2025 01:06:47,040 --> 01:06:49,080 TRYING TO GET TO AS MANY AS WE 2026 01:06:49,080 --> 01:06:49,560 CAN. 2027 01:06:49,560 --> 01:06:51,760 FIRST QUESTION FOR DR. O'KEEFE, 2028 01:06:51,760 --> 01:06:53,840 ARE THE FRACTIONS OBTAINED 2029 01:06:53,840 --> 01:06:56,120 THROUGH YOUR PROTOCOL STANDARD 2030 01:06:56,120 --> 01:07:00,320 OR DOES THE METHOD CHANGE 2031 01:07:00,320 --> 01:07:05,720 DEPENDING ON THE ORGANISM YOU'RE 2032 01:07:05,720 --> 01:07:06,720 MUTED. 2033 01:07:06,720 --> 01:07:07,680 >>SORRY ABOUT THAT. 2034 01:07:07,680 --> 01:07:13,960 SO THE METHOD IS UNIFORM FOR 2035 01:07:13,960 --> 01:07:14,520 EXAMPLE, FOR PLANT ORGANIC 2036 01:07:14,520 --> 01:07:15,280 EXTRACTS ALL GO THROUGH THE 2037 01:07:15,280 --> 01:07:16,440 METHOD, MARINE ORGANIC EXTRACTS 2038 01:07:16,440 --> 01:07:17,000 DO. 2039 01:07:17,000 --> 01:07:18,760 GO THROUGH A SIMILAR METHOD BUT 2040 01:07:18,760 --> 01:07:22,960 FOR EXAMPLE THE MARINE AQUEOUS 2041 01:07:22,960 --> 01:07:26,920 GOES THROUGH A DIFFERENT METHOD 2042 01:07:26,920 --> 01:07:27,240 THAN OTHERS. 2043 01:07:27,240 --> 01:07:27,880 IT CAN CHANGE DEPENDING UPON THE 2044 01:07:27,880 --> 01:07:32,960 TYPE OF EXTRACT BEING PRE 2045 01:07:32,960 --> 01:07:36,720 FRACTIONATED. 2046 01:07:36,720 --> 01:07:38,240 >>THANK YOU. 2047 01:07:38,240 --> 01:07:40,400 ANOTHER FOR DR. O'KEEFE. 2048 01:07:40,400 --> 01:07:42,960 YOU PRESENTED A LOT OF DATA ON 2049 01:07:42,960 --> 01:07:45,960 THE RESOURCES BEING DEVELOPED 2050 01:07:45,960 --> 01:07:51,600 BUT WHAT DOES YOUR GROUP DO TO 2051 01:07:51,600 --> 01:07:53,040 ADVANCE AS NATURAL THERAPEUTICS 2052 01:07:53,040 --> 01:07:53,200 IS. 2053 01:07:53,200 --> 01:07:54,400 >>WE WORK WITH A VARIETY OF 2054 01:07:54,400 --> 01:07:54,680 FOLKS. 2055 01:07:54,680 --> 01:07:58,120 IN THE NCI, THERE IS THE NCI 2056 01:07:58,120 --> 01:08:00,240 NEXT PROGRAM WHICH CAN TAKE 2057 01:08:00,240 --> 01:08:01,040 PROJECTS FROM SOMETHING THAT IS 2058 01:08:01,040 --> 01:08:04,040 DISCOVERED AND HAS SOME BASIC 2059 01:08:04,040 --> 01:08:05,880 DATA UP THROUGH CLINICAL 2060 01:08:05,880 --> 01:08:06,640 DEVELOPMENT OF THAT. 2061 01:08:06,640 --> 01:08:08,600 WE HAVE A PROJECT I'M WORKING 2062 01:08:08,600 --> 01:08:10,720 WITH FOLKS AT THE CHILDREN'S 2063 01:08:10,720 --> 01:08:12,120 HOSPITAL PHILADELPHIA RIGHT NOW 2064 01:08:12,120 --> 01:08:13,360 FOR THAT SORT OF THINGS. 2065 01:08:13,360 --> 01:08:20,880 WE ALSO HAVE A STEPPING STONES 2066 01:08:20,880 --> 01:08:21,760 PROGRAM. 2067 01:08:21,760 --> 01:08:22,800 ALSO HELPS RESEARCHERS WITH 2068 01:08:22,800 --> 01:08:25,200 GRANTS TRY AND MOVE THINGS DOWN 2069 01:08:25,200 --> 01:08:30,280 THE TRANSLATIONAL LINE. 2070 01:08:30,280 --> 01:08:30,640 >>THANK YOU. 2071 01:08:30,640 --> 01:08:32,680 MOVING TO DR. ROGER LININGTON. 2072 01:08:32,680 --> 01:08:34,960 SOMEONE WANTS TO KNOW HOW CAN 2073 01:08:34,960 --> 01:08:37,480 PEOPLE PARTNER OR HOW DO YOU 2074 01:08:37,480 --> 01:08:39,120 FIND PEOPLE TRAINED TO DO 2075 01:08:39,120 --> 01:08:42,080 HIGH-THROUGHPUT SCREENING IN 2076 01:08:42,080 --> 01:08:42,680 THEIR PARTICULAR DEPARTMENT THEY 2077 01:08:42,680 --> 01:08:44,400 DON'T NECESSARILY HAVE ALL THE 2078 01:08:44,400 --> 01:08:46,120 NECESSARY RESOURCES TO DO ALL OF 2079 01:08:46,120 --> 01:08:46,520 THE PARTS OF THIS. 2080 01:08:46,520 --> 01:08:48,840 SO DO YOU HAVE ANY SUGGESTIONS 2081 01:08:48,840 --> 01:08:52,200 FOR HOW PEOPLE WHO ARE DEFICIENT 2082 01:08:52,200 --> 01:08:53,760 IN ONE ASPECT OR ANOTHER CAN 2083 01:08:53,760 --> 01:08:56,280 FIND PEOPLE TO PARTNER WITH? 2084 01:08:56,280 --> 01:08:59,200 >>THAT'S A GOOD QUESTION. 2085 01:08:59,200 --> 01:09:00,520 I THINK THE NUMBER OF GROUPINGS 2086 01:09:00,520 --> 01:09:02,400 WHO ARE EQUIPPED TO DO BOTH 2087 01:09:02,400 --> 01:09:03,640 SIDES EQUALLY IS RELATIVELY LOW. 2088 01:09:03,640 --> 01:09:06,640 I WOULD SAY BOTH OF THOSE FIELDS 2089 01:09:06,640 --> 01:09:08,240 ARE SORT OF RICH IN ROBUST 2090 01:09:08,240 --> 01:09:09,880 FIELDS WHICH HAVE HUNDREDS OF 2091 01:09:09,880 --> 01:09:11,440 INVESTIGATORS IN THEM. 2092 01:09:11,440 --> 01:09:13,560 SO CERTAINLY ON THE METABOLOMICS 2093 01:09:13,560 --> 01:09:16,200 AND SCREENING SIDE METABOLOMICS 2094 01:09:16,200 --> 01:09:20,320 IS A ENORMOUS SUBJECT AREA, 2095 01:09:20,320 --> 01:09:20,920 METABOLOMICS ASSOCIATION OF 2096 01:09:20,920 --> 01:09:24,440 NORTH AMERICA IS A PLACE TO 2097 01:09:24,440 --> 01:09:24,640 START. 2098 01:09:24,640 --> 01:09:26,920 I WOULD SAY THAT THERE IS A 2099 01:09:26,920 --> 01:09:28,160 DISCONNECT AT THE MOMENT BETWEEN 2100 01:09:28,160 --> 01:09:30,480 THE TIME REQUIRED TO DO 2101 01:09:30,480 --> 01:09:31,800 HIGH-THROUGHPUT SCREENING ON 2102 01:09:31,800 --> 01:09:35,880 50,000 WELLS AND THE TIME TO 2103 01:09:35,880 --> 01:09:37,640 REQUIRE MASS SPECTROMETRY DATA 2104 01:09:37,640 --> 01:09:40,400 ON 50,000 WELLS. 2105 01:09:40,400 --> 01:09:41,640 THE MASS SPEC DATA ACQUISITION 2106 01:09:41,640 --> 01:09:43,800 IS SLOWER AND THAT'S A 2107 01:09:43,800 --> 01:09:44,080 CHALLENGE. 2108 01:09:44,080 --> 01:09:46,080 ONE OF THE THINGSING THAT WE ARE 2109 01:09:46,080 --> 01:09:47,360 WORKING ON AT THE MOMENT 2110 01:09:47,360 --> 01:09:48,400 MULTIPLEXING METHODS TO ALLOW 2111 01:09:48,400 --> 01:09:50,760 YOU TO ACQUIRE THOSE MASS 2112 01:09:50,760 --> 01:09:53,600 SPECTROMETRY DATA AS 2113 01:09:53,600 --> 01:09:55,600 COMPUTATIONAL AND DECONVOLUTE 2114 01:09:55,600 --> 01:09:56,360 THEM AFTERWARDS. 2115 01:09:56,360 --> 01:09:58,360 WHEN THAT IS RELEASED, THAT WILL 2116 01:09:58,360 --> 01:10:00,360 REDUCE THE AMOUNT OF MACHINE 2117 01:10:00,360 --> 01:10:00,760 TIME REQUIRED. 2118 01:10:00,760 --> 01:10:02,760 THEN CONTINUE MAKES ITABLE TO 2119 01:10:02,760 --> 01:10:07,320 USE DEPARTMENTAL CONTRACT 2120 01:10:07,320 --> 01:10:10,120 FACILITIES MASS SPEC FACILITIES 2121 01:10:10,120 --> 01:10:11,080 WITHOUT PUNISHINGLY HIGH COSTS 2122 01:10:11,080 --> 01:10:12,120 FOR ACCESS TO INSTRUMENT TIME. 2123 01:10:12,120 --> 01:10:14,040 I THINK THERE ARE TECHNOLOGIES 2124 01:10:14,040 --> 01:10:16,400 COMING ALONG WHICH WILL 2125 01:10:16,400 --> 01:10:17,120 DRAMATICALLY DECREASE THE COST 2126 01:10:17,120 --> 01:10:18,720 TO DATA ACQUISITION AND 2127 01:10:18,720 --> 01:10:20,400 HOPEFULLY IMPROVE THROUGH PUT 2128 01:10:20,400 --> 01:10:22,520 AND MAKE IT EASIER FOR PEOPLE TO 2129 01:10:22,520 --> 01:10:22,760 DO THAT. 2130 01:10:22,760 --> 01:10:23,120 >>THANK YOU. 2131 01:10:23,120 --> 01:10:24,240 AND THEN ONE MORE QUESTION. 2132 01:10:24,240 --> 01:10:26,560 IT'S A BIT OF A HYBRID BETWEEN 2133 01:10:26,560 --> 01:10:29,800 YOU, BARRY AND ROGER. 2134 01:10:29,800 --> 01:10:32,360 FOR NP ANALYST, THE PERSON IS 2135 01:10:32,360 --> 01:10:34,280 ASKING, IS THERE EXISTING MS 2136 01:10:34,280 --> 01:10:39,800 DATA ON THE NCI NATURAL PRODUCTS 2137 01:10:39,800 --> 01:10:40,000 LIBRARY? 2138 01:10:40,000 --> 01:10:40,680 IF SO, IS THERE A WAY TO COMBINE 2139 01:10:40,680 --> 01:10:43,400 WITH MY BIOASSAY DATA TO TRY TO 2140 01:10:43,400 --> 01:10:46,040 FIGURE OUT WHAT THE LIBRARY IS 2141 01:10:46,040 --> 01:10:46,880 RESPONSIBLE FOR CERTAIN 2142 01:10:46,880 --> 01:10:47,200 ACTIVITIES? 2143 01:10:47,200 --> 01:10:48,080 >>THAT'S A GREAT QUESTION. 2144 01:10:48,080 --> 01:10:51,200 WE WOULD LOVE TO ACQUIRE DATA ON 2145 01:10:51,200 --> 01:10:51,760 THE WHOLE LIBRARY. 2146 01:10:51,760 --> 01:10:54,480 THAT'S A PRETTY AMBITIOUS 2147 01:10:54,480 --> 01:10:54,720 OBJECTIVE. 2148 01:10:54,720 --> 01:10:55,360 THERE ARE A LOT OF FRACTIONS IN 2149 01:10:55,360 --> 01:10:57,640 THERE BUT WE ARE RUNNING A PILOT 2150 01:10:57,640 --> 01:11:00,400 AT THE MOMENT. 2151 01:11:00,400 --> 01:11:01,720 WE WILL RUN MASS SPEC DATA ON A 2152 01:11:01,720 --> 01:11:03,040 SET OF 50,000 FRACTIONS AND 2153 01:11:03,040 --> 01:11:04,960 THOSE DATA WILL BE RETURNED TO 2154 01:11:04,960 --> 01:11:08,200 THE NCI AND SO PROVIDED THAT YOU 2155 01:11:08,200 --> 01:11:10,000 WORK WITH THE NCI TO DEVELOP 2156 01:11:10,000 --> 01:11:14,200 YOUR MTA, IN PRINCIPLE THOSE 2157 01:11:14,200 --> 01:11:14,920 DATA COULD BE MADE AVAILABLE TO 2158 01:11:14,920 --> 01:11:15,520 YOU. 2159 01:11:15,520 --> 01:11:18,560 SO YES, WE ARE STARTING AN EARLY 2160 01:11:18,560 --> 01:11:19,600 PILOT AT THE MOMENT AND WE'LL 2161 01:11:19,600 --> 01:11:23,280 SEE HOW THAT GOES AND WITH LUCK 2162 01:11:23,280 --> 01:11:24,080 WE WILL BE ABLE TO DO MORE IN 2163 01:11:24,080 --> 01:11:24,360 THE FUTURE. 2164 01:11:24,360 --> 01:11:25,440 >>ANYTHING ELSE TO ADD, BARRY? 2165 01:11:25,440 --> 01:11:28,400 >>JUST ONE THING TO FOLLOW-UP 2166 01:11:28,400 --> 01:11:29,120 WHAT ROGER SAID. 2167 01:11:29,120 --> 01:11:31,240 WORN OF THE ISSUES WE DEAL IN 2168 01:11:31,240 --> 01:11:32,680 NATURAL PRODUCTS IS ECK QUITABLE 2169 01:11:32,680 --> 01:11:33,840 DISTRIBUTION AND BENEFIT SHARING 2170 01:11:33,840 --> 01:11:35,720 WITH COUNTRIES THAT HAVE ALLOWED 2171 01:11:35,720 --> 01:11:37,720 THESE COLLECTIONS TO TAKE PLACE. 2172 01:11:37,720 --> 01:11:40,400 IF WE DID METABOLOMICS ON THE 2173 01:11:40,400 --> 01:11:41,920 WHOLE NCI LABORY AND MADE NA 2174 01:11:41,920 --> 01:11:44,360 GLOBALLY AVAILABLE TO EVERYONE 2175 01:11:44,360 --> 01:11:47,120 FOR FREE AND WITHOUT ANY SORT OF 2176 01:11:47,120 --> 01:11:48,600 AGREEMENT TO ENABLE BENEFIT 2177 01:11:48,600 --> 01:11:49,400 SHARING WITH HOST COUNTRIES, 2178 01:11:49,400 --> 01:11:51,240 THAT REALLY WOULD GO AGAINST THE 2179 01:11:51,240 --> 01:11:52,240 AGREEMENTS WITH THOSE HOST 2180 01:11:52,240 --> 01:11:53,960 COUNTRIES THAT ALLOWED THE 2181 01:11:53,960 --> 01:11:56,040 COLLECTIONS TO TAKE PLACE IN THE 2182 01:11:56,040 --> 01:11:56,400 FIRST PLACE. 2183 01:11:56,400 --> 01:11:58,280 AND SO WHAT WE ARE TRYING TO DO 2184 01:11:58,280 --> 01:12:00,600 IS WORK OUT MECHANISMS THAT ARE 2185 01:12:00,600 --> 01:12:02,360 EQUITABLE FOR THEM AS WELL SO 2186 01:12:02,360 --> 01:12:06,280 PEOPLE WILL BE WILLING TO CYB AN 2187 01:12:06,280 --> 01:12:06,800 MTA THAT GAINER TEASE SOME 2188 01:12:06,800 --> 01:12:07,400 BENEFIT SHARING RIGHTS TO GET 2189 01:12:07,400 --> 01:12:11,240 ACCESS TO THAT LARGE DATASET SO 2190 01:12:11,240 --> 01:12:12,800 THOSE HOST COUNTRIES CAN STILL 2191 01:12:12,800 --> 01:12:14,560 HAVE A SEAT AT THE TABLE SHOULD 2192 01:12:14,560 --> 01:12:17,840 ANYTHING BE DEVELOPED. 2193 01:12:17,840 --> 01:12:18,240 >>ALL RIGHT. 