1
00:00:04,905 --> 00:00:07,875
LET'S GET STARTED. I'M JUN

2
00:00:07,875 --> 00:00:10,310
HUH FROM THE EXPERIMENTAL

3
00:00:10,310 --> 00:00:12,379
IMMUNOLOGY BRANCH OF THE NCI. IT

4
00:00:12,379 --> 00:00:16,216
IS REALLY MY GREAT PLEASURE TO

5
00:00:16,216 --> 00:00:17,751
WELCOME TODAY'S SPEAKER JUN HUH

6
00:00:17,751 --> 00:00:20,487
FOR HARVARD MEDICAL SCHOOL AND

7
00:00:20,487 --> 00:00:22,789
JUN RECEIVED HIS UNDERGRADUATE

8
00:00:22,789 --> 00:00:25,959
AND MASTERS DEGREE FROM SOLE

9
00:00:25,959 --> 00:00:29,162
NATIONAL UNIVERSITY IN KOREA. IN

10
00:00:29,162 --> 00:00:33,333
MICROBIOLOGY. SEAOUL. AFTERWARDS

11
00:00:33,333 --> 00:00:35,102
HE DECIDED TO MOVE EAST,

12
00:00:35,102 --> 00:00:36,970
CROSSING THE PACIFIC OCEAN

13
00:00:36,970 --> 00:00:38,939
LANDING IN CALIFORNIA AND DID

14
00:00:38,939 --> 00:00:41,642
HIS Ph.D. INCAL TECH. STUDYING

15
00:00:41,642 --> 00:00:44,177
DROSOPHILA AND THEN DECIDED TO

16
00:00:44,177 --> 00:00:47,915
MOVE UP AND GO TO VERTEBRATE AND

17
00:00:47,915 --> 00:00:49,683
LUCKILY FOR US IMMUNOLOGIST HE

18
00:00:49,683 --> 00:00:53,287
DID POST-DOCTORAL WORK MOVING

19
00:00:53,287 --> 00:00:57,024
AGAIN EAST IN NEW YORK AND DAN

20
00:00:57,024 --> 00:00:58,492
(INAUDIBLE) LAB HE DID

21
00:00:58,492 --> 00:00:59,526
PHENOMENAL WORK ON

22
00:00:59,526 --> 00:01:00,761
INTERLEUKIN-17 PRODUCING CELLS

23
00:01:00,761 --> 00:01:04,164
OR TH 17 CELLS. AND LOOKING AT

24
00:01:04,164 --> 00:01:06,300
TRANSCRIPTION FACTOR GAMMA T AND

25
00:01:06,300 --> 00:01:09,903
HOW IT IS REGULATED BY SMALL

26
00:01:09,903 --> 00:01:14,975
MOLECULE LIKE DINGOXIN. THEN

27
00:01:14,975 --> 00:01:17,945
DECIDED TO MOVE FURTHER EAST TO

28
00:01:17,945 --> 00:01:20,681
U MASS WORCESTER WHERE HE BECAME

29
00:01:20,681 --> 00:01:22,549
ASSISTANT PROFESSOR AND THEN GOT

30
00:01:22,549 --> 00:01:25,419
A BREAK THROUGH IN IMMUNOLOGY

31
00:01:25,419 --> 00:01:27,521
AND NEURAL DEVELOPMENT, THEY

32
00:01:27,521 --> 00:01:30,090
FOUND MATURE IL 17 IS REGULATING

33
00:01:30,090 --> 00:01:31,758
AUTISM, NEURAL DEVELOPMENT IN

34
00:01:31,758 --> 00:01:33,627
MICE AND THEN FURTHER FOUND OUT

35
00:01:33,627 --> 00:01:37,097
THE MICROBIOME TO INFLUENCE SIP

36
00:01:37,097 --> 00:01:39,266
1. PHENOMENALLY SUCCESSFUL THEN

37
00:01:39,266 --> 00:01:42,269
DECIDED TO MOVE EVEN MORE EAST

38
00:01:42,269 --> 00:01:44,604
AND NORTH, ENDED UP IN HARVARD

39
00:01:44,604 --> 00:01:46,039
WHERE HE IS NOW ASSOCIATE

40
00:01:46,039 --> 00:01:49,176
PROFESSOR. AND I HOPE HE'S NOT

41
00:01:49,176 --> 00:01:50,610
MOVING FURTHER BECAUSE THE ONLY

42
00:01:50,610 --> 00:01:55,115
OTHER PLACE TO GO IS NOVA

43
00:01:55,115 --> 00:01:58,185
SCONOVASCOTIA. SCIENTIFICALLY JS

44
00:01:58,185 --> 00:02:01,788
JUST PHENOMENAL. HE IS A

45
00:02:01,788 --> 00:02:03,090
FIELDIST AND PIONEERING AND

46
00:02:03,090 --> 00:02:05,726
TRAIL BLAZING PERSON. HE'S ALSO

47
00:02:05,726 --> 00:02:07,761
VERY SWEET AND NICE GUY AND I

48
00:02:07,761 --> 00:02:09,997
LOVE TO LISTEN TO HIS TALK. I

49
00:02:09,997 --> 00:02:11,598
LISTEN HIM LIKE A FEW TIMES AND

50
00:02:11,598 --> 00:02:13,400
ALWAYS AMAZED HOW HE DEVELOPED

51
00:02:13,400 --> 00:02:14,768
HIS STORY AND I HOPE YOU WILL

52
00:02:14,768 --> 00:02:17,004
ENJOY IT AS MUCH AS I DO. AND

53
00:02:17,004 --> 00:02:19,339
WITHOUT FURTHER ADIEU, WELCOME,

54
00:02:19,339 --> 00:02:26,413
JUN, TO THE NIH.

55
00:02:26,413 --> 00:02:29,483
>> THANK YOU VERY MUCH FOR
THE

56
00:02:29,483 --> 00:02:35,088
KIND INTRODUCTION. I THINK I

57
00:02:35,088 --> 00:02:36,757
WILL MOVE EAST. THIS IS MY FIRST

58
00:02:36,757 --> 00:02:42,529
TIME TO THE SEMINAR AT NIH SO I

59
00:02:42,529 --> 00:02:45,198
THOUGHT BRIEFLY WHAT WE DO IN MY

60
00:02:45,198 --> 00:02:47,534
LAB AND THEN INITIALLY TELL YOU

61
00:02:47,534 --> 00:02:49,970
ABOUT PUBLISHED WORK SHOWING THE

62
00:02:49,970 --> 00:02:54,174
ROLE OF MICROMETABOLITE OF

63
00:02:54,174 --> 00:02:55,409
BIOLIPID, THIS IS ALL PUBLISHED

64
00:02:55,409 --> 00:02:58,345
SO GIVE YOU A SUMMARY THEN MOVE

65
00:02:58,345 --> 00:03:04,184
TO THE STORY TH 17 IN REGULATING

66
00:03:04,184 --> 00:03:05,886
NEURAL ACTIVITY. I WANT SHARE

67
00:03:05,886 --> 00:03:07,287
WITH YOU UNPUBLISHED WORK AS

68
00:03:07,287 --> 00:03:12,359
WELL. SO MANY OF YOU KNOW THIS

69
00:03:12,359 --> 00:03:17,297
IS A GRAPH BUT GRAPH ON YOUR

70
00:03:17,297 --> 00:03:20,167
RIGHT, COVID IS THE FIRST STORY

71
00:03:20,167 --> 00:03:25,238
BUT AS SOCIETY WE HAVEN'T DONE

72
00:03:25,238 --> 00:03:28,542
GOOD JOB, THE RATE HAVE BEEN

73
00:03:28,542 --> 00:03:32,813
OVER THE YEARS. LOOK AT GRAPH ON

74
00:03:32,813 --> 00:03:36,483
YOUR RIGHT, THOSE ARE VERY

75
00:03:36,483 --> 00:03:38,618
DIFFERENT IMAGE, THE PREVALENCE

76
00:03:38,618 --> 00:03:41,922
RATE OF MANY IMMUNE RELATED

77
00:03:41,922 --> 00:03:44,257
DISORDER AND FOR SOME REASON

78
00:03:44,257 --> 00:03:47,127
NOBODY KNOW FOR SURE IT HAS BEEN

79
00:03:47,127 --> 00:03:49,162
STUDIED ON THE STEADY RISE. I

80
00:03:49,162 --> 00:03:51,731
WANT TO SHOW YOU ANOTHER GRAPH

81
00:03:51,731 --> 00:03:53,700
WHICH IS PREVALENCE RATE OF

82
00:03:53,700 --> 00:03:55,068
NEUROLOGICAL DISORDERS SUCH AS

83
00:03:55,068 --> 00:03:57,170
AUTISM AND HERE YOU SEE DIRECTLY

84
00:03:57,170 --> 00:04:02,242
THE STEADY INCREASE OVER THE

85
00:04:02,242 --> 00:04:03,043
TRAINING YEAROR YEARS AND

86
00:04:03,043 --> 00:04:05,412
ACCORDING TO RECENT DATA CDC ONE

87
00:04:05,412 --> 00:04:07,214
OUT OF 36 CHILDREN BORN IN THE

88
00:04:07,214 --> 00:04:09,249
STATES ARE DIAGNOSED WITH AUTISM

89
00:04:09,249 --> 00:04:12,619
SPECTRUM DISORDER. SO

90
00:04:12,619 --> 00:04:14,754
ESSENTIALLY 30% OF CHILDREN TEND

91
00:04:14,754 --> 00:04:16,690
TO BE ON THIS SPECTRUM. WE CAN

92
00:04:16,690 --> 00:04:20,560
SPEND HOURS DISCUSSING ONE MAY

93
00:04:20,560 --> 00:04:22,028
UNDERLIE SUCH STEADY INCREASE

94
00:04:22,028 --> 00:04:25,398
BUT ONE THING THAT IS ABUNDANTLY

95
00:04:25,398 --> 00:04:31,905
CLEAR TO ME GENETIC MUTATION MAY

96
00:04:31,905 --> 00:04:34,141
NOT EXPLAIN ALONE, DIFFICULT TO

97
00:04:34,141 --> 00:04:36,443
IMAGINE MORE GENETIC MUTATION

98
00:04:36,443 --> 00:04:43,350
OVER PAST 20 YEARS YEARS. IMPORT

99
00:04:43,350 --> 00:04:44,451
ROLE OF THE ENVIRONMENTAL

100
00:04:44,451 --> 00:04:47,320
FACTORS NON-GENETIC FACTORS BUT

101
00:04:47,320 --> 00:04:50,690
WHAT THOSE FACTORS ARE ANOTHER

102
00:04:50,690 --> 00:04:52,492
TOPIC FOR DISCUSSION. BUT YOU

103
00:04:52,492 --> 00:04:55,262
MIGHT HAVE -- WE ARE FOCUSING ON

104
00:04:55,262 --> 00:04:58,131
PERHAPS IN MY MIND TWO MOST

105
00:04:58,131 --> 00:05:00,567
IMPORTANT NON-GENETIC FACTORS

106
00:05:00,567 --> 00:05:02,602
THAT CAN INFLUENCE HUMAN HEALTH.

107
00:05:02,602 --> 00:05:08,642
ONE IS MICROBIOME. AND WHAT

108
00:05:08,642 --> 00:05:13,680
HAPPENED DURING PREGNANCY. THIS

109
00:05:13,680 --> 00:05:16,049
IS A FACTOR THAT INFLUENCE FETUS

110
00:05:16,049 --> 00:05:18,285
AND CAN HAVE LONG TERM EFFECT IN

111
00:05:18,285 --> 00:05:22,822
OUR HEALTH. OVER THE YEARS MOST

112
00:05:22,822 --> 00:05:26,726
FOCUSING ON TWO FACTOR TRYING TO

113
00:05:26,726 --> 00:05:30,597
UNDERSTAND HOW THAT CAN

114
00:05:30,597 --> 00:05:32,299
INFLUENCE ANIMAL HEALTH MOSTLY

115
00:05:32,299 --> 00:05:34,734
MOUSE HEALTH. WE WILL BE FOCUS

116
00:05:34,734 --> 00:05:36,102
ON THE ROLE HAVING A SYSTEM IN

117
00:05:36,102 --> 00:05:39,239
THE MIDDLE. THIS IS THE SYSTEM

118
00:05:39,239 --> 00:05:42,576
IN INTERMEDIATE SIGNAL FROM THE

119
00:05:42,576 --> 00:05:43,310
MICROBIOME, REMEMBER WHAT

120
00:05:43,310 --> 00:05:45,245
HAPPENED IN PREGNANCY AND THOSE

121
00:05:45,245 --> 00:05:48,248
IMMUNE CELLS THAT INFLUENCE GUT

122
00:05:48,248 --> 00:05:49,115
HEALTH, ALSO IN A BRAIN

123
00:05:49,115 --> 00:05:51,318
FUNCTION. SO THAT'S WHAT TRUE

124
00:05:51,318 --> 00:05:54,888
ORGAN THAT MY LAB AND MOSTLY

125
00:05:54,888 --> 00:06:05,398
FOCUS ON. IN TERM OF CYTOKINE,

126
00:06:10,870 --> 00:06:13,206
IL 17, I DON'T NEED TO GIVE THE

127
00:06:13,206 --> 00:06:15,542
AUDIENCE INTERLEUKIN-17 IS

128
00:06:15,542 --> 00:06:16,610
HISTOROCK ILY KNOWN TO HAVE

129
00:06:16,610 --> 00:06:18,645
IMMUNE RELATED PROTECTING US

130
00:06:18,645 --> 00:06:20,580
FROM INVADING PATHOGENESIS,

131
00:06:20,580 --> 00:06:24,551
EXTRA CELL BACTERIA AND FUNGAL

132
00:06:24,551 --> 00:06:26,920
INFECTION BUT IL 17 IS SHOWN TO

133
00:06:26,920 --> 00:06:29,022
CONTRIBUTE TO DIFFERENT

134
00:06:29,022 --> 00:06:30,724
AUTOIMMUNE INFLAMMATORY DISORDER

135
00:06:30,724 --> 00:06:33,293
AND OUR WORK ALSO WORK FROM

136
00:06:33,293 --> 00:06:37,597
(INAUDIBLE) LAB SHOW THAT

137
00:06:37,597 --> 00:06:39,266
INTERLEUKIN 17 SHOW IMPACT ON

138
00:06:39,266 --> 00:06:40,400
NEURAL DEVELOPMENT AND FUNCTION

139
00:06:40,400 --> 00:06:42,235
AND NEURONAL REGENERATION OF

140
00:06:42,235 --> 00:06:48,842
INJURY. IMMUNE FUNCTION CAN BE

141
00:06:48,842 --> 00:06:54,447
INDUCED BY IL 17 AND PREVIOUSLY

142
00:06:54,447 --> 00:06:58,151
SHOWN, I WAS ABLE TO IDENTIFY

143
00:06:58,151 --> 00:06:59,619
MOLECULE WITH HORMONAL

144
00:06:59,619 --> 00:07:03,156
DIFFERENTIATION OF THE MOLECULE

145
00:07:03,156 --> 00:07:06,226
BUT BE SURE BY TRANSCRIPTION

146
00:07:06,226 --> 00:07:08,228
FACTOR RECEPTOR THAT SIT IN THE

147
00:07:08,228 --> 00:07:10,096
CONSERVATIVE'S SEAT AND CONTROL

148
00:07:10,096 --> 00:07:13,300
TH 17 PROGRAM AND ALSO SHOW

149
00:07:13,300 --> 00:07:14,234
(INAUDIBLE) CAN IMMUNOSUPPRESS

150
00:07:14,234 --> 00:07:17,037
THE FUNCTION OF GAMMA T AND TH

151
00:07:17,037 --> 00:07:20,640
17 CELLS. SO WE CAME IN

152
00:07:20,640 --> 00:07:22,976
WONDERING WHETHER THERE'S

153
00:07:22,976 --> 00:07:25,745
NATURAL LIGAND OR INHIBITOR OF

154
00:07:25,745 --> 00:07:28,515
TH 17 CELL THAT MAY ALSO BIND TO

155
00:07:28,515 --> 00:07:32,419
GAMMA T AND ALSO SUPPRESS

156
00:07:32,419 --> 00:07:34,421
SUPPRESS GAMMA CELL. WE

157
00:07:34,421 --> 00:07:36,022
HYPOTHESIZE WITH WACK TIERIA

158
00:07:36,022 --> 00:07:37,490
GAVE THE ABILITY TO CONTROL

159
00:07:37,490 --> 00:07:40,360
DEVELOPMENT OF FUNCTIONAL TH 17

160
00:07:40,360 --> 00:07:42,796
CELL BY PRODUCING SUCH A SMALL

161
00:07:42,796 --> 00:07:46,366
MOLECULE THAT CAN BIND TO GAMMA

162
00:07:46,366 --> 00:07:49,703
T. TO MAKE LONG STORY SHORT

163
00:07:49,703 --> 00:07:53,606
IDENTIFY METABOLITE WITH

164
00:07:53,606 --> 00:07:55,942
MODULATORY ACTIVITY WE DECIDE TO

165
00:07:55,942 --> 00:07:58,311
FOCUS ON BIOACIDACID.  THE REASE

166
00:07:58,311 --> 00:08:00,647
FOCUS ON BIOACID IS AT THE TIME

167
00:08:00,647 --> 00:08:02,682
OTHER KNOWN GAMMA LIGAND WITH

168
00:08:02,682 --> 00:08:08,221
AGONISTIC OR ANTAGONISTIC

169
00:08:08,221 --> 00:08:10,690
ACTIVITY (INDISCERNIBLE) CORE

170
00:08:10,690 --> 00:08:12,359
CHOLESTEROL DERIVATIVE AND SOME

171
00:08:12,359 --> 00:08:14,894
OF YOU MAY KNOW DERIVED FROM

172
00:08:14,894 --> 00:08:17,797
CHOLESTEROL AND TONS OF VIRUSES

173
00:08:17,797 --> 00:08:20,133
ARE ABLE TO SEE IN OUR SYSTEM

174
00:08:20,133 --> 00:08:24,170
AND THE BIAS ARE SUBJECT TO THE

175
00:08:24,170 --> 00:08:30,176
MODIFICATION OF WHETHER THEY

176
00:08:30,176 --> 00:08:32,178
HAVE ABILITY TO CONTROL TH 17

177
00:08:32,178 --> 00:08:33,079
FUNCTION.  THIS IS PUBLISHED

178
00:08:33,079 --> 00:08:34,981
WORK. SO I'M GOING TO GIVE YOU

179
00:08:34,981 --> 00:08:38,318
HIGHLIGHT OF THE STORY. WE

180
00:08:38,318 --> 00:08:41,254
WANTED TO KNOW IN VITRO SCREEN

181
00:08:41,254 --> 00:08:43,990
USING PRIMARY T-CELL CULTURE

182
00:08:43,990 --> 00:08:45,892
READ OUT WE USE A TH 17

183
00:08:45,892 --> 00:08:52,899
REGULATORY T-CELL, IDENTIFY TRUE

184
00:08:52,899 --> 00:08:56,169
BIAS, ACID DERIVATIVE, TH 17

185
00:08:56,169 --> 00:08:59,539
CELLS INHIBITED TH 17 CELL AND

186
00:08:59,539 --> 00:09:02,709
ENHANCE REGULATORY T-CELL IN

187
00:09:02,709 --> 00:09:06,513
VITRO. SO WHEN WE FIRST IDENTIFY

188
00:09:06,513 --> 00:09:11,718
THE SCA WE CONFIRM BIND TO HUMAN

189
00:09:11,718 --> 00:09:16,389
OLIGOBACTERIA IN VITRO WITH A

190
00:09:16,389 --> 00:09:20,226
MICROMOLAR. AND SUPPRESS

191
00:09:20,226 --> 00:09:23,763
TRANSCRIPTION ACTIVITY BECAUSE

192
00:09:23,763 --> 00:09:25,832
WHEN WE USE (INAUDIBLE)

