>>I'M SUSAN WEISS AND
HERE TODAY SERVING AT THE
DESIGNATED FEDERAL OFFICIAL FOR
THE BRAIN MULTICOUNCIL WORKING
GROUP AND WANT TO WELCOME YOU TO
THE 25TH MEETING OF THE WORKING
GROUP. AS ALWAYS THANK YOU
FOR YOUR TIME AND CONTRIBUTIONS
TO THE EFFORT AND MEETING TODAY
BEGINS WITH THE OPEN SESSION
THAT IS BEING VIDEOCAST AND
RECORDED AND WILL BE ARCHIVED ON
NI HMENT AND BRAIN WEBSITES AND
WE HAVE A NEW ATTENDEE TODAY.
ALEXIS WHO IS A REPRESENTATIVE
TODAY THAT HAS A BACKGROUND IN
NEUROSCIENCE AND WILL BE THE
LAST MEETING FOR DAVID WHO HAS
BEEN SERVING IN NATIONAL
INSTITUTE ON AGING
REPRESENTATIVE AND WE ARE
GRATEFUL TO HIM FOR HIS
COMMITMENT AND CONTRIBUTION TO
BRANL AND JOHN WILL THANK HIM IN
THE PRESENTATION IN A FEW
MINUTES AND UPDATE FOR BRAIN
DIRECTOR AND I AND FOLLOWED BY
HIGHLIGHTS ON NEUROETHICS
WORKING GROUP AND HAPPY TO HAVE
DR. HUGO WHO WILL DO A
PRESENTATION ON HIS WORK ON
ENGINEERING FLIES TO STUDY GENE
PROTEIN FUNCTION AND MOST KNOW
THAT THE MULTICOUNCIL WORKING
GROUP IS NOT A FORMAL ADVISORY
GROUP ABOUT YOU WAS ESTABLISHED
BECAUSE OF THE RECOGNIZED NEED
FOR DIVERSE EXPERTISE IN VARIOUS
DISCIPLINES TO PROPERLY ASSESS
RESEARCH BEING SUPPORTED THROUGH
BRAIN. SOME MEMBERS ARE FROM
ADVISORY COUNCILS FROM 10
PARTICIPATING INSTITUTES AND
CENTERS WITH ADDITIONAL AT LARGE
MEMBERS APPOINTED TO SUPPLEMENT
THE WORKING GROUP'S EXPERTISE
AND WE HAD SEVERAL EXOFISH YOEF
MEMBERS FROM DARPA, FDA, ARPA
AND NSF AND FEDERAL PARTNERS
INVOLVED IN THE BRAIN INITIATIVE
AND DEPEND ON THE MULTICOUNCIL
WORKING GROUP FOR ONGOING
OVERSIGHT AND SCIENTIFIC VISION
AND PROGRESS FOR FEEDBACK AND
CONCEPT FOR CLEARANCES -- AND
DURING CLOSED SESSION FOR INPUT
ON FUNDING PLANS AND GOING TO
CLOSED SESSIONALLY GO OVER
OPERATING PROCEDURES THAT L-
BEGIN 30 MINUTES AFTER CLOSE OF
OPEN SESSION AROUND 2:15 P.M..
NOTE A DIFFERENT ZOOM LINK FOR
THE SESSION FOR MEMBERS OF
COUNCIL AND GOVERNMENT EMPLOYEES
ONLY AND REMINDER THAT THE OPEN
SESSION IS BEING VIDEOCAST AND
RECORDED AND A FEW HOUSEKEEPING
ITEMS DURING THE PRESENTATIONS
WE ASKED YOU TO PLEASE MUTE YOUR
LINE AND DURING DISCUSSIONS WE
WOULD LIKE YOU TO MAKE SURE YOUR
VIDEO IS ON. PLEASE USE THE
RAISE HAND OPTION IF YOU HAVE
QUESTIONS AND WE WILL CALL ON
YOU TO UNMUTE YOURSELF ONCE
AGAIN, THANKING ALL OF THE STAFF
WHOSE HARD WORK WENT INTO
PREPARING FOR THIS MEETING.
KRISTEN AND NINA AND DEB AND
MICHELLE PIERSON. I'M VERY
GRATEFUL TO THEM AS I'M SURE ALL
WHO HAVE INTERACTED WITH THEM
WILL AGREE THEY ARE OUTSTANDING
COLLEAGUES AND IS A PRIVILEGE TO
WORK WITH THEM. I COULDN'T DO
WHAT I'M DOING WITHOUT THEIR
HELP AHEAD OF TIME AND DURING
THE MEETING IF ANYONE HAS
TECHNICAL PROBLEMS PUTTING IN
THE CHAT WHO TO CONTACT TO GET
HELP WITH THAT. CLOSED SESSION
WILL BE FROM 2:15 TO 5 AND GOING
TO TURN IT OVER TO JOHN FOR HIS
INTRODUCTION.
THANK YOU.
>> THANK YOU, SUSAN. ECHOING
SUSAN'S THANKS TO ALL OF THE
STAFF THAT MAKE THE MEETINGS NOT
ONLY POSSIBLE BUT INFORMATIVE
AND WELL-ORGANIZED.
THANK YOU ALL TO THE STAFF WHO
HAVE BEEN INVOLVED AND SUSAN
MENTIONED IT ALREADY.
LET'S SEE. I HAVE AN UPDATE. I
WILL TRY TO BE BRIEF TO LEAVE
TIME FOR DISCUSSION AND HAVE AN
HOUR SET ASIDE FOR THIS. UNLESS
I GET DISTRACTED I WON'T TAKE UP
THE ENTIRE HIRE. LET'S SEE.
ARE YOU SEEING WHAT LOOKS TO BE
THE PROPER SCREEN?
>> YES.
>> COOL. UPDATE WHAT IS GOING
ON SINCE LAST TIME WE MET BACK
IN JANUARY. AS SUSAN MENTIONED,
DAVE HOLTSMAN IS LEADING THIS
AND FOR THE NATIONAL INSTITUTE
ON AGING. DAVE, THANK SO YOU
MUCH. YOU GAVE SO MUCH SERVICE
TO NIA AND.
>> THANK YOU VERY MUCH, JOHN.
IT HAS BEEN A PLEASURE WORKING
WITH THE BRAIN INITIATIVE IN THE
LAST FEW YEARS.
>> PLEASURE IS MINE AND WITH A
FEW MEMBERS I LEARN A LOT FROM
YOU AND ALL YOU GIVE. THANKS
AGAIN.
QUICK NOTE ON STAFFING. WE HAD
A FEW CHANGES IN THE IMMEDIATE
OFFICE OF THE BRAIN DIRECTOR JOE
BRINGS EXPERTISE IN
COMPUTATIONAL NEUROSCIENCE AND
ADVISING ME IN OTHER AREAS DATA
SCIENCE AND INFORMATICS AND
WELCOMING SANDRA WHO TOOK OVER
PROGRAM ANALYST AND OPERATION
AND YOU SEE A COPY AND WILL HEAR
FROM HER IF I NEED TO FIND YOU
OR YOU ME WE HAVE A NEW TEAM
LEAD, SUSAN WHO LEADS THE
DEFINITION OF NEUROSCIENCE AND
BEHAVIOR AND IS WORKING CLOSELY
WITH OFFICE OF DATA SCIENCE
STRATEGY ACROSS NIH FOR
IMPLEMENTATION OF NIH STRATEGIC
PLAN FOR DATA SCIENCE. SHE HAS
BEEN QUITE INVOLVED IF IN BRAIN
AS WELL AS OTHER TRANS-NIH
INITIATIVES AND ARE DELIGHTED
SHE HAS AGREED TO TAKE ON THE
ROLE TO CO-LEAD TEAM DATA WITH
DR. MING JOHN AND 9 BRAIN
SCIENTIFIC TEAMS ARE HERE THAT
OVERSEE THE PORTFOLIO AND
SUSAN'S NAME IS HIGHLIGHTED
UNDER TEAM DATA AND NONE OF ANY
OF WHAT WE DO WOULD BE POSSIBLE
WITHOUT HUMONGOUS EFFORT OF WELL
OVER 100 OR 130 STAFF WORKING
ACROSS NIH AND AMONG 10ICS AND
ODS.
THEY ARE ALL LISTED HERE AND SEE
A DUPLICATION AND INEVITABLY
SOMEONE WILL E-MAIL ME LATER AND
SAY YOU MISSED ME AND IF TRUE
LET US KNOW. I APOLOGIZE AND UP
TO DATE LIST OF FOLKS WORKING ON
THIS AND THANKS FOR ALL YOU DO
AND CAN'T SAY ENOUGH AND QUICK
UPDATE WHERE WE ARE BUDGETWISE
FOR CURRENT FISCAL YEAR WE WORK
FOR A BUDGET OF $680 MILLION AND
AGAIN YOU CAN SEE THAT SOURCE OF
FUNDING COMES FROM ONE PLACE AND
EACH RECEIVES A LEVEL OF FUNDING
AND BEFORE THAT STARTING IN 27
TAENWE RECEIVE FUNDS FOR 20TH
CENTURY CURE ACTS ENACTED IN
2016 AND THIS YEAR IS A VERY
LARGE AMOUNT OF FUNDING.
OVERALL WE ARE ENJOYING A NICE
INCREASE FROM FY22 TO 23 FOR
$680 MILLION MANY
MIGHT OR SHOULD BE AWARE THAT IT
SHOULD BE NEGOTIATED AND STAY
TUNED. WE ARE LOOKING TO SEE IT
SHAKE OUT FOR 2024 AND WE
INVESTED OVER $3 BILLION INTO
1300 BRAIN PROJECTS SINCE 2014
AND HOPE AGREE WE HAVE MADE
EMARK BLE PROGRESS TOWARDS THE
MISSION IN THE LAST 9 OR 10
YEA
YEARS.
WE HAVE GREAT NEWS TO SHARE AND
CONGRATULATIONS TO RECIPIENTS OF
ALUMNI FOUNDATIONS BRAIN CRIES
TO DR.S CHRISTINE HOLT AND --
THESE THREE INDIVIDUALS HAVE
MADE GREAT CONTRIBUTIONS AND HAS
BEEN WONDERFUL TO SEE THESE
UNFOLD OVER THE YEARS AND DR.
GREENBERG IS AMONG BRAIN-FUNDED
INVESTIGATORS AND HOPE TO
HIGHLIGHT IT HERE AND DELIGHTED
TO SAY EARLIER THIS MONTH FOR
FORMER OR CURRENTLY FUNDED BRAIN
INVESTIGATORS ARE ELECTED INTO
NATIONAL ACADEMY OF SCIENCES AND
IN THE CLASS OF 120 MEMBERS AND
FELLOW MEMBER AND CLEELG FROM
BERKELEY MADE REALLY GREAT
CONTRIBUTIONS TO THE ROLE OF
ACTIVITY IN DEVELOPING CIRCUITS
IN THE VISUAL SYSTEM IN
PARTICULAR TRAVELING WAVE AND
RECEIPTIN IN A LOOKING AT
DEVELOPMENT IN CELLS AND CIRCUIT
AT LARGE AND BEEN A PIONEER
LOOKING AT [INDISCERNIBLE]
SPECIFICATION AND DEVELOPING CNS
IN PARTICULAR FOR INTERNEURONS
AND UNDERSTANDING NEURAL
MECHANISMS OF DECISION MAKING,
HE IS AT COLUMBIA AND GOOD
FRIEND AND COLLEAGUE AT ALLAN
INSTITUTE MAKING UP
UNDERSTANDING OF THE STRUCTURE
OF MAMMALIAN SDENT AND WE ARE
DELIGHTED THAT THEY HAVE BEEN SO
NICELY RECOGNIZED AND VERY
RECENTLY HOWARD HUES MEDICAL
INSTITUTE LAUNCHED AN EXCITING
PROGRAM AND SELECTED 31
EXCEPTIONAL EARLY CAREER FACULTY
WITH POTENTIAL TO BECOME LEADERS
IN RESEARCH FIELDS AND CREATING
DIVERSE AND INCLUSIVE LAB IN
WHICH EVERYBODY CAN THRIVE AND
BELIEVE THAT SCHOLARSHIPS COULD
INVOLVE UPWARDS OF $8.9 MILLION
OVER 10 YEARS [INDISCERNIBLE] IN
THE BLUE HALO IS A BRAIN -- WE
ARE THRILLED FOR ALL THESE YOUNG
INVESTIGATORS AND IN PARTICULAR
TO SEE SOMEBODY WHO WAS FUNDED
THROUGH BRAIN AND SOMEBODY WE
PUT VERY WELL PLACED CONFIDENCE
IN AND ALSO RECOGNIZING HAVING A
GREAT CAREER AND EVENTS GOING ON
AND COMING UP.
WE HELD BRAIN QUANTIFICATION OF
SYNCHRONIZATION WORKSHOP
FOCUSING ON TECHNOLOGIES AND
MOMENTOUS AS WELL FIRST HYBRID
EVENT WE PROMOTED SINCE THE
PANDEMIC AND GOAL WAS TO
IDENTIFY NEW TECHNOLOGIES FOR
UNRAVELING BIOLOGICAL BASIS OF
BEHAVIOR AND COGNITION PART OF
THE PROGRAM AND THERE ARE GREAT
TALKS THERE AND KEY TAKEAWAYS
AROUND SUCH TECHNOLOGIES AND
CONSIDERATIONS FOR CENSOR DESIGN
TAIL YOORD FOR DIFFERENT
APPLICATIONS AND SCENARIOS AND
HEARD COOL STUFF FROM ELECTRICAL
ENGINEERS ABOUT LOW POWER
DESIGNS FOR INTEGRATED CIRCUITS
AND [INDISCERNIBLE], ET CETERA
AND MINIATURIZATION AND USE OF
MULTIMODAL CENSORS AND
HIGHLIGHTING THE IMPORTANCE OF
DATA SCIENCE AND UNRAVELING AND
CONSOLIDATING THIS INFORMATION.
AGAIN, THE VERY, VERY -- THE
VERY EXTREME IMPORTANCE OF
SHARING DATA AND MAKING IT
ACCESSIBLE AND USING ALSO THE
DATA IN AN ETHICAL WAY THAT IS
QUITE A REVEALING WORKSHOP AND
COMING P BIG BRAIN MEETING WILL
BE A HYBRID EVENT IN PERSON AND
NORTH BETHESDA AS WELL AS
VIRTUAL AND THREE TERRIFIC
PLENARY LECTURES PLANNED AND
[INDISCERNIBLE] FROM DUKE
UNIVERSITY WILL TALK ABOUT THE
ETHICAL IMPLICATIONS OF USE OF
OUR DATE FRAU OUR BRAINS AND DR.