2194 01:12:18,240 --> 01:12:20,400 ONE MORE QUESTION FOR ROGER. 2195 01:12:20,400 --> 01:12:25,000 HOW DO YOU TEST FOR SYNERGISTIC 2196 01:12:25,000 --> 01:12:26,600 EFFECTS OF CONSTITUENTS PLANT 2197 01:12:26,600 --> 01:12:28,160 BASED NATURAL PRODUCTS? 2198 01:12:28,160 --> 01:12:30,520 IT IS ONE WE THINK ABOUT A LOT. 2199 01:12:30,520 --> 01:12:32,080 >>THIS STAY REALLY INTERESTING 2200 01:12:32,080 --> 01:12:32,320 PROBLEM. 2201 01:12:32,320 --> 01:12:36,040 SO THE CURRENT VERSION OF THIS 2202 01:12:36,040 --> 01:12:36,560 ONLY TAKES SINGLE AGENTS. 2203 01:12:36,560 --> 01:12:42,440 IT ASSUMES EVERY AGENTS ACTS ON 2204 01:12:42,440 --> 01:12:42,800 ITS OWN. 2205 01:12:42,800 --> 01:12:48,360 SO VERY RECENTLY A GROUP JUST 2206 01:12:48,360 --> 01:12:52,400 PUBLISHED A PAPER IN THE -- IS 2207 01:12:52,400 --> 01:12:53,760 IT PUBLISHED YET? 2208 01:12:53,760 --> 01:12:56,400 IF IT'S NOT PUBLISHED IT'S 2209 01:12:56,400 --> 01:12:58,960 COMING OUT ANY SECOND IN THE 2210 01:12:58,960 --> 01:13:00,400 JOURNAL OF NATURAL PRODUCTS. 2211 01:13:00,400 --> 01:13:03,960 SO YOU CAN MAKE COMPUTATIONAL 2212 01:13:03,960 --> 01:13:05,880 PAIRS ESSENTIALLY, WHERE YOU 2213 01:13:05,880 --> 01:13:07,440 TAKE EVERY COMPONENT AND YOU 2214 01:13:07,440 --> 01:13:09,240 COMPARE IT WITH EVERY OTHER 2215 01:13:09,240 --> 01:13:10,800 COMPONENT AND YOU MAKE THESE 2216 01:13:10,800 --> 01:13:15,080 PAIRINGS AND THEN ALLOW THE 2217 01:13:15,080 --> 01:13:15,720 STATISTICAL PROGRAM TO SEE THERE 2218 01:13:15,720 --> 01:13:17,600 ARE ANY PAIRING THAT SHOWS UP 2219 01:13:17,600 --> 01:13:19,800 REPEATEDLY IN THE DATASET TO 2220 01:13:19,800 --> 01:13:22,600 START TO FIND EXAMPLES WHERE A 2221 01:13:22,600 --> 01:13:24,800 ALONE DOESN'T HAVE ANY EFFECT, B 2222 01:13:24,800 --> 01:13:25,920 ALONE DOESN'T HAVE ANY EFFECT 2223 01:13:25,920 --> 01:13:28,520 BUT WHEN YOU SEE THE AB PAIR YOU 2224 01:13:28,520 --> 01:13:29,600 DO SEE THE EFFECT. 2225 01:13:29,600 --> 01:13:34,640 THIS IS ONE WAY TO LOOK AT THAT 2226 01:13:34,640 --> 01:13:36,160 SYNERGISTIC. 2227 01:13:36,160 --> 01:13:39,400 IT DOESN'T TAKE INTO ACCOUNT 2228 01:13:39,400 --> 01:13:39,880 FAMILY-WIDE GROUPINGS. 2229 01:13:39,880 --> 01:13:40,760 >>THANK YOU. 2230 01:13:40,760 --> 01:13:42,080 QUESTION FOR DR. MANDE HOLFORD. 2231 01:13:42,080 --> 01:13:46,640 YOU GAVE SOME PRETTY INTERESTING 2232 01:13:46,640 --> 01:13:50,400 IDEAS FOR RESOURCES FOR THESE 2233 01:13:50,400 --> 01:13:50,960 VENOM PRODUCING ORGANISMS. 2234 01:13:50,960 --> 01:13:54,400 DO YOU HAVE AN OPTIMISTIC 2235 01:13:54,400 --> 01:13:54,960 TIMEFRAME FOR WHEN YOU THINK 2236 01:13:54,960 --> 01:13:56,680 THEY MIGHT BE READY FOR 2237 01:13:56,680 --> 01:13:58,160 PRIME-TIME. 2238 01:13:58,160 --> 01:13:58,880 >>OPTIMISTICALLY I WOULD SAY 2239 01:13:58,880 --> 01:13:59,960 HOPEFULLY IN THE NEXT 5 YEARS, 2240 01:13:59,960 --> 01:14:02,120 ALL DEPENDING ON GRANT FUNDING. 2241 01:14:02,120 --> 01:14:05,840 WHAT WE CAN AND CAN'T DO. 2242 01:14:05,840 --> 01:14:06,960 THE KNOWLEDGE BASE CAN COME ON 2243 01:14:06,960 --> 01:14:11,280 PRETTY QUICKLY WITH VERY LOW 2244 01:14:11,280 --> 01:14:12,360 FUNDING IS POSSIBLE FOR US TO 2245 01:14:12,360 --> 01:14:14,120 COLLATE THE DATA THAT IS ALL 2246 01:14:14,120 --> 01:14:15,080 RIGHT OUT THERE, WHAT IS NEEDED 2247 01:14:15,080 --> 01:14:17,120 TO REALLY MAKE IT USEFUL ARE 2248 01:14:17,120 --> 01:14:17,800 MORE GENOMES. 2249 01:14:17,800 --> 01:14:19,560 SO AS GENOMES BECOME CHEAPER AND 2250 01:14:19,560 --> 01:14:22,280 PEOPLE ARE ABLE TO DO MORE 2251 01:14:22,280 --> 01:14:24,640 GENOMES, THERE ARE ONLY A FEW, A 2252 01:14:24,640 --> 01:14:25,960 FEW SNAKES, PLATYPUS HAS BEEN 2253 01:14:25,960 --> 01:14:29,200 DONE BUT IN TERMS OF MARINE 2254 01:14:29,200 --> 01:14:31,120 ORGANISMS THERE WERE VERY FEW 2255 01:14:31,120 --> 01:14:33,120 OTHER THAN NEDARIANS AND THE FOX 2256 01:14:33,120 --> 01:14:34,640 JELLYFISH AND THINGS OF THAT 2257 01:14:34,640 --> 01:14:35,280 SORT. 2258 01:14:35,280 --> 01:14:39,000 SO WE JUST NEED MORE GENOMES BUT 2259 01:14:39,000 --> 01:14:39,600 I THINK DRIVING THAT KNOWLEDGE 2260 01:14:39,600 --> 01:14:42,040 BASE WOULD HELP TO GALVANIZE THE 2261 01:14:42,040 --> 01:14:43,800 COMMUNITY AND HELP STANDARDS AND 2262 01:14:43,800 --> 01:14:48,480 PROTOCOLS SO WE CAN SHARE DATA 2263 01:14:48,480 --> 01:14:49,080 ROBUSTLY AND WITHOUT QUESTION 2264 01:14:49,080 --> 01:14:56,200 ABOUT QUALITY AND DATA. 2265 01:14:56,200 --> 01:14:59,880 AND THAT CAN COME ON LINE QUITE 2266 01:14:59,880 --> 01:15:03,200 FASTER THAN THE ORGANOIDS. 2267 01:15:03,200 --> 01:15:04,400 >>ONE MORE QUESTION FOR BARRY. 2268 01:15:04,400 --> 01:15:06,720 CAN YOU GIVE ANY EXAMPLES OF 2269 01:15:06,720 --> 01:15:09,440 THERAPEUTICS THAT HAVE COME 2270 01:15:09,440 --> 01:15:11,200 SPECIFICALLY OUT OF THE NCI 2271 01:15:11,200 --> 01:15:13,440 NATURAL PRODUCTS LIBRARY? 2272 01:15:13,440 --> 01:15:15,120 >>OVER THE YEARS THINGS 2273 01:15:15,120 --> 01:15:16,560 INCLUDING TAXOL WERE REGALLY 2274 01:15:16,560 --> 01:15:23,840 COLLECTED THROUGH THE NCI 2275 01:15:23,840 --> 01:15:24,080 PROGRAM. 2276 01:15:24,080 --> 01:15:25,400 -- SIGNIFICANT PARTICIPATIONING 2277 01:15:25,400 --> 01:15:29,080 AND NOW SOLD AS HALLOW DEN, A 2278 01:15:29,080 --> 01:15:30,480 COUPLE OF ANTI-CANCER AGENTS. 2279 01:15:30,480 --> 01:15:33,360 THE PROTEIN GRAY BITS IN IS 2280 01:15:33,360 --> 01:15:35,920 CURRENTLY IN CLINICAL TRIALS FOR 2281 01:15:35,920 --> 01:15:39,160 SARS-COV-2 PREVENTION. 2282 01:15:39,160 --> 01:15:39,520 >>WONDERFUL. 2283 01:15:39,520 --> 01:15:41,680 CATHERINE DO WE HAVE ANYMORE 2284 01:15:41,680 --> 01:15:43,160 TIME OR DO WE NEED TO MOVE ON? 2285 01:15:43,160 --> 01:15:46,040 >>LET'S TAKE ONE MORE AND THEN 2286 01:15:46,040 --> 01:15:48,440 ANYTHING WE DIDN'T GET TO, DON'T 2287 01:15:48,440 --> 01:15:51,160 WORRY, WE WILL GRAB THEM FOR 2288 01:15:51,160 --> 01:15:53,280 LATER BUT WE NEED TO MOVE ON TO 2289 01:15:53,280 --> 01:15:54,320 OUR NEXT SESSION. 2290 01:15:54,320 --> 01:15:55,960 SO ONE FINAL QUESTION YOU WANT 2291 01:15:55,960 --> 01:15:56,840 TO POSE? 2292 01:15:56,840 --> 01:15:57,080 >>SURE. 2293 01:15:57,080 --> 01:15:58,880 I GUESS ANOTHER FOR BARRY. 2294 01:15:58,880 --> 01:16:01,560 CAN THESE LIBRARIES BE UPSCALED 2295 01:16:01,560 --> 01:16:02,880 WHEN THE MOLECULES ARE FOUND, 2296 01:16:02,880 --> 01:16:03,960 FOR EXAMPLE, PARTICULARLY 2297 01:16:03,960 --> 01:16:07,360 COMPLEX MOLECULES THAT CAN'T BE 2298 01:16:07,360 --> 01:16:08,160 SYNTHESIZED, IS THERE POTENTIAL 2299 01:16:08,160 --> 01:16:09,760 TO OBTAIN ENOUGH PRODUCTS TO 2300 01:16:09,760 --> 01:16:12,000 KEEP THE PIPELINE ROLLING? 2301 01:16:12,000 --> 01:16:12,280 >>YES. 2302 01:16:12,280 --> 01:16:12,920 THAT IS A GOOD POINT. 2303 01:16:12,920 --> 01:16:15,600 AND ONE OF THE WAYS WE HAVE 2304 01:16:15,600 --> 01:16:16,120 BUILT THIS PROGRAM WAS ON 2305 01:16:16,120 --> 01:16:16,800 PARALLEL PROCESSING. 2306 01:16:16,800 --> 01:16:20,840 SO THE SAME WAY WE MIGHT DO 88 2307 01:16:20,840 --> 01:16:22,360 FRACTIONATION SIMULTANEOUSLY, 2308 01:16:22,360 --> 01:16:25,120 WITH 215 MILLIGRAMS EACH, WE 2309 01:16:25,120 --> 01:16:26,280 DOCK THAT ALL WITH ONE ORGANISM 2310 01:16:26,280 --> 01:16:28,520 AND THE SAME WAY WITH THE SECOND 2311 01:16:28,520 --> 01:16:29,840 STAGE PURIFICATION WHERE WE ARE 2312 01:16:29,840 --> 01:16:31,960 DOING 22 SUB FRACTIONS WITH ONE 2313 01:16:31,960 --> 01:16:33,600 MILLIGRAM INJECTED. 2314 01:16:33,600 --> 01:16:35,800 WE DOCK THAT WITH 44 THINGS 2315 01:16:35,800 --> 01:16:37,560 OVERNIGHT ON ONE INSTRUMENT. 2316 01:16:37,560 --> 01:16:39,440 WE HAVE 3 OF THOSE AND CAN DO 2317 01:16:39,440 --> 01:16:39,960 OVER 100 A NIGHT. 2318 01:16:39,960 --> 01:16:43,280 WE CAN DO THAT WITH 5 MILLIGRAM 2319 01:16:43,280 --> 01:16:45,000 INJECTIONS ON THE SAME COLUMNS 2320 01:16:45,000 --> 01:16:45,400 FROM THE SAME THING. 2321 01:16:45,400 --> 01:16:47,560 SO WE COULD PROCESS 20 GRAMS OF 2322 01:16:47,560 --> 01:16:49,600 EXTRACT IN LESS THAN A WEEK TO 2323 01:16:49,600 --> 01:16:51,040 GET THE AMOUNT OF MATERIAL 2324 01:16:51,040 --> 01:16:53,840 NECESSARY FOR THAT FIRST ANIMAL 2325 01:16:53,840 --> 01:16:54,640 TRIAL OR TO MOVE THINGS FURTHER 2326 01:16:54,640 --> 01:16:54,840 DOWN. 2327 01:16:54,840 --> 01:16:57,360 AND THEN AS FAR AS NEW THINGS 2328 01:16:57,360 --> 01:16:59,000 CONCENTRATING ON CULTURAL 2329 01:16:59,000 --> 01:17:01,880 ORGANISMS SO WE CAN SCALE THOSE 2330 01:17:01,880 --> 01:17:04,360 UP AGAIN WITH PROCESSING AND THE 2331 01:17:04,360 --> 01:17:08,920 FACILITY WE BUILT. 2332 01:17:08,920 --> 01:17:10,840 >>THANK YOU VERY MUCH. 2333 01:17:10,840 --> 01:17:12,440 >>THANK YOU TO ALL OF OUR 2334 01:17:12,440 --> 01:17:13,600 SPEAKERS. 2335 01:17:13,600 --> 01:17:14,520 WONDERFUL TALKS AND FASCINATING 2336 01:17:14,520 --> 01:17:15,960 AND THE QUESTIONS HAVE BEEN 2337 01:17:15,960 --> 01:17:16,360 FLOWING. 2338 01:17:16,360 --> 01:17:18,080 SO WE'LL GET ANY ADDITIONAL 2339 01:17:18,080 --> 01:17:20,400 QUESTIONS OUT TO THE GROUP. 2340 01:17:20,400 --> 01:17:23,440 I'M GOING TO TURN THINGS OVER TO 2341 01:17:23,440 --> 01:17:25,040 PATRICK TO TAKE IT INTO OUR NEXT 2342 01:17:25,040 --> 01:17:27,160 SESSION WHERE WE WILL HEAR FROM 2343 01:17:27,160 --> 01:17:29,800 OUR FELLOW NIH COLLEAGUES WITH 2344 01:17:29,800 --> 01:17:33,120 SOME THEIR PRIORITIES AROUND 2345 01:17:33,120 --> 01:17:36,000 THIS RESEARCH SO PATRICK TAKE IT 2346 01:17:36,000 --> 01:17:36,200 AWAY. 2347 01:17:36,200 --> 01:17:37,520 >>WE ARE MOVING INTO THE 2348 01:17:37,520 --> 01:17:39,080 SESSION FROM OUR NIH PARTNERS 2349 01:17:39,080 --> 01:17:41,160 AND IN PARTICULAR, ON THEIR 2350 01:17:41,160 --> 01:17:42,960 PERSPECTIVES ON THE WEBINAR 2351 01:17:42,960 --> 01:17:49,080 THEMES WE HAVE HEARD AND NATURAL 2352 01:17:49,080 --> 01:17:49,960 PRODUCTS RESEARCH IN THE CONTEXT 2353 01:17:49,960 --> 01:17:54,120 OF THEIR INSTITUTE OR CENTER 2354 01:17:54,120 --> 01:17:54,880 PRIORITIES. 