BEFORE WE BEGIN, THE
AUDIENCE ARE WELCOME TO USE THE
LIVE FEEDBACK BUTTON TO ENTER
YOUR QUESTIONS AND COMMENTS, AND
DR. BELKAID WILL ADDRESS THEM AT
THE END OF THE LECTURE.
AND WITH THAT, I'D LIKE TO
INVITE THE CHAIR OF THE WSA, DRY
A FEW WORDS.
>> HI, THANK YOU, DORIS.
OKAY.
BEFORE WE BEGIN, I'D JUST LIKE
TO GIVE A BIT OF BACKGROUND
ABOUT THE NIH WOMEN SCIENTIST
ADVISERS OR THE WSA.
THIS COMMITTEE WAS FORMED IN
RESPONSE TO TASK FORCE
RECOMMENDATIONS BACK IN 1993, 30
YEARS AGO THIS YEAR.
BASED ON THE CONCERN THAT WOMEN
WERE UNDERREPRESENTED WITHIN THE
NIH INTRAMURAL PROGRAM AND THAT
REMAINS TRUE TODAY.
WITHIN EACH INSTITUTE, THERE'S
AN ELECTED WSA REPRESENTATIVE OR
REPRESENTATIVES.
THE REPRESENTATIVES REGULARLY
MEET WITH NIH INTRAMURAL
LEADERSHIP TO WORK TOWARDS
EQUALITY FOR WOMEN.
TO IDENTIFY BARRIERS TO WOMEN IN
SCIENCE AND TO PROMOTE WOMEN IN
SCIENCE.
THIS LECTURE IS ONE OF OUR
ANNUAL LECTURES TO PROMOTE WOMEN
IN SCIENCE BY HIGHLIGHTING BOTH
THE LEGACY OF AN OUTSTANDING
WOMAN SCIENTIST AND THE AMAZING
ACCOMPLISHMENTS OF OUR CURRENT
WOMEN SCIENTISTS.
WITH THAT SAID, I'D LIKE TO SAY
A FEW WORDS ABOUT ANITA ROBERTS.
ANITA ROBERTS WAS BORN IN
PITTSBURGH.
SHE ATTENDED OVERLAND COLLEGE
AND EARNED HER DOCTORATE DEGREE
IN BIOCHEMISTRY FROM THE
UNIVERSITY OF WISCONSIN IN 1968.
AFTER HER POSTDOCTORAL RESEARCH
AT HARVARD UNIVERSITY,
DR. ROBERTS JOINED THE NIH IN
1976.
SHE SPENT 30 YEARS AT THE
NATIONAL CANCER INSTITUTE AND
BECAME THE CHIEF OF THE
LABORATORY OF CELL REGULATION
AND SARS KNOW GENESIS IN 1995.
SHE'S WELL-KNOWN FOR HER
PIONEERING WORK ON TRANSFORMING
GROWTH FACTOR BETA OR TGF BETA
AND ITS ROLE IN WOUND HEALING,
CARCINOGENESIS AND AUTOIMMUNE
KEYS.
DISEASE.
HER PUBLISHED WORK HAS BEEN
INCLUDED AMONG THE TOP 50 MOST
CITED RESEARCH PAPERS AND SHE
HAS BEEN THE THIRD MOST CITED
FEMALE SCIENTIST IN THE WORLD.
DR. ROBERTS WAS THE RECIPIENT OF
MANY AWARDS AND HONORS.
SUCH AS THE FASEB EXCELLENCE
AWARD FOR DISTINGUISHED SCIENCE.
DR. ROBERT WAS NOT ONLY A HIGHLY
ACCOMPLISHED SCIENTIST, BUT AN
OUTSTANDING MENTOR.
SHE PROVIDED A WONDERFUL EXAMPLE
OF HOW TO BALANCE FAMILY, AND
WORK LIFE, AND WAS UNFAILINGLY
WARM, CARING, ENTHUSIASTIC AND
SUPPORTIVE.
I DIDN'T KNOW DR. ROBERTS
PERSONALLY, BUT THOSE WHO DID
KNOW HER INDICATE THAT SHE WAS
NOT ONLY A TREMENDOUS SCIENTIST
BUT A WONDERFUL HUMAN BEING, WHO
IS DEEPLY MISSED.
AND IN THE END, I THINK THAT
SAYS IT ALL.
AND THAT'S WHY WE HONOR HER
TODAY.
I'D LIKE TO THANK THE PEOPLE WHO
HAVE HELPED TO PUT THIS LECTURE
TOGETHER.
DR. DORIS WU AND EVA HALSBERG,
D. ANDREWS, OUR INTRAMURAL
PROGRAM SPECIALIST WHO ORGANIZES
ALL OF THE WSA ACTIVITIES, KENNY
KUMAR, ANALYST MANAGEMENT,
FELICE HARPER, ENGINEER ON THE
PRODUCTION TEAM, JOY JACKSON
FERRAR, JONATHAN BENNETT, EVENTS
MANAGEMENT TELEVISION OPERATIONS
CENTER ENGINEER, AND JEFF, THE
BROADCAST ENGINEER.
USE THE LIVE FEEDBACK BUTTON TO
ENTER YOUR QUESTIONS.
THERE'S ALSO CLOSED CAPTION
AVAILABLE AND THERE'S A BUTTON
AT THE BOTTOM OF THE VIDEOCAST
FOR CLOSED CAPTION.
YOUR QUESTIONS WILL BE READ AT
THE END, AND OUR SPEAKER WILL
ADDRESS YOUR QUESTIONS AT THE
END.
SO WITH THAT, I'LL TURN IT OVER
TO OUR WSA FELLOWS COMMITTEE
REPRESENTATIVE, DR. EVA
HELLSBERG TO INTRODUCE THE
SPEAKER.
>> THANK YOU, MARY, AND GOOD OF
A NOON, EVERYONE.
I'M DELIGHTED TO INTRODUCE YOU
TO TODAY'S SPEAKER FOR THIS
YEAR'S ANITA ROBERTS LECTURE,
DR. YASMINE BELKAID.
SHE'S A DISTINGUISHED
INVESTIGATOR AT THE NATIONAL
INSTITUTE OF ALONG ERG AND ALLED
INFECTIOUS DISEASES AT THE
NATIONAL INSTITUTES OF HEALTH.
SHE OBTAINED HER MASTERS IN
BIOCHEMISTRY AT THE UNIVERSITY
OF SCIENCE AND TECHNOLOGY IN
ALGIERS, AND HER PH.D. FROM THE
PASTEUR INSTITUTE IN FRANCE.
FOLLOWING A POSTDOCTORAL
FELLOWSHIP AT THE NATIONAL
INSTITUTES OF HEALTH, ON IMMUNE
REGULATION DURING INFECTION, SHE
STARTED HER RESEARCH PROGRAM AT
THE CHILDREN'S HOSPITAL RESEARCH
FOUNDATION IN CINCINNATI.
IN 2005, SHE JOINED NIAID AND
WAS APPOINTED SENIOR SCIENTIST
IN 2008.
HER LABORATORY EXPLORES
FUNDAMENTAL MECHANISMS THAT
REGULATE TISSUE HOMEOSTASIS AND
HOST IMMUNE RESPONSES AND
UNCOVERED KEY ROLES FOR THE
MICROBIOTA AND DIETARY FACTORS
IN THE CONTROL OF IMMUNITY AND
PROTECTION TO PATHOGENS.
DR. BELKAID IS THE CHIEF OF THE
LABORATORY OF HOST IMMUNITY AND
MICROBIOME, THE DIRECTOR OF THE
TRANS-NIH CENTER FOR HUMAN
IMMUNOLOGY, AND IS THE FOUNDER
AND DIRECTOR OF THE NIAID
MICROBIOME PROGRAM.
DR. BELKAID IS A MEMBER OF THE
NATIONAL ACADEMY OF SCIENCES,
THE AMERICAN ACADEMY OF ARTS AND
SCIENCES, THE NATIONAL ACADEMY
OF MADISON AND RECIPIENT OF
NUMEROUS AWARDS, INCLUDING THE
LURY SIZE IN BIOMEDICAL
SCIENCES, THE SANOFI INSTITUTE
AWARD AND THE AAI EXCELLENCE IN
MENTORING AWARD.
SHE HAS PUBLISHED OVER 200
MANUSCRIPTS, OF WHICH SEVERAL
PUBLISHED IN SCIENCE, NATURE,
CELL, OR IMMUNITY, ATTESTING THE
CROSS-DISCIPLINARY IMPACT OF HER
RESEARCH.
AS OF JANUARY 2024, DR. BELKAID
WILL SERVE AS THE DIRECTOR
GENERAL OF THE PASTEUR INSTITUTE
IN FRANCE.
WE WILL FAREWELL HER WITH A
SMILE IN ONE EYE AND A TEAR IN
THE OTHER.
THAT MUCH IS CLEAR.
BUT BEYOND HER SCIENTIFIC
ACHIEVEMENTS, SHE TRAINED OVER
70 YOUNG SCIENTISTS, INCLUDING
MASTER, PH.D., MD PH.D. AND
POSTDOCTORAL FELLOWS.
ALL HAVE REMAINED ASSOCIATED
WITH RESEARCH OR MEDICINE, WITH
22 OUT OF 27 POSTDOCTORAL FEL
FELLOWS IN INDEPENDENT ACADEMIC
POSITIONS AT MAJOR RESEARCH
INSTITUTIONS WITHIN THE U.S. AND
INTERNATIONALLY.
ALL HER PREVIOUS GRADUATE
MEDICAL STUDENTS ARE CURRENTLY
IN INDEPENDENT ACADEMIC
POSITIONS OR FINISHING THEIR
MEDICAL TRAINING.
SHE HAS ALSO BEEN INVOLVED IN
TEACHING IN THE CONTEXT OF HER
POSITION AS ADJUNCT PROFESSOR AT
THE UNIVERSITY OF PENNSYLVANIA,
AND HAS ORGANIZED SEVERAL
ADVANCED IMMUNOLOGY COURSES.
LIKE DR. ANITA ROBERTS,
DR. YASMINE BELKAID HAS A
PROFOUND COMMITMENT TO
MENTORSHIP AND EDUCATION OF THE
NEXT GENERATION OF SCIENTISTS.
THIS IMPORTANT VALUE WAS
RECENTLY RECOGNIZED BY THE 2023
MENTORING AWARD FROM THE
AMERICAN ASSOCIATION OF
IMMUNOLOGISTS.
I REACHED OUT TO SOME OF HER
PREVIOUS MENTEES FOR COMMENTS,
AND I WANT TO SHARE A FEW OF THE
WORDS THAT DR. BELKAID'S MENTEES
PROVIDED.
10 OUT OF 10 CONTACTED PEOPLE
REPLIED INSTANTLY,
ENTHUSIASTICALLY, AND TRULY
HEARTFELT.
HERE'S WHAT THEY SAID.
I ADMIRE HER SENSE OF WONDER THE
MOST.
HER IMAGINATION AND HER ABILITY
TO THINK OUTSIDE THE BOX ARE
WHAT MAKE HER A TRULY GREAT
SCIENTIST.
I WAS ABLE TO ABSORB SOME OF HER
SENSE OF WONDER AND IMAGINATION
WHEN APPROACHING DIFFICULT
SCIENTIFIC PROBLEMS.
AS I'M NOW A PHYSICIAN
SCIENTIST, THIS HELPS ME DIG
DEEPER INTO PROBLEM SOLVING WHEN
APPROACHING COMPLEX PATIENTS
WITHOUT A CLEAR DIAGNOSIS.
YASMINE IS ALWAYS THERE FOR HER
TRAINEES.
DESPITE HER BUSY SCHEDULE, SHE'S
ALWAYS WILLING TO SET UP
MEETINGS TO DISCUSS CAREER
QUESTIONS, GRANTS, OR JUST TO
CATCH UP ON SCIENCE.
WHEN I JOINED HER LAB, IT WAS
CLEAR SHE WOULD HAVE AN ENORMOUS
IMPACT ON THE SCIENCE WORLD, AND
IT IS SO EXCITING TO SEE HER
REWARDED FOR THIS IMPACT.
