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>> GOOD AFTERNOON.

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I WILL

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INTRODUCE ANDY.

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IT'S TRULY A PLEASURE.

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ANDY IS -- I WOULD LIKE ONLY TO

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SAY THAT HE IS A FANTASTIC

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SCIENTIST AND AN EVEN BETTER

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PERSON, AND I THINK THAT WILL

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QUALIFY HIM FULLY, BUT I WILL,

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YOU KNOW, GIVE YOU A FEW

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DETAILS.

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ANDY RECEIVED HIS CFBS FROM THE

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UNIVERSITY OF SUTHERLAND U.K.

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AND UNIVERSITY OF NEW CASTLE IN

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THE U.K.

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HIS RESEARCH WAS INITIALLY

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FOCUSED ON THE GENETIC

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DETERMINANTS OF DEMENTIA.

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HE DID HIS POSTDOCTORAL WORK AT

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THE MAYO CLINIC AND THEN MOVED

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TO THE NATIONAL INSTITUTE ON

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AGING AND BECAME LABORATORY

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CHIEF IN 2008.

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IN 2016, HE BECAME ANION  AN NIA

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DISTINGUISHED INVESTIGATOR AND

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DIRECTOR OF THE NEW CENTER FOR

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ALZHEIMER'S DISEASE AND RELATED

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DEMENTIA, CARD.

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IN THIS NEW ROLE, ANDY HAS

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DEMONSTRATED THAT HE'S NOT ONLY

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A WONDERFUL SCIENTIST BUT ALSO A

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LEADER OF PEOPLE AND A WONDERFUL

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ORGANIZER.

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ANDY HAS ORGANIZED -- HAS

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PUBLISHED MORE THAN 700

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ARTICLES, SO NEVER TRY TO PRINT

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HIS CV BECAUSE YOU HAVE TO SAVE

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TREES.

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HIS WORK HAS WORKED MOSTLY ON

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THE GENETIC OR NEUROLOGICAL

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DISORDER, INCLUDING PARKINSON'S

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DISEASE, DYSTONIA, ATAXIA,

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DEMENTIA, AND LEWY BODY DISEASE

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AND -- REALLY TO GLIMPSE AN

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OPPORTUNITY FOR TREATMENT THAT

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CAN BE OPEN IN THE FUTURE IN A

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FIELD THAT REALLY NEEDS NEW

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TREATMENT, NEW EFFECTIVE

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TREATMENT DESPERATELY.

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ANDY SERVES ON SEVERAL EDITORIAL

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BOARDS AND ADVISORY BOARDS AND

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AS THE GOOD SCIENTIST HE IS, HE

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HAS WON MANY, MANY AWARDS.

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THE AWARD FOR PARKINSON'S

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DISEASE RESEARCH, AWARD FOR

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OUTSTANDING ACHIEVEMENT IN

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PARKINSON'S DISEASE RESEARCH AND

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THE AMERICAN ACADEMY OF

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NEUROLOGY DISORDER AWARD.

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THANK YOU, ANDY, FOR ACCEPTING

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TO GIVE THIS LECTURE, WE ARE

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HEADING FOR A TREAT, AND I LOOK

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FORWARD TO LISTENING FROM YOU OF

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YOUR WONDERFUL SCIENCE.

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>> THANK YOU, LUIGI, THANK YOU

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SO MUCH FOR THE KIND

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INTRODUCTION.

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AND IT'S A REAL PLEASURE TO GIVE

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THIS TALK TODAY.

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I WISH IT WAS IN PERSON.

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BUT THIS WILL HAVE TO DO.

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SO I'VE BEEN IN THE INTRAMURAL

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RESEARCH PROGRAM AS LUIGI SAID

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FOR 21 YEARS NOW, WHICH IF

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SOMEONE HAD TOLD ME THAT 21

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YEARS AGO, I WOULD NEVER HAVE

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BELIEVED IT.

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BUT KIND OF THE THEME OF -- AN

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UNDERLYING THEME OF THIS TALK IS

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HOW SPECIAL THE INTRAMURAL

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PROGRAM IS.

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AND I THINK THAT'S A LARGE PART

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OF THE REASON WHY SO MANY OF US

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WHO CAME HERE SLIGHTLY LESS GREY

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AND QUITE A LOT YOUNGER TEND TO

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HANG AROUND FOR A WHILE, BECAUSE

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IT REALLY IS A WONDERFUL PLACE

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TO WORK.

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MANY OF YOU KNOW THIS ALREADY,

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BUT THERE ARE SOME -- I THINK

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WE'RE IN A REALLY PRIVILEGED

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POSITION IN INTRAMURAL RESEARCH

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PROGRAM.

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WE CAN DO SOME THINGS THAT ARE

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SLIGHTLY DIFFERENT TO THE REST

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OF THE WORLD, LARGELY BECAUSE OF

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THE THINGS I HAVE WRITTEN HERE.

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WE HAVE STABLE, GENEROUS

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RESOURCES, WE'RE PRETTY SECURE,

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OUR REVIEW ISN'T ENTIRELY

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PROSPECTIVE, WE CAN DEFINE OUR

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OWN METRICS OF SUCCESS, WE CAN

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FAIL, WE HAVE THIS TOLERANCE FOR

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FAILURE.

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AND ALL OF THESE THINGS, I

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THINK, COME TOGETHER TO MEAN

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THAT WE CAN TAKE ON SOME THINGS

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THAT CAN'T READILY BE TAKEN ON.

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AND THIS WILL BE PART OF THE

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THEME OF WHAT I'M GOING TO TALK

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ABOUT TODAY.

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REALLY THE THEME IS WE'VE USED

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OUR POSITION OR I'VE USED MY

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POSITION IN MY LAB AND MY

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COLLEAGUES IN THE LAB TOO, TO

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REALLY CREATE A COOPERATIVE

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RESEARCH NETWORK, AND I'M GOING

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TO TALK ENTIRELY ABOUT

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PARKINSON'S TODAY, AND I'M GOING

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TO TALK ENTIRELY ABOUT

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PARKINSON'S GENETICS TODAY.

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BUT I WOULD SAY THIS CERTAINLY

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STRETCHES TO OTHER DISEASES BUT

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ALSO OUTSIDE OF GENETICS, INTO

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FUNCTIONAL DOMAINS.

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AND WE'VE REALLY TAKEN THAT

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SERIOUSLY IN OUR LAB AS LUIGI

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MENTIONED, I RAN THE LAB OF

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NEUROGENETICS FOR A FAIRLY LONG

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TIME, BUT WE HAD A COLLECTIVE

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MANAGEMENT STRUCTURE AND ALL THE

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LEADERS WERE ON THE SAME PAGE

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ABOUT HOW WE CAN ESSENTIALLY USE

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OUR POSITION IN THE INTRAMURAL

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PROGRAM AND THE COLLABORATIVE

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FRAMEWORK OF OUR LAB TO REALLY

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EFFECT FUNDAMENTAL CHANGE IN

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NEURODEGENERATIVE DISEASE

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RESEARCH.

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SO I'M GENETICIST, WE ARE

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INCREDIBLY SIMPLE PEOPLE, WE ARE

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THE SIMPLEST OF SCIENTISTS, I

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THINK.

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AS YOU CAN SELL TELL  TELL BY
THIS

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FRAMEWORK HERE, REALLY, I THINK

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THIS IS WORTH THINKING ABOUT AT

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THE BEGINNING OF EVERY TALK

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THAT'S CENTERED ON GENETICS.

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WHY DO WE FOCUS ON TRYING TO

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IDENTIFY GENES THAT UNDERLIE

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DISEASE?

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OF COURSE THE IDEA IS, IF YOU

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CAN FIND A GENE THAT IS

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CAUSATIVE ORIS  OR A RISK FACTOR
FOR

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DISEASE, IT'S LIKE SEEING THE

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OPENING TITLE SEQUENCE OF A

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MOVIE.

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IT GIVES YOU AN IDEA ABOUT WHAT

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THE MOVIE -- WHERE THE MOVIE IS

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GOING TO GO.

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YOU GET AN IDEA OF KIND OF WHAT

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THE FRAMEWORK IS FOR THE MOVIE,

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AND YOU GET A STARTING POINT TO

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START TO TRY AND TEASE OUT

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WHAT'S GOING TO HAPPEN.

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SO WE USE GENETICS AS A STARTING

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POINT TO UNDERSTAND THE

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PATHOBIOLOGY OF DISEASE.

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ALL WITH THE IDEA OF NOT JUST

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UNDERSTANDING BIOLOGY, BUT WITH

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IDENTIFYING VIABLE POINTS FOR

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THERAPEUTIC INTERVENTION.

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I THINK OVER RECENT YEARS, IN

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THE LAST DECADE OR SO, WE'VE

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REALIZED THAT THERE IS MORE TO

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IT THAN JUST THAT.

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THAT IT'S NOT ENOUGH JUST TO

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UNDERSTAND THE BIOLOGY OF THE

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DISEASE AND LOOK FOR TARGETS,

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BUT FOR PARTICULARLY THE

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DISEASES THAT WE WORK ON, LATE

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ONSET NEURODEGENERATIVE

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DISEASES, WE NEED TO DISSECT THE

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DISEASE AS WELL.

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WE NEED TO BE ABLE TO PREDICT

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WHEN SOMEONE IS GOING TO GET A

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DISEASE WELL BEFORE THE ONSET OF

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SIGNS AND SYMPTOMS, AND WE ALSO

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NEED TO BE ABLE TO CLASSIFY THE

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DISEASE INTO MECHANISTIC

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SUBTYPES.

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SO THIS IS ALL MOVING TOWARDS

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THE NOTION OF BEING ABLE TO

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IDENTIFY THE RIGHT PATIENT AT

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THE RIGHT TIME AND APPLY THE

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RIGHT TARGET.

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SO I'M GOING TO TALK ABOUT THE

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WORK FROM MY LAB.

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THIS IS NOT THE ONLY GENETICS

200
00:07:12,640 --> 00:07:14,360
WORK THAT'S BEEN GOING ON IN

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PARKINSON'S DISEASE.

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OTHER GROUPS HAVE BEEN WORKING

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AROUND THE WORLD ON PD BUT I

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THINK WE'VE HAD A REALLY

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OUTSIZED CONTRIBUTION.

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SO I'M GOING TO TALK ABOUT THE

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THINGS THAT WE'VE REALLY

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CONTRIBUTED TO, AND I'M GOING TO

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SPLIT IT INTO TWO BROAD DOMAINS.

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FIRST OF ALL, KNOW  MONOGENIC
DISEASE

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AND THEN COMPLEX DISEASE.

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SO IT'S GOING TO BE A LITTLE

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ASYNCHRONOUS BECAUSE WE DID BOT

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AT THE SAME TIME.

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SO I'LL TALK ABOUT PROGRESS,

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THEN I'M GOING TO TALK ABOUT

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WHERE WE'RE GOING NEXT, WHAT THE

218
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CHALLENGES ARE THAT I SEE IN

219
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THIS PARTICULAR SPACE.

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SO SO REALLY THIS IS THE FIRST
--

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BEFORE I MOVED TO THE U.S., I

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WORKED IN THE GENETICS OF

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DEMENTIA WITH LEWY BODIES AND

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ALZHEIMER'S DISEASE.

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WHEN I MOVED TO THE U.S. AROUND

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00:07:59,720 --> 00:08:03,240
1999, I STARTED TO WORK ON

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00:08:03,240 --> 00:08:04,240
PARKINSON'S DISEASE, AND THIS

228
00:08:04,240 --> 00:08:13,520
WAS REALLY ONE OF THE FIRST

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PIECES OF WORK WE STARTED TO

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WORK ON.

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00:08:18,040 --> 00:08:19,840
IT'S WHAT I'VE BEEN INVOLVED IN

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IN THE MOST RECENT FIVE OR SIX

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YEARS.

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SO THIS WAS A FAMILY THAT WE

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STUDIED ACTUALLY FROM THE D.C. 

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AREA, THIS IS A BLACK FAMILY

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WITH PARKINSON'S DISEASE.

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INCREDIBLY SURPRISINGLY AT THE

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TIME, WE FOUND THAT THE MUTATION

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UNDERLYING THE DISEASE WAS A

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SPINOCEREBELLAR ATAXIA TYPE 3.

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THESE SYMPTOMS REALLY WEREN'T

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ASSOCIATED WITH PARKINSON'S

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DISEASE.

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AS WE STARTED TO COLLECT MORE

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FAMILIES AND LOOK AT MORE

247
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LITERATURE IN THIS SPACE, IT

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00:08:50,880 --> 00:08:51,600
BECAME APPARENT THAT WHAT WE

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00:08:51,600 --> 00:08:54,680
WERE SEEING HERE IS THAT A

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00:08:54,680 --> 00:08:56,400
GENETIC CAUSE OF DISEASE CAN

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00:08:56,400 --> 00:09:01,320
PRESENT IN DIFFERENT WAYS BASED

252
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ON ANCESTRAL BACKGROUND.

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00:09:04,760 --> 00:09:07,600
SO THIS FINDING BACK -- WHICH WE

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00:09:07,600 --> 00:09:09,560
MADE ACTUALLY IN 1999 TOOK US

255
00:09:09,560 --> 00:09:11,320
2 1/2 YEARS TO PUBLISH BECAUSE

256
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ACTUALLY NOBODY BELIEVED IT,

257
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THEY THOUGHT IT WAS JUST SIMPLY

258
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MISDIAGNOSIS OF DISEASE, AND

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THAT IN PART IS BECAUSE

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00:09:20,880 --> 00:09:22,360
PARKINSON'S DISEASE IS REALLY

261
00:09:22,360 --> 00:09:23,560
TRADITIONALLY A WHITE CONSTRUCT.

262
00:09:23,560 --> 00:09:25,120
WHAT WE KNOW ABOUT PARKINSON'S

263
00:09:25,120 --> 00:09:26,000
DISEASE, WHAT WE KNOW ABOUT THE

264
00:09:26,000 --> 00:09:27,680
CLINICAL PRESENTATION OF

265
00:09:27,680 --> 00:09:29,280
PARKINSON'S DISEASE IS BASED

266
00:09:29,280 --> 00:09:30,560
LARGELY ON WORK DONE IN

267
00:09:30,560 --> 00:09:34,520
INDIVIDUALS OF NORTHERN EUROPEAN

268
00:09:34,520 --> 00:09:35,480
ANCESTRY.

269
00:09:35,480 --> 00:09:37,360
I WILL COME BACK TO THIS POINT

270
00:09:37,360 --> 00:09:40,960
LATER ON IN THE SLIDE.

271
00:09:40,960 --> 00:09:42,680
NOT LONG AFTER MOVING TO THE

272
00:09:42,680 --> 00:09:44,360
U.S., WE MADE THIS DISCOVERY.

273
00:09:44,360 --> 00:09:46,360
SO THE FIRST GENE THAT WAS FOUND

274
00:09:46,360 --> 00:09:53,760
IN PARKINSON'S DISEASE WAS FOUND

275
00:09:53,760 --> 00:09:55,960
IN 1997 AT NHGRI IN THE

276
00:09:55,960 --> 00:09:58,480
INTRAMURAL PROGRAM AND IT WAS

277
00:09:58,480 --> 00:10:02,080
THIS GENE ALPHA SYNUCLEIN, A

278
00:10:02,080 --> 00:10:05,960
CONSTITUENT PART OF LEWY BODIES,

279
00:10:05,960 --> 00:10:08,720
THE PATHOMO NICK HALLMARK FOR

280
00:10:08,720 --> 00:10:09,120
PARKINSON DISEASE.

281
00:10:09,120 --> 00:10:10,560
THE MUTATIONS THAT HAD BEEN

282
00:10:10,560 --> 00:10:13,320
FOUND WERE POINT MUTATIONS SO

283
00:10:13,320 --> 00:10:16,520
THEY WERE QUALITATIVE CHANGES IN

284
00:10:16,520 --> 00:10:16,760
SYNUCLEIN.

285
00:10:16,760 --> 00:10:18,080
WHAT WE FOUND IN 2003 WAS

286
00:10:18,080 --> 00:10:20,320
ACTUALLY A RARE CAUSE OF

287
00:10:20,320 --> 00:10:22,320
PARKINSON'S DISEASE IS THESE

288
00:10:22,320 --> 00:10:24,160
QUANTITATIVE CHANGES IN

289
00:10:24,160 --> 00:10:24,960
SYNUCLEIN WHERE EXTRA GENE

290
00:10:24,960 --> 00:10:27,360
COPIES OF LEAD TO EXTRA

291
00:10:27,360 --> 00:10:28,120
PRODUCTION OF SYNUCLEIN AND THAT

292
00:10:28,120 --> 00:10:34,600
IS ENOUGH TO DRIVE DISEASE IN

293
00:10:34,600 --> 00:10:35,760
INDIVIDUALS 20s OR 30s.

294
00:10:35,760 --> 00:10:37,440
SO THIS TOOK A LONG TIME TO

295
00:10:37,440 --> 00:10:38,760
FIND, THIS CERTAINLY TOOK MANY

296
00:10:38,760 --> 00:10:39,760
YEARS TO FIND, AND IT'S

297
00:10:39,760 --> 00:10:41,720
SOMETHING THAT YOU COULD FIND

298
00:10:41,720 --> 00:10:43,200
NOW IN A COUPLE OF DAYS WITH

299
00:10:43,200 --> 00:10:44,160
MODERN TECHNOLOGY.

300
00:10:44,160 --> 00:10:47,280
BUT AT THE TIME, IT WAS FAIRLY

301
00:10:47,280 --> 00:10:48,160
GROUNDBREAKING.

302
00:10:48,160 --> 00:10:51,520
IT TOLD US WHAT I'VE ALREADY

303
00:10:51,520 --> 00:10:52,640
STATED, JUST INCREASING THE

304
00:10:52,640 --> 00:10:54,040
AMOUNT OF SYNUCLEIN WAS ENOUGH

305
00:10:54,040 --> 00:10:55,640
TO CAUSE DISEASE, AND THIS IS A

306
00:10:55,640 --> 00:10:58,000
MECHANISM WHICH I THINK STILL

307
00:10:58,000 --> 00:11:00,360
HOLDS TRUE TODAY, AND IS

308
00:11:00,360 --> 00:11:02,000
RELEVANT NOT ONLY FOR MUTATIONS

309
00:11:02,000 --> 00:11:04,080
BUT FOR RISK FACTORS.