193
00:09:25,832 --> 00:09:26,533
COEFFICIENT ACTIVITY AND

194
00:09:26,533 --> 00:09:29,436
MOREOVER IT IS SUPPRESS TH 17

195
00:09:29,436 --> 00:09:31,805
CELL DIFFERENTIATION WHEN WE ADD

196
00:09:31,805 --> 00:09:35,241
INTO THE IN VITRO CULTURE.

197
00:09:35,241 --> 00:09:40,280
RELATED TO THE CELLS ACID IN

198
00:09:40,280 --> 00:09:44,317
SUCH A PHENOTYPE IN VIVO WHEN WE

199
00:09:44,317 --> 00:09:47,220
ADMINISTER THE SINGLE MOUSE WITH

200
00:09:47,220 --> 00:09:49,422
(INAUDIBLE) WE ARE ABLE TO

201
00:09:49,422 --> 00:09:52,792
DETECT THIS, WE DO TH 17

202
00:09:52,792 --> 00:09:54,861
CHILDRENIATION, THIS IS A

203
00:09:54,861 --> 00:09:57,197
BACTERIA DEPENDENT TH 17

204
00:09:57,197 --> 00:09:59,265
DIFFERENTIATION MODEL. HOWEVER

205
00:09:59,265 --> 00:10:01,067
THE SAME (INAUDIBLE) REGULATORY

206
00:10:01,067 --> 00:10:04,170
T-CELL PERCENTAGE. THEN THIS IS

207
00:10:04,170 --> 00:10:05,405
THE FUN OF SCIENCE IN WAY WE

208
00:10:05,405 --> 00:10:07,841
WANT TO IDENTIFY BACTERIA OR

209
00:10:07,841 --> 00:10:10,176
BACTERIA ENZYME THAT PRODUCE TH

210
00:10:10,176 --> 00:10:12,545
17 MODULATORY BIOACID, WE

211
00:10:12,545 --> 00:10:16,549
COLLABORATED WITH OUR COLLEAGUE

212
00:10:16,549 --> 00:10:20,353
AT HMS AND BASICALLY SCREEN

213
00:10:20,353 --> 00:10:24,257
THOUSANDS OF HUMAN BACTERIA

214
00:10:24,257 --> 00:10:27,393
INDIVIDUALLY USING LCMS. AND

215
00:10:27,393 --> 00:10:31,030
BASED ON EACH WE INCLUDED THE

216
00:10:31,030 --> 00:10:34,033
INOCULATE ONE BACTERIA AND IN

217
00:10:34,033 --> 00:10:36,536
PREVIOUS AMINO ACID AS PRECURSOR

218
00:10:36,536 --> 00:10:38,972
MOLECULE AND THEN WE ARE ABLE TO

219
00:10:38,972 --> 00:10:43,710
IDENTIFY BACTERIA STRAIN THAT

220
00:10:43,710 --> 00:10:46,946
CONVERT ACETYLCHOLINE ACID. THIS

221
00:10:46,946 --> 00:10:50,383
IS THE TRUE FORCE SPEARHEADED BY

222
00:10:50,383 --> 00:10:51,751
(INDISCERNIBLE) FORMER POST DOC,

223
00:10:51,751 --> 00:10:55,522
WE ARE ABLE TO SUCCESSFULLY

224
00:10:55,522 --> 00:10:56,956
IDENTIFY BACTERIA AND BACTERIA

225
00:10:56,956 --> 00:11:00,093
ENZYME THAT CAN GENERATE THIS TH

226
00:11:00,093 --> 00:11:03,229
77 MODULATORY OR INHIBITOR

227
00:11:03,229 --> 00:11:06,032
BIOACID IN VITRO AND IN VIVO. IN

228
00:11:06,032 --> 00:11:08,902
TERMS OF HUMAN RELEVANCE WE

229
00:11:08,902 --> 00:11:10,803
COLLABORATED WITH (INAUDIBLE) IN

230
00:11:10,803 --> 00:11:18,478
OUR LAB, WE LOOK AT THE CELL TH

231
00:11:18,478 --> 00:11:21,514
INHIBITOR ASSAY, IN PATIENT WITH

232
00:11:21,514 --> 00:11:22,549
IGG PATIENT VERSUS HEALTHY

233
00:11:22,549 --> 00:11:24,517
CONTROL AND WE FOUND THIS IDD

234
00:11:24,517 --> 00:11:29,622
PATIENT WITH IDD THEY HAVE

235
00:11:29,622 --> 00:11:32,258
DEVELOP BACTERIA IN THEIR SYSTEM

236
00:11:32,258 --> 00:11:36,129
CONTROL, THIS IS CORRELATION BUT

237
00:11:36,129 --> 00:11:38,498
THAT DATA IS POSITIONED WITH OUR

238
00:11:38,498 --> 00:11:43,436
HYPOTHESIS, BACTERIAL IN TH

239
00:11:43,436 --> 00:11:45,638
FUNCTION AND PARTICIPATION, THEY

240
00:11:45,638 --> 00:11:47,307
MAY BE EXPOSED TO INFLAMMATION

241
00:11:47,307 --> 00:11:49,075
BECAUSE THEY DON'T HAVE AS MUCH

242
00:11:49,075 --> 00:11:51,511
MATERIAL CELLS IN THEIR SYSTEM. 

243
00:11:51,511 --> 00:11:53,212
AND MOREOVER WHEN WE LOOK AT

244
00:11:53,212 --> 00:11:57,684
GENE EXPRESSION CHANGES WE FOUND

245
00:11:57,684 --> 00:11:59,652
IN CORRELATION BETWEEN LEVEL OF

246
00:11:59,652 --> 00:12:02,522
HCA AND EXPRESSION OF TH 17 SUCH

247
00:12:02,522 --> 00:12:06,059
AS IL 17 SO SUGGESTING EVEN IN

248
00:12:06,059 --> 00:12:08,861
HUMAN THE LEVEL OF MATERIAL

249
00:12:08,861 --> 00:12:13,166
CELLS MAY BE CORRELATED WITH TH

250
00:12:13,166 --> 00:12:15,101
17 PROGRAM. SO FROM ALL THIS

251
00:12:15,101 --> 00:12:17,270
DATA WE ARE ABLE TO FIND

252
00:12:17,270 --> 00:12:18,838
PARTICULAR BIAS AND PARTICULAR

253
00:12:18,838 --> 00:12:21,574
TYPES OF BACTERIA IN THE GUT,

254
00:12:21,574 --> 00:12:24,177
THEY CAN CONVERT THIS BACTERIA

255
00:12:24,177 --> 00:12:27,680
CAN CONVERT THE INKNOCK LOUSE

256
00:12:27,680 --> 00:12:30,817
BIAS SUCH AS ACETYLCHOLINE ASHED

257
00:12:30,817 --> 00:12:33,386
AND T-CELL INTO TH 17 OR T

258
00:12:33,386 --> 00:12:36,823
MODULATORY BIOASSAY AND THIS

259
00:12:36,823 --> 00:12:40,760
BACTERIA GENERATED SMALL

260
00:12:40,760 --> 00:12:43,796
MOLECULE BIOACID CUP INFLUENCE

261
00:12:43,796 --> 00:12:46,132
SYSTEM BY DIRECTLY INTERACTING

262
00:12:46,132 --> 00:12:47,567
WITH IN THIS CASE IN VITRO HOST

263
00:12:47,567 --> 00:12:49,469
TRANSCRIPTION FACTOR AND IN

264
00:12:49,469 --> 00:12:51,804
DOING SO MAY IMMUNOSUPPRESS

265
00:12:51,804 --> 00:12:53,606
INFLAMMATION. LIKEWISE,

266
00:12:53,606 --> 00:12:55,174
DIFFERENT TYPES OF BIAS, I

267
00:12:55,174 --> 00:12:56,843
DIDN'T HAVE TIME TO TALK ABOUT

268
00:12:56,843 --> 00:12:59,746
THIS BUT ANOTHER BIAS REGULATORY

269
00:12:59,746 --> 00:13:03,850
T-CELL DIFFERENTIATION MOSTLY IN

270
00:13:03,850 --> 00:13:08,054
VIVO, IN THIS CASE RECEPTOR, WE

271
00:13:08,054 --> 00:13:11,557
DO NOT CARE ABOUT -- THIS BIAS

272
00:13:11,557 --> 00:13:13,259
WITHIN (INAUDIBLE) BUT SHOWING

273
00:13:13,259 --> 00:13:19,766
AN EXAMPLE OF HOW BACTERIA

274
00:13:19,766 --> 00:13:22,001
UTILIZE THE HOST BACTERIA

275
00:13:22,001 --> 00:13:23,436
MODIFYING THEM AND CONTROLLING

276
00:13:23,436 --> 00:13:29,809
IMMUNE RESPONSES. AROUND THE

277
00:13:29,809 --> 00:13:30,877
SAME TIME (INDISCERNIBLE) IN

278
00:13:30,877 --> 00:13:35,915
JAPAN, THEY COMPARED BIAS IN THE

279
00:13:35,915 --> 00:13:39,919
CENTRAL AREA, PEOPLE WHO LIVE

280
00:13:39,919 --> 00:13:41,788
OVER 100 YEARS OLD VERSUS

281
00:13:41,788 --> 00:13:45,725
HEALTHY 80 YEARS OLD PEOPLE AND

282
00:13:45,725 --> 00:13:47,326
FOUND WHY (INAUDIBLE) IS

283
00:13:47,326 --> 00:13:49,162
COMPARABLE THEY FOUND OLDER

284
00:13:49,162 --> 00:13:52,298
IMMUNE MODULATORY BIAS WE

285
00:13:52,298 --> 00:13:56,269
IDENTIFY IN THE SENNARYIANS HAVE

286
00:13:56,269 --> 00:13:59,072
HIGHER IMMUNOMODULATORY BIAS

287
00:13:59,072 --> 00:14:00,873
THEIR GUT. THIS DATA DOESN'T

288
00:14:00,873 --> 00:14:02,775
MEAN THIS BILE ACID CAN MAKE

289
00:14:02,775 --> 00:14:04,677
THESE PEOPLE LIVE LONGER BUT

290
00:14:04,677 --> 00:14:06,646
AGAIN, PERHAPS THERE'S SOME

291
00:14:06,646 --> 00:14:07,580
CONNECTION CONTRIBUTION OF THIS

292
00:14:07,580 --> 00:14:10,383
IMMUNE MODULATORY BIAS AND THEIR

293
00:14:10,383 --> 00:14:12,285
HEALTH. JUST GOING TO GIVE YOU A

294
00:14:12,285 --> 00:14:13,219
BRIEF OVERVIEW OF THE TYPE OF

295
00:14:13,219 --> 00:14:15,088
WORK WE ARE DOING IN KIND OF

296
00:14:15,088 --> 00:14:17,557
STUDYING THE RELATIVE

297
00:14:17,557 --> 00:14:18,791
INTERESTING BETWEEN GUT BACTERIA

298
00:14:18,791 --> 00:14:20,493
AND IMMUNE CELL IN THE PERIPHERY

299
00:14:20,493 --> 00:14:21,961
AND THE CONTEXT OF GUT

300
00:14:21,961 --> 00:14:24,097
INFLAMMATION. NOW I WANT TO

301
00:14:24,097 --> 00:14:27,967
CHANGE GEAR AND TELL YOU

302
00:14:27,967 --> 00:14:30,503
DIFFERENT STORY, BETWEEN IMMUNE

303
00:14:30,503 --> 00:14:32,371
CELLS AND THE BRAIN. THE CELLS

304
00:14:32,371 --> 00:14:34,741
IN THE BRAIN. FOR THIS WORK WE

305
00:14:34,741 --> 00:14:37,243
DID COLLABORATE WITH GLORIA

306
00:14:37,243 --> 00:14:45,218
NEUROSCIENTIST AT MIT. AND WE

307
00:14:45,218 --> 00:14:46,986
DID HERE SO IF YOU HAVE A

308
00:14:46,986 --> 00:14:48,387
DIFFICULT QUESTION JUST WAIT AND

309
00:14:48,387 --> 00:14:53,526
ASK HER THOSE QUESTIONS, OKAY? I

310
00:14:53,526 --> 00:14:56,763
WANT TO ALSO BEFORE I GET INTO

311
00:14:56,763 --> 00:14:58,231
THIS, CANCER IMMUNOTHERAPY THIS

312
00:14:58,231 --> 00:15:01,367
IS ONE FINDING THAT REALLY

313
00:15:01,367 --> 00:15:03,903
CHANGED THE FIELD THE WAY WE

314
00:15:03,903 --> 00:15:06,706
TREAT CANCER PATIENTS. AND THEN

315
00:15:06,706 --> 00:15:08,841
BASICALLY THIS IS A WAY TO THIS

316
00:15:08,841 --> 00:15:11,110
IS HARNESSING OUR OWN IMMUNE

317
00:15:11,110 --> 00:15:13,045
SYSTEM AND IN DOING SO PEOPLE

318
00:15:13,045 --> 00:15:16,916
ARE ABLE TO RESTORE RE-ESTABLISH

319
00:15:16,916 --> 00:15:18,885
BALANCE, MAINTAIN THIS BALANCE.

320
00:15:18,885 --> 00:15:21,154
SO THE REASON WHY I MENTION THIS

321
00:15:21,154 --> 00:15:23,289
IS BECAUSE MY DREAM IS THAT

322
00:15:23,289 --> 00:15:25,591
PERHAPS SOME DAY WE MAYBE ABLE

323
00:15:25,591 --> 00:15:30,163
TO UTILIZE A SIMILAR APPROACH

324
00:15:30,163 --> 00:15:31,798
BECAUSE THE SYSTEM SYSTEM

325
00:15:31,798 --> 00:15:35,168
BASICALLY BALANCED, WHEN THINGS

326
00:15:35,168 --> 00:15:37,937
GO AWRY THEY CAN GET DEPLOYED TO

327
00:15:37,937 --> 00:15:41,641
DIFFERENT TISSUE. AND RESTORE

328
00:15:41,641 --> 00:15:42,875
HOMEOPATHIC BALANCE, THAT IS HOW

329
00:15:42,875 --> 00:15:44,977
WE ARE DOING IN THE SYSTEM TO

330
00:15:44,977 --> 00:15:47,980
SOME DAY IN THE FUTURE I HOPE

331
00:15:47,980 --> 00:15:52,618
THAT WE MAY BE ABLE TO SEE NOVEL

332
00:15:52,618 --> 00:15:55,221
IMMUNOTHERAPY THAT CAN BE USED

333
00:15:55,221 --> 00:15:59,292
TO TREAT AND TRAIN DISORDER,

334
00:15:59,292 --> 00:16:01,327
THAT'S WHEY I INCLUDE THAT. LIKE

335
00:16:01,327 --> 00:16:04,230
MANY OTHER GOOD IDEAS, YOU ARE

336
00:16:04,230 --> 00:16:05,898
NOT FIRST ONE TO THINK ABOUT SO

337
00:16:05,898 --> 00:16:07,500
THIS IS IMMUNOTHERAPY FOR

338
00:16:07,500 --> 00:16:08,734
NEUROLOGICAL DISORDERS. IT HAS

339
00:16:08,734 --> 00:16:12,805
BEEN USED BEFORE. SO SOMETIME

340
00:16:12,805 --> 00:16:15,575
AGO PEOPLE WANTED TO TRANSFER

341
00:16:15,575 --> 00:16:17,410
THIS AWESOME POWER OF

342
00:16:17,410 --> 00:16:19,345
INFLAMMATION AND THEY WANT TO --

343
00:16:19,345 --> 00:16:22,014
BY TRANSFERRING THIS

344
00:16:22,014 --> 00:16:25,284
INFLAMMATION THEY WANT TO TREAT

345
00:16:25,284 --> 00:16:28,888
PSYCHIATRIC PATIENTS AND

346
00:16:28,888 --> 00:16:30,556
POTENTIALLY DRAWING PLOT IN A

347
00:16:30,556 --> 00:16:32,391
PATIENT THAT INFECTD WITH

348
00:16:32,391 --> 00:16:35,394
MALARIA AND BY TRANSFERRING THAT

349
00:16:35,394 --> 00:16:37,296
BLOOD INTO (INAUDIBLE) PATIENT

350
00:16:37,296 --> 00:16:41,500
THEY WANTED TO CURE THAT

351
00:16:41,500 --> 00:16:47,139
SYMPTOM. APPARENTLY THIS

352
00:16:47,139 --> 00:16:50,509
APPROACH WE EASILY TEND TO

353
00:16:50,509 --> 00:16:53,846
IMAGINE GOOD PRESENCE OF

354
00:16:53,846 --> 00:16:57,283
PATIENTS IN THIS NEW -- THE

355
00:16:57,283 --> 00:16:59,285
ARTIFACT, IMMUNE ACTIVATION.