2355 01:17:54,880 --> 01:17:57,400 JOINING US TODAY ARE DR. YALI FU 2356 01:17:57,400 --> 01:17:59,960 FROM NCI'S DEVELOPMENTAL 2357 01:17:59,960 --> 01:18:00,560 THERAPEUTICS PROGRAM; DR. D.P. 2358 01:18:00,560 --> 01:18:01,640 MOHAPATRA FROM THE NATIONAL 2359 01:18:01,640 --> 01:18:06,720 INSTITUTE OF NEUROLOGICAL 2360 01:18:06,720 --> 01:18:07,280 DISORDERS AND STROKE'S PAIN, 2361 01:18:07,280 --> 01:18:08,760 SOMATOSENSATION, AND 2362 01:18:08,760 --> 01:18:11,640 GLIA/NEUROIMMUNE BIOLOGY 2363 01:18:11,640 --> 01:18:12,800 PROGRAM; DR. MICHELLE BOND FROM 2364 01:18:12,800 --> 01:18:14,560 THE NATIONAL INSTITUTE OF 2365 01:18:14,560 --> 01:18:16,280 GENERAL MEDICAL SCIENCES' 2366 01:18:16,280 --> 01:18:23,760 DIVISION OF PHARMACOLOGY, 2367 01:18:23,760 --> 01:18:24,280 PHYSIOLOGY AND BIOLOGICAL 2368 01:18:24,280 --> 01:18:25,240 CHEMISTRY; AND DR. RYAN RANALLO 2369 01:18:25,240 --> 01:18:27,760 FROM THE NATIONAL INSTITUTE OF 2370 01:18:27,760 --> 01:18:30,720 ALLERGY AND INFECTIOUS DISEASES 2371 01:18:30,720 --> 01:18:36,400 AND CO-CHAIR OF THE TRANS-NIH 2372 01:18:36,400 --> 01:18:36,920 MICROBIOME WORKING GROUP. 2373 01:18:36,920 --> 01:18:39,520 WE POSED A FEW QUESTIONS TO OUR 2374 01:18:39,520 --> 01:18:40,400 COLLEAGUES TO GUIDE THEIR 2375 01:18:40,400 --> 01:18:42,720 COMMENTS TODAY: 2376 01:18:42,720 --> 01:18:44,880 WE'LL START WITH THE FIRST 2377 01:18:44,880 --> 01:18:46,800 QUESTION WHICH IS, HOW DO THE 2378 01:18:46,800 --> 01:18:49,040 EMERGING IDEAS IN NATURAL 2379 01:18:49,040 --> 01:18:50,840 PRODUCTS RESEARCH PRESENTED IN 2380 01:18:50,840 --> 01:18:53,920 THIS WEBINAR INTERSECT WITH YOUR 2381 01:18:53,920 --> 01:18:59,480 IC STRATEGIC PLAN? 2382 01:18:59,480 --> 01:19:05,160 I DIWANT TO THE START FIRST WITH 2383 01:19:05,160 --> 01:19:06,640 RYAN FIRST. 2384 01:19:06,640 --> 01:19:07,920 >>THANK YOU, PATRICK, THANK YOU 2385 01:19:07,920 --> 01:19:10,240 FOR INVITING ME AND THANKS FOR 2386 01:19:10,240 --> 01:19:13,280 ALLOWING ME THE OPPORTUNITY TO 2387 01:19:13,280 --> 01:19:15,280 SPEAK. 2388 01:19:15,280 --> 01:19:18,480 IN TERMS OF PREPARATION FOR MY 2389 01:19:18,480 --> 01:19:19,840 COMMENT, I THINK I HAVE AT LEAST 2390 01:19:19,840 --> 01:19:23,360 SOME ASPECT OF ALL THREE TALKS I 2391 01:19:23,360 --> 01:19:25,960 CAN TALK ABOUT. 2392 01:19:25,960 --> 01:19:28,000 WE DON'T HAVE A DEDICATED 2393 01:19:28,000 --> 01:19:32,160 PROGRAM TO NATURAL PRODUCT 2394 01:19:32,160 --> 01:19:34,480 RESEARCH BUT AS I THOUGHT ABOUT 2395 01:19:34,480 --> 01:19:39,280 WHERE THIS INTERSECTS, THE 2396 01:19:39,280 --> 01:19:40,160 NATURAL PRODUCT FOCUS AREA 2397 01:19:40,160 --> 01:19:42,280 DOESN'T INTERSECT WITH NIAID'S 2398 01:19:42,280 --> 01:19:43,960 ANTIBIOTIC RESISTANCE RESEARCH 2399 01:19:43,960 --> 01:19:44,240 FRAMEWORK. 2400 01:19:44,240 --> 01:19:46,760 IT'S PART OF OUR OVERALL 2401 01:19:46,760 --> 01:19:49,760 STRATEGIC PLAN AND WE HAD A 2402 01:19:49,760 --> 01:19:51,480 FORWARD-LEADING DOCUMENT PUT OUT 2403 01:19:51,480 --> 01:19:53,360 IN 2019 AND PART OF THAT 2404 01:19:53,360 --> 01:19:55,280 DOCUMENT TALKS ABOUT SOME OF THE 2405 01:19:55,280 --> 01:19:57,680 ASPECTS OF HIGH-THROUGHPUT 2406 01:19:57,680 --> 01:20:00,920 SCREENING FOR NEW ANTIBIOTICS. 2407 01:20:00,920 --> 01:20:03,640 AND ONE SECTION WITHIN THERE AND 2408 01:20:03,640 --> 01:20:04,960 I'LL QUOTE FURTHER, EXPLORING 2409 01:20:04,960 --> 01:20:08,400 NATURAL PRODUCTS, THE SOURCE OF 2410 01:20:08,400 --> 01:20:09,280 MANY TWISTING ANTIBIOTICS COULD 2411 01:20:09,280 --> 01:20:12,560 ALSO ENHANCE LIBRARIES OF NEW 2412 01:20:12,560 --> 01:20:15,200 CHEMICALS STARTING POINT FOR 2413 01:20:15,200 --> 01:20:15,760 ANTIBIOTIC COMPOUNDS. 2414 01:20:15,760 --> 01:20:17,240 SO OUR INSTITUTE'S MISSION IS TO 2415 01:20:17,240 --> 01:20:18,720 SUPPORT BASIC AND APPLIED 2416 01:20:18,720 --> 01:20:21,320 RESEARCH TO BETTER UNDERSTAND 2417 01:20:21,320 --> 01:20:24,040 TREAT AND ULTIMATELY PREVENT 2418 01:20:24,040 --> 01:20:24,520 DISEASES. 2419 01:20:24,520 --> 01:20:26,840 A LOT OF THE NATURAL PRODUCT 2420 01:20:26,840 --> 01:20:29,520 RESEARCH FOCUSES ON 2421 01:20:29,520 --> 01:20:30,240 ANTIMICROBIALS BUT ALSO SOME 2422 01:20:30,240 --> 01:20:31,680 REAL INNOVATION THAT IS MAYBE I 2423 01:20:31,680 --> 01:20:33,320 CAN TOUCH ON LATER IN TERMS OF 2424 01:20:33,320 --> 01:20:36,120 HOW THIS WORKS WITH MICROBIAL 2425 01:20:36,120 --> 01:20:39,000 ECOLOGY AND OTHER MICROBIAL 2426 01:20:39,000 --> 01:20:41,120 PRODUCTS THAT WE ARE LEARNING 2427 01:20:41,120 --> 01:20:41,320 ABOUT. 2428 01:20:41,320 --> 01:20:43,120 I'LL STOP THERE FOR TIME AND LET 2429 01:20:43,120 --> 01:20:43,440 OTHERS SPEAK. 2430 01:20:43,440 --> 01:20:48,360 THANK YOU. 2431 01:20:48,360 --> 01:20:48,800 >>THANK YOU. 2432 01:20:48,800 --> 01:20:50,440 DID ANY OTHER PO WANT TO THE 2433 01:20:50,440 --> 01:21:00,920 VOLUNTEER TO CHIME IN NEXT? 2434 01:21:01,200 --> 01:21:03,120 >>I'M MICHELLE BOND FROM THE 2435 01:21:03,120 --> 01:21:03,720 INITIAL INSTITUTE OF GENERAL 2436 01:21:03,720 --> 01:21:04,080 MEDICAL SCIENCE. 2437 01:21:04,080 --> 01:21:08,960 SO THANK YOU PATRICK AND ALL FOR 2438 01:21:08,960 --> 01:21:09,440 MY PARTICIPATION TODAY. 2439 01:21:09,440 --> 01:21:10,480 THERE WERE SOME REALLY GREAT 2440 01:21:10,480 --> 01:21:12,800 THINGS THAT WE GOT TO HEAR 2441 01:21:12,800 --> 01:21:14,600 ABOUT, BOTH FROM THE STANDPOINT 2442 01:21:14,600 --> 01:21:15,280 OF TECHNOLOGIES THAT ARE 2443 01:21:15,280 --> 01:21:16,400 AVAILABLE AND THE QUESTIONS THAT 2444 01:21:16,400 --> 01:21:18,640 CAN BE ANSWERED WITH THEM. 2445 01:21:18,640 --> 01:21:22,080 SO, WHAT I'LL POINT OUT IS THAT 2446 01:21:22,080 --> 01:21:24,240 NIGMS SUPPORTS BASIC RESEARCH 2447 01:21:24,240 --> 01:21:25,080 THAT INCREASES OUR UNDERSTANDING 2448 01:21:25,080 --> 01:21:28,560 OF BIOLOGICAL PROCESSES AND LAYS 2449 01:21:28,560 --> 01:21:29,680 THE FOUNDATION FOR ADVANCES OF 2450 01:21:29,680 --> 01:21:32,360 DISEASE, DIAGNOSIS AND TREATMENT 2451 01:21:32,360 --> 01:21:33,560 AND PREVENTION. 2452 01:21:33,560 --> 01:21:35,840 AND SO, RATHER THAN HAVING A 2453 01:21:35,840 --> 01:21:37,000 PARTICULAR FUNDING OPPORTUNITY 2454 01:21:37,000 --> 01:21:38,120 ANNOUNCEMENT OR SOMETHING LIKE 2455 01:21:38,120 --> 01:21:40,640 THAT TO TALK ABOUT, WHAT I THINK 2456 01:21:40,640 --> 01:21:43,040 IS IMPORTANT TO POINT OUT IS 2457 01:21:43,040 --> 01:21:44,480 THAT MANY OF THE THINGS THAT 2458 01:21:44,480 --> 01:21:47,440 WERE DISCUSSED TODAY, ALIGN IN 2459 01:21:47,440 --> 01:21:49,600 THE SENSE THAT NIGMS SUPPORTS 2460 01:21:49,600 --> 01:21:50,640 TRAINING AND DEVELOPMENT FOR 2461 01:21:50,640 --> 01:21:52,280 BOTH INDIVIDUALS AND 2462 01:21:52,280 --> 01:21:54,200 INSTITUTIONS, RESEARCH PROJECT 2463 01:21:54,200 --> 01:21:55,840 GRANTS, LATER STAGE TECHNOLOGY 2464 01:21:55,840 --> 01:21:57,280 DEVELOPMENT AND DISSEMINATION 2465 01:21:57,280 --> 01:22:01,960 SUCH AS RPDT CENTERS AND 2466 01:22:01,960 --> 01:22:04,600 TECHNOLOGIES, USER RESOURCES OR 2467 01:22:04,600 --> 01:22:05,280 COMMERCIALIZATION THROUGH A 2468 01:22:05,280 --> 01:22:09,240 NUMBER OF DIFFERENT FUNDING 2469 01:22:09,240 --> 01:22:09,560 OPPORTUNITIES. 2470 01:22:09,560 --> 01:22:10,800 AND SO I'D BE HAPPY TO TALK 2471 01:22:10,800 --> 01:22:12,680 ABOUT THOSE IN MORE DETAIL BUT I 2472 01:22:12,680 --> 01:22:14,600 THINK THERE IS A PLACE FOR 2473 01:22:14,600 --> 01:22:18,720 NATURAL PRODUCTS RESEARCH IN 2474 01:22:18,720 --> 01:22:20,720 MANY OF THOSE INDIVIDUAL AREAS 2475 01:22:20,720 --> 01:22:24,400 ALL THE WAY FROM TRAINING 2476 01:22:24,400 --> 01:22:26,880 THROUGH COMMERCIALIZATION AND I 2477 01:22:26,880 --> 01:22:28,640 WILL STOP AND ANSWER QUESTIONS 2478 01:22:28,640 --> 01:22:33,600 AS THEY COME UP. 2479 01:22:33,600 --> 01:22:35,360 >>THANK YOU, MICHELLE. 2480 01:22:35,360 --> 01:22:38,360 DP WOULD YOU LIKE TO GO NEXT. 2481 01:22:38,360 --> 01:22:38,640 >>SURE. 2482 01:22:38,640 --> 01:22:41,760 THANK YOU AGAIN FOR INVITING US 2483 01:22:41,760 --> 01:22:48,920 TO THIS REALLY EXCITING -- I'M 2484 01:22:48,920 --> 01:22:51,240 VERY INTERESTED IN WORK ON VENOM 2485 01:22:51,240 --> 01:22:51,840 FOR PAIN. 2486 01:22:51,840 --> 01:22:53,360 SO IT WAS REALLY WONDERFUL 2487 01:22:53,360 --> 01:22:56,400 LISTENING TO THAT LECTURE. 2488 01:22:56,400 --> 01:23:01,280 FROM NINDS SIDE, WE ARE 2489 01:23:01,280 --> 01:23:04,400 INTERESTED IN ALL STARTING FROM 2490 01:23:04,400 --> 01:23:08,680 BASIC SCIENCE, THERAPEUTIC 2491 01:23:08,680 --> 01:23:11,080 DEVELOPMENT, MANAGEMENT AND IN 2492 01:23:11,080 --> 01:23:14,800 FACT LOOKING INTO MY OWN YEARS 2493 01:23:14,800 --> 01:23:17,920 OF INTEREST IN BIOLOGY NATURAL 2494 01:23:17,920 --> 01:23:20,520 PRODUCTS HAVE BEEN TREMENDOUSLY 2495 01:23:20,520 --> 01:23:30,960 BENEFICIAL FOR THIS AREA. 2496 01:23:36,040 --> 01:23:40,320 AND NATURAL PRODUCTS HIGHLIGHTED 2497 01:23:40,320 --> 01:23:44,680 AS HEAVILY INTERESTED IN NATURAL 2498 01:23:44,680 --> 01:23:46,800 PRODUCTS. 2499 01:23:46,800 --> 01:23:53,280 NEW JEN, THERAPEUTICS THROUGH 2500 01:23:53,280 --> 01:23:57,240 INITIATIVE LONG TERM. 2501 01:23:57,240 --> 01:24:01,280 WE HAVE BEEN SUPPORTING A LOT OF 2502 01:24:01,280 --> 01:24:11,800 STUDIOS AND WE HAVE REALLY BIG 2503 01:24:12,600 --> 01:24:13,600 THINGS FOR A DIFFERENT PROGRAM 2504 01:24:13,600 --> 01:24:24,320 THAT WE HAVE WE HAVE TIME BUT 2505 01:24:24,320 --> 01:24:28,840 I'M HAPPY -- 2506 01:24:28,840 --> 01:24:29,600 >>THANK YOU VERY MUCH. 2507 01:24:29,600 --> 01:24:31,360 AND DR. YALI FU. 2508 01:24:31,360 --> 01:24:35,400 >>THIS IS YALI FU FROM THE 2509 01:24:35,400 --> 01:24:35,920 NATIONAL CANCER INSTITUTE. 2510 01:24:35,920 --> 01:24:38,240 I WANT TO CONGRATULATE MY 2511 01:24:38,240 --> 01:24:43,040 COLLEAGUES AT THE NCCIH FOR THIS 2512 01:24:43,040 --> 01:24:44,400 EXCITING WEBINAR. 2513 01:24:44,400 --> 01:24:45,480 I LEARNED A LOT. 2514 01:24:45,480 --> 01:24:49,960 IT'S EXCITING TO HEAR THIS NEW 2515 01:24:49,960 --> 01:24:52,120 DEVELOPMENT PRESENTED BY ALL 2516 01:24:52,120 --> 01:24:54,640 THREE SPEAKERS. 2517 01:24:54,640 --> 01:24:56,520 I'M FROM THE SAME DIVISION AS 2518 01:24:56,520 --> 01:24:59,600 FIRST SPEAKER, DR. O'KEEFE, AS 2519 01:24:59,600 --> 01:25:01,160 MANY OF YOU KNOW. 2520 01:25:01,160 --> 01:25:05,520 NCI HAS FRANK LONGO HISTORY OF 2521 01:25:05,520 --> 01:25:08,080 COLLECTING AND SCREENING AND 2522 01:25:08,080 --> 01:25:14,200 LOOKING AT ANTI-CANCER AND 2523 01:25:14,200 --> 01:25:16,000 ANTI-HIV AGENTS FROM THE NATURAL 2524 01:25:16,000 --> 01:25:18,080 PRODUCTS AND THE COLLECTIONS 2525 01:25:18,080 --> 01:25:21,000 THAT DR. O'KEEFE TALKED ABOUT 2526 01:25:21,000 --> 01:25:23,720 CAME FROM THAT PAST MORE THAN 50 2527 01:25:23,720 --> 01:25:24,400 YEARS OF HISTORY. 2528 01:25:24,400 --> 01:25:29,520 AT THIS TIME, IN TERMS OF GRANT 2529 01:25:29,520 --> 01:25:34,280 SUPPORT, WE STILL HAVE NATURAL 2530 01:25:34,280 --> 01:25:35,520 PRODUCT DISCOVERY PROGRAM. 