310
00:11:04,080 --> 00:11:06,240
IT TOLD US -- IT ALSO TOLD US

311
00:11:06,240 --> 00:11:08,760
THAT WE HAD TO BE REALLY CAREFUL

312
00:11:08,760 --> 00:11:12,200
ABOUT MODELING, HOWEVER,

313
00:11:12,200 --> 00:11:13,520
EXPRESSION LEVELS -- THAT

314
00:11:13,520 --> 00:11:15,200
CERTAINLY HAS AN IMPACT ON THE

315
00:11:15,200 --> 00:11:18,960
IMPLICATIONS OF THE MODELS.

316
00:11:18,960 --> 00:11:20,320
LASTLY, IT TOLD US SOMETHING

317
00:11:20,320 --> 00:11:21,360
ABOUT THERAPEUTIC OPPORTUNITIES.

318
00:11:21,360 --> 00:11:23,360
IF PRODUCING TOO MUCH SYNUCLEIN

319
00:11:23,360 --> 00:11:25,600
CAN CAUSE RARE DISEASE, A RARE

320
00:11:25,600 --> 00:11:27,160
FORM OF PARKINSON'S DISEASE, AND

321
00:11:27,160 --> 00:11:28,800
WE THINK THE COMMON VARIABILITY

322
00:11:28,800 --> 00:11:31,560
ALSO AFFECTS SYNUCLEIN LEVELS,

323
00:11:31,560 --> 00:11:33,960
THEN MAYBE TARGETING SYNUCLEIN

324
00:11:33,960 --> 00:11:35,600
CLEARANCE OR REDUCING ITS

325
00:11:35,600 --> 00:11:37,720
EXPRESSION IS A VIABLE PART OF

326
00:11:37,720 --> 00:11:38,360
THERAPEUTIC INTERVENTION AND

327
00:11:38,360 --> 00:11:39,160
I'LL TALK A LITTLE MORE ABOUT

328
00:11:39,160 --> 00:11:40,000
THAT LATER.

329
00:11:40,000 --> 00:11:41,320
NOT LONG AFTER THAT, A YEAR OR

330
00:11:41,320 --> 00:11:47,200
SO LATER, OUR LAB ALONG WITH A

331
00:11:47,200 --> 00:11:49,840
COUPLE OF COLLABORATORS AND SOME

332
00:11:49,840 --> 00:11:54,480
COMPETING LABS FOUND THE LRRK2

333
00:11:54,480 --> 00:11:56,160
MUTATION THAT CAUSE PRETTY

334
00:11:56,160 --> 00:11:58,440
TYPICAL PARKINSON'S DISEASE.

335
00:11:58,440 --> 00:12:02,960
SO THIS LRRK2 -- KINASE.

336
00:12:02,960 --> 00:12:05,080
WHAT WAS PARTICULARLY

337
00:12:05,080 --> 00:12:06,760
INTERESTING ABOUT THIS DISCOVERY

338
00:12:06,760 --> 00:12:08,360
WAS THAT ALL OF THE PREVIOUS

339
00:12:08,360 --> 00:12:09,760
GENES THAT HAD BEEN IDENTIFIED

340
00:12:09,760 --> 00:12:12,840
AND ASSOCIATED WITH --

341
00:12:12,840 --> 00:12:13,960
ASSOCIATED WITH RARE FORMS OF

342
00:12:13,960 --> 00:12:16,600
DISEASE WERE GENERALLY QUITE

343
00:12:16,600 --> 00:12:19,400
RARE, SO SYNUCLEIN MUTATIONS

344
00:12:19,400 --> 00:12:21,240
WERE EXTREMELY RARE.

345
00:12:21,240 --> 00:12:24,400
THIS IS NOT TRUE FOR LRRK2.

346
00:12:24,400 --> 00:12:28,160
LRRK2 MUTATIONS, PARTICULARLY

347
00:12:28,160 --> 00:12:30,360
ONE MUTATION OF THE KINASE

348
00:12:30,360 --> 00:12:33,120
DOMAIN, THIS IS RESPONSIBLE FOR

349
00:12:33,120 --> 00:12:34,680
ABOUT 1 IN 50 CASES OF

350
00:12:34,680 --> 00:12:36,080
PARKINSON'S DISEASE IN NORTH

351
00:12:36,080 --> 00:12:36,440
AMERICA.

352
00:12:36,440 --> 00:12:40,320
SO ABOUT 20,000 INDIVIDUALS IN

353
00:12:40,320 --> 00:12:47,400
NORTH AMERICA HAVE PARKINSON'S

354
00:12:47,400 --> 00:12:49,560
DISEASE.  THIS CHANGES PRETTY

355
00:12:49,560 --> 00:12:53,440
DRASTICALLY FROM POPULATION TO

356
00:12:53,440 --> 00:12:54,520
POPULATION.

357
00:12:54,520 --> 00:12:57,840
IF YOU LOOK NE NORTH AFRICA

358
00:12:57,840 --> 00:13:01,600
POPULATION, IT'S ALMOST 1 IN 2.

359
00:13:01,600 --> 00:13:03,080
THIS WAS ALSO A REALLY GREAT

360
00:13:03,080 --> 00:13:05,760
LEARNING EXPERIENCE FOR ME.

361
00:13:05,760 --> 00:13:07,400
THIS WAS A GREAT LEARNING

362
00:13:07,400 --> 00:13:08,000
EXPERIENCE ABOUT THE POWER OF

363
00:13:08,000 --> 00:13:12,200
THE INTRAMURAL PROGRAM AND ABOUT

364
00:13:12,200 --> 00:13:13,360
COLLABORATION.

365
00:13:13,360 --> 00:13:14,600
WE KNEW IN THOSE DAYS, WE WERE

366
00:13:14,600 --> 00:13:15,960
RACING OTHERS TO FIND THIS GENE

367
00:13:15,960 --> 00:13:18,000
AND WE KNEW THE WAY TO DO THIS

368
00:13:18,000 --> 00:13:20,840
WAS TO COLLABORATE.

369
00:13:20,840 --> 00:13:22,320
SO USING THE RESOURCES WE COULD

370
00:13:22,320 --> 00:13:24,360
BRING TO BEAR FROM THE IRP,

371
00:13:24,360 --> 00:13:28,240
ABILITY TO SEQUENCE AT GREAT

372
00:13:28,240 --> 00:13:29,400
SPEED, BRING INFORMATION

373
00:13:29,400 --> 00:13:30,640
TOGETHER, WE WORKED WITH GROUPS

374
00:13:30,640 --> 00:13:33,000
FROM SPAIN, LONDON, AND REALLY

375
00:13:33,000 --> 00:13:35,560
THAT COLLABORATION AND THAT

376
00:13:35,560 --> 00:13:37,960
SPEED LED US TO WIN THIS RACE TO

377
00:13:37,960 --> 00:13:39,560
IDENTIFY THE GENE.

378
00:13:39,560 --> 00:13:40,920
THE SECOND PART THAT I THINK WAS

379
00:13:40,920 --> 00:13:44,680
REALLY REVEALING WAS THE BEAUTY

380
00:13:44,680 --> 00:13:46,360
OF THE INTRAMURAL PROGRAM IN

381
00:13:46,360 --> 00:13:49,000
THAT WE CAN PIVOT VERY QUICKLY

382
00:13:49,000 --> 00:13:50,920
AND WE CAN CHANGE RESOURCES VERY

383
00:13:50,920 --> 00:13:51,600
QUICKLY.

384
00:13:51,600 --> 00:13:55,120
SO THE DAY WE FOUND THIS MODEL,

385
00:13:55,120 --> 00:13:57,000
COOKSON, WHO'S A PI OOF WORKED

386
00:13:57,000 --> 00:14:01,240
WITH FOR 25 YEARS, BEEN

387
00:14:01,240 --> 00:14:03,560
WONDERFUL TO WORK WITH, MARK

388
00:14:03,560 --> 00:14:05,040
COOKSON CHANGED THE DIRECTION OF

389
00:14:05,040 --> 00:14:05,960
HIS LAB ALMOST OVERNIGHT TO

390
00:14:05,960 --> 00:14:08,200
START WORKING ON LRRK2.

391
00:14:08,200 --> 00:14:11,160
AND ACTUALLY THE WORK HE DID

392
00:14:11,160 --> 00:14:12,640
SHOWING KINASE ACTIVITY WAS KEY

393
00:14:12,640 --> 00:14:19,560
FOR THE -- GAIN OF FUNCTION --

394
00:14:19,560 --> 00:14:20,800
CONSEQUENCES WHICH I'LL TALK A

395
00:14:20,800 --> 00:14:24,120
LITTLE BIT ABOUT LATER.

396
00:14:24,120 --> 00:14:26,200
NOT LONG AFTER THIS, AND AGAIN

397
00:14:26,200 --> 00:14:28,560
IN THIS THEME OF FINDING

398
00:14:28,560 --> 00:14:29,920
MUTATIONS THAT PRESENT

399
00:14:29,920 --> 00:14:33,440
DIFFERENTLY, OR CAN HAVE

400
00:14:33,440 --> 00:14:34,960
DIFFERENT OUTCOMES, WE FOUND

401
00:14:34,960 --> 00:14:38,760
THIS GENE, PLA2G6, WHICH HAD

402
00:14:38,760 --> 00:14:40,960
PREVIOUSLY BEEN SHOWN TO

403
00:14:40,960 --> 00:14:42,880
MUTATIONS PREVIOUSLY ASSOCIATE

404
00:14:42,880 --> 00:14:44,960
WITH AN INFANTILE

405
00:14:44,960 --> 00:14:45,480
NEURODEGENERATIVE DISEASE.

406
00:14:45,480 --> 00:14:49,360
WE SHOWED THESE CAN CAUSE A

407
00:14:49,360 --> 00:14:49,960
DYSTONIA-PARKINSONISM SYNDROME.

408
00:14:49,960 --> 00:14:51,640
SO NOW WE'RE AROUND 2009, WE'VE

409
00:14:51,640 --> 00:14:53,960
GONE THROUGH THESE EXPERIENCES

410
00:14:53,960 --> 00:14:56,760
OF INDIVIDUAL GENE HUNTING

411
00:14:56,760 --> 00:14:58,560
ESCAPADES WHERE WE'RE CHASING

412
00:14:58,560 --> 00:15:01,240
GENES LIKE CRAZY, STARTING TO

413
00:15:01,240 --> 00:15:02,560
THINK ABOUT WORKING MORE

414
00:15:02,560 --> 00:15:04,200
COLLABORATIVELY WITH OTHER

415
00:15:04,200 --> 00:15:05,160
GROUPS.

416
00:15:05,160 --> 00:15:08,040
GENETICS WAS AN INCREDIBLY

417
00:15:08,040 --> 00:15:09,240
COMPETITIVE ENDEAVOR BACK IN THE

418
00:15:09,240 --> 00:15:10,760
LATE '90S AND EARLY 2,000s,

419
00:15:10,760 --> 00:15:12,280
BUT AROUND THIS TIME, OUR GROUP

420
00:15:12,280 --> 00:15:14,520
REALLY STARTED TO THINK ABOUT

421
00:15:14,520 --> 00:15:15,440
THE POWER OF WORKING WITH

422
00:15:15,440 --> 00:15:18,360
OTHERS.

423
00:15:18,360 --> 00:15:21,400
SO IN 2009, ALONG WITH AROUND 10

424
00:15:21,400 --> 00:15:22,640
OR SO OTHER INVESTIGATORS FROM

425
00:15:22,640 --> 00:15:26,400
AROUND THE WORLD, WE FORMED THIS

426
00:15:26,400 --> 00:15:28,360
CONSORTIUM, THE INTERNATIONAL PD

427
00:15:28,360 --> 00:15:29,520
GENOMICS CONSORTIUM, AND THE

428
00:15:29,520 --> 00:15:31,400
IDEA HERE WAS TO CREATE A GROUP

429
00:15:31,400 --> 00:15:33,760
THAT COULD WORK TOGETHER REALLY

430
00:15:33,760 --> 00:15:36,560
QUICKLY AND SHARE DATA VERY

431
00:15:36,560 --> 00:15:39,280
QUICKLY WITHOUT TOO MANY

432
00:15:39,280 --> 00:15:41,840
INENCUMBRANCES.

433
00:15:41,840 --> 00:15:43,240
AGAIN, THE IRP WAS REALLY

434
00:15:43,240 --> 00:15:48,680
ESSENTIAL IN THE SUCCESS OF IGC.

435
00:15:48,680 --> 00:15:51,160
WE WERE ABLE TO PROVIDE QUICK

436
00:15:51,160 --> 00:15:52,280
SEQUENCING, QUICK RESOURCES TO

437
00:15:52,280 --> 00:15:53,560
GET THINGS OFF THE GROUND AND

438
00:15:53,560 --> 00:15:54,760
GET THINGS MOVING.

439
00:15:54,760 --> 00:15:55,840
WHEREAS THE OTHER INVESTIGATORS

440
00:15:55,840 --> 00:15:57,880
WERE HAVING TO WRITE GRANTS AND

441
00:15:57,880 --> 00:15:59,320
APLAY FOR FUNDING, WE COULD

442
00:15:59,320 --> 00:16:00,480
REALLY SEED PROGRESS VERY, VERY

443
00:16:00,480 --> 00:16:01,440
QUICKLY AND I'LL TALK A LITTLE

444
00:16:01,440 --> 00:16:06,600
BIT MORE ABOUT THAT LATER.

445
00:16:06,600 --> 00:16:11,040
IPDGC HAS ALSO DISCOVERED

446
00:16:11,040 --> 00:16:11,960
MUTATIONS, FASCINATING CAUSE OF

447
00:16:11,960 --> 00:16:14,440
PARKINSON'S DISEASE, AND ALSO

448
00:16:14,440 --> 00:16:16,600
CREATED A NETWORK TO KIND OF

449
00:16:16,600 --> 00:16:21,280
CORRECT OR COURSE CORRECT THE

450
00:16:21,280 --> 00:16:26,360
LITERATURE, NOW GENETICS IS

451
00:16:26,360 --> 00:16:28,480
RELATIVELY ACCESSIBLE FOR MANY

452
00:16:28,480 --> 00:16:29,960
PEOPLE.

453
00:16:29,960 --> 00:16:31,520
WHAT THIS HAS EFFECTIVELY LED

454
00:16:31,520 --> 00:16:34,000
TO, THOUGH, IN THE PARKINSON'S

455
00:16:34,000 --> 00:16:35,680
FIELD IS A VERY LARGE NUMBER OF

456
00:16:35,680 --> 00:16:38,800
GENES PUBLISHED OR MUTATIONS AND

457
00:16:38,800 --> 00:16:43,360
GENES PUBLISHED THAT JUST REALLY

458
00:16:43,360 --> 00:16:43,840
PROBABLY AREN'T RIGHT.

459
00:16:43,840 --> 00:16:46,480
SO WE'VE BEEN ABLE TO USE THE

460
00:16:46,480 --> 00:16:48,040
STRUCTURE OF THE IPDGC TO

461
00:16:48,040 --> 00:16:49,960
CORRECT THE LITERATURE AS TIME

462
00:16:49,960 --> 00:16:50,760
HAS GONE ON.

463
00:16:50,760 --> 00:16:52,480
ACTUALLY THIS HAS BEEN A DOUBLE

464
00:16:52,480 --> 00:16:57,400
WHAMMY BECAUSE EVE USED THIS 
WE'VE USED T
HIS

465
00:16:57,400 --> 00:16:59,560
PROGRESS TO TRAIN STUDENTS.

466
00:16:59,560 --> 00:17:01,880
THEY'RE TASKED WITH CHECKING UP

467
00:17:01,880 --> 00:17:04,240
ON NEW GENES AND PUBLISHING

468
00:17:04,240 --> 00:17:10,600
THESE STUDIES IN VERY LARGE

469
00:17:10,600 --> 00:17:13,040
COHORTS.

470
00:17:13,040 --> 00:17:14,840
SO WHERE HAS THIS WORK IN

471
00:17:14,840 --> 00:17:16,000
MONOGENIC DISEASE LED US?

472
00:17:16,000 --> 00:17:17,960
IT'S LED US TO AROUND 17 OR SO

473
00:17:17,960 --> 00:17:19,240
PLAUSIBLE GENES THAT CONTAIN

474
00:17:19,240 --> 00:17:23,400
MUTATIONS THAT CAUSE PARKINSON'S

475
00:17:23,400 --> 00:17:25,320
DISEASE.

476
00:17:25,320 --> 00:17:27,200
I SAID I WOULD TALK ONLY ABOUT

477
00:17:27,200 --> 00:17:29,720
THE THINGS THAT WE REALLY

478
00:17:29,720 --> 00:17:30,040
HEAVILY DROVE.

479
00:17:30,040 --> 00:17:31,520
I'M GOING TO MAKE ONE EXCEPTION.

480
00:17:31,520 --> 00:17:33,560
SO THIS IS WORK REALLY DRIVEN BY

481
00:17:33,560 --> 00:17:36,080
ELLEN SIDRANSKI.

482
00:17:36,080 --> 00:17:39,360
WE CERTAINLY PARTICIPATED IN

483
00:17:39,360 --> 00:17:40,960
MIKE NOLES, A YOUNG STATISTICIAN

484
00:17:40,960 --> 00:17:43,160
AT THE TIME, THE LEAD ANALYST

485
00:17:43,160 --> 00:17:47,280
FOR THIS, BUT THIS IS REALLY

486
00:17:47,280 --> 00:17:49,360
BEAUTIFUL WORK THAT ELLEN DROVE

487
00:17:49,360 --> 00:17:56,480
THAT SHOWED GLUCOCEREBROSIDASE

488
00:17:56,480 --> 00:18:00,160
MUTATIONS, A RECESSIVE FORM THAT

489
00:18:00,160 --> 00:18:03,280
CAUSED GAUCHER'S DISEASE, A

490
00:18:03,280 --> 00:18:04,800
SIGNIFICANT RISK FACTOR FOR

491
00:18:04,800 --> 00:18:05,520
PARKINSON'S DISEASE.

492
00:18:05,520 --> 00:18:07,680
THERE HAD BEEN IMPLICATIONS

493
00:18:07,680 --> 00:18:13,760
BEFORE THIS, IMPLICATING -- I

494
00:18:13,760 --> 00:18:15,040
THINK THIS PUBLICATION REALLY

495
00:18:15,040 --> 00:18:16,800
PROVED THIS BEYOND A DOUBT.