YASMINE SHOWED ME THAT IT WAS
POSSIBLE TO ME, A STRONG WOMAN
AND NOT TO APOLOGIZE FOR BEING
ME.
MAYBE MORE IMPORTANTLY, SHE ALSO
SHOWED ME THAT I COULD BE A
SCIENTIST AND A MOM, AND NOW I
GET TO SHOW MY SON JUST HOW FUN
IT IS TO PLAY IN THE LAB, JUST
AS I REMEMBER YASMINE DID WITH
HER DAUGHTER WHEN I WAS A
POSTDOC.
IN THIS ERA OF HIGH ACADEMIC
ATTRITION, ESPECIALLY AMONGST
WOMEN, PEOPLE OF COLOR, AND
OTHER UNDERREPRESENTED
MINORITIES, WE NEED HEROS LIKE
DR. YASMINE BELKAID TO SERVE AS
ROLE MODELS, GUIDES, AND
CHAMPIONS.
YASMINE'S ENTHUSIASM FOR
FOSTERING THE CAREERS OF THE
NEXT GENERATION THROUGH
RESPECTFUL FEEDBACK, CONTINUED
SPONSORSHIP, AND EAGERNESS TO
INVEST IN HER MENTEES, ALL WHILE
PERFORMING BREAKTHROUGH RESEARCH
IN IMMUNOLOGY, MAKE HER A
STANDOUT SCIENTIFIC STAR AND
MENTOR.
THE IMPACT OF HER WIDESPREAD
CITIZENSHIP AND MENTORSHIP WILL
BE FELT FOR DECADES TO COME.
AND I FEEL GRATEFUL TO HAVE HER
AS A MENTOR, COLLEAGUE, AND
FRIEND.
SHE SUPPORTED ME A LOT AS A
MENTOR.
SOMETHING I APPRECIATE MOST IS
THAT SHE STRONGLY BELIEVED IN ME
ALL THE WAY THROUGH MY POSTDOC.
SHE WAS ALWAYS REINFORCING THAT
I CAN DO IT, AND THE REASONS SHE
THOUGHT WHY.
I THINK SHE ACTUALLY BELIEVED IN
ME MUCH MORE THAN I BELIEVED IN
MYSELF AT THAT TIME.
WHICH MEANT A LOT COMING FROM
SOMEONE AS SUCCESSFUL AND HONEST
AS HER.
SHE WAS VERY SUPPORTIVE TO
EVERYONE, ESPECIALLY DURING
COVID, UNDERSTANDING HOW IT WAS
DIFFICULT FOR EVERYONE,
ESPECIALLY INTERNATIONAL PEOPLE
THAT COULDN'T GO HOME, AND
TALKING THROUGH HOW WE FELT
ABOUT IT.
SHE WENT ABOVE AND BEYOND IN
TERMS OF THE AMOUNT OF TIME SHE
SPENT HELPING ME WRITE GRANTS
AND PAPERS, PREPARING AND
REHEARSING TALKS, PREPARING JOB
APPLICATION DOCUMENTS, VISION
FOR MY OWN LAB, ET CETERA.
IT WAS A GREAT TRAINING
EXPERIENCE.
THESE EXAMPLES ABSOLUTE LEHIGH
LIGHT HOW DR. BELKAID
EXEMPLIFIES MANY OF THE SAME
QUALITIES THAT MADE DR. ANITA
ROBERTS SUCH A TRULY OUTSTANDING
SCIENTIST AND MENTOR.
IT'S A PLEASURE TO HONOR AND
WELCOME DR. YASMINE BELKAID
TODAY TO PRESENT THE 2023 ANITA
B. ROBERTS LECTURE.
>> THANK YOU SO MUCH, I HAVE TO
ADMIT I WAS NOT PREPARED FOR THE
EMOTIONAL -- THESE WONDERFUL
COMMENTS OF THE TRAINEES, I'M
REALLY CHOKED UP.
BUT THANK YOU SO MUCH FOR THE
WOMEN ADVISORY COMMITTEE AND FOR
YOU, EVA, FOR THIS INCREDIBLE
INTRODUCTION AND FOR THE
KINDNESS OF HIGHLIGHTING THE
WORK WE HAVE BEEN DOING WITHIN
THE NIH OVER THE LAST FEW YEARS.
SO I HAVE TO SAY, IT'S AN
ENORMOUS PRIVILEGE TO GIVE THIS
LECTURE NOT ONLY BECAUSE YOU
SELECTED ME FOR THIS LECTURE BUT
BECAUSE IT ALLOWED ME TO
DISCOVER, REALIZING THAT
ACTUALLY, YES, SHE WAS AN
EXTRAORDINARY MENTOR AND CITIZEN
BUT ONE THING EXTREMELY CLOSE TO
MY HEART IS HER SCIENCE IS VERY
CLOSE TO THE SCIENCE ACTUALLY
I'M DOING OVER THE LAST FEW
YEARS,, LEADING TO
IMMUNOREGULATION AND REPAIR.
SO IT WAS ACTUALLY REALLY
EXTRAORDINARY TO DISCOVER HER AS
NOT ONLY A SCIENTIST BUT ALSO
THE FIELD OF INVESTIGATION SHE
HAD REALLY OPENED THE DOOR FOR
PEOPLE LIKE ME.
SO WHO AM I?
I THINK IT WAS BRIEFLY
MENTIONED, AND I JUST WANTED TO
HIGHLIGHT FOR THE BEAUTY OF THE
FACT THAT WE ARE ALL COMING FROM
DIFFERENT ENVIRONMENTS, THAT I
WAS BORN AND RAISED IN ALGERIA,
WHERE I DID MY UNDERGRADUATE
TRAINING, AND I JUST WANTED TO
HIGHLIGHT TWO PEOPLE, IN
PARTICULAR, THAT HAD BEEN
ABSOLUTELY INSTRUMENTAL IN MY
DECISION TO BECOME A SCIENTIST,
AND THESE WERE ACTUALLY MY TWO
GRANDMOTHERS.
SO MY FIRST GRANDMOTHER IN
ALGERIA, THE ONE THAT WAS
ACTUALLY NIGERIAN WAS VERY
YOUNG, ALMOST A CHILD WHEN SHE
WAS MARRIED TO SOMEONE THAT WAS
DECADES OLDER THAN HER, SHE
NEVER WENT TO SCHOOL, SHE NEVER
HAD AN EDUCATION.
THIS IS NOT A PICTURE OF MY
GRANDMOTHER.
THIS IS ACTUALLY -- BUT THIS IS
ACTUALLY HOW SHE WAS DRESSED,
AND IT WAS DURING THE
COLONIZATION OF FRANCE, SHE
NEVER REALLY HAD ANY REAL
PROSPECT BUT WHAT SHE HAD WHICH
WAS TRULY EXTRAORDINARY AND TO
THIS DAY I WISH I WOULD HAVE
ASKED HER THE QUESTION, SHE HAD
AN ENORMOUS RESPECT FOR
EDUCATION.
AND SOMEHOW, SHE UNDERSTOOD
THESE YOUNG WOMEN THAT REALLY
NEVER WENT TO SCHOOL, THEIR
EDUCATION WAS A SALVATION FOR
HER DAUGHTERS AND HER CHILDREN,
AND SHE REALLY BECAME A FORCEFUL
ADVOCATE OF THE EDUCATION OF HER
OWN CHILDREN.
MY OTHER GRANDMOTHER WAS FRENCH,
DESPITE THE FACT MY MOM WAS IN
ALGERIA, MY OTHER GRANDMOTHER
WAS A PHARMACIST BY TRAINING,
SHE WAS, IN FACT, THE FIRST
WOMAN IN HER COUNTY TO REALLY
HAVE A SCIENTIFIC DEGREE.
AND WHEN I WAS A CHILD, VISITING
HER, I REMEMBER GOING TO HER
LABORATORY, PHARMACY IN FRANCE
AT THE TIME HAD LABORATORIES AND
REALLY LOOKING AT THE WONDERS OF
ALL THE EXTRAORDINARY MOLECULES
AND PRODUCTS AND YOU COULD
ACTUALLY MAKE MEDICINE, THAT WAS
ACTUALLY ONE OF THE FUNCTIONS OF
PHARMACISTS AT THE TIME.
SO I THINK THOSE TWO
EXTRAORDINARY WOMEN SOMEHOW DID
EXTRAORDINARY THING AND PAVED
THE WAY FOR ME AND PEOPLE IN MY
FAMILY TO MOVE FORWARD AND HAVE
BEEN SINCE THEN BEEN
INSPIRATION.
SO I WAS BORN AND RAISED IN
ALGERIA WHERE I WENT TO
UNIVERSITY AND I BECAME
FASCINATED FROM THE GET-GO BY
INFECTIOUS DISEASE.
THIS REALLY BECAME SOMETHING
THAT REALLY HAD BECOME MY LONG
LIFE OBSESSION, TRYING TO
UNDERSTAND HOW MICROBIOTA ARE
ABLE TO PERSIST IN THE HOST AND
I STARTED TO WORK ON INFECTIOUS
DISEASE -- ALSO WAS A PATHOGEN I
WORKED ON WHEN I WAS LUCKY
ENOUGH TO HAVE INTERNSHIP AT THE
WHO IN SWITZERLAND.
SO THIS REALLY EXPLORATION OF
HOST MICROBE INTERACTION LED ME
TO GO TO THE NEXT STEP, WHICH
WAS TO DO A PH.D. IN PARIS, AND
THE FIRST THING I WANTED TO
MENTION IS THAT WHEN I WAS IN
ALGIERS, I HAD THE OPPORTUNITY
TO DO INTERNSHIP WHICH REALLY
LED TO THE PASTEUR INSTITUTE IN
PARIS ALLOWING ME TO EXPLORE
THIS QUESTION HOW DO MICROBES
PERSIST WHICH TO BE HONEST HAS
BEEN THE DOMINANT QUESTION FOR
MY WHOLE LIFE.
OF COURSE THAT'S TYPICAL ME.
SO AFTER MY PH.D., I WAS LUCKY
ENOUGH TO MOVE TO THE NIH WHERE
I WAS ABLE TO DO A FELLOWSHIP
AND EXPLORE THE FA FASCINATING
QUESTION, I CAME BACK TO THE NIH
WHERE I HAVE BEEN SINCE THEN.
I'M GOING TO BE MOVING BACK HOME
TO PASTEUR INSTITUTE IN
JANUARY '24 AND I'M LOOKING
FORWARD TO WORKING NOT ONLY
WITHIN PARIS BUT OF COURSE
WITHIN THE 33 INSTITUTES ACROSS
THE PLANET IN WHICH PASTEUR IS
REPRESENTED.
SO I AM AN IMMUNOLOGIST BY
TRAINING, WHICH MEANS THAT A LOT
OF THE QUESTIONS I'M GOING TO
TRY TO ADDRESSED TO WILL BE
HAPPENING THROUGH THE LENS OF
THE IMMUNE SYSTEM.
THE ONE POINT I WANTED TO
DISCUSS WITH YOU AT THIS STAGE
IS HOW DO WE SEE THE IMMUNE
SYSTEM?
MANY OF YOU MAY HAVE HEARD ABOUT
THE IMMUNE SYSTEM AS AN ATTACK
SYSTEM, WHICH IS THE ONE THAT IS
NECESSARY IN THE CONTEXT OF
INFECTION, IN THE CONTEXT OF
VACCINE.
AND THIS IS REALLY ONE OF THE
FUNCTIONS OF THE IMMUNE SYSTEM,
IT REALLY PROTECTS US AGAINST
INFECTION.
THE WORK THAT WE AND MANY OTHERS
HAVE DONE IN THE FIELD OVER THE
LAST 20 YEARS HAS REALLY
REPOSITIONED THE IMMUNE SYSTEM
TO A MORE COMPLEX ROLE.
WHERE THE IMMUNE SYSTEM IS, IS
ACTUALLY AN ASSOCIATION OF
DIFFERENT CELLS THAT CAN VERY
QUICKLY MOVE ACROSS TISSUE,
EXPAND, CONTRACT, AND THE
FUNCTION IS REALLY WAY MORE TO
CONTROL THE HOMEOSTASIS OF THE
HOST.