356
00:16:59,285 --> 00:17:00,453
ALTERNATIVELY THIS APPROACH MUST

357
00:17:00,453 --> 00:17:02,855
HAVE BEEN SUCCESSFUL TO SOME

358
00:17:02,855 --> 00:17:07,627
DEGREE BECAUSE THE HISTORY 1927

359
00:17:07,627 --> 00:17:09,695
NOBEL PRIZE WAS GIVEN FOR

360
00:17:09,695 --> 00:17:11,464
THERAPY OF MALARIA INOCULATION

361
00:17:11,464 --> 00:17:13,566
IN TREATING CERTAIN FORM OF

362
00:17:13,566 --> 00:17:16,035
DEMENTIA. SO THIS IMMUNE --

363
00:17:16,035 --> 00:17:20,172
NEURAL IMAGING, IS NOTHING NE N.

364
00:17:20,172 --> 00:17:24,844
THE FAST FORWARD IF YOU LOOK AT

365
00:17:24,844 --> 00:17:27,380
THIS PHENOMENON, I BRIEFLY

366
00:17:27,380 --> 00:17:28,748
INTRODUCED INCREASING RATE

367
00:17:28,748 --> 00:17:32,285
PREVALENCE RATE OF AUTISM BUT

368
00:17:32,285 --> 00:17:34,520
AMONG THIS PARAMOUNT (INAUDIBLE)

369
00:17:34,520 --> 00:17:36,556
CHILDREN THEY NOTED THAT WHEN

370
00:17:36,556 --> 00:17:37,924
THEY ARE CHILDREN WERE EXPOSED

371
00:17:37,924 --> 00:17:43,229
TO INFLAMMATION CERTAIN

372
00:17:43,229 --> 00:17:45,264
PERCENTAGE OF CHILDREN WITH

373
00:17:45,264 --> 00:17:46,966
AUTISM THEIR SYMPTOM, TALKING

374
00:17:46,966 --> 00:17:49,402
ABOUT THEIR CORE SYMPTOM, WHICH

375
00:17:49,402 --> 00:17:54,407
IS ASSOCIATED WITH (INAUDIBLE)

376
00:17:54,407 --> 00:17:55,775
BEHAVIOR THEIR (INAUDIBLE)

377
00:17:55,775 --> 00:17:58,244
IMPROVED. THIS IS IS SO CALLED

378
00:17:58,244 --> 00:18:01,547
FEVER EFFECT. SO FEVER EFFECT

379
00:18:01,547 --> 00:18:04,817
WHEN CHILDREN HAVE A FEVER THEIR

380
00:18:04,817 --> 00:18:06,185
SYMPTOM GET (INDISCERNIBLE)

381
00:18:06,185 --> 00:18:08,421
DRAMATICALLY IMPROVE. THIS IS AN

382
00:18:08,421 --> 00:18:10,222
ARTICLE I BROUGHT HERE AND MORE

383
00:18:10,222 --> 00:18:13,392
RECENT STUDY THEY LOOK AT MORE

384
00:18:13,392 --> 00:18:14,760
THAN 200 CHILDREN WITH AUTISM

385
00:18:14,760 --> 00:18:18,698
AND ACCORDING TO THIS STUDY 17%

386
00:18:18,698 --> 00:18:22,335
OF THESE CHILDREN THEY SHOW

387
00:18:22,335 --> 00:18:24,670
PEOPLE VISITATION OF AUTISM

388
00:18:24,670 --> 00:18:27,139
RELATED SYMPTOM. THEY SAY

389
00:18:27,139 --> 00:18:29,141
INTERESTING AND WEIRD. AUTISM IS

390
00:18:29,141 --> 00:18:32,778
LIKE A NEURAL DEVELOPMENT

391
00:18:32,778 --> 00:18:35,014
DISORDER BUT CORE SYMPTOM

392
00:18:35,014 --> 00:18:37,249
IMPROVED WHEN THEY IMPROVED

393
00:18:37,249 --> 00:18:38,584
INFLAMMATION. SO BASED ON THIS

394
00:18:38,584 --> 00:18:42,021
STUDY, ANOTHER STUDY ARTICLE

395
00:18:42,021 --> 00:18:43,589
SHOWING PEOPLE WITH BEHAVIOR

396
00:18:43,589 --> 00:18:45,858
PROBLEM IN SOME CHILDREN WITH

397
00:18:45,858 --> 00:18:47,660
AUTISM, AND SOME VARIATION STUDY

398
00:18:47,660 --> 00:18:51,063
TO STUDY VARIATION. I THINK

399
00:18:51,063 --> 00:18:52,398
SOMEWHERE BETWEEN 70% OF

400
00:18:52,398 --> 00:18:57,370
CHILDREN WITH AUTISM SHOW FEVER

401
00:18:57,370 --> 00:19:00,139
MITIGATION. ANOTHER STUDY WITH

402
00:19:00,139 --> 00:19:02,708
6% OF CHILDREN, I THINK

403
00:19:02,708 --> 00:19:10,649
SOMEWHERE BETWEEN LIKE 6 TO 17%,

404
00:19:10,649 --> 00:19:12,318
NOBODY KNOW FOR SURE THE FACTOR

405
00:19:12,318 --> 00:19:14,253
IN THE PHENOTYPE, MY LAB WE ARE

406
00:19:14,253 --> 00:19:16,989
TRYING TO INITIATE HUMAN STUDY.

407
00:19:16,989 --> 00:19:22,561
WE ARE COLLABORATING WITH

408
00:19:22,561 --> 00:19:26,565
AUTISTIC -- WE ARE GOING TO

409
00:19:26,565 --> 00:19:30,036
START TO IDENTIFY IMMUNE

410
00:19:30,036 --> 00:19:31,537
CORRELATES POSITIVELY OR

411
00:19:31,537 --> 00:19:32,438
NEGATIVELY ASSOCIATED WITH A

412
00:19:32,438 --> 00:19:35,975
FEVER. SO HOPEFULLY IF THERE IS

413
00:19:35,975 --> 00:19:39,178
A CHANCE IN A FEW YEARS I CAN

414
00:19:39,178 --> 00:19:44,617
SHARE IT WITH YOU MORE EXCITING

415
00:19:44,617 --> 00:19:50,556
FINDIFINDIFINDING. BASED ORANGEN

416
00:19:50,556 --> 00:19:51,924
OBSERVATION WE DECIDED TO USE

417
00:19:51,924 --> 00:19:55,327
MOUSE MODEL FOR AWETISM AND THEN

418
00:19:55,327 --> 00:19:56,462
TRY TO UNDERSTAND AUTISM AND TRY

419
00:19:56,462 --> 00:20:00,166
TO UNDERSTAND THE UNDERLYING

420
00:20:00,166 --> 00:20:01,734
MECHANISM THAT IMPROVE I BELIEVE

421
00:20:01,734 --> 00:20:04,870
FLAYMATION ASSOCIATED WITH --

422
00:20:04,870 --> 00:20:06,739
THIS WAS PUBLISHED AWARD BUT IN

423
00:20:06,739 --> 00:20:08,307
ORDER TO STUDY THAT WE FIRST

424
00:20:08,307 --> 00:20:14,647
NEED TO USE A MOUSE MODEL IN

425
00:20:14,647 --> 00:20:19,151
AUTISM THERE'S NO BIOMARKER

426
00:20:19,151 --> 00:20:22,555
ESSENTIALLY A PHENOTYPIC BASIS

427
00:20:22,555 --> 00:20:24,690
STUDY SCIENTISTS GENERATE MANY

428
00:20:24,690 --> 00:20:26,892
REFER TO AUTISM MODEL, SOME

429
00:20:26,892 --> 00:20:28,694
REQUIRE GENETIC MUTATION. OTHER

430
00:20:28,694 --> 00:20:30,029
AUTISM MODEL DEPENDENT ON

431
00:20:30,029 --> 00:20:31,497
ENVIRONMENTAL FACTOR AND ONE

432
00:20:31,497 --> 00:20:34,834
MODEL THAT WE OFTEN USE IS HUMAN

433
00:20:34,834 --> 00:20:36,869
ACTIVATION MODEL. THIS IS A VERY

434
00:20:36,869 --> 00:20:42,374
-- THIS MODEL IS BASED ON HUMAN

435
00:20:42,374 --> 00:20:45,644
EPIDEMIOLOGICAL STUDY. IN

436
00:20:45,644 --> 00:20:46,912
RESPONSE TO SOME INFLAMMATION

437
00:20:46,912 --> 00:20:50,349
DURING PREGNANCY. SECOND

438
00:20:50,349 --> 00:20:52,718
TRIMESTER, LATE FIRST TRIMESTER

439
00:20:52,718 --> 00:20:55,287
PREGNANCY. THEIR CHILDREN HAVE A

440
00:20:55,287 --> 00:20:57,289
CHANCE TO DEVELOP

441
00:20:57,289 --> 00:20:58,324
NEURODEVELOPMENTAL DISORDER

442
00:20:58,324 --> 00:20:59,792
SIGNIFICANT INCREASE SO THIS IS

443
00:20:59,792 --> 00:21:10,269
AN APPROVAL REPORTED AGAIN,

444
00:21:10,703 --> 00:21:13,839
STUDY IN DENMARK, THEY HAD THIS

445
00:21:13,839 --> 00:21:16,775
STUDY IN DENMARK SINCE 1980, A

446
00:21:16,775 --> 00:21:19,011
WOMAN HOSPITALIZED DURING

447
00:21:19,011 --> 00:21:20,679
PREGNANCY, CHILDREN -- A CHANCE

448
00:21:20,679 --> 00:21:24,083
TO DEVELOP AUTISM SIGNIFICANTLY

449
00:21:24,083 --> 00:21:26,285
INCREASE. SO WE UTILIZE THIS

450
00:21:26,285 --> 00:21:27,620
MODEL IN MICE DURING PREGNANCY

451
00:21:27,620 --> 00:21:31,190
WE GIVE THEM INFLAMMATION,

452
00:21:31,190 --> 00:21:35,961
INJECT THEM WITH POLYIC AND

453
00:21:35,961 --> 00:21:39,598
LIGAND AND COMPARABLE TO HUMAN

454
00:21:39,598 --> 00:21:42,902
SECOND TRIMESTER OR LATE FIRST

455
00:21:42,902 --> 00:21:48,908
TRIMESTER. AND THEN -- LED WAIT

456
00:21:48,908 --> 00:21:52,711
TWO MONTHS, THEIR OFF SPRING

457
00:21:52,711 --> 00:21:55,114
(INAUDIBLE) COMPARE TO OFFSPRING

458
00:21:55,114 --> 00:21:59,451
PREVIOUS INJECTION TO THE MOTHER

459
00:21:59,451 --> 00:22:03,455
THEY SHOW INCREASE BEHAVIOR,

460
00:22:03,455 --> 00:22:05,024
SHOW (INAUDIBLE) SO OF COURSE

461
00:22:05,024 --> 00:22:06,025
NOBODY KNOW FOR SURE WHETHER

462
00:22:06,025 --> 00:22:09,395
THESE MICE ARE AUTISTIC BUT WE

463
00:22:09,395 --> 00:22:14,900
CAN SAY THESE MICE DURING

464
00:22:14,900 --> 00:22:16,001
PREGNANCY MANY MONTHS LATER

465
00:22:16,001 --> 00:22:17,136
THERE'S BEHAVIOR CHANGES SO

466
00:22:17,136 --> 00:22:20,072
USING THIS MOUSE MODEL WE WANT

467
00:22:20,072 --> 00:22:22,908
TO TEST WHETHER THIS MICE MODEL,

468
00:22:22,908 --> 00:22:26,579
WHEN THIS MOUSE SHOWING AUTISM

469
00:22:26,579 --> 00:22:29,081
LIKE BEHAVIOR WHEN THEY REACH

470
00:22:29,081 --> 00:22:30,182
(INAUDIBLE). WHAT HAPPEN IF WE

471
00:22:30,182 --> 00:22:32,418
GIVE THEM TO ANOTHER IMMUNE

472
00:22:32,418 --> 00:22:34,553
STIMULUS, RIGHT? SO COMPLICATED,

473
00:22:34,553 --> 00:22:39,024
RIGHT? SO INFLAMMATION DURING

474
00:22:39,024 --> 00:22:40,426
PREGNANCY CAN PROMOTE AUTISM

475
00:22:40,426 --> 00:22:43,862
BEHAVIOR. WE ARE ASKING THAT

476
00:22:43,862 --> 00:22:48,200
INFLAMMATION ONCE THE CIRCUIT IS

477
00:22:48,200 --> 00:22:49,168
COMPLETELY ESTABLISHED WHETHER

478
00:22:49,168 --> 00:22:52,404
THAT INFLAMMATION CAN MITIGATE

479
00:22:52,404 --> 00:22:54,406
BEHAVIOR SYMPTOM THAT IS WHAT WE

480
00:22:54,406 --> 00:22:59,211
DECIDED TO ASK. SOME MAY NOT BE

481
00:22:59,211 --> 00:23:00,579
FAMILIAR WITH BEHAVIOR STUDY,

482
00:23:00,579 --> 00:23:02,481
THIS IS A WIDELY ESTABLISHED

483
00:23:02,481 --> 00:23:04,516
MODEL BY IMMUNE BIOLOGIST,

484
00:23:04,516 --> 00:23:06,352
CONTROL MICE WAS GIVEN A CHOICE,

485
00:23:06,352 --> 00:23:09,388
THIS MOUSE SPEND MORE TIME WITH

486
00:23:09,388 --> 00:23:12,057
THEIR SOCIAL TARGET INSTEAD OF

487
00:23:12,057 --> 00:23:13,092
SPENDING TIME (INAUDIBLE) FOR

488
00:23:13,092 --> 00:23:15,728
DURATION OF 10 TO 15 MINUTES WE

489
00:23:15,728 --> 00:23:18,998
SHIFT THE MOUSE AND BY

490
00:23:18,998 --> 00:23:21,400
QUANTIFYING RELATIVE TIME SPENT

491
00:23:21,400 --> 00:23:25,004
IN ASSOCIATED TARGETS IN TARGET

492
00:23:25,004 --> 00:23:27,273
WE CAN QUANTIFY THE SOCIAL

493
00:23:27,273 --> 00:23:29,074
OPPORTUNITY THERE. SO

494
00:23:29,074 --> 00:23:30,876
ESTABLISHED STUDY, THAT IS WHAT

495
00:23:30,876 --> 00:23:32,344
BUT YOU SEE FROM THE CONTROL

496
00:23:32,344 --> 00:23:33,279
MICE. WHAT HAPPENED IF YOU DO

497
00:23:33,279 --> 00:23:37,483
THE SAME EXPERIMENT WITH THE

498
00:23:37,483 --> 00:23:39,952
MICE, P POSED TO INFLAMMATION IN

499
00:23:39,952 --> 00:23:42,087
MICE DURING PREGNAN PREGNANCY. T

500
00:23:42,087 --> 00:23:43,622
INTEREST IN SOCIAL TARGET. THEY

501
00:23:43,622 --> 00:23:45,190
SPEND EQUAL AMOUNT BETWEEN TWO

502
00:23:45,190 --> 00:23:47,059
TARGET BUT OVERALL THEY ARE

503
00:23:47,059 --> 00:23:50,329
MOVING DISTANCE, THEY ARE

504
00:23:50,329 --> 00:23:51,230
INVESTIGATION TIME ARE

505
00:23:51,230 --> 00:23:58,370
COMPARABLE. NO MAJOR INHIBITORY

506
00:23:58,370 --> 00:23:59,738
EFFECT SO JUST SPENDING TIME

507
00:23:59,738 --> 00:24:00,806
WITH TARGET. THIS IS A

508
00:24:00,806 --> 00:24:02,074
QUANTIFICATION I WANT TO SHOW

509
00:24:02,074 --> 00:24:04,610
YOU. THIS IS CONTROL MICE, 70%

510
00:24:04,610 --> 00:24:07,746
TIME SOCIAL TARGET AND MICE THEY

511
00:24:07,746 --> 00:24:11,817
-- EVEN WITH OR WITHOUT -- THEY

512
00:24:11,817 --> 00:24:13,519
SPEND SMALL MEDIAN AMOUNT OF

513
00:24:13,519 --> 00:24:15,287
TIME WITH SOCIAL TARGET SO

514
00:24:15,287 --> 00:24:18,324
SOCIAL DEFICIT BEHAVIOR

515
00:24:18,324 --> 00:24:20,326
PHENOTYPE. WE GIVE ANOTHER

516
00:24:20,326 --> 00:24:22,361
IMMUNE STIMULUS.  WE DECIDED TO

517
00:24:22,361 --> 00:24:26,432
USE APF BECAUSE WHEN YOU GIVE

518
00:24:26,432 --> 00:24:30,102
NO, MA'AM MULTI-IT WILL -- WE

519
00:24:30,102 --> 00:24:31,337
DECIDE TO GIVE A DIFFERENT

520
00:24:31,337 --> 00:24:36,475
STIMULUS. WHAT HAPPENED IS WE

521
00:24:36,475 --> 00:24:40,946
SAW SOCIAL ABILITY. WITH HIGHER

522
00:24:40,946 --> 00:24:43,749
LEVEL OF MOUSE DEVELOP BEHAVIOR,

523
00:24:43,749 --> 00:24:46,118
EVERYTHING COMES OUTS TO -- WE

524
00:24:46,118 --> 00:24:50,589
GIVE PEERS THAT IS NOVEL, THEIR

525
00:24:50,589 --> 00:24:54,226
OVERALL INDUCE PHENOTYPE WAS

526
00:24:54,226 --> 00:24:59,531
STILL CELL TEMPORALLY ROBUST

527
00:24:59,531 --> 00:25:02,434
RESCUE SOCIAL ABILITY PHENOTYPE.