496
00:18:16,800 --> 00:18:18,120
AND AGAIN, THIS WAS ABOUT

497
00:18:18,120 --> 00:18:23,560
BRINGING PEOPLE TOGETHER, AND I

498
00:18:23,560 --> 00:18:25,320
THINK IT'S NO SURPRISE THAT

499
00:18:25,320 --> 00:18:28,160
SOMEONE FROM THE INTRAMURAL

500
00:18:28,160 --> 00:18:32,560
PROGRAM, ELLEN, WAS ABLE TO

501
00:18:32,560 --> 00:18:34,520
BRING GROUPS TOGETHER FROM

502
00:18:34,520 --> 00:18:35,480
AROUND THE WORLD.

503
00:18:35,480 --> 00:18:37,400
SO WE HAVE GENES THAT CONTAIN

504
00:18:37,400 --> 00:18:39,280
DISEASE-CAUSING MUTATIONS, A

505
00:18:39,280 --> 00:18:41,000
COUPLE OF MODERATE RISK PROTEIN

506
00:18:41,000 --> 00:18:42,960
CODING VARIANTS THAT I MENTIONED

507
00:18:42,960 --> 00:18:52,920
HERE, AND ALSO ACTUALLY AGE 

508
00:18:52,920 --> 00:18:54,560
AGING-SPECIFIC VARIANTS.

509
00:18:54,560 --> 00:18:56,080
SO AGAIN SPEAKING TO THE POWER

510
00:18:56,080 --> 00:18:57,120
OF THE INTRAMURAL PROGRAM, THIS

511
00:18:57,120 --> 00:18:58,720
WAS SOMETHING WE GOT INVOLVED IN

512
00:18:58,720 --> 00:18:59,960
REALLY, REALLY EARLY.

513
00:18:59,960 --> 00:19:02,120
BECAUSE AT THE TIME, WHEN WE

514
00:19:02,120 --> 00:19:06,080
STARTED DOING THIS IN 2004,

515
00:19:06,080 --> 00:19:07,560
2005, HIGH CONTENT GENOTYPING

516
00:19:07,560 --> 00:19:12,920
WAS REALLY NEW TECHNOLOGY, AND

517
00:19:12,920 --> 00:19:14,800
THERE WAS STILL A HUGE AMOUNT OF

518
00:19:14,800 --> 00:19:16,560
BAIT AS TO WOULD THIS REALLY

519
00:19:16,560 --> 00:19:18,320
WORK, WOULD GENOME-WIDE

520
00:19:18,320 --> 00:19:19,560
ASSOCIATION WORK.

521
00:19:19,560 --> 00:19:23,320
AND WE WERE ABLE TO TOLERATE THE

522
00:19:23,320 --> 00:19:25,160
POTENTIAL OF IT NOT WORKING,

523
00:19:25,160 --> 00:19:26,600
BRINGING GENOME-WIDE GENOTYPING

524
00:19:26,600 --> 00:19:27,760
INTO THE LAB AND JUST BEGIN

525
00:19:27,760 --> 00:19:29,600
WORKING AND BEGIN GENERATING

526
00:19:29,600 --> 00:19:30,160
DATA.

527
00:19:30,160 --> 00:19:32,720
ACTUALLY OUR FIRST STUDY WAS THE

528
00:19:32,720 --> 00:19:34,680
FIRST STUDY TO RELEASE

529
00:19:34,680 --> 00:19:37,000
GENOME-WIDE GENOTYPING SNP DATA

530
00:19:37,000 --> 00:19:37,840
INTO THE PUBLIC DOMAIN.

531
00:19:37,840 --> 00:19:40,160
I THINK IT WAS ONLY THE THIRD

532
00:19:40,160 --> 00:19:43,160
GENOME-WIDE ASSOCIATION STUDY

533
00:19:43,160 --> 00:19:44,080
PUBLISHED AT THE TIME.

534
00:19:44,080 --> 00:19:47,040
WE PUBLISHED IT IN 2006.

535
00:19:47,040 --> 00:19:48,720
AND IT WAS AN EMBARRASSINGLY

536
00:19:48,720 --> 00:19:52,360
SMALL NUMBER OF SAMPLES, 267

537
00:19:52,360 --> 00:19:53,560
CASES AND 267 CONTROLS.

538
00:19:53,560 --> 00:19:58,600
SO AS YOU CAN SEE IN THIS PLOT

539
00:19:58,600 --> 00:20:00,120
HERE, ZERO NEW LOCI, AS ONE

540
00:20:00,120 --> 00:20:00,760
WOULD EXPECT.

541
00:20:00,760 --> 00:20:02,640
BUT IT WAS INCREDIBLY USEFUL FOR

542
00:20:02,640 --> 00:20:05,000
US, IT WAS INCREDIBLY USEFUL FOR

543
00:20:05,000 --> 00:20:06,640
US BECAUSE IT TAUGHT US

544
00:20:06,640 --> 00:20:07,680
IMMEDIATELY THE RIGHT THING TO

545
00:20:07,680 --> 00:20:09,520
DO WAS TO PUT DATA INTO THE

546
00:20:09,520 --> 00:20:10,640
PUBLIC DOMAIN SO THAT IT COULD

547
00:20:10,640 --> 00:20:12,320
BE MINED BY OTHERS AND ACTUALLY

548
00:20:12,320 --> 00:20:13,560
ADDED TO BY OTHERS.

549
00:20:13,560 --> 00:20:16,480
THE DATA IS ESSENTIALLY DIGITAL

550
00:20:16,480 --> 00:20:20,360
IN ITS FORM, SO CONTRIBUTING THE

551
00:20:20,360 --> 00:20:21,640
DATA TO THE GENERAL PUBLIC OR

552
00:20:21,640 --> 00:20:23,080
THE GENERAL RESEARCH PUBLIC

553
00:20:23,080 --> 00:20:24,960
MEANS THAT OTHERS CAN ADD

554
00:20:24,960 --> 00:20:27,200
SAMPLES AND WE CAN INCREASE

555
00:20:27,200 --> 00:20:28,760
SAMPLE SIZES.

556
00:20:28,760 --> 00:20:30,400
IT ALSO SHOWED THAT WE COULD

557
00:20:30,400 --> 00:20:31,760
HANDLE THE DATA, WE COULD DO

558
00:20:31,760 --> 00:20:32,760
THIS KIND OF WORK IN THE LAB,

559
00:20:32,760 --> 00:20:34,560
AND I THINK THIS WAS REALLY KEY

560
00:20:34,560 --> 00:20:35,760
IN MAKING US A LEADER IN THIS

561
00:20:35,760 --> 00:20:39,320
SPACE.

562
00:20:39,320 --> 00:20:41,120
NOT MUCH LONGER AFTER THIS, IN

563
00:20:41,120 --> 00:20:42,560
2009, AGAIN, AROUND THIS TIME

564
00:20:42,560 --> 00:20:43,640
THAT WE'RE STARTING TO THINK

565
00:20:43,640 --> 00:20:48,160
ABOUT REALLY COLLABORATING

566
00:20:48,160 --> 00:20:48,920
HEAVILY, WE WORKED WITH A

567
00:20:48,920 --> 00:20:51,040
COMPETING GROUP, THE GROUP THAT

568
00:20:51,040 --> 00:20:55,200
WE'D BEEN RACING TO DISCOVER THE

569
00:20:55,200 --> 00:20:56,560
LRRK2 MUTATION BACK IN 2004, AND

570
00:20:56,560 --> 00:20:58,640
WE BROUGHT TOGETHER GENOME-WIDE

571
00:20:58,640 --> 00:21:00,080
DATA FROM THE U.S. AND FROM

572
00:21:00,080 --> 00:21:06,120
GERMANY, AND STARTED TO IDENTIFY

573
00:21:06,120 --> 00:21:07,920
NEW RISK LOCI.

574
00:21:07,920 --> 00:21:09,760
THE TWO YOU SEE HERE, ONE IS IN

575
00:21:09,760 --> 00:21:11,240
SYNUCLEIN, SO AGAIN, YOUR

576
00:21:11,240 --> 00:21:13,280
MUTATIONS IN SYNUCLEIN CAUSE

577
00:21:13,280 --> 00:21:15,080
PARKINSON'S DISEASE, BUT NOW WE

578
00:21:15,080 --> 00:21:16,320
KNOW THE COMMON VARIABILITY

579
00:21:16,320 --> 00:21:18,160
AROUND SYNUCLEIN IS A RISK

580
00:21:18,160 --> 00:21:19,120
FACTOR FOR PARKINSON'S DISEASE.

581
00:21:19,120 --> 00:21:21,640
THE OTHER IS A LOCUS ON

582
00:21:21,640 --> 00:21:22,160
CHROMOSOME 17 THAT'S VERY

583
00:21:22,160 --> 00:21:22,960
INTERESTING.

584
00:21:22,960 --> 00:21:28,400
IT CONTAINS THE GENE MICROTUBULE

585
00:21:28,400 --> 00:21:28,960
ASSOCIATED PROTEIN TAU.

586
00:21:28,960 --> 00:21:31,720
WE DON'T KNOW IF TAU IS THE

587
00:21:31,720 --> 00:21:33,200
EFFECTOR GENE THERE, BUT THIS IS

588
00:21:33,200 --> 00:21:34,360
AN IMPORTANT FINDING.

589
00:21:34,360 --> 00:21:35,960
NOT MUCH LONGER AFTER THAT, OF

590
00:21:35,960 --> 00:21:43,520
COURSE, WE FORMED IPDGC AND HAVE

591
00:21:43,520 --> 00:21:45,160
BEEN INCREDIBLY PRODUCTIVE EVEN

592
00:21:45,160 --> 00:21:46,360
MORE SO IN THE COMPLEX SPACE.

593
00:21:46,360 --> 00:21:48,000
AGAIN, WE WERE ABLE TO BRING

594
00:21:48,000 --> 00:21:49,120
RESOURCES TO BEAR FROM THE

595
00:21:49,120 --> 00:21:51,000
INTRAMURAL RESEARCH PROGRAM TO

596
00:21:51,000 --> 00:21:54,960
REALLY GET THIS CONSORTIUM

597
00:21:54,960 --> 00:21:56,400
STARTED AND REALLY START TO PUSH

598
00:21:56,400 --> 00:21:58,560
DOWN ON THE ACCELERATOR FROM DAY

599
00:21:58,560 --> 00:22:00,080
ONE, AND I THINK THAT WAS

600
00:22:00,080 --> 00:22:02,360
ABSOLUTELY KEY.

601
00:22:02,360 --> 00:22:03,560
SO IPDGC THEN STARTED TO RAMP

602
00:22:03,560 --> 00:22:06,000
UP, WE STARTED TO GENERATE

603
00:22:06,000 --> 00:22:07,440
GENOTYPE DATA, STARTED TO BRING

604
00:22:07,440 --> 00:22:08,960
DATA TOGETHER INTO ONE SPACE.

605
00:22:08,960 --> 00:22:14,160
2011, WE MOVED TO 11 NEW LOCI,

606
00:22:14,160 --> 00:22:16,560
AND ACTUALLY FOR THE FIRST TIME

607
00:22:16,560 --> 00:22:18,320
STARTED TO DO IMPUTATION.

608
00:22:18,320 --> 00:22:22,360
IMTEU PAITION WAS IMPUTATION WAS
REALLY ST
ARTING

609
00:22:22,360 --> 00:22:27,160
TO GET USED AROUND 2010, 20 LEN.

610
00:22:27,160 --> 00:22:33,400
IN PARTNERSHIP WITH THE WELLCOME

611
00:22:33,400 --> 00:22:34,400
TRUST -- WE WERE STARTING TO

612
00:22:34,400 --> 00:22:34,960
GAIN SOME TRACTION.

613
00:22:34,960 --> 00:22:39,360
AS YOU CAN SEE, ONE OF THE

614
00:22:39,360 --> 00:22:41,760
REALLY NEAT THINGS ABOUT

615
00:22:41,760 --> 00:22:42,560
GENOME-WIDE ASSOCIATION STUDIES

616
00:22:42,560 --> 00:22:44,120
ON THE BOTTOM LEFT-HAND SIDE OF

617
00:22:44,120 --> 00:22:45,240
THE SCREEN S THEY'RE PREDICTABLE

618
00:22:45,240 --> 00:22:46,160
IN NATURE.

619
00:22:46,160 --> 00:22:47,960
YOU KIND OF KNOW HOW MANY MORE

620
00:22:47,960 --> 00:22:49,320
LOCI YOU'RE GOING TO GET BASED

621
00:22:49,320 --> 00:22:53,960
ON HOW MANY MORE SAMPLES YOU

622
00:22:53,960 --> 00:22:54,720
ADD.

623
00:22:54,720 --> 00:22:56,920
SO WE CONTINUED TO ADD OVER THAT

624
00:22:56,920 --> 00:22:57,640
TIME.

625
00:22:57,640 --> 00:23:01,320
2014, NOW WE'RE STARTING TO

626
00:23:01,320 --> 00:23:02,400
REALLY GET SOMEWHERE.

627
00:23:02,400 --> 00:23:06,920
WE'D GONE FROM A SPACE ONLY

628
00:23:06,920 --> 00:23:08,080
SEVEN OR EIGHT YEARS PREVIOUSLY

629
00:23:08,080 --> 00:23:11,000
WHERE WE WERE GENOTYPING

630
00:23:11,000 --> 00:23:11,840
260 SAMPLES TO THE SPACE HERE

631
00:23:11,840 --> 00:23:14,920
WHERE WE'RE GENOTYPING 19,000

632
00:23:14,920 --> 00:23:16,760
CASES, AND ALMOST 100,000

633
00:23:16,760 --> 00:23:19,160
CONTROLS, AND REALLY STARTING TO

634
00:23:19,160 --> 00:23:21,160
IDENTIFY NUMEROUS LOCI

635
00:23:21,160 --> 00:23:22,600
ASSOCIATED WITH PARKINSON'S

636
00:23:22,600 --> 00:23:24,120
DISEASE.

637
00:23:24,120 --> 00:23:25,800
A FEW YEARS LATER, WE STARTED TO

638
00:23:25,800 --> 00:23:29,080
WORK WITH INDUSTRY.

639
00:23:29,080 --> 00:23:32,560
SO THIS IS INCLUDING DATA FROM A

640
00:23:32,560 --> 00:23:36,000
GROUP AT GENENTECH WHO WERE KIND

641
00:23:36,000 --> 00:23:37,960
OF ACADEMIC INDUSTRY, AND AGAIN,

642
00:23:37,960 --> 00:23:40,000
REALLY EXPANDING THE NUMBER OF

643
00:23:40,000 --> 00:23:41,800
RISK LOCI, EXPANDING THE NUMBER

644
00:23:41,800 --> 00:23:45,400
OF CASES, SO 26,000 CASES,

645
00:23:45,400 --> 00:23:52,360
400,000 CONTROLS.

646
00:23:52,360 --> 00:23:54,280
THEN MOST RECENTLY, IN 2019, WE

647
00:23:54,280 --> 00:23:56,280
HAVE THE LARGEST JOE NEEM WIDE

648
00:23:56,280 --> 00:24:00,160
ASSOCIATION STUDY REALLY DRIVEN

649
00:24:00,160 --> 00:24:02,280
BY MIKE NOLES I MENTIONED

650
00:24:02,280 --> 00:24:03,920
EARLIER, IN COLLABORATION WITH

651
00:24:03,920 --> 00:24:07,280
23ANDME, AND HERE WE WERE ABLE

652
00:24:07,280 --> 00:24:09,960
TO IDENTIFY 90 INDEPENDENT RISK

653
00:24:09,960 --> 00:24:10,160
LOCI.

654
00:24:10,160 --> 00:24:11,560
WHEN YOU START TO BRING THOSE

655
00:24:11,560 --> 00:24:12,880
RISK LOCI TOGETHER, YOU CAN

656
00:24:12,880 --> 00:24:15,080
CREATE THINGS LIKE GENETIC RISK

657
00:24:15,080 --> 00:24:16,200
SCORES AND GIVE EACH INDIVIDUAL

658
00:24:16,200 --> 00:24:18,120
WITHIN YOUR GENOME WHAT

659
00:24:18,120 --> 00:24:19,240
ASSOCIATION A RISK SCORE, AND

660
00:24:19,240 --> 00:24:23,160
YOU CAN SEE IN THE BOTTOM

661
00:24:23,160 --> 00:24:26,960
RIGHT-HAND CORNER OUR ABILITY TO

662
00:24:26,960 --> 00:24:32,760
KREE 

663
00:24:32,760 --> 00:24:34,560
PREDICT -- AROUND 70%, IT'S

664
00:24:34,560 --> 00:24:38,160
DEFINITELY NOT PERFECT, BUT IT

665
00:24:38,160 --> 00:24:40,160
WORKS EXTREMELY WELL WHEN YOU

666
00:24:40,160 --> 00:24:41,600
START TO BRING IN DIFFERENT

667
00:24:41,600 --> 00:24:43,640
TYPES OF DATA, YOU START TO USE

668
00:24:43,640 --> 00:24:45,200
GENETICS AS PART OF THE

669
00:24:45,200 --> 00:24:46,560
MULTIMODAL PREDICTOR FOR

670
00:24:46,560 --> 00:24:49,440
DISEASE.

671
00:24:49,440 --> 00:24:50,560
ONE OF THE THINGS WE'D DONE

672
00:24:50,560 --> 00:24:51,800
REALLY EARLY ON, WHICH I HAVEN'T

673
00:24:51,800 --> 00:24:56,200
SHOWN, IS START TO USE THESE

674
00:24:56,200 --> 00:24:57,480
TYPE OF GENOME-WIDE APPROACHES

675
00:24:57,480 --> 00:24:59,200
NOT JUST FOR DISEASE BUT FOR

676
00:24:59,200 --> 00:25:00,560
LOOKING AT OTHER TRAITS, SO

677
00:25:00,560 --> 00:25:03,600
WE'VE DONE A WHOLE SERIES OF

678
00:25:03,600 --> 00:25:06,200
WORK IN GENERATING QTL DATA IN

679
00:25:06,200 --> 00:25:08,960
HUMAN BRAIN, SO EXPRESSION PTL

680
00:25:08,960 --> 00:25:12,200
DATA, DNA METHYLATION, QTL DATA,

681
00:25:12,200 --> 00:25:17,160
AND MERGING THE QTL DATA FROM

682
00:25:17,160 --> 00:25:23,200
BRAIN, OUR TISH  EU OF TISSUE OF
INTEREST,

683
00:25:23,200 --> 00:25:24,960
WITH PARKINSON'S DISEASE OR ANY

684
00:25:24,960 --> 00:25:26,600
OTHER DISEASES WE WERE WORKING

685
00:25:26,600 --> 00:25:27,800
ON AND LOOKING FOR INTERSECTION,

686
00:25:27,800 --> 00:25:28,960
IS THIS ASSOCIATED WITH DISEASE,

687
00:25:28,960 --> 00:25:30,760
IF SO, WHAT EFFECT DOES THAT

688
00:25:30,760 --> 00:25:32,200
HAVE ON GENE EXPRESSION, WHAT

689
00:25:32,200 --> 00:25:33,600
GENE DOES IT AFFECT, WHAT

690
00:25:33,600 --> 00:25:36,560
DIRECTION, AND WHAT TISSUE.