[INDISCERNIBLE] WHO IS HERE
TODAY WILL TALK ABOUT NEW
APPROACHES TO PERSONALIZED
TREATMENT OF NEUROPSYCHIATRIC
AND OTHER BRAIN DISORDERS AND
FROM BAILEY UNIVERSITY FROM
ROBBINGE FELLER UNIVERSITY WILL
TELL US ABOUT -- USING DROS FILL
YA AS A MODEL SYSTEM AND
PRETITLE EVENT FOR TRAINEES
BUILDING OUT EARLY CAREER
COMMUNITY HELD NIGHT BEFORE ON
SUNDAY.
ENCOURAGE EVERYBODY TO
PARTICIPATE AND CAPPED OUT ON
IN-PERSON REGISTRATION AND IS
INFINITE ROOM FOR YOU TO
REGISTER VIRTUALLY AND PLEASE DO
SO IF YOU HAVEN'T ALREADY. WILL
BE TERRIFIC MEETING AND SURE
THAT WE ARE VERY MUCH LOOKING
FORWARD TO THAT. ANOTHER
UPCOMING MEETING IN JULY, JULY
17TH THROUGH 18TH IS NEW
WORKSHOP ON ETHICS OF SHARING
INDIVIDUAL LEVEL HUMAN BRAIN
DATA COLLECTED IF IN BIOMEDICAL
RESEARCH AND GOAL WILL BE TO
EXPLORE WAYS TO CATEGORIZE HUMAN
BRAIN DATA BY POTENTIAL RISKS OF
DATA SHARING AND DIFFERENCES IN
HOW TO TREAT DATA ARTICULATING
POINTS TO CONSIDER FOR
RESEARCHERS DISCLOSING POTENTIAL
RISKS TO HUMAN SUBJECTS SHARING
HUMAN BRAIN DATA AND TWO-DAY
WORKSHOP AND ARE VERY MUCH
LOOKING FORWARD TO THIS.
IT WILL DOVE-TAIL WITH OUR
ONGOING DISCUSSIONS ABOUT THE
VALUE AND POTENTIAL RISK FOR
DATA SHARING IN THE SPACE AND
LAUNCHED EFFORTS HAPPENING
ACROSS NIH IN THE DATA SHARING
SPACE AND STAY TUNED FOR THAT.
IT WILL BE HYBRID. IF YOU CAN'T
MAKE IT IN PERSON YOU WILL TUNE
IN TO SEE WHAT IS GOING ON
THERE.
BRAIN SIGNED ON TO THIS SOMATIC
CELL GENOME EDITING CHALLENGE
WHERE THERE WILL BE TWO GOALS
HERE AND ONE IS TO DEVELOP
PROGRAMMABLE DELIVERY SYSTEMS
FOR GENE EDITING AND CROSSING
BLOOD/BRAIN BARRIERS AND
CHALLENGE MECHANISM FUNDED BY
COMMON FUND COMANAGED BY
NATIONAL CENTER FOR ADVANCING
TRANSITIONAL SCIENCES AND MCATS
AND BRAIN INITIATIVE AND NHLBI
SIGNED ON AND INFORMATIONAL
WEBINAR COMING UP NEXT WEEK AND
WE ARE EXCITED ABOUT THIS AND
THINK IT WILL COMPLEMENT THIS AS
WELL AS PARTICIPATION IN GENOME
THERAPY CONSORTIUM.
THIS HAS THE BRAIN KEEPING
PRESENCE THERE TO HOMEFULLY FUND
INCREDIBLE BREAKTHROUGHS AND
THAT TIME OF YEAR I WOULD LIKE
TO GIVE UPDATE ON BRAIN
DEMOGRAPHICS THAT ARE
DEMOGRAPHICS OVER FY22 THAT
ENDED IN SEPTEMBER OF LAST YEAR
I WILL SUMMARIZE THIS QUICKLY
HERE. YOU SHOULD HAVE THE FULL
DECK IN YOUR ELECTRONIC COUNCIL
BOOK. WE WILL POST THE FULL
DECK ONLINE SO YOU CAN ALSO
REFER TO THAT AND OTHERS WHO ARE
TUNING IN VIA WEBCAST CAN GO TO
THE WEBSITE AND FIND IT AND
SHOULD LIVE ON THE PDP PAGE AND
IF WE LOOK AT EXPERTISE THAT IS
REPRESENTED IN THE BRAIN
PORTFOLIO AFTER NEUROSCIENCE AND
ABOUT 1/3 OF INVESTIGATORS
IDENTIFY AS ENGINEERS OR PEOPLE
WITH ENGINEERING EXPERIENCE.
IN TERMS OF INDIVIDUALS FROM
DIVERSE BACKGROUNDS WE HAVE TO
REPORT THERE IS ROUGHLY SIMILAR
FUNDING RATES BETWEEN LIMITED
MEN AND HIGHLIGHTED IN THAT OVAL
DOWN THERE AND CAREER STAGE AND
THEY HAVE ABOUT SAME FUNDING
RATE AND YOUNG FOLKS DO BETTER
THAN OLD FOLKS OR LATER STAGE
FOLKS AND IN TERMS OF GEOGRAPHIC
DISTRIBUTION NOT SHOWING HERE
PERFORMANCE SIDES OF 42 OF 50
STATE AND CHALLENGE OF
INSTITUTION TYPE BRAIN FUNDING
FAVORS HEAVILY R1 OR HIGHLY
RESEARCHED INTENSIVE
INSTITUTIONS AND IS WHAT IT
LOOKS LIKE AND SEE OVERALL
SUMMARY IN UPPER RIGHT-HAND
BUBBLE AND TO BE CANDID IT LOOKS
ABOUT THE SAME AS LAST YEAR AND
ARE NOT MOVING THE NEEDLE IN A
HUGE WAY AND ARE SIGNS OF HOPE
AND I WILL SHOW IT TO YOU IN THE
NEXT FEW SLIDES.
WE TALKED A BIT IN THE PAST
ABOUT STRATEGIES FOR BUILDING A
STRONGER MORE DIVERSE WORKFORCE
TO GET TALENT OFF SIDELINES TO
LEVERAGE THEM FOR GOALS AND
MISSION HERE.
WE HAVE DIVERSITY FOCUSED
TRAINING PROGRAMS I WILL TALK
ABOUT LATER AND WE HAVE CAPACITY
BUILDING PROGRAMS BUILDING IN
MINORITY SERVING INSTITUTIONS
AND INSTITUTIONS FROM IDEA
ELVIBL STATES AND WHAT I'M
SHOWING HERE THIS DIVERSE
PERSPECTIVE THAT IS BRAIN
INNOVATION THAT REQUIRES IN ALL
NEW AND REISSUED BAR PHASE
EXCEPT FOR TRAINING R PHASE AND
THAT THE INVESTIGATORS DETAIL IN
RESEARCH STRATEGY HOW DIVERSE
PERSPECTIVES WHETHER THEY BE
SCIENTIFIC DIVERSE PERSPECTIVES
OR PERSONAL DIVERSE PERSPECTIVES
AND CAREER STAGE AND WHAT HAVE
YOU AND INSTITUTIONAL GEOGRAPHIC
HOW IT WILL LEAD TO BETTER
SCIENCE THAT NEEDS TO BE
SUMMARIZED IN A ONE-PAGE
ATTACHMENT AS PLAN FOR ENHANCING
DIVERSE PERSPECTIVES THAT IS
PART OF THE SCORED APPLICATION
AND BRAIN INNOVATION WE STARTED
AND THOUGHT AS A PILOT PROJECT
LESS THAN 2 YEARS AGO THAT HAS
BEEN TAKEN UP IN 130. WE CALL
THEM NOFOS RIGHT NOW NOTICE OF
FUNDING OPPORTUNITIES WE CALMED
FUNDING OPPORTUNITY
ANNOUNCEMENTS IN 130 OF
ANNOUNCEMENTS ACROSS 19
INSTITUTE AND CENTERS SEEING
CUMULATIVE DISTRIBUTION OVER
TIME SINCE WE LAUNCHED THIS IN
2021 AND BRAIN OF COURSE IS IN
LEAD AT 41. YOU CAN SEE THE
DISTRIBUTION DOWN HERE THAT IS
BEING TAKEN UP AND STARTING TO
SEE RESULTS FROM THIS AND VERY
EARLY DAYS I WILL GIVE YOU A
SNAPSHOT OR EARLY LOOK AT THE
EFFECT OF THE PDP OVER 2022 AND
WHERE THERE IS RELATIVELY FEW R
FACED WITH PDPS AND NEVERTHELESS
GIVES EARLY GLIMPSE WHERE YOU
ARE AND SEE ON LEFT-HAND SIDE OF
THE FIGURE THAT THE PERCENTAGE
OF WOMEN EITHER IN THE APPLICANT
POOL, WHICH IS IN THE DIAMONDS
OR IN THE AWARDEE POOL THAT IS
IN THE DARK BLUE CIRCLES.
WE HAVE NOT MOVED THE NEEDLE
QUICKLY. WE ARE SEEING A
GRADUAL INCREASE IN
REPRESENTATION OF WOMEN IN PI
COAL AND INCLUDES MPIS THROUGH
2014 AND 2022. JUST SHY OF I
THINK 19 OR 20%.
IT HAS BEEN A SLOW GROWTH. IF
YOU LOOK ON THE RIGHT THOUGH,
THERE IS REASON FOR SOME HOPE.
IF YOU LOOK AT THE APPLICATIONS
THAT WE FUNDED OR CONSIDERED FOR
FUNDING IN FY22, THERE SEEMS TO
BE AT LEAST INITIALLY A BIT OF A
BUMP IN NUMBER OF AWARDED
APPLICATIONS IN R PHASE
CONTAINED IN PDP VERSUS NOT AND
IN NOISE WE DON'T KNOW STRONG
CAVEAT TO CONSIDER AND COULD BE
EARLY SIGN THAT PDP IS MAKING A
DIFFERENCE IN DIVERSIFYING PDP
POOL ON BASIS OF GENDER AND ARE
HOPEFUL FOR THAT. STAY TUNED.
IT IS A WORK IN PROGRESS AND
SOMETHING WE ARE VERY, VERY
COMMITTED TO.
SITUATION WITH INDIVIDUALS FROM
UNDER-REPRESENTED GROUPS IS NOT
SO GREAT TO BE QUITE HONEST AND
SEE HERE VERY LOW LEVEL WHERE
NUMBERS ARE BOUNCING BETWEEN 3
AND 8% AND HOVERING AROUND 10%
AND CHALLENGE LOOKING AT NUMBERS
IS NUMBER OF INDIVIDUALS IS VERY
SMALL AND DATA IS NOISY AND
JUMPS AND BUMPS HERE WE CAN'T
PUT TOO MUCH PAGE IN EXCEPT TO
SAY WE ARE NOT MOVING NEEDLE
APPRECIATIVELY UPWARDS THAT IS
OF CONCERN AND LOOKING AT DATA
APPLICATIONS WITH AND WITHOUT
PDP AND SEE NUMBER OF APPLICANTS
THAT STAYED MORE OR LESS THE
SAME AND AGAIN IS SMALL SAMPLE
SIZE AND PERHAPS IS A NARROWING
OF THE GAP BETWEEN APPLICANTS
AND AWARDEES WITH AND WITHOUT
PDPS AND CAUTION THAT THIS IS A
SNAPSHOT WE HAVE TO KEEP AN EYE
ON THIS AND DO OUR BEST TO
RECRUIT AND ENGAGE LARGER SWATH
OF THE SCIENTIFIC COMMUNITY AND
BETTER REPRESENTATION OF TALENT
AND VIEWPOINTS ACROSS BIOMEDICAL
ENTERPRISE THAT IS THE STORY
HERE WITH UNDER-REPRESENTED
MINORITIES.
NOW, ONE THING WE HAVE LOOKED AT
QUITE CAREFULLY AND CLOSELY IS
COMPOSITION OF
MULTI-INVESTIGATOR TEAMS AND WE
CAN SEE THIS APPEARS THAT WE ARE
SEEING A HIGHER PROPORTION OF
MULTI-INVESTIGATOR TEAMS THAT
ARE OF MIXED GENDER AND WITHOUT
PDP ABOUT HALF OF THESE GAINS
WERE ALL MALE AND LESS THAN 1/3
WERE MIXED MALE AND FEMALE AND
SEEING HERE PERHAPS A FAIRLY
LARGE INCREASE TO ALMOST 60%.
50 OR 60% MIXED GENDER TEAMS AND
CONCOMBINANT INCREASE IN ALL
MALE TEAMS AND GIVING ANOTHER
CAVEAT THAT SOME DIFFERENCE AND
NOT ALL DIFFERENCE MIGHT BE
ATTRIBUTABLE TO GREATER
REPORTING OF GENDER PLUS OR
MINUS PDP THAT IS A BIT OF
UNCERTAINTY HERE. BUT, IF I
WOULD LOOK AT THIS AS GLASS HALF
FULL, I THINK IT COULD BE
SIGNALING I HOPE A TREND TOWARDS
MORE DIVERSE TEAMS AT LEAST IN
TERMS OF GENDER AND IN TERMS OF
RACE ETHNICITY THIS HAS GONE UP
50% FROM 8% OR 50% TO FOURTD%
AND NUMBERS ARE QUITE LOW AND
COULD BE IN NOISE. AT LEAST NO
THE IN NEGATIVE BUT POTENTIALLY
POSITIVE TREND AND SOMETHING WE
ARE KEEPING A CLOSE EYE ON AND
HAPPY TO TALK ABOUT IT IN
DISCUSSION PERIOD AND YOU HAVE
ENTIRE DECK NEXT CB AND WE ARE
ALWAYS HAPPY TO ENGAGE WITH
EVERYBODY ON THIS TOPIC AS I
HOPE I HAVE RELAYED TO YOU OVER
THE LAST FEW YEARS AND
DIVERSIFYING AND STRENGTHENING
WORKFORCE IS CORE VALUE AT BRAIN
INITIATIVE AND COULD USE
EVERYBODY'S INPUT AND HELP TO
REACH THAT GOAL.