SO CONTROLLING OF INFECTION IS
ONLY ONE OF THE ASPECTS OF THE
IMMUNE SYSTEM, A LOT OF THE
SYSTEM IS REMODELED TO CONTROL,
TO REPAIR AND SO FORTH.
AND TO DO THAT, WORK THAT WE
HAVE DONE OVER THE LAST YEARS
HIGHLIGHTED THE FACT THAT THE
IMMUNE SYSTEM DOESN'T DO THAT
ALONE.
IT CAN COOPT ELEMENTS SUCH AS
THE MICROBIOTA, NUTRITION, EVEN
THE ENVIRONMENT AND IN SOME
CASES EVEN SOME PATHOGENS CAN BE
UTILIZED FOR THE PROPER
EDUCATION OF THE IMMUNE SYSTEM
FOR SUBSEQUENT OPTIMAL STATE.
WHAT I'M GOING TO DISCUSS WITH
YOU TODAY IS A LINE OF RESEARCH
THAT IS REALLY LINKED DOMINANTLY
TO THE ROLE OF THE MICROBIOTA.
SO THIS IS A VERSION OF THE
SLIDE YOU HAVE SEEN NUMEROUS
TIMES OVER THE LAST FEW YEARS
WHICH IS THIS REALLY
REDISCOVERY, THIS IS NOT A NEW
FINDING BUT THE REDISCOVERY OVER
THE LAST 15 YEARS THAT WE ARE A
COMPOSITE OF SPECIES AND HUMAN
CELLS.
IN FACT THERE IS WAY MORE
MICROBES IN OUR BODY THAN OUR
OWN CELLS AND COLLECTIVELY THESE
MICROBES REALLY PROVIDE THIS
EXTRAORDINARY ADVANTAGE FOR THE
HOST BY CONTROLLING NUMEROUS
PHYSIOLOGICAL ASPECTS, AND IN
PARTICULAR CAN PROVIDE FUNCTION
THAT WE ARE DEVOID.
SO OVER THE LAST FEW YEARS, WE
ARE REALLY LUCKY AT THE NIH TO
BE ABLE TO START A PROGRAM, WE'D
LIKE TO HIGHLIGHT THE FACT THIS
IS SOMETHING TRULY EXTRAORDINARY
ABOUT THE INTERNAL PROGRAM OF
THE NIH.
YOU CAN ACTUALLY START SOMETHING
COMPLETELY NEW AND YOU CAN TAKE
REALLY LARGE RISK WHICH IS
REALLY WHAT I WAS ABLE TO DO AND
THIS WAS SUPPORTED BY THE FACT
THAT I WAS AT NIAID AND
SUPPORTED BY THE FACT THAT MY
LEADERSHIP REALLY BELIEVED IN
STARTING SOMETHING COMPLETELY IN
YOU.
NEW.
THIS ALLOWED US TO UNCOVER YEARS
AGO THAT MICROBIOTA WAS ABLE TO
CONTROL THE IMMUNE SYSTEM.
WHAT DO I MEAN BY THAT?
THE MICROBE THAT WAS IN THE GUT
AT THE TIME, THIS WAS THE FIRST
LINE OF WORK WE DID, TO PROMOTE
DEVELOPMENT OF THE IMMUNE
SYSTEMS ABOUT LU ITS FUNCTION,
ALLOWING THE HOST TO BE BETTER
PROTECTED AGAINST INFECTION.
FOR EXAMPLE, IF YOU WERE ABLE TO
GIVE BROAD ANTIBIOTICS TO A
HOST, THIS HOST WOULD BE LESS
ABLE TO CONTROL INFECTION.
THIS LINE OF WORK EXTENDED
SUBSEQUENTLY TO NUMEROUS OTHER
FIELDS THAT RELATE TO IMMUNOLOGY
AND IN PARTICULAR VACCINE, WHERE
THE WORK HIGHLIGHTED THE FACT
THAT IN HUMAN, BROAD SPECTRUM
ANTIBIOTIC CAN ACTUALLY DECREASE
THE QUALITY OF ANTIBODY
GENERATED IN THE CONTEXT OF
VACCINE AND MAKE THEM LESS
CAPABLE TO NEUTRALIZE VIRUSES.
WORK THAT WAS DONE IN PART BY MY
COLLEAGUE AT THE NIH
HIGHLIGHTING THE IMPORTANCE OF
THE MICROBIOTA IN THE CONTROL OF
HUMAN -- THERAPY HIGHLIGHTING
THE SPECIFIC MICROBE IN THE GUT
CAN ACTUALLY INFLUENCE THE
INTENSITY OF THE RESPONSE.
AND BEAUTIFULLY HE WAS ABLE TO
SHOW WITH HIS COLLEAGUES IN
PITTSBURGH A FEW YEARS AGO THAT
IF YOU TAKE TH THE MY MICROBIOTO
TRANSFER THE MICROBIOTA CAN
ACTUALLY RESTORE RESPONSIVENESS
IN AN INDIVIDUAL THAT WAS NOT
ABLE TO RESPOND.
SO THIS LED TO MORE STUDY BUT
EXTRAORDINARILY MORE THE
PRINCIPLE OF THE POWER OF THE
MICROBIOTA IN BOOSTING IMMUNITY.
BUT OF COURSE THE MICROBIOTA CAN
HAVE NUMEROUS NEGATIVE IMPACT,
AND IT HAS BEEN SHOWN IN
NUMEROUS SETTINGS SUCH AS
ALLERGY, AUTOIMMUNITY, OR
INFLAMMATORY BOWEL DISEASE, FOR
EXAMPLE, THE MICROBIOTA BECOMES
A LIABILITY, AND THE HOST STARTS
TO SEE THESE MICROBES IN AN
INFLAMMATORY WAY AND BECOMES
PART OF THE INFLAMMATORY
PROCESSES.
SO CLEARLY THE POINT I WANTED TO
MAKE WITH THIS SLIDE IS THAT THE
MICROBIOTA IS REALLY INTERTWINED
WITH OUR IMMUNE SYSTEM, AND
THERE'S OF COURSE A LARGE NUMBER
OF QUESTIONS THAT WE STILL NEED
TO ADDRESS.
AND ONE OF THEM WHICH IS A
QUESTION WE DECIDED TO FOCUS ON
OVER THE LAST COUPLE OF YEARS IS
HOW THE MICROBIOTA IS SEEN BY
THE IMMUNE SYSTEM.
WE KNOW IT IS CONTROLLING THE
IMMUNE SYSTEM BUT WHAT WAS NOT
REALLY CLEAR IS HOW THE MY --
HOW THE IMMUNE SYSTEM IS ABLE TO
REACT IN A POSITIVE WAY TO THESE
MICROBES.
SO MOST OF WHAT WE KNEW ABOUT
THE IMMUNE SYSTEM HAD ACTUALLY
BEEN DONE BY WORK THAT WAS DONE
IN THE FIELD IN THE CONTEXT OF
INFECTION.
OR IN THE CONTEXT OF VACCINE.
WHAT WE KNEW FROM THE BEAUTIFUL
FRAMEWORK THAT WAS POSTULATED AT
THE NIH IS THAT FOR THE IMMUNE
SYSTEM TO RECOGNIZE THERE IS
ACTUALLY AN INFECTION OR AN
AGGRESSION, IT NEEDED
SOME DEGREE OF INFLAMMATION AND
TISSUE DAMAGE.
AND THIS WAS COINED AS A --
MODEL.
THIS REALLY WAS AN ALARM SYSTEM
THAT ALLOWED THE IMMUNE SYSTEM
TO ENGAGE AND COME AND CONTROL
THE INVADING AGENT.
THIS IS THE VERY CORE OF THE
PRINCIPLE OF AN ADJUVANT IN THE
CONTEXT OF VACCINE.
TO THIS IS EXTREMELY IMPORTANT
AND ALSO THE CLASS OF IMMUNITY
THAT IN SOME CASES CAN BE --
BECAUSE IT'S CREATING
IMMUNOPATHOLOGY.
BUT THIS IMMUNITY HAS REALLY
ABSOLUTELY NOTHING TO DO WITH
THE MICROBIOTA.
HOWEVER WE KNOW
THAT IS ABLE TO ENGAGE THE
IMMUNE SYSTEM AND IT CAN HAVE A
LARGE NUMBER OF ANTIBODIES
WITHIN THE GUT OR IN THE
SYSTEMIC CIRCULATION OR T-CELLS
IN THE TISH TEU TISSUE THAT REE
THOSE NONINVASIVE MICROBES.
SO THIS FOR US WAS A AN ENIGMA.
-- SPECIFIC FOR MICROBES THAT
ARE NOT ABLE TO COLONIZE US, AND
I'M GOING TO DISCUSS BRIEFLY
THESE FINDINGS PUBLISHED, SOME
MORE RECENT, AND I'LL FINISH BY
ONGOING WORK THAT RELATE TO THE
MECHANISM BY WHICH THE
MICROBIOTA IS ABLE TO
COMMUNICATE WITH THE IMMUNE
SYSTEM IN SUCH A PEACEFUL WAY
YET PHYSIOLOGICAL WAY.
SO THIS WHOLE JOURNEY STARTED
WHEN WE MOVED AWAY FROM THE GI
TRACT, ALTHOUGH WE STILL WORK IN
THE GI TRACT, BUT WE WERE VERY
MUCH INSPIRED, WHEN SHRUTI NAIK
WAS VERY INSPIRED BY THE WORK OF
MY COLLEAGUE AT THE NIH THAT HAD
REALLY PIONEERED THE EXPLORATION
OF THE SKIN MICROBIOME IN HUMAN.
WHAT THEY HAD DISCOVERED WAS
THAT THE HUMAN SKIN WAS --
COMMUNITY VERY MUCH DEFINED BY
THE UNIQUE ECOSYSTEM IN THEECH
EACH OFTHESE ENVIRONMENTS WAS AO
IMPOSE.
SO SHRUTI DECIDED TO EXPLORE THE
POSSIBILITY THAT THE MICROBIOTA
IN THE SKIN COULD CONTROL LOCAL
IMMUNITY.
JUST A COUPLE OF WORD OF WHERE
THOSE MICROBES ARE, THEY'RE NOT
JUST FLOATING AROUND THE SKIN.
THEY ARE VERY MUCH SUND UNDER IP
STRUCTURE SUCH AS SWEAT GLANDS
SO THEY'RE VERY MUCH DEEP INSIDE
THE TISSUE YET OUTSIDE OF THE
TISSUE.
SO WHAT SHE WAS ABLE TO SHOW IS
TOGETHER WITH NICOLAS, STAFF
SCIENTIST, IS THAT THE
MICROBIOTA, IMMUNITY TO THE
MICROBIOTA SO WHEN YOU HAVE A
NEW MICROBE AT THE SURFACE OF
THE SKIN, YOU DEVELOP A LARGE
NUMBER OF LYMPHOCYTES THAT ARE
SPECIFIC FOR THESE MICROBES.
THESE LYMPHOCYTES ACCUMULATE IN
THE TISSUE AND ARE ABLE TO
PRODUCE CYTOKINE THAT CAN
ENHANCE THE ABILITY OF
KERATINOCYTES TO BE BETTER ABLE
TO PROTECT THEMSELVES AGAINST
INFECTION.
SO ADAPTIVE IMMUNITY TO THE
MICROBIOTA PROVIDED THIS BROAD
INNATE IMMUNITY AGAINST
SUBSEQUENT IN INFECTION.
WORK DONE BY JO SHOWED IN THESE
T-CELLS SPECIFIC TO THE
MICROBIOTA ARE VERY DIFFERENT
FROM T-CELLS GENERATED AGAINST
PATHOGEN, IN THE SENSE THEY ARE
VERY PLASTIC.
THEY CAN CHANGE THE PROGRAM AND
FUNCTION BASED ON THE
CIRCUMSTANCES WITHIN THE TISSUE
AND IN THE CONTEXT OF AN INJURY
CAUSE BID DAMAGE IED BY DAMAGE ,
THEY'RE ABLE TO PRODUCE FACTORS
THAT ALLOW THE REGENERATION OF
THE EPITHELIUM.