691
00:25:36,560 --> 00:25:37,800
WHILE SOMEWHAT SHOWING THAT DATA

692
00:25:37,800 --> 00:25:39,280
HERE, I'M SHOWING SOME SIMILAR

693
00:25:39,280 --> 00:25:41,320
DATA, WHICH IS REALLY SINGLE

694
00:25:41,320 --> 00:25:43,640
CELL EXPRESSION DATA HERE, AND I

695
00:25:43,640 --> 00:25:46,560
THINK THAT MUCH AS GENETICS HAS

696
00:25:46,560 --> 00:25:47,960
BEEN REVOLUTIONIZED BY

697
00:25:47,960 --> 00:25:50,680
TECHNOLOGY OVER THE PAST 20

698
00:25:50,680 --> 00:25:53,040
YEARS, I THINK THE NEXT KIND OF

699
00:25:53,040 --> 00:25:53,640
FOUNDATIONAL FUNCTIONAL STEPS

700
00:25:53,640 --> 00:25:57,560
ARE BEING REVOLUTIONIZED WITH

701
00:25:57,560 --> 00:25:59,440
SINGLE CELL METHODOLOGIES.

702
00:25:59,440 --> 00:26:02,840
WHAT THIS SIMPLY IS HERE IS AN

703
00:26:02,840 --> 00:26:03,840
ANALYSIS WHERE YOU TAKE ALL OF

704
00:26:03,840 --> 00:26:05,240
YOUR GENES UNDERNEATH YOUR RISK

705
00:26:05,240 --> 00:26:07,200
LOCI AND YOU LOOK AT THEIR

706
00:26:07,200 --> 00:26:08,000
EXPRESSION IN SINGLE CELL

707
00:26:08,000 --> 00:26:08,400
DATASETS.

708
00:26:08,400 --> 00:26:10,160
THIS IS A SINGLE CELL DATASET

709
00:26:10,160 --> 00:26:12,760
FROM MOUSE, AND YOU LOOK TO SEE

710
00:26:12,760 --> 00:26:14,840
WHETHER THOSE GENES UNDERNEATH

711
00:26:14,840 --> 00:26:16,640
YOUR GENOME-WIDE ASSOCIATION

712
00:26:16,640 --> 00:26:17,520
PEAKS ARE PARTICULARLY EXPRESSED

713
00:26:17,520 --> 00:26:18,760
IN ANY PARTICULAR CELL TYPE.

714
00:26:18,760 --> 00:26:20,560
SO THIS TELLS YOU SOMETHING

715
00:26:20,560 --> 00:26:24,160
ABOUT THE CELLULAR CONTEXT OF

716
00:26:24,160 --> 00:26:24,720
RISK.

717
00:26:24,720 --> 00:26:25,760
WHAT WE SEE HERE IS THAT

718
00:26:25,760 --> 00:26:28,200
GENERALLY, NOT EXCLUSIVELY, BUT

719
00:26:28,200 --> 00:26:32,160
GENERALLY, GENOME-WIDE

720
00:26:32,160 --> 00:26:32,920
ASSOCIATION -- FOR PARKINSON'S

721
00:26:32,920 --> 00:26:34,240
DISEASE, THE GENES UNDERNEATH

722
00:26:34,240 --> 00:26:38,280
THOSE ARE HIGHLY EXPRESSED IN

723
00:26:38,280 --> 00:26:40,920
NEURONS, PARTICULARLY NEURONS,

724
00:26:40,920 --> 00:26:42,160
SUBSTANTIA NIGRA AND -- NEURONS

725
00:26:42,160 --> 00:26:43,760
THIS IS NOT EXCLUSIVE.

726
00:26:43,760 --> 00:26:46,280
THERE ARE SOME REALLY NEAT DATA

727
00:26:46,280 --> 00:26:47,600
COMING OUT SHOWING THE

728
00:26:47,600 --> 00:26:49,760
PARTICULAR GENES HAVE EFFECTS ON

729
00:26:49,760 --> 00:26:51,080
OTHER CELL TYPES, BUT IT TELLS

730
00:26:51,080 --> 00:26:52,560
YOU THAT A GOOD PLACE TO START

731
00:26:52,560 --> 00:26:53,680
MODELING AND TRYING TO

732
00:26:53,680 --> 00:26:55,240
UNDERSTAND THE EFFECTS OF

733
00:26:55,240 --> 00:26:56,960
GENETIC VARIABILITY ASSOCIATED

734
00:26:56,960 --> 00:27:08,240
WITH RISK FOR PD IS DOPE ANY
DOPE  -- NEUR
ONS.

735
00:27:08,240 --> 00:27:09,000
UNDERSTANDING FUNCTIONAL

736
00:27:09,000 --> 00:27:09,840
PATHWAYS ASSOCIATED WITH

737
00:27:09,840 --> 00:27:11,280
PARKINSON'S DISEASE, THIS IS

738
00:27:11,280 --> 00:27:17,960
WORK DONE -- REALLY A MONUMENT

739
00:27:17,960 --> 00:27:19,200
TUS EFFORT BRINGING TOGETHER A

740
00:27:19,200 --> 00:27:21,480
LARGE AMOUNT OF GENOTYPE DATA, A

741
00:27:21,480 --> 00:27:27,960
LARGE AMOUNT OF EXPRESSION DATA,

742
00:27:27,960 --> 00:27:28,960
TRANSCRIPT OMIC COMMUNITY MAPS,

743
00:27:28,960 --> 00:27:31,280
REALLY STARTS TO GIVE US A

744
00:27:31,280 --> 00:27:34,040
FLAVOR OF -- AN IDEA OF WHAT ARE

745
00:27:34,040 --> 00:27:36,080
THE KEY CONTRIBUTORS IN TERMS OF

746
00:27:36,080 --> 00:27:37,600
MECHANISM FOR RISK IN

747
00:27:37,600 --> 00:27:38,800
PARKINSON'S DISEASE THAT ARE

748
00:27:38,800 --> 00:27:40,360
BEING DRIVEN GENETICALLY, AND

749
00:27:40,360 --> 00:27:43,160
HERE YOU CAN SEE THAT THE THINGS

750
00:27:43,160 --> 00:27:44,800
SHE IDENTIFIED ARE COLLABORATORY

751
00:27:44,800 --> 00:27:47,280
SIGNALING PATHWAYS, CELL DEATH

752
00:27:47,280 --> 00:27:49,360
MACHINERY AND MITOCHONDRIAL

753
00:27:49,360 --> 00:27:50,840
HOMEOSTASIS.

754
00:27:50,840 --> 00:27:52,400
WE'VE ALSO LOOKED OUTSIDE OF

755
00:27:52,400 --> 00:27:55,440
JUST RISK FOR DISEASE, SO YOU

756
00:27:55,440 --> 00:27:57,960
CAN DO A GENETIC ANALYSIS ON

757
00:27:57,960 --> 00:28:00,960
ALMOST ANYTHING.

758
00:28:00,960 --> 00:28:03,400
SOMETHING VERY OBVIOUS TO DO

759
00:28:03,400 --> 00:28:06,080
HERE, TO LOOK AT AGE OF ONSET.

760
00:28:06,080 --> 00:28:07,840
I HAD ASSUMED WHEN WE DID THIS,

761
00:28:07,840 --> 00:28:10,640
AND WE HAD GOOD EVIDENCE FOR

762
00:28:10,640 --> 00:28:11,920
THIS, THAT SIMPLY WE WOULD FIND

763
00:28:11,920 --> 00:28:13,720
THE SAME THINGS THAT WE'D FOUND

764
00:28:13,720 --> 00:28:16,080
FOR RISK THAT WE'D FIND FOR AGE

765
00:28:16,080 --> 00:28:17,560
OF ONSET.

766
00:28:17,560 --> 00:28:20,720
SO WE KNEW THAT THE MORE -- THE

767
00:28:20,720 --> 00:28:23,520
HIGHER GENETIC RISK SCORE, THE

768
00:28:23,520 --> 00:28:24,760
YOUNGER YOUR AGE OF CONCEPT IS

769
00:28:24,760 --> 00:28:25,920
LIKELY TO BE.

770
00:28:25,920 --> 00:28:27,240
AND BY AND LARGE, THAT'S TRUE,

771
00:28:27,240 --> 00:28:28,920
WHEN YOU DO A GENOME-WIDE

772
00:28:28,920 --> 00:28:30,160
ASSOCIATION STUDY AND YOU LOOK

773
00:28:30,160 --> 00:28:32,320
AT THE BETA VALUES FOR RISK

774
00:28:32,320 --> 00:28:34,360
VERSUS THE BETA VALUES FOR AGE

775
00:28:34,360 --> 00:28:37,920
OF ONSET AS WE'VE DONE ON THIS

776
00:28:37,920 --> 00:28:38,520
PLOT ON THE RIGHT-HAND SIDE,

777
00:28:38,520 --> 00:28:42,800
THEY LINE YOU IN A DIAGONAL, THE

778
00:28:42,800 --> 00:28:45,520
SAME LOCI IDENTIFIED AS RISK

779
00:28:45,520 --> 00:28:49,240
FACTORS FOR DISEASE ALSO

780
00:28:49,240 --> 00:28:53,200
MODULATE AGE OF ONSET.

781
00:28:53,200 --> 00:28:55,240
THE MAP T LOCUS, ONE OF THE

782
00:28:55,240 --> 00:28:57,680
FIRST YOU IDENTIFY WHEN YOU DO A

783
00:28:57,680 --> 00:28:59,360
GENOME-WIDE ASSOCIATION STUDY IN

784
00:28:59,360 --> 00:29:01,400
PD HAS ABSOLUTELY NO EFFECT ON

785
00:29:01,400 --> 00:29:02,760
AGE OF ONSET.

786
00:29:02,760 --> 00:29:04,560
SO I THINK THIS IS A REALLY

787
00:29:04,560 --> 00:29:06,960
INTERESTING OBSERVATION, WE'RE

788
00:29:06,960 --> 00:29:09,760
WORKING PRETTY HARD AT TRYING TO

789
00:29:09,760 --> 00:29:11,240
UNDERSTAND THAT.

790
00:29:11,240 --> 00:29:13,920
UNFORTUNATELY THE TAU LOCUS IS

791
00:29:13,920 --> 00:29:16,040
INCREDIBLY COMPLICATED, ABOUT A

792
00:29:16,040 --> 00:29:17,760
1 1/2 MILLION BASE PAIR

793
00:29:17,760 --> 00:29:19,480
INVERSION ON CHROME ZONE 17, BUT

794
00:29:19,480 --> 00:29:20,800
WHAT WE'RE REALLY SEEING HERE

795
00:29:20,800 --> 00:29:22,240
IS, THERE'S SOMETHING THAT

796
00:29:22,240 --> 00:29:23,800
AFFECTS WHETHER YOU GET DISEASE

797
00:29:23,800 --> 00:29:25,360
BUT HAS NO EFFECT WHATSOEVER ON

798
00:29:25,360 --> 00:29:27,600
WHEN YOU GET DISEASE.

799
00:29:27,600 --> 00:29:28,560
THIS IS AN EXCEPTION FROM THE

800
00:29:28,560 --> 00:29:31,880
NORM.

801
00:29:31,880 --> 00:29:35,120
WE'VE ALSO LOOKED AT GENETIC

802
00:29:35,120 --> 00:29:36,440
INFLUENCE ON GENETIC FORMS OF

803
00:29:36,440 --> 00:29:37,040
DISEASE.

804
00:29:37,040 --> 00:29:38,760
I MENTIONED EARLIER CARRYING A

805
00:29:38,760 --> 00:29:43,160
SINGLE GBA MUTATION IS A RISK

806
00:29:43,160 --> 00:29:47,200
FACTOR FOR PARK SONS DISEASE,

807
00:29:47,200 --> 00:29:49,680
INCREASES SOMEWHERE BETWEEN

808
00:29:49,680 --> 00:29:50,000
2 AND 5 FOLD.

809
00:29:50,000 --> 00:29:55,080
BY DOING A JOE  GENOME WIDE

810
00:29:55,080 --> 00:29:56,280
ASSOCIATION STUDY, WE CAN START

811
00:29:56,280 --> 00:30:01,360
TO IDENTIFY GENETIC RISK FACTORS

812
00:30:01,360 --> 00:30:06,760
THAT MODULATE THE PENETRANCE OF

813
00:30:06,760 --> 00:30:07,200
GBA MUTATIONS.

814
00:30:07,200 --> 00:30:11,440
YOU SEE TWO BIG HITS HERE,

815
00:30:11,440 --> 00:30:16,040
SYNUCLEIN AND -- IT SHOWS UP

816
00:30:16,040 --> 00:30:19,320
EVERYWHERE WITH EVERYTHING.

817
00:30:19,320 --> 00:30:20,000
CTSB WAS PARTICULARLY

818
00:30:20,000 --> 00:30:21,800
INTERESTING AND I'LL COME BACK

819
00:30:21,800 --> 00:30:22,760
TO THAT IN A SECOND.

820
00:30:22,760 --> 00:30:26,360
WHAT WE DID SHOW IS THAT IN

821
00:30:26,360 --> 00:30:28,000
GENERAL, ALL OF THE GENETIC RISK

822
00:30:28,000 --> 00:30:33,880
FACTORS FOR TYPICAL DISEASE, FOR

823
00:30:33,880 --> 00:30:36,840
THOSE THAT DON'T CARRY THE

824
00:30:36,840 --> 00:30:38,440
MUTATION, IF YOU PUSH THOSE INTO

825
00:30:38,440 --> 00:30:40,000
A GENETIC RISK SCORE, THAT

826
00:30:40,000 --> 00:30:41,960
GENETIC RISK SCORE AFFECTS

827
00:30:41,960 --> 00:30:45,680
WHETHER A GBA CARRIER GETS

828
00:30:45,680 --> 00:30:47,160
DISEASE OR NOT.

829
00:30:47,160 --> 00:30:48,520
SO IN GENERAL, THE MECHANISMS

830
00:30:48,520 --> 00:30:51,200
BETWEEN TYPICAL PD AND

831
00:30:51,200 --> 00:30:52,760
GBA-LINKED PD SEEM TO OVERLAP.

832
00:30:52,760 --> 00:30:55,160
WE DON'T EXCLUSIVELY -- THEY

833
00:30:55,160 --> 00:30:56,560
DON'T EXCLUSIVELY OVERLAP BUT

834
00:30:56,560 --> 00:30:57,800
SEEM TO OVERLAP FOR THE MOST

835
00:30:57,800 --> 00:30:58,400
PART.

836
00:30:58,400 --> 00:31:01,520
THIS IS THE ONE EXCEPTION.

837
00:31:01,520 --> 00:31:05,360
SO THE CTSB LOCUS, WHICH I

838
00:31:05,360 --> 00:31:07,560
SHOWED TWO SLIDES AGO, CTSB

839
00:31:07,560 --> 00:31:09,320
CERTAINLY SHOWS UP AS A RISK

840
00:31:09,320 --> 00:31:10,640
FACTOR FOR TYPICAL PARKINSON'S

841
00:31:10,640 --> 00:31:12,560
DISEASE, BUT IF IT'S MUCH, MUCH,

842
00:31:12,560 --> 00:31:15,480
MUCH STRONGER IN GBA-LINKED

843
00:31:15,480 --> 00:31:16,960
DISEASE, ABOUT THREE TIMES AS

844
00:31:16,960 --> 00:31:19,320
STRONG AS GBA-LINKED DISEASE.

845
00:31:19,320 --> 00:31:20,440
AND WHAT IS PARTICULARLY

846
00:31:20,440 --> 00:31:25,240
COMPELLING ABOUT THIS IS

847
00:31:25,240 --> 00:31:26,200
LYSOSOMAL PROTEASE.

848
00:31:26,200 --> 00:31:29,000
WE OF COURSE KNOW THAT GLUCOVEE

849
00:31:29,000 --> 00:31:31,640
BRO SIDASE IS A LYSOSOMAL

850
00:31:31,640 --> 00:31:33,880
PROTEIN, SO JUST THE VERY FACT

851
00:31:33,880 --> 00:31:35,840
THAT OUT OF ALL OF THE GENES WE

852
00:31:35,840 --> 00:31:38,920
COULD FIND A LYSOSOMAL CYSTINE

853
00:31:38,920 --> 00:31:41,400
PRO TEE'S POPS UP TELLS ME

854
00:31:41,400 --> 00:31:42,720
SOMETHING MECHANISTICALLY IS

855
00:31:42,720 --> 00:31:44,560
GOING ON THERE AND WE'RE SEEING

856
00:31:44,560 --> 00:31:46,600
A GENUINE GENE BY GENE

857
00:31:46,600 --> 00:31:49,160
INTERACTION AND MAYBE SOME HINTS

858
00:31:49,160 --> 00:31:53,440
OF MECHANISTIC SUBTYPES.

859
00:31:53,440 --> 00:31:56,800
SO THIS HAS LED US TO THIS

860
00:31:56,800 --> 00:31:58,520
SPACE, ALL THERE WORK THAT I'VE

861
00:31:58,520 --> 00:31:59,840
TALKED ABOUT THIS FAR.