WE TALKED A LOT IN LAST FEW
YEARS OF BRAIN 2.0 PROJECTS AND
ATLAS NETWORK THAT IS FOCUSED ON
BUILDING BRAIN CELL ATLASES IN
HUMANS AND FEW OTHER MODEL
ORGANISMS AND ARE JUST IN THE
PROS OF LAUNCHING BRAIN
INITIATIVE CONNECTIVITY ACROSS
SKANS AND BRAIN CONNECTS
CONNECTIVITY PROJECT AND GROUP
LOOKED AT FUNDING PLAN LAST
ROUND IN CLOSED SESSION AND
LOOKING FORWARD TO ISSUING
AWARDS BY LATER IN SUMMER AND
EARLY FALL AND TOOLKIT FOR
PRECISION BRAIN ACCESS
LEVERAGING INFORMATION COMING
OUT OF BRAIN CENSUS TO BUILD A
TOOLKIT FOR PRECISION ACCESS
BASED ON MOLECULAR IDENTITY AND
BRIEF UPDATE WHERE WE ARE WITH
THESE WE LAUNCHED FIRST AWARDS
LAST YEAR WE HAVE NIEBT MILLION
OF AWARDS SECOND ROUND OF
APPLICATIONS ARE CURRENTLY UNDER
REVIEW AND SEE AT AUGUST COUNCIL
AND EXPECT TO ISSUE THOSE AWARDS
BY END OF THE CALENDAR YEAR.
THE [INDISCERNIBLE] PROJECT
DESIGNED FOR DEVELOPING TOOLS
FOR PRECISION BRAIN CELL ACCESS
AND WE FUNDED PILOT GRANT PHASE
$30 MILLION ACROSS 6 PROJECTS
AND NOW HAVE NEW RFA OUT FOR
MOLECULAR PAYLOAD CENTERS URM1
MECHANISM FOR FIRST RECEIVED
DATE COMING UP NEXT MONTH AND
CONNECTIVITY PROJECTS WITH HE
ARE EXPECTING TO ISSUE FIRST
ABARREDS LATER THIS SUMMER AND
SECOND RECEIVED DATE FOR AWARDS
IS COMING UP NEXT MONTH AND
PROJECTS HAVE BEEN MADE POSSIBLE
BY CONGRESSIONALLY DIRECTED
FUNDS ALLOWING US TO INVEST
SIGNIFICANT AMOUNT OF RESOURCES
INTO PROJECTS THAT WILL LAY
FOUNDATION FOR TRANSFORMATIVE
RESEARCH IN YEARS TO COME WE
HAVE LAUNCHED BRAIN BEHAVIOR
QUANTITY FICTION SYNCHRONIZATION
PROGRAM AND THAT IS VALIDATION
OF NEXT GENERATION TOOLS AND
METHODS AS WELL AS ANALYTICAL
APPROACHES TO IDENTIFY AND
QUANTIFY COMPLEX BEHAVIORS
COMBINING MOST SIMULTANEOUS
RECORDINGS OF CONNECTIVITY AND
ISSUED FIRST TWO RFAS FOR THIS
PROGRAM AND THAT IS THE R61 THAT
IS THE PILOT PHASE PROJECTS FOR
LOOKING AT HUMAN BEHAVIORAL
QUANTIFICATION SYNCHRONIZATION
AS WELL AS EARLY STAGE R34
MECHANISM FOR DOING PARALLEL
PROJECTS IN NON-HUMAN MODELS AND
WE EXPECT FIRST AWARDS TO BE
MADE IN THE FALL OF THIS YEAR
AND WILL BE A SECOND RECEIPT
DATE COMING UP FOR THE HUMAN
PROJECTS IN FEBRUARY OF NEXT
YEAR TOGETHER WITH THESE
PROJECTS COMING UP WITH FIRST
RECEIPT DATE IN JULY OF THIS
YEAR DATA COORDINATION AND
ARTIFICIAL INTELLIGENCE CENTER
FOR THE BBQS PROJECT AND
COORDINATION CENTER WILL OVERSEE
DATA MANAGEMENT AND STANDARDS
AND DEVELOPMENT AND ORGANIZATION
OF MACHINE LEARNING AND
ARTIFICIAL INTELLIGENCE
RESOURCES AND WILL SET UP
MANAGED DATA ECOSYSTEM FOR
DISSEMINATION AND TRAINING AND
COURT NATION FOR ALL DATA THAT
COMES OUT OF THIS. YOU CAN
APPRECIATE THAT NOW THAT WE GET
INTO MORE DEEPLY NEW METHODS FOR
QUANTIFYING AND ORGANIZING
ASSAYS TOGETHER AND WITH -- THIS
WILL CHALLENGE US FROM DATA
SCIENCE POINT OF VIEW AND
IMPORTANCE OF SETTING UP
COORDINATION CENTER TO MANAGE
THIS GROUP AS A CONSORTIUM.
OKAY.
WE RECENTLY ISSUED R61
MECHANISM AS A KIND OF LEAD-IN
FOR OUR RESEARCH OPPORTUNITIES
IN HUMANS PROGRAM AND PREVIOUSLY
HAVE R34 AND IDEA BEHIND THIS
TYPE OF MECHANISM IS TO LEAD UP
TO AND PROVIDE A RUNWAY FOR
LARGER SCALE U01 PROJECTS AND
OPPORTUNITY AND HUMAN SPACE AND
WAS FELT THAT R61 MECHANISM WAS
BETTER AND PROVIDES MORE
RESOURCES FOR INVESTIGATORS WHO
ARE PERFORMING BASIC
EXPERIMENTAL STUDIES FOR HUMANS
AND CURRENT RECEIPT DATES OF
2025 AND YOU SEE BUDGET IS
LIMITED TO MAXIMUM OF 700,$700,
OF DIRECT COST IN A YEAR AND
ALLOWING FOLKS TO GET MORE DONE
AND MAKE PROGRESS IN PREVIOUS
R34 MECHANISMS AND FUNDING
ANNOUNCEMENTS AND UN1 WHICH IS
THE -- LET'S SEE. U AND 1 I
MENTIONED IN PROJECT AND ABOUT.
BQS U24 COORDINATION CENTER AND
R61 AS WELL EXPLORATORY GRANTS
FOR RESEARCH OPPORTUNITY FOR
HUMANS AND HAVE A FEW NEW
REISSUES HERE AND AT BOTTOM WE
SIGNED ON FOR A FEW NIH-WIDE
PARTNERSHIPS AND FIRST IS REWARD
PROGRAM WHOSE GOAL IS ORGANIZING
BREADTH AND RESEARCH SUPPORTED
BY NIH.
SECOND IS SIPA PROGRAM
SUPPORTING EDUCATIONAL
ACTIVITIES ENCOURAGING
INDIVIDUALS FROM DIVERSE
BACKGROUNDS TO PARTICIPATE AND
FIND CAREERS IN RESEARCH THAT IS
A KIND OF JUST A VERY BRIEF
SUMMARY OF NEW FUNDING
OPPORTUNITIES AND WOULD LIKE TO
HIGHLIGHT TRAINING OPPORTUN
OPPORTUNITIES.
WE HAVE GENERAL F32 AWARD AND
SUPPLEMENTIARY AWARDS AND
DIVERSE MECHANISMS AND F99K00B
SPAN AWARDS THAT IS FUNDING
SENIOR LEVEL GRADUATE STUDENTS
FINISHING OFF DISSERTATION
RESEARCH IN F99 PHASE AND CARRY
WITH THEM FUNDS IN K00 PHASE FOR
POST DOCTORAL FELLOW SHCHS THAT
GIVES ENTRAY TO FINDING TERRIFIC
TRAINING OPPORTUNITIES FOR POST
DOCTORAL PHASE AND WE HAVE OF
COURSE THE BRAIN K99R00 PROGRAM
THAT UNLIKE PARENT K99 PROGRAM
ACROSS NIH IS DIVERSITY FOCUSED
FOR UNDERREPRESENTATIVE GROUPS
AND WOMEN HERE ARE CONSIDERED
UNDERREPRESENTATIVE GROUP AND WE
HAVE ONGOING SUPPLEMENT MANY
EBBING NIX TO BRING IN TRAINEES
AT MANY, MANY DIFFERENT LEVELS
FROM DIVERSE BACKGROUNDS TO HELP
PROMOTE ENTRY INTO BIOMEDICAL
WORKFORCE.
MANY WE ENCOURAGE AND MANY OF
THEM DO WIND UP ACTUALLY
APPLYING FOR COMPETITIVE FUND
AND THIS IS WHAT GENERAL PICTURE
LOOKS LIKE IN TERMS OF BRAIN
FUNDING AND STAY TUNED. MORE TO
COME IN THE NEXT COUPLE OF
MONTHS.
THAT IS THE UPDATE OF WHAT IS
GOING ON ADMINISTRATIVELY AND
PROGRAMWISE AND WOULD LIKE TO DO
AT EACH MEETING AND GIVING A FEW
HIGHLIGHTS OF RECENT ADVANCES OF
INVESTIGATORS FUNDING THERE OUT
IN THE WILD AND COOL PAPER CAME
OUT IN CURRENT BIOLOGY EARLIER
THIS YEAR.
BOB'S GROUP USED UNSUPERVISED
MACHINE LEARNING TECHNIQUE MO
SEEK DOING VIDEO TRACKING ON
ANIMALS AND CLASSIFYING
QUANTIFYING BEHAVIORS BASED ON
DECOMPOSING MOVEMENTS OF
BEHAVIORS INTO DISCRETE POSES OR
WHAT THEY CALL SYLLABLES AND USE
IT HERE TO QUANTIFY OPEN FIELD
BEHAVIOR AND ACTUALLY OF FEMALE
AND MALE MICE ACROSS -- FEMALE
MICE ACROSS PHASES OF
REPRODUCTIVE CYCBLE AND WHAT
SCHEMATIC LOOKS LIKE THERE AND
EACH MOUSE THEY SORT SYLLABLES
WITH DIFFERENT POSES BY FRACTION
OF USE AND SUCCESSION AND USE
DIMENSIONALITY REDUCTION TO
COMPARE NOT ONLY ACROSS
INDIVIDUALS AS WELL AS BETWEEN
AND IN INDIVIDUAL AT DIFFERENT
TIMES AND ACROSS PHASES OF
ESTHER CYCLE THAT GETS AT NOTION
THAT I WILL CALL IT NOTION
GENEROUSLY AND BEHAVIOR AND
MANY, MANY DECADES THIS WAS USED
AS A REASON FOR EXCLUDING FEMALE
ANIMALS FROM STUDY.
WHAT THEY FIND QUITE
INTERESTINGLY IS FEMALE
SPONTANEOUS BEHAVIOR REFLECTING
INDIVIDUAL VARIATION THAT IS
GREATER IN VARIATION TO
AINTEREST IBUTE ACROSS ESTHER
PHASE AND THIS IS JUST THE
DIMENSIONALITY AND THE FACTOR C
AND COVARIATION ON RIGHT YOU SEE
HOOER THAT AMOUNT OF VARIATION
YOU CAN SEE IN BEHAVIORS
ATTRIBUTABLE TO ESTHER PHASES
FAR LESS THAN WHAT YOU ATTRIBUTE
TO SPONTANEOUS BEHAVIOR THAT IS
QUITE INTERESTING AND MORE
INTERESTING IS MAELD THIS
UNDERSCORES IMPORTANCE OF
INCLUDING SEX AS A BIOLOGICAL
VARIABLE BUT UNDERCUTS THE
NOTION OF EXCLUDING FEMALES
BECAUSE OF THIS ESTHER CYCLE
CONTRIBUTION THAT IS A NICE
STUDY THAT I THINK SHOWS THE
POINT IN AN ELEGANT WAY USING A
SOPHISTICATED AND ELEGANT
TECHNIQUE AND I TALKED ABOUT
GROUP FROM [INDISCERNIBLE] GROUP
IN THE PAST ABOUT VIRUSES AS
VECTORS FOR ACCESSING BRAIN CELL
TYPES.
IF YOU -- TALKING TO FOLKS IN
GENE THERAPY WORLD TELLING ME
THREE MOST IMPORTANT THINGS TO
CONSIDER ARE DELIVERY, DELIVERY,
AND DELIVERY AND ONE MODE OF
DELIVERY THAT IS QUITE
ATTRACTIVE IS TO BE ABLE TO
DELIVER A VECTOR WITH A PAYLOAD
INTO THE BLOOD STREAM THAT WILL
FIND WAY INTO THE BRAIN AND
TARGET CELL TYPES THAT WE CARE
ABOUT AND IF ONE CAN TO AVOID
LIVER. THERE ARE MANY TOXIC
SIDE-EFFECTS ASSOCIATED WITH
MANY GENE THERAPY CONSTRUCTS AND
THESE VECTORS ARE CURRENTLY IN
USE IN GENE THERAPIES AND WIDELY
USED FOR NEUROSCIENCE AND MODEL
SYSTEMS AND USED IN PAST AND
DIRECTED EVOLUTION TO FIND IN
MECHANISM OR PROTEIN AGNOSTIC
WAY VECTORS THAT CROSS
BLOOD/BRAIN BARRIER DOING IT
SUCCESSFULLY USING EVOLUTIONARY
APPROACHES AND FACTORS AVOIDING
LIVER WHICH IS ALSO OF GREAT USE
AND THEY HAVE TAKEN VECTORS
ASKING CAN WE USE THESE TO
IDENTIFY ACTUAL RECEPTORS IN
VASCULATURE THAT MIGHT BE
RESPONSIBLE FOR GETTING VECTORS
ACROSS BLOOD/BRAIN BARRIER INTO
THE TARGET TISSUE AND WHAT THEY
DID HERE AND THEY FLIPPED THEIR
APPROACH AROUND 180°.
USING A SERIES OF QUITE COOL
EXPERIMENTS I DON'T HAVE TIME TO
GET IN HERE THEY FOUND TWO NOVEL
RECEPTORS THAT WERE EXPRESSED IN
THE VASCULATURE.