SO THIS CLASS OF IMMUNITY IS A
DIFFERENT CLASS OF IMMUNITY THAT
IS NOT HERE TO CONTROL AN
INVADING AGENT, IT IS A CLASS OF
IMMUNITY TO WHICH WE REFER AS
HOMEOSTATIC COMMUNITY THAT GOES
TO THE TISSUE AND BROADLY
CONTROLS AND PROTECTS THE HOST
AGAINST MICROBES AGAINST DAMAGE.
MORE RECENTLY, MICHEL JOINED THE
LABORATORY BEFORE HE STARTED HIS
OWN GROUP A COUPLE MONTHS AGO
AND DECIDED TO CONTINUE THE
EXPLORATION OF THIS QUESTION AND
HE WANTED TO UNDERSTAND IN
PARTICULAR WHAT OTHER FUNCTION
THIS IMAGE TO THE MICROBIOTA
COULD HAVE AND POSTULATED JUST
ONLY SCRATCHING THE SURFACE OF
THE COMPLEXITY OF FUNCTION THOSE
T-CELLS COULD EXERT ON THE
TISSUE.
AND THE CONCEPT THAT HE REALLY
WANTED TO ACTUALLY PROPOSE AND
MOVE FORWARD AND SOMETHING THAT
HE'S ACTUALLY NOW DEVELOPING IN
HIS OWN LABORATORY IS THIS
CONCEPT OF MULTISYSTEM REPAIR.
WHAT DO I MEAN BY THAT?
AS IMMUNOLOGISTS WHO ARE PEOPLE
THAT WORK ON THE EPITHELIUM, ALL
OF US WHEN WE LOOK AT TISSUE
DAMAGE, WE LOOK AT THE
REGENERATION AND REPAIR FROM ONE
SINGLE A ANGLE.
THE REALITY IS IF WE WANT TO
REGENERATE AN ENTIRE ORGAN, WHAT
WE NEED IS FOR ALL THOSE
DIFFERENT SYSTEMS INCLUDING THE
NERVOUS SYSTEM TO BE REBUILT IN
A HIGHLY COHERENT WAY.
SO WHAT MICHEL ACTUALLY
POSTULATED IS THAT THE
MICROBIOTA BECAUSE OF IT'S
CORROBORATION WITH THE HOST MAY
BE ABLE TO IMPOSE A CLASS OF
IMMUNITY THAT COULD REALLY TAP
INTO THIS MULTISYSTEM
PHYSIOLOGICAL REGENERATION OF
THE TISSUE.
AND HE DECIDED TO EXPLORE THIS
SPECIFIC QUESTION WHICH MEA
ACTUALLY SURPRISE SOME OF YOU
HERE THAT MAY BE CLINICIANS IS
STAPHYLOCOCCUS YOU YO AUREUS.
THE ISOLATES ARE NOT PATHOGENIC
AND THEY CAN ACTUALLY COLONIZE
ON THE SKIN, IN FACT, THE
STRAINS THAT WE HAVE ISOLATED
CAME FROM A MOUSE FACILITY THAT
WE HAVE AT THE NIH.
AND PROPOSED BECAUSE THIS
MICROBE CAN IN COME
CIRCUMSTANCES CAUSE INFECTION,
MAYBE IN THIS CASE, IT MAY BE
ABLE TO PROMOTE IMMUNITY THAT
ALLOWED GENERATION.
SO TO ADDRESS THIS QUESTION WHAT
MICHEL DID WAS HAVE ANIMALS
ENGINEERED TO HAVE T-CELLS THAT
ARE ALL SPECIFIC FOR THE
MICROBES, PLY THEM APPLY TO THEE
OF THE SKIN, T-CELLS SPECIFIC TO
STAPH AUREUS CAN ACCUMULATE --
TIME 17 PROGRAM, A CLASS OF
IMMUNITY THAT HAS BEEN SHOWN TO
BE VERY IMPORTANT TO HOST
MICROBIOTA INTO ACTION.
WHAT WAS REALLY INTERESTING AND
SURPRISING IS WHEN MICHEL
STARTED TO LOOK AT THE BEHAVIOR,
THIS IMAGING THAT ALLOWS TO LOOK
AT THE BEHAVIOR OF THE CELLS IN
AN INTACT ANIMAL, THERE IS NO
SURGERY, THE ANIMAL IS
ENGINEERED TO EXPRESS DIFFERENT
COLORS AND YOU CAN VISUALIZE
ACTUALLY THE BEHAVIOR OF THE
CELLS.
SO USING THIS APPROACH YOU CAN
SEE IN THE T-CELLS SPECIFIC FOR
THE MICROBIOTA IN YELLOW, ARE
ABLE TO BE IN CLOSE PROXIMITY TO
THE SENSORY NERVE, SENSORY
FIBERS WITHIN THE SKIN, AND THIS
CAN BE QEUNT FI BE QUANTIFIED OT
IN CLOSE PROXIMITY TO THE
SENSORY NERVES.
SO ALL ORGANS ARE -- BY SENSORY
FIBERS OF FUNDAMENTAL IMPORTANCE
FOR SENSATION BUT THESE FIBERS
ALSO CONTROL OTHER FUNCTION IN
THE TISSUE INCLUDING THE IMMUNE
SYSTEM.
SO THIS OBSERVATION THAT MICHEL
HAD LED HIM TO HYPOTHESIZE
SPECIFIC T-CELLS MAY PLAY A ROLE
IN REGENERATION OF THE NERVE AND
TO ADDRESS THIS QUESTION WHAT HE
DID WAS TO DO A VERY SIMPLE
APPROACH THAT IS A VERY GENTLE
PUNCH BIOPSY IN THE SKIN.
IN THIS CONTEXT THE ANIMAL IS
COLONIZED AT THE SURFACE OF THE
SKIN WITH STAPH AUREUS, THERE'S
A SMALL BIOPSY IN THE SKIN AND
YOU CAN SEE THE ACCUMULATION OF
THE CD4 T-CELLS AT THE EDGE OF
THE WOUND, AND YOU CAN SEE THIS
IS ACTUALLY DENSIFIED IF YOU
HAVE STAPH AUREUS AT THE SURFACE
OF THE CONTROL ANIMAL AND THIS
IS -- BY THE BETA THREE TUBULIN
MARKER THAT ALLOWS TO STAIN FOR
ALL THE FIBERS.
SO THIS IS ACTUALLY QUANTIFIED
ON THE RIGHT WHEN YOU CAN SEE
THAT THE PRESENCE OF STAPH
AUREUS ENHANCED SIGNIFICANTLY
THE ABILITY OF THE NERVE TO
REGENERATE IN THE CONTEXT OF AN
INJURY.
AN INJURY THAT COULD BE, FOR
EXAMPLE, A NEEDLE SCRATCH THAT
YOU HAD IN THE SKIN.
SO THE QUESTION THAT MICHEL HAD
WAS TO TRY TO SEE IF THIS
REGENERATION WAS A DIRECT EFFECT
OF THE BACTERIA OR IT WAS
ACTUALLY HAPPENING VIA THE
IMMUNE SYSTEM.
AND THE REASON IT COULD HAVE
HAPPENED TO THE BACTERIA IS
BECAUSE BACTERIA THEMSELF CAN
PRODUCE NUMEROUS FACTORS ABLE TO
MANIPULATE THE HOST.
SO WHAT MIC HMM EL DID IN THIS
CONTEXT, THE ANIMAL HAD BEEN
ENGINEERED TO REMOVE TYPE 17
WHEN THEY ENTER IN THE TISSUE.
SO THE JARGON HERE, WHAT WE HAVE
IS JUST A BUNCH BIOPSY IN AN
ANIMAL THAT HASN'T RECEIVED
STAPH AUREUS, AND YOU CAN SEE
THE REGENERATION OF THE FIBERS.
IN A CONTROL ANIMAL THAT WE SEE
STAPH AUREUS, YOU HAVE MASSIVE
REGENERATION OF THE FIBER THAT
YOU CAN SEE HERE, AND YOU CAN
SEE IN THE ANIMAL WHERE THERE IS
NO TYPE 17 RESPONSE BY THE
T-CELLS YOU CAN SEE THIS
REGENERATION IS REALLY
ABROGATED, THIS IS QUANTIFIED ON
THE RIGHT, WHEN YOU CAN SEE THE
DENSE FICK ODENSIFICATION -- BL7
RESPONSES IN THE SKIN.
SO THE IMMUNE RESPONSE TO THE
MICROBE IS WHAT ACCELERATES THE
REGENERATION OF THE NERVES.
SO NERVES CAN ACTUALLY RESPOND
TO CYTOKINES, AND THERE IS
ACTUALLY AN INCREASING
LITERATURE IN THE FIELD
HIGHLIGHTING THE ROLE OF IL-17
IN THE CONTROL SENSORY OF
NERVES, IN PARTICULAR IN THE
CONTEXT OF BEHAVIOR THE IN THE
BRAIN.
THE ROLE OF IL-17 -- ONCE AGAIN
HE DID A VERY SIMPLE EXPERIMENT,
THE ANIMAL HAD BEEN COLONIZED
GENTLY WITH STAPH AUREUS AND
THERE IS A SMALL PUNCH BIOPSY IN
THE SKIN.
HERE WE'RE ONLY SHOWING THE
EXPERIMENT WHERE THE ANIMAL HAD
BEEN COLONIZED WITH STAPH
AUREUS.
THIS IS A DENSIFICATION OF THE
FIBER IF YOU HAVE THE BACTERIA
ON THE SURFACE OF THE SKIN.
SOME OF THEM ARE SENSORINEURAL,
EXPRESSED BY THE CPIG THAT IS
IMPORTANT AND EXPRESSED BY
SENSORY FIBERS, AND YOU CAN SEE
THERE IS SIGNIFICANTLY DECREASE
IN THE NEVER THEMSELVES CANNOT
RESPOND TO IL-17.
THIS IS ACTUALLY ALSO HAPPENING
IN THE CONTEXT OF THOSE SENSORY
NEURONS.
SO THIS ACTUALLY INDICATES THAT
DIRECT RESPONSE OF THE NERVES TO
IL-17 IS ACTUALLY REQUIRED TO
IMPOSE THIS REGENERATION
PROCESS.
AND THIS IS QUANTIFIED ON THE
RIGHT WHEN YOU CAN SEE THERE'S A
DECREASE OF THE ORIGINATION
PROCESS IF THE NERVES CANNOT
SENSE IL-17 AND SIMILARLY IN THE
CONTEXT OF THE CGRP EXPRESSING
FIBERS.
SO THIS REALLY POSITIONED AN
INTERESTING NEW ROLE FOR IL-17
BY T-CELLS AS IMPORTANT FACTORS
THAT ACTUALLY ALLOW THE
REGENERATION OF THE PERIPHERAL
NERVOUS SYSTEM.
SO THE MODEL MICHEL IS WORKING
ON AT THE MOMENT IS NOW FURTHER
EXPLORING IN THE CONTEXT OF HIS
OWN LABORATORY IS THAT WHEN YOU
ENCOUNTER A NEW MICROBE,
SOMETHING THAT WE HAVE ALL THE
TIME, IF YOU ACTUALLY CHANGE
HOTEL ROOMS, SHAKE THE HANDS OF
SOMEONE, YOU'RE GOING TO SLOWLY,
SLOWLY INTEGRATE NEW MICROBES
WITHIN YOUR OWN ECOSYSTEM.
EVERY TIME YOU SEE A NEW
MICROBE, YOU'RE GOING TO DEVELOP
AN IMMUNE RESPONSE.
THESE T-CELLS WILL ACCUMULATE
WITHIN THE TISSUE AND WE FIND
WHEN THEY ARE IN CLOSE PROXIMITY
TO THE SENSORY NEURON, THIS IS
TRUE FOR STAPH AUREUS, BUT THIS
IS ALSO TRUE FOR ALL THE
MICROBES WE HAVE ACTUALLY WORKED
ON AND THIS IS ACTUALLY -- WHERE
THE T-CELLS ARE IN VERY CLOSE
PROXIMITY TO THOSE FIBERS.