862
00:31:59,840 --> 00:32:01,600
17 GENES THAT CONTAIN MUTATIONS

863
00:32:01,600 --> 00:32:03,680
THAT CAUSE DISEASE, A COUPLE OF

864
00:32:03,680 --> 00:32:08,200
MODERATE RISK FACTORS AND 90

865
00:32:08,200 --> 00:32:08,960
INDEPENDENT -- WE ACTUALLY DON'T

866
00:32:08,960 --> 00:32:10,360
KNOW THE GENES FOR THE VAST

867
00:32:10,360 --> 00:32:15,640
MAJORITY OF THEM.

868
00:32:15,640 --> 00:32:19,160
WE'VE COME A FAIRLY LONG WAY.

869
00:32:19,160 --> 00:32:20,360
LIKEWISE, THE UNDERSTANDING OF

870
00:32:20,360 --> 00:32:23,000
THE MECHANISM OF THESE GENES AND

871
00:32:23,000 --> 00:32:25,800
THEIR PRODUCTS HAS ALSO COME A

872
00:32:25,800 --> 00:32:26,560
FAIRLY LONG WAY.

873
00:32:26,560 --> 00:32:28,080
MANY OF THESE HAVE STARTED TO BE

874
00:32:28,080 --> 00:32:30,480
LINKED TOGETHER MECHANISTICALLY,

875
00:32:30,480 --> 00:32:34,080
SO MARK COOKSON'S LAB HERE AT

876
00:32:34,080 --> 00:32:35,400
NIH -- HAS LINKED SOME OF THESE

877
00:32:35,400 --> 00:32:36,160
TOGETHER.

878
00:32:36,160 --> 00:32:38,160
GENETICALLY WE'VE LINKED THINGS

879
00:32:38,160 --> 00:32:38,560
TOGETHER.

880
00:32:38,560 --> 00:32:40,960
SO WE'RE REALLY STARTING TO GET

881
00:32:40,960 --> 00:32:44,520
TOWARDS DEFINING A NETWORK OF

882
00:32:44,520 --> 00:32:48,160
GENES THAT UNDERLIE DISEASE

883
00:32:48,160 --> 00:32:49,640
PROCESSES.

884
00:32:49,640 --> 00:32:51,560
THIS HAS HAD AN IMPACT

885
00:32:51,560 --> 00:32:54,080
THERAPEUTICALLY, SO IF WE JUST

886
00:32:54,080 --> 00:32:56,360
THINK ABOUT THE MAJOR GENES THAT

887
00:32:56,360 --> 00:32:57,640
WE'VE IDENTIFIED AND I'VE TALKED

888
00:32:57,640 --> 00:33:02,480
ABOUT TODAY, ALPHA SINAI CLEAN,

889
00:33:02,480 --> 00:33:05,240
THERE ARE CURRENTLY 15 TRIALS

890
00:33:05,240 --> 00:33:06,360
ONGOING TARGETING SYNUCLEIN,

891
00:33:06,360 --> 00:33:08,800
MANY TARGETING CLEARANCE OR

892
00:33:08,800 --> 00:33:12,960
CELL-TO-CELL TRANSPORT OF

893
00:33:12,960 --> 00:33:14,680
SYNUCLEIN.

894
00:33:14,680 --> 00:33:16,160
MARK'S WORK HAS SHOWN THE KINASE

895
00:33:16,160 --> 00:33:17,440
ACTIVITY IS PART OF THE TOXIC

896
00:33:17,440 --> 00:33:20,560
GAIN OF FUNCTION AND WE KNOW

897
00:33:20,560 --> 00:33:22,160
KINASE ACTIVITY IS INCREASED IN

898
00:33:22,160 --> 00:33:26,760
MUTATION CARRIERS, SO THERE ARE

899
00:33:26,760 --> 00:33:28,160
TWO CURRENT TRIALS TARGETING

900
00:33:28,160 --> 00:33:31,920
LRRK2 AND INTERESTINGLY A VERY

901
00:33:31,920 --> 00:33:33,120
LARGE CLINICAL PHASE 3 TRIAL

902
00:33:33,120 --> 00:33:42,560
BEGINNING NOW RUN BY DENALI.

903
00:33:42,560 --> 00:33:43,880
GLUCOCEREBROSIDASE, FOUR CURRENT

904
00:33:43,880 --> 00:33:44,720
GBA-DIRECTED THERAPIES IN

905
00:33:44,720 --> 00:33:45,160
TRIALS.

906
00:33:45,160 --> 00:33:46,960
THERE'S A TON OF WORK GOING ON

907
00:33:46,960 --> 00:33:51,920
IN INDIVIDUALS THAT CARRY THESE

908
00:33:51,920 --> 00:33:53,880
MUTATIONS, TO UNDERSTAND THE

909
00:33:53,880 --> 00:33:54,400
NATURAL HISTORY.

910
00:33:54,400 --> 00:33:56,920
SO I THINK IDENTIFYING THESE

911
00:33:56,920 --> 00:33:58,040
MUTATIONS IS HAVING A REALLY

912
00:33:58,040 --> 00:34:00,480
LARGE EFFECT.

913
00:34:00,480 --> 00:34:02,160
SO IF WE OVERLAY WHAT I TALKED

914
00:34:02,160 --> 00:34:05,760
ABOUT SO FAR, I THINK WE

915
00:34:05,760 --> 00:34:06,760
CERTAINLY HAVEN'T SUCCEEDED, BUT

916
00:34:06,760 --> 00:34:08,200
WE'VE KIND OF HIT THE THINGS WE

917
00:34:08,200 --> 00:34:10,560
SAID WE WOULD TRY AND HIT.

918
00:34:10,560 --> 00:34:12,200
WE'RE USING GENETICS TO

919
00:34:12,200 --> 00:34:13,480
UNDERSTAND THE PATHOBIOLOGY,

920
00:34:13,480 --> 00:34:15,480
WE'RE USING TO IDENTIFY TARGETS,

921
00:34:15,480 --> 00:34:17,960
WE'RE STARTING NOW, BUT I'D SAY

922
00:34:17,960 --> 00:34:20,200
IN THE EARLY DAYS, TO USE TO TRY

923
00:34:20,200 --> 00:34:21,760
AND DISSECT THE DISEASE, TO TRY

924
00:34:21,760 --> 00:34:23,360
AND PREDICT WHO'S GOING TO GET

925
00:34:23,360 --> 00:34:24,960
DISEASE BEFORE THEY GET IT, TO

926
00:34:24,960 --> 00:34:26,640
TRY AND FIND MECHANISTIC

927
00:34:26,640 --> 00:34:27,800
SUBTYPES OF DISEASE.

928
00:34:27,800 --> 00:34:29,600
ALL WITH THIS AIM TOWARDS

929
00:34:29,600 --> 00:34:30,640
PRECISION TREATMENTS.

930
00:34:30,640 --> 00:34:34,160
MATCHING THE RIGHT PATIENT TO

931
00:34:34,160 --> 00:34:35,320
THE RIGHT TREATMENT AT THE RIGHT

932
00:34:35,320 --> 00:34:37,200
TIME.

933
00:34:37,200 --> 00:34:38,240
SO SUMMARY OF WHERE WE ARE SO

934
00:34:38,240 --> 00:34:38,960
FAR.

935
00:34:38,960 --> 00:34:40,760
I THINK WE MADE REALLY

936
00:34:40,760 --> 00:34:42,560
SIGNIFICANT PROGRESS IN THE

937
00:34:42,560 --> 00:34:44,200
GENETICS OF PD.

938
00:34:44,200 --> 00:34:46,200
ORIGINALLY THIS WAS DRIVEN BY

939
00:34:46,200 --> 00:34:48,560
INDIVIDUAL LABS, NOW IT'S JUST

940
00:34:48,560 --> 00:34:49,200
MASSIVELY COLLABORATIVE.

941
00:34:49,200 --> 00:34:50,400
I WILL SAY THE PARKINSON'S

942
00:34:50,400 --> 00:34:52,240
DISEASE FIELD IS AN INCREDIBLY

943
00:34:52,240 --> 00:34:55,120
NICE ONE TO WORK IN, VERY

944
00:34:55,120 --> 00:34:55,440
COLLABORATIVE.

945
00:34:55,440 --> 00:34:57,680
I THINK THE COLLABORATION WAS

946
00:34:57,680 --> 00:34:58,560
ENABLED BY THE WILLINGNESS OF

947
00:34:58,560 --> 00:34:58,920
THAT COMMUNITY.

948
00:34:58,920 --> 00:35:00,520
IT WAS A GOOD COMMUNITY.

949
00:35:00,520 --> 00:35:02,480
BUT ALSO WHAT WAS KEY WAS THE

950
00:35:02,480 --> 00:35:06,000
USE OF THE IRP, TO REALLY SERVE

951
00:35:06,000 --> 00:35:07,160
AS AN ANCHOR FOR THAT

952
00:35:07,160 --> 00:35:07,560
COLLABORATION.

953
00:35:07,560 --> 00:35:10,840
AS A SAFE PLACE TO START WORK

954
00:35:10,840 --> 00:35:13,320
AND TO REALLY GENERATE DATA AND

955
00:35:13,320 --> 00:35:14,440
BRING PEOPLE TOGETHER, THAT

956
00:35:14,440 --> 00:35:16,440
WORKED INCREDIBLY WELL.

957
00:35:16,440 --> 00:35:18,760
WE NOW HAVE A DOZEN OR SO GENES

958
00:35:18,760 --> 00:35:20,200
THAT CONTAIN MUTATIONS THAT

959
00:35:20,200 --> 00:35:23,560
CAUSE DISEASE, 90 OR SO, RISK

960
00:35:23,560 --> 00:35:24,000
LOCI.

961
00:35:24,000 --> 00:35:26,040
AS I TALKED ABOUT, I THINK THE

962
00:35:26,040 --> 00:35:30,720
CELLULAR CONTEXT IS LARGELY

963
00:35:30,720 --> 00:35:31,480
DOPAMINERGIC, WE'RE STARTING TO

964
00:35:31,480 --> 00:35:33,560
GET A HANDLE ON THE FUNCTION AND

965
00:35:33,560 --> 00:35:37,600
WHAT IS THIS NETWORK OF GENES

966
00:35:37,600 --> 00:35:39,240
AND THEIR PRODUCTS THAT

967
00:35:39,240 --> 00:35:40,640
CONTRIBUTE TO DISEASE.

968
00:35:40,640 --> 00:35:42,240
I THINK THAT SOME OF THE THINGS

969
00:35:42,240 --> 00:35:44,320
I'M REALLY EXCITED ABOUT ARE

970
00:35:44,320 --> 00:35:46,360
THESE OUTLIARS, THESE GENETIC

971
00:35:46,360 --> 00:35:47,560
FACTORS THAT HAVE MORE OF AN

972
00:35:47,560 --> 00:35:48,960
EFFECT ON AGE OF ONSET OR LESS

973
00:35:48,960 --> 00:35:50,720
OF AN EFFECT ON AGE OF ONSET

974
00:35:50,720 --> 00:35:52,080
THAN THEY DO ON RISK.

975
00:35:52,080 --> 00:35:54,800
AND I THINK THESE ARE

976
00:35:54,800 --> 00:35:55,640
PARTICULARLY EXCITING FOR US TO

977
00:35:55,640 --> 00:36:01,320
CHASE OVER THE COMING PERIOD.

978
00:36:01,320 --> 00:36:02,800
SO GIVEN THAT, WHICH I THINK IS

979
00:36:02,800 --> 00:36:04,760
PRETTY SUCCESSFUL, WHERE DO WE

980
00:36:04,760 --> 00:36:06,760
GO NEXT?

981
00:36:06,760 --> 00:36:08,400
SO HERE'S WHERE IT'S NOT SO

982
00:36:08,400 --> 00:36:11,080
SUCCESSFUL.

983
00:36:11,080 --> 00:36:12,800
SO THE HERITABLE COMPONENT OF

984
00:36:12,800 --> 00:36:15,520
PARKINSON'S DISEASE NOW WE KNOW

985
00:36:15,520 --> 00:36:17,400
IS ABOUT 25%, SO THE AVERAGE

986
00:36:17,400 --> 00:36:20,680
PARKINSON'S DISEASE PATIENT, 25%

987
00:36:20,680 --> 00:36:22,200
OF THEIR LIABILITY, 25% OF THE

988
00:36:22,200 --> 00:36:26,120
REASON THEY HAVE DISEASE IS

989
00:36:26,120 --> 00:36:26,360
GENETICS.

990
00:36:26,360 --> 00:36:31,480
WE ONLY KNOW I'DITE OF ABOUT 
IDENTITY OF 
ABOUT A

991
00:36:31,480 --> 00:36:32,760
THIRD OF THAT SO WE HAVE MORE TO

992
00:36:32,760 --> 00:36:33,280
FIND.

993
00:36:33,280 --> 00:36:34,600
THE VAST MAJORITY OF WORK WE'VE

994
00:36:34,600 --> 00:36:38,360
DONE HAS BEEN IN NORTHERN

995
00:36:38,360 --> 00:36:38,960
EUROPEAN ANCESTRY.

996
00:36:38,960 --> 00:36:40,720
SO PARKINSON'S DISEASE IS

997
00:36:40,720 --> 00:36:48,560
CLEARLY A GLOBAL DISEASE, BUT WE

998
00:36:48,560 --> 00:36:53,080
HAVE -- IF WE ARE TO TREAT THIS

999
00:36:53,080 --> 00:36:54,080
GLOBAL DISEASE AND USING THIS

1000
00:36:54,080 --> 00:36:56,560
SCHEMA AGAIN, WE HAVE TO REALLY

1001
00:36:56,560 --> 00:36:58,760
INVEST IN UNDERSTANDING GENETIC

1002
00:36:58,760 --> 00:37:02,200
BASIS OF DISEASE IN GLOBAL

1003
00:37:02,200 --> 00:37:02,520
POPULATIONS.

1004
00:37:02,520 --> 00:37:05,680
SO I'M GOING TO TALK AS I'M IN

1005
00:37:05,680 --> 00:37:08,680
THE LAST 10, 15 MINUTES OR SO,

1006
00:37:08,680 --> 00:37:10,560
ABOUT THIS PROGRAM, THE GLOBAL

1007
00:37:10,560 --> 00:37:12,280
PARKINSON'S GENETICS PROGRAM, SO

1008
00:37:12,280 --> 00:37:13,760
THIS IS A PARTNERSHIP BETWEEN US

1009
00:37:13,760 --> 00:37:16,240
AND THE ALIGNING SCIENCE ACROSS

1010
00:37:16,240 --> 00:37:17,560
PARKINSON'S INITIATIVE THAT ARE

1011
00:37:17,560 --> 00:37:18,640
SUPPORTING THIS WORK AND THE

1012
00:37:18,640 --> 00:37:20,000
MICHAEL J. FOX FOUNDATION WHO

1013
00:37:20,000 --> 00:37:23,080
ARE WORKING EXTREMELY CLOSELY

1014
00:37:23,080 --> 00:37:26,400
WITH US ON THIS PROGRAM.

1015
00:37:26,400 --> 00:37:28,480
SO THE MISSION OF THE GLOBAL

1016
00:37:28,480 --> 00:37:30,280
PARKINSON'S GENETICS PROGRAM IS

1017
00:37:30,280 --> 00:37:31,880
TO DRAMATICALLY UNDERSTAND OUR

1018
00:37:31,880 --> 00:37:33,120
UNDERSTANDING OF THE BASIS OF PD

1019
00:37:33,120 --> 00:37:36,320
AND TO MAKE THAT KNOWLEDGE

1020
00:37:36,320 --> 00:37:36,920
GLOBALLY RELEVANT.

1021
00:37:36,920 --> 00:37:39,200
WHAT I'M GOING TO TALK A LITTLE

1022
00:37:39,200 --> 00:37:41,040
BIT HERE ABOUT IS NOT REALLY

1023
00:37:41,040 --> 00:37:42,760
RESULTS BUT HOW WE'RE TRYING TO

1024
00:37:42,760 --> 00:37:42,960
DO THAT.

1025
00:37:42,960 --> 00:37:44,560
WE'RE FUNDED AS A RESOURCE,

1026
00:37:44,560 --> 00:37:46,280
WE'RE SUPPORTED AS A RESOURCE

1027
00:37:46,280 --> 00:37:47,600
PROGRAM, SO THE IDEA IS THAT WE

1028
00:37:47,600 --> 00:37:49,960
ARE NOT A SPACE WHERE WE TAKE

1029
00:37:49,960 --> 00:37:51,160
ALL OF THE GENETICS AND WE

1030
00:37:51,160 --> 00:37:52,520
PROVIDE ALL OF THE ANSWERS BUT

1031
00:37:52,520 --> 00:37:53,920
RATHER WE PROVIDE THE TOOLS AND

1032
00:37:53,920 --> 00:37:57,640
THE RESOURCES AND THE DATA TO

1033
00:37:57,640 --> 00:37:59,520
ASK QUESTIONS.

1034
00:37:59,520 --> 00:38:01,640
TO ALLOW INVESTIGATORS TO ASK

1035
00:38:01,640 --> 00:38:04,720
GENETIC QUESTIONS.

1036
00:38:04,720 --> 00:38:06,360
SO WE HAVE THREE PRIMARY

1037
00:38:06,360 --> 00:38:07,760
SCIENTIFIC OUTCOMES WE'RE

1038
00:38:07,760 --> 00:38:11,440
ATTEMPTING TO ATTACK.

1039
00:38:11,440 --> 00:38:13,200
UNDERSTANDING A COMPLEX DISEASE,

1040
00:38:13,200 --> 00:38:15,560
WE'RE TARGETING UP  150,000

1041
00:38:15,560 --> 00:38:16,200
INDIVIDUALS.

1042
00:38:16,200 --> 00:38:18,240
IDENTIFYING AND PROVING RAPIDLY

1043
00:38:18,240 --> 00:38:20,360
NEW GENETIC CAUSES OF DISEASE,

1044
00:38:20,360 --> 00:38:23,960
SO TO DO THIS WILL BE ALL GINO

1045
00:38:23,960 --> 00:38:26,120
SEQUENCING, 10,000 INDIVIDUALS,

1046
00:38:26,120 --> 00:38:27,760
LONG -- SEQUENCING A COUPLE

1047
00:38:27,760 --> 00:38:28,680
THOUSAND INDIVIDUALS, AND DOING

1048
00:38:28,680 --> 00:38:30,160
ALL OF THIS AND MAKING ALL OF

1049
00:38:30,160 --> 00:38:33,640
THIS GLOBALLY RELEVANT.