2531 01:25:35,520 --> 01:25:38,160 LIKE BARRY ALLUDED TO. 2532 01:25:38,160 --> 01:25:40,360 WE HAVE A NEXT PROGRAM WHICH 2533 01:25:40,360 --> 01:25:42,400 SUPPORTS NEW AGENTS THAT IS NOT 2534 01:25:42,400 --> 01:25:44,360 JUST LIMITED TO NATURAL PRODUCTS 2535 01:25:44,360 --> 01:25:48,400 BUT ALSO NEW CHEMICAL ENTITIES, 2536 01:25:48,400 --> 01:25:52,000 THERAPEUTIC APPROACH AND THE 2537 01:25:52,000 --> 01:25:54,040 STEPPING STONE PATHWAY THAT WE 2538 01:25:54,040 --> 01:25:58,080 HAVE IS SUPPORTING EXTRAMURAL 2539 01:25:58,080 --> 01:26:03,160 FUNDED RO1 PROJECT GENERATED 2540 01:26:03,160 --> 01:26:05,640 LEADS THAT NEED A LITTLE BIT OF 2541 01:26:05,640 --> 01:26:05,880 A BOOST. 2542 01:26:05,880 --> 01:26:12,400 SO NCI CAN INVOLVE SOME INTERNAL 2543 01:26:12,400 --> 01:26:14,400 DEVELOPMENT RESOURCES TO HELP 2544 01:26:14,400 --> 01:26:19,880 ACADEMIC RESEARCHERS TO PUSH 2545 01:26:19,880 --> 01:26:21,840 FORWARD THESE LEADS FOR FURTHER 2546 01:26:21,840 --> 01:26:22,400 DEVELOPMENT. 2547 01:26:22,400 --> 01:26:24,160 FROM THE NATURAL PRODUCTS 2548 01:26:24,160 --> 01:26:27,600 STANDPOINT, WE ARE STILL VERY 2549 01:26:27,600 --> 01:26:30,000 INTERESTED IN ALL SORTS OF 2550 01:26:30,000 --> 01:26:30,400 NATURAL PRODUCTS. 2551 01:26:30,400 --> 01:26:32,840 HOW DOES THIS, THE LANDSCAPE 2552 01:26:32,840 --> 01:26:36,120 CHANGE OVER THE PAST 10-15 2553 01:26:36,120 --> 01:26:36,720 YEARS? 2554 01:26:36,720 --> 01:26:42,000 AS YOU CAN SEE THAT LIKE 2555 01:26:42,000 --> 01:26:43,480 DR. ROGER LININGTON SAID AS 2556 01:26:43,480 --> 01:26:45,600 OPPOSED TO HAVING THE 2557 01:26:45,600 --> 01:26:46,880 INTERSECTION OF CHEMISTRY WITH 2558 01:26:46,880 --> 01:26:49,960 THE BIOLOGICAL ACTIVITY DURING 2559 01:26:49,960 --> 01:26:54,680 THE ITERATIVE FRACTIONATION. 2560 01:26:54,680 --> 01:26:57,160 THERE IS A URGENT NEED LIKE 2561 01:26:57,160 --> 01:26:59,000 DR. O'KEEFE MENTIONED FOR 2562 01:26:59,000 --> 01:27:04,360 HIGH-THROUGHPUT AND HIGH SPEED 2563 01:27:04,360 --> 01:27:09,520 DECONVOLUTION AND IDENTIFYING 2564 01:27:09,520 --> 01:27:11,480 DERATIFICATION, IDENTIFYING 2565 01:27:11,480 --> 01:27:11,880 INTERESTING LEADS. 2566 01:27:11,880 --> 01:27:12,480 IN ADDITION TO THE TRADITIONAL 2567 01:27:12,480 --> 01:27:17,840 WAY OF THINKING ABOUT FINDING 2568 01:27:17,840 --> 01:27:19,360 NEW NATURAL PRODUCTS AS 2569 01:27:19,360 --> 01:27:23,120 THERAPEUTIC AGENT WHETHER FROM 2570 01:27:23,120 --> 01:27:25,000 VENOM OR MY REASON ORGANISMS OR 2571 01:27:25,000 --> 01:27:30,320 MICROBES OR PLANTS, THE -- 2572 01:27:30,320 --> 01:27:32,400 MARINE -- WE ARE LOOKING AT A 2573 01:27:32,400 --> 01:27:35,480 LOT OF IMMUNOLOGY AS WE KNOW, 2574 01:27:35,480 --> 01:27:37,400 AND WE CAN LOOK AT THE NATURAL 2575 01:27:37,400 --> 01:27:41,320 PRODUCTS IN TERMS OF HOW THEY 2576 01:27:41,320 --> 01:27:44,400 MODULATE IMMUNE SYSTEM AS 2577 01:27:44,400 --> 01:27:45,160 OPPOSED TO JUST ONE SIMPLE 2578 01:27:45,160 --> 01:27:48,120 PROTEIN TARGET AND THINKING IN 2579 01:27:48,120 --> 01:27:48,840 TERMS OF COMBINATION THERAPY 2580 01:27:48,840 --> 01:27:54,120 EITHER WITH CHEMO OR WITH 2581 01:27:54,120 --> 01:27:54,760 IMMUNOAGENTS. 2582 01:27:54,760 --> 01:27:59,320 IN ADDITION, WE ALSO LOOKING AT 2583 01:27:59,320 --> 01:28:00,280 THE ADDITIONAL CHEMISTRY 2584 01:28:00,280 --> 01:28:03,560 PERSPECTIVE IN TERMS OF 2585 01:28:03,560 --> 01:28:04,720 MONITORING, IN TERMS OF 2586 01:28:04,720 --> 01:28:08,120 GENERATING NEW LEADS AND WE HAVE 2587 01:28:08,120 --> 01:28:10,480 PEOPLE LIKE -- WORKING ON THE 2588 01:28:10,480 --> 01:28:13,720 NEXT GENERATION OF NEW AGENTS 2589 01:28:13,720 --> 01:28:14,920 AND AND MANIPULATING COMPLEX 2590 01:28:14,920 --> 01:28:16,720 NATURAL PRODUCTS. 2591 01:28:16,720 --> 01:28:17,880 AND ANOTHER INTERESTING TWIST WE 2592 01:28:17,880 --> 01:28:24,360 SEE RECENTLY IS A PLANT-BASED 2593 01:28:24,360 --> 01:28:24,880 VESICLE DELIVERY AGENT. 2594 01:28:24,880 --> 01:28:29,600 AND SO THESE ARE CLEARLY WE NEED 2595 01:28:29,600 --> 01:28:34,240 NEW TOOLS AND TECHNOLOGIES TO 2596 01:28:34,240 --> 01:28:35,800 MOVE THE NATURAL PRODUCT FIELD 2597 01:28:35,800 --> 01:28:37,360 TO THE NEXT LEVEL. 2598 01:28:37,360 --> 01:28:38,800 TODAY I THINK WE HEARD ABOUT 2599 01:28:38,800 --> 01:28:39,480 THESE NEW DEVELOPMENTS. 2600 01:28:39,480 --> 01:28:45,120 WE DO NEED THIS FIELD TO 2601 01:28:45,120 --> 01:28:45,840 REINVENT OURSELVES LIKE THE 2602 01:28:45,840 --> 01:28:48,760 SPEAKERS HAVE SHOWN. 2603 01:28:48,760 --> 01:28:52,400 SO THE PUBLIC AND THE GENERAL 2604 01:28:52,400 --> 01:28:54,680 PUBLIC HEALTH CAN BENEFIT STILL 2605 01:28:54,680 --> 01:28:57,320 FROM THE HUGE RESERVOIR OF 2606 01:28:57,320 --> 01:28:57,720 NATURAL RESOURCES. 2607 01:28:57,720 --> 01:29:04,280 THANK YOU. 2608 01:29:04,280 --> 01:29:05,880 >>THANK YOU VERY MUCH. 2609 01:29:05,880 --> 01:29:11,280 NOW I WOULD ALSO LIKE TO EXPRESS 2610 01:29:11,280 --> 01:29:13,600 NCCIH'S ANSWER TO THIS QUESTION 2611 01:29:13,600 --> 01:29:14,640 AS WELL IN THE CONTEXT OF WHAT 2612 01:29:14,640 --> 01:29:16,440 WE HAVE HEARD FROM THE WEBINAR 2613 01:29:16,440 --> 01:29:19,920 SO FAR. 2614 01:29:19,920 --> 01:29:23,240 AND THAT'S THAT NCCIH HAS A 2615 01:29:23,240 --> 01:29:24,720 BROUGHT INTEREST IN STUDYING THE 2616 01:29:24,720 --> 01:29:26,000 BIOLOGICAL ACTIVITIES OF NATURAL 2617 01:29:26,000 --> 01:29:28,160 PRODUCTS INCLUDING PREBIOTICS, 2618 01:29:28,160 --> 01:29:30,560 PROBIOTICS, DIETARY SUPPLEMENTS, 2619 01:29:30,560 --> 01:29:32,360 BOTANICALS AND VITAMINS AND 2620 01:29:32,360 --> 01:29:34,800 ALTHOUGH WE ARE ONE OF THE 2621 01:29:34,800 --> 01:29:37,600 SMALLER ICs AT NIH 2622 01:29:37,600 --> 01:29:39,640 HISTORICALLY AROUND HALF OF OUR 2623 01:29:39,640 --> 01:29:40,600 PORTFOLIO HAS BEEN IN NATURAL 2624 01:29:40,600 --> 01:29:43,640 PRODUCT FUNDING. 2625 01:29:43,640 --> 01:29:47,080 AND OUR NEW STRATEGIC PLAN FOR 2626 01:29:47,080 --> 01:29:50,440 2021-2025 REALLY EMPHASIZES AN 2627 01:29:50,440 --> 01:29:52,320 ORGANIZING PRINCIPLE CALLED 2628 01:29:52,320 --> 01:29:53,760 WHOLE PERSON HEALTH WHICH AIMS 2629 01:29:53,760 --> 01:29:56,520 TO IDENTIFY GAPS IN OUR 2630 01:29:56,520 --> 01:29:57,200 KNOWLEDGE ON THE PROGRESSION 2631 01:29:57,200 --> 01:30:01,600 FROM HEALTH TO DISEASE AND FROM 2632 01:30:01,600 --> 01:30:03,800 DISEASE TO HEALTH. 2633 01:30:03,800 --> 01:30:06,760 THIS FOR EXAMPLE, COULD INCLUDE 2634 01:30:06,760 --> 01:30:07,480 RESEARCH THAT EMPLOYS 2635 01:30:07,480 --> 01:30:10,440 BIOINFORMATIC METHODS TO ADDRESS 2636 01:30:10,440 --> 01:30:12,440 SYSTEMS LEVEL-TYPE RESEARCH AND 2637 01:30:12,440 --> 01:30:16,000 WE HAVE REALLY ROBUST FRAMEWORK 2638 01:30:16,000 --> 01:30:17,040 FOR CLINICAL RESEARCH AS WELL 2639 01:30:17,040 --> 01:30:19,320 FROM BASIC AND MECHANISTIC 2640 01:30:19,320 --> 01:30:21,400 THROUGH FEASIBILITY STUDIES 2641 01:30:21,400 --> 01:30:24,480 THROUGH PRAGMATIC CLINICAL 2642 01:30:24,480 --> 01:30:24,680 TRIALS. 2643 01:30:24,680 --> 01:30:27,920 AND SO WITH THAT, FIRST QUESTION 2644 01:30:27,920 --> 01:30:29,520 ANSWERED, I DID WANT TO MOVE TO 2645 01:30:29,520 --> 01:30:33,280 OUR SECOND QUESTION FOR OUR 2646 01:30:33,280 --> 01:30:34,560 PROGRAM STAFF. 2647 01:30:34,560 --> 01:30:38,600 THAT IS, COULD YOU HIGHLIGHT ANY 2648 01:30:38,600 --> 01:30:41,280 INITIATIVES OR FUNDING 2649 01:30:41,280 --> 01:30:42,040 OPPORTUNITIES FROM YOUR 2650 01:30:42,040 --> 01:30:42,760 INSTITUTE THAT FACILITATES 2651 01:30:42,760 --> 01:30:44,400 LEVERAGING NATURAL PRODUCTS 2652 01:30:44,400 --> 01:30:48,720 RESEARCH RESOURCES? 2653 01:30:48,720 --> 01:30:50,520 AND DON'T WANT TO PICK ON 2654 01:30:50,520 --> 01:30:56,080 ANYONE, BUT I GUESS WE COULD 2655 01:30:56,080 --> 01:31:02,520 START WITH GM FIRST. 2656 01:31:02,520 --> 01:31:05,480 >>ONE OF THE THINGS I WOULD 2657 01:31:05,480 --> 01:31:08,760 HIGHLIGHT IS WE SUPPORT VEST 2658 01:31:08,760 --> 01:31:09,520 RESEARCH. 2659 01:31:09,520 --> 01:31:12,560 SO WHEN WE ARE THINKING FUNDING 2660 01:31:12,560 --> 01:31:13,200 OPPORTUNITY ANNOUNCEMENTS THAT 2661 01:31:13,200 --> 01:31:14,600 MIGHT BE APPROPRIATE, IT'S 2662 01:31:14,600 --> 01:31:18,120 SOMETHING THAT IS COMING FROM 2663 01:31:18,120 --> 01:31:19,760 INVESTIGATORS WHO ARE INTERESTED 2664 01:31:19,760 --> 01:31:22,520 IN A PARTICULAR QUESTION AND 2665 01:31:22,520 --> 01:31:24,440 THOSE ANSWERS. 2666 01:31:24,440 --> 01:31:26,560 SO, THE TYPES OF QUESTIONS THAT 2667 01:31:26,560 --> 01:31:28,320 INDIVIDUALS OFTEN ASK, IN 2668 01:31:28,320 --> 01:31:29,560 ASSOCIATION WITH NATURAL 2669 01:31:29,560 --> 01:31:32,320 PRODUCTS EFFORTS AT NIGMS 2670 01:31:32,320 --> 01:31:33,960 INCLUDE WHAT ARE THE PRINCIPLES, 2671 01:31:33,960 --> 01:31:35,920 MECHANISMS AND PROCESSES THAT 2672 01:31:35,920 --> 01:31:37,800 UNDERLIE LIVING ORGANISMS AND 2673 01:31:37,800 --> 01:31:39,680 WHAT ARE THE PRODUCTS PRODUCED 2674 01:31:39,680 --> 01:31:42,160 BY THOSE ORGANISMS THAT MAKE UP 2675 01:31:42,160 --> 01:31:42,800 FOR THE FOUNDATION FOR THE 2676 01:31:42,800 --> 01:31:44,000 DEVELOPMENT OF THERAPEUTICS IN 2677 01:31:44,000 --> 01:31:46,000 THE LONG RUN? 2678 01:31:46,000 --> 01:31:47,240 AND WHERE ARE THESE COMPOUNDS 2679 01:31:47,240 --> 01:31:48,960 MADE? 2680 01:31:48,960 --> 01:31:50,120 NIGMS, AMONG OTHER AREAS, 2681 01:31:50,120 --> 01:31:51,800 SUPPORTS NATURAL PRODUCTS 2682 01:31:51,800 --> 01:31:53,280 DISCOVERY AND ANALYSIS AS WELL 2683 01:31:53,280 --> 01:31:58,520 AS NATURAL PRODUCTS SYNTHESIS 2684 01:31:58,520 --> 01:31:58,920 AND BIOSYNTHESIS. 2685 01:31:58,920 --> 01:32:00,400 I WOULD LIKING TO HIGHLIGHT A 2686 01:32:00,400 --> 01:32:02,400 COUPLE OF RESEARCH PROJECT GRANT 2687 01:32:02,400 --> 01:32:03,120 FUNDING OPPORTUNITY 2688 01:32:03,120 --> 01:32:04,880 ANNOUNCEMENTS THAT MAINLY HAVE 2689 01:32:04,880 --> 01:32:06,880 INTEREST, SPECIFICALLY OUR 2690 01:32:06,880 --> 01:32:07,920 TECHNOLOGY DEVELOPMENT SERIES. 2691 01:32:07,920 --> 01:32:13,360 SO IT IS A PAIR OF R21 AND RO1 2692 01:32:13,360 --> 01:32:14,200 FUNDING OPPORTUNITY 2693 01:32:14,200 --> 01:32:16,920 ANNOUNCEMENTS IN WHICH FOR THE 2694 01:32:16,920 --> 01:32:19,560 R21 THE OBJECTIVE IS TO PROVIDE 2695 01:32:19,560 --> 01:32:21,720 A PROOF-OF-CONCEPT. 2696 01:32:21,720 --> 01:32:24,040 IT'S VERY EXPLORATORY AND 2697 01:32:24,040 --> 01:32:27,160 REQUIRES THAT THERE IS NO 2698 01:32:27,160 --> 01:32:28,040 PRELIMINARY DATA WITHIN THE 2699 01:32:28,040 --> 01:32:28,440 APPLICATION. 