528
00:25:02,434 --> 00:25:03,502
THE SAME BEHAVIOR PHENOTYPE AS

529
00:25:03,502 --> 00:25:09,641
WELL.  SO WE ARE ABLE TO

530
00:25:09,641 --> 00:25:11,977
RECAPITULATE WHAT IS SHOWN IN

531
00:25:11,977 --> 00:25:16,281
HUMAN IN CERTAIN AUTISTIC

532
00:25:16,281 --> 00:25:18,417
INDIVIDUAL CORE SYMPTOMS CAN

533
00:25:18,417 --> 00:25:21,086
IMPROVE. NEXT QUESTION IS IS

534
00:25:21,086 --> 00:25:23,122
PEOPLE OR IS IT OTHER NON-FEVER

535
00:25:23,122 --> 00:25:26,125
RELATED IMMUNE MOLECULE? HOW DO

536
00:25:26,125 --> 00:25:28,127
WE INDUCE FEVER? WE INDUCE

537
00:25:28,127 --> 00:25:31,663
INFLAMMATION. NEURAL BALANCE

538
00:25:31,663 --> 00:25:35,868
WITH ALL NEW TECHNIQUE AND THEN

539
00:25:35,868 --> 00:25:38,437
BASICALLY BY INHIBITING NEURONAL

540
00:25:38,437 --> 00:25:40,973
ACTIVITY IN CERTAIN BRAIN AREA,

541
00:25:40,973 --> 00:25:44,510
HYPOTHALAMIC REGION. YOU DO

542
00:25:44,510 --> 00:25:46,545
THAT, INFLUENCE PARTICULAR BRAIN

543
00:25:46,545 --> 00:25:49,314
LOCUST YOU CAN INCREASE, IN THIS

544
00:25:49,314 --> 00:25:52,718
CASE NO INFLAMMATION. SO WHAT WE

545
00:25:52,718 --> 00:25:54,520
ASK IS INCREASE THE TEMPERATURE

546
00:25:54,520 --> 00:25:56,355
AND THAT CAN HAPPEN, THE MOUSE

547
00:25:56,355 --> 00:26:00,225
STILL SHOW REDUCE ASSOCIATED

548
00:26:00,225 --> 00:26:02,895
PHENOTYPE SUGGESTING THAT IN

549
00:26:02,895 --> 00:26:06,031
THIS CASE INCREASING TEMPERATURE

550
00:26:06,031 --> 00:26:09,401
IS NOT SUFFICIENT OR MITIGATING

551
00:26:09,401 --> 00:26:13,872
BEHAVIOR ABNORMALITY. SO FACING

552
00:26:13,872 --> 00:26:19,311
A FEVER, FOR VARIOUS REASON WE

553
00:26:19,311 --> 00:26:21,547
CYTOKINES MEASURE CYTOKINE WITH

554
00:26:21,547 --> 00:26:23,816
OR WITHOUT INJECTION AND NOTICE

555
00:26:23,816 --> 00:26:26,952
THAT FIRST COMPARE TO CONTROL

556
00:26:26,952 --> 00:26:32,224
GROUP, (INAUDIBLE) APS INDUCE

557
00:26:32,224 --> 00:26:34,493
MORE CYTOKINE PRODUCTION IN MIL

558
00:26:34,493 --> 00:26:37,896
STRENGTH SO WE PUBLISHED A PAPER

559
00:26:37,896 --> 00:26:42,768
IN IMMUNITY LAST YEAR SO MICE

560
00:26:42,768 --> 00:26:43,502
IMMUNOSYSTEM REMEMBER WHAT

561
00:26:43,502 --> 00:26:44,636
HAPPENED DURING PREGNANCY AND

562
00:26:44,636 --> 00:26:47,072
IMMUNE SYSTEM WHEN THEY GET

563
00:26:47,072 --> 00:26:50,309
(INAUDIBLE) THEY BECOME MORE

564
00:26:50,309 --> 00:27:00,752
HYPERACTIVATED. SO PROMOTE

565
00:27:03,922 --> 00:27:04,756
BEHAVIOR BY ACTING ON THE STRESS

566
00:27:04,756 --> 00:27:06,391
PATHWAY. IN THIS CASE WE THOUGHT

567
00:27:06,391 --> 00:27:11,530
MAYBE IL 17 HERE, SOME OTHER

568
00:27:11,530 --> 00:27:14,032
REASON PLAY AN IMPORTANT ROLE

569
00:27:14,032 --> 00:27:17,202
MITIGATING THE SOCIAL ABILITY

570
00:27:17,202 --> 00:27:20,105
PHENOTYPE SO QUESTION WILL IL 17

571
00:27:20,105 --> 00:27:21,673
LEAD TO BEHAVIOR RESCUE. FIRST

572
00:27:21,673 --> 00:27:24,443
WE INTRODUCE WE INHIBITED IL 17

573
00:27:24,443 --> 00:27:26,712
ACTIVITY IN THE BRAIN BY

574
00:27:26,712 --> 00:27:28,514
INTRODUCING BELONGING ANTIBODY

575
00:27:28,514 --> 00:27:31,350
TO CNS ALL PUBLISHED SO LET ME

576
00:27:31,350 --> 00:27:33,085
MOVE A LITTLE QUICKLY BECAUSE I

577
00:27:33,085 --> 00:27:37,456
WANT TO SHARE WITH YOU PUBLISHED

578
00:27:37,456 --> 00:27:38,156
LITERATURE. SO IN THIS CASE

579
00:27:38,156 --> 00:27:43,228
BLOCKING IL 17 ACTIVITY IN THE

580
00:27:43,228 --> 00:27:47,366
BRAIN THEN WE NEURONAL DETECT

581
00:27:47,366 --> 00:27:49,268
INCREASE SOCIAL ABILITY, IF WE

582
00:27:49,268 --> 00:27:51,003
BLOCK INTERFERON GAMMA AND

583
00:27:51,003 --> 00:27:55,140
(INAUDIBLE) SO IL 17 ACTIVITY IN

584
00:27:55,140 --> 00:27:57,943
THE BRAIN MAY PLAY A ROLE IN

585
00:27:57,943 --> 00:28:01,179
MITIGATING SOCIAL DEFICIT.  

586
00:28:01,179 --> 00:28:04,616
PREVIOUSLY (INAUDIBLE) IDENTIFY

587
00:28:04,616 --> 00:28:08,287
IMPORTANT BRAIN AREA THAT WHERE

588
00:28:08,287 --> 00:28:09,588
INCREASE NEURONAL ACTIVITY LED

589
00:28:09,588 --> 00:28:13,759
TO BEHAVIOR ABNORMALITY AND THEN

590
00:28:13,759 --> 00:28:15,661
SUPPRESS NEURAL ACTIVITY SHE WAS

591
00:28:15,661 --> 00:28:18,297
ABLE TO TEMPORALLY RESCUE

592
00:28:18,297 --> 00:28:19,264
BEHAVIOR ABNORMALITY. WE THOUGHT

593
00:28:19,264 --> 00:28:22,401
MAYBE THIS INFLAMMATION CAN ALSO

594
00:28:22,401 --> 00:28:24,536
INFLUENCE THIS NEURONAL

595
00:28:24,536 --> 00:28:26,672
ACTIVITY, AUTOTISSIC MOUSE FOR

596
00:28:26,672 --> 00:28:28,574
VARIOUS AUTISM MODEL HAVE

597
00:28:28,574 --> 00:28:29,608
INCREASE BRAIN ACTIVITY NEURAL

598
00:28:29,608 --> 00:28:30,542
ACTIVITY IN THIS PARTICULAR

599
00:28:30,542 --> 00:28:33,111
BRAIN AREA. AND THEN WE THOUGHT

600
00:28:33,111 --> 00:28:35,781
PERIPHERAL INFLAMMATION,

601
00:28:35,781 --> 00:28:36,915
FOLLOWING THIS INJECTION NOT

602
00:28:36,915 --> 00:28:39,685
ONLY RESCUE BUT BEHAVIOR

603
00:28:39,685 --> 00:28:43,622
ABNORMALITY BUT MAY INFLUENCE

604
00:28:43,622 --> 00:28:44,790
INCREASING NEURAL ACTIVITY, THAT

605
00:28:44,790 --> 00:28:47,926
IS WHAT WE SEE AND HYPOTHESIZE

606
00:28:47,926 --> 00:28:52,931
SO SUPPORT THAT BASED ON SHOWING

607
00:28:52,931 --> 00:28:56,101
PERIPHERY REDUCE THIS

608
00:28:56,101 --> 00:28:57,202
(INAUDIBLE) SURROGATE MICE

609
00:28:57,202 --> 00:28:59,338
NEURONAL ACTIVITY AND THIS IS A

610
00:28:59,338 --> 00:29:00,539
BRAIN SPECIFIC BECAUSE WHEN YOU

611
00:29:00,539 --> 00:29:02,241
GET OTHER BRAIN REGION THERE IS

612
00:29:02,241 --> 00:29:03,809
NO CHANGE EVEN WITH INCREASE

613
00:29:03,809 --> 00:29:05,577
NEURONAL ACTIVITY. SO

614
00:29:05,577 --> 00:29:07,546
INTERESTING TO SEE KEY BRAIN

615
00:29:07,546 --> 00:29:10,015
AREA MEDIATED THAT IS IMPORTANT

616
00:29:10,015 --> 00:29:12,718
FOR BEHAVIOR ABNORMALITY,

617
00:29:12,718 --> 00:29:16,788
PERIPHERAL INFLAMMATION IS

618
00:29:16,788 --> 00:29:17,990
INTRODUCED TO ESTABLISH BACK TO

619
00:29:17,990 --> 00:29:20,959
BASELINE. THEN WE GOT THE SAME

620
00:29:20,959 --> 00:29:23,729
WHEN WE DID THE (INAUDIBLE) IN

621
00:29:23,729 --> 00:29:29,067
THIS CASE AS WELL INDUCE THE

622
00:29:29,067 --> 00:29:32,170
DIGOXIN NEURAL ACTIVITY CAN BE

623
00:29:32,170 --> 00:29:35,107
PREVENTED IF WE BLOCK ANTIBODY

624
00:29:35,107 --> 00:29:37,909
SUGGESTING THAT THIS CHANGE IN

625
00:29:37,909 --> 00:29:41,980
NEURAL ACTIVITY REQUIRES IL 17. 