1050
00:38:33,640 --> 00:38:35,160
SO PRIORITIZING COLLECTION OF

1051
00:38:35,160 --> 00:38:37,080
NEW SAMPLES AND NEW COHORTS,

1052
00:38:37,080 --> 00:38:39,040
CREATION OF NEW COHORTS FROM

1053
00:38:39,040 --> 00:38:41,480
BLACK AMERICANS, SUB-SAHARAN

1054
00:38:41,480 --> 00:38:43,240
AFRICA, NORTH AFRICA, SOUTH AND

1055
00:38:43,240 --> 00:38:45,760
CENTRAL AMERICA, THE CARIBBEAN,

1056
00:38:45,760 --> 00:38:48,640
EAST ASIA, CENTRAL ASA.

1057
00:38:48,640 --> 00:38:51,040
AS IMPORTANT, I THINK, AS

1058
00:38:51,040 --> 00:38:53,040
ANYTHING TO ACHIEVE THESE

1059
00:38:53,040 --> 00:38:54,600
SCIENTIFIC OUTCOMES, WE HAVE

1060
00:38:54,600 --> 00:38:56,200
THESE REALLY STRONG STRUCTURAL

1061
00:38:56,200 --> 00:38:57,360
PRIORITIES.

1062
00:38:57,360 --> 00:38:59,160
SO DEMOCRATIZING THE DATA,

1063
00:38:59,160 --> 00:39:00,680
MAKING THE DATA AVAILABLE AND

1064
00:39:00,680 --> 00:39:02,120
USABLE FOR THE RESEARCH

1065
00:39:02,120 --> 00:39:07,840
COMMUNITY AND FOR THE FOLKS

1066
00:39:07,840 --> 00:39:09,440
ACTUALLY -- COOPERATING WITH

1067
00:39:09,440 --> 00:39:10,960
EVERYBODY, AGAIN, THE IDEA IS TO

1068
00:39:10,960 --> 00:39:12,240
CREATE A STUCK TREUR IN WHICH

1069
00:39:12,240 --> 00:39:13,640
REALLY A COLLECTIVE WHERE

1070
00:39:13,640 --> 00:39:15,000
INVESTIGATORS FROM ALL OVER THE

1071
00:39:15,000 --> 00:39:16,600
WORLD HAVE EQUAL ACCESS TO

1072
00:39:16,600 --> 00:39:18,440
RESOURCES AND ARE ABLE TO

1073
00:39:18,440 --> 00:39:19,560
ANALYZE TATA.

1074
00:39:19,560 --> 00:39:21,400
ALL THIS HAS TO BE DONE USING

1075
00:39:21,400 --> 00:39:26,960
SAFE, RESPONSIBLE  RESPONSIBLE
DATA SHARIN
G,

1076
00:39:26,960 --> 00:39:29,480
WE'RE PROMOTING DIVERSITY IN RAO

1077
00:39:29,480 --> 00:39:30,560
SEARCH AS WELL AS THE WORK WE'RE

1078
00:39:30,560 --> 00:39:32,120
DOING AND I'LL TALK A LITTLE

1079
00:39:32,120 --> 00:39:34,240
ABOUT THAT, AND BEING AS

1080
00:39:34,240 --> 00:39:35,160
TRANSPARENT AS WE POSSIBLY CAN.

1081
00:39:35,160 --> 00:39:36,600
SO WE HAVE THIS ORGANIZATIONAL

1082
00:39:36,600 --> 00:39:38,720
SCHEME THAT INCLUDES A WHOLE

1083
00:39:38,720 --> 00:39:40,440
SERIES OF WORKING GROUPS.

1084
00:39:40,440 --> 00:39:41,800
IT ALSO INCLUDES SOMETHING

1085
00:39:41,800 --> 00:39:43,360
REALLY NEAT, WHICH IS WE HAVE

1086
00:39:43,360 --> 00:39:51,880
LEADS AND CO  CO-LEAGUE

1087
00:39:51,880 --> 00:39:52,760
INVESTIGATOR, NEW TO PARKINSON'S

1088
00:39:52,760 --> 00:39:54,160
DISEASE, SO YOU GET THIS REALLY

1089
00:39:54,160 --> 00:39:55,960
NICE MIX OF LEADERS WHO ARE THE

1090
00:39:55,960 --> 00:39:59,760
UP AND COMING LEADERS OF THE

1091
00:39:59,760 --> 00:40:00,920
FIELD ALONG WITH THE OLDER

1092
00:40:00,920 --> 00:40:04,440
ESTABLISHED INDIVIDUALS.

1093
00:40:04,440 --> 00:40:10,320
THE WAY THAT IT WORKS IS THAT WE

1094
00:40:10,320 --> 00:40:11,440
ACCEPT DATA AND SAMPLES FROM

1095
00:40:11,440 --> 00:40:12,960
INDIVIDUALS, SO CLINICAL DATA,

1096
00:40:12,960 --> 00:40:16,600
SOMETIMES GENETIC DATA, DNA,

1097
00:40:16,600 --> 00:40:18,760
BLOOD, TISSUE, WE DO ALL OF THE

1098
00:40:18,760 --> 00:40:20,160
HARMONIZATION CENTRALLY, WE

1099
00:40:20,160 --> 00:40:22,560
PRODUCE ALL OF THE EITHER

1100
00:40:22,560 --> 00:40:24,560
SEQUENCE DATA OR GENOTYPE DATA,

1101
00:40:24,560 --> 00:40:25,840
RETURN THAT TO THE

1102
00:40:25,840 --> 00:40:26,760
INVESTIGATORS, AND THEN WE'VE

1103
00:40:26,760 --> 00:40:28,560
WORKED WITH A REALLY FANTASTIC

1104
00:40:28,560 --> 00:40:30,560
PROGRAM, THE ACCELERATING

1105
00:40:30,560 --> 00:40:32,960
MEDICINES PARTNERSHIP FOR

1106
00:40:32,960 --> 00:40:34,040
PARKINSON'S DISEASE PROGRAM, TO

1107
00:40:34,040 --> 00:40:39,040
ALLOW US TO SHARE GP2 DATA IN

1108
00:40:39,040 --> 00:40:39,320
REALTIME.

1109
00:40:39,320 --> 00:40:40,640
SO AGAIN, THE IDEA HERE IS FOR

1110
00:40:40,640 --> 00:40:42,360
US TO GENERATE DATA AND GET IT

1111
00:40:42,360 --> 00:40:45,120
OUT TO THE EXEUNT AS  COMMUNITY
AS QUICKLY

1112
00:40:45,120 --> 00:40:46,920
AS POSSIBLE, SO THERE WILL BE NO

1113
00:40:46,920 --> 00:40:48,520
WAITING FOR PUBLICATION, NO

1114
00:40:48,520 --> 00:40:50,800
EMBARGOES, IT'S ABOUT GETTING

1115
00:40:50,800 --> 00:40:52,880
DATA OUT AS QUICKLY AS POSSIBLE.

1116
00:40:52,880 --> 00:40:55,600
THE OTHER PART OF THIS PROCESS

1117
00:40:55,600 --> 00:40:58,160
IS THAT THE MPD STRUCTURE

1118
00:40:58,160 --> 00:40:59,960
INCLUDES NOT ONLY A DATA STORE

1119
00:40:59,960 --> 00:41:01,800
BUT THE COMPLETE RESOURCES TO

1120
00:41:01,800 --> 00:41:02,960
ACTUALLY DO DATA ANALYSES IN

1121
00:41:02,960 --> 00:41:03,400
PLACE.

1122
00:41:03,400 --> 00:41:04,840
SO WHAT THIS EFFECTIVELY MEANS

1123
00:41:04,840 --> 00:41:07,720
IS THE DATA IS REALLY TRULY

1124
00:41:07,720 --> 00:41:08,440
DEMOCRATIZED.

1125
00:41:08,440 --> 00:41:10,320
ANYBODY WHO HAS ACCESS TO THE

1126
00:41:10,320 --> 00:41:12,760
INTERNET CAN ACCESS THE DATA.

1127
00:41:12,760 --> 00:41:14,280
CAN SPIT OUT POWERFUL RESOURCES

1128
00:41:14,280 --> 00:41:16,040
TO ANALYZE THE DATA IN PLACE,

1129
00:41:16,040 --> 00:41:18,680
AND WE WILL PAY FOR THAT

1130
00:41:18,680 --> 00:41:19,920
ANALYSES, SO WE COVER THE COSTS

1131
00:41:19,920 --> 00:41:22,160
OF THAT ANALYSES.

1132
00:41:22,160 --> 00:41:23,480
SO NOW INDIVIDUALS WHO ARE

1133
00:41:23,480 --> 00:41:28,960
CONTRIBUTING SAMPLES FROM LEGOS,

1134
00:41:28,960 --> 00:41:31,560
FOR EXAMPLE, ARE ABLE TO LOG ON,

1135
00:41:31,560 --> 00:41:37,000
ACCESS OUR RESOURCES AS PART OF

1136
00:41:37,000 --> 00:41:38,960
THIS PROJECT AND ANALYZE

1137
00:41:38,960 --> 00:41:39,240
GP2 DATA.

1138
00:41:39,240 --> 00:41:40,880
THERE IS AN ADDITIONAL FACT TO

1139
00:41:40,880 --> 00:41:42,560
THIS, WHICH IS AROUND TRAINING,

1140
00:41:42,560 --> 00:41:44,760
WHICH I'LL COME BACK TO LATER.

1141
00:41:44,760 --> 00:41:47,480
SO WHERE ARE WE IN GP2?

1142
00:41:47,480 --> 00:41:49,560
WE'RE ENDING REALLY THE STARTUP

1143
00:41:49,560 --> 00:41:52,560
PHASE, BEGINNING IN YEAR THREE.

1144
00:41:52,560 --> 00:41:54,320
DONE A HUGE AMOUNT IN TERMS OF

1145
00:41:54,320 --> 00:41:54,880
UNDERSTANDING THE ISSUES OF

1146
00:41:54,880 --> 00:41:56,680
COMPLIANCE AND OPERATIONS.

1147
00:41:56,680 --> 00:41:58,560
THIS, I WILL SAY, HAS BEEN

1148
00:41:58,560 --> 00:42:00,920
INCREDIBLY CHALLENGING.

1149
00:42:00,920 --> 00:42:02,160
GENETICS IS RELATIVELY EASY.

1150
00:42:02,160 --> 00:42:05,280
TRYING TO NAVIGATE THE CHANGING

1151
00:42:05,280 --> 00:42:07,160
ENVIRONMENT OF WHERE DATA CAN BE

1152
00:42:07,160 --> 00:42:08,480
AND HOW DATA CAN MOVE

1153
00:42:08,480 --> 00:42:10,920
PARTICULARLY BETWEEN COUNTRIES,

1154
00:42:10,920 --> 00:42:15,040
MUCH MORE CHALLENGING.

1155
00:42:15,040 --> 00:42:16,880
A WHOLE SERIES OF THINGS ABOUT

1156
00:42:16,880 --> 00:42:18,520
HOW DATA AND SAMPLES SHOULD

1157
00:42:18,520 --> 00:42:22,480
FLOW, HOW WE EVALUATE PROJECTS,

1158
00:42:22,480 --> 00:42:26,640
HOW WE ENSURE THAT IF SOMEONE

1159
00:42:26,640 --> 00:42:28,400
PROPOSES TO ANALYZE SAMPLES,

1160
00:42:28,400 --> 00:42:30,200
THAT WE MAKE SURE THERE IS

1161
00:42:30,200 --> 00:42:31,960
INCLUES 

1162
00:42:31,960 --> 00:42:33,480
INCLUSION FROM OUR

1163
00:42:33,480 --> 00:42:43,560
UNDERREPRESENTED COLLEAGUES WHO

1164
00:42:43,560 --> 00:42:46,160
WHO -- WHICH ALLOWS US TO LOOK

1165
00:42:46,160 --> 00:42:47,360
AT NEURODEGENERATIVE ASSOCIATED

1166
00:42:47,360 --> 00:42:48,000
VARIANTS ACROSS ANCESTRIES.

1167
00:42:48,000 --> 00:42:51,480
SO THIS IS A 2 MILLION VARIANT

1168
00:42:51,480 --> 00:42:52,800
ARRAY THAT IS NOW COMMERCIALLY

1169
00:42:52,800 --> 00:42:54,760
AVAILABLE.

1170
00:42:54,760 --> 00:43:00,200
FORM STRATEGIC PARTNERSHIPS, I'D

1171
00:43:00,200 --> 00:43:05,920
MENTIONED AMP PD, THE MICHAEL J.

1172
00:43:05,920 --> 00:43:06,600
FOX ASSOCIATION, SEVERAL GROUPS

1173
00:43:06,600 --> 00:43:09,520
THAT HAD ALREADY STARTED TO

1174
00:43:09,520 --> 00:43:10,760
COLLECT SAMPLES FROM AROUND THE

1175
00:43:10,760 --> 00:43:11,080
WORLD.

1176
00:43:11,080 --> 00:43:13,400
A REALLY IMPORTANT PART OF THIS,

1177
00:43:13,400 --> 00:43:15,920
AGAIN, GIVEN OUR AIM, WHICH IS

1178
00:43:15,920 --> 00:43:17,280
TO TRY AND LEVEL THE PLAYING

1179
00:43:17,280 --> 00:43:19,160
FIELD FOR RESEARCHERS AROUND THE

1180
00:43:19,160 --> 00:43:22,080
WORLD, IS TO BUILD GLOBAL WILL

1181
00:43:22,080 --> 00:43:23,560
AND TO BUILD CAPACITY AT THOSE

1182
00:43:23,560 --> 00:43:25,480
RESEARCH SITES THAT HAVE

1183
00:43:25,480 --> 00:43:26,560
TRADITIONALLY BEEN

1184
00:43:26,560 --> 00:43:26,960
UNDERREPRESENTED.

1185
00:43:26,960 --> 00:43:28,400
SO I TALKED A LITTLE BIT ABOUT

1186
00:43:28,400 --> 00:43:30,000
HAVING RESOURCES FOR THOSE SITES

1187
00:43:30,000 --> 00:43:32,680
TO BE ABLE TO ACCESS AND ANALYZE

1188
00:43:32,680 --> 00:43:33,760
DATA, BUT OF COURSE TRAINING IS

1189
00:43:33,760 --> 00:43:34,800
KEY HERE.

1190
00:43:34,800 --> 00:43:36,680
SO WE HAVE CREATED SEVERAL

1191
00:43:36,680 --> 00:43:38,840
TRAINING MODULES THAT ARE --

1192
00:43:38,840 --> 00:43:42,000
THERE ARE 50 TRAINING MANUALS

1193
00:43:42,000 --> 00:43:43,440
HERE THAT GO FROM SOUP TO NUTS.

1194
00:43:43,440 --> 00:43:45,360
IF YOU'VE NEVER LOGGED ON TO A

1195
00:43:45,360 --> 00:43:50,480
DPEUTER TO 

1196
00:43:50,480 --> 00:43:52,160
COMPUTER TO DO ANALYSIS, IT

1197
00:43:52,160 --> 00:43:54,960
TAKES YOU TO THAT FUNCTIONAL

1198
00:43:54,960 --> 00:43:56,920
ANALYSES YOU CAN PERFORM.

1199
00:43:56,920 --> 00:43:58,400
THESE 50 LESSONS ARE TRANSLATED

1200
00:43:58,400 --> 00:43:59,800
INTO MORE THAN 100 DIFFERENT

1201
00:43:59,800 --> 00:44:00,360
LANGUAGES.

1202
00:44:00,360 --> 00:44:01,760
AGAIN, TRYING TO REDUCE THE

1203
00:44:01,760 --> 00:44:03,640
BARRIER FOR FOLKS TO BE ABLE TO

1204
00:44:03,640 --> 00:44:06,760
ACCESS THIS RESOURCE AND LEARN

1205
00:44:06,760 --> 00:44:08,360
AND ALLOW US TO CREATE A GROUP

1206
00:44:08,360 --> 00:44:11,320
OF EXPERTS AROUND THE WORLD THAT

1207
00:44:11,320 --> 00:44:12,320
CAN GENERATE INTERESTING

1208
00:44:12,320 --> 00:44:18,760
RESEARCH QUESTIONS.

1209
00:44:18,760 --> 00:44:19,960
THAT LEARNING MANAGEMENT SYSTEM

1210
00:44:19,960 --> 00:44:21,800
HAS MORE THAN 500 USERS NOW,

1211
00:44:21,800 --> 00:44:23,120
AROUND A THIRD OF WHICH ARE FROM

1212
00:44:23,120 --> 00:44:26,920
LOW TO MEDIUM INCOME COUNTRIES.

1213
00:44:26,920 --> 00:44:29,640
WE HAVE LIVE Q & A SESSIONS WITH

1214
00:44:29,640 --> 00:44:31,400
LMS USERS, HELPING THEM NAVIGATE

1215
00:44:31,400 --> 00:44:32,680
THE PROCESS AND HELPING THEM

1216
00:44:32,680 --> 00:44:34,120
DEAL WITH ANY PARTICULAR

1217
00:44:34,120 --> 00:44:37,680
ANALYTICAL QUESTIONS THEY HAVE.

1218
00:44:37,680 --> 00:44:40,280
AS PART OF GP2, WE HAVE HELPED

1219
00:44:40,280 --> 00:44:41,640
SUPPORT A COMPETITIVE PH.D.

1220
00:44:41,640 --> 00:44:42,840
PROGRAM, SO I MENTIONED THAT WE

1221
00:44:42,840 --> 00:44:48,440
HAVE REALLY IN THE FIRST PHASE

1222
00:44:48,440 --> 00:44:50,560
TARGETED NEW COLLECTIONS ACROSS

1223
00:44:50,560 --> 00:44:53,600
AFRICA, SOUTH AMERICA, AND

1224
00:44:53,600 --> 00:44:54,360
THROUGHOUT ASIA.

1225
00:44:54,360 --> 00:44:56,200
THIS WAS TARGETED FOR CENTRAL

1226
00:44:56,200 --> 00:44:57,840
SOUTH AMERICA AND ASIA, SO WE

1227
00:44:57,840 --> 00:45:00,800
HAVE NEW PH.D. PROGRAMS, WORKING

1228
00:45:00,800 --> 00:45:03,960
ON GP2, THESE STUDENTS FROM

1229
00:45:03,960 --> 00:45:06,160
MEXICO, CHILE, TAIWAN AND

1230
00:45:06,160 --> 00:45:06,560
BRAZIL.