WHEN THERE IS AN INJURY, AND
THIS HAPPENS ALL THE TIME THIS,
INJURY CAN BE CAUSED BY CUTS,
COULD BE CAUSED BY I INFECTION,
ANY FORM OF DAMAGE THAT WOULD
ACTUALLY HAPPEN TO THE TISSUE,
THE MICROBES ARE STILL AT THE
SURFACE OF THE SKIN.
THEY ARE COMMENSALS.
BUT THEY'RE NOW BROUGHT BACK
INSIDE THE TISSUE IN AN IMFLAM
TRI WAY AND BECAUSE THEY'RE
ACTUALLY PRESENT IN THE TISSUE,
THE T-CELLS SPECIFIC FOR THEM
ARE GOING TO BE RECALLED,
THEY'RE GOING TO REEXPAND, THE
VERY SAME THING THAT WILL HAPPEN
IN THE CON TECH OF AN INFECTION.
THOSE T-CELLS PRODUCE LARGER --
AND IL-17 CAN ACT DIRECTLY ON
THE SENSORY FIBERS AND --
DAMAGED NERVES UPREGULATE -- AND
THIS REALLY ALLOWS THIS
COMMUNICATION BETWEEN 17 AND THE
NERVES TO REALLY PROMOTE
REGENERATION OF THESE FIBERS
COMING TO THE REGENERATION OF
THE SENSORY NETWORK WITHIN THE
TISSUE.
WHY THIS ACTUALLY IS COMING
CLOSER TO THE HYPOTHESIS
DEVELOPED BY MICHEL IS THAT THE
SENSORY NEURONS ARE NOT ONLY, OF
COURSE, OF -- BUT THE SENSORY
NEURONS ARE SO VERY IMPORTANT TO
ALLOW THE REGENERATION OF ALL
THOSE STRUCTURES IN THE TISSUE,
FOR EXAMPLE, THAT WE GUIDE HE
REGENERATION OF THE VASCULATURE
AND ACTUALLY CAN CONTRIBUTE TO
THE REGENERATION OF THE
EPITHELIUM.
SO MICHEL REALLY WAS ON TO
SOMETHING BECAUSE INDEED BY
TACKLING THE NERVOUS SYSTEM,
MAYBE THIS IMAGING OF THE
MICROBIOTA CAN ALLOW IN A MORE
PHYSIOLOGICAL WAY TO REVEAL THE
ENTIRE TISH TEU SOMETHING THAT
WILL ACTUALLY BE EXPLORED IN HIS
OWN LABORATORY IN THE NEXT FEW
YEARS.
SO IN COMPLETION OF THIS FIRST
PART, I WANTED TO ACTUALLY
HIGHLIGHT THE EFFECT THAT THE
MICROBIOTA IS REALLY ABLE TO
INDUCE A LARGE AMOUNT OF IMMUNE
RESPONSES, AND IN PARTICULAR,
STRANGELY ENOUGH, IT'S
CONSTANTLY RECOGNIZED BY OUR
IMMUNE SYSTEM, AND OUR ADAPTIVE
IMMUNE SYSTEM, THE VERY SAME
THAT WE HAVE IN VACCINE AND
PATHOGEN.
THE DIFFERENCE IS ALL OF THAT
HAPPENED IN A VERY SILENT
NON-INFLAMMATORY WAY.
THESE T-CELLS CAN ACTUALLY
TRAVEL ACROSS TISSUE, REEXPAND,
CONTRACT, STAY FOR A LONG TIME,
A WAY THE MICROBIOTA CAN EXPAND
ITS FUNCTION ACROSS TISSUES.
AND IT ALLOWS NOT ONLY THE
PROTECTION OF THE TISSUE
ENHANCING IMMUNE DEFENSES,
EPITHELIAL REPAIR BUT ALSO ALLOW
REGENERATION -- REALLY MANY OF
THE FUNCTIONS MAY BE ACTUALLY
UNCOVERED IN THE CONTEXT OF THIS
RELATIONSHIP.
THIS REALLY OPENED NEW DOORS IN
TERMS OF REGENERATION.
IL-17 COULD BE A POTENTIAL
THERAPEUTIC TARGET TO ACTUALLY
REPAIR IN THE CONTEXT OF SENSORY
RECOVERY, SOMETHING THAT HAPPEN
IN THE CONTEXT OF DAMAGE OR
SURGERY, OR WHEN WE KNOW THERE
IS ACTUALLY DEFECT IN REPAIR.
SO -- DOWNSTREAM OF 17 COULD
BECOME A WAY BY WHICH WE CAN
ACTUALLY REGENERATE TISSUE.
AND I JUST WANTED TO ACTUALLY
HIGHLIGHT THIS COULD POTENTIALLY
GO IN A NEGATIVE WAY, JEREMIE
DELALEU -- WHAT HE'S ACTUALLY
LOOKING AT IS HOW IT HAPPENED IN
THE CONTEXT OF HEIGHTENED LEVEL
OF IL-17, SOMETHING THAT WOULD
HAPPEN IN THE CONTEXT OF
PSORIASIS, FOR EXAMPLE.
WHAT HE ACTUALLY HAS AS EARLY
EVIDENCE IS THE HEIGHTENED LEVEL
OF 17 TRUE ACTION OF THE NERVES
CREATE THE ON SI OPPOSITE, THIS
MASSIVE SPREAD OF NEURONS IN THE
TISSUE, SOMETHING THAT OF COURSE
CAN HAVE NEGATIVE CONSEQUENCES
FOR PAIN AND CAN HAVE NEGATIVE
CONSEQUENCES FOR SUBSEQUENT
INFLAMMATION.
SO TRYING TO UNDERSTAND THE
RELATIONSHIP TWINE THE CYTOKINES
IN THE CONTEXT OF
INFLAMMATION -- TO ACTUALLY
TARGET THIS FUNDAMENTAL
COMPARTMENT OF TISSUES AND ALLOW
NOT ONLY THE REGENERATION OF
THOSE FIBERS BUT ALSO PREVEN
PREVENTING -- REGENERATION --
THAT -- CAUSATIVE OF CHRONIC
LONG TERM PAIN.
SO THE SECOND PART OF THIS TALK
IS GOING TO BE ABOUT HOW THIS IS
STARTING.
SO WE KNOW ACTUALLY DOWNSTREAM
OF THIS IMMUNITY TO THE
MICROBIOTA WE HAVE THIS PROFOUND
EFFECT ON HOST PHYSIOLOGY BUT TO
TRY TO EXPLORE THE MECHANISM
THAT THE MICROBIOTA WAS ABLE TO
ENGAGE IN SUCH A QUIESCENT WAY
THE IMMUNE SYSTEM.
SO THE FIRST CLUE ABOUT HOW THIS
COULD WORK CAME FROM THE WORK OF
SAMIRA IN THE LABORATORY WHEN
SHE WAS DOING A VERY SIMPLE
EXPERIMENT APPLYING A NEW
MICROBE AT THE SURFACE OF THE
SKIN OF AN ANIMAL, AN ANIMAL
THAT HAS ITS OWN MICROBIOTA AND
LOOKING AT THE SKIN OF THE
KERATINOCYTES, THERE IS NO
INFLAMMATION, THERE IS NO
SWELLING, THIS IS BASICALLY
HAVING A SMALL MICROBE AT THE
SURFACE OF THE SKIN.
BUT WHAT SHE SAW THAT WAS VERY
SURPRISING IS THAT THE TISSUE
RESPONDED AS IT HAD BEEN
INFECTED WITH A VIRUS.
THE PRIMARY SIGNATURE THAT WE
SAW IN THE TISSUE WAS AN
ANTIVIRAL SIGNATURE.
SO THIS WAS VERY SURPRISING
BECAUSE CLEARLY WE DIDN'T HAVE
INFECTION WITH A VIRUS, WE HAD
AN EXOGENOUS ENCOUNTER WITH A
SKIN MICROBE.
BUT THIS ACTUALLY OF COURSE
BROUGHT US BACK TO RE-THINK
SOMETHING THAT IS OF FUNDAMENTAL
IMPORTANCE THAT IS, YES, WE HAVE
AN EXOGENOUS MICROBIOME.
BACTERIA, FUNGI, PROTOZOANS, BUT
WHAT WE ALSO HAVE IS AN
ENDOGENOUS VIROME.
-- RETROVIRUSES THAT ARE IN
FACT REMNANT THAT EVOLUTIONARILY
HAVE ACTUALLY BEEN INTEGRATED
WITHIN THE -- GENOME.
AND SO THESE ELEMENTS ARE NO
LONGER VIRUSES, THEY BASICALLY
HAVE BEEN FRAGMENTED, THEY HAVE
BEEN CONTROLLED, THEY HAVE BEEN
SUPPRESSED, BUT HOWEVER, SOME OF
THOSE ELEMENTS HAVE -- IN THE
ABILITY TO JUST BE ACTIVE AND
PROMOTED BIOLOGICAL FUNCTION IN
THE HOST.
SO THE FACT THAT WE HAVE THIS
STRANGE ANTIVIRAL SIGNATURE
POINTED TO THE POSSIBILITY OF A
CROSSTALK BETWEEN THE MICROBIOTA
AND THIS REMARKABLE ENDOGENOUS
VIROME THAT WE HAVE.
THIS QUESTION IN THE LABORATORY
WAS ADDRESSED BY TWO REMARKABLE
FELLOWS, WHO TODAY DJALMA HAS
MOVED TO SAO PAULO UNIVERSITY.
THEY FOUND A DISSCREEN BUT
SIGNIFICANT UPREGULATION, SO
THIS POINTED TO THE FACT THAT
MAYBE THE MICROBIOTA COULD BE
REACTIVATING A FEW OF THOSE
RETROVIRUSES.
THOSE RETROVIRUSES CAN HAVE A
LIFECYCLE, AND IF THERE IS
ENCODED -- TRANSCRIPTASE IN THE
GENOME THAT COULD CONDITION VERT
THIS ELEMENT INTO DNA, SOME OF
THOSE ELEMENTS CAN BECOME DNA
AND THIS DNA THAT WILL
ACTUALLY -- THE HOST COULD BE
SENSED BY THE CELL AS A
SIGNATURE OF A VIRAL INFECTION.
SO WHAT HE DECIDED TO DO, IF IT
PREVENTS THE ABILITY OF THIS
ELEMENT TO BECOME DNA, COULD YOU
ACTUALLY PREVENT THE ABILITY OF
THE IMMUNE SYSTEM TO SENSE THE
MICROBIOTA?
SO FOR THAT THEY UTILIZED A
CLASS OF DRUG USED IN THE
CONTEXT OF HIV PREVENTION, CURE
OR TREATMENT WHICH IS, OF
COURSE, THIS ANTIRETROVIRAL
TREATMENT.
YOU CAN SEE IF YOU HAVE A
CONTROL, THEY HAVE VERY FEW
T-CELLS IN THE SKIN.
IF YOU APPLY A NEW MICROBE,
THERE IS AN HANSMENT OF THE
NUMBER OF T-CELLS IN THE SKIN.
IF YOU TREAT THE ANIMAL WITH
A -- TRANSCRIPTASE YOU
COMPLETELY PREVENT THE ABILITY
OF THE HOST TO DEVELOP RESPONSE
TO THE MICROBE.
SO THIS ACTUALLY INDICATES -- IN
THE HOST, SOMETHING THAT WOULD
ALLOW THOSE ELEMENTS TO BECOME
AND TO BE CONVERTED INTO DNA IS
NECESSARY FOR THE ABILITY OF THE
HOST TO SENSE THE MICROBIOTA.
THIS CAN BE VISUALIZED MORE
CLEAR LEGAL BY IMAGING WHEN YOU
CAN SEE HERE THAT THERE IS AN
ACCUMULATION OF T-CELLS IN THE
EPIDERMIS OF THE ANIMAL AND YOU
CAN SEE THE ANTI-RT
SIGNIFICANTLY DECREASED THE
ABILITY OF THE MICROBIOTA TO
INDUCE T-CELL RESPONSE THAT HAS
A POSITIVE EFFECT ON THE IMMUNE
SYSTEM.
SO CLEARLY THE ANTIRETROVIRAL --
THE -- AND THE ERVs ARE
CONTRIBUTING TO THE ABILITY OF
THE HOST TO SENSE THE MICROB
MICROBIOTA.