2700 01:32:28,440 --> 01:32:30,440 THE TECHNOLOGY DEVELOPMENT RO1 2701 01:32:30,440 --> 01:32:36,720 IS FOR PROTOTYPE VALIDATION AND 2702 01:32:36,720 --> 01:32:38,240 THIS SHOULD NOT INCLUDE ANY SORT 2703 01:32:38,240 --> 01:32:40,400 OF BIOLOGICAL HYPOTHESES. 2704 01:32:40,400 --> 01:32:44,200 HOWEVER, IN MANY CASES, WE HAVE 2705 01:32:44,200 --> 01:32:45,560 INDIVIDUALS WHO ARE INTERESTED 2706 01:32:45,560 --> 01:32:47,360 IN ADDRESSING THIS AND IN THAT 2707 01:32:47,360 --> 01:32:50,160 CASE, THE PARENT RO1 IS 2708 01:32:50,160 --> 01:32:51,360 APPROPRIATE AS WELL AS OUR R35. 2709 01:32:51,360 --> 01:32:55,880 SO THIS IS THE LAST ONE I'D LIKE 2710 01:32:55,880 --> 01:32:57,400 TO HIGHLIGHT, WHICH IS THE 2711 01:32:57,400 --> 01:32:58,000 MAXIMIZING INVESTIGATORS 2712 01:32:58,000 --> 01:33:00,760 RESEARCH AWARD. 2713 01:33:00,760 --> 01:33:03,400 AND IT COMES IN TWO FLAVORS, ONE 2714 01:33:03,400 --> 01:33:05,080 IS FOR EARLY-STAGE INVESTIGATORS 2715 01:33:05,080 --> 01:33:06,080 AND THE SECOND IS FOR NEW 2716 01:33:06,080 --> 01:33:08,400 INVESTIGATORS AND ESTABLISHED 2717 01:33:08,400 --> 01:33:08,960 INVESTIGATORS. 2718 01:33:08,960 --> 01:33:11,520 AND THIS IS INTENDING TO SUPPORT 2719 01:33:11,520 --> 01:33:13,960 RATHER THAN SPECIFIC AIMS BY 2720 01:33:13,960 --> 01:33:16,680 PROGRAM OR RESEARCH WITHIN AN 2721 01:33:16,680 --> 01:33:21,040 INDIVIDUAL'S LAB AND WITH FEW 2722 01:33:21,040 --> 01:33:24,200 EXCEPTIONS IT WOULD BE THE AWARD 2723 01:33:24,200 --> 01:33:26,160 FROM NIGMS AND EFFORT 2724 01:33:26,160 --> 01:33:26,480 COMMITMENT. 2725 01:33:26,480 --> 01:33:29,240 THAT BEING SAID TO PURSUE WHAT 2726 01:33:29,240 --> 01:33:32,240 IS MOST INTERESTING WITHIN THE 2727 01:33:32,240 --> 01:33:34,440 NIGMS MISSION AND IS NOT TIED TO 2728 01:33:34,440 --> 01:33:34,800 SPECIFIC AIMS. 2729 01:33:34,800 --> 01:33:38,240 SO I WOULD SAY THAT THESE ARE 2730 01:33:38,240 --> 01:33:41,240 SOME OF THE MOST APPROPRIATE AND 2731 01:33:41,240 --> 01:33:42,280 INTERESTING FUNDING OPPORTUNITY 2732 01:33:42,280 --> 01:33:43,320 ANNOUNCEMENTS AND SHOULD ANYONE 2733 01:33:43,320 --> 01:33:44,560 HAVE ANY QUESTIONS, YOU'RE 2734 01:33:44,560 --> 01:33:47,840 WELCOME TO REACH OUT TO ME AND 2735 01:33:47,840 --> 01:33:52,720 I'D BE HAPPY TO TALK TO YOU. 2736 01:33:52,720 --> 01:33:53,080 >>THANK YOU. 2737 01:33:53,080 --> 01:34:00,240 NEXT WE CAN MOVE TO RYAN. 2738 01:34:00,240 --> 01:34:01,840 >>SO THAT WAS HARD TO FOLLOW. 2739 01:34:01,840 --> 01:34:03,520 THAT WAS REALLY WELL 2740 01:34:03,520 --> 01:34:04,200 ARTICULATED. 2741 01:34:04,200 --> 01:34:06,240 IN THE SAME VAIN, NIAID IS LARGE 2742 01:34:06,240 --> 01:34:10,240 LOO AN INVESTIGATOR-INITIATED 2743 01:34:10,240 --> 01:34:10,600 PORTFOLIO. 2744 01:34:10,600 --> 01:34:13,520 WE DRIVE A LOT OF FUNDING 2745 01:34:13,520 --> 01:34:15,360 DECISIONS BY OUR PUBLISHED PAY 2746 01:34:15,360 --> 01:34:15,720 LINE. 2747 01:34:15,720 --> 01:34:17,720 BUT I DO HAVE A COUPLE OF THINGS 2748 01:34:17,720 --> 01:34:20,120 THAT I WANTED TO HIGHLIGHT THAT 2749 01:34:20,120 --> 01:34:23,720 AS I SAID, IT REALLY ALLIANCE 2750 01:34:23,720 --> 01:34:28,360 WITH OUR STRATEGIC PLAN ON 2751 01:34:28,360 --> 01:34:32,400 ANTIMICROBIALS AND ANY TYPE OF 2752 01:34:32,400 --> 01:34:34,480 NATURAL PRODUCTS THAT CAN IMPACT 2753 01:34:34,480 --> 01:34:35,720 HOST IMMUNITY OF THE UM MINE 2754 01:34:35,720 --> 01:34:37,600 DEVELOPMENT AND IMMUNOLOGICAL 2755 01:34:37,600 --> 01:34:37,880 DISEASES. 2756 01:34:37,880 --> 01:34:38,920 WE RECENTLY JOINED UP WITH A 2757 01:34:38,920 --> 01:34:42,240 COUPLE OF ICs TO PARTICIPATE 2758 01:34:42,240 --> 01:34:46,720 IN A FOA CALLED -- IT'S A 2759 01:34:46,720 --> 01:34:50,480 PROGRAM ANNOUNCEMENT 21-253. 2760 01:34:50,480 --> 01:34:53,280 IT'S TITLED -- IT'S AN RO1, NO 2761 01:34:53,280 --> 01:34:54,720 CLINICAL TRIAL REQUIRED ENTITLED 2762 01:34:54,720 --> 01:34:55,720 IDENTIFICATION OF 2763 01:34:55,720 --> 01:34:57,640 CHARACTERIZATION OF BIOACTIVE 2764 01:34:57,640 --> 01:35:01,560 MICROBIAL METABOLITES FOR 2765 01:35:01,560 --> 01:35:04,920 ADVANCING RESEARCH ON HOST -- OR 2766 01:35:04,920 --> 01:35:06,240 DIET MICROBE HOST INTERACTIONS. 2767 01:35:06,240 --> 01:35:09,600 THE GOAL FOR NIAID'S PROGRAM AS 2768 01:35:09,600 --> 01:35:11,240 A PARTICIPATION ON THIS FOA IS 2769 01:35:11,240 --> 01:35:13,040 TO IDENTIFY MICROBIAL 2770 01:35:13,040 --> 01:35:14,160 METABOLITES THAT IMPACT 2771 01:35:14,160 --> 01:35:16,840 MICROBIAL VIABILITY, PATHOGEN 2772 01:35:16,840 --> 01:35:18,560 INVASION, THESE COMPOUNDS THAT 2773 01:35:18,560 --> 01:35:21,800 CAN DISARM PATHOGENS. 2774 01:35:21,800 --> 01:35:24,800 WE KNOW THERE ARE MICROBIAL 2775 01:35:24,800 --> 01:35:25,320 METABOLITES THAT ALTER AND 2776 01:35:25,320 --> 01:35:28,240 IMPACT HOST IMMUNE SYSTEM 2777 01:35:28,240 --> 01:35:29,080 DEVELOPMENT AND HOST IMMUNITY, 2778 01:35:29,080 --> 01:35:30,400 INFLAMMATION AND THE DEVELOPMENT 2779 01:35:30,400 --> 01:35:31,480 OF IMMUNOLOGICAL DISEASES. 2780 01:35:31,480 --> 01:35:34,400 AND WE ARE QUITE INTERESTED IN 2781 01:35:34,400 --> 01:35:35,920 THIS AREA. 2782 01:35:35,920 --> 01:35:38,840 IT ALLIANCE WITH MY ROLE AS THE 2783 01:35:38,840 --> 01:35:40,200 CO-CHAIR OF THE TRANSMICROBIOME 2784 01:35:40,200 --> 01:35:44,280 WORKING GROUP IN TERMS OF OUR 2785 01:35:44,280 --> 01:35:46,200 INTEREST, BUT WE RECENTLY FUNDED 2786 01:35:46,200 --> 01:35:49,440 FOUR RO1s ON THIS PROGRAM AND 2787 01:35:49,440 --> 01:35:52,760 SOME OF THESE RO1S ALIGN WITH 2788 01:35:52,760 --> 01:35:55,960 IDENTIFYING GENE CLUSTERS FOR 2789 01:35:55,960 --> 01:35:57,960 NATURAL PRODUCT PRODUCTION. 2790 01:35:57,960 --> 01:35:58,880 THE OTHER PROGRAM THAT WAS 2791 01:35:58,880 --> 01:36:00,880 LAUNCHED A FEW YEARS AGO IS 2792 01:36:00,880 --> 01:36:04,560 SOMETHING CALLED THE CHEMISTRY 2793 01:36:04,560 --> 01:36:06,640 CENTER FOR COMBATING ANTIBIOTIC 2794 01:36:06,640 --> 01:36:08,160 RESISTANT BACTERIA. 2795 01:36:08,160 --> 01:36:12,480 IT IS A PROGRAM THAT IS AN NIAID 2796 01:36:12,480 --> 01:36:13,520 LED INITIATIVE. 2797 01:36:13,520 --> 01:36:16,400 IT'S A CHEMISTRY CENTER, AN 2798 01:36:16,400 --> 01:36:18,080 INNOVATIVE CHEMISTRY CENTER 2799 01:36:18,080 --> 01:36:20,760 FOCUSED ON SYNTHESIS AND 2800 01:36:20,760 --> 01:36:23,000 DELIVERY OF RATIONALLY DESIGNED 2801 01:36:23,000 --> 01:36:29,720 LIBRARIES FOR USING GRAM 2802 01:36:29,720 --> 01:36:30,320 NEGATIVE ANTIBACTERIAL DRUG 2803 01:36:30,320 --> 01:36:30,920 DISCOVERY PROGRAMS TO CREATE A 2804 01:36:30,920 --> 01:36:31,880 LARGE COLLECTION OF CHEMICAL 2805 01:36:31,880 --> 01:36:34,720 MATTER SPECIFICALLY TARGETING 2806 01:36:34,720 --> 01:36:36,320 GRAM NEGATIVES ALIGNING WITH OUR 2807 01:36:36,320 --> 01:36:38,080 STRATEGIC PLAN, AS I SAID. 2808 01:36:38,080 --> 01:36:39,120 AND THEN THE LAST THING I WANTED 2809 01:36:39,120 --> 01:36:41,680 TO MENTION AND IT'S NOT A 2810 01:36:41,680 --> 01:36:42,320 FULL-FLEDGED PROGRAM BUT IT'S AN 2811 01:36:42,320 --> 01:36:44,000 EXAMPLE OUT OF MY PROGRAM. 2812 01:36:44,000 --> 01:36:44,880 MY PROGRAM IS A PORTFOLIO 2813 01:36:44,880 --> 01:36:48,280 MANAGER FOCUSED ON THE GUT 2814 01:36:48,280 --> 01:36:50,200 MICROBIOME. 2815 01:36:50,200 --> 01:36:54,480 AND ONE BACTERIA CLUSTER 2816 01:36:54,480 --> 01:36:58,440 PRODUCES A NATURAL HIGHLY TOXIC 2817 01:36:58,440 --> 01:37:02,040 COMPOUND TOXIN CALLED BOTCH LINE 2818 01:37:02,040 --> 01:37:02,280 UM TOXIN. 2819 01:37:02,280 --> 01:37:03,680 IT'S A NATURAL PRODUCT THAT IS 2820 01:37:03,680 --> 01:37:05,920 REFERRED TO AS BOTOX USED TO 2821 01:37:05,920 --> 01:37:06,720 TREAT THERAPEUTICALLY. 2822 01:37:06,720 --> 01:37:10,000 SO JUST WANTED TO SAY THAT IS A 2823 01:37:10,000 --> 01:37:12,440 NASCENT PROGRAM BUT IT IS ONE 2824 01:37:12,440 --> 01:37:15,000 THAT WE HOLD BOTH FROM A 2825 01:37:15,000 --> 01:37:17,440 BIODEFENSE PERSPECTIVE AND FOR 2826 01:37:17,440 --> 01:37:20,040 NATURAL PRODUCT DEVELOPMENT 2827 01:37:20,040 --> 01:37:20,360 PERSPECTIVE. 2828 01:37:20,360 --> 01:37:23,600 AND THEN THE LAST THING I'LL 2829 01:37:23,600 --> 01:37:24,240 MENTION AND AGAIN, JUST TRYING 2830 01:37:24,240 --> 01:37:27,480 TO GET IT ALL IN, IS THE NATURAL 2831 01:37:27,480 --> 01:37:29,360 PRODUCT BASED THERAPEUTICS 2832 01:37:29,360 --> 01:37:30,600 PROGRAM, IT'S BASICALLY LOOKING 2833 01:37:30,600 --> 01:37:33,680 AT ASPECTS OF THE GUT MICROBIOME 2834 01:37:33,680 --> 01:37:36,520 AND MICROBIAL ECOLOGY AS A WAY 2835 01:37:36,520 --> 01:37:38,800 TO PRODUCE BOTH MICRO-BASED 2836 01:37:38,800 --> 01:37:42,040 THERAPEUTICS AND SO-CALLED LIVE 2837 01:37:42,040 --> 01:37:42,720 BIOTHERAPEUTICS OR NEXT 2838 01:37:42,720 --> 01:37:47,800 GENERATION PROBIOTICS 2839 01:37:47,800 --> 01:37:48,400 PRINCIPALLY DIFFERENT IN TERMS 2840 01:37:48,400 --> 01:37:48,840 OF NATURAL PRODUCTS. 2841 01:37:48,840 --> 01:37:49,440 THEY OPERATE ON PRINCIPLES OF 2842 01:37:49,440 --> 01:37:49,960 DRUG DISCOVERY AND DRUG 2843 01:37:49,960 --> 01:37:51,040 DEVELOPMENT THAT WE DON'T QUITE 2844 01:37:51,040 --> 01:37:53,960 UNDERSTAND IN TERMS OF MICROBIAL 2845 01:37:53,960 --> 01:37:54,200 ECOLOGY. 2846 01:37:54,200 --> 01:37:56,920 AND THEN THE LAST PART ARE THE 2847 01:37:56,920 --> 01:37:59,520 PRODUCTS THESE MICROBIAL 2848 01:37:59,520 --> 01:38:00,440 COMMUNITIES PRODUCE. 2849 01:38:00,440 --> 01:38:01,880 WE KNOW THEY PRODUCE ANTIBIOTICS 2850 01:38:01,880 --> 01:38:04,240 AND TOXINS AND OTHER THINGS THAT 2851 01:38:04,240 --> 01:38:06,880 EFFECT THE OVERALL DYNAMICS OF 2852 01:38:06,880 --> 01:38:07,400 THESE ECOLOGYIES. 2853 01:38:07,400 --> 01:38:11,320 AND SO WITH THAT, I'LL STOP AND 2854 01:38:11,320 --> 01:38:13,680 SAY THOSE ARE MOSTLY OUR 2855 01:38:13,680 --> 01:38:16,600 INTEREST IN THIS AREA. 2856 01:38:16,600 --> 01:38:20,160 AND THAT WE DO HAVE A 2857 01:38:20,160 --> 01:38:21,600 PRE-CLINICAL SERVICES PROGRAM 2858 01:38:21,600 --> 01:38:23,240 THAT SUPPORTS ALL THERAPEUTIC 2859 01:38:23,240 --> 01:38:24,320 DEVELOPMENT. 2860 01:38:24,320 --> 01:38:26,160 IT'S A FREE SERVICE FOR 2861 01:38:26,160 --> 01:38:28,320 PROMISING DISCOVERIES TO HELP 2862 01:38:28,320 --> 01:38:31,320 MOVE PRODUCTS ALONG THE PRODUCT 2863 01:38:31,320 --> 01:38:33,360 DEVELOPMENT PIPELINE AND WE HAVE 2864 01:38:33,360 --> 01:38:35,880 PROVIDED IN VITRO AND MICROBIAL 2865 01:38:35,880 --> 01:38:37,240 TESTING, ANIMAL TESTING, 2866 01:38:37,240 --> 01:38:37,560 APPROXIMATE. 