626
00:29:41,980 --> 00:29:45,283
IN ORDER TO UNDERSTAND WHY

627
00:29:45,283 --> 00:29:47,452
(INAUDIBLE) MORE TRAJECTORY WITH

628
00:29:47,452 --> 00:29:50,889
IL 17 CAN MEDIATE THE BEHAVIOR

629
00:29:50,889 --> 00:29:53,158
RESCUE, WE FIRST LOOK AT

630
00:29:53,158 --> 00:29:55,060
EXPRESSION OF IL 17 RECEPTOR,

631
00:29:55,060 --> 00:29:59,064
THIS IS IL 17A SUB UNIT USING

632
00:29:59,064 --> 00:30:02,300
RNA SCOPE. THIS IS RNA. THEN WE

633
00:30:02,300 --> 00:30:05,237
SAW THERE THERE IS EXPRESSION OF

634
00:30:05,237 --> 00:30:06,271
RNA INTO (INAUDIBLE) OF THE

635
00:30:06,271 --> 00:30:10,342
CORTEX. WHEN WE MOVE THAT IL 17

636
00:30:10,342 --> 00:30:13,211
RECEPTOR EXPRESSION USING

637
00:30:13,211 --> 00:30:16,448
(INAUDIBLE) ONE THING TO MENTION

638
00:30:16,448 --> 00:30:19,885
FOR IMMUNO-- PEOPLE WITH

639
00:30:19,885 --> 00:30:20,719
IMMUNOBACKGROUND, IN THE SYSTEM

640
00:30:20,719 --> 00:30:26,591
BRAIN IS STEADY, SO YOU CAN

641
00:30:26,591 --> 00:30:28,427
DELIVER THE CRE PROTEIN IN

642
00:30:28,427 --> 00:30:31,463
LOCALIZED BRAIN AREA, IN DOING

643
00:30:31,463 --> 00:30:34,199
SO YOU CAN INFECT THAT PERSON

644
00:30:34,199 --> 00:30:35,934
NOT THE NEIGHBORING REGION. ONLY

645
00:30:35,934 --> 00:30:37,502
THAT PART. SO THAT'S WHAT WE

646
00:30:37,502 --> 00:30:43,008
DID. THIS BRAIN AREA WE GET RID

647
00:30:43,008 --> 00:30:46,478
OF REACCEPT EXPRESSION AND THAT

648
00:30:46,478 --> 00:30:50,816
BRINGS BACK RESCUE. SO YOU KNEE

649
00:30:50,816 --> 00:30:53,185
IL 17 RECEPTOR A SUB UNIT

650
00:30:53,185 --> 00:30:54,653
CORTICAL BRAIN AREA. AT THAT

651
00:30:54,653 --> 00:30:57,522
TIME WE ALSO DID A EXPERIMENT IN

652
00:30:57,522 --> 00:31:01,359
THIS CASE WE INCLUDE PROTEIN

653
00:31:01,359 --> 00:31:03,061
DIRECTLY INTO THIS -- ON TOP OF

654
00:31:03,061 --> 00:31:07,466
THIS CRITICAL AREA BY DELIVERING

655
00:31:07,466 --> 00:31:09,468
WHOLE IN THE CANNELLA AND IL 17

656
00:31:09,468 --> 00:31:12,971
INTRODUCTION OF IL 17 RAY LOAN

657
00:31:12,971 --> 00:31:15,006
IS SUFFICIENT FOR SOCIAL

658
00:31:15,006 --> 00:31:16,908
BEHAVIOR SUGGESTING IL 17

659
00:31:16,908 --> 00:31:19,511
RECEPTOR IS NECESSARY IL 17

660
00:31:19,511 --> 00:31:21,213
PROTEIN IS SUFFICIENT TO INDUCE

661
00:31:21,213 --> 00:31:24,116
BEHAVIOR ABNORMALITY. THEN LATER

662
00:31:24,116 --> 00:31:30,122
WE ALSO ACHIEVE THE SAME GOAL,

663
00:31:30,122 --> 00:31:31,289
SOCIAL ABILITY, THIS IS GENETIC

664
00:31:31,289 --> 00:31:35,861
MOUSE MODEL OF AUTISM, THIS IS

665
00:31:35,861 --> 00:31:38,029
ONE OF THE MUTATION THAT ARE

666
00:31:38,029 --> 00:31:40,332
FOUND FOR HUMAN AUTISTIC

667
00:31:40,332 --> 00:31:41,633
PATIEPATIENT. IN THIS CASE THOUH

668
00:31:41,633 --> 00:31:43,301
THEY HAVE THE SAME GENETIC

669
00:31:43,301 --> 00:31:46,705
MUTATION WHEN WE INCREASE IL 17

670
00:31:46,705 --> 00:31:52,244
IN PERIPHERY IT IS SUFFICIENT TO

671
00:31:52,244 --> 00:31:55,313
PROMOTE PHENOTYPE BASICALLY MICE

672
00:31:55,313 --> 00:31:58,650
SPEND MUCH TIME EACH OTHER BUT

673
00:31:58,650 --> 00:32:00,352
IN THIS CASE FOUR HOURS AFTER WE

674
00:32:00,352 --> 00:32:02,320
INCREASE IL 17 LEVEL IN

675
00:32:02,320 --> 00:32:03,488
PERIPHERY, THE MOUSE SPEND MORE

676
00:32:03,488 --> 00:32:06,925
TIME WITH EACH OTHER AND THIS

677
00:32:06,925 --> 00:32:08,593
RESCUE PHENOTYPE LAST AROUND A

678
00:32:08,593 --> 00:32:11,463
FEW DAYS. THIS APPROACH IS NOT

679
00:32:11,463 --> 00:32:14,599
RESTRICTED TO MIA. BUT WHEN --

680
00:32:14,599 --> 00:32:16,668
OR SHANK 3 BUT WHEN WE BRING IN

681
00:32:16,668 --> 00:32:17,736
MULTIPLE OTHER PROTEIN MOUSE

682
00:32:17,736 --> 00:32:20,772
MODEL FOR AUTISM, WE ARE ABLE TO

683
00:32:20,772 --> 00:32:22,908
(INAUDIBLE) GENETIC MUTATION AS

684
00:32:22,908 --> 00:32:26,044
WELL AS WE INCREASE IL 17 IN

685
00:32:26,044 --> 00:32:27,879
PERIPHERY, BEHAVIOR SYMPTOM IS

686
00:32:27,879 --> 00:32:28,914
SIGNIFICANT WAS SIGNIFICANTLY

687
00:32:28,914 --> 00:32:34,152
IMPROVED.  SO SO FAR I TOLD YOU

688
00:32:34,152 --> 00:32:37,088
THAT IL 17 WHETHER THIS LAB

689
00:32:37,088 --> 00:32:38,890
INCREASE MANY THE BRAIN OR IN

690
00:32:38,890 --> 00:32:41,526
THE PERIPHERY, THEN YOU HAVE

691
00:32:41,526 --> 00:32:43,695
THIS MITIGATION OF BEHAVIOR

692
00:32:43,695 --> 00:32:46,998
PHENOTYPE WHICH IS INCLUDE

693
00:32:46,998 --> 00:32:49,267
SOCIAL ABILITY. SO THE QUESTION

694
00:32:49,267 --> 00:32:52,470
IS, WHY IL 17? WHAT IS SPECIFIC

695
00:32:52,470 --> 00:32:57,409
ABOUT IL 17? I GAVE A LOT OF

696
00:32:57,409 --> 00:32:59,144
THOUGHT ABOUT THIS FROM THE NEXT

697
00:32:59,144 --> 00:33:01,813
FEW SLIDES I WANT TO SHOW YOU

698
00:33:01,813 --> 00:33:06,251
ANOTHER DATA FROM MY OWN

699
00:33:06,251 --> 00:33:09,354
PERSONAL THOUGHTS. SO I WANT

700
00:33:09,354 --> 00:33:10,388
HEAR YOUR (INAUDIBLE). SO WHEN I

701
00:33:10,388 --> 00:33:13,992
FIRST THINK ABOUT IL 17 THIS IS

702
00:33:13,992 --> 00:33:17,229
INTERLEUKIN-17. i, I BEGIN TO

703
00:33:17,229 --> 00:33:20,398
WONDER OF COURSE WHENEVER I WANT

704
00:33:20,398 --> 00:33:23,668
TO SEEK ANSWER THE FIRST THING I

705
00:33:23,668 --> 00:33:29,541
DO IS RELY ON GOOGLE SO I WONDER

706
00:33:29,541 --> 00:33:31,877
WHAT INTERLEUKIN IS. I CHECK

707
00:33:31,877 --> 00:33:33,345
THIS DEFINITION AND IT SAYS A

708
00:33:33,345 --> 00:33:35,480
GROUP OF CYTOKINES EXPRESSED AND

709
00:33:35,480 --> 00:33:37,148
SECRETED BY WHITE BLOOD CELLS.

710
00:33:37,148 --> 00:33:39,117
AND THEN THE QUESTION IS, OKAY

711
00:33:39,117 --> 00:33:45,223
WHAT ARE THE CYTOKINES? I CHECK

712
00:33:45,223 --> 00:33:47,225
AGAIN THE GLOSSARY AND CYTOKINE

713
00:33:47,225 --> 00:33:48,827
IS ANY FORM OF SUBSTANCES SUCH

714
00:33:48,827 --> 00:33:51,997
AS INTERLEUKIN AND GROWTH FACTOR

715
00:33:51,997 --> 00:33:53,031
SECRETED BY CERTAIN CELLS OF THE

716
00:33:53,031 --> 00:33:56,668
IMMUNE SYSTE SYSTEM. SO INTERLES

717
00:33:56,668 --> 00:33:59,537
CYTOKINE AND CYTOKINE IS

718
00:33:59,537 --> 00:34:02,107
INTERLEUKIN. SO I WONDER

719
00:34:02,107 --> 00:34:03,441
CYTOKINE KIND OF UNDERSTANDING

720
00:34:03,441 --> 00:34:04,809
WHERE IT CAME FROM BUT WHAT

721
00:34:04,809 --> 00:34:10,548
ABOUT INTERLEUKIN? COULD BE

722
00:34:10,548 --> 00:34:12,183
CULTURAL BARRIER, SO PLEASE

723
00:34:12,183 --> 00:34:14,319
EXCUSE ME. I FOUND ON GOOGLE AN

724
00:34:14,319 --> 00:34:19,224
ARGUE SAYING THAT WILL IS A

725
00:34:19,224 --> 00:34:21,426
SWITCH AROUND, SOME OF YOU MAY

726
00:34:21,426 --> 00:34:25,530
HAVE BEEN THERE, I NEVER HEARD

727
00:34:25,530 --> 00:34:28,433
THE TERM. EXCUSE MY POOR

728
00:34:28,433 --> 00:34:30,568
PRONUNCIATION. THE CITY, AND I

729
00:34:30,568 --> 00:34:33,605
GUESS THIS IS LIKE A LAKE. YOU

730
00:34:33,605 --> 00:34:35,106
SEE A CITY BETWEEN TWO LAKES. 

731
00:34:35,106 --> 00:34:37,509
THAT IS WHY IT IS CALLED THE

732
00:34:37,509 --> 00:34:40,512
INTERLAKEN. APPARENTLY THE

733
00:34:40,512 --> 00:34:42,113
INTERLEUKIN FAMILY IS NAMED

734
00:34:42,113 --> 00:34:46,084
AFTER LOCATION ENCOMPASSING

735
00:34:46,084 --> 00:34:48,219
(INAUDIBLE) 1973. HOW WE START

736
00:34:48,219 --> 00:34:50,889
TO CALL IMMUNE SECRETED IN SIGHT

737
00:34:50,889 --> 00:34:53,091
COIN INTERLEUKIN ACCORDING TO

738
00:34:53,091 --> 00:34:57,128
THIS. SO AGAIN, I'M OPEN TO

739
00:34:57,128 --> 00:35:00,198
CORRECTION ON PRONUNCIATION.

740
00:35:00,198 --> 00:35:06,371
YESTERDAY, OUR LAB -- MY THOUGHT

741
00:35:06,371 --> 00:35:08,540
PROCESS, WHENEVER I THINK ABOUT

742
00:35:08,540 --> 00:35:09,407
INTERLEUKIN YOU THINK

743
00:35:09,407 --> 00:35:11,009
INTERLEUKIN-17 SO IMMUNE RELATED

744
00:35:11,009 --> 00:35:13,611
RIGHT? SO I NEXT THING YOU KNOW

745
00:35:13,611 --> 00:35:21,653
I WENT TO TEST, THE STRUCTURE,

746
00:35:21,653 --> 00:35:28,627
FAMOUS CYTOKINE, STRUCTURE THEN

747
00:35:28,627 --> 00:35:30,962
LIKE A PIONEER HERE SITTING

748
00:35:30,962 --> 00:35:35,867
THROUGH BUT THESE CELL SIGH COIN

749
00:35:35,867 --> 00:35:38,670
RECEPTOR, WITH THE RECEPTOR

750
00:35:38,670 --> 00:35:40,872
CASCADE THROUGH LEAD TO

751
00:35:40,872 --> 00:35:42,674
ACTIVATION OF JAK STAT PATHWAY. 

752
00:35:42,674 --> 00:35:49,314
SO THIS IS A REALLY -- THAT'S

753
00:35:49,314 --> 00:35:54,886
KIND OF CYTOKINE. RIGHT? SO THEN

754
00:35:54,886 --> 00:35:56,388
(INAUDIBLE) STRUCTURE PROCESS

755
00:35:56,388 --> 00:35:59,157
DIMER SOME MONOMER, SOME

756
00:35:59,157 --> 00:36:00,992
CYTOKINE DIMER BUT IF YOU LOOK

757
00:36:00,992 --> 00:36:07,265
AT IL 17 THIS IS JUST IL 17.

758
00:36:07,265 --> 00:36:09,968
DIMER, STRUCTURE AND THE

759
00:36:09,968 --> 00:36:12,237
STRUCTURE I CHECK THIS EARLIER

760
00:36:12,237 --> 00:36:14,672
WORK. BY THE WAY THIS DOWN

761
00:36:14,672 --> 00:36:18,810
SIGNALING NF KAPPA B. THEN WHEN

762
00:36:18,810 --> 00:36:23,848
I LOOK AT THE OLD LITERATURE,

763
00:36:23,848 --> 00:36:25,784
CHILDREN AND OTHER GROUP SHOW

764
00:36:25,784 --> 00:36:27,352
THE STRUCTURE IS OFTEN FOUND IN

765
00:36:27,352 --> 00:36:32,190
PROTEIN FAMILY CALLED NEURAL

766
00:36:32,190 --> 00:36:36,494
GROWTH FACTOR KNEW TROPHIN. I

767
00:36:36,494 --> 00:36:37,529
DON'T HAVE BACKGROUND IN

768
00:36:37,529 --> 00:36:38,696
STRUCTURAL BIOLOGY BUT USE FROM

769
00:36:38,696 --> 00:36:41,166
OTHER CYTOKINE AND DOWNSTREAM

770
00:36:41,166 --> 00:36:43,835
SIGNALING FROM OTHER CYTOKINES.

771
00:36:43,835 --> 00:36:46,838
SO THIS IS OUR PAPER. THAT

772
00:36:46,838 --> 00:36:49,474
ACCORDING TO IL 17 SOCIAL

773
00:36:49,474 --> 00:36:52,043
ABILITY IN MOUSE MODEL FOR

774
00:36:52,043 --> 00:36:54,279
AUTISM. THEN SO LIKE AROUND THE

775
00:36:54,279 --> 00:36:57,482
SAME -- LIKE A YEAR, TWO YEAR

776
00:36:57,482 --> 00:36:59,484
LATER, THE GROUP AT CORNELL --

777
00:36:59,484 --> 00:37:02,020
WEILL CORNELL UNIVERSITY, HE

778
00:37:02,020 --> 00:37:06,324
FOUND IL 17 INCREASE SOCIAL

779
00:37:06,324 --> 00:37:10,962
ABILITY IN WILD TYPE MICE. SO

780
00:37:10,962 --> 00:37:13,565
THIS CONFIRMED EARLIER WORK. BUT

781
00:37:13,565 --> 00:37:16,067
THERE IS ALSO A GROUP THAT EVEN

782
00:37:16,067 --> 00:37:19,504
OLDER THAN US, SO IN 2017, GROUP

783
00:37:19,504 --> 00:37:23,475
IN UK, THEY STUDY C ELEGANS.

784
00:37:23,475 --> 00:37:26,111
THEY DID FOUR GENETIC SCREEN TO

785
00:37:26,111 --> 00:37:30,448
IDENTIFY MOLECULE THAT INHIBIT

786
00:37:30,448 --> 00:37:33,685
-- DUE TO NATURE OF THIS THE

787
00:37:33,685 --> 00:37:36,354
LEVEL OF OXIDANT AVAILABLE --

788
00:37:36,354 --> 00:37:40,759
PHOTO AVAILABILITY C ELEGANS

789
00:37:40,759 --> 00:37:42,861
SOMETIMES KIND OF GROUPED

790
00:37:42,861 --> 00:37:43,761
TOGETHER, SOMETIMES INDIVIDUAL

791
00:37:43,761 --> 00:37:47,265
MOVE AROUND. RIGHT? SO THEY DID

792
00:37:47,265 --> 00:37:48,766
UNBIASED FOUR GENETIC SCREEN AND

793
00:37:48,766 --> 00:37:51,369
THEY WERE ABLE TO IDENTIFY IL 17

794
00:37:51,369 --> 00:37:55,640
AND IL 17 CENTER OF A KEY

795
00:37:55,640 --> 00:37:58,343
MOLECULE THAT INCREASE

796
00:37:58,343 --> 00:38:00,178
(INAUDIBLE) IN C ELEGANS. THEY

797
00:38:00,178 --> 00:38:04,582
SHOW IL 17 REACC RECEPTOR EXPREG

798
00:38:04,582 --> 00:38:06,351
IN NEURONS THAT PROMOTE

799
00:38:06,351 --> 00:38:07,852
AGGREGATION BEHAVIOR. THEY SHOW

800
00:38:07,852 --> 00:38:10,655
THAT IL 17 LIGAND CAN PROMOTE

801
00:38:10,655 --> 00:38:15,059
PHENOTYPE AS WELL. SO VERY

802
00:38:15,059 --> 00:38:16,294
EXCITING, OTHER GROUP

803
00:38:16,294 --> 00:38:18,329
(INAUDIBLE) MORE REASON TO ME

804
00:38:18,329 --> 00:38:20,899
WAS THAT IF YOU THINK ABOUT IT C

805
00:38:20,899 --> 00:38:23,001
ELEGANS THEY DON'T HAVE

806
00:38:23,001 --> 00:38:26,037
(INAUDIBLE). SO WHEN WE THINK OF

807
00:38:26,037 --> 00:38:28,940
IL 17 INTERLEUKIN 17, IT IS THE

808
00:38:28,940 --> 00:38:31,976
CYTOKINE THAT PRODUCED BY

809
00:38:31,976 --> 00:38:36,848
T-CELL, T 77 TH 3 IL 17. THOSE

810
00:38:36,848 --> 00:38:37,882
CELLS DON'T (INAUDIBLE) C

811
00:38:37,882 --> 00:38:40,385
ELEGANS BUT EVEN SO C ELEGANS

812
00:38:40,385 --> 00:38:43,621
NOT ONLY HAVE IL 17 BUT USING

813
00:38:43,621 --> 00:38:46,991
NEURAL MODULATOR. AND IL 17 IS

814
00:38:46,991 --> 00:38:49,160
ONE THOSE AGING CYTOKINE MUCH

815
00:38:49,160 --> 00:38:51,596
EARLIER IN DEVELOPMENT THAN

816
00:38:51,596 --> 00:38:55,266
INTERFERON GAMMA. SO THIS DATA

817
00:38:55,266 --> 00:38:57,869
TO MANY E SUGGESTS THAT IL 17

818
00:38:57,869 --> 00:39:01,339
COULD HAVE EVOLVED AS A NEURAL

819
00:39:01,339 --> 00:39:03,541
MODULATOR THAT REGULATORS

820
00:39:03,541 --> 00:39:06,077
AGGREGATION BEHAVIOR SOCIAL

821
00:39:06,077 --> 00:39:08,379
BEHAVIOR PHENOTYPE, (INAUDIBLE)

822
00:39:08,379 --> 00:39:10,648
FOR WHATEVER REASON IMMUNE CELLS

823
00:39:10,648 --> 00:39:14,319
FOR OTHER PURPOSES SO JUST MY

824
00:39:14,319 --> 00:39:19,891
IDEA. SO THIS IS GOING BACK TO

825
00:39:19,891 --> 00:39:23,161
SOME DATA, RIGHT? SO WE THEN

826
00:39:23,161 --> 00:39:27,332
BEGAN WONDERING HOW IL 17

827
00:39:27,332 --> 00:39:32,470
ENHANCE SOCIAL ABILITY? IN ORDER

828
00:39:32,470 --> 00:39:34,172
(INAUDIBLE) ON THIS INVASIVE

829
00:39:34,172 --> 00:39:38,309
TECHNIQUE, WHERE TO TREAT THE

830
00:39:38,309 --> 00:39:40,678
WHOLE BRAIN WE HAVE TO INTRODUCE

831
00:39:40,678 --> 00:39:42,213
(INAUDIBLE) TO THE BRAIN, SO

832
00:39:42,213 --> 00:39:44,716
MANY INVASIVE -- SO IT IS NOT

833
00:39:44,716 --> 00:39:48,519
EASY TO DO THAT, VERY ROUTINE SO

834
00:39:48,519 --> 00:39:49,754
WE WANTS TO TEST AND UNDERSTAND

835
00:39:49,754 --> 00:39:52,190
THIS ROLE MECHANISM WHICH

836
00:39:52,190 --> 00:39:53,024
(INAUDIBLE) SOCIAL ABILITY, WE

837
00:39:53,024 --> 00:39:55,159
NEED TO COME UP WITH DIFFERENT

838
00:39:55,159 --> 00:39:58,363
METHOD TO ACHIEVE THE SAME GOAL,

839
00:39:58,363 --> 00:40:00,398
INCREASE (INAUDIBLE) IN THE

840
00:40:00,398 --> 00:40:07,739
BRAIN BASICALLY. SO MY

841
00:40:07,739 --> 00:40:09,140
(INAUDIBLE) CAME UP WITH THIS

842
00:40:09,140 --> 00:40:13,511
IDEA. WHAT IF WE JUST

843
00:40:13,511 --> 00:40:17,615
(INAUDIBLE) ITALY? THERE'S

844
00:40:17,615 --> 00:40:19,550
(INDISCERNIBLE) TO THE BRAIN,

845
00:40:19,550 --> 00:40:21,753
MANY SMALL MOLECULE AND ANTIBODY

846
00:40:21,753 --> 00:40:26,457
PRETTY SURE THOSE ARE

847
00:40:26,457 --> 00:40:29,994
(INAUDIBLE) GET TO CNS.