SO WHAT HAS BEEN SHOWN IN THE
FIELD IS THAT DNA CAN ACTUALLY
BE SENSED BY MECHANICAL
MACHINERY REFERRED TO AS A C
GAS -- MACHINERY.
THESE ARE INNATE SEN SENSORS TO
ALLOW ANTIVIRAL RESPONSES.
THIS IS WHAT WE KNOW ABOUT
RESPONSES TO VIRUSES, FOR
EXAMPLE.
SO I WANTED TO SEE IF THIS
PATHWAY COULD ALSO ACCOUNT FOR
THE ABILITY OF THIS ERV TO
COMMUNICATE WITH THE HUMAN
SYSTEM IN THE CONTEXT OF A
MICROBIOTA ENCOUNTER.
HERE I'M SHOWING YOU DATA IN THE
CONTEXT OF KERATINOCYTES IN
WHICH THE ANIMALS HAVE BEEN
ENGINEERED TO REMOVE STING
EXPRESSIONS OR REMOVE THIS
INNATE SENSING OF DNA FROM THE
KERATINOCYTES AND ONLY THE
KERATINOCYTES.
IN THIS CASE, YOU CAN SEE THE
POST ASSOCIATION WITH
CD8 T-CELLS THAT ARE IMPOSED ARE
SIGNIFICANTLY DECREASED.
THE MAI T-CELLS AND OTHERS --
PRODUCING LARGE AMOUNT OF
CYTOKINES ARE SIGNIFICANTLY
DECREASED AND ANOTHER POPULATION
THAT IS INCREASED SIGNIFICANTLY
DECREASED.
SO THIS REALLY SHOWS THAT THE
EXTERNAL BARRIER OF THE HOST,
THE KERATIN SIGN LAYER OF SKIN,
IS REALLY THE ONE THAT IS ABLE
TO SENSE THOSE VIRTUAL ELEMENTS
IN THE CONTEXT OF A -- AND
REALLY -- IMMUNE RESPONSES.
SO INITIALLY, WE THOUGHT THAT
ACTUALLY THIS COMMUNICATION.
MICROBIOTA AND IMMUNE SYSTEM WAS
MORE DIRECT BUT WHAT WE ACTUALLY
DID NOT REALIZE UNTIL THIS WORK
IS THAT THIS ACTUALLY HAPPENED
THROUGH ANOTHER -- SOMEHOW
THERE'S AN EXTRAORDINARY
DIALOGUE BETWEEN ALL THOSE
DIFFERENT ELEMENTS THAT ALLOW
THE COORDINATION OF LOCAL TISSUE
IMMUNITY.
SOMEHOW, THE EXOGENOUS -- AS A
WAY TO INITIATE AND DISCUSSION
AND COMMUNICATION OF THE IMMUNE
SYSTEM ALLOWING IMMUNE RESPONSE
TO HAPPEN, AND THIS INNATE
MACHINERY THAT HAS BEEN
DOMINANTLY STUDIED IN THE
CONTEXT OF ANTIVIER RESPONSES IS
ALSO PLAYING -- RESPONSE TO
MICROBIOTA.
SO I USED TO REFER TO THE
MICROBIOTA AS AN ADJUVANT OF THE
IMMUNE SYSTEM, BUT A REAL --
ADJUVANT OF THIS ENTIRE
CASCADE -- ERVs IN THEIR OWN
GENOME.
SO THE MODEL WE HAVE IS THE
FOLLOWING ONE.
THE MICROBIOTA IS COMMUNICATING
WITH THE IMMUNE SYSTEM THROUGH
INNATE MOLECULES THAT I
EXPRESSED AT THE SURFACE.
THIS CAN ACTUALLY, OF COURSE,
ENGAGE THE KERATINOCYTES THROUGH
INNATE SENSING.
YOU CAN SEE HERE THAT DOWNSTREAM
OF THE TLR SIGNALING THAT REMAIN
TO BE UNDERSTOOD, THERE'S AN
UPREGULATION OF ENDOGENOUS
RETROVIRUSES.
THE WHAT IS EXTREMELY
INTERESTING IS THAT EVERY CELL
OF THE BODY EXPRESSES DIFFERENT
CLASS OF THOSE ELEMENTS AND HOW
THIS IS REGULATED REMAINS TO BE
FULLY ADDRESSED.
KERATINOCYTES THEMSELVES EXPRESS
VERY SPECIFIC ELEMENTS IN THE
CONTEXT OF THIS RELATIONSHIP.
THESE ELEMENTS CAN BE REVERSE
TRANSCRIBED INTO DNA AND THE DNA
NOW TELLS THE CELLS THAT IT'S
INFECTED.
AND THIS SMALL DEGREE OF
INFECTION ALLOW IN ACTIVATION OF
THE KERATINOCYTE IN A WAY THAT
ALLOW THE ENGAGEMENT OF THE
IMMUNE SYSTEM AND THE PEACEFUL
WAY -- THAT BROADLY PROMOTE
ANTIMICROBIAL DEFENSES AND
REPAIR.
BUT THIS DOES NOT CAUSE
INFLAMMATION BECAUSE THESE
EVENTS ARE VERY DISCRETE AND
HAPPEN WITH A VERY LOW BIOMASS
OF MICROBE.
BUT THIS VERY SAME DIALOGUE CAN
BECOME PATHOGENIC.
IF WE CHANGE THE DIET OF THE
ANIMAL AND PLACE THEM ON HIGH
FAT DIET, THE VERY SAME MICROBE
PLACED AT THE SURFACE OF THE
SKIN NOW CAUSE ABERRANT
EXPRESSION OF RETROVIRUSES AND
THIS IS NOW CAUSATIVE OF
INFLAMMATORY PROCESSES.
TO CLEARLY THE LEVEL OF ECK
PRETION OF THOSE ELEMENTS,
SOMETHING THAT CAN BE CONTROLLED
BY NUTRITION IS GOING TO -- TO
BE SENSED IN A WAY THAT EITHER
HOMEOSTATIC OR INFLAMMATORY.
SO THIS ACTUALLY OPENED A DOOR
TO NUMEROUS LINES OF RESEARCH IN
THE LABORATORY AND IN
PARTICULAR, TO TRY TO UNDERSTAND
THE RELATIONSHIP BETWEEN THE
MICROBIOTA AND THESE ADDITIONAL
RETROVIRUSES, HOW INFECTION --
CAN ACTUALLY AFFECT IF
RELATIONSHIP.
IN LINE WITH THAT, I JUST WANTED
TO HIGHLIGHT ONGOING PROJECT IN
THE LABORATORY BY FOUR
REMARKABLE FELLOWS THAT ACTUALLY
HIGHLIGHT THE FACT THAT THIS
RELATIONSHIP WE HAVE UNCOVERED
IN THE SKIN HAPPENED TO BE WAY
MORE PREVALENT AT ALL THE
DIFFERENT TISSUE WE HAVE
EXPLORED THIS FAR.
FOR EXAMPLE, ALEX IS NOW
EXPLORING THE ROLE OF ADAPTIVE
RESPONSE VIRTUAL ELEMENTS IN THE
CONTEXT OF MILD STRESS AND HOW
THIS CAN ACTUALLY CONTROL TISSUE
PHYSIOLOGY.
CLAUDIA IS ACTUALLY LOOKING AT
HOW ERV EXPRESSION IN THE GUT
CAN CONTRIBUTE TO THE
ACQUISITION OF ORAL TOLERANCE
AND FOUND A VERY -- BETWEEN ERV
EXPRESSION AND REGULATORY
T-CELLS.
DJALMA IS ABLE TO ACTUALLY
DEMONSTRATE IN HIS OWN
LABORATORY RIGHT NOW THAT ERV
WITHIN THE LUNGS PLAY A
FUNDAMENTAL ROLE IN THE ABILITY
OF THE HOST TO DEVELOP
EXPERIMENTAL ASTHMA, SHOWING
MANY WHEN UNCONTROLLED CAN
BECOME A SOURCE OF INFLAMMATION.
AND FINALLY, ELISHA IN THE
LABORATORY IS ALSO EXPLORING THE
ROLE OF ERVs WITHIN THE IMMUNE
SYSTEM OF THE FEMALE
REPRODUCTIVE TRACT.
SO FAR EVERY SINGLE PROJECT WE
HAVE ACTUALLY TACKLED REALLY
HIGHLIGHTS A ROLE FOR THOSE
ELEMENTS IN EITHER THE CONTROL
OF IMMUNE STUDIES AND
INFLAMMATION.
I BELIEVE THIS LINE OF RESEARCH
IS -- OTHER LINES OF
INVESTIGATION -- BASED ON THESE
FINDINGS.
BUT JUST TO FINISH, I JUST
WANTED TO SPEND TWO MINUTES TO
HIGHLIGHT WHERE WE'RE GOING AND
WHERE WE HOPE TO BE ABLE TO GO
IN HUMAN, AND HOW WE HOPE TO BE
ABLE TO VALIDATE THIS FINDING IN
A HUMAN SETTING.
SO ONE STUDY I WANTED TO
HIGHLIGHT HERE IS A STUDY THAT
WAS ACTUALLY DONE IN
COLLABORATION WITH KEVIN HALL
WHO'S ACTUALLY A PHYSICIST
WORKING AT NIDDK WHO HAS
ACTUALLY DEVELOPED REALLY
REMARKABLE COHORT OF HEALTHY
INDIVIDUALS COMING TO THE
CLINICAL CENTER, PLACED ON VERY
SPECIFIC DIET AND IN PARTICULAR,
A VEGAN OR KEETGE KETOGENIC DIE.
THEY ARE ONLY CONSUMING THE FOOD
ACTUALLY PROVIDED AND IT'S A
HIGHLY CONTROLLED STUDY.
SO KEVIN PUBLISHED BEAUTIFUL
WORK RECENTLY, AND VERENA LINK
HAS REALLY EXPLORED THROUGH THE
LNS OF -- DATA THE CONTRIBUTION
OF THIS DIET TO OUR IMMUNE
SYSTEM AND ENDOGENOUS RETROVIRUS
EXPRESSION.
I JUST WANTED TO SLOW ONE SLIDE
FROM THE WORK OF VERENA, THIS IS
ONLY A TWO WEEKS INTERVENTION OF
DIET.
YOU CAN SEE IF YOU COMPARE
INDIVIDUAL VEGAN DIET AND
COMPARE THEM TO BASELINE --
EVERY SINGLE INDIVIDUAL THAT
WERE PLACED ON THE VEGAN DIET
HAD ACTUALLY ENHANCED SIGNATURE
OF INNATE IMMUNITY AND ANTIVILE
RESPONSE IN THE BLOOD.
IN CONTRAST, IF PEOPLE WERE
PLACED ON THE KE KETOGENIC DIETD
RESPONSE TO T-CELLS AND B CELLS.
IT'S QUITE REMARKABLE TO THINK
THAT TWO WEEKS INTERVENTION CAN
HAVE SUCH A STRONG EFFECT ON THE
IMMUNE SYSTEM OF THE HOST.
WHAT IS REMARKABLE IN THIS
COHORT, THIS WAS A VERY DIVERSE
COHORT WITH PEOPLE THAT WERE
DIFFERENT AGE, DIFFERENT GENDER,
DIFFERENT BMIs, DIFFERENT
ORIGIN, EVERYTHING WAS ORIENT.
THAT ACTUALLY SAID, THE DIET WAS
ACTUALLY STRONGER THAN THE
ENVIRONMENT -- AND I FIND THAT'S
QUITE REMARKABLE.
SO NOT TO GIVE ADVICE OF WHAT WE
SHOULD BE EATING BUT THE POINT I
WANTED TO SAY HERE IS THAT
NUTRITION HAS A REMARKABLE AND
PROFOUND IMPACT ON OUR IMMUNE
SYSTEM.
THE REASON I'M SHOWING YOU THAT
HERE AS A TEASER FOR MAYBE WHERE
WE'RE GOING TO GO LATER IS THAT
THE DIET HAS ALSO PROFOUND
IMPACT ON THE EXPRESSION OF
ENDOGENOUS RETROVIRUSES.