2867 01:38:37,560 --> 01:38:40,080 K, PD AND OTHER TYPES OF 2868 01:38:40,080 --> 01:38:40,720 THERAPEUTIC DEVELOPMENT TESTING. 2869 01:38:40,720 --> 01:38:43,880 AND I'LL STOP THERE. 2870 01:38:43,880 --> 01:38:45,720 >>THANK YOU, RYAN. 2871 01:38:45,720 --> 01:38:51,160 AND NEXT WE CAN MOVE TO DR. 2872 01:38:51,160 --> 01:38:51,880 MOHAPATRA. 2873 01:38:51,880 --> 01:38:54,120 SO, WE HAVE, AS I JUST ALLUDED 2874 01:38:54,120 --> 01:38:56,400 TO BEFORE, WE HAVE A LOT OF 2875 01:38:56,400 --> 01:39:06,720 DIFFERENT FUNDING OPPORTUNITIES 2876 01:39:06,720 --> 01:39:10,360 I HAVE A SLIDE I'D LIKE TO 2877 01:39:10,360 --> 01:39:11,000 SHARE. 2878 01:39:11,000 --> 01:39:12,600 >>ALSO CAN YOU SPEAK UP A 2879 01:39:12,600 --> 01:39:14,080 LITTLE BIT? 2880 01:39:14,080 --> 01:39:14,920 YOU'RE A LITTLE SOFT. 2881 01:39:14,920 --> 01:39:16,400 >>IS THAT BETTER NOW? 2882 01:39:16,400 --> 01:39:17,080 >>YES. 2883 01:39:17,080 --> 01:39:19,920 >>OKAY. 2884 01:39:19,920 --> 01:39:20,560 LET ME JUST SHARE -- LET ME KNOW 2885 01:39:20,560 --> 01:39:24,200 IF YOU CAN SEE MY -- 2886 01:39:24,200 --> 01:39:27,920 >>WE CAN INDEED. 2887 01:39:27,920 --> 01:39:31,840 >>THROUGH THE NIH INITIATIVE OR 2888 01:39:31,840 --> 01:39:33,720 HELPING TO END ADDICTION LONG 2889 01:39:33,720 --> 01:39:38,880 TERM INITIATIVE, WE HAVE THREE 2890 01:39:38,880 --> 01:39:40,400 OF THE PROGRAMS IN THE PAIN 2891 01:39:40,400 --> 01:39:41,960 MANAGEMENT SIDE STARTING FROM 2892 01:39:41,960 --> 01:39:42,760 THE DISCOVERY. 2893 01:39:42,760 --> 01:39:48,400 YOU CAN SEE ON THE LEFT SIDE 2894 01:39:48,400 --> 01:39:50,720 FROM DISCOVERY WHERE GOOD 2895 01:39:50,720 --> 01:39:52,920 VALIDATION FOR THERAPEUTICS OR 2896 01:39:52,920 --> 01:39:57,680 PLANNING STUDIES TO DEVELOPMENT 2897 01:39:57,680 --> 01:40:02,720 AND THEN PRODUCING THE LEAD AND 2898 01:40:02,720 --> 01:40:05,240 THEN OPTIMIZE AND ALSO HAVE 2899 01:40:05,240 --> 01:40:12,440 PROGRAM WITH ANIMAL MODELS FOR 2900 01:40:12,440 --> 01:40:17,000 PAIN THERAPEUTIC PROGRAM. 2901 01:40:17,000 --> 01:40:21,480 AND ALSO SCREENING MULTIPLE 2902 01:40:21,480 --> 01:40:25,400 THERAPEUTICS LIKE SCREENING STEM 2903 01:40:25,400 --> 01:40:28,720 CELL-BASED ASSAYS AND NOW WE 2904 01:40:28,720 --> 01:40:36,000 HAVE HUMAN CELL-BASED GENE ASS 2905 01:40:36,000 --> 01:40:38,560 ASSAYS. 2906 01:40:38,560 --> 01:40:41,240 JOINT PAIN SPECIFIC AS MODEL 2907 01:40:41,240 --> 01:40:43,640 DEVELOPMENT AND THEN CLINICAL 2908 01:40:43,640 --> 01:40:46,080 TRIALS. 2909 01:40:46,080 --> 01:40:49,000 SO NATURAL URN OUTS ALL OF THESE 2910 01:40:49,000 --> 01:40:50,240 HERE WHERE YOU CAN UTILIZE THE 2911 01:40:50,240 --> 01:40:54,720 NATURAL PRODUCT TO UNDERSTAND 2912 01:40:54,720 --> 01:40:58,760 AND DISCOVER AND VALIDATE A 2913 01:40:58,760 --> 01:40:59,480 TARGET AND DEVELOP NEW 2914 01:40:59,480 --> 01:41:01,920 THERAPEUTICS AND UTILIZE NATURAL 2915 01:41:01,920 --> 01:41:04,320 PRODUCTS TO UNDERSTAND THE 2916 01:41:04,320 --> 01:41:07,800 BIOLOGY OF HUMAN PAIN CONDITION 2917 01:41:07,800 --> 01:41:11,200 AND THOSE NATURAL PRODUCTS ONCE 2918 01:41:11,200 --> 01:41:13,040 THEY HAVE A LEAD, THEY CAN GO 2919 01:41:13,040 --> 01:41:14,600 THROUGH THE THERAPEUTIC 2920 01:41:14,600 --> 01:41:16,320 DEVELOPMENT AND SCREENING 2921 01:41:16,320 --> 01:41:19,040 PROGRAMS BUT ALSO SMALL BUSINESS 2922 01:41:19,040 --> 01:41:21,920 PROGRAMS CAN SUPPORT THOSE 2923 01:41:21,920 --> 01:41:26,000 ALONGSIDE LIKE CLINICAL STUDIES 2924 01:41:26,000 --> 01:41:28,480 INCLUDING CLINICAL TRIALS. 2925 01:41:28,480 --> 01:41:33,040 AND JUST TO LET THE GENERAL 2926 01:41:33,040 --> 01:41:35,560 E-MAIL FOR THE INITIATIVE, IF 2927 01:41:35,560 --> 01:41:36,720 YOU'RE INTERESTED IN ANY OF 2928 01:41:36,720 --> 01:41:39,800 THESE, SEND AN E-MAIL TO THIS 2929 01:41:39,800 --> 01:41:44,400 SPECIFIC E-MAIL ID AND THEY WILL 2930 01:41:44,400 --> 01:41:45,520 SEND EACH INDIVIDUAL -- EACH OF 2931 01:41:45,520 --> 01:41:54,000 THESE PROGRAM AND THEY HAVE 2932 01:41:54,000 --> 01:41:55,040 CONTACTS FOR YOUR SPECIFIC 2933 01:41:55,040 --> 01:41:55,320 INTEREST. 2934 01:41:55,320 --> 01:41:56,680 IN ADDITION TO THESE INITIATIVES 2935 01:41:56,680 --> 01:41:59,800 AND NINDS, WE STILL REMAIN 2936 01:41:59,800 --> 01:42:03,200 HEAVILY INTERESTED IN THE 2937 01:42:03,200 --> 01:42:04,000 NATURAL PRODUCTS AND 2938 01:42:04,000 --> 01:42:06,480 UNDERSTANDING THE BIOLOGY OF 2939 01:42:06,480 --> 01:42:13,880 THESE AS WELL AS MANAGEMENT I'LL 2940 01:42:13,880 --> 01:42:15,880 STOP THERE. 2941 01:42:15,880 --> 01:42:17,360 >>THANK YOU, DP. 2942 01:42:17,360 --> 01:42:26,680 AND ON TO NCI. 2943 01:42:26,680 --> 01:42:27,560 >>HI. 2944 01:42:27,560 --> 01:42:31,040 NCI STILL ARE INTERESTED IN 2945 01:42:31,040 --> 01:42:33,400 NATURAL PRODUCTS. 2946 01:42:33,400 --> 01:42:38,080 I HAVE ALWAYS BEEN AND LIKE 2947 01:42:38,080 --> 01:42:42,720 NIGMS, WE SUPPORT ALL LEVELS OF 2948 01:42:42,720 --> 01:42:44,400 INVESTIGATOR-INITIATED PROJECTS 2949 01:42:44,400 --> 01:42:51,280 FROM R15, RL3, R21, R01 AND 2950 01:42:51,280 --> 01:42:52,240 PROGRAM PROJECT, P01. 2951 01:42:52,240 --> 01:42:56,640 WE HAVE CURRENTLY LONGSTANDING 2952 01:42:56,640 --> 01:43:02,040 PROGRAM PROJECT WITH A GROUP AT 2953 01:43:02,040 --> 01:43:05,200 THE -- HE WAS AT OHIO STATE 2954 01:43:05,200 --> 01:43:05,880 UNIVERSITY. 2955 01:43:05,880 --> 01:43:08,880 AND SO -- YES, IN COLLABORATION 2956 01:43:08,880 --> 01:43:11,680 WITH SEVERAL OTHER INSTITUTIONS 2957 01:43:11,680 --> 01:43:14,040 AND COMPANIES. 2958 01:43:14,040 --> 01:43:17,440 IN TERMS OF SPECIAL INITIATIVES, 2959 01:43:17,440 --> 01:43:19,640 RECENTLY TRANS-NCI, WE DEVELOPED 2960 01:43:19,640 --> 01:43:21,680 WITH ANOTHER -- JUST OUR 2961 01:43:21,680 --> 01:43:23,080 DIVISION, A DIVISION CANCER 2962 01:43:23,080 --> 01:43:24,960 TREATMENT AND DIAGNOSIS WITH 2963 01:43:24,960 --> 01:43:28,080 DIVISION OF CANCER PREVENTION 2964 01:43:28,080 --> 01:43:32,400 POPULATION SCIENCES AND OTHERS. 2965 01:43:32,400 --> 01:43:38,560 WE HAVE SENT OUT A NOSI CANIS 2966 01:43:38,560 --> 01:43:41,080 AND TREATMENT OF CANCER-RELATED 2967 01:43:41,080 --> 01:43:41,920 PAIN. 2968 01:43:41,920 --> 01:43:42,880 -- CANNABIS. 2969 01:43:42,880 --> 01:43:45,080 THIS IS STILL ACTIVE. 2970 01:43:45,080 --> 01:43:47,720 ONE CAN LOOK IT UP IF YOU'RE 2971 01:43:47,720 --> 01:43:48,600 INTERESTED. 2972 01:43:48,600 --> 01:43:50,400 IN ADDITION WE ARE ALSO 2973 01:43:50,400 --> 01:43:56,040 INTERESTED IN MICROBIOME AND HOW 2974 01:43:56,040 --> 01:44:06,560 DISPARITY RELATED PROJECTS IN 2975 01:44:12,200 --> 01:44:14,440 ADDITION TO NATURAL SOURCES AND 2976 01:44:14,440 --> 01:44:16,400 NEW NOVEL TARGETS USING NATURAL 2977 01:44:16,400 --> 01:44:20,120 PRODUCTS TOO. 2978 01:44:20,120 --> 01:44:24,720 IN ADDITION, SOME OF THESE VERY 2979 01:44:24,720 --> 01:44:29,360 POTENT TOXINS COULD BE USED AS 2980 01:44:29,360 --> 01:44:33,120 WARHEAD FOR THE -- DRUG 2981 01:44:33,120 --> 01:44:33,640 CONJUGATES TO DELIVER 2982 01:44:33,640 --> 01:44:37,040 SPECIFICALLY TO THE TARGET TUMOR 2983 01:44:37,040 --> 01:44:38,920 CELLS AND TUMOR ENVIRONMENT. 2984 01:44:38,920 --> 01:44:42,040 SO THESE ARE THE THINGS THAT I 2985 01:44:42,040 --> 01:44:43,440 LIKE TO HIGHLIGHT. 2986 01:44:43,440 --> 01:44:47,280 IF YOU HAVE ANY QUESTIONS, FEEL 2987 01:44:47,280 --> 01:44:54,760 FREE TO E-MAIL ME THANK YOU. 2988 01:44:54,760 --> 01:44:56,360 >>THANK YOU. 2989 01:44:56,360 --> 01:44:58,760 FROM THE NCCIH PERSPECTIVE, I 2990 01:44:58,760 --> 01:45:00,360 WOULD LIKE TO HIGHLIGHT A 2991 01:45:00,360 --> 01:45:02,440 FUNDING OPPORTUNITY IN BASIC AND 2992 01:45:02,440 --> 01:45:05,160 MECHANISTIC RESEARCH ON NATURAL 2993 01:45:05,160 --> 01:45:08,000 PRODUCTS AS AN EXAMPLE. 2994 01:45:08,000 --> 01:45:09,800 AND THIS IS A NOTICE OF SPECIAL 2995 01:45:09,800 --> 01:45:13,240 INTEREST OR NOSI THAT IS LINKED 2996 01:45:13,240 --> 01:45:16,400 TO THE PARENT RO1 OR R21 ON 2997 01:45:16,400 --> 01:45:21,480 FUNDAMENTAL SCIENCE RESEARCH ON 2998 01:45:21,480 --> 01:45:22,080 COMPLEMENTARY AND INTEGRATIVE 2999 01:45:22,080 --> 01:45:22,640 HEALTH APPROACHES. 3000 01:45:22,640 --> 01:45:23,680 AND SOME KEY POINTS FROM THIS 3001 01:45:23,680 --> 01:45:24,720 FUNDING OPPORTUNITY ARE 3002 01:45:24,720 --> 01:45:26,920 MECHANISMS OF COMPLEMENTARY AND 3003 01:45:26,920 --> 01:45:30,000 INTEGRATIVE HEALTH INTERVENTIONS 3004 01:45:30,000 --> 01:45:32,520 AND TECHNOLOGY DEVELOPMENT 3005 01:45:32,520 --> 01:45:33,560 RESEARCH. 3006 01:45:33,560 --> 01:45:39,000 AND FOR THE MECHANISMS OF CIH 3007 01:45:39,000 --> 01:45:40,840 INTERVENTIONS AREAS OF HIGH 3008 01:45:40,840 --> 01:45:42,200 PROGRAM PRIORITY COULD INCLUDE 3009 01:45:42,200 --> 01:45:43,640 EXPLORING THE MECHANISTIC 3010 01:45:43,640 --> 01:45:46,080 EFFECTS OF MULTIMODAL 3011 01:45:46,080 --> 01:45:47,000 INTERVENTIONS OR INTEGRATIVE 3012 01:45:47,000 --> 01:45:50,400 HEALTH APPROACHES ON ONE OR MORE 3013 01:45:50,400 --> 01:45:52,360 PHYSIOLOGICAL SYSTEMS AND THEIR 3014 01:45:52,360 --> 01:45:53,000 INTERACTIONS ON ANIMAL MODELS 3015 01:45:53,000 --> 01:45:55,280 AND IN IN TERMS OF THE 3016 01:45:55,280 --> 01:45:56,320 TECHNOLOGY AND METHOD 3017 01:45:56,320 --> 01:46:00,400 DEVELOPMENT COMPONENT OF THIS 3018 01:46:00,400 --> 01:46:01,240 FUNDING OPPORTUNITY, THIS 3019 01:46:01,240 --> 01:46:02,560 INCLUDES FOR EXAMPLE, TARGETED 3020 01:46:02,560 --> 01:46:05,720 AND UNTARGETED BIOINFORMATIC 3021 01:46:05,720 --> 01:46:07,720 APPROACHES THAT IDENTIFY ACTIVE 3022 01:46:07,720 --> 01:46:09,360 COMPONENTS IN A NATURAL PRODUCT 3023 01:46:09,360 --> 01:46:09,840 MIXTURE. 3024 01:46:09,840 --> 01:46:12,400 OR THE DEVELOPMENT OF PHENOTYPIC 3025 01:46:12,400 --> 01:46:15,120 MODELS CAPABLE OF ILLUMINATING 3026 01:46:15,120 --> 01:46:19,000 MECHANISMS OF ACTION. 3027 01:46:19,000 --> 01:46:22,160 AND AS DR. DR. MOHAPATRA 3028 01:46:22,160 --> 01:46:24,720 MENTIONED IN TERMS OF THE HEAL 3029 01:46:24,720 --> 01:46:26,880 INITIATIVE, NCCIH ALSO SIGNED ON 3030 01:46:26,880 --> 01:46:32,160 TO THE PHASED R61-R33 IGNITE 3031 01:46:32,160 --> 01:46:33,960 INNOVATION GRANT TO NURTURE 3032 01:46:33,960 --> 01:46:35,280 INITIAL TRANSLATIONAL EFFORTS 3033 01:46:35,280 --> 01:46:37,840 FUNDING OPPORTUNITY ANNOUNCEMENT 3034 01:46:37,840 --> 01:46:41,040 AND IF YOU'RE NOT FAMILIAR WITH 3035 01:46:41,040 --> 01:46:42,560 THESE MECHANISMS, IT'S BY-PART 3036 01:46:42,560 --> 01:46:46,840 FUNDING OPPORTUNITY WHERE -- TWO 3037 01:46:46,840 --> 01:46:48,320 PART -- SPECIFIC MILESTONES ARE 3038 01:46:48,320 --> 01:46:49,040 MET IN THE FIRST PHASE BEFORE 3039 01:46:49,040 --> 01:46:51,600 FUNDING IS GIVEN FOR THE 3040 01:46:51,600 --> 01:46:54,840 CONTINUATION OF THE GRANT AND 3041 01:46:54,840 --> 01:46:56,400 THE R33 PHASE. 