ONE IS THE PROTEIN CALLED LYSCC1
WHICH IS RESTRICTED TO MOUSE
MIRRORING VASCULATURE ALLOWING
ENTRY OF THESE THREE THAT MEANS
THAT THEY GET IN WELL AND FOUND
QUITE INTERESTINGLY THE
EXPRESSION OF TYPE 4 CARBONIC
AND HYDROS THAT ALLOW ENTRY OF
THESE TWO ENGINEERED VIRUSES
INTO THE CELLS AND WHAT IS COOL
IS THIS IS CONSERVED ACROSS
VERTEBRATES AND THINKING IF THIS
IS CONSERVED ACROSS VERTEBRATES
MAYBE ONE CAN FIND A VIRUS
WORKING ACROSS MULTIPLE
MAMMALIAN SPECIES AND THEY
SHOWED THAT INDEED LET'S SEEIN
DEED WHEN THEY LOOK AT THE ENTRY
OF GFP-TAGGED VECTOR THAT SHOULD
USE CARBONIC AND HYDROS FOR
ENTRY, THESE WERE DEVELOPED IF
IN IN VITRO AND CELL-BASE AD
SAYS AND SEEING HERE NICE ENTRY
OF PARENT VECTOR INTO THE BRAIN
AS WELL AS INTO THE LIVER
SOMEWHAT AS WELL AS AN
ENGINEERED VIRUS THAT SHOULD
BIND TO CARBONIC [INDISCERNIBLE]
4 AND MOUSE KNOCKOUT LACKING
CARBONIC N HIDE RACE 4 YOU CAN
STILL SEE ACCESS TO LIVER AND
OBLATE ACCESS TO THE BRAIN AND
DEMONSTRATES THEY HAVE INDEED
SELECTED VIRUS GET AGO CROSS
BLOOD BRAIN BARRIER AND BINDING
TO THIS AND NOW THEY WENT ON TO
USE ALPHA FOLD BASED INSILICO
PREDICTIONS OF NCAPSIS TO VERIFY
OR PREDICT THIS BIENTDING
AFFINITY AND SPECIFICITY THAT
SEEMED TO WORK OUT PRETTY
NICELY. WHAT THIS MEANS IS THEY
NOW CAN USE INSILICO TRICKS AS
WELL AS BIOCHEMICAL VALIDATION
TO TUNE AND TWEAK TARGETING OF
ENGINEERED VIRUSES BASED ON
KNOWN INTERACTION OF THE
RECEPTOR. OKAY?
THAT IS KIND OF COOL AND THEY
ARE NOT THERE YET AND WHO CAN
SEE IN TERMS OF RELATIVE ENTRY
OF THE ENGINEERED CONSTRUCTS IN
CELL CULTURE AND ASSAY AND
GETTING INTO MOUSE RECEPTOR
MOUSE CARBONIC HIDE DRAS FROM
HUMAN SEQUENCES BUT HAVE
SOMETHING NOW TO WORK WITH.
THIS IS A NICE DEVELOPMENT AND
ANOTHER REASON I BRING THIS
PAPER UP HERE TODZ IS IN THE
PAST WE HAVE TALKED ABOUT
CAPACITY BUILDING U24 GRANTS
THAT WE HAVE GIVEN OUT. WE HAVE
GIVEN OUT ONE GOING ON 2 RIGHT
N
NOW.
FIRST WE GAVE OUT WAS BETWEEN
COLLABORATION BETWEEN CAL TECH
GROUP ANDY STEEL AT CAL POLY
POMONA 20 OR 30 MINUTES EAST OF
CAL TECH AND HISPANIC-SERVING
INSTITUTION AND COOL AND GIVING
ACCESS TO STUDENTS WITH
COGNITIVE RESEARCH AND CONCERNS
ABOUT AUGMENTING PROVIDING A
SERVICE TO THE LARGER R & D
GRANT AND REALLY COOL THING IS A
CO-AUTHOR IN THE PAPER I TOLD
YOU ABOUT WAS ANAYA CROSS-BEE A
SOPHOMORE WHO CONTRIBUTE TODAY
THIS PURE SCIENCE PAPER LOOKING
FORWARD TO SEEING ADDITIONAL
CONTRIBUTIONS FROM STUDENTS
INVOLVED IF IN THESE CAPACITY
BUILDING EFFORTS TO HELP IN
PRODUCTION BUT TO DRIVE RESEARCH
AND DEVELOPMENT OF VERY, VERY
POWERFUL VECTORS AND MYSELF IT
IS A COOL SCIENTIFIC STORY AND
IS N OF 1 THAT WE ARE PERHAPS ON
THE RIGHT TRACK TO BRINGING
STUDENTS IN TO HAVE
OPPORTUNITIES TO REALLY LEARN
ABOUT SCIENCE AND FALL IN LOVE
WITH SCIENCE AND HOPEFULLY
PURSUE A CAREER AND LIFE DURING
THIS KIND OF WORK AND IN NEXT
TWO STUDIES I WANT TO HIGHLIGHT
FOR YOU QUICKLY, THEY SERVED TO
HIGHLIGHT TRANSLATION OF BRAIN
DEVELOPED TECHNOLOGIES IN A
CLINICALLY IMPORTANT DOMAIN.
SO, HERE IS A PAPER THAT WAS
JUST PUBLISHED TWO YEARS AGO
FROM THE GROUP AT UCSF.
[INDISCERNIBLE] CHANG AND STAR.
HERE, THEY HAVE USED
INTERCRANIAL REPORTING TO
PREDICT IN OBJECTIVE WAY STATES
INTERNAL STATES RELATE TODAY
CHRONIC PAIN AND IN OTHER WORDS
IS VERY IMPORTANT TO DEVELOP
OBJECTIVE MARKERS FOR CHRONIC
PAIN TO COME UP WITH BETTER
TREATMENTS.
THIS IS A CASE STUDY WHERE THEY
HAVE FOUR PARTICIPANTS AND THREE
WITH POST TRUCK PAIN AND ANOTHER
WITH PHANTOM LIMB PAIN PLANTED
WITH ELECTRODES IN INTERIOR
SINGULAR CORTEX AS WELL AS
ORBITAL FRONTAL CORTEX AND SEE
SCHEMATIC FROM ONE PATIENT HERE
AND THEY RECORD RECORDINGS OVER
MANY MONTHS AND DO A CAREFUL
SERIES OF MEASUREMENTS REPORT
THE PAIN STATES VALIDATED ACROSS
ASSAYS AND DOING THAT BACK WITH
MEASUREMENTS OF NEURAL ACTIVITY
AND USE POWER FEATURES FROM
THESE DATA.
TO TRAIN A MODEL TO DECODE WHAT
THEY WOULD ATTRIBUTE TO A HIGH
VERSUS LOW-PAYING STATE AND
MODELS REVEAL THAT ACTIVITY IN
ORBITAL FRONTAL CORTEX
CORRELATED QUITE WELL COULD BE
USED AS BIOMARKER OF CHRONIC
PAIN ACROSS ALL FOUR PATIENTS
DESPITE HIGH INTERVARIABILITY
AND SHOW ALSO THAT IN AT LEAST
THREE OUT OF THE FOUR CASES
PATTERNS WERE QUITE DISTINCT
FROM THOSE GENERATED IN RESPONSE
TO ACUTE PAIN OR HEAT STIMULUS
AND COOL THING IS WE ARE GEING
CLOSER TO HAVING OBJECTIVE
BIOMARKER FOR PAIN GOING TO
DOCTOR AND SHOULDER HURTS HOW
MUCH ON A SCALE OF 1 TO BETWEEN?
FUZZY WAY OF REPORTING AND WE
DON'T GET MOMENT TO MOMENT
INFORMATION FROM THIS AND HERE
NO YOU WE ARE SEEING DEVELOPMENT
OF NEURAL ACTIVITY BIOMARKERS
LIKE WE HAVE SEEN IN OTHER
STUDIES IN EATING DISORDERS AND
VARIOUS MOOD DISORDERS THAT
REALLY HAS POTENTIAL TO PERFORM
DEEP BRAIN STIMULATION THERAPIES
AND CLOSE THERAPIES FOR
PERSONALIZED PAIN MANAGEMENT
MAKING US THRILLED ABOUT THIS
RESEARCH IS SCIENCE ADVANCING
AND INTERFACE BETWEEN BRAIN
INITIATIVE DEVELOPING
TECHNOLOGIES AND HEAL INITIATIVE
SEEKING TO HELP PHYSICIANS AND
PATIENTS MANAGE PAIN AND REDUCE
BURDEN OF OPIOID AND OTHER DRUGS
OF POTENTIALLY ABUSED.
THIS IS VERY EXCITING AND MANL
NOW THEY ARE LOOKING TO SEE AND
FIRST OF ALL TO EXTEND STUDY TO
MORE PATIENT AND ALSO LOOKING TO
SEE IF CAN BE USED IN
PERSONALIZED DVS PARADIGM TO
CONTROL PATIENT'S PAIN AND
BEAUTIFUL INTERSECTION BETWEEN
TWO NIH-WIDE PROGRAMS AND ONE
DEVELOPING TECHNOLOGIES IN BRAIN
AND ANOTHER TO ADDRESS A LARGE
SPECTRUM OF DEVASTATING HUMAN
BRAIN AND BEHAVIORAL DISORDERS
RELATED TO IN THIS CASE PAIN.
OKAY.
SO, THE FINAL EXAMPLE I WILL
GIVE YOU HERE IS A PAPER
PUBLISHED FROM CAPITAL GROSSO
GROUP HERE IN MEDICINE AND HAD
TWO STROKE PATIENTS WITH KRON IB
UPPER LIMB PARESIS AND LOSS OF
USE OF ARMS, UPPER LIMBS, ARMS
AND HANDS, DUE TO STROKE. IDEA
HERE WAS TO IMPLANT SPINAL CORD
STIMULATORS AND EPIDURAL SPINAL
CORD STIMULATORS TO SEE IF THEY
CAN HELP RECOVER FUNCTION.
SO, SIMPLISTICALLY ONE CAN THINK
OF COMMAND COMING DOWN FROM THE
BRAIN THAT -- THAT INTERSECTS OR
INTERACTS WITH AND INSTRUCTS THE
LOCAL CIRCUITRY THAT IS FOUND IN
THE SPINAL CORD.
SO, IF THERE IS A LESION THAT
PREVENTS A STRONG
[INDISCERNIBLE] FROM COMING DOWN
AND THEREFORE LOSS OF MOTOR
FUNCTION OR MOTOR CONTROL OVER
THE LIMB, PERHAPS IF ONE CAN
TURN UP THE GAIN AS IT WERE OR
REDUCE PLASTICITY IN LOCAL
SPINAL CORD THAT PERHAPS COULD
HELP RECOVER LOCAL FUNCTION AND
THIS WITH GREG'S GROUP HAS SHOWN
AMAZING EFFICACY IN USING THIS
KIND OF SPINAL CORD STIMULATION
FOR MOTOR RECOVERY AND SPINAL
CORD INJURY PATIENTS STILL
SIGNAL COMING DOWN AND HERE IS
BEING APPLIED TO HIGH LEVEL AND
CERVICAL LEVEL RECOVERY IN THE
STROKE PATIENTS.
SO, THEY OPTIMIZE THE
STIMULATION PROTOCOLS WITH EACH
INDIVIDUAL AND TWO PATIENTS HERE
THAT ARE VERY EARLY FIRST IN
HUMAN TRIALS THAT THEN LED TO
INCREASED MUSCLE ACTIVATIONS YOU
CAN SEE HERE IN THE CURVES IN
BLUE FOR EXAMPLE AND RECENTLY
PATIENT NO. 1 SUFFERED HER
STROKE 9 YEARS PRIOR TO THE
STUDY THAT WAS QUITE INTERESTING
AND QUITE FASCINATING TO SEE
THIS EFFECT.
THE AMAZING THING WAS THAT
IMPROVEMENTS IN -- IN MOTOR
CONTROL AND STRENGTH, THEY WERE
JUST PRETTY MUCH IMMEDIATE.
IT ALSO LASTED UP TO 4 WEEKS.
THE LAST TIME THAT THEY CHECKED
ON THIS WITH PATIENTS.
WHICH SUGGESTS THAT THERE IS
SOME PLASTICITY GOING ON IN THE
CIRCUIT ITSELF WHICH IS SEEN IN
THE SPINAL CORD INJURY STUDIES.
THIS COULD BE QUITE EXCITING IN
TERMS OF LONG-TERM RECOVERY
FUNCTION OVER TIME.
I WANT TO JUST SHOW YOU A VIDEO
THEY PROVIDED IN SUPPLEMENT TO
THE STUDY AND IF A PICTURE IS
WORTH 1,000 WORDS, A VIDEO IS
WORTH A MILLION.
THIS IS THE PATIENT WITH
LEFT-SIDE HEMIPORESIS AND SEE
SHE IS STRUGGLING TO EVEN PICK
UP THE FORK. GOAL HERE IS TO
STAB THAT THING. I THINK IT IS
A CHICKEN NUGGET. DIP IT IN THE
SAUCE AND BRING IT UP TO HER
MOUTH.
SO, THIS IS WITH STIMULATION.
AGAIN, THIS IS 9 YEARS AFTER HER
STR
STROKE.
SO, CAN'T GIT GET THERE. NEEDS
A LITTLE HELP. THERE. OKAY?
SO, THE NEXT CLIP WILL BE FROM
WITH A STIMULATOR ON.
SHE STILL NEEDS A LITTLE HELP.
FINE MOTOR CONTROL IS STILL NOT
QUITE THERE.
I HOPE THAT YOU CAN SEE A
SIGNIFICANT DIFFERENCE IN HER
ABILITY TO DO THIS AND
ACCOMPLISH THIS TASK. SHE AND
WE ARE HAPPY TO SEE THAT AND
THIS IS QUITE EXCITING AND VERY
EARLY STAGE AND ONLY TWO PATIENT
AND OTHER PATIENT HAD SOME
IMPROVEMENT AND DEFICITS WERE A
BIT MORE SERIOUS TO OVERCOME.
ON RELATIVE SCALE COMPARED TO
OTHER INTERVENTIONS THAT WE HAVE
TALKED ABOUT HERE PLACED ON
EPIDURAL STIMULATOR, THIS SEEMS
TO BE A BIT LESS INVOLVED AND
AMAZING THING IS REPETITY THAT
PATIENTS CAN RECOVER FUNCTION
YEARS AND YEARS AFTER THAT. AND
HOPEFULLY LEADING TO
LONG-LASTING FUNCTIONAL RECOVERY
AND WHAT UNDERLIES RECOVERY AND
AGAIN IS A TOPIC OF REALLY QUITE
FASCINATING STUDY IN LOWER
SPINAL CORD INJURY CASE WHERE
THEY ACTUALLY HAVE IDENTIFIED
CIRCUITS AND CELLS INVOLVED
BASED ON CELL ATLASING AND
UNDERSTAND PLASTICITY OF WHAT IS
GOING ON IN CIRCUITS LOTS TO
COME ON CLINICAL SIDE AND
PRESUMABLY LEADS TO BETTER
THERAPIES AND TREATMENTS.