EACH INDIVIDUAL EXPRESS
DIFFERENT LEVELS WHICH IS
ACTUALLY CONTRIBUTING TO YOU
DIVERSITY, BUT WHAT WAS REALLY
STRIKING IS THE CLASS OF GENES
THAT WERE THE MOST AFFECTED BY
DIET WERE THOSE LINKED TO THESE
ENDOGENOUS RETROVIRUSES.
WE DO NOT KNOW AT THIS STAGE IF
THIS IS THE REASON WE HAD -- ON
THE IMMUNE SYSTEM, BUT IF YOU
REMEMBER MY TALK, YOU
REMEMBER -- CAN BECOME A SOURCE
OF INNATE ACTIVATION FOR THE
IMMUNE SYSTEM.
IF SOME OF THOSE ELEMENTS ARE
DRAMATICALLY CHANGED BY DIET, BY
LIPID SENSING OR EXPRESSION OF
DIFFERENT MOLECULES, THIS CAN
HAVE A PROFOUND IMPACT ON THE
IMMUNE SYSTEM.
THIS IS ACTUALLY WHERE WE HOPE
TO BE ABLE TO CONTINUE THIS
JOURNEY TO TRY TO UNDERSTAND --
DIET AND HOW IMPACTING ERVs
AND HOW -- CAN ALSO HAVE AN
IMPACT ON OUR IMMUNE SYSTEM.
SO IN CONCLUSION OF MY TALK, ALL
OF WHAT WE DO IS BASED ON REALLY
OBSERVING THOSE PARTNERS, AND
REALLY TRYING TO UNDERSTAND THE
LOGIC BY WHICH THOSE MICROBES
HAVE ACTUALLY CO-EVOLVED WITH US
AND THIS RELATIONSHIP WE HAVE
WITH THEM AND WE HOPE THAT
ACTUALLY EXPLORING THIS
RELATIONSHIP AND DEVELOPING A
MECHANISTIC UNDERSTANDING, WE
MAY BE ABLE TO DEVISE A CLASS OF
THERAPY THAT MAY BE MORE
PHYSIOLOGICALLY EMBEDDED WITH
THIS EVOLUTIONARY PROCESS AND BE
ABLE TO DEVELOP NOVEL TARGET
THAT CAN ALLOW REGENERATION OF
TISSUE, AS IN THE CONTEXT OF 17
AND SENSORY -- REGENERATION.
SO I THINK THERE IS A LOT TO
CONTINUE TO OBSERVE IN THE FIELD
OF HOST -- THIS IS A VERY YOUNG
FIELD AND I THINK THERE IS STILL
AN ENORMOUS AMOUNT OF DISCOVERY
MOVING FORWARD.
SO I HAVE TO THANK ALL THE
REMARKABLE PEOPLE THAT HAVE
ACTUALLY DONE THE WORK OVER THE
LAST FEW YEARS.
I HAVE THE PRIVILEGE TO WORK
WITH TRULY OUTSTANDING
SCIENTISTS, AND THEY ALL HAVE
ACTUALLY CONTRIBUTED ONE WAY OR
ANOTHER TO THE PROJECTS OF EACH
OTHER.
IT'S A HIGHLY COLLABORATIVE
ENVIRONMENT, PEOPLE HAVE BEEN
REMARKABLY GENEROUS WITH THEIR
CREATIVITY, THEIR MIND, THEIR
COLLABORATION AND I COULD NOT
HAVE ACTUALLY -- I HAVE ALSO
WONDERFUL COLLABORATORS OVER THE
LAST FEW YEARS.
WONDERFUL COLLABORATION AMONG
NEUROSCIENTISTS WITHIN THE NIH
CAMPUS THAT HAVE REALLY HELPED
US DEVELOP THIS PROJECT OF
SENSORY NEURON YONS.
ONGOING COLLABORATION, MICHAEL
FISH BACK -- FOR VACCINE DESI
DESIGN, -- ROLE MODEL IN TERMS
OF -- SCIENCE.
ONGOING WORK, LONG TERM
COLLABORATORS ON PUSHING THE
BOUNDARIES OF -- SOMETHING WE
HAVE LEARNED A LOT FROM THEM.
AND MANY OTHER PEOPLE THAT HAVE
CONTRIBUTED OVER THE NEXT TWO
YEARS, AND I JUST DECIDED TO PUT
THIS SLIDE BECAUSE IT'S
IMPOSSIBLE FOR ME TO BE ABLE TO
SAY THANK YOU ENOUGH T TO THIS
REMARKABLE COMMUNITY OF MEEM
I'VE BEEN LUCKY ENOUGH TO BE
ABLE TO WORK WITH AT THE NIH.
I THANK YOU ALL FOR YOUR
ATTENTION.
>> THANK YOU, DR. BELKAID.
THAT WAS A FABULOUS LECTURE,
TONS OF BIOLOGY.
IT'S REALLY INTERESTING.
AND YOU KNOW, AS BIOLOGY ALWAYS
EXCEEDS OUR IMAGINATION, I JUST
WAS WONDERING THROUGHOUT YOUR
CAREER, HAVE YOU COME ACROSS
ANYTHING THAT TOTALLY SURPRISES
YOU?
>> THAT'S THE THING, I'M ALWAYS
ABSOLUTELY AMAZED, AND IF YOU
TELL ME -- I'M SURPRISED
CONSTANTLY BY THE DISCOVERY AND
OBSERVATION THAT I'VE MADE.
I THINK ONE OF THE WORK WE'RE
DOING RIGHT NOW FOR EXAMPLE THAT
I FOUND SO INTRIGUING IS FOR
EXAMPLE THE FACT THAT IMMUNE
CELLS OF THE MODEL CAN EVEN
CONTROL LACTATION.
I MEAN, I THINK EVERYTHING IS
AMAZING.
IF YOU REALLY PAY ATTENTION TO
WHAT IS HAPPENING, I THINK THE
WONDER IS REALLY NOT THE
PROBLEM.
I THINK THERE IS SO MANY UNKNOWN
QUESTIONS.
AND THE ONE THING THAT I WANT TO
SAY HERE, IF THERE ARE TRAINEES
LISTENING TO THAT, THERE ARE SO
MANY UNANSWERED QUESTIONS.
WHEN PEOPLE THINK THAT BIOLOGY
IS CROWDED, IT IS CROWDED ALL IN
THE SAME PLACES, BUT THERE ARE
SO MANY THINGS THAT ARE LINKED
TO PHYSIOLOGY, THAT ARE LINKED
TO MATERNAL HEALTH, WOMEN'S
HEALTH, TO EARLY LIFE, TO
PREGNANCY, TO DEVELOPMENT, THAT
ARE REALLY MOSTLY UNKNOWN.
SO I THINK -- I CANNOT TELL YOU
IF THERE'S ONE THING THAT
SURPRISES ME BECAUSE I THINK I'M
SURPRISED 25 TIMES A WEEK.
BUT --
>> OKAY.
WELL, HERE ARE SOME QUESTIONS
FROM THE CHAT.
FROM THE SUBMISSION.
DO YOU THINK THAT THE
IMMUNOLOGICAL CHANGES OBSERVED
UPON DIET CHANGE AFTER TWO WEEKS
WOULD BE MAINTAINED LIFE-LONG IF
THE INDIVIDUALS KEEP A VEGAN
DIET, OR KETO, OR DO YOU THINK
THIS IS A DIRECT RESPONSE -- YOU
KNOW, A TEMPORARY THING?
>> SO I THINK THAT'S A VERY,
VERY IMPORTANT POINT, AND THE
STUDY WAS NOT DESIGNED TO STUDY
THAT.
I THINK KEVIN WILL PROBABLY WORK
ON THAT FURTHER, WE'LL SEE THE
DURATION OF THE EFFECT.
IT DIFFICULT TO KNOW.
IF IT'S THE CHANGE IN THE DIET
OR THE -- CHANGE TO THE
PREVIOUS.
SO FOR EXAMPLE, WHAT WE FIND IS
LIKE IF YOU CHANGE CALORIE
INTAKE OF -- YOU CAN
DRAMATICALLY REMODEL THE IMMUNE
SYSTEM AND THEN EVENTUALLY IT
STABILIZES, SO IT IS POSSIBLE
THAT ACTUALLY YOU MAY HAVE THIS
BURST OF REWIRING AND MAYBE IT'S
STABILIZED LATER.
WE DON'T KNOW.
I THINK IT WOULD BE FASCINATING
TO EXPLORE.
I THINK WHAT WOULD BE
FASCINATING TO DO IS MORE
RIGOROUSLY CONTROLLED DIETARY
INTERVENTION IN HUMAN.
THE PROBLEM IS THERE'S A LOT OF
NOISE IN THE FIELD, BUT NOT MUCH
MMECHANISTIC OR REALLY DONE IN
CLINICAL SETTINGS THAT ALLOW
RIGOROUS UNDERSTANDING.
SO I THINK THE JURY IS STILL OUT
ABOUT THE DURATION AND ALSO WHAT
IS STILL OUT IS WHAT HAPPENED
WITHIN THE TISSUE OF THE
INDIVIDUAL AND HOW THOSE DIET
CAN ACTUALLY INFLUENCE CERTAIN
BIOLOGICAL STATES, WHICH KIND OF
DIET WOULD BE MORE DESIRABLE IN
THE CONTEXT OF REGENERATION, IF
YOU HAVE GUT INFLAMMATION, SO WE
DON'T KNOW THAT YET, BUT I DO
THINK AND I HOPE I HAVE
CONVINCED PEOPLE HERE THAT THE
POWER THAT A DIET CAN HAVE ON
THE IMMUNE SYSTEM CAN BECOME AN
ASSET, AN ASSET WE COULD USE A
COMPLEMENTARY -- BUT HOW ABOUT
USING THE DIET THAT IS REALLY
ALIGNED WITH A PHYSIOLOGICAL
DIRECTION WE ACTUALLY WANT TO
PUSH THE IMMUNE SYSTEM.
>> SO COULD YOU EXPAND ON HOW
THE IMMUNE PROFILE WAS DEFINED
AFTER THE IMPLEMENTATION OF
DIFFERENT DIETS?
>> YES.
IT WAS ACTUALLY VERY POORLY
DESCRIBED.
THIS WAS ENTIRELY IN THE BLOOD
AND ALSO IN THE CONTEXT OF
THE -- WHEN YOU LOOKED AT THE
MICROBIOTA, WE LOOKED AT THE
URINE.
SO WE LOOK AT, YOU KNOW, FACTORS
THAT YOU CAN ACTUALLY COLLECT.
IT WAS NOT LOOKED AT IN TISSUE,
AND THAT'S SOMETHING THAT WOULD
BE REALLY INTERESTING, IF WE CAN
DO A SMALL BIOPSY OR -- SKIN TO
SEE HOW THE SKIN HAS REMODELED
WOULD BE REALLY INTERESTING.
IT WAS ENTIRELY DONE BY LOOKING
AT THE BLOOD, THE URINE, SO
FORTH, AND DONE USING A
COMPLEMENTARY STRATEGY.
SO WHEN I SHOWED, THE SLIDE WAS
RNA SEQ BUT IT WAS ALSO DONE IN
OTHER WAYS.
WE HAD FLOW CYTOMETRY, WE HAD
MANY DIFFERENT ASSAYS THAT WE
WERE ABLE TO UTILIZE TOGETHER.
>> OKAY.
ONE MORE SCIENCE QUESTION BEFORE
I GO TO THE LEHMANN QUESTION.
LAYMAN QUESTION.
ARE PEOPLE WITH HIV OR
ANTIRETROVIRAL MORE SUSCEPTIBLE
TO SKIN INFECTIONS OR OTHER
INFECTIONS?
>> SO THAT'S A SUPER IMPORTANT
QUESTION, SO I HAVE TO SAY THAT
WE HAVE JUST STARTED -- WE'RE
STARTING JUST A COLLABORATION AT
THE NIH WAS ACTUALLY GOING TO BE
ABLE TO BEGIN TO REALLY LOOK AT
THIS QUESTION MORE SERIOUSLY BY
LOOKING AT PEEP PUT PEOPLE PUT ,
ANTIRETROVIRAL, TO LOOK AT
BEFORE AND AFTER WHAT HAPPENED
TO THE TISSUE.
