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>>WELCOME BACK TO THE
ASSAY

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WORKSHOP. WE ARE EXCITED FOR YOU

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TO BE HERE TODAY.  WE HAD AN

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AMAZING DAY YESTERDAY. WITH A

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LOT OF DISCUSSIONS AND HOPEFULLY

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YOU LEARNED A LOT AND IT WAS

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BENEFICIAL FOR YOUR RESEARCH. WE

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ARE LOOKING FORWARD TO AN

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AMAZING DAY TWO TONS OF

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DISCUSSIONS AND A LOT OF

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LEARNING HAPPENING. SO I AM

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EDITOR IN CHIEF AND ASSAY

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GUIDANCE MANUAL AND LEAD OF THE

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ASSAY GUIDANCE MANUAL

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TRANSLATIONAL RESOURCES PROGRAM

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HERE AT THE NATIONAL CENTER FOR

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ADVANCING TRANSLATIONAL SCIENCES

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AND I WILL BE HOSTING THE

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WORKSHOP TODAY.  LET ME SHARE

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THE AGENDA FOR DAY TWO. WE WILL

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HAVE AMAZING THREE SESSIONS

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TODAY. LOOKING FORWARD TO THEM.

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THE FIRST SESSION WILL BE ON

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EWETY OF THE EXISTING 3 --

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UTILITY OF 3D MODELS FOR

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ANTIVIRAL DRUG DEVELOPMENT,

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THAT'S SESSION 2. AND THEN IT

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WILL START NOW AND SPAN ALL THE

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WAY TO 2:30. WE WILL THEN HAVE

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ANOTHER SESSION THIS AFTERNOON,

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SESSION 3 WHICH WILL BE ON USING

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ROBUST AND REPRODUCIBILITY 3D

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MODELS THROUGH DRUG DISCOVERY

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AND DEVELOPMENT. AND WE WILL

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CONCLUDE WITH A CLOSING SESSION

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ON SUMMARIES OF DISCUSSIONS AND

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PERSPECTIVES ON THE CHALLENGES

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AHEAD.  SO STAY TUNED WITH US

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AND ENJOY TODAY.  AND BEFORE I

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INTRODUCE CHAIR OF SESSION 1 I

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WOULD LIKE TO REMIND EVERYONE

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THAT YOU CAN ASK QUESTIONS

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THROUGHOUT THE TALKS THROUGH THE

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Q&A CHAT BOX AND WE WILL GET
TO

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THESE QUESTIONS AT THE END OF

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THE EACH SESSION. THERE IS A

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DISCUSSION AND Q&A TIME

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DEDICATED TO ANSWER YOUR

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QUESTIONS.  AND WE GOT PLENTY OF

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QUESTIONS YESTERDAY, HOPEFULLY

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WE GET A LOT OF QUESTIONS TODAY

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AND WE WILL COVER AS MANY

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QUESTIONS AS POSSIBLE. SO WE

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WILL START WITH SESSION 2 NOW,

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AGAIN ENTITLED UTILITY OF

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EXISTING 3D TISSUE MODELS FOR

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ANTIVIRAL DRUG DEVELOPMENT. THIS

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SESSION IS CHAIRED BY DR. ANN

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EAKIEAKIEAKIN. DR. EAKIN IS SENR

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SCIENTIFIC OFFICER, OFFICE OF

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BIODEFENSE RESEARCH RESOURCES

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AND TRANSLATIONAL RESEARCH IN

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THE DIVISION OF MICROBIOLOGY AND

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INFECTIOUS DISEASES OF THE

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NATIONAL INSTITUTES OF ALLERGY

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AND INFECTIOUS DISEASES HERE AT

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THE NATIONAL INSTITUTES OF

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HEALTH. THANK YOU SO MUCH, ANN

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FOR BEING HERE. I WILL PASS THE

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BATON TO YOU.

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>> EXCELLENT. AGAIN TO ALL

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PARTICIPANTS WELCOME BACK TO THE

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MEETING. I THINK IT WAS A

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FABULOUS DAY YESTERDAY,

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EXCELLENT SPEAKERS, SET THE BAR

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PRETTY HIGH FOR THE SPEAKERS

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TODAY BUT I AM QUITE CONFIDENT

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THAT WE CAN DELIVER. SO VERY

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PLEASED TO LEAD THE SESSION 2

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DISCUSSION. AGAIN ON THE UTILITY

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OF -- UTILITY OF EXISTING 3D

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TISSUE MODELS FOR ANTIVIRAL DRUG

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DEVELOPMENT. WE HAVE SIX REALLY

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FABULOUS SPEAKERS AND AGAIN

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PLEASE DON'T HOLD BACK, WRITE

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YOUR QUESTIONS IN AS THE TALKS

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GO ALONG AND WE WILL HAVE PLENTY

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OF TIME FOR Q&A AT THE END.
IF

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YOUR QUESTION IS DIRECTED I

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WOULD LIKE TO ASK TO SPECIFIC

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SPEAKER IF YOU CAN PUT THEIR

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NAME IN THE FRONT THAT WILL HELP

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ME COORDINATE THAT DISCUSSION,

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IF IT IS TO ALL THE SPEAKERS

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THAT IS GREAT. THAT CAN WORK

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TOO. SO LET'S GO AHEAD AND KICK

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OFF WITH OUR FIRST SPEAKER OF

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THE SESSION. DR. DONALD INGBAR.

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DR. INGBAR IS THE FOUNDING

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DIRECTOR OF THE WYSS INSTITUTE

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FOR BIOLOGICALLY INSPIRED

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ENGINEERING AT HARVARD

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UNIVERSITY. HE'S A FOLKMAN

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PROFESSOR OF VASCULAR BIOLOGY AT

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HARVARD MEDICAL SCHOOL AND

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VASCULAR BIOLOGY PROGRAM AT

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BOSTON CHILDREN'S HOSPITAL. AND

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PROFESSOR OF BIOENGINEERING AT

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THE HARVARD JOHN A PAULSON

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SCHOOL OF ENGINEERING AND

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APPLIED SCIENCES. HE RECEIVED

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MULTIPLE DEGREES INCLUDING M.D.

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AND Ph.D. FROM YALE

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UNIVERSITY, DR. INGBAR IS

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PIONEER IN THE FIELD OF

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BIOLOGICALLY INSPIRED