THAT IS IT FOR ME AND RIGHT NOW
AND YOU CAN STAY UP TO DATE
THROUGH VARIOUS CHANNELS HERE.
OF COURSE, FOR ANYBODY
INTERESTED IN BRAIN FUNDING,
YOUR BEST AND NO. 1 SOURCE FOR
LEARNING MORE IS TO FIGURE OUT
WHO THE PROMO OFFICER IS FOR
THOSE STUDIES.
I LISTED IN THE TEAM LEADS TO
CONTACT ONE OF THE FOLKS. THEY
WILL SEND YOU TO THE RIGHT
PLACE. YOU CAN LEARN MORE
SCANNING Q.R. CODE AND GOING TO
THE WEBSITE. WITH THAT, I WILL
TAKE QUESTIONS.
>> NOT SEEING ANY HANDS RAISED
YET.
>> I WILL GIVE THEM A MINUTE.
RIGHT?
>> YEAH. THAT LAST ONE BROUGHT
TEARS TO MY EYES.
IT IS AMAZING.
>> YEAH. IT IS GOOD TO SEE --
IT IS GREAT TO SEE.
>> SHE IS SO YOUNG, YOU KNOW?
>> YEAH.
>> I PRESENTED THAT SLIDE AS
RECENT SOCIETY OF BIOLOGICAL
PSYCHIATRY AND I DON'T KNOW IF
YOU WERE THERE. I HAVE TO STOP
THE LECTURE. ENTIRE ROOM OF
1,000 PEOPLE BROKE OUT IN
APPLAUSE.
>> I REMEMBER THAT.
>> TOUCHING.
>> YEAH.
>> JIM?
>> HI, JOHN. THANK YOU FOR
THAT PRESENTATION. IT IS REALLY
AMAZING TO SORT OF SEE THE
THINGS THAT ARE HAPPENING. I
DID ACTUALLY HAVE A QUESTION
THOUGH ABOUT THE GENDER OF BRAIN
INVESTIGATORS AS WELL AS
UNDER-REPRESENTED MINORITIES AND
INCREASES YOU ARE SEEING AND
THINK THAT INCREASES ALBEIT
SMALL ARE THEY NEW INVESTIGATORS
OR MORE ESTABLISHED
INVESTIGATORS STARTING TO GET
FUNDING IN THIS AREA?
>> COULDN'T TELL YOU.
GOOD TO LOOK AT.
>> SHORT ANSWERS WE DON'T KNOW
REQUESTED DATE AYOU FROM ON HIGH
AND HAD IT SENT TO US AND DON'T
KNOW WHAT COMES WITH THAT.
>> I WILL GET BACK TO YOU.
MAYBE SHE CAN ANSWER. I'M NOT
SO FAMILIAR WITH HOW MUCH
ADDITIONAL STUFF COMES WITH
THIS. WE CAN PROBABLY FIGURE IT
OUT.
>> MIGHT BEAR ON WHAT AUDIENCE
YOU ARE ACTUALLY GETTING TO AND
WHAT AUDIENCE TO BE BETTER ABOUT
GETTING TO.
>> RIGHT. ABSOLUTELY.
KRYSTAL IS OUR DATA. SHE WILL
LOOK INTO IT.
SAMIR?
>> THANK YOU, JOHN. REALLY
INSPIRING SUMMARY.
CLARIFICATION QUESTION ON GENOME
EDITOR CHALLENGE.
>> IS THAT THROUGH BRAIN
INITIATIVE OR IN PARTNERSHIP
WITH IT OR SEPARATE FROM NIH
ENTIRELY.
>> LET ME CLARIFY COMMON FUND
PROGRAM SOMATIC CELL GENOME
EDITING INITIATIVE THAT AS NAME
APPLIES IS TO DEVELOP NEW
TECHNOLOGIES FOR GENE EDITING
GENE THERAPIES USING GENE
EDITING COMMON PROJECT SOURCE OF
FUNDING ANNOUNCED CHALLENGED
PRIZE MECHANISM IN HOPES GETTING
OUT OF THE BOX NEW
TRANSFORMATIVE METHODS PRECISION
GENE EDITING AND FOR GETTING
PAYLOADS ACROSS BLOOD BRAIN
BARRIER AND COMMON PROJECT
COMANAGED BY NCATS AND NDS AND
WE LEARN BD THAT GETTING GREAT
CASE OF SCIENCE FOMO THAT
COMPLEMENTS WHAT WE ARE DOG AND
WANT TO SEE THIS PROGRAM
SUCCEED.
WE ARE SIGNED ON TO IT DEPENDING
ON PROJECTS COMING IN WE MAY PAY
FOR SOME OF THEM. PROGRAM IS
FULLY FUNDED AND GOOD FOR US TO
BE INVOLVED FOR A COUPLE
REASONS.
ONE, TO BE ABLE TO FUND GREAT
SCIENCE IN OUR SPACE IF IT COMES
IN AND GIVES DIRECT VISIBILITY
WHAT WILL BE OUT THERE. YOU CAN
IMAGINE A LOT OF OVERLAP.
NOW, THEY ARE LOOKING FOR OUT OF
THE BOX TECHNOLOGIES AND WHEN WE
LAUNCHED THE PROGRAM INITIAL
CALL WAS FOR DEVELOPING VECTORS
TO ACCESS BRAIN CELL TYPES.
WE LEFT IT OPEN AND DID NOT
RESTRICT IT TO VECTORS AND
DIDN'T RESTREKT ANY ONE VECTOR
VIRAL AND NONVIRAL AND TURNING
OUT STRONGEST APPLICATIONS THAT
CAME IN WERE EV BASED AND WILL
SEE WHAT COMES IN, IN FUTURE AND
PRETTY COOL STUFF GOING IN
NANOPARTICLE DELIVERY SPACE AND
HAVEN'T SEEN IT YET AND PERHAPS
WILL SEE IT COME IN AND PERHAPS
SOMETHING WILL COME IN THAT WILL
BE REALLY COOL AND KNOW THERE IS
SOMETHING GOING ON OUT THERE IN
THE NONBRAIN SPACE SO FAR IN
NONVIRAL DELIVERY ACROSS
BLOOD/BRAIN BARRIER AND ARE
KEEPING EYES OPEN AND LOOKING
FOR OPPORTUNITIES TO PUSH THIS
SCIENCE FORWARD.
>> [INDISCERNIBLE].
>> ABSOLUTELY. YEAH.
>> THANK YOU.
>> >> DAVID.
>> YEAH. GENE THERAPY SPACE
BOTH ARMENT MENTARIUM AND GRAND
PRIZE AND INTRODUCTIONS AND
COLLEAGUES INVOLVED AT FDA AND
ENTIRE BIOLOGIC CENTERS IS
INTERESTING ADVANCING THERAPIES
TO HUMAN TRANSLATION AND TALKING
ABOUT MANUFACTURING AND VARIETY
OF PURCHASES AND HAPPY TO
PROVIDE CONNECTIONS AS THEY GET
CLOSER TO [INDISCERNIBLE].
>> APPRECIATE THAT. SO FAR ALL
DIRECTLY BRAIN FUNDED PROJECTS
ARE NOT IN HUMAN CLINICAL SPACE
AND ARE REALLY JUST DEVELOPING
GROUNDWORK TOOLS.
YOU CAN SEE WE ARE REALLY HOPING
WHATEVER WE DEVELOP FOR
NON-HUMAN MODELS COULD BE
APPLIED ONE EXAMPLE I GAVE YOU
GENE THERAPY CONSORTIUM HAS FDA
FOLKS AND BETTER AND SOMETHING
TO BE IN TOUCH WITH YOU ABOUT SO
WE CAN STAY AHEAD OF THE GAME
NOT PLAYING CATCH UP ONCE WE
FIND THESE THINGS.
>> OKAY. OTHER QUESTIONS OR
COMMENTS?
>> OUR GROUP HAS BEEN RUNNING
POINT CONTENT BETWEEN BRAIN AND
COMMON FUND PROJECT AND SCG
PROJECT AND IF ANY QUESTIONS YOU
CAN FIND, FIND ME AND WE CAN
TALK MORE ABOUT THAT.
>> OKAY. OTHERS?
HOW ARE WE DOING ON TIME?
>> WE ARE FINE AND A LITTLE
AHEAD. 8 MINUTES AHEAD. WE CAN
MOVE TO DR. GRADY IF SHE IS --
>> CHRISTINE, YOU HERE?
>> I'M HERE.
>> GREAT TO SEE YOU.
>> NICE TO SEE YOU.
THANK YOU FOR THE VIDEO WORTH A
MILLION WORDS.
IT WAS BEAUTIFUL. READY FOR ME.
>> WE ARE READY, YEAH.
>> THANKS FOR PUTTING ME ON THE
AGENDA I'M CHRISTINE GRADY.
I THOUGHT I WOULD DO IN A FEW
MINUTES THREE THINGS.
ONE IS JUST SAY A WORD ABOUT
WHAT NEUROETHICS WORKING GROUP
IS FOR ANYBODY THAT DOESN'T KNOW
MULTICOUNCIL WORKING GROUP.
IT WAS AN ACRONYM GIVEN TO IT BY
HANK WHO USED TO BE ON THE
COUNCIL. IT -- THE NOOG IS A
GROUP OF NEUROENL CYSTS AND
NEUROSCIENTISTS WITH BRAIN AND
INPUT RELATED TO ETHICAL AND
SOCIAL IMPLICATIONS OF BRAIN
FUNDED RESEARCH AND ARE MEMBERS
WE SHARE AND SEVERAL PEOPLE PART
OF THE MULTICOUNCIL WORKING
GROUP ARE ALSO MEMBERS OF NOOG.
IN DOING AND PROVIDING INPUT WE
HELP TO IDENTIFY ETHICAL
CHALLENGES THAT THE BRAIN MIGHT
ENCOUNTER IN WORK THEY ARE DOING
AND PROVIDE ETHICS CONSULTATIONS
TO RESEARCHERS FUNDED BY BRAIN
AND PROGRAM STAFF AND IDENTIFY
NEUROETHICS RESEARCH QUESTIONS
THAT MIGHT BE IMPORTANT TO BE
ADDRESSED AND PROVIDE GUIDANCE
ON KEY ETHICAL CHALLENGES.
I WANTED TO TALK ABOUT TWO
THINGS WE ARE ONE THAT WE ARE
PLANNING AND THAT WE HAVE JUST
COMPLETED AND ONE IS A WORKSHOP
BEING PLANNED FOR JULY OF THIS
YEAR.
THIS IS A WORKSHOP THAT IS ON
THE ETHICS OF SHARING INDIVIDUAL
LEVEL HUMAN BRAIN DATA THAT IS
COLLECTED IN RESEARCH. IT IS
PLANNED FOR JULY 7 TAENTH AND
18TH AND WILL BE A HYBRID
MEETING AND WE HOPE THAT PEOPLE
WILL BE IN PERSON IN BETHESDA.
IT WILL ALSO BE AN OPTION TO
PARTICIPATE VIRTUALLY.
WORKSHOP WAS MOTIVATED BY NUMBER
OF ONGOING DISCUSSIONS ABOUT
DATA SHARING. FIRST IT CAN
ACCELERATE SCIENTIFIC PROGRESS
MAXIMIZING SOCIAL VALUE OF
RESEARCH SEEMING TO BE
IMPERATIVE TO SHARE DATA WHEN
POSSIBLE AND NUMBER OF POLICIES
INCLUDING ONE THAT BRAIN
INITIATIVE HAS ON SHARING DATA
AND PEOPLE WORRIED IN THE PAST
ABOUT POTENTIAL OF RISKS SHARING
HUMAN DATA FOR INDIVIDUAL
PARTICIPANTS AND GROUPS IMPACTED
ABOUT I -- THAT MIGHT BE
IMPACTED BY INFERENCES MADE FROM
THE DATA.
THERE MIGHT BE PARTICULAR
CONCERN ABOUT HARMS ARISING FROM
SHARING NEURAL DATA AND NEURAL
DATA IS NOT A MONOLITH AS YOU
ALL KNOW.
KINDS OF HARMS AND EXTENT TO
WHICH SHARING DATA CAN CAUSE
HARM LIKELY VARIES CONSIDERABLY
BY NATURE OF THE DATA AND
WORKSHOP IS AIMING TO DETERMINE
WHETHER OR NOT CATEGORIZING
NEURAL DATA BY POTENTIAL RISKS
OF DATA SHARING MIGHT HELP
INFORM RESEARCH PARTICIPANTS
ABOUT RISKS OF DATA SHARING AND
RESEARCHERS ABOUT THE KINDS OF
SAFEGUARDS THAT THEY MAY WANT OR
THAT THEY SHOULD IMPLEMENT WHEN
THEY ARE COLLECTING DATA AND
SHARING DATA.
PROPOSAL AT MOMENT AND PLAN AT
MOMENT IS TO BRING TOGETHER
RELEVANT STAKEHOLDERS TO ADDRESS
A FEW KEY QUESTIONS LIKE WHAT
TYPE OF DATA DO DIFFERENT
NEUROTECHNOLOGIES COLLECT AND
STORE?
WHAT INFERENCES CAN BE MADE FROM
DATA AND RISKS SHARING FROM DATA
AND WHAT WE SHOULD TELL
POTENTIAL PARTICIPANTS ABOUT
THOSE RISK MOORNDZ INFORMATION
ABOUT THAT WILL COME SOON AND
HOPEFULLY SOME WILL BE
INTERESTED IN PARTICIPATING.
SECOND THING TO TELL YOU ABOUT
IS A CONSULT DONE BY NOOG AT
JANUARY MEETING.
NEUROETHICS WORKING GROUP MEETS
TWICE A YEAR, ONCE IN JANUARY
AND ONCE IN AUGUST. WE DON'T
MEET IN MAY AS YOU ALL DO.
JANUARY WE HAD A CONSULT
RECENTLY IN THE LAST FEW WEEKS,
ACTUALLY. DR. FARHANI PRESENTED
SUMMARY OF CONSULT TO NIMH
CONSULT AND CONSULT WAS ABOUT
THE BRAIN INITIATIVE CELL ATLAS
NETWORK THAT IS AS YOU KNOW
BUILDING REFERENCE BRAIN CELL
ATLAS FOUNDATIONAL FRAMEWORK
ACROSS SPECIES STUDY OF BRAIN
EVOLUTION AND FUNCTION BY CAN
ACRONYM OF THAT PRIMARILY POST
MORTEM AND SOMETIMES LIVING
DONORS FROM SURGICAL RESECTIONS
AND BICAN IS COLLECTING AND
SHARING PRIMARY SEQUENCE DATE
THAW IS POTENTIALLY
RE-IDENTIFIABLE THAT RAISES
QUESTIONS ABOUT THE RELATIVE
MERITS AND RISKS OF OPEN ACCESS
VERSUS CONTROLLED ACCESS OF
THOSE GENOMIC PRIMARY SEQUENCING
DATA THAT IS WHAT THE CONSULT
WAS ABOUT.