848
00:40:29,994 --> 00:40:31,229
INITIALLY SHE TOLD ME THAT, I

849
00:40:31,229 --> 00:40:33,164
SAID NO, DON'T DO THAT, IT IS

850
00:40:33,164 --> 00:40:36,501
NOT GOING TO WORK. BUT LIKE MANY

851
00:40:36,501 --> 00:40:37,635
OTHER GOOD POST DOC SHE DIDN'T

852
00:40:37,635 --> 00:40:42,206
LISTEN TO ME. INTRODUCE THE IL

853
00:40:42,206 --> 00:40:45,944
17 SHE SHOWED ME THE BIAS IN IL

854
00:40:45,944 --> 00:40:51,382
17 SAID COME ON SHE WASN'T

855
00:40:51,382 --> 00:40:52,550
DISCOURAGING I (INAUDIBLE) BACK

856
00:40:52,550 --> 00:40:55,520
ON MICE AND IL 17 AND EVEN IN

857
00:40:55,520 --> 00:40:58,690
THE CASE OF (INDISCERNIBLE) IN A

858
00:40:58,690 --> 00:41:01,759
CORE TEST THERE IS INCREASE OF

859
00:41:01,759 --> 00:41:03,127
(INAUDIBLE) IN THE CORTICAL

860
00:41:03,127 --> 00:41:09,834
ASSAY. AND THEN WHAT TYPE OF IN

861
00:41:09,834 --> 00:41:12,537
VITRO, THAT IS JUAN WAY TO MAKE

862
00:41:12,537 --> 00:41:15,173
SOCIAL ABILITY, ANOTHER WAY IS

863
00:41:15,173 --> 00:41:17,575
DOING THE SOCIAL INTERACTION.

864
00:41:17,575 --> 00:41:20,945
PUTTING TUMORS -- MEASURING TIME

865
00:41:20,945 --> 00:41:22,980
SPENT WITH EACH OTHER QUANTIFY

866
00:41:22,980 --> 00:41:25,650
SOCIAL BEHAVIOR PHENOTYPE.

867
00:41:25,650 --> 00:41:27,385
CONTROL MICE GOOD ITERATION, MY

868
00:41:27,385 --> 00:41:31,289
MICE NOT SO GOOD INTERACTION.

869
00:41:31,289 --> 00:41:35,560
THEN WHEN (INDISCERNIBLE) GIVE

870
00:41:35,560 --> 00:41:37,562
INCREASE INTRANASALLY SHE WAS

871
00:41:37,562 --> 00:41:43,234
ABLE TO DETECT INCREASE SOCIAL

872
00:41:43,234 --> 00:41:45,670
-- THIS INCREASE FOUR TO EIGHT

873
00:41:45,670 --> 00:41:48,673
HOURS AND THEN THEY WENT BACK TO

874
00:41:48,673 --> 00:41:51,009
THIS BASELINE. SO NOW FINALLY WE

875
00:41:51,009 --> 00:41:54,379
HAVE A SYSTEM THAT ALLOW US TO

876
00:41:54,379 --> 00:41:56,781
INTRODUCE IL 17 OR INCREASE INTO

877
00:41:56,781 --> 00:41:58,916
THE BRAIN. WHAT DO WE DO NEXT?

878
00:41:58,916 --> 00:42:03,588
SO THEN WE DECIDE TO ASK, OKAY,

879
00:42:03,588 --> 00:42:06,924
HAVING IL 17 THERE, PEOPLE TALK

880
00:42:06,924 --> 00:42:08,793
ABOUT A AN F, MOST CASES BUT YOU

881
00:42:08,793 --> 00:42:12,697
CAN GET THE LITERATURE THEY ARE

882
00:42:12,697 --> 00:42:17,101
LIKE (INAUDIBLE) LIGAND. FIVE

883
00:42:17,101 --> 00:42:20,271
DIFFERENT IL 17 SUB UNIT. EACH

884
00:42:20,271 --> 00:42:24,409
SUB UNIT IN THE FORM MULTI-LAYER

885
00:42:24,409 --> 00:42:25,810
COMPLEX, TWO DIFFERENT SUB UNIT

886
00:42:25,810 --> 00:42:32,550
THE MOST FAMOUS IL 17 IS 17A

887
00:42:32,550 --> 00:42:33,851
COMPLEX INITIAL SIGNAL BUT THERE

888
00:42:33,851 --> 00:42:35,853
ARE MANY OTHER LIGANDS. SO WE

889
00:42:35,853 --> 00:42:39,957
DECIDE TO TEST THEM ALL. WHICH

890
00:42:39,957 --> 00:42:41,859
ASSAY ENHANCE SOCIAL ABILITY? SO

891
00:42:41,859 --> 00:42:44,062
TO MAKE LONG STORY SHORT WE CAN

892
00:42:44,062 --> 00:42:48,599
DETECT IL A, B, F RESCUE SOCIAL

893
00:42:48,599 --> 00:42:50,735
ABILITY DEFICIT.  NOT ONLY SO,

894
00:42:50,735 --> 00:42:56,174
THIS ABEF SOCIAL ABILITY GOES TO

895
00:42:56,174 --> 00:42:58,609
MITIGATE THE BEHAVIOR PHENOTYPE

896
00:42:58,609 --> 00:43:00,912
SO TWO COURSE ALTERNATIVE CAN BE

897
00:43:00,912 --> 00:43:03,414
WITH OR -- ADDITION OF FOUR

898
00:43:03,414 --> 00:43:05,349
DIFFERENT LIGANDS OF BIAS

899
00:43:05,349 --> 00:43:11,656
(INAUDIBLE) SO I JUST TOLD YOU

900
00:43:11,656 --> 00:43:15,126
RESCUE SOCIAL ABILITY STEP ONE,

901
00:43:15,126 --> 00:43:17,562
IF YOU LOOK AT THAT, THEY ARE --

902
00:43:17,562 --> 00:43:19,897
YOU CAN ESSENTIALLY DETECT

903
00:43:19,897 --> 00:43:21,732
DIFFERENT RECEPTOR SUB UNIT, RA

904
00:43:21,732 --> 00:43:25,470
RC AND RB.  SO THEN WE NEXT ASK

905
00:43:25,470 --> 00:43:28,840
WE WANTED TO ASK WHERE ARE THESE

906
00:43:28,840 --> 00:43:31,909
RECEPTORS EXPRESSED IN THE

907
00:43:31,909 --> 00:43:34,178
BRAIN? AS SOME OF YOU MAY KNOW,

908
00:43:34,178 --> 00:43:37,849
THE CYTOKINE EXPRESSION

909
00:43:37,849 --> 00:43:38,850
(INAUDIBLE) SO THERE ARE

910
00:43:38,850 --> 00:43:40,218
ANTIBODIES ARE TERRIBLE. DON'T

911
00:43:40,218 --> 00:43:41,686
BUY THOSE ANTIBODIES.  THEY

912
00:43:41,686 --> 00:43:43,087
DIDN'T WORK. WE BASICALLY TESTED

913
00:43:43,087 --> 00:43:46,958
THEM ALL. SO THEN IF YOU DO

914
00:43:46,958 --> 00:43:49,627
BASICALLY SPATIAL TRANSCRIPTOME,

915
00:43:49,627 --> 00:43:52,296
YOU GET ALL THE INFORMATION YOU

916
00:43:52,296 --> 00:43:57,101
NEED. THERE'S SO MANY TO

917
00:43:57,101 --> 00:43:58,503
INVOLVE, WE COULDN'T GET THE

918
00:43:58,503 --> 00:43:59,637
RESOLUTION WE WANTED TO ACHIEVE

919
00:43:59,637 --> 00:44:02,240
SO WE DECIDE TO THROUGH THE

920
00:44:02,240 --> 00:44:04,675
PANDEMIC WE SAID OKAY, LET'S

921
00:44:04,675 --> 00:44:07,145
MAKE MICE, JUST USE GENETICS TO

922
00:44:07,145 --> 00:44:09,080
IDENTIFY WHERE THEY THEY ARE

923
00:44:09,080 --> 00:44:13,217
LOCATED SO WE BASED GENETICS ON

924
00:44:13,217 --> 00:44:14,418
(INDISCERNIBLE) BY TRANSFERRING

925
00:44:14,418 --> 00:44:17,188
THE CRE DEPENDENTS BIOSAY TO THE

926
00:44:17,188 --> 00:44:19,657
BRAIN WE BASICALLY ARE ABLE TO

927
00:44:19,657 --> 00:44:21,726
MAP OUT AND KNOW WHERE THEY ARE

928
00:44:21,726 --> 00:44:24,595
LOCATED. SO IF YOU ASK WHERE IS

929
00:44:24,595 --> 00:44:29,167
CYTOKINE EXPRESSED, BEFORE WE DO

930
00:44:29,167 --> 00:44:30,768
THIS EXPERIMENT, THE TRUE

931
00:44:30,768 --> 00:44:31,669
GENERAL ANSWER IS I DON'T KNOW

932
00:44:31,669 --> 00:44:35,106
OR EVERYWHERE. WE START TO LOOK

933
00:44:35,106 --> 00:44:37,909
AT THIS, WELL -- THAT IS NOT THE

934
00:44:37,909 --> 00:44:41,379
CASE. EVERY SINGLE BRAIN,

935
00:44:41,379 --> 00:44:42,847
DIFFERENT EXPRESSION PATTERN.

936
00:44:42,847 --> 00:44:47,618
RA, THERE IS A HIGH EXPRESSION

937
00:44:47,618 --> 00:44:49,220
RB SO SOME THROUGHOUT THE CORTEX

938
00:44:49,220 --> 00:44:54,592
BUT RC WHICH IS LIKE RECEPTORS

939
00:44:54,592 --> 00:44:56,594
IN INCH 90%, THIS IS ALL

940
00:44:56,594 --> 00:44:59,430
NEURONS. ONLY WE JUST TESTED

941
00:44:59,430 --> 00:45:01,999
NEURONAL EXPRESSION. AND REA IS

942
00:45:01,999 --> 00:45:04,001
MORE SPARSE. SO WE THOUGHT THAT

943
00:45:04,001 --> 00:45:06,037
BASED ON THIS DATA, I TOLD YOU

944
00:45:06,037 --> 00:45:11,442
THAT RA RB RC RESCUE, TO

945
00:45:11,442 --> 00:45:13,978
SEPARATE PHENOTYPE BASED ON THIS

946
00:45:13,978 --> 00:45:15,112
LIGAND, SPACING. BASED ON THIS

947
00:45:15,112 --> 00:45:17,882
DATA WE KNOW THE CORTICAL AREA

948
00:45:17,882 --> 00:45:19,750
AROUND HERE IS IMPORTANT FOR THE

949
00:45:19,750 --> 00:45:21,752
SOCIAL RESCUE, BASED ON THIS

950
00:45:21,752 --> 00:45:24,589
DATA WE THOUGHT RA AND RD PLAY A

951
00:45:24,589 --> 00:45:27,091
ROLE BUT NOT RC. THEN WE TOOK

952
00:45:27,091 --> 00:45:30,728
GENETIC -- BEFORE THAT WE

953
00:45:30,728 --> 00:45:33,364
SEQUENCE THAT'S WHY IT IS GREEN,

954
00:45:33,364 --> 00:45:35,833
WE PUT THE DIFFERENT EXPRESSION

955
00:45:35,833 --> 00:45:37,201
NEURONS ARE DISTANT SO THEY HAVE

956
00:45:37,201 --> 00:45:41,105
A DIFFERENT PROGRAM. THEN SO

957
00:45:41,105 --> 00:45:43,774
NEXT WE ASK WHAT HAPPENED WHICH

958
00:45:43,774 --> 00:45:47,745
GENETICALLY REMOVING -- COULD RB

959
00:45:47,745 --> 00:45:52,450
RC RA PREVIOUS ISSUE THAT RA IS

960
00:45:52,450 --> 00:45:54,051
CRITICAL. SO WE HAVE TO

961
00:45:54,051 --> 00:45:56,487
(INAUDIBLE) RC USING, THIS IS

962
00:45:56,487 --> 00:46:02,026
THE MOST NEURONAL CELL WHEN YOU

963
00:46:02,026 --> 00:46:05,429
REMOVE 17A AND 17E DEPENDENT

964
00:46:05,429 --> 00:46:07,732
RESCUE WERE NOT AFFECTED. SO

965
00:46:07,732 --> 00:46:10,635
THIS DATA IS RC IS DISPENSABLE

966
00:46:10,635 --> 00:46:14,572
AND AT LEAST FOR THIS SOCIAL

967
00:46:14,572 --> 00:46:16,641
RESCUE. WHAT ABOUT RB, WHEN HE

968
00:46:16,641 --> 00:46:20,344
YOU REMOVE RB LIGAND RESCUE THIS

969
00:46:20,344 --> 00:46:23,914
PHENOTYPE. THIS DATA SUGGESTS

970
00:46:23,914 --> 00:46:27,118
THAT (INAUDIBLE) RA RB PLAY A

971
00:46:27,118 --> 00:46:32,990
CRITICAL ROLE IN RESCUE, THEN WE

972
00:46:32,990 --> 00:46:34,125
GENERATED ANOTHER MOUSE LINE, IN

973
00:46:34,125 --> 00:46:38,229
DOING SO WE ARE ABLE TO IDENTIFY

974
00:46:38,229 --> 00:46:41,432
(INAUDIBLE) RC -- RB AND RA AND

975
00:46:41,432 --> 00:46:45,102
THEN USING RA CRE MICE ANOTHER

976
00:46:45,102 --> 00:46:48,906
MOUSE WE GENERATED WE CAN INDUCE

977
00:46:48,906 --> 00:46:50,641
RB BASED ON DOUBLE POSITIVE

978
00:46:50,641 --> 00:46:54,645
CELLS, THE RB EXPRESSION WE NO

979
00:46:54,645 --> 00:46:57,348
LONGER SEE RESCUE PHENOTYPE

980
00:46:57,348 --> 00:46:58,716
SUGGESTING THAT THESE CELLS THAT

981
00:46:58,716 --> 00:47:00,418
EXPRESS -- THEY NEED TO EXPRESS

982
00:47:00,418 --> 00:47:05,723
BOTH RA AND RB.  TO THIS LIGAND.