3042 01:46:56,400 --> 01:46:57,960 THIS FUNDING OPPORTUNITY, WE AND 3043 01:46:57,960 --> 01:47:00,400 OTHER INSTITUTES THAT ARE SIGNED 3044 01:47:00,400 --> 01:47:02,480 ON TO THIS ANNOUNCEMENT ARE 3045 01:47:02,480 --> 01:47:03,920 FIRST INTERESTED IN DEVELOPMENT 3046 01:47:03,920 --> 01:47:06,120 OF NEW IN VITRO OR EX-VIVO 3047 01:47:06,120 --> 01:47:09,520 ASSAYS AND SCREENING EFFORTS TO 3048 01:47:09,520 --> 01:47:10,720 IDENTIFY NOVEL THERAPEUTIC 3049 01:47:10,720 --> 01:47:14,600 AGENTS FOR NEUROLOGICAL AND 3050 01:47:14,600 --> 01:47:16,240 NEUROMUSCULAR DISORDERS. 3051 01:47:16,240 --> 01:47:18,960 AND THAT REALLY IN THE R61 PHASE 3052 01:47:18,960 --> 01:47:20,480 SUPPORTS THE INITIAL DEVELOPMENT 3053 01:47:20,480 --> 01:47:21,720 REFINEMENT AND VALIDATION OF 3054 01:47:21,720 --> 01:47:25,800 THESE ASSAYS AND THEN THE R33 3055 01:47:25,800 --> 01:47:26,800 PHASE ITERATIVE SCREENING AND 3056 01:47:26,800 --> 01:47:29,000 CHARACTERIZATION OF THE 3057 01:47:29,000 --> 01:47:31,440 THERAPEUTIC AGENT FROM THE 3058 01:47:31,440 --> 01:47:35,560 SCREEN INCLUDING DESIGN AND 3059 01:47:35,560 --> 01:47:38,480 PREPARATION FOR FURTHER 3060 01:47:38,480 --> 01:47:40,920 CHARACTERIZATION OF OTHER AGENTS 3061 01:47:40,920 --> 01:47:42,000 RELATED TO THE INITIAL HITS 3062 01:47:42,000 --> 01:47:46,200 USING A MEDICINAL CHEMISTRY 3063 01:47:46,200 --> 01:47:47,080 APPROACH. 3064 01:47:47,080 --> 01:47:49,640 AND SO, SO WITH THAT SNAPSHOT OF 3065 01:47:49,640 --> 01:47:51,080 DIFFERENT FUNDING OPPORTUNITIES 3066 01:47:51,080 --> 01:47:54,280 AND HOW THE WEBINAR THEMES 3067 01:47:54,280 --> 01:47:57,880 INTERSECT WITH VARIOUS NIH 3068 01:47:57,880 --> 01:47:59,120 PRIORITIES, I WOULD NOW LIKE TO 3069 01:47:59,120 --> 01:48:05,720 THANK EACH OF OUR PROGRAM FERNAL 3070 01:48:05,720 --> 01:48:08,920 COLLEAGUES AND MOVE INTO THE Q&A 3071 01:48:08,920 --> 01:48:11,880 SESSION AND WE WOULD BE GLAD TO 3072 01:48:11,880 --> 01:48:12,480 TAKE SOME QUESTIONS FROM THE 3073 01:48:12,480 --> 01:48:12,680 CHAT. 3074 01:48:12,680 --> 01:48:15,840 THE FIRST QUESTION THAT WE HAVE 3075 01:48:15,840 --> 01:48:16,920 IS FOR DR. MOHAPATRA. 3076 01:48:16,920 --> 01:48:21,240 IT IS, IS THERE A MECHANISM FOR 3077 01:48:21,240 --> 01:48:26,160 BIOTECH COMPANIES TO ASSESS SOME 3078 01:48:26,160 --> 01:48:28,840 OF THE OPPORTUNITIES THAT YOU 3079 01:48:28,840 --> 01:48:31,040 MENTIONED? 3080 01:48:31,040 --> 01:48:36,760 >>ABSOLUTELY. 3081 01:48:36,760 --> 01:48:40,400 ALL THE DEVELOPMENT PROGRAMS AND 3082 01:48:40,400 --> 01:48:46,720 OPTIMIZING AND ALL OPEN TO -- 3083 01:48:46,720 --> 01:48:47,800 ENCOURAGED TO APPLY. 3084 01:48:47,800 --> 01:48:50,880 AND THE I CAN GIVE YOU THE 3085 01:48:50,880 --> 01:48:52,960 NUMBER AND MORE THAN 60 3086 01:48:52,960 --> 01:48:54,840 COMPANIES ARE IN THE SBIR BASE 3087 01:48:54,840 --> 01:49:01,080 ON THE PAIN SIDE RIGHT NOW. 3088 01:49:01,080 --> 01:49:01,800 GOOD IF YOU'RE INTERESTED IN 3089 01:49:01,800 --> 01:49:08,120 THAT AND THEN LOOK INTO THE SBIR 3090 01:49:08,120 --> 01:49:10,640 PROGRAM AND WE GO DOWN TO THE 3091 01:49:10,640 --> 01:49:21,080 PROGRAM CONTACT AND MAKE 3092 01:49:21,640 --> 01:49:23,520 SPECIFIC INTEREST. 3093 01:49:23,520 --> 01:49:24,000 >>THANK YOU. 3094 01:49:24,000 --> 01:49:25,560 >>I'M GOING TO PICK UP A 3095 01:49:25,560 --> 01:49:29,280 QUESTION THAT CAME IN IN OUR 3096 01:49:29,280 --> 01:49:29,880 EARLIER SESSION WHICH IS, I'M 3097 01:49:29,880 --> 01:49:31,560 GOING DROP IT INTO THE CHAT 3098 01:49:31,560 --> 01:49:32,120 HERE. 3099 01:49:32,120 --> 01:49:33,840 IT WAS ONE ABOUT WHETHER OR NOT 3100 01:49:33,840 --> 01:49:36,200 THERE IS ANY EFFORT TO COLLECT 3101 01:49:36,200 --> 01:49:40,840 PATIENT DATA SINCE MANY PATIENTS 3102 01:49:40,840 --> 01:49:43,840 ARE TAKING -- I BELIEVE NATURAL 3103 01:49:43,840 --> 01:49:45,120 PRODUCTS, AND THEY ARE SORT OF 3104 01:49:45,120 --> 01:49:46,840 WONDERING POTENTIALLY COULD THIS 3105 01:49:46,840 --> 01:49:48,400 DATA PROVIDE A SIGNAL FOR THE 3106 01:49:48,400 --> 01:49:50,840 TYPE OF NATURAL PRODUCTS AND THE 3107 01:49:50,840 --> 01:49:54,200 TYPE OF CANCER SPECIFIED THERE? 3108 01:49:54,200 --> 01:49:55,360 I DON'T KNOW IF ANYBODY -- IF 3109 01:49:55,360 --> 01:49:56,920 ANY OF OUR SPEAKERS OR ANY OF 3110 01:49:56,920 --> 01:50:00,400 OUR PROGRAM FOLKS WOULD LIKE TO 3111 01:50:00,400 --> 01:50:10,880 MAYBE TAKE ON THAT QUESTION? 3112 01:50:10,880 --> 01:50:19,240 >>I CAN TAKE THAT. 3113 01:50:19,240 --> 01:50:21,680 PRIMARY HUMAN TISSUES ASSOCIATED 3114 01:50:21,680 --> 01:50:23,600 WITH PAIN AND PROCESSING PAIN, 3115 01:50:23,600 --> 01:50:25,120 LIKE ALL STAGES OF THE PAIN 3116 01:50:25,120 --> 01:50:28,120 PROCESSING IS BEING COLLECTED 3117 01:50:28,120 --> 01:50:35,360 FOR MULTIMODAL -- AND FOR ONE 3118 01:50:35,360 --> 01:50:42,720 AREA -- COLLECT THE DATA 3119 01:50:42,720 --> 01:50:48,600 ASSOCIATED, INCLUDING PREVIOUS 3120 01:50:48,600 --> 01:50:51,760 THERAPEUTIC DRUGS AND SO THOSE 3121 01:50:51,760 --> 01:50:52,960 METADATA ARE COLLECTED AND COULD 3122 01:50:52,960 --> 01:51:01,720 BE TAKEN INTO ACCOUNT WHEN 3123 01:51:01,720 --> 01:51:06,760 THESE -- 3124 01:51:06,760 --> 01:51:15,320 [ INAUDIBLE ] 3125 01:51:15,320 --> 01:51:18,760 >>DR. O'KEEFE OR PATRICK, IF 3126 01:51:18,760 --> 01:51:24,760 THERE IS ANY THOUGHTS THERE? 3127 01:51:24,760 --> 01:51:30,960 YALI FU? 3128 01:51:30,960 --> 01:51:32,800 YOU'RE MUTED IF YOU WANTED TO 3129 01:51:32,800 --> 01:51:36,360 COMMENT ON THAT QUESTION AT ALL. 3130 01:51:36,360 --> 01:51:37,600 THE QUESTION ABOUT, IS THERE AN 3131 01:51:37,600 --> 01:51:38,920 EFFORT TO COLLECT PATIENT DATA 3132 01:51:38,920 --> 01:51:41,560 SINCE MANY ARE TAKING NATURAL 3133 01:51:41,560 --> 01:51:42,840 PRODUCTS, POTENTIALLY COULD THIS 3134 01:51:42,840 --> 01:51:44,240 DATA PROVIDE A SIGNAL FOR THE 3135 01:51:44,240 --> 01:51:50,000 TYPE OF NATURAL PRODUCT IN THE 3136 01:51:50,000 --> 01:51:54,320 CANCER TYPE? 3137 01:51:54,320 --> 01:51:55,720 >>THIS IS A LITTLE BIT 3138 01:51:55,720 --> 01:51:56,200 COMPLICATED, I THINK. 3139 01:51:56,200 --> 01:52:01,440 THERE ARE A LOT OF IN THE 15, 20 3140 01:52:01,440 --> 01:52:05,680 YEARS AGO, A BIG BOOST ABOUT 3141 01:52:05,680 --> 01:52:09,080 THAT SUPPLEMENT AND TAKING -- 3142 01:52:09,080 --> 01:52:11,880 ARE PURE. 3143 01:52:11,880 --> 01:52:16,320 I HAVEN'T SEEN HOW THIS HAS 3144 01:52:16,320 --> 01:52:20,600 GUIDED THE CURRENT MOLECULAR 3145 01:52:20,600 --> 01:52:24,400 GENOMIC-BASED CANCER RESEARCH. 3146 01:52:24,400 --> 01:52:26,000 I HAVE TO SAY. 3147 01:52:26,000 --> 01:52:28,400 BUT I THINK WE SHOULD THIS KIND 3148 01:52:28,400 --> 01:52:29,920 OF DATABASE. 3149 01:52:29,920 --> 01:52:35,160 IT WOULD BE VARIABLE BUT SOME OF 3150 01:52:35,160 --> 01:52:36,280 THESE I DON'T KNOW LIKE A 3151 01:52:36,280 --> 01:52:38,480 DIVISION CANCER PREVENTION HAS 3152 01:52:38,480 --> 01:52:40,400 SOME KIND OF, THIS KIND OF MASS 3153 01:52:40,400 --> 01:52:45,360 DATA THAT I KNOW THEY DO HAVE 3154 01:52:45,360 --> 01:52:49,240 VITAMIN E, BUT I DON'T KNOW 3155 01:52:49,240 --> 01:52:51,720 ABOUT COMPLEX NATURAL PRODUCTS, 3156 01:52:51,720 --> 01:52:52,640 TAKING IT FOR YEARS AND YEARS 3157 01:52:52,640 --> 01:53:00,040 AND DO THEY HAVE LONGITUDINAL 3158 01:53:00,040 --> 01:53:10,440 AND DATASETS ON THIS. 3159 01:53:12,240 --> 01:53:13,360 >>THANK YOU. 3160 01:53:13,360 --> 01:53:14,800 I DON'T SEE ANY CONTINUING 3161 01:53:14,800 --> 01:53:17,240 QUESTIONS FROM THE VIDEOCAST. 3162 01:53:17,240 --> 01:53:22,560 AND I DID HAVE A QUESTION FOR 3163 01:53:22,560 --> 01:53:23,160 THE STAFF, PROGRAM STAFF THAT 3164 01:53:23,160 --> 01:53:28,560 ARE HERE, AND THAT IS THE USE OF 3165 01:53:28,560 --> 01:53:29,840 DIFFERENT FUNDING OPPORTUNITY 3166 01:53:29,840 --> 01:53:30,800 ANNOUNCEMENTS AND THE MECHANISM 3167 01:53:30,800 --> 01:53:36,400 YOU USE AT YOUR INSTITUTE. 3168 01:53:36,400 --> 01:53:40,520 IS THERE A PARTICULAR FUNDING 3169 01:53:40,520 --> 01:53:42,760 MECHANISM YOUR INSTITUTE TENDS 3170 01:53:42,760 --> 01:53:46,000 TO GRAVITATE TOWARDS FOR THE 3171 01:53:46,000 --> 01:53:46,280 AUDIENCE? 3172 01:53:46,280 --> 01:53:47,720 I'LL START BY ANSWERING THE 3173 01:53:47,720 --> 01:53:49,800 QUESTION ON BEHALF OF NCCIH AND 3174 01:53:49,800 --> 01:53:56,400 THE THAT IS THAT WHILE WE DO 3175 01:53:56,400 --> 01:53:58,360 ACCEPT INVESTIGATOR-INITIATED 3176 01:53:58,360 --> 01:54:02,400 APPLICATIONS, WE ARE ALSO QUITE 3177 01:54:02,400 --> 01:54:04,080 PRIVY TO THE NOSI. 3178 01:54:04,080 --> 01:54:05,560 SO WE GENERATE A LOT OF NOTICES 3179 01:54:05,560 --> 01:54:08,520 OF SPECIAL INTEREST, DECLARE A 3180 01:54:08,520 --> 01:54:09,840 PARTICULAR AREA THAT WE ARE 3181 01:54:09,840 --> 01:54:10,440 FOCUSING ON. 3182 01:54:10,440 --> 01:54:12,640 I KNOW THAT IS NOT THE SAME 3183 01:54:12,640 --> 01:54:13,320 ACROSS NIH AND I WANTED TO GIVE 3184 01:54:13,320 --> 01:54:17,560 THE OPPORTUNITY FOR MY 3185 01:54:17,560 --> 01:54:20,720 COLLEAGUES TO WEIGH IN ON THEIR 3186 01:54:20,720 --> 01:54:25,720 INSTITUTE. 3187 01:54:25,720 --> 01:54:28,840 >>THIS IS MICHELLE FROM NIGMS. 3188 01:54:28,840 --> 01:54:30,720 I WILL START AND EMPHASIZE AGAIN 3189 01:54:30,720 --> 01:54:34,040 THAT NIGMS IS VERY MUCH 3190 01:54:34,040 --> 01:54:35,000 INTERESTED IN 3191 01:54:35,000 --> 01:54:37,000 INVESTIGATOR-INITIATED EFFORTS. 3192 01:54:37,000 --> 01:54:39,240 SO, THE AREAS IN WHICH WE ARE 3193 01:54:39,240 --> 01:54:42,240 INTERESTED IN SUPPORTING 3194 01:54:42,240 --> 01:54:43,560 SCIENTIFIC RESEARCH ARE DEFINED 3195 01:54:43,560 --> 01:54:44,560 ON OUR WEBSITE. 3196 01:54:44,560 --> 01:54:48,400 THERE IS AN AGGRESSIVE WEB PAGE 3197 01:54:48,400 --> 01:54:51,160 WITH DIVISION CONTACTS AND THE 3198 01:54:51,160 --> 01:54:53,960 AREAS IN WHICH WE ARE INTERESTED 3199 01:54:53,960 --> 01:54:58,520 IN ADDITION, I THINK THAT THE 3200 01:54:58,520 --> 01:55:00,400 NIGMS AND 35 MERA IS ONE THAT IS 3201 01:55:00,400 --> 01:55:01,360 ROUTINELY HIGHLIGHTED IN THE 3202 01:55:01,360 --> 01:55:02,840 LAST FEW YEARS AS SOMETHING THAT 3203 01:55:02,840 --> 01:55:05,840 IS OF INTEREST FOR NIGMS TO 3204 01:55:05,840 --> 01:55:15,120 SUPPORT RESEARCH PROJECT GRANT 3205 01:55:15,120 --> 01:55:15,360 EFFORTS. 