1231
00:45:06,560 --> 00:45:09,120
WE'VE ALSO SUPPORTED CLINICAL

1232
00:45:09,120 --> 00:45:11,720
TRAINING FOR CLINICIANS FROM

1233
00:45:11,720 --> 00:45:15,160
AFRICA, SO THESE ARE CLINICIANS

1234
00:45:15,160 --> 00:45:17,800
FROM ETHIOPIA, GHANA, NOW IN A A

1235
00:45:17,800 --> 00:45:19,240
MASTER'S CLINICAL PROGRAM IN

1236
00:45:19,240 --> 00:45:20,840
PARTNERSHIP WITH THE UNIVERSITY

1237
00:45:20,840 --> 00:45:23,160
COLLEGE LONDON, WHERE THEY COME

1238
00:45:23,160 --> 00:45:24,240
OVER AND TRAIN SPECIFICALLY IN

1239
00:45:24,240 --> 00:45:25,480
MOVEMENT DISORDERS.

1240
00:45:25,480 --> 00:45:26,840
OFTEN THESE ARE COUNTRIES WHERE

1241
00:45:26,840 --> 00:45:30,440
THERE ARE NO MOVEMENT DISORDER

1242
00:45:30,440 --> 00:45:31,960
SPECIALISTS, WHERE THERE MAY

1243
00:45:31,960 --> 00:45:33,760
ONLY BE ONE OR TWO NEUROLOGISTS.

1244
00:45:33,760 --> 00:45:35,840
SO AGAIN, THIS IDEA OF TRYING TO

1245
00:45:35,840 --> 00:45:37,880
BUILD GLOBAL WILL AND CAPACITY.

1246
00:45:37,880 --> 00:45:42,440
WE'VE WORKED WITH FUNDERS ON

1247
00:45:42,440 --> 00:45:44,160
CREATING RFAs THAT REALLY

1248
00:45:44,160 --> 00:45:45,560
TARGET DIVERSITY, EQUITY AND

1249
00:45:45,560 --> 00:45:48,360
INCLUSION AND HOW TO ACCESS

1250
00:45:48,360 --> 00:45:50,880
GP2 DATA, HOW HOW TO USE

1251
00:45:50,880 --> 00:45:52,960
GP2 DATA, AND WE'RE EVEN

1252
00:45:52,960 --> 00:45:54,160
PRODUCING DALE TA FOR SOME OF

1253
00:45:54,160 --> 00:45:57,680
THESE SUCCESSFUL APPLICANTS.

1254
00:45:57,680 --> 00:45:58,360
WE'VE ALSO BROUGHT PEOPLE

1255
00:45:58,360 --> 00:45:58,920
TOGETHER.

1256
00:45:58,920 --> 00:46:02,120
WE RUN HACKATHONS FOCUSED ON

1257
00:46:02,120 --> 00:46:04,080
LEARNING HOW TO DO ANALYSES AND

1258
00:46:04,080 --> 00:46:05,000
BRINGING TEAMS TOGETHER AROUND

1259
00:46:05,000 --> 00:46:07,960
THE WORLD, SO ESSENTIALLY WHAT

1260
00:46:07,960 --> 00:46:10,240
YOU DO IS BRING A GROUP OF

1261
00:46:10,240 --> 00:46:11,120
INDIVIDUALS TOGETHER WITH

1262
00:46:11,120 --> 00:46:12,200
DIFFERENT SKILLSETS, THEY ARE

1263
00:46:12,200 --> 00:46:18,520
PUT INTO TEAMS AND THEY SET 
ACCEPT A

1264
00:46:18,520 --> 00:46:20,560
CHALLENGE OF SOME KIND THEY HAVE

1265
00:46:20,560 --> 00:46:22,320
TO DO OVER TWO OR THREE DAYS.

1266
00:46:22,320 --> 00:46:23,600
USUALLY A CODING CHALLENGE.

1267
00:46:23,600 --> 00:46:27,440
THE LAST ONE WE RAN INCLUDED

1268
00:46:27,440 --> 00:46:29,040
ALMOST 50 PARTICIPANTS FROM A

1269
00:46:29,040 --> 00:46:30,320
DOES DIFFERENT COUNTRIES.

1270
00:46:30,320 --> 00:46:32,160
WE ALSO HAVE MEETINGS TO BRING

1271
00:46:32,160 --> 00:46:34,000
THE COMMUNITY TOGETHER WITH A

1272
00:46:34,000 --> 00:46:36,880
LARGE NUMBER OF ATTENDEES.

1273
00:46:36,880 --> 00:46:37,960
GP2 HAS ALSO SUPPORTED THE

1274
00:46:37,960 --> 00:46:39,360
CREATION OF A NEW COHORT.

1275
00:46:39,360 --> 00:46:41,880
THIS IS THE BLACK AND AFRICAN

1276
00:46:41,880 --> 00:46:43,240
AMERICAN CONNECTIONS TO PD STUDY

1277
00:46:43,240 --> 00:46:49,320
OR THE BACK PD STUDY.

1278
00:46:49,320 --> 00:46:52,080
BLACK AND AFRICAN AMERICAN

1279
00:46:52,080 --> 00:46:53,360
PARKINSON'S DISEASE PATIENTS ARE

1280
00:46:53,360 --> 00:46:56,160
INCREDIBLY UNDERREPRESENTED IN

1281
00:46:56,160 --> 00:46:58,600
PARKINSON'S RESEARCH, SO OUR AIM

1282
00:46:58,600 --> 00:47:00,760
IS TO COLLECT AROUND 500,000

1283
00:47:00,760 --> 00:47:01,840
PATIENTS.

1284
00:47:01,840 --> 00:47:05,360
THE FIRST PART AIMED AT

1285
00:47:05,360 --> 00:47:06,280
UNDERSTANDING GENETICS, HOPING

1286
00:47:06,280 --> 00:47:07,640
THIS WOULD FORK AS THE HUB FOR

1287
00:47:07,640 --> 00:47:14,320
FUTURE STUDIES, AND GP2 ALSO

1288
00:47:14,320 --> 00:47:16,680
STARTED -- WITH THE IDEA

1289
00:47:16,680 --> 00:47:17,360
ALLOWING THESE GROUPS FROM

1290
00:47:17,360 --> 00:47:18,960
AROUND THE WORLD TO REALLY

1291
00:47:18,960 --> 00:47:19,880
EXECUTE THEIR OWN RESEARCH

1292
00:47:19,880 --> 00:47:23,520
PROJECTS.

1293
00:47:23,520 --> 00:47:24,200
SO WHERE ARE WE?

1294
00:47:24,200 --> 00:47:25,360
I TOLD YOU ABOUT ALL THE THINGS

1295
00:47:25,360 --> 00:47:27,000
WE PLANNED AND HOW IT'S GONE.

1296
00:47:27,000 --> 00:47:29,360
SO SO FAR, WE'RE STILL ONLY TWO

1297
00:47:29,360 --> 00:47:30,120
YEARS IN.

1298
00:47:30,120 --> 00:47:31,960
WE'RE ABOUT TO REALLY START

1299
00:47:31,960 --> 00:47:33,760
RAMPING UP.

1300
00:47:33,760 --> 00:47:37,080
WE HAVE 170 COHORTS.

1301
00:47:37,080 --> 00:47:38,920
AT SOME POINT IN THE PROCESS OF

1302
00:47:38,920 --> 00:47:45,720
ONBOARDING INTO GP2, UP  170,000

1303
00:47:45,720 --> 00:47:47,480
SAMPLES AVAILABLE, NOW GENOTYPES

1304
00:47:47,480 --> 00:47:49,920
OVER 20,000 SAMPLES AND THE

1305
00:47:49,920 --> 00:47:52,280
FIRST 5,000 ARE ACTUALLY

1306
00:47:52,280 --> 00:47:54,440
RELEASED, ARE AVAILABLE IN AMP

1307
00:47:54,440 --> 00:47:56,000
P, YOU CAN GO THERE NOW AND

1308
00:47:56,000 --> 00:48:01,760
ACCESS JOE KNOW TYPE DATA FROM
GENOTYPE DA
TA FROM THOSE

1309
00:48:01,760 --> 00:48:02,160
SITES.

1310
00:48:02,160 --> 00:48:04,200
IT'S CERTAINLY BETTER THAN IT

1311
00:48:04,200 --> 00:48:06,000
WAS, BUT THERE ARE COUNTRIES WE

1312
00:48:06,000 --> 00:48:08,880
NEED TO FOCUS ON AND REALLY

1313
00:48:08,880 --> 00:48:09,840
IMPROVE REP 16 TAITION.

1314
00:48:09,840 --> 00:48:13,160
SO THERE ARE A CON OF THINGS WE

1315
00:48:13,160 --> 00:48:19,560
CAN DO IN PD -- SORRY -- IN GP2,

1316
00:48:19,560 --> 00:48:20,920
AND OF COURSE THERE ARE THE

1317
00:48:20,920 --> 00:48:22,760
OBVIOUS GENETIC THINGS I KIND OF

1318
00:48:22,760 --> 00:48:24,920
TALK ABOUT ON THE LEFT-HAND SIDE

1319
00:48:24,920 --> 00:48:27,480
OF THIS SLIDE CENTERED AROUND

1320
00:48:27,480 --> 00:48:29,240
DISCOVERY, FINDING NEW RISK

1321
00:48:29,240 --> 00:48:30,560
FACTORS, FINDING NEW GENES,

1322
00:48:30,560 --> 00:48:34,080
FINDING MODIFIERS, ALSO CREATING

1323
00:48:34,080 --> 00:48:35,040
RESOURCES, PROVIDING INDIVIDUALS

1324
00:48:35,040 --> 00:48:35,960
WHO ARE WORKING ON THE

1325
00:48:35,960 --> 00:48:40,520
FUNCTIONAL SIDE OF THIS WORK

1326
00:48:40,520 --> 00:48:44,160
WITH DIVERSE IPS LINES, WITH

1327
00:48:44,160 --> 00:48:45,000
DIVERSE BRAIN TISSUE.

1328
00:48:45,000 --> 00:48:46,240
BUT THERE ARE MORE AND MORE

1329
00:48:46,240 --> 00:48:48,280
OTHER THINGS COMING ALONG, MO

1330
00:48:48,280 --> 00:48:50,280
EMERGING OPPORTUNITIES AND

1331
00:48:50,280 --> 00:48:51,040
ADJACENT OPPORTUNITIES.

1332
00:48:51,040 --> 00:48:53,040
THIS REALLY SPEAKS TO, I THINK,

1333
00:48:53,040 --> 00:48:54,360
THE POWER OF WHAT WE'RE TRYING

1334
00:48:54,360 --> 00:48:55,200
TO CREATE HERE.

1335
00:48:55,200 --> 00:48:57,080
AGAIN, WE'RE NOT TRYING TO

1336
00:48:57,080 --> 00:48:58,760
CREATE SOMETHING WHERE GP2 DOES

1337
00:48:58,760 --> 00:49:01,560
ALL OF THE ANALYSIS, AND WE'RE

1338
00:49:01,560 --> 00:49:02,760
DONE.

1339
00:49:02,760 --> 00:49:04,200
WE'RE TRYING TO CREATE A

1340
00:49:04,200 --> 00:49:05,880
FRAMEWORK THAT ALLOWS OTHERS TO

1341
00:49:05,880 --> 00:49:08,640
BE ABLE TO ACCESS DATA AND

1342
00:49:08,640 --> 00:49:10,560
RESOURCES IN ORDER TO BE ABLE TO

1343
00:49:10,560 --> 00:49:13,160
EFFECT RESEARCH ON A GLOBAL

1344
00:49:13,160 --> 00:49:17,800
SCALE.

1345
00:49:17,800 --> 00:49:18,600
SO A SUMMARY.

1346
00:49:18,600 --> 00:49:20,240
I THINK IT MAKES SENSE TO GIVE

1347
00:49:20,240 --> 00:49:22,240
AN OVERALL SUMMARY OF WHAT I'VE

1348
00:49:22,240 --> 00:49:22,880
TALKED ABOUT TODAY.

1349
00:49:22,880 --> 00:49:24,840
I THINK PROGRESS IN PD HAS BEEN

1350
00:49:24,840 --> 00:49:26,080
REALLY SUBSTANTIAL OVER THE LAST

1351
00:49:26,080 --> 00:49:26,920
25 YEARS.

1352
00:49:26,920 --> 00:49:29,520
WE'VE LITERALLY GONE FROM ZERO

1353
00:49:29,520 --> 00:49:32,600
TO 100 IN THAT PERIOD OF TIME.

1354
00:49:32,600 --> 00:49:35,040
I THINK WHAT IS CRITICAL FOR

1355
00:49:35,040 --> 00:49:36,920
PARKINSON'S DISEASE, LIKE MANY

1356
00:49:36,920 --> 00:49:40,360
OTHER DISEASES, IS THAT WITH WE
HAVE

1357
00:49:40,360 --> 00:49:41,880
TO EXPAND THIS WORK TO ENCOMPASS

1358
00:49:41,880 --> 00:49:46,160
DIVERSE POPULATIONS.

1359
00:49:46,160 --> 00:49:49,280
IT IS, OF COURSE -- IT IS, OF

1360
00:49:49,280 --> 00:49:50,240
COURSE, IMPERATIVE THAT WE DO

1361
00:49:50,240 --> 00:49:51,400
SO, NOT JUST BECAUSE IT'S THE

1362
00:49:51,400 --> 00:49:54,000
RIGHT THING TO DO, BUT OF COURSE

1363
00:49:54,000 --> 00:49:56,040
IT IS, BUT ALSO BECAUSE

1364
00:49:56,040 --> 00:49:58,760
SCIENTIFICALLY, IT'S ESSENTIAL.

1365
00:49:58,760 --> 00:49:59,400
IT'S ESSENTIAL BECAUSE IT SPEEDS

1366
00:49:59,400 --> 00:50:07,120
UP OUR ABILITY TO MAP NEW LOCI,

1367
00:50:07,120 --> 00:50:08,680
THAT HAVE A PARTICULAR GENETIC

1368
00:50:08,680 --> 00:50:09,760
FORM AND, THEREFORE, WOULD BE

1369
00:50:09,760 --> 00:50:12,160
USEFUL FOR APPLYING CLINICAL

1370
00:50:12,160 --> 00:50:12,440
TRIALS.

1371
00:50:12,440 --> 00:50:14,480
THERE ARE JUST A MYRIAD OF

1372
00:50:14,480 --> 00:50:16,880
REASONS THAT WE REALLY NEED TO

1373
00:50:16,880 --> 00:50:18,360
FOCUS IN THIS SPACE.

1374
00:50:18,360 --> 00:50:22,000
OUR AIM IN CREATING GP2 REALLY

1375
00:50:22,000 --> 00:50:23,760
IS AN EXTENSION OF WHAT WE'VE

1376
00:50:23,760 --> 00:50:26,960
DONE IN GPDC AND IN THE LAB MORE

1377
00:50:26,960 --> 00:50:30,240
BROADLY, IS TO CREATE A GLOBAL

1378
00:50:30,240 --> 00:50:34,520
RESEARCH COMMUNITY, AVOIDING

1379
00:50:34,520 --> 00:50:35,720
COMPLETELY THE APPROACHES THAT

1380
00:50:35,720 --> 00:50:36,720
HAVE SOMETIMES BEEN USED IN THE

1381
00:50:36,720 --> 00:50:39,120
PAST, WHERE WELL FUNDED LABS

1382
00:50:39,120 --> 00:50:41,640
HAVE COME IN, TAKEN SAMPLES AND

1383
00:50:41,640 --> 00:50:42,640
WAY AND PUBLISHED.

1384
00:50:42,640 --> 00:50:44,560
WE'RE REALLY TRYING TO WORK WITH

1385
00:50:44,560 --> 00:50:47,680
THESE COMMUNITIES TO CREATE A

1386
00:50:47,680 --> 00:50:51,160
RISING TIDES.

1387
00:50:51,160 --> 00:50:54,840
ANY SUCCESS WE'VE HAD HAS BEEN

1388
00:50:54,840 --> 00:50:55,920
ESSENTIAL IN THAT SUCCESS, HAS

1389
00:50:55,920 --> 00:50:56,960
BEEN THE IRP.

1390
00:50:56,960 --> 00:50:58,560
IT REALLY IS A SPECTACULAR PLACE

1391
00:50:58,560 --> 00:50:59,520
TO WORK, I THINK.

1392
00:50:59,520 --> 00:51:01,320
I THINK IT ALLOWS US TO DO SOME

1393
00:51:01,320 --> 00:51:04,200
THINGS THAT JUST CAN'T QUITE BE

1394
00:51:04,200 --> 00:51:06,360
DONE EASILY OR AS EFFECTIVELY IN

1395
00:51:06,360 --> 00:51:10,320
THE OUTSIDE WORLD.

1396
00:51:10,320 --> 00:51:11,560
I'M NOT SAYING EVERYONE SHOULD

1397
00:51:11,560 --> 00:51:13,160
BE DOING PROJECTS LIKE THIS, I'M

1398
00:51:13,160 --> 00:51:14,760
NOT SAYING ALL RESEARCH SHOULD

1399
00:51:14,760 --> 00:51:15,800
BE DONE LIKE THIS, BUT I THINK

1400
00:51:15,800 --> 00:51:17,520
THERE'S SOME REALLY UNIQUE AND

1401
00:51:17,520 --> 00:51:18,520
SPECIAL THINGS ABOUT THE IRP

1402
00:51:18,520 --> 00:51:23,560
THAT REALLY ALLOWS US TO EFFECT

1403
00:51:23,560 --> 00:51:25,160
CHANGE, AND IT'S BEEN AN

1404
00:51:25,160 --> 00:51:29,160
ABSOLUTE PLEASURE TO WORK IN THE

1405
00:51:29,160 --> 00:51:30,400
IRP OVER THE LAST 20 YEARS OR

1406
00:51:30,400 --> 00:51:30,680
SO.

1407
00:51:30,680 --> 00:51:32,080
I STARTED TO PUT TOGETHER A

1408
00:51:32,080 --> 00:51:33,720
THANK YOU SLIDE BUT THERE ARE

1409
00:51:33,720 --> 00:51:34,960
TOO MANY PEOPLE TO THANK.