983
00:47:05,723 --> 00:47:07,825
AND PRODUCE SOCIAL RESCUE

984
00:47:07,825 --> 00:47:11,028
PHENOTYPE. SO THE QUESTION WE

985
00:47:11,028 --> 00:47:16,167
ARE ASKING SO OKAY RB AND RA ARE

986
00:47:16,167 --> 00:47:18,936
IMPORTANT. BUT HERE WE HAVE A

987
00:47:18,936 --> 00:47:22,173
PROBLEM. I ALREADY TOLD YOU 17A

988
00:47:22,173 --> 00:47:24,842
AND THEN A F E RESCUE THE

989
00:47:24,842 --> 00:47:27,044
PHENOTYPE, RIGHT? CONTAIN THE

990
00:47:27,044 --> 00:47:29,046
SOCIAL ABILITY INDUCE SOCIAL

991
00:47:29,046 --> 00:47:31,816
ABILITY ESTIMATE BUT WE FOUND RB

992
00:47:31,816 --> 00:47:34,151
IS IMPORTANT, NOT RC IMPORTANT

993
00:47:34,151 --> 00:47:35,786
BUT ALL THE DATA OUT THERE

994
00:47:35,786 --> 00:47:39,757
SUGGEST THAT YOU NEED RA AND RC

995
00:47:39,757 --> 00:47:42,493
FOR 17A. SO I TOLD YOU 17A LEADS

996
00:47:42,493 --> 00:47:45,896
TO SOCIAL RESCUE BUT THAT YOU

997
00:47:45,896 --> 00:47:47,832
NEED EXPRESSION OF RC AND

998
00:47:47,832 --> 00:47:49,834
NEURONAL CELL, YOU DON'T NEED RC

999
00:47:49,834 --> 00:47:52,636
-- HOW DOES THIS WORK? HOW DOES

1000
00:47:52,636 --> 00:47:55,172
THE RESCUE BECAUSE RC IS NOT

1001
00:47:55,172 --> 00:47:57,508
REQUIRED? SO WE HIGH BOTH SIZE

1002
00:47:57,508 --> 00:48:02,146
THAT PERHAPS -- HYPOTHESIZE 17A

1003
00:48:02,146 --> 00:48:05,783
FUNCTION BASED ON 17E, BASED ON

1004
00:48:05,783 --> 00:48:07,318
EVERYTHING I TRY TO SHARE WITH

1005
00:48:07,318 --> 00:48:10,221
YOU WE INTRODUCE 17A

1006
00:48:10,221 --> 00:48:14,692
INTRANASALLY AND FOUND THAT 17E

1007
00:48:14,692 --> 00:48:17,027
ADMINISTRATION LEAD TO

1008
00:48:17,027 --> 00:48:20,698
EXPRESSION OF 17E BY mRNA AND

1009
00:48:20,698 --> 00:48:23,200
ALSO PROTEIN AS WELL. SO 17A CAN

1010
00:48:23,200 --> 00:48:27,171
INCREASE IL 17E AND IL 17E CAN

1011
00:48:27,171 --> 00:48:31,041
FUNCTION THROUGH RA RB. SO NEXT

1012
00:48:31,041 --> 00:48:35,479
PERSON, OKAY, IF REALLY THE CASE

1013
00:48:35,479 --> 00:48:40,551
17A CAN MODULATE NEURAL

1014
00:48:40,551 --> 00:48:43,721
ACTIVITY, SO WE DID THE -- WE

1015
00:48:43,721 --> 00:48:46,056
MEASURED THE NEURAL ACTIVITY

1016
00:48:46,056 --> 00:48:49,693
FROM THE BRAIN AREA IMPORTANT

1017
00:48:49,693 --> 00:48:52,863
FOR THIS SOCIAL ABILITY

1018
00:48:52,863 --> 00:48:55,232
PHENOTYPE THEN APPLY 17A

1019
00:48:55,232 --> 00:48:57,902
COMPARED TO -- THIS IS IMMEDIATE

1020
00:48:57,902 --> 00:49:00,204
RESPONSE. WHEN WE ADD 17A OPT

1021
00:49:00,204 --> 00:49:02,873
PETRI DISHES WE MEASURE THIS

1022
00:49:02,873 --> 00:49:06,544
NEURAL ACTIVITY FROM 17RB

1023
00:49:06,544 --> 00:49:08,212
POSITIVE CELL WE CAN SEE IMAGE

1024
00:49:08,212 --> 00:49:10,147
OF THIS NEURAL ACTIVITY, FROM

1025
00:49:10,147 --> 00:49:12,249
POSITION OF 17A SUGGESTING THAT

1026
00:49:12,249 --> 00:49:14,618
17E CAN FUNCTION AS NEURAL

1027
00:49:14,618 --> 00:49:16,153
MODULATOR. IN THIS CASE. SO NEXT

1028
00:49:16,153 --> 00:49:20,057
QUESTION WE ASKED, OKAY, EVEN IF

1029
00:49:20,057 --> 00:49:22,593
THAT IS THE CASE 17A REQUIRES

1030
00:49:22,593 --> 00:49:24,628
17A WE PERFORMED AN EPISTATIC

1031
00:49:24,628 --> 00:49:29,800
EXPERIMENT. SO IN THIS CASE WE

1032
00:49:29,800 --> 00:49:33,537
GENERATED 17A AND THIS

1033
00:49:33,537 --> 00:49:35,873
BACKGROUND WHEN WE GIVE 17A OR E

1034
00:49:35,873 --> 00:49:40,678
WE ARE ABLE TO SEE SOCIAL

1035
00:49:40,678 --> 00:49:42,012
ABILITY PHENOTYPE. HOWEVER THE

1036
00:49:42,012 --> 00:49:46,484
SAME EXPERIMENT WITH 17E ON

1037
00:49:46,484 --> 00:49:48,586
MICE, 17E WHILE CAN ENHANCE

1038
00:49:48,586 --> 00:49:49,720
SOCIAL ABILITY 17 A NO LONGER

1039
00:49:49,720 --> 00:49:51,488
DOES THAT. SO THIS DATA

1040
00:49:51,488 --> 00:49:53,524
SUGGESTING THAT 17E IS

1041
00:49:53,524 --> 00:49:55,459
(INAUDIBLE) TO 17A AND I ALREADY

1042
00:49:55,459 --> 00:49:58,796
TOLD YOU 17A CAN ENHANCE 17E. 

1043
00:49:58,796 --> 00:50:00,798
SO ALL THIS DATA TOGETHER IS

1044
00:50:00,798 --> 00:50:07,004
JUST A MODEL THAT 17A

1045
00:50:07,004 --> 00:50:08,606
POTENTIALLY ACT IN NON-NEURONAL

1046
00:50:08,606 --> 00:50:10,608
CELL WE DON'T KNOW NATURE OF THE

1047
00:50:10,608 --> 00:50:13,444
CELL AND LEAD TO INCREASE 17E

1048
00:50:13,444 --> 00:50:19,183
AND THIS 17E IN -- RECEPTOR A

1049
00:50:19,183 --> 00:50:21,785
AND RECEPTOR B COMPLEX AND IN

1050
00:50:21,785 --> 00:50:24,154
DOING SO BRING DOWN INCREASE

1051
00:50:24,154 --> 00:50:25,756
HYPERNEURAL ACTIVITY BACK TO

1052
00:50:25,756 --> 00:50:28,225
BASELINE, THEN BASICALLY ENHANCE

1053
00:50:28,225 --> 00:50:30,794
SOCIAL ABILITY IN THIS ANIMAL

1054
00:50:30,794 --> 00:50:33,597
MODEL. THEN WE FOUND THAT

1055
00:50:33,597 --> 00:50:37,601
(INAUDIBLE) IL 17A AND E CAN

1056
00:50:37,601 --> 00:50:38,702
ENHANCE SOCIAL ABILITY

1057
00:50:38,702 --> 00:50:40,771
PHENOTYPE, NOT ONLY SO THIS THIS

1058
00:50:40,771 --> 00:50:42,373
CAN BE APPLICABLE TO

1059
00:50:42,373 --> 00:50:44,875
DIFFERENTIATED MOUSE MODEL OF

1060
00:50:44,875 --> 00:50:46,143
AUTISM, NOT JUST -- DIFFERENT

1061
00:50:46,143 --> 00:50:48,879
MOUSE WITH AUTISM, ADDITIONAL

1062
00:50:48,879 --> 00:50:51,181
17A OR E SUFFICIENT TO ENHANCE

1063
00:50:51,181 --> 00:50:53,317
PHENOTYPE. SO I HOPE THAT I WAS

1064
00:50:53,317 --> 00:50:55,619
ABLE TO CONVINCE YOU THAT THIS

1065
00:50:55,619 --> 00:51:00,190
PATHWAY TO REGULATORY MECHANISM

1066
00:51:00,190 --> 00:51:02,826
CYTOKINE OR IN THIS LIGAND HAD

1067
00:51:02,826 --> 00:51:06,397
ABILITY TO CONTROL NEURAL

1068
00:51:06,397 --> 00:51:07,898
ACTIVITY, MAY HAVE MORE ANCIENT

1069
00:51:07,898 --> 00:51:12,303
FUNCTION. SO BASICALLY WE THINK

1070
00:51:12,303 --> 00:51:15,072
AHEAD. WE ARE THINKING ABOUT

1071
00:51:15,072 --> 00:51:16,573
IMMUNOTHERAPY FOR THE DISORDER.

1072
00:51:16,573 --> 00:51:19,777
CAN WE COME UP WITH A WAY TO

1073
00:51:19,777 --> 00:51:23,881
EDUCATE IN CELLS FROM THE GUT IN

1074
00:51:23,881 --> 00:51:26,483
VITRO, CAN WE -- IT IS NOT CLEAR

1075
00:51:26,483 --> 00:51:27,518
WHETHER (INAUDIBLE) CAN

1076
00:51:27,518 --> 00:51:28,852
INFLUENCE CELL BRAIN NEURAL

1077
00:51:28,852 --> 00:51:31,155
ACTIVITY ACTUALLY BUT CAN WE

1078
00:51:31,155 --> 00:51:32,723
UTILIZE THE (INAUDIBLE) CELL AS

1079
00:51:32,723 --> 00:51:36,794
A VEHICLE TO PRODUCE -- TO

1080
00:51:36,794 --> 00:51:38,395
IMPACT NEURAL ACTIVITY IN THE

1081
00:51:38,395 --> 00:51:41,799
BRAIN AND THEN IN DOING SO

1082
00:51:41,799 --> 00:51:45,703
VENOUS CELL CAN ACT AS A SEARCH

1083
00:51:45,703 --> 00:51:51,976
BY ENGAGING IN CYTOKINE RECEPTOR

1084
00:51:51,976 --> 00:51:55,012
ACTIVITY. SO WE THINK THIS

1085
00:51:55,012 --> 00:51:56,313
PATHWAY IS IMMUNE TOE BRAIN

1086
00:51:56,313 --> 00:52:01,852
CIRCUIT IS REALLY IMPORTANT AND

1087
00:52:01,852 --> 00:52:05,122
I HOPE I'M SURE GLORIA WILL

1088
00:52:05,122 --> 00:52:06,824
SHARE WITH YOU SOME OTHER DATA

1089
00:52:06,824 --> 00:52:11,996
FOCUSED ON DIFFERENT CYTOKINE

1090
00:52:11,996 --> 00:52:17,301
RECEPTORS, TO ATEN THE TALK. SO

1091
00:52:17,301 --> 00:52:21,905
BASICALLY SUMMARY. I HAVE

1092
00:52:21,905 --> 00:52:24,108
(INAUDIBLE) CYTOKINE MODULATED

1093
00:52:24,108 --> 00:52:26,176
BY NEURAL ACTIVITY. WE IDENTIFY

1094
00:52:26,176 --> 00:52:27,611
POTENTIAL LIGANDS THAT HAVE SUCH

1095
00:52:27,611 --> 00:52:29,647
ACTIVITY, WE MAP OUT THE BRAIN

1096
00:52:29,647 --> 00:52:32,316
AREA, THAT EXPRESS DIFFERENT

1097
00:52:32,316 --> 00:52:34,184
RECEPTOR SUB UNIT AND THEN WE

1098
00:52:34,184 --> 00:52:37,488
ARE ABLE TO SHOW GENETICALLY WE

1099
00:52:37,488 --> 00:52:38,822
CHALLENGE RECEPTOR TO PLAY A

1100
00:52:38,822 --> 00:52:40,591
ROLE IN MODULATING THE SOCIAL

1101
00:52:40,591 --> 00:52:45,429
ABILITY OF PHENOTYPE. 

1102
00:52:45,429 --> 00:52:47,297
SOCIOIBILITY OF PHENOTYPE. THIS

1103
00:52:47,297 --> 00:52:49,667
WORK ESSENTIALLY IS DONE BY --

1104
00:52:49,667 --> 00:52:51,602
THROUGH COLLABORATION BY

1105
00:52:51,602 --> 00:52:56,874
(INAUDIBLE) IN MY LAB AND --

1106
00:52:56,874 --> 00:52:59,043
PUBLISHED THE WORK I SHOW YOU,

1107
00:52:59,043 --> 00:53:01,779
THIS IS PEOPLE I WANT TO END, MY

1108
00:53:01,779 --> 00:53:04,314
FUNDING SOURCES.  THANK YOU VERY

1109
00:53:04,314 --> 00:53:06,216
MUCH FOR YOUR ATTENTION. HAPPY

1110
00:53:06,216 --> 00:53:11,388
TO TAKE ANY QUESTIONS.

1111
00:53:11,388 --> 00:53:12,389
>> THANK YOU VERY MUCH,
THAT WAS

1112
00:53:12,389 --> 00:53:14,525
REALLY A LOVELY TALK. I DIDN'T

1113
00:53:14,525 --> 00:53:17,127
KNOW THAT IL 17 IS A HAPPY HOUR

1114
00:53:17,127 --> 00:53:23,667
CYTOKINE. BUT I THINK TIME FOR

1115
00:53:23,667 --> 00:53:23,934
QUESTIONS.

1116
00:53:23,934 --> 00:53:26,537
>> VERY NICE TALK.  THANK
YOU. I

1117
00:53:26,537 --> 00:53:28,972
WAS WONDERING MAYBE I MISSED

1118
00:53:28,972 --> 00:53:31,275
THIS POINT. WHICH SOURCE OR

1119
00:53:31,275 --> 00:53:34,378
WHICH SOURCES MIGHT BE FOR IL

1120
00:53:34,378 --> 00:53:36,713
17E? BECAUSE IF I REMEMBER

1121
00:53:36,713 --> 00:53:38,382
CORRECTLY, I'M MAINLY FOCUSING

1122
00:53:38,382 --> 00:53:43,420
ON THE SKIN AND THERE IT IS NOT

1123
00:53:43,420 --> 00:53:43,887
HEMATOPOIETIC CELLS.

1124
00:53:43,887 --> 00:53:47,124
>> I DIDN'T CARRY THAT BUT

1125
00:53:47,124 --> 00:53:49,159
NEURONAL CELL AND NON-NEURONAL

1126
00:53:49,159 --> 00:53:50,594
CELLS PRODUCE, THEY ARE

1127
00:53:50,594 --> 00:53:52,796
PRODUCING IL 17E IN THE BRAIN

1128
00:53:52,796 --> 00:53:56,667
EVEN AT STEADY STATE AND UPON

1129
00:53:56,667 --> 00:53:56,967
(INAUDIBLE)

1130
00:53:56,967 --> 00:53:59,236
>> THANK YOU.

1131
00:53:59,236 --> 00:54:01,205
>> GREAT TALK. THAT WAS
REALLY

1132
00:54:01,205 --> 00:54:04,575
-- SO IN YOUR AUTISM MODELS, DO

1133
00:54:04,575 --> 00:54:07,878
WE SEE DECREASING IL 17A OR

1134
00:54:07,878 --> 00:54:10,280
EXPRESSION FOR RECEPTORS AND ANY

1135
00:54:10,280 --> 00:54:11,548
IDEA HOW IT CAN BE RELATED?

1136
00:54:11,548 --> 00:54:14,952
>> IT IS COMPLICATED
OBVIOUSLY.

1137
00:54:14,952 --> 00:54:16,987
IL 17 AS MENTIONED I DIDN'T TALK

1138
00:54:16,987 --> 00:54:19,590
ABOUT THAT EARLIER WORK BUT IL

1139
00:54:19,590 --> 00:54:21,792
17 IN THE MODEL DURING PREGNANCY

1140
00:54:21,792 --> 00:54:24,995
CAN PROMOTE PHENOTYPE IN THE

1141
00:54:24,995 --> 00:54:27,331
OFFSPRING. THEN THAT IS LIKE A

1142
00:54:27,331 --> 00:54:28,966
STRESS PATHWAY WE SHOW THAT IT

1143
00:54:28,966 --> 00:54:35,539
IS ENGAGE INDUCE UPR PATHWAY, SO

1144
00:54:35,539 --> 00:54:39,176
GETTING BACK TO YOUR QUESTION,

1145
00:54:39,176 --> 00:54:42,546
YEAH, I (INAUDIBLE) THE QUESTION

1146
00:54:42,546 --> 00:54:45,082
WHETHER LIGANDS PLAY -- HAVE A

1147
00:54:45,082 --> 00:54:48,919
PHYSIOLOGICAL FUNCTION TO

1148
00:54:48,919 --> 00:54:50,387
MODULATE SOCIABILITY. I WAS ABLE

1149
00:54:50,387 --> 00:54:53,290
TO CONVINCE (INAUDIBLE) TO

1150
00:54:53,290 --> 00:54:56,260
GENERATE KNOCK ON MICE, REMOVE

1151
00:54:56,260 --> 00:55:00,097
ALL LIGAND. SO CAN WE SHOW THAT

1152
00:55:00,097 --> 00:55:04,434
A, B, E, PLAY A ROLE AND MOVE

1153
00:55:04,434 --> 00:55:07,304
ONLY ONE LIGAND SUFFICIENT TO

1154
00:55:07,304 --> 00:55:09,339
INDUCE THE PHENOTYPE, BASED ON

1155
00:55:09,339 --> 00:55:10,741
(INAUDIBLE) DATA WE MAY HAVE TO

1156
00:55:10,741 --> 00:55:14,011
SEE SOME EFFECT SO SHE IS DOING

1157
00:55:14,011 --> 00:55:15,479
MOUSE CROSS -- BUT IT IS MANY

1158
00:55:15,479 --> 00:55:16,480
THAT DIFFICULT BECAUSE A AND F

1159
00:55:16,480 --> 00:55:19,716
ARE MANY THE SAME LOCI SO IT IS

1160
00:55:19,716 --> 00:55:20,984
A TRUE KNOCK OUT.  HOPEFULLY I

1161
00:55:20,984 --> 00:55:23,854
DON'T KNOW BUT I'M JUST -- MY

1162
00:55:23,854 --> 00:55:25,122
GUESS IS MAYBE SEE SOME

1163
00:55:25,122 --> 00:55:26,557
PHENOTYPE THERE. HAPPY TO TALK

1164
00:55:26,557 --> 00:55:27,257
WITH YOU MORE ABOUT THAT.

1165
00:55:27,257 --> 00:55:30,961
>> THANK YOU. 

1166
00:55:30,961 --> 00:55:34,097
>> VERY INTERESTING TALK.
SO MY

1167
00:55:34,097 --> 00:55:36,767
QUESTION IS I'M THINKING THE

1168
00:55:36,767 --> 00:55:38,569
MECHANISM TO HOW INTERLEUKIN 17

1169
00:55:38,569 --> 00:55:42,139
IS GOING TO INCREASE THE

1170
00:55:42,139 --> 00:55:43,507
SOCIOIBILITY RATE. DO YOU KNOW

1171
00:55:43,507 --> 00:55:46,877
BY CHANCE WHEN YOU KNOCK OUT IL

1172
00:55:46,877 --> 00:55:49,012
17 OR RECEPTOR, THERE HAVE BEEN

1173
00:55:49,012 --> 00:55:52,249
SOME CHANGES IN THE TRANSMISSION

1174
00:55:52,249 --> 00:55:54,318
ACTIVITY? SOME CHANGES IN THE

1175
00:55:54,318 --> 00:55:56,420
NEURAL TRANSMISSION ACTIVITY

1176
00:55:56,420 --> 00:55:59,156
LIKE SOME NEURONS ESPECIALLY FOR

1177
00:55:59,156 --> 00:56:01,525
EXAMPLE SEROTONIN LEVELS SOME

1178
00:56:01,525 --> 00:56:03,861
PEOPLE THEY THINK SEROTONIN

1179
00:56:03,861 --> 00:56:09,933
LEVELS THAT WHEN THEY BECOME

1180
00:56:09,933 --> 00:56:11,001
KNOCK DOWN (INAUDIBLE) ANY OTHER

1181
00:56:11,001 --> 00:56:14,104
STUFF. AND I WAS WONDERING IL 17

1182
00:56:14,104 --> 00:56:15,806
THAT ALSO WHEN YOU INCREASE IL

1183
00:56:15,806 --> 00:56:17,874
17 THAT ALSO INCREASE OR CHANGE

1184
00:56:17,874 --> 00:56:20,911
THE LEVELS INTO THE SEROTONIN

1185
00:56:20,911 --> 00:56:22,980
ACTIVITY OR RECEPTORS OF

1186
00:56:22,980 --> 00:56:25,682
SEROTONIN CHANGED IN YOUR MODEL,

1187
00:56:25,682 --> 00:56:27,117
HOW THESE HAS BEEN CHANGED.