3206 01:55:15,360 --> 01:55:16,640 >>I CAN ADD TO THAT. 3207 01:55:16,640 --> 01:55:25,680 SO FROM NINDS PROSPECT, WE HAVE 3208 01:55:25,680 --> 01:55:28,120 REALLY GOTTEN -- IN TERMS OF 3209 01:55:28,120 --> 01:55:30,000 WHAT IS THE NEED? 3210 01:55:30,000 --> 01:55:38,360 WHAT IS THE GOAL? 3211 01:55:38,360 --> 01:55:43,560 WE TEND TO -- WHICH ARE MORE 3212 01:55:43,560 --> 01:55:50,840 LIKE A MECHANISM OR EVEN LIKE -- 3213 01:55:50,840 --> 01:55:54,080 THERE ARE MECHANISMS LIKE 3214 01:55:54,080 --> 01:55:56,400 THERAPEUTIC PROGRAM AND -- THEY 3215 01:55:56,400 --> 01:56:02,560 HAVE A LOT OF LIKE CONTRACT AND 3216 01:56:02,560 --> 01:56:05,640 A LOT OF OTHER -- WHICH BRING 3217 01:56:05,640 --> 01:56:08,400 THE COLLECTIVE THEME OF DRUG 3218 01:56:08,400 --> 01:56:10,480 DEVELOPMENT SO THEY CAN REALLY 3219 01:56:10,480 --> 01:56:13,080 SUPPORT AND CHANNEL YOUR DRUG 3220 01:56:13,080 --> 01:56:14,920 DEVELOPMENT OR THERAPEUTIC 3221 01:56:14,920 --> 01:56:16,600 DEVELOPMENT FROM THE VERY BASIC 3222 01:56:16,600 --> 01:56:20,400 CONCEPT OF EARLY STAGES ALL THE 3223 01:56:20,400 --> 01:56:22,800 WAY THROUGH THE TRIALS AND THEN 3224 01:56:22,800 --> 01:56:24,280 ULTIMATELY PUSHING TOWARDS THE 3225 01:56:24,280 --> 01:56:26,520 PHASE II TRIALS. 3226 01:56:26,520 --> 01:56:29,440 SO WE TRIED TO, BASED ON A NEED 3227 01:56:29,440 --> 01:56:34,040 BASIS AND BASED ON WHAT THE GOAL 3228 01:56:34,040 --> 01:56:35,000 IS THERE. 3229 01:56:35,000 --> 01:56:37,400 THAT IS OUR APPROACH. 3230 01:56:37,400 --> 01:56:41,200 FOR MOST BASICS, WE TRY TO GO 3231 01:56:41,200 --> 01:56:43,080 THROUGH THE INVESTIGATOR 3232 01:56:43,080 --> 01:56:47,960 INITIATED BUT MANY COME WITH 3233 01:56:47,960 --> 01:56:52,520 THERAPEUTIC OR DEVICE 3234 01:56:52,520 --> 01:56:54,600 DEVELOPMENT BUT MORE TOWARDS THE 3235 01:56:54,600 --> 01:56:57,840 WELL STRUCTURED AND SUPPORTED 3236 01:56:57,840 --> 01:57:01,640 PROGRAM WHERE THERAPEUTIC 3237 01:57:01,640 --> 01:57:09,720 DEVELOPMENT CAN BE A TARGET. 3238 01:57:09,720 --> 01:57:14,400 >>NCI SIDE, I KNOW FROM MY 3239 01:57:14,400 --> 01:57:18,000 DIVISION WE ARE GRAVITATING 3240 01:57:18,000 --> 01:57:19,160 TOWARDS MORE TRADITIONAL 3241 01:57:19,160 --> 01:57:22,600 INVESTIGATOR INITIATED RO1s. 3242 01:57:22,600 --> 01:57:26,640 I THINK THAT TAKES A BIG PART OF 3243 01:57:26,640 --> 01:57:30,920 OUR OVERALL FUNDING PORTFOLIO. 3244 01:57:30,920 --> 01:57:34,920 WE HAVE SMALLER PROJECTS AND 3245 01:57:34,920 --> 01:57:40,200 R15, R21 AND R33 WHICH ARE 3246 01:57:40,200 --> 01:57:42,320 PHASE-IN PROJECTS WITH 3247 01:57:42,320 --> 01:57:43,600 MILESTONES REQUIREMENTS. 3248 01:57:43,600 --> 01:57:45,720 AND THEN WE HAVE PROGRAM 3249 01:57:45,720 --> 01:57:45,920 PROJECT. 3250 01:57:45,920 --> 01:57:52,400 WE HAVE A HUGE CHUNK OF R35 IS 3251 01:57:52,400 --> 01:57:53,800 FROM INVESTIGATORS. 3252 01:57:53,800 --> 01:57:57,880 THESE ARE REVIEWED NOT BY 3253 01:57:57,880 --> 01:58:00,640 SPECIFIC AIMS AND TRADITIONAL 3254 01:58:00,640 --> 01:58:02,400 RO1s BUT RATHER BY THE VISION 3255 01:58:02,400 --> 01:58:04,840 AND THE LONG TERM PERSPECTIVE OF 3256 01:58:04,840 --> 01:58:06,240 THE INVESTIGATOR. 3257 01:58:06,240 --> 01:58:08,520 AND ALL OF THESE ANNOUNCEMENTS 3258 01:58:08,520 --> 01:58:11,880 CAN BE FOUND FROM OUR WEBSITE OR 3259 01:58:11,880 --> 01:58:17,360 NIH GUIDE OF JUST A SEARCH UNDER 3260 01:58:17,360 --> 01:58:18,720 NCI. 3261 01:58:18,720 --> 01:58:22,000 OUR DIVISION OF CANCER 3262 01:58:22,000 --> 01:58:22,560 PREVENTION, I THINK THEY ARE 3263 01:58:22,560 --> 01:58:23,600 INTERESTED IN NATURAL PRODUCTS 3264 01:58:23,600 --> 01:58:28,240 AS A CHEMO PREVENTIVE AGENTS AND 3265 01:58:28,240 --> 01:58:32,560 THEN IN COMBINATION WITH -- 3266 01:58:32,560 --> 01:58:36,440 CHEMO AND IMMUNOTHERAPY AS WELL. 3267 01:58:36,440 --> 01:58:40,080 SO, THESE ARE THE PROBABLY JUST 3268 01:58:40,080 --> 01:58:45,080 THE LANDSCAPE OF OUR FUNDING 3269 01:58:45,080 --> 01:58:46,920 PURCHASE RIGHT NOW. 3270 01:58:46,920 --> 01:58:48,680 >>GREAT. 3271 01:58:48,680 --> 01:58:48,920 THANK YOU. 3272 01:58:48,920 --> 01:58:50,920 AND GIVEN THAT WE ARE RIGHT AT 3273 01:58:50,920 --> 01:58:53,920 THE TOP OF THE HOUR, I DID WANT 3274 01:58:53,920 --> 01:58:56,200 TO THANK EACH OF THE PROGRAM 3275 01:58:56,200 --> 01:58:59,960 STAFF FROM EACH OF OUR SISTER 3276 01:58:59,960 --> 01:59:02,120 INSTITUTES AND THANK ALL THE 3277 01:59:02,120 --> 01:59:03,520 AUDIENCE AS WELL FOR THE 3278 01:59:03,520 --> 01:59:05,880 QUESTIONS AND I DID WANT TO NOW 3279 01:59:05,880 --> 01:59:10,720 MOVE INTO THE LAST PART OF OUR 3280 01:59:10,720 --> 01:59:12,080 AGENDA WHICH IS TO DR. HOP TO 3281 01:59:12,080 --> 01:59:14,800 OFFER A FEW CLOSING REMARKS TO 3282 01:59:14,800 --> 01:59:16,120 CLOSE US OUT. 3283 01:59:16,120 --> 01:59:18,640 >>THANK YOU, PATRICK. 3284 01:59:18,640 --> 01:59:22,320 I THINK MY OVERALL THEME FOR 3285 01:59:22,320 --> 01:59:24,000 TODAY IS, IT'S EXCITING TIMES. 3286 01:59:24,000 --> 01:59:26,720 IT'S EXCITING TIMES TO BE IN 3287 01:59:26,720 --> 01:59:27,240 NATURAL PRODUCTS RESEARCH. 3288 01:59:27,240 --> 01:59:30,440 I THINK WE HEARD SOME REALLY 3289 01:59:30,440 --> 01:59:32,160 INCREDIBLY STRONG TALKS FROM OUR 3290 01:59:32,160 --> 01:59:34,120 THREE SPEAKERS, DEVELOPING SOME 3291 01:59:34,120 --> 01:59:38,600 REALLY SOPHISTICATED RESOURCES 3292 01:59:38,600 --> 01:59:39,160 THAT ARE ONLINE OR WILL BE 3293 01:59:39,160 --> 01:59:42,240 COMING ON LINE VERY SOON, WHICH 3294 01:59:42,240 --> 01:59:47,480 I THINK IN GENDERS A LOT OF 3295 01:59:47,480 --> 01:59:48,080 ENTHUSIASM FOR THIS COMMUNITY. 3296 01:59:48,080 --> 01:59:48,680 AND FOR WHAT THE FUTURE HOLDS. 3297 01:59:48,680 --> 01:59:50,160 WE HEARD A LOT FROM THE NIH 3298 01:59:50,160 --> 01:59:52,360 FOLKS ABOUT THEIR CONTINUED 3299 01:59:52,360 --> 01:59:54,720 INTEREST IN COMMITMENT TO 3300 01:59:54,720 --> 01:59:56,400 NATURAL PRODUCTS RESEARCH 3301 01:59:56,400 --> 01:59:58,320 THROUGH A VARIETY OF WAYS. 3302 01:59:58,320 --> 02:00:01,560 THERE IS RESOURCES AVAILABLE 3303 02:00:01,560 --> 02:00:03,160 BOTH TO HELP INVESTIGATORS GET 3304 02:00:03,160 --> 02:00:05,480 THEIR FOOTED IN DOOR IN TERMS OF 3305 02:00:05,480 --> 02:00:06,840 GRANT FUNDING BUT ALSO RESOURCES 3306 02:00:06,840 --> 02:00:09,240 WE HEARD TO HELP PEOPLE IF THEY 3307 02:00:09,240 --> 02:00:10,440 HAVE REALLY STRONG PRODUCTS THAT 3308 02:00:10,440 --> 02:00:12,200 NEED A LITTLE BIT OF HELP WITH 3309 02:00:12,200 --> 02:00:12,480 DEVELOPMENT. 3310 02:00:12,480 --> 02:00:14,120 SO THERE IS INTERNAL RESOURCES 3311 02:00:14,120 --> 02:00:16,400 AS WELL AS GREAT RESOURCES. 3312 02:00:16,400 --> 02:00:17,240 SO I THINK THE FUTURE IS BRIGHT. 3313 02:00:17,240 --> 02:00:20,400 I KNOW THAT NCCIH AND THE REST 3314 02:00:20,400 --> 02:00:24,440 OF THE FOLKS OUR PARTNERS AT 3315 02:00:24,440 --> 02:00:25,080 NIH, CONTINUE TO BE INTERESTED 3316 02:00:25,080 --> 02:00:27,280 IN NATURAL PRODUCTS FOR ALL OF 3317 02:00:27,280 --> 02:00:28,400 THE OBVIOUS REASONS THAT WE 3318 02:00:28,400 --> 02:00:29,080 HEARD ABOUT TODAY. 3319 02:00:29,080 --> 02:00:31,800 AND SO, FOR THAT, I THINK THAT I 3320 02:00:31,800 --> 02:00:34,600 WOULD ENCOURAGE OUR AUDIENCE TO 3321 02:00:34,600 --> 02:00:35,920 KEEP SUBMITTING THE APPLICATIONS 3322 02:00:35,920 --> 02:00:37,240 AND KEEP COMMUNICATING WITH US 3323 02:00:37,240 --> 02:00:39,640 ABOUT YOUR IDEAS AND WE WILL DO 3324 02:00:39,640 --> 02:00:41,600 OUR BEST TO WORK WITH YOU AND 3325 02:00:41,600 --> 02:00:44,680 POINT YOU IN THE RIGHT DIRECTION 3326 02:00:44,680 --> 02:00:47,520 ABOUT THE BEST POTENTIAL TO 3327 02:00:47,520 --> 02:00:48,040 SUPPORT THIS IDEA. 3328 02:00:48,040 --> 02:00:52,160 AND WITH THAT, I GUESS I WILL 3329 02:00:52,160 --> 02:00:52,760 TURN IT OVER TO CATHERINE AND 3330 02:00:52,760 --> 02:00:54,720 WRAP THINGS UP. 3331 02:00:54,720 --> 02:00:55,400 >>THANK YOU SO MUCH, CRAIG AND 3332 02:00:55,400 --> 02:00:57,680 PATRICK AND THEN A HUGE THANK 3333 02:00:57,680 --> 02:01:01,160 YOU TO OUR SPEAKERS DR. ROGER 3334 02:01:01,160 --> 02:01:01,720 LININGTON. 3335 02:01:01,720 --> 02:01:03,480 DR. MANDE HOLFORD. 3336 02:01:03,480 --> 02:01:10,560 >>DR.O KEEP, OUR NIH PARTNERS. 3337 02:01:10,560 --> 02:01:13,360 DR. MOHAPATRA AND OTHERS. 3338 02:01:13,360 --> 02:01:14,160 THOSE WERE FASCINATING TALKS AND 3339 02:01:14,160 --> 02:01:17,000 WONDERFUL TO HEAR FROM EVERYONE 3340 02:01:17,000 --> 02:01:17,200 TODAY. 3341 02:01:17,200 --> 02:01:17,800 THANK YOU TO OUR AUDIENCE FOR 3342 02:01:17,800 --> 02:01:19,680 JOINING US FOR ASKING YOUR 3343 02:01:19,680 --> 02:01:20,360 QUESTIONS AND IF TWEE DIDN'T GET 3344 02:01:20,360 --> 02:01:24,440 TO A QUESTION THAT YOU HAD 3345 02:01:24,440 --> 02:01:24,840 TODAY, DON'T WORRY. 3346 02:01:24,840 --> 02:01:25,920 WE WILL COLLECT ANY UNANSWERED 3347 02:01:25,920 --> 02:01:28,240 QUESTIONS AND SHARE THEM WITH 3348 02:01:28,240 --> 02:01:29,160 OUR PLANNING TEAM. 3349 02:01:29,160 --> 02:01:32,400 AND I ALSO WANT TO REMIND YOU 3350 02:01:32,400 --> 02:01:35,800 THAT THIS WAS RECORDED BY THE 3351 02:01:35,800 --> 02:01:36,720 NIH VIDEOCAST SERVICE TODAY AND 3352 02:01:36,720 --> 02:01:39,160 IT WILL BE ARCHIVED AND STORED 3353 02:01:39,160 --> 02:01:40,600 ON THE NIH VIDEOCAST WEBSITE FOR 3354 02:01:40,600 --> 02:01:42,400 FUTURE VIEWING. 3355 02:01:42,400 --> 02:01:45,240 SO CIRCLE IN THERE AND SEE THESE 3356 02:01:45,240 --> 02:01:47,440 FASCINATING TALKS AND HEAR THESE 3357 02:01:47,440 --> 02:01:49,000 PERSPECTIVES TO YOUR HEART'S 3358 02:01:49,000 --> 02:01:49,240 CONTENT. 3359 02:01:49,240 --> 02:01:53,400 WE HOPE YOU'LL JOIN US ON APRIL 3360 02:01:53,400 --> 02:01:55,040 28 FOR OUR SECOND WEBINAR IN 3361 02:01:55,040 --> 02:01:56,400 THIS SERIES. 3362 02:01:56,400 --> 02:02:00,320 AND WE'LL BE BACK WITH WITH OUR 3363 02:02:00,320 --> 02:02:00,520 TEAM. 3364 02:02:00,520 --> 02:02:02,600 SO AGAIN, A HUGE THANK YOU AND 3365 02:02:02,600 --> 02:02:08,040 I'M GOING CLOSE IT OUT NOW AND 3366 02:02:08,040 --> 02:02:08,560 EVERYBODY HAVE A WONDERFUL 3367 02:02:08,560 --> 02:02:08,800 EVENING. 3368 02:02:08,800 --> 02:02:09,040 BYE-BYE. 3369 02:02:09,040 --> 02:02:19,360 THANK YOU VERY MUCH.