IN JANUARY, THE NOOG HEARD FROM
SEVERAL PROGRAM STAFF ABOUT THIS
ISSUE AND SOME OTHER ENTITIES AT
NIMH THAT HAVE CHOSEN CLOSED AND
OPEN DATA SHARING AND DR. ELLEN
CLAYTON AN EXPERT IN THE FIELD
OF PRIVACY SHARING AND DATA AND
COUPLE TAKEAWAY POINTS PRESENTED
TO NIMH COUNCIL.
ONE IS APPARENTLY INSUFFICIENT
OR NO CLEAR EVIDENCE THAT IS
QUANTIFYING EITHER ADDED
BENEFITS OR ADDED RISKS OF
OPENED DATA SHARING RELATIVE TO
CONTROL DATA SHARING AND WITHOUT
THOSE KINDS OF CLEAR -- WITHOUT
THAT CLEAR EVIDENCE, IT IS
REALLY HARD TO DETERMINE WHAT
THE RELATIVE MERITS ARE AND HOW
TO -- AND WHAT -- HOW THE STUDY
SHOULD BE PROCEEDED.
THE GROUP FELT THAT IN THE
ABSENCE OF CLEAR DATA
QUANTIFYING RISKS AND BENEFITS
THAT WE SHOULD HAVE MORE
ARTICULATION OR MORE CLEAR
ARTICULATION OF WHAT BENEFITS
ARE IN ORDER TO JUSTIFY
POTENTIAL RISKS.
AND ALSO SUGGESTED THAT MAYBE
IMBEDDING ADDITIONAL BIOEDGE CIS
IN [INDISCERNIBLE] PROJECTS
ALTHOUGH THERE IS SOME INVOLVED
THAT COULD CONSIST OF SOME
CHALLENGES AND COLLECTING THESE
KINDS OF DATA AS WELL.
THAT IS ALL I WANTED TO TELL YOU
ABOUT THE NOOG. I'M HAPPY TO
ANSWER ANY QUESTIONS OR IF ANY
OF THE OTHER MEMBERS OF NOOG WHO
WANT TO ADD TO WHAT I SAID OR
WANT TO JOIN IN, GO AHEAD.
>> THANK YOU, CHRISTINE.
>> YOU'RE WELCOME, JOHN.
I WISH I HAD A FANCY VIDEO TO
SHOW.
>> WE WILL GET YOU ONE.
>> OKAY.
WELL, STAY TUNED. LOTS OF GREAT
STUFF IS HAPPENING IN THIS
SPACE. I REALLY APPRECIATE
EFFORTS OF CHRISTINE AND
[INDISCERNIBLE] AS CO-CHAIRS BUT
ENTIRE GROUP HAS REALLY BROUGHT
TO LIGHT VERY IMPORTANT AND
REALLY INTERESTING TOPICS FOR
DISCUSSION.
WE REALLY DO BENEFIT FROM ALL OF
THAT.
>> OKAY. HUGO, YOUR CAMERA IS
ON. I TAKE IT YOU ARE READY ON
YOUR END?
>> I AM.
>> WE HAVE A TREAT TODAY AT
TODAY'S MEETING AND SCIENTIFIC
PRESENTATION FROM ONE OF THE
NCWG MEMBERS AND [INDISCERNIBLE]
REPRESENTATIVE FROM CHILD HEALTH
NICHD DRAND BELLIAN AND IS
DISTINGUISHED PROFESSOR AT
COLLEGE OF MEDICINE AND LAB IS
VERY WELL KNOWN FOR DEVELOPING
VARIOUS GENETIC SCREENS IN
DROSPHILIA TO UNRAVEL THEM IN --
IN RECOGNITION OF AS MANY
IMPORTANT CONTRIBUTIONS IS AN
ELECTED MEMBER OF AMERICAN
ASSOCIATION OF ARTS AND SCIENCES
AS WELL AS NATIONAL ACADEMY OF
SCIENCES AND HUGO WILL TELL US
ABOUT HIS WORK TODAY ON
ENGINEERING FLIES AND STUDYING
GENE AND PROTEIN FUNCTION. ALL
YOURS.
>> THANK YOU. SEE MY LAST
SLIDE?
>> WE ARE SEEING --
>> YES.
>> ALL RIGHT.
>> TODAY I WILL TALK ABOUT
ENGINEERING FLIES AND CRISPR
HEAVY TALK I WILL WARN THAW IS
MOSTLY DESCRIBING HOW WE DEVELOP
TECHNOLOGY AND HOW TECHNOLOGY
HAS BEEN REALLY HELPFUL HELPING
PATIENTS TO PARTICIPATE IN
UNDIAGNOSED RESEARCH. MUCH HAS
BEEN DONE BY TALENTED ASSISTANT
PROFESSOR IN THE LAB AND I WILL
START FIRST WITH UNDIAGNOSED
DISEASES NETWORK.
PATIENTS CAN APPLY TO
UNDIAGNOSED DISEASE NETWORK AND
IS A LOT OF PATIENTS
UNDIAGNOSED. WORLDWIDE
ESTIMATED 400 MILLION OF THESE
PATIENTS THAT TYPICALLY UNDERGO
WHAT WE CALL A DIAGNOSTIC
ODYS
ODYSSEY.
THEY GO FROM A DOCTOR TO
HOSPITAL TO ANOTHER ONE AND GET
TESTS. THEY ARE STILL NOT
DIAGNOSED.
WHEN REACHING THIS POINT THEY
WANT TO REALLY BE DIAGNOSED THEY
CAN APPLY TO COORDINATION
CENTNER HARVARD OF UNDIAGNOSED
DISEASES NETWORK AND GET
ASSIGNED A CLINICAL UNIT IN ANY
STATES AND IS 12 CLINICAL SIDES
AND THEY WILL DO A FREE
PHENOTYPIC WORKOUT AND WORK WITH
FILES FROM PATIENTS SEEING IF
THERE IS ANYTHING ELSE THEY HAVE
TO DO AND ESSENTIALLY TRY TO
PROVIDE DIAGNOSIS. MANY TIMES
THEY CANNOT AND WILL START TO
SEQUENCE THREE INDIVIDUALS AND
SHOULD SAY THAT MANY PATIENTS
PARTICIPATING HERE ARE CHILDREN
AND WOULD SAY 60 TO 70% OF
PARTICIPANTS ARE CHILDREN ALMOST
ALL OR MOST HAVE NEUROLOGICAL
PHENOTYPES AND THEY SEQUENCE
PARENTS DOING WHOLE GENOME
SEQUENCING OF PARENTS AND KIDS
AND FIND A FEW VARIANTS IF IN
GENES THAT THEY SUBMIT TO MODEL
ORGANISM SCREENING CENTER. THEY
DON'T KNOW IF THEY ARE CAUSE OF
THE DISEASE OR NOT.
IDEA IS TO MODEL THEM IN MODEL
ORGANISMS AND WE DEVELOP THIS
TOOL AND BIOINFORMATIC TOOL
CALLED MARVEL THAT IS REALLY A
COMPENDIUM OF DATA FROM ALL
KINDS OF HUMAN GENETICS
DATABASES AND MODEL ORGANISM
DATA BASES TO PROBE WHAT WE CAN
WITH FUNCTION OF WHAT THE GENE
WOULD BE IF PHENOTYPE WITH THE
PATIENT MATCHES ANYTHING BEING
OBSERVED IN THE MODEL ORGANISM
MOST ARE NEW HUMAN GENE AS
ASSOCIATED WITH HUMAN DISEASE
AND WE NEED TO PRIORITIZE IN
WHICH MODEL ORGANISM WE WILL
MODEL AND THOSE -- THAT IS 20 TO
25% OF GENES AND GENES SUPER
CONSERVED AND WHERE AMINO ACIDS
ARE CONSERVED AND GENES ARE
CONSERVED IN -- ANYTHING
IN-BETWEEN MAJORITY OF GENES IS
MODELS IN DROSPHILIA THAT HAS
BIG TEARS WOW SEE BECAUSE OF
ELEGANT TECHNOLOGIES AVAILABLE
DEVELOPED IN THE FRUIT FLY FIELD
AND I WILL START WITH A GENERAL
INTRODUCTION WHAT WE DO.
EFFECTED INDIVIDUAL HAS A
[INDISCERNIBLE] TRUE FOR AET 5%
OF GENES SUBMITTED IN
UNDIAGNOSED DISEASES NETWORK AND
FIRST THING WE DO IS CREATE THIS
ALLELE. WHAT IT IS, IT IS
ARTIFICIAL [INDISCERNIBLE] PUT
IN ONE OF FIRST INTERONS OF GENE
OR CODING INTERON OF GENE AND
SPLICED DONOR UPSTREAM OF SPLICE
ACCEPTOR AND WILL EXPLAIN
TECHNOLOGY IN DETAIL IN SOME OF
NEXT SLIDES AND THIS LEADS TO
INSERTION OF THIS POLY A THAT
ARRESTS TRANSCRIPTION WHAT YOU
GET IS A SHORT MESSAGE WITH T2A
SIDE THAT WILL ARREST DURING
TRANSLATION AND PRODUCING L4 PRO
E- TEEN THIS PROTEIN IS
EXPRESSING PROPER SPATIAL
EXPRESSION PATTERN TO BE USED TO
DO A VARIETY OF EXPERIMENTS THAT
ARE VERY IMPORTANT IF YOU WANT
TO ADDRESS FUNCTIONS OF THESE
GENES MODELING HUMAN THERE.
FIRST, WHERE IS GENE EXPRESSED
SURPRISINGLY FOR 70% OF GENES WE
DON'T KNOW WHERE GENES ARE
EXPRESSED AND BY CROSSING THIS
WITH INSERTION TO US
[INDISCERNIBLE] WE CAN IDENTIFY
CELLS THAT EXPRESS GENE AND CAN
DO PHENOTYPIC ANALYSIS AND
CELLULAR ALTERATION AND
METABOLOMICS SINGLE CELL
SEQUENCING TO PROBE INTO
MECHANISM AND GENE NOT STUDIED
WELL WILL DISCOVER WHAT GENE HAS
AND IF STUDIED WE CAN PROVIDE IN
VIVO DATA FOR WHAT IS ASSOCIATED
WITH LOSS OF THE FUNCTION OF THE
GENE. IMPORTANTLY WE CAN USE
RESCUE ASSAYS AND HERE WE CAN
PUT IN HUMAN REFERENCE CDNA AND
SEE IF IT RESCUES FLY MUTATION
AND MOST ARE REALLY SEVERE LOSS
OF FUNCTION MUTATIONS AND NOW WE
CAN DETERMINE AND TEST HUMAN
VARIANTS FOUND IN PATIENT AS
SESING IF HUMAN VARIANTS EFFECT
FUNCTION OF THE PROTEIN OR NOT.
THIS TYPICALLY ALLOWS US TO
DETERMINE IF LOSS OF FUNCTION OR
GAIN OF FUNCTION AND IS
[INDISCERNIBLE] FROM YOU WANT TO
KNOW STARTING THERAPY IF
FUNCTIONING LOSS OR GAIN THAT
MAKES A DIFFERENCE IN THE
APPROACH AND SECOND STRATEGY WE
USE A SIMILAR STRATEGY USING
CRISPR INTEGRATING ARTIFICIAL
AXON THAT HERE WE INTEGRATED HAS
NO SPLICED DONOR. THIS HAS A
SPLICED DONOR AND MEANS IT WILL
BE PART OF THE PROTEIN IF ALL IN
FRAME AND IDEA IS THEN TO
INTEGRATE THIS TAG OR SPLICED
DONOR GFP SPLICED DONOR AND
CREATE AN ARTIFICIAL AXON IN THE
GENE LEADING TO GFE FUSION
PROTEIN AND 75 TO 80% OF THESE
INSERTIONS DON'T DISRUPT PROTEIN
FUNCTION AND INSERT IN SUCH A
WAY NOT TO DISRUPT PROTEIN
FUNCTION AND ALLOWS TO DO
PROTEIN LOCALIZATION STUDIES AND
LIVE GFP STAINING AND THIS BRAIN
LOOKING AT LIVE GFP FOR THIS A
GENE OR STAYING WITH ANTIGENE FP
LOOKING AT WHAT ANTIBODY REVEALS
AND OFTEN PATTERNS ARE QUITE
SIMILAR AS YOU WOULD EXPECT.
NOW ONCE YOU HAVE THEM LET'S SAY
GENE EFFECTING DEVELOPMENT LET
FLIES DEVELOPING ADULTHOOD AND
USING THIS STRATEGY TO REMOVE
THE PROTEIN THAT IS THIS
NANOANTI-BODY AND YOU WILL HAVE
A LOSS OF THE PROTEIN YOU CAN
MONITOR THE LOSS. YOU CAN STAIN
FOR GFP AND CREATE ADULT FLIES
LACKING A SPECIFIC PROTEIN AND
THEN AFTER A WHILE YOU CAN DO
PHENOTYPIC ASSAY AND YOU CAN
RETURN THE PROTEIN. IT IS A
TEMPERATURE SENSITIVE PHENOMENA.
AT 18 PROTEIN WILL BE THERE AND
28, PROTEIN WILL GRADUALLY
DISAPPEAR AND BRINGING FLIES
BACK TO 18, PROTEIN WILL
REAPPEAR. YOU CAN DETERMINE IF
YOU MADE A LESION THAT CAN OR
CANNOT BE CORRECTED BY RESTORING
THE PROTEIN FUNCTION.
THIS CAN, AGAIN, ALSO BE
IMPORTANT IN THE CONTEXT OF SOME
HUMAN DISEASE.
HERE I, SHOW YOU, YOU KNOW, A
FEW PATTERNS OF [INDISCERNIBLE]
THAT WERE EITHER STAINED LIFE OR
LOOKED AT LIVE OR STAINED WITH
GFP. YOU SEE PATTERNS ARE
SIMILAR AND WITH ANTIBODY YOU
REVEAL MORE STAINING IN QUITE A
FEW CASES THAT SOMETIMES IS
PRETTY DRAMATIC AS SHOWN HERE
AND IN GENERAL PATTERNS ARE
QUITE MATCHING. YOU CAN DO LIVE
GFP STAINING OR STAIN WITHIN AN
ANTIBODY.