1188
00:56:27,117 --> 00:56:31,221
>> YEAH. SO WE THINK IL 17
A AND

1189
00:56:31,221 --> 00:56:33,523
E FUNCTION AS NEURAL MODULATOR

1190
00:56:33,523 --> 00:56:36,727
AND THEN AS TO -- VERY IMPORTANT

1191
00:56:36,727 --> 00:56:38,862
HOW THIS NEURAL MODULATOR WORK

1192
00:56:38,862 --> 00:56:42,899
BY INFLUENCING NEURAL TRANSM

1193
00:56:42,899 --> 00:56:44,268
TRANSMITTER IT IS NOT WELL UN.

1194
00:56:44,268 --> 00:56:48,939
SO WE DON'T KNOW BUT IF YOU -- I

1195
00:56:48,939 --> 00:56:52,843
OFTEN USE THIS (INAUDIBLE)

1196
00:56:52,843 --> 00:56:56,280
OXYTOCIN AS AN EXAMPLE, THOUGH

1197
00:56:56,280 --> 00:56:57,848
OXYTOCIN HAS BEEN STUDIED MANY,

1198
00:56:57,848 --> 00:57:02,486
MANY YEARS, THEY ARE -- CRITICAL

1199
00:57:02,486 --> 00:57:04,054
NEURAL MODULATOR BUT HOW THEY

1200
00:57:04,054 --> 00:57:07,057
WORK IS STILL NOT CLEAR SO TELL

1201
00:57:07,057 --> 00:57:08,692
YOU THAT UNDERSTANDING THE

1202
00:57:08,692 --> 00:57:10,594
MOLECULAR MECHANISM BY WHICH

1203
00:57:10,594 --> 00:57:11,595
NEURAL MODULATOR WORKS.

1204
00:57:11,595 --> 00:57:13,964
>> THEY DIDN'T CHECK THE
LEVELS

1205
00:57:13,964 --> 00:57:16,833
IN THE KNOCK OUT MODELS? YOU

1206
00:57:16,833 --> 00:57:18,935
MENTION SOMETHING ABOUT THE

1207
00:57:18,935 --> 00:57:20,671
ACTUAL POTENTIAL HOW THAT IS

1208
00:57:20,671 --> 00:57:22,205
IMPROVED SO THAT TELL YOU HOW

1209
00:57:22,205 --> 00:57:25,542
MANY (INAUDIBLE) IS GOING ON.

1210
00:57:25,542 --> 00:57:30,814
>> COULD BE -- SO MANY, SO
MANY

1211
00:57:30,814 --> 00:57:31,882
CANDIDATES WE HAVEN'T CHECKED

1212
00:57:31,882 --> 00:57:32,082
THEM.

1213
00:57:32,082 --> 00:57:33,317
>> THANK YOU.

1214
00:57:33,317 --> 00:57:34,518
>> THANK YOU VERY MUCH FOR
THE

1215
00:57:34,518 --> 00:57:39,923
INTERESTING TALK. SO I HAVE A

1216
00:57:39,923 --> 00:57:42,159
QUESTION, THE SMALL MOLECULE

1217
00:57:42,159 --> 00:57:46,029
IDENTIFY FOR INHIBITING R GAMMA

1218
00:57:46,029 --> 00:57:48,532
P FUNCTION. R GAMMA P IS NOT THE

1219
00:57:48,532 --> 00:57:50,167
ONLY PH 17 SO I HAVE TWO

1220
00:57:50,167 --> 00:57:54,404
QUESTIONS BUT BASED ON THIS. THE

1221
00:57:54,404 --> 00:57:58,642
FIRST ONE IS (INAUDIBLE) LIKE RC

1222
00:57:58,642 --> 00:58:01,611
3 IL 17 IS ALSO INHIBITED AND

1223
00:58:01,611 --> 00:58:05,716
THE SECOND ONE IS R GAMMA T IS

1224
00:58:05,716 --> 00:58:09,619
ALSO EXPRESSED IN (INAUDIBLE)

1225
00:58:09,619 --> 00:58:12,122
FOR SURVIVAL OF THE CELLS SO

1226
00:58:12,122 --> 00:58:14,458
WONDERING IF YOU GIVE MORE

1227
00:58:14,458 --> 00:58:19,363
INHIBITOR MOLECULAR IF CYTOKINE

1228
00:58:19,363 --> 00:58:21,264
ALSO AFFECTED?

1229
00:58:21,264 --> 00:58:25,402
>> HAVING THE SYSTEM
OURSELVES

1230
00:58:25,402 --> 00:58:27,437
PREVIOUSLY SHOW R GAMMA

1231
00:58:27,437 --> 00:58:31,108
INHIBITOR CAN ALSO SUPPRESS ILC

1232
00:58:31,108 --> 00:58:33,643
3 FUNCTION AND THEN MANY

1233
00:58:33,643 --> 00:58:36,646
(INAUDIBLE) STARTED A CLINICAL

1234
00:58:36,646 --> 00:58:38,949
TRIAL WITH INHIBITOR AND THEY

1235
00:58:38,949 --> 00:58:41,485
STOPPED THE TRIAL BECAUSE OF THE

1236
00:58:41,485 --> 00:58:43,653
DEVELOPMENT OF MELANOMA, ABOUT

1237
00:58:43,653 --> 00:58:45,956
DOUBLE IN -- THAT HAPPEN DURING

1238
00:58:45,956 --> 00:58:48,658
THE TIME SITE DEVELOPMENT SO FOR

1239
00:58:48,658 --> 00:58:51,027
R GAMMA INHIBITOR, POST DOC

1240
00:58:51,027 --> 00:58:53,497
APPOINTED CELL IN ILC 3 SEEM TO

1241
00:58:53,497 --> 00:58:56,867
BE AFFECTED BUT WHETHER OR NOT

1242
00:58:56,867 --> 00:58:58,368
THE BIAS (INAUDIBLE) INFLUENCE

1243
00:58:58,368 --> 00:58:59,503
THE SAME WE HAVEN'T TESTED THAT.

1244
00:58:59,503 --> 00:59:01,805
>> THANK YOU.

1245
00:59:01,805 --> 00:59:06,042
>> HI. SO AUTISM IS
CORRELATED

1246
00:59:06,042 --> 00:59:09,813
WITH A NUMBER OF AUTOIMMUNE AND

1247
00:59:09,813 --> 00:59:11,715
ALLERGIC DISEASE INCLUDING

1248
00:59:11,715 --> 00:59:13,817
PSORIASIS WHICH IS 17 MEDIATED.

1249
00:59:13,817 --> 00:59:15,685
I'M WONDERING YOUR THOUGHTS ONE

1250
00:59:15,685 --> 00:59:17,621
ON POSSIBLE CAUSATION IN TERMS

1251
00:59:17,621 --> 00:59:19,289
OF WHY THESE MIGHT COME TOGETHER

1252
00:59:19,289 --> 00:59:21,658
BUT ALSO THIS MIGHT LIMIT

1253
00:59:21,658 --> 00:59:23,360
UTILITY OF THIS AS THERAPEUTIC.

1254
00:59:23,360 --> 00:59:26,329
IF YOU HAVE PEOPLE ALREADY

1255
00:59:26,329 --> 00:59:28,665
EXCESSIVE 17 PATHWAY.

1256
00:59:28,665 --> 00:59:31,635
>> RIGHT. I THINK
PARTICULARLY

1257
00:59:31,635 --> 00:59:34,738
DURING PREGNANCY, ALLERGIC

1258
00:59:34,738 --> 00:59:36,006
RESPONSE THERE IS A PAPER

1259
00:59:36,006 --> 00:59:38,341
SHOWING THAT'S SOME CORRELATION

1260
00:59:38,341 --> 00:59:41,111
AND THEN SOME PSORIATIC PATIENT

1261
00:59:41,111 --> 00:59:43,246
HAVE DEVELOPED AWE TIM SYMPTOMS

1262
00:59:43,246 --> 00:59:45,248
SO WHETHER OR NOT -- SO WE DON'T

1263
00:59:45,248 --> 00:59:46,516
KNOW, SHORT ANSWER WE DON'T KNOW

1264
00:59:46,516 --> 00:59:48,952
BUT IN TERMS THERAPEUTICS,

1265
00:59:48,952 --> 00:59:50,120
(INAUDIBLE) INDICATED AND OTHERS

1266
00:59:50,120 --> 00:59:54,491
SHOW THAT INCREASE IL 17 ALONE

1267
00:59:54,491 --> 00:59:56,159
IS NOT -- NOT REALLY

1268
00:59:56,159 --> 00:59:59,129
INFLAMMATORY. NOT INFLAMMATORY.

1269
00:59:59,129 --> 01:00:01,364
WHEN I PRESENT WAY OTHER

1270
01:00:01,364 --> 01:00:02,899
CYTOKINES INTERFERON GAMMA

1271
01:00:02,899 --> 01:00:06,536
(INAUDIBLE) INFLAMMATION. SO I

1272
01:00:06,536 --> 01:00:10,040
THINK YOUR QUESTION THERE ARE

1273
01:00:10,040 --> 01:00:13,176
(INAUDIBLE) FIRST I DON'T KNOW,

1274
01:00:13,176 --> 01:00:14,744
SECOND MAYBE.

1275
01:00:14,744 --> 01:00:15,378
>> THANK YOU.

1276
01:00:15,378 --> 01:00:20,417
>> THAT WAS A GREAT TALK.
SO THE

1277
01:00:20,417 --> 01:00:23,854
IL 17 IN RESPONSE TO INFECTION

1278
01:00:23,854 --> 01:00:26,456
OR PRESUMABLY THAT'S PERIPHERAL

1279
01:00:26,456 --> 01:00:27,724
IL 17. THAT HAS TO GO INTO THE

1280
01:00:27,724 --> 01:00:32,062
BRAIN. DOES THAT PASS THROUGH

1281
01:00:32,062 --> 01:00:33,663
BLOOD BRAIN BARRIER EASILY?

1282
01:00:33,663 --> 01:00:37,634
>> WHEN THE CYTOKINES GET

1283
01:00:37,634 --> 01:00:40,837
INDUCED IN THE CONTEXT OF

1284
01:00:40,837 --> 01:00:43,673
INFLAMMATION, THIS IS LIKE ONE

1285
01:00:43,673 --> 01:00:45,742
THING THAT FIELD PEOPLE NOTICE

1286
01:00:45,742 --> 01:00:48,678
FOR MANY, MANY YEARS BUT STILL

1287
01:00:48,678 --> 01:00:50,514
IS NOT CLEAR NOBODY UNDERSTAND

1288
01:00:50,514 --> 01:00:53,083
MOLECULAR MECHANISM WHICH IS

1289
01:00:53,083 --> 01:00:55,919
WHEN YOU GIVE MICE WITH APS

1290
01:00:55,919 --> 01:00:57,854
EXPOSE MICE WITH VIRAL INFECTION

1291
01:00:57,854 --> 01:01:00,957
THERE IS TEMPORALLY INCREASE

1292
01:01:00,957 --> 01:01:03,326
PERMEABILITY IN THE BBB. SO YOU

1293
01:01:03,326 --> 01:01:06,696
ARE INDUCING INFLAMMATION, GIVE

1294
01:01:06,696 --> 01:01:09,332
SOME TIME THEN YOUR BRAIN MOUSE

1295
01:01:09,332 --> 01:01:14,104
BRAIN IS TURN BLUE. SO THIS

1296
01:01:14,104 --> 01:01:15,105
INFLAMMATION HAS AN AMAZING

1297
01:01:15,105 --> 01:01:17,707
ABILITY TO INCREASE

1298
01:01:17,707 --> 01:01:19,342
PERMEABILITY. THAT IS A GOOD

1299
01:01:19,342 --> 01:01:22,546
REASON FOR THAT. BECAUSE THAT IS

1300
01:01:22,546 --> 01:01:26,883
WHAT THAT NEED TO HAPPEN DURING

1301
01:01:26,883 --> 01:01:29,185
INFLAMMATION WHEN INUNDATED BY

1302
01:01:29,185 --> 01:01:31,755
INFECTION. SO IN THAT CONTEXT,

1303
01:01:31,755 --> 01:01:35,625
INFLAMMATORY CONTEXT I

1304
01:01:35,625 --> 01:01:36,526
ABSOLUTELY (INAUDIBLE) IN THE

1305
01:01:36,526 --> 01:01:37,093
BRAIN MECHANISM.

1306
01:01:37,093 --> 01:01:40,830
>> LAST QUESTION. THANK
YOU FOR

1307
01:01:40,830 --> 01:01:42,599
THAT TALK.  THAT WAS AWESOME. SO

1308
01:01:42,599 --> 01:01:44,601
I JUST HAD A QUESTION ON THE

1309
01:01:44,601 --> 01:01:45,602
MATERNAL IMMUNE ACTIVATION

1310
01:01:45,602 --> 01:01:48,104
MODEL.  WHEN YOU CHALLENGE WITH

1311
01:01:48,104 --> 01:01:50,340
POLYIC AND THEN LATER SEE AUTISM

1312
01:01:50,340 --> 01:01:52,008
PHENOTYPE MANY THE OFFSPRING, DO

1313
01:01:52,008 --> 01:01:53,577
YOU THINK THERE'S ANY

1314
01:01:53,577 --> 01:01:54,978
COMMONALITY TO THE ANTIGEN

1315
01:01:54,978 --> 01:01:57,013
RESTRICTION TO THE TH 17 CELLS

1316
01:01:57,013 --> 01:01:59,616
GENERATED IN THE OFFSPRING?

1317
01:01:59,616 --> 01:02:01,518
PERHAPS LIKE TWO POLYIC BECAUSE

1318
01:02:01,518 --> 01:02:03,954
I KNOW REACH TOUT LPSO, ANY

1319
01:02:03,954 --> 01:02:05,255
CORRELATION FOR THE ANTIGEN

1320
01:02:05,255 --> 01:02:08,158
RESEARCH OF THOSE T-CELLS?

1321
01:02:08,158 --> 01:02:14,965
>> WE DON'T KNOW. SO I
MEAN, WE

1322
01:02:14,965 --> 01:02:19,636
CAN INDUCE SIMILAR PHENOTYPE BY

1323
01:02:19,636 --> 01:02:21,538
TRANSPORTING T-CELL MICE DURING

1324
01:02:21,538 --> 01:02:28,044
PREGNANCY.  SO TCL NOT

1325
01:02:28,044 --> 01:02:28,979
NECESSARILY (INAUDIBLE) BUT

1326
01:02:28,979 --> 01:02:32,182
WHETHER -- WE ALSO DETECT --

1327
01:02:32,182 --> 01:02:36,920
OFFSPRING SIDE THERE ARE SECOND

1328
01:02:36,920 --> 01:02:40,123
CHALLENGE IT BUT WHETHER OR NOT

1329
01:02:40,123 --> 01:02:43,460
THIS -- CHANGE IN TISSUE THAT

1330
01:02:43,460 --> 01:02:47,564
PUTS FORWARD -- AND THIS ISSUE

1331
01:02:47,564 --> 01:02:48,865
DIFFERENCE IMMUNE (INAUDIBLE)

1332
01:02:48,865 --> 01:02:52,669
DURING PREGNANCY CAN INDUCE

1333
01:02:52,669 --> 01:02:53,203
CHANGES IN OFF SPRIEST MT.

1334
01:02:53,203 --> 01:02:55,138
SYSTEM. SO I THINK DOSE

1335
01:02:55,138 --> 01:02:58,208
DEPENDENT ON PATHOGEN, LIKE

1336
01:02:58,208 --> 01:03:01,911
ANTIGENS, IT  IT IS NOT --

1337
01:03:01,911 --> 01:03:05,281
>> THANK YOU VERY MUCH. SO
I SAW

1338
01:03:05,281 --> 01:03:08,051
THAT STORY GOT PRESENTED AS

1339
01:03:08,051 --> 01:03:10,487
SUBMITTED SO MAYBE WE CAN SEND

1340
01:03:10,487 --> 01:03:13,089
SOME FLOWERS FOR IL 17,

1341
01:03:13,089 --> 01:03:14,891
CHOCOLATE COATED WITH IL 17.

1342
01:03:14,891 --> 01:03:17,027
GOOD LUCK WITH YOUR STORY. THANK

1343
01:03:17,027 --> 01:03:18,762
YOU, EVERYONE FOR COMIN COMING 

1344
01:03:18,762 --> 01:03:28,938
[APPLAUSE]