1410
00:51:34,960 --> 00:51:36,920
THESE ARE FOLKS WORKING IN MY

1411
00:51:36,920 --> 00:51:39,520
LAB OR I'M WORKING WITH ON

1412
00:51:39,520 --> 00:51:40,520
VARIOUS PROJECTS.

1413
00:51:40,520 --> 00:51:42,760
I WOULD LOVE TO GIVE A PICTURE

1414
00:51:42,760 --> 00:51:44,840
OF GP2 BUT THERE ARE AROUND 500

1415
00:51:44,840 --> 00:51:45,760
MEMBERS, SO THAT WOULD BE

1416
00:51:45,760 --> 00:51:47,720
DIFFICULT TO DO, BUT THE CLEAR

1417
00:51:47,720 --> 00:51:50,680
MESSAGE HERE IS, ALTHOUGH I'M

1418
00:51:50,680 --> 00:51:52,560
THE MESSENGER, THIS INVOLVES

1419
00:51:52,560 --> 00:51:55,000
HUNDREDS OF PEOPLE WHO WERE ALL

1420
00:51:55,000 --> 00:51:56,800
WILLING TO WORK TOGETHER IN A

1421
00:51:56,800 --> 00:51:57,880
COLLABORATIVE, EASY WAY, AND

1422
00:51:57,880 --> 00:51:59,960
IT'S BEEN A REAL PLEASURE TO BE

1423
00:51:59,960 --> 00:52:02,200
A PART OF THAT OVER THE LAST 20

1424
00:52:02,200 --> 00:52:02,880
YEARS.

1425
00:52:02,880 --> 00:52:04,440
I DON'T KNOW THAT I HAVE ANOTHER

1426
00:52:04,440 --> 00:52:07,040
20 YEARS OF IT IN ME, BUT I

1427
00:52:07,040 --> 00:52:08,440
GUESS WE'LL SEE.

1428
00:52:08,440 --> 00:52:11,120
SO WITH THAT, I WILL STOP AND

1429
00:52:11,120 --> 00:52:11,960
THANK YOU FOR YOUR KIND

1430
00:52:11,960 --> 00:52:16,880
ATTENTION.

1431
00:52:16,880 --> 00:52:18,280
>> THANK YOU VERY MUCH, ANDY.

1432
00:52:18,280 --> 00:52:19,440
THAT WAS A WONDERFUL

1433
00:52:19,440 --> 00:52:24,680
PRESENTATION.

1434
00:52:24,680 --> 00:52:27,960
WE HAVE ONE QUESTION IN THE

1435
00:52:27,960 --> 00:52:28,520
CHAT.

1436
00:52:28,520 --> 00:52:33,200
THE MESSAGE IS, DATA ON -- AND

1437
00:52:33,200 --> 00:52:37,440
ANCESTRIES IS VERY INTRIGUING.

1438
00:52:37,440 --> 00:52:40,560
HOW PRODUCTIVE DO YOU THINK IT

1439
00:52:40,560 --> 00:52:44,600
WOULD BE MINING FOR GENETIC LOCI

1440
00:52:44,600 --> 00:52:46,120
THAT -- RESILIENCE?

1441
00:52:46,120 --> 00:52:48,160
DO YOU HAVE ANY SUGGESTION ON

1442
00:52:48,160 --> 00:52:49,160
APPROACH IN THIS AREA?

1443
00:52:49,160 --> 00:52:50,160
>> I CAN TELL YOU, WE HAVE

1444
00:52:50,160 --> 00:52:52,160
SOMEONE IN OUR LAB THAT IS

1445
00:52:52,160 --> 00:52:54,720
REALLY INTERESTED IN THIS NOTION

1446
00:52:54,720 --> 00:52:55,240
OF RESILIENCE.

1447
00:52:55,240 --> 00:52:59,360
I MENTIONED HER EARLIER, SARAH

1448
00:52:59,360 --> 00:53:00,400
BANDRESS S IGA.

1449
00:53:00,400 --> 00:53:02,160
I THINK WE HAVE A WAYS TO GO IN

1450
00:53:02,160 --> 00:53:03,640
THAT SPACE, FRANKLY, BUT I DO

1451
00:53:03,640 --> 00:53:05,120
THINK IT'S A REALLY INTERESTING

1452
00:53:05,120 --> 00:53:05,600
IDEA.

1453
00:53:05,600 --> 00:53:10,360
AND THE IDEA OF WHETHER

1454
00:53:10,360 --> 00:53:11,760
RESILIENCE IS ONE OF THE THINGS

1455
00:53:11,760 --> 00:53:12,600
WE'D SEE, LET ME STEP BACK A

1456
00:53:12,600 --> 00:53:13,240
LITTLE BIT.

1457
00:53:13,240 --> 00:53:14,680
ONE OF THE THINGS WE SEE

1458
00:53:14,680 --> 00:53:15,560
SURPRISINGLY IS THERE'S NOT A

1459
00:53:15,560 --> 00:53:19,520
LOT OF GENETIC OVERLAP BETWEEN

1460
00:53:19,520 --> 00:53:22,080
MANY NEURODEGENERATIVE DISEASES.

1461
00:53:22,080 --> 00:53:23,240
SO ALZHEIMER'S DISEASE AND

1462
00:53:23,240 --> 00:53:25,000
PARKINSON'S DISEASE ARE PRETTY

1463
00:53:25,000 --> 00:53:25,960
DIFFERENT GENETICALLY, BUT I DO

1464
00:53:25,960 --> 00:53:27,360
WONDER, AND THIS IS REALLY

1465
00:53:27,360 --> 00:53:29,160
DRIVEN BY SARAH'S RESUCH,

1466
00:53:29,160 --> 00:53:30,680
WHETHER THERE MIGHT BE SHARED

1467
00:53:30,680 --> 00:53:33,520
FACTORS FOR RESILIENCE ACROSS

1468
00:53:33,520 --> 00:53:36,920
THESE DISEASES.

1469
00:53:36,920 --> 00:53:43,480
SO I THINK IT'S A GOOD IDEA.

1470
00:53:43,480 --> 00:53:44,880
>> I WANTED TO ASK YOU A

1471
00:53:44,880 --> 00:53:46,080
QUESTION IF I DON'T MIND.

1472
00:53:46,080 --> 00:53:47,280
I REALLY ENJOY YOUR

1473
00:53:47,280 --> 00:53:47,840
PRESENTATION.

1474
00:53:47,840 --> 00:53:52,720
I THINK THAT THERE IS KIND OF A

1475
00:53:52,720 --> 00:53:55,040
TRADEOFF IN THE FIELD OF

1476
00:53:55,040 --> 00:53:55,680
NEURODEGENERATIVE DISEASE

1477
00:53:55,680 --> 00:53:58,760
BETWEEN THE NEED TO

1478
00:53:58,760 --> 00:53:59,960
HYPERPHENOTYPE, SO BREAK ALL THE

1479
00:53:59,960 --> 00:54:02,760
PHENOTYPE IN MANY, MANY

1480
00:54:02,760 --> 00:54:03,960
DIFFERENT SUBGROUPS, AND AT THE

1481
00:54:03,960 --> 00:54:05,960
SAME TIME, PEOPLE ARE TALKING

1482
00:54:05,960 --> 00:54:09,840
ABOUT, YOU KNOW, GLOBAL

1483
00:54:09,840 --> 00:54:14,160
MECHANISMS, OVERALL PATHWAY THAT

1484
00:54:14,160 --> 00:54:16,640
AFFECT THE MULTIPLE

1485
00:54:16,640 --> 00:54:17,280
NEURODEGENERATIVE DISEASE AT THE

1486
00:54:17,280 --> 00:54:18,280
SAME TIME.

1487
00:54:18,280 --> 00:54:25,240
HOW WE ADDRESS THIS --

1488
00:54:25,240 --> 00:54:26,560
INTERPRETATION OF

1489
00:54:26,560 --> 00:54:27,360
NEURODEGENERATIVE DISEASE, I

1490
00:54:27,360 --> 00:54:28,480
WONDER IF YOU'VE EVER THOUGHT

1491
00:54:28,480 --> 00:54:29,960
ABOUT IT.

1492
00:54:29,960 --> 00:54:31,800
>> I THINK I UNDERSTAND YOUR

1493
00:54:31,800 --> 00:54:32,360
QUESTION.

1494
00:54:32,360 --> 00:54:34,760
I MEAN, I THINK THE CHALLENGE

1495
00:54:34,760 --> 00:54:37,840
FOR US HAS BEEN -- MUCH OF WHAT

1496
00:54:37,840 --> 00:54:40,640
WE DO IS DEPENDENT ON NUMBERS.

1497
00:54:40,640 --> 00:54:41,760
SO EXTREMELY DEEP PHENOTYPING

1498
00:54:41,760 --> 00:54:43,960
WHERE YOU START TO SEE

1499
00:54:43,960 --> 00:54:45,400
DIFFERENCES CLINICALLY,

1500
00:54:45,400 --> 00:54:46,680
PATHOLOGICALLY, OR MAYBE, YOU

1501
00:54:46,680 --> 00:54:48,560
KNOW, MECHANISTICALLY IF YOU'RE

1502
00:54:48,560 --> 00:54:52,520
LOOKING AT BIOMARKERS, IS

1503
00:54:52,520 --> 00:54:54,360
JUST -- WE JUST CAN'T QUITE GET

1504
00:54:54,360 --> 00:54:55,440
THERE IN TERMS OF THE NUMBERS.

1505
00:54:55,440 --> 00:54:59,320
THERE ARE SOME GROWING STUDIES.

1506
00:54:59,320 --> 00:55:00,440
CERTAINLY IN THE AD FIELD AND

1507
00:55:00,440 --> 00:55:07,200
ALSO IN THE PD FIELD, THE PKMI

1508
00:55:07,200 --> 00:55:12,640
STUDY, WHERE LONG -- STARTING TO

1509
00:55:12,640 --> 00:55:14,000
GET US TO WHETHER THERE ARE

1510
00:55:14,000 --> 00:55:14,360
SUBTYPES.

1511
00:55:14,360 --> 00:55:18,280
I THINK ONE OF THE THINGS THAT

1512
00:55:18,280 --> 00:55:20,440
WE'VE TRIED AND I THINK IS THE

1513
00:55:20,440 --> 00:55:22,360
WAY FORWARD IS TO STOP THINKING

1514
00:55:22,360 --> 00:55:23,560
ABOUT PHENOTYPING IN TERMS OF

1515
00:55:23,560 --> 00:55:25,480
WHAT IS BEING PRESENTED TO US

1516
00:55:25,480 --> 00:55:27,000
CLINICALLY, WHAT IS BEING

1517
00:55:27,000 --> 00:55:29,080
PRESENTED TO A CLINICIAN AS THEY

1518
00:55:29,080 --> 00:55:31,440
SEE THE PATIENT AND RATHER

1519
00:55:31,440 --> 00:55:34,160
TAKING QUANTITATIVE MEASURES AND

1520
00:55:34,160 --> 00:55:37,840
USING APPROACHES LIKE AI OR ML

1521
00:55:37,840 --> 00:55:39,560
TO TELL US WHAT PROGRESSION

1522
00:55:39,560 --> 00:55:41,240
LOOKS LIKE, TO TELL US WA

1523
00:55:41,240 --> 00:55:42,840
SUBTYPES LOOK LIKE.

1524
00:55:42,840 --> 00:55:46,080
WE HAVE A COMPUTER SCIENTIST IN

1525
00:55:46,080 --> 00:55:47,240
OUR GROUP WHO HAS BEEN WORKING

1526
00:55:47,240 --> 00:55:49,120
ON THIS IN PD AND CERTAINLY

1527
00:55:49,120 --> 00:55:53,800
STARTS TO SEE, BASED ON

1528
00:55:53,800 --> 00:55:55,000
PRESENTATION AND PROGRESSION,

1529
00:55:55,000 --> 00:55:56,560
DIFFERENT CLUSTERS OF MD,

1530
00:55:56,560 --> 00:55:57,800
DIFFERENT CLUSTERS OF PD

1531
00:55:57,800 --> 00:55:59,840
PATIENTS.

1532
00:55:59,840 --> 00:56:02,600
>> TWO MORE QUESTIONS.

1533
00:56:02,600 --> 00:56:14,160
ONE FROM CAN THESE BE USED TO

1534
00:56:14,160 --> 00:56:15,960
UNDERSTAND -- FACTORS ACROSS THE

1535
00:56:15,960 --> 00:56:16,160
WORLD?

1536
00:56:16,160 --> 00:56:20,080
>> THE MAJORITY OF THE -- IN THE

1537
00:56:20,080 --> 00:56:20,920
GP2 STUDY HAVE ALREADY BEEN

1538
00:56:20,920 --> 00:56:22,760
COLLECTED THERE, NARE

1539
00:56:22,760 --> 00:56:24,200
PERSPECTIVE COLLECTIONS THAT

1540
00:56:24,200 --> 00:56:24,960
WERE EXISTING.

1541
00:56:24,960 --> 00:56:26,800
HOWEVER, THERE ARE QUITE A FEW,

1542
00:56:26,800 --> 00:56:28,680
PARTICULARLY IN UNDERREPRESENTED

1543
00:56:28,680 --> 00:56:30,680
POPULATIONS, THAT ARE ONGOING.

1544
00:56:30,680 --> 00:56:36,800
SO WE HAVE STARTED TO DO THINGS

1545
00:56:36,800 --> 00:56:37,640
LIKE DEPLOY QUESTIONNAIRES ON

1546
00:56:37,640 --> 00:56:42,040
DIET AND EXPOSURE.

1547
00:56:42,040 --> 00:56:44,520
THAT IS A TOUGH THING TO DO FOR

1548
00:56:44,520 --> 00:56:46,720
SURE, AS LUIGI KNOWS BETTER THAN

1549
00:56:46,720 --> 00:56:48,160
ANYONE ACTUALLY, BUT WE'RE AT

1550
00:56:48,160 --> 00:56:49,880
LEAST STARTING TO GET THERE.

1551
00:56:49,880 --> 00:56:51,400
THIS KIND OF ILLUSTRATES MAYBE

1552
00:56:51,400 --> 00:56:53,800
THE POTENTIAL OF GP2.

1553
00:56:53,800 --> 00:56:56,160
IT'S SET UP AS A GENETIC STUDY,

1554
00:56:56,160 --> 00:56:57,680
BUT IF SOMEONE COMES ALONG WITH

1555
00:56:57,680 --> 00:56:59,000
A RESEARCH QUESTION LIKE THAT,

1556
00:56:59,000 --> 00:57:00,200
WE HAVE THE CONNECTIONS ALL IN

1557
00:57:00,200 --> 00:57:02,400
PLACE TO BE ABLE TO INITIATE A

1558
00:57:02,400 --> 00:57:03,960
STUDY, TO BE ABLE TO TAKE A

1559
00:57:03,960 --> 00:57:06,360
STUDY LIKE THAT FORWARD?

1560
00:57:06,360 --> 00:57:11,760
>> I HAVE ONE QUESTION, HAVE YOU

1561
00:57:11,760 --> 00:57:16,160
FOUND NON-CODING VARIANT, FOR

1562
00:57:16,160 --> 00:57:19,600
IMAM, -- UTRS, SOMETHING THAT IS

1563
00:57:19,600 --> 00:57:20,920
NOT CODED?

1564
00:57:20,920 --> 00:57:23,720
>> AS CAUSATIVE?

1565
00:57:23,720 --> 00:57:25,520
>> AS CAUSATIVE.

1566
00:57:25,520 --> 00:57:31,800
>> AS CAUSATIVE, NO, NOT REALLY.

1567
00:57:31,800 --> 00:57:33,880
OF COURSE AS RISK, YES, TONS OF

1568
00:57:33,880 --> 00:57:34,960
THEM, IT'S KIND OF UNDERSTANDING

1569
00:57:34,960 --> 00:57:38,160
WHAT THE FUNCTIONAL REGION IS.

1570
00:57:38,160 --> 00:57:39,560
I THINK THIS MIGHT, THOUGH, IN

1571
00:57:39,560 --> 00:57:41,520
PART BE BECAUSE WE WEREN'T

1572
00:57:41,520 --> 00:57:42,360
REALLY LOOKING.

1573
00:57:42,360 --> 00:57:44,760
SO MY GUESS IS, THERE ARE THINGS

1574
00:57:44,760 --> 00:57:47,520
IN UTRs, THERE ARE THINGS IN

1575
00:57:47,520 --> 00:57:51,000
REGULATORY REGIONS THAT MAY

1576
00:57:51,000 --> 00:57:51,840
AFFECT -- THAT MAY NOT JUST

1577
00:57:51,840 --> 00:57:55,680
AFFECT A RISK THAT MAY BE

1578
00:57:55,680 --> 00:57:56,360
CAUSATIVE, WE JUST HAVEN'T

1579
00:57:56,360 --> 00:57:56,800
LOOKED.

1580
00:57:56,800 --> 00:57:58,720
ONE OF THE THINGS ABOUT

1581
00:57:58,720 --> 00:58:03,480
TRANSFORMATIVE TECHNOLOGIES, IS

1582
00:58:03,480 --> 00:58:04,360
LONG -- SEQUENCING AND MY HOPE

1583
00:58:04,360 --> 00:58:06,240
IS I WILL HELP RESOLVE SOME OF

1584
00:58:06,240 --> 00:58:07,680
THOSE THINGS THAT WE'VE MISSED.

1585
00:58:07,680 --> 00:58:08,000
>> OKAY.

1586
00:58:08,000 --> 00:58:11,520
THANK YOU SO MUCH, ANDY, FOR

1587
00:58:11,520 --> 00:58:14,480
YOUR SCIENCE, FOR YOUR

1588
00:58:14,480 --> 00:58:17,480
GENEROSITY, FOR PRODUCING THIS

1589
00:58:17,480 --> 00:58:21,520
WONDERFUL -- I'M SURE WE'RE

1590
00:58:21,520 --> 00:58:22,360
REFLECTING THE HELP OF THE

1591
00:58:22,360 --> 00:58:22,680
POPULATION.

1592
00:58:22,680 --> 00:58:24,200
AND THANK YOU, EVERYBODY, THAT

1593
00:58:24,200 --> 00:58:24,960
HAS BEEN LISTENING.

1594
00:58:24,960 --> 00:58:25,520
THIS CONCLUDES OUR PRESENTATION.

1595
00:58:25,520 --> 00:58:36,760
>> THANK YOU.