ALL RIGHT.
SO, LET'S KIND OF DIG INTO SOME
OF THE INTRICK KASSYS RELATED TO
THE TECHNOLOGY WE USE CRISPR TO
GENERATE THESE TARGETED
INSERTIONS AND WE DO THIS IN
CONTEXT OF UNDIAGNOSED DISEASES
NETWORK AND GOAL IS TO REALLY
THAT IS SUPPORTED BY DOING A
GENE DISRUPTION PROGRAM
DISRUPTING 9,000 FLY GENES THAT
HAVE HUMAN HOMOLOGS AND DOING
THIS SYSTEMATICALLY CREATE ALL
THESE STO STALKS NOT THERE YET
AND CREATED 3,000 SO FAR BUT
HOPE IS TO DO THIS
SYSTEMATICALLY. HOPE AND
ADVANTAGE OF THIS TECHNOLOGY IS
REALLY HELPING US IN MANY CASES
TO DIAGNOSE OR HELP TO DIAGNOSE
HUMAN DISEASE AND STARTED THIS
PROGRAM GENERATING CONSTRUCTS
WITH 1KB HOMOLOGY ARMS AND
EXPRESSING KAS 9 INJECT VECTOR
WITH CONSTRUCT AND IN KAS 9
INSERTING INTO CODING INTERIM OF
A GENE. THIS IS THE MARKER WE
USE.
ORIGINALLY, THESE WERE NOT SO
EASY TO MAKE NEEDING 1KB
HOMOLOGY ON EITHER SIDE AND NEED
THIS RELATIVELY LARGE INSET AND
SPEND A BIT OF TIME CLONING TO
GET THIS DONE AND IS VERY USEFUL
AS A PROOF OF PRINCIPLE.
IT WAS VERY KIND OF REWARDING TO
SEE ALL OF THE APPLICATIONS THAT
WERE INVOLVED HERE.
FIRST, YOU CAN DISRUPT A GENE
AND CREATE SEVERE LOSS OF
FUNCTION AND SECOND YOU CAN
IMMEDIATELY DO A CONTROL AS TO
HAVE YOU GENERATED OTHER LESIONS
IN THE GENOME WHILE YOU PROVIDED
THIS OR CREATED THIS INSERT WITH
CRISPR?
STRATEGY HERE IS USING THIS THAT
YOU PRODUCE IN THE CELLS WHERE
YOU Z -- THIS GENE IS EXPRESSED
AND CROSS TO US FLIPPASE.
BECAUSE FRT SITES ARE ON THIS,
THIS WILL EXCISE THE CONSTRUCT
AND RERESTORE THE NORMAL
PHENOTYPE. YOU WILL REVERT TO
THE PHENOTYPE CROSSING TO THIS
FLIP AND THAT IS VERY NICE AND
SIMPLE CONTROL TO SHOW WHATEVER
PHENOTYPE YOU CHARACTERIZED IS
DUE TO INSERTION NOT TO SECOND
SITE MUTATION AND YOU CAN
OBVIOUSLY USE THIS STRATEGY
REMOVING MUTATION IN DIFFERENT
TISSUE AND DO THIS
SYSTEMATICALLY ASSESSING WHICH
TISSUE REQUIRES FUNCTION OF THIS
PROTEIN THAT IS OBVIOUSLY NOT A
NICE FEATURE.
SECOND, YOU CAN USE THIS TO
REPLACE THIS CASSETTE WITH AN
AXON THAT ENCODES GFP THAT I
MENTIONED BEFORE. THIS WILL
LEAD TO ARTIFICIAL AXON THAT IS
INSERTED BETWEEN TWO CODING
AXONS AND CREATE A PROTEIN
FUSION.
THIRD INSERTION TO BE USED AND
RESCUING GENE MENTION BRG YOU
CAN START WITH FLY CDNA AND IF
THAT RESCUES THAT IS ALMOST
ALWAYS THE CASE AND YOU PUT IN
HUMAN CDNA AND TEST VARIANT.
SO, TALKING ABOUT HUMAN
[INDISCERNIBLE] WE NEED TO
CREATE THESE HUMAN CDNAS AND WE
GATHER LIBRARY OF 33,000 FULL
LENGTH US HUMAN CDNA AND
SYSTEMATICALLY PUTTING UNDER
CONTROL OF UIS AND MAKE
TRANSGENIC FLIES FIRST VECTORS
MAKING TRANSGENIC FLIES SO WE
CAN CREATE A LIBRARY OF 10,000
STALKS THAT EACH CARRY HUMAN
CDNA AND SO FAR GENERATED 7,000
OR 800,000 HUMAN CDNAS AAND
CREATED MORE THAN 5,000
TRANSGENIC STALKS AND THEY ALLOW
US TO VERY QUICKLY TEST IF WE
CAN HUMANIZE THE FLY AND DO
THESE HUMANIZATION EXPERIMENTS
TESTING IN CONTEXT OF HUMAN
DISEASE AND PROBLEM WE RUN INTO
WITH THIS STRATEGY IS WE
COULDN'T APPLY THIS TO ABOUT 50%
OF GENES.
THEY DON'T HAVE INTERONS AND ARE
LARGE ENOUGH TO INTEGRATE THE
T2A-GAL4 REGULATORY ELEMENTS
PRESENT IN THESE ARE THERE
INSERTING T2A-GAL 4A WHEN NO
INTERIMS ARE SMALL WE LIKE TO
INSERT GAL 4 AND CAN'T DO THIS
USING THIS STRATEGY AND GIVEN
50% OF THEM DON'T HAVE
OPPORTUNITY TO TAG THEM WE HAD
TO DEVELOP A NEW TAGGING
TECHNOLOGY THAT IS HERE TO
REPLACE CODING SEQUENCE OF THE
GENE EXPRESSING TWO GUIDE RNAS
AND INSERT THESE WITH A
TRANSFORMATION MARKER THAT IS
FLYING BY FRT SITES AND BY DOING
THAT YOU REPLACE ENTIRE CODING
SEQUENCE OF THE GENE AND USE
THIS CO-ZACK SEQUENCE BECAUSE
YOU WANT TO MAKE SURE THAT YOU
KNOW TRANSLATION IS EFFICIENT.
THIS GIVES A SIMILAR RESULT AND
LEADS TO PRODUCTION OF GAL 4 IN
THE SPATIAL AND TECH PORAL
EXPRESSION PATTERN OF THE GENE
THAT IS TAGGED AND THIS IS A
EXAMPLE TO SHOW YOU A FEW
[INDISCERNIBLE] OF BRAINS OF
STALKS WE CREATED WITH THEM IN
MANY HUNDREDS OF THESE AND
TYPICALLY 80% OF GENES EXPRESSED
IN A NERVOUS SYSTEM TRUE FOR
T2A-GAL 4 AND YOU SEE IN THESE
BRAINS DIFFERENT EXPRESSION
PATTERNS GENERATED BY CROSSING
KOZAK GAL 4 STRAIN WITH US RFP
PROTEIN AND DISCOVERED A LOT OF
NEW EXPRESSION PATTERNS FOR
GENES THAT WERE OBVIOUSLY NOT
CHARACTERIZED BEFORE.
SO, THIS TECHNOLOGY IS NICE.
IT IS PRETTY LABOR INTENSIVE.
IF WE WANT TO DO 10,000 STALKS
AND PARTICIPATE IN THIS NETWORK
WHEN YOU NEED PCR OR
[INDISCERNIBLE] EXTRACTION AND
PERFORMING GOLDEN GATE ASSEMBLY
INCLUDING KAS SET YOU WANT TO
INTEGRATE INTO THE GENE
VERIFICATION RESTRICTION ENZYMES
AND DO SEQUENCING.
THIS APPROACH IS NOT VERY KIND
OF -- IT IS LABOR INTENSIVE.
AND QUITE EXPENSIVE FOR THIS
WITH WHEN YOU HAVE TO DO
THOUSANDS OF THEM.
SO, IN ADDITION, ABOUT 20 TO 25%
OF THE CASE IS THE STRATEGY
FAILS AND YOU HAVE TO START
AGAIN. WE DECIDED TO DEVELOP A
NEW TECHNOLOGY THAT WE THINK
COULD BE USED ACTUALLY IN MANY
SPECIES THAT IS THAT WE
DEVELOPED A VECTOR THAT IS SHOWN
HERE.
AND INSTEAD OF USING 1KB HOM OL
ARMS WE USE 200 TO 200 BASE PAIR
HOMOLOGY ARMS ON EITHER SIDE
THERE AND DO THAT BY GUIDE RNA1
TARGET SITE THAT IS NOT PRESENT
IN THE FLY GENOME AND IDEA IS
TO INJECT PLASMA THAT CRISPR
CUTTING RNA1 WILL FREE UP AN ARM
OR PIECE OF DNA FLANKED ON
EITHER SIDE 200 BASE PAIR
HOMOLOGY ARMS TO INSERT QUITE
EFFICIENTLY. YOU GENERATE
VECTOR AND CREATE 2 GUIDE RNAS
AND INJECT AND BY DOING SO YOU
FIRST GENERATE LINEAR FRAGMENT
OF DNA THAT CAN THEN COMBINE
WITH THE TARGET GUIDE R IN. A
INTEGRATE INTO THE GENE.
TO OUR SURPRISE, THIS METHOD WAS
SIGNIFICANTLY MORE EFFICIENT
THAN 1KB HOMOLOGY ARM STRAIGHT
JI AND WILL COME BACK TO THAT.
THIS IS, YOU KNOW, NOT THE
STRATEGY OF CHOICE.
HOWEVER, YOU NEED TO MAKE THREE
VECTORS AND MAKE A VECTOR AND
DONOR AND GUIDE RNA1 AND GUIDE
RNA TARGET. THE IDEA WAS LET'S
OPTIMIZE THIS AND BRING GUIDE
RNAS INTO THIS VECTOR. SO, WE
CAN ASK THE COMPANY TO
SYNTHESIZE A VECTOR THAT HAS
GUIDE RNA200 BASE PAIR HOMOLOGY
ARMS AND TWO GUIDE RNAS TO JUST
CLONE INTO THIS VECTOR AND
FRAGMENT. WE ARE READY FOR
INJECTIONS THAT WOULD BE MUCH
MORE EFFICIENT AND CHEAPER. IT
IS ALL DONE BY SYNTHESIS.
SO SHORTER HOMOLOGY ARMS ARE
CREATED BY A COMPANY AND ARE
VERY CHEAP. WE CAN DO IT FOR
$80 PER VECTOR AND THEY ARE
EFFICIENT AND QUITE FLEXIBLE.
WE CAN OBVIOUSLY TARGET WHATEVER
WE WANT. WE THEN CREATED
ANOTHER VEKT YR THAT WE INCLUDED
A GUIDE RNA1. THAT IS GUIDE RNA
NOT PRESENT IN THE FLY GENOME
WITH TRNA AND NOW IN THE -- WE
ASKED A COMPANY TO MAKE THIS
PIECE OF DNA HERE, WHICH IS 570
BASE PAIRS TO CODE THE GUIDE RNA
WE TARGET IN THE GENOME FLANKED
BY ONE SIDE WITH GUIDE RNA AND
HOMOLOGY ARMS MULTIPLE CLONING
SITE THAT WE CAN EASILY INSERT
WHATEVER PIECE OF DNA WE WANT.
WE NOW ORDER THIS FROM THE
COMPANY AND THEY PROVIDE US WITH
THIS VECTOR FOR ABOUT 80 OR $100
DEPENDING ON THE SIZE OF THE
INSERT.
THIS MADE IT EVEN MORE EFFICIENT
AGAIN.
NOW, YOU CREATE AND PRODUCE TWO
GUIDE RNAS IN THE SAME PLAS MID
AND EVERYTHING IS DELIVERED NECK
WI MOLAR RATIOS SO YOU CAN
REALLY GET AN EFFICIENT
INTEGRATION SYSTEM AND SYSTEM
ALLOWS US TO BRING INTO THESE
VECTORS DIFFERENT CLONES AND
DIFFERENT SIZES AND DIFFERENT
STRUCTURES OR DIFFERENT TAGS
LIKE SPLICE ACCEPTOR DONOR
T2A-GAL 4 AND PIECES OF DNA WE
WANT AND QUITE EFFICIENCY
ELIMINATES NEED TO CLONE GRNA
AND INCREASES TRANSFORMATION
EFFICIENCY AND WE ARE CURRENTLY
AT 85% TRANSFORMATION
EFFICIENCY. I DON'T THINK WE
WILL BE ABLE TO IMPROVE THAT.
MOREOVER IT IS MUCH CHEAPER THAN
WHAT WE DID BEFORE RESPECT TO
GFP TAGGING YOU CAN ARGUE
TAGGING GFP IN A -- BETWEEN TWO
CODING AXONS THAT WILL BE
DETRIMENTAL AND IN FACT IS NOT
DETRIMENTAL AT ALL AND IN FACT
IS LESS DETRIMENTAL TO CREATE
ARTIFICIAL AXON WITH GFP
INTERNALLY AND PUTTING IT AT CAR
BOXIL TERM AND [INDISCERNIBLE]
IN THIS CASE WE TAG THIS GENE IN
EVERY SPACE WE COULD INTERNALLY
OR CORE BOXY TERNLLY AND TERNLLY
INTO PROTEIN AND IN ALL CASES
PROTEIN WAS FUNCTIONAL.
THERE WAS NO PHENOTYPE
ASSOCIATED WITH INSERTIONS OF
THOSE GFPS.
FINALLY, THE LAST STRATEGY THAT
WE ARE JUST STARTING TO USE IS
REALLY TO HUMANIZE FLY BY
COMPLETELY REPLACING GENE CODING
SEQUENCE WITH FLY WITH HUMAN CD
IN IT AND WORKS NICELY WHEN
THERE IS NO INTERNAL CONTROL
SITES AND NO INTERNAL ENHANCERS
AND GENE IS RELATIVELY SMALL TO
INSERT HUMAN SEED THAT IS THE
REFERENCE OR WILD TYPE SEED OR
PUT IN VARIANT THAT IS
IDENTIFIED IN THE PATIENTS AND
THIS STRATEGY ALSO IS NICELY
WORKING AND ALTHOUGH WE DON'T
HAVE A LOT OF DATA YET TO SEE
HOW EFFICIENT THE SYSTEM WORKS.