WE KNOW ACTUALLY THOSE
TREATMENTS -- OF COURSE THEY ARE
PRPROTECTIVE AND THEY ACTUALLY
HAVE SAVED LIVES, BUT THEREFORE
THEY STILL HAVE CONSEQUENCES,
METABOLIC CO CONSEQUENCES,
CARDIOVASCULAR CONSEQUENCES AND
WE DON'T REALLY KNOW WHY, SO
THIS IS SOMETHING I THINK WE'LL
ACTUALLY BE ABLE TO EXPLORE WITH
HER, TO BE ABLE TO LOOK AT THE
TISSUE BEFORE AND AFTER THE
START OF THE TREATMENT TO REALLY
TRY TO UNDERSTAND WHAT HAS BEEN
REMODELED.
THE ONE THING THAT I WANTED TO
SAY IS, REMEMBER, WE'RE LOOKING
AT A VERY SPECIFIC MOMENT IN AN
ANIMAL THAT ARE NIGH EE. IF YOU
WERE ACTUALLY TO MEET A HUMAN,
YOU HAVE A LOT OF -- IN YOUR
LIFE BEFORE YOU HAVE PUT ON
THOSE TREATMENT AND MAYBE AT
THAT STAVE -- ACTIVATION THAT
YOU CAN BE MAIBL NOT AS
DEPENDENT ON THESE SIGNALS.
THAT SAID I THINK THE JURY IS
STILL HOW THE IN TERMS OF DOING
RIGOROUS ANALYSIS OF HOW THE
TISSUE ARE AFFECTED.
FOR EXAMPLE IN THE VAGINAL
COMPARTMENT, THE IMMUNE SYSTEM
WAS ACTUALLY AFFECTED IN WOMEN
IN THE CONTEXT OF THOSE
TREATMENTS.
SO THAT'S ACTUALLY AN
INTERESTING THING TO TRY TO
INTEGRATE AND UNDERSTAND WHAT
ASPECT IS AFFECTED AND WHAT IT
ACTUALLY MEANS FOR THE LONG
TERM.
>> RIGHT.
SO ALONG THE LINE, THERE'S A
QUESTION THAT ASKS, HAVE YOU OR
OTHER INVESTIGATORS EXPLORED THE
EFFECT OF ALVIDROX BETWEEN THE
MICROBIOME AND THE HOST TO
CONTROL THE REPAIR?
>> THAT'S A VERY, VERY
INTERESTING QUESTION BECAUSE, OF
COURSE, THOSE DRUGS IN THEORY
COULD POTENTIALLY, IF THERE
IS -- ON BACTERIA, COULD
ACTUALLY AFFECT THEM.
IN THE MODEL WE HAVE UTILIZED,
WE HAVEN'T FOUND DIRECT
CONSEQUENCES, IT HAPPENED
INDEPENDENTLY OF THE BACTERIA
ITSELF SO IT WAS NOT CHANGING
THE MICROBIOTA FUNCTION.
SO -- BUT I THINK THIS IS A
VERY, VERY IMPORTANT POINT THAT
IS LIKELY TO HAPPEN IN HUMANS,
AND I THINK THIS IS SOMETHING
VERY IMPORTANT TO UNDERSTAND
BECAUSE THOSE DRUGS CAN ALSO
AFFECT THE BEHAVIOR OF BACTERIA.
SO THAT INTERESTING THAT MAY BE
TAKEN INTO ACCOUNT IN
UNDERSTANDING OF HOW LONG TERM
TREATMENTS SHAPE POST
PHYSIOLOGY.
>> OKAY.
SO THIS IS A DIFFERENT QUESTION.
CAN IL-17 PLAY A ROLE IN
NEUROREGENERATION IN CNS?
>> THAT WOULD BE GREAT.
[LAUGHTER]
WE REALLY DON'T KNOW.
AND I THINK THIS ROLE OF 17 IN
REGENERATION OF THE NERVE,
MICHEL'S OBSERVATION THIS YEAR,
SO I HOPE THIS IS SOMETHING
THAT'S GOING TO CONTINUE AND I
KNOW THERE ACTUALLY IS PLENTY OF
PROJECT AND TRYING TO UNDERSTAND
HOW OTHER NERVES MAY BE AFFECTED
AND MAY HELP REGENERATION.
ONE THING INTERESTING IS THERE'S
A GROWING BODY OF LITERATURE,
BEAUTIFUL WORK THAT IS DONE, HAS
HIGHLIGHTED FOR EXAMPLE
BEHAVIOR, ANXIETY-LIKE BEHAVIOR
CAN ACTUALLY BE CHANGED BY
HEIGHTENED LEVEL OF 17 OR LACK
OF 17 IN THE DEVELOPMENT WINDOW.
AND THERE'S EVEN LIKE MORE AND
MORE EVIDENCE IN 17 PRIMARY
ROLE -- TO REALLY INTERSECT WITH
THE NERVOUS SYSTEM.
SO I REALLY THINK THIS IS REALLY
LIKELY A POSSIBILITY THAT IT MAY
BE IMPORTANT IN ACTUALLY
REGENERATION OF NERVES AND, WHO
KNOWS, MAYBE OF -- THAT HAVE SO
FAR NOT BEEN ABLE TO REGENERATE.
>> SO EVA WANTED TO KNOW IF YOU
CATCH A COLD, WILL YOU GO VEGAN?
>> SO I SAID I WAS NOT GOING TO
GIVE ADVICE OF FOOD BECAUSE --
>> RIGHT.
OKAY, FINE.
>> THAT SAID, I THINK IT'S TOO
EARLY.
BUT AGAIN, I REALLY, REALLY
THINK THAT -- AND PEOPLE HAVE
ACTUALLY DONE SIMILAR STUDIES
PRIOR WHEN CHANGING THE DIET AND
SEE DIFFERENT CLASS OF
INFECTION, FOR EXAMPLE, AND
SHOWED THAT YOU CAN HAVE A
STRIKING DIFFERENCES
EXPERIMENTALLY TO DIFFERENT
DIETS.
SO I DON'T KNOW WHICH DIET YOU
SHOULD BE TAKING AT THE MOMENT,
BUT THE ONE THING I KNOW AND THE
ONE THING THAT WE NEED TO PAY
ATTENTION IS WHAT'S GOING TO
HAPPEN OVER THE NEXT FEW YEARS
IN TERMS OF GUIDELINES.
BECAUSE I REALLY DO THINK THAT
IF WE DEVELOP MORE AND MORE OF
THESE STUDIES, AND I THINK THE
CLINICAL CENTER OF THE NIH IS A
WONDERFUL PLACE TO BE ABLE TO
ADDRESS THIS KIND OF QUESTION,
WE MIGHT BE ABLE TO UNDERSTAND
HOW TO BOOST VACCINE RESPONSES,
ONE THING IS SUPER INTERESTING
IS WOMEN RESPOND MORE TO DIET
THAN MEN, SO IT'S MORE FELT BY
THE IMMUNE SYSTEM THAN ACTUALLY
IN THE MEN.
THAT'S A VERY INTERESTING
FEATURE.
SO IF A WOMAN IS ACTUALLY MORE
REACTIVE IN THE CONTEXT OF
DIETARY NUTRITION, WE NEED TO
INTEGRATE THAT ALSO BECAUSE
THERE IS AN OPPORTUNITY TO
UNDERSTAND BETTER HOW TO
MANIPULATE THE IMMUNE SYSTEM IN
A GENDER SPECIFIC MATTER.
>> THIS IS A NON-SCIENCE
QUESTION.
THANK YOU FOR THE AMAZING TALK.
AND FOR BEING SUCH AN IMPORTANT
ROLE MODEL.
DO YOU HAVE ANY ADVICE FOR YOUNG
WOMEN SCIENTISTS HOW TO SUCCEED
IN THEIR CAREERS?
>> THAT'S A VERY BIG QUESTION.
I THINK -- I THINK WHAT YOU HAVE
TO DO IS YOU HAVE TO SURROUND
YOURSELF WELL.
I MEAN, I THINK SOMETHING I HAVE
LEARNED A BIT TOO LATE IN MY
LIFE IS THE IMPORTANCE OF
RELATIONSHIP, MENTORSHIP.
I THINK I WAS SO DRIVEN BY
SURVIVAL THAT I JUST DIDN'T
UNDERSTAND THE IMPORTANCE OF
THIS NETWORK.
THE ONE THAT YOU GUYS ARE
GENERATING TO THIS WOMEN'S
ADVISORY GROUP.
I THINK YOU NEED THE COMMUNITY,
YOU NEED A VILLAGE, YOU NEED A
TOWN, YOU NEED PEOPLE AROUND
YOU, YOU NEED TO FIND SPONSOR,
YOU NEED TO DEVELOP RELATION
RELATIONSHIP.
DON'T BELIEVE YOU'RE GOING TO BE
ABLE TO DO IT ALONE.
THERE'S AN ENORMOUS AMOUNT OF
GOODWILL AROUND YOU THAT YOU
JUST HAVE TO ACTUALLY GO AND
IDENTIFY AND CREATE THOSE
RELATIONSHIPS.
AND SURROUND YOURSELF WITH
PEOPLE THAT ARE REALLY BELIEVING
IN YOU.
JUST MAKE SURE THAT YOUR FRIENDS
ARE ALSO YOUR CHEERLEADERS, THAT
THEY ARE HERE TO JUST PROTECT
YOU IN THE MOMENTS THAT ARE
DIFFICULT, SURROUND YOURSELF BY
PEOPLE THAT WILL ACTUALLY BE
HERE TO HELP YOU.
I THINK THIS REALLY IS THE ONE
THING THAT I THINK I WISH I HAD
LEARNED EARLIER, THE IMPORTANCE
OF COMMUNITY RELATIONSHIP AND
SURROUNDING YOURSELF BY PEOPLE
THAT ACTUALLY HELP YOU TO GOING
THROUGH DIFFICULT MOMENTS.
WE ALL HAVE DOUBTS, WE ALL HAVE
CRISIS MOMENTS, AND SURVIVING
THOSE MOMENTS IS DIFFICULT TO DO
ALONE.
AND THE OTHER THING IS, YOU'RE
GOING TO HAVE TO LEARN TO LIVE
WITH SOME FORM OF STRANGE
SCHIZOPHRENIA THAT IS SCIENCE,
WHERE YOU STILL HAVE DOUBT IN
YOURSELF AND SAY GO FOR IT.
IF YOU CAN MANAGE THIS BIZARRE
THING THAT IS REALLY THE
COEXISTENCE OF THE
ACKNOWLEDGMENT OF YOUR
LIMITATION, YOUR DOUBTS, YOUR
ANXIETY, WHICH I THINK IS OKAY,
KEEP IT, IT MAKES YOU HONEST AS
A PERSON, BUT AT THE SAME TIME,
WHY NOT GIVE IT A TRY?
THIS KIND OF ATTITUDE, THE
OPPOSITE OF EACH OTHER, BUT I
THINK JUST GIVE A TRY TO THE
NEXT STEP.
STOP GIVING YOURSELF EXCUSES
THAT YOU CAN'T DO IT, BECAUSE
NONE OF US, WE CAN CONVINCE
OURSELF INFINITELY POSSIBILITIES
TO DO IT.
SO GIVE IT A TRY, THAT'S MY
ADVICE.
>> I AGREE.
LEARN TO TRUST YOURSELF.
I THINK THAT'S REALLY IMPORTANT.
AND SEEK HELP WHEN YOU NEED IT.
>> YEP.
>> YEAH.
NOW WITH THAT, LET ME SEE, I
DON'T SEE ANY OTHER QUESTIONS
COMING IN, AND I JUST WANT TO
THANK YOU AGAIN FOR THE FABULOUS
LECTURE, AND THE BEST OF LUCK IN
YOUR NEW POSITION.
I'M SURE NIH WILL BE MISSING
YOU.
OH --
THAT'S RIGHT, YOUR LAB
YOU'RE STILL COMING BACK.
THANK YOU.
I'D LIKE TO CLOSE THE LECTURE
FOR TODAY.
THANK YOU ALL FOR ATTENDING.