FINALLY, IN THE LAST TWO SLIDES
I WANT TO COME BACK TO, YOU
KNOW, THIS NETWORK AND WHAT WE
HAVE ACHIEVED IN THE LAST FEW
YEARS.
BY USING THIS TECHNOLOGY TO
MODEL HUMAN DISEASE IN FLIES AND
THIS SLIDE SUMMARIZES KIND OF
THE WORK THAT WE HAVE DONE AND
HOW WE HAVE HELPED UNDIAGNOSED
DISEASES NETWORK IN IDENTIFYING
NEW GENES ASSOCIATED WITH NEW
HUMAN DISEASE AND YOU CAN SEE
THAT TECHNOLOGY THAT WE HAVE
DEVELOPED IN FRUIT FLIES IS
BEING QUITE PRODUCTIVE AND
ALLOWED US TO HELP IN DIAGNOSIS
OF MORE THAN 50 NEW HUMAN
DISEASES.
ONE OF THE INTERESTING FEATURES
IS OBVIOUSLY YOU CAN CONTINUE TO
WORK ON THESE TEAMS AND DISCOVER
NEW INTERACTING PARTNERS AND
MOLECULAR MECHANISMS AND FLIES
OFFER YOU OPPORTUNITY TO SCREEN
FOR DRUGS AND WE TYPICALLY TAKE
FDA APPROVED DRUGS AND IN THIS
CASE RAPA MAI ASEEN IN THIS CASE
OR [INDISCERNIBLE] AND ONCE WE
HAVE A BETTER UNDERSTANDING OF
MECHANISM OF GENE USING PROTEIN
TAGS MASS SPECK AND INTERACTIVE
PROTEINS LOCALIZATION AND
EXPRESSION OF ALL THESE GENES
AND COME UP WITH NOVEL PATHWAYS
TO START SCREENING FDA APPROVED
DRUGS AND SEE IF DRUGS WORK AND
IN SOME CASES THESE DRUGS LIKE
IN THIS CASE HERE CRIP ROW MEAN
OR RAPA MAI CIN ARE USED ALREADY
IN PATIENTS THAT ARE EFFECTED BY
MUTATIONS IN THE CORRESPONDING
GENES LISTED HERE.
I THINK THAT THE WHOLE APPROACH
IS OBVIOUSLY VERY HEAVILY BASED
ON TECHNOLOGY DEVELOPMENT THAT
IS OBVIOUSLY IN THE SPIRIT OF
WHAT BRAIN DOES AND AT SAME TIME
YOU CAN EXPLORE BIOLOGY QUITE
RAPIDLY AND YOU CAN START TO
THINK ABOUT DRUG DEVELOPMENT
ONCE YOU UNDERSTAND THE
MECHANISM BETTER.
IN SUMMARY, TECHNOLOGICAL
UPGRADES BASED ON CRISPR REALLY
RESULT IN A VERY SIGNIFICANT
AMOUNT OF TIME SAVING AND COST
SAVING AND IS ALLOWING US TO DO
THOUSANDS OF HOPEFULLY 9 OR
10,000 GENES IN THE FRUIT FLY
AND ALLOW US TO HAVE GENE
PROTEIN FUNCTION RAPIDLY AND
CRITICAL REAGENTS TO MODEL HUMAN
DISEASE PROVIDING L4 AND HUMAN
CDNA CONTRIBUTING TO NUMEROUS
NEW HUMAN DISEASES AND CURRENTLY
AT ABOUT 50 AND PROVIDES 2 TO
SCREEN DRUGS AND WHOLE
TECHNOLOGY IS REALLY A USEFUL
DEVELOPMENT.
SO, I WILL END HERE
ACKNOWLEDGING THE PEOPLE AND
THIS HAS BEEN A KEY PLAYER HERE
AND THERE IS MANY PEOPLE IN THE
LAB THAT OBVIOUSLY DO ALL THESE
TECHNOLOGIES AND INJECTIONS AND
WE HAVE A LOT OF TECHNICIANS
INVOLVED AND OBVIOUSLY HAVE TO
-- NINDS FOR UDM FUNDING AND
THIS HAS BEEN A COLLABORATION
WITH THE LAB AT HARVARD AND
SPROULING LAB AT CARNEGIE.
THANK YOU.
>> THANK YOU, HUGO. THAT IS THE
TOUR DE FORCE.
DO WE HAVE QUESTIONS?
>> I HAVE A FEW GEEKY MOLECULAR
BUY OL QUESTIONS BUT WILL V- LET
JAMES ASK FIRST.
>> THANK YOU FOR THE
PRESENTATION. IT WAS VERY
INTRIGUING. YOU ARE ABLE TO
DISCOVER THESE GENES AND IS THE
GOAL OF THE PROJECT AND WONDER
HOWEVER IF YOU LOOKED INTO
ASPECTS OF TRANSLATIONAL
REGULATION AND I HAVE BEEN
INTERESTED IN EVOLUTIONARY
CONTROL OF TRANSLATIONAL
MECHANISM DIVERSITY AND IF YOU
PUT HUMAN REFERENCED GENES CDNAS
BACK INTO DROSPHILIA CELLS YOU
HAVE DIFFERENCE IN CODON USAGE
AND DO THIS ACROSS THOUSANDS OF
DIFFERENT GENES NOW.
THERE MIGHT BE INSIGHT TO BE
GAINED IN TERMS OF AMOUNT OF
PROTEIN MADE AND RATE OF PROTEIN
MADE AND STRUCTURE OF RNAS GOING
IN AND WONDER IF ANYONE IN YOUR
GROUP OR OTHER GROUPS TRY TO
LOOK AT ASPECTS OR TRANSLATIONAL
REGULATION BASED UPON THIS GROUP
THAT YOU CREATED.
>> WE HAVE NOT DONE THAT. THAT
IS BECAUSE WE ARE OVERWHELMED
WITH REQUESTS FROM UDM AND
ACTUALLY WORLDWIDE.
I MEAN, WHEN WE START TO PUBLISH
PAPERS WE GET SO MANY REQUESTS
FOR SO MANY GENES THAT WE ARE
WAY BEHIND AND WE CANNOT CATCH
UP WITH, YOU KNOW, THE REQUESTS.
SO, WE ARE DIGGING TYPICALLY A
POST DOC WILL DIG INTO BIOLOGY
TO KIND OF FIND OUT WHICH
PATHWAYS EFFECT IT AND WHICH
CELLS EXPRESS GENES, ET CETERA.
WE ARE NOT REALLY INTERESTED IN
IF THE HUMAN GENE FAILS TO
RESCUE THAT IS THE CASE ANYWHERE
FROM 30 TO 50% OF THE TIMES
DEPENDING HOW YOU DEFINE RISK.
WE ARE NOT PURSUING THAT. WE
COULD DO CODON OPTIMIZATION AND
COULD DO A LOT OF WORK. YOU
KNOW, THERE IS A NEED TO GO IN
HIGHER THROUGHPUT WHICH IS WHERE
LIMITATIONS ARE.
>> BRIAN?
>> YES. VERY INTERESTING WORK.
QUICK QUESTION HERE. IN TERMS
OF SHARING OF REAGENTS, YOU HAVE
TALKED TO PEOPLE AT ADD GENE
ABOUT DEPOSITING CONSTRUCTS
THERE.
>> EVERYTHING WE DO IS
DEPOSITED IN BLOOMINGTON STOCK
CENTER OR IF THEY REFUSE KEY
OTOSTOCK CENTER OR BLOOMINGTON
DROSPHILIA REPOSITORY AND
DEPOSITING 6 TO 7,000 US HUMAN
CDAS AND CHEAPER GOING
COMMERCIALLY AND $40 FOR CLONE
AND YOU GET VERIFIED US HUMAN
SEED AND EVERYTHING IS PUBLICLY
AVAILABLE AND REPOSITED IN, YOU
KNOW, IN STOCKS.
>> YEAH. I GUESS THE QUESTION
IS, YOU KNOW, I APPRECIATE THAT
MANY, MANY PEOPLE WANT ACCESS TO
YOUR RESOURCES.
YOU WERE SAYING YOU ARE HAVING
TROUBLE SORT OF KEEPING UP WITH
THE REQUESTS.
AND IS IT BECAUSE OF THE CURRENT
SORT OF DEPOSITORIES ARE NOT
SUCH FOR WHAT PEOPLE ARE ASKING
FOR OR OTHERS.
>> WELL, THE KEY IS, YOU KNOW,
OVERSEE, WE ARE SUPPORTED BY
ORIP TO CREATE REAGENTS AND
SUPPORT OF UDN IS VERY MINIMAL.
SO, WE ARE KIND OF STRAPPED ON
PERSONNEL.
YOU NEED POST DOCS AND WE HAVE
TECHNICIANS CREATING REAGENTS
DOING PHENOTYPIC ANALYSIS AND
MASS SPECK AND ALL OTHER
REQUIREMENTS REQUIRE POST DOCS
THAT TACKLE 1 ORE 2 OR SOMETIMES
THREE GENES OVER 1 OR 2 YEAR
PERIOD AND YOU NEED FOR EACH OF
THESE STORIES, YOU NEED A POST
DOC THAT IS INVESTED AND IN THE
BEGINNING IS PRETTY EASY GETTING
TO DIAGNOSIS REQUIRES ONE STOCK
MADE AND PUBLISHING IS ORDER
THAT IS DIFFICULT.
YOU NEED TO FIND PATIENTS SECOND
AND THIRD AND 4TH PATIENT AND
SECOND AND THIRD AND 4TH MODEL
AND DIFFERENT ALLELES HOW THEY
BEHAVE AND CORRELATION WITH
PHENOTYPES IN PATIENTS THAT
REQUIRES LABOR AND EFFORT TRYING
TO FIGURE OUT THAT REQUIRES
RESOURCES AND BEING RESOURCE
LIMITED.
>> THANKS A LOT. THAT IS
HELPFUL. OTHER QUESTIONS?
HUGO, FASCINATED BY OBSERVATION
OR RESULT THAT YOU CAN JOB TH
THESE-A QUESTION HOW YOU ASSESS
FUNCTION ACROSS SO MANY
DIFFERENT GENES 95% OF THE TIME
OR 80% OF THE TIME? WHAT IS
ACTUAL DATA ON THAT?
I IMAGINE I GUESS PART OF THE
OTHER QUESTION IS DO YOU KIND OF
LOOK AT PREDICTIVE PROTEIN
STRUCTURE TO DECIDE WHERE TO PUT
THESE THINGS.
>> VERY GOOD QUESTION.
IN THE BEGINNING WE HAVE NO
CHOICE AND MIMIC INSERTIONS AND
PICK INTERON AND PUT IN THE
CASSETTE AND WE NOW KNOW WHAT
PORTIONS OF CDNA ENCODED IN
PROTEINS AND PICK DOMAINS NOT
TRANSMEMBRANE DOMAINS BETWEEN
FUNCTIONAL DOMAINS OF THE
PROTEIN AND GET BETWEEN NOW 85
AND 90% REVERSION OF THE
PHENOTYPE AND START WITH T2A-GAL
4 AND WE HAD PHENOTYPES BEFORE
WE STARTED AND BRING IN GFP AND
THEY ARE GONE.
>> FUF FUNCTIONAL, THAT IS
IMPRESSIVE. THANKS.
>> IT SHOULD BE APPLICABLE TO
EVERY MODEL ORGANISM, I THINK.
ELECTRONIC TAGGING ALLOWS YOU TO
PICK WHERE YOU WANT TO TAG THE
PROTEIN.
IT IS MUCH EASIER THAN AMINO
[INDISCERNIBLE] WHICH IS MORE
TOXIC IN OUR HANDS AND WE HAVE
DONE THE STUDY AND SHOWN THAT
AMINO AND CAR BOXY AMINO
TARGETING PEPTIDE AND IF YOU
HAVE -- AND HAVE PC DOMAIN YOU
KILL IT IF YOU CAN PICK A DOMAIN
IN CENTER OF PROTEIN THAT IS
ACTUALLY PREFERRED STRATEGY.
>> YOU HAVE A WAY OF GOING AND
BASICALLY REVERTING PHENOTYPE
POTENTIALLY.
BUT YEAH.
OKAY. BUT YOU DO HAVE ADVANTAGE
OF FLIES WHERE YOU HAVE ACCESS
AND IT WILL BE A LOT HIGHER.
>> WE SPENT 5 OR 6 YEARS TO GET
TO 85% EFFICIENCY; RIGHT?
STARTING FROM SCRATCH. THAT WAS
REALLY IMPORTANT AND BRINGING
COSTS DOWN AND ORIGINALLY WAS
$2,000 PER STOCK AND ARE AT $800
AND HAVE BEEN ABLE TO REALLY
OPTIMIZE TECHNOLOGY IN THIS.
>> ANYBODY IN THE GROUP
DEPLOYED THIS ON A SMALLER SCALE
SAY IN FISH OR MICE.
>> THERE IS A TEAM AT STANFORD
THAT HAS DONE IT IN FISH WITH
T2A-GAL 4 AND REFERRED TO ME
THEY HAD SUCCESS IN THE FIRST
RUN.
>> IMPRESSIVE. OKAY. THANKS.
OTHER QUESTIONS?
>> JUST EMPHASIZING HOW
IMPORTANT HUGO'S WORK HAS BEEN
ON UNDIAGNOSED DISEASE NAILED
DOWN DISCOVERIES THAT HAVE BEEN
LEAD FOR THERAPIES.
SO, IT HAS REALLY BEEN A
FANTASTIC PROGRAM.
>> THANK YOU.
>> I DON'T SEE ANY OTHER HANDS
UP.
SUSAN, LOOKS LIKE WE ARE ON
TIME.
>> A LITTLE AHEAD.
THANK YOU VERY MUCH. THAT WAS
AN AMAZING PRESENTATION. THANK
YOU, DOCTOR. WE ARE SCHEDULED
TO RESUME THE CLOSED SESSION AT
2:15.
IF YOU COULD COME BACK ON AND,
AGAIN, THIS IS A DIFFERENT LINK
THAN BEFORE AND IS ONLY FOR
COUNCIL MEMBERS AND MEMBERS OF
THE FEDERAL GOVERNMENT.
SO, WE LOOK FORWARD TO TALKING
TO YOU THEN ABOUT THE FUNDING
PLANS WE WANTED TO GET YOUR
FEEDBACK ON. HAVE A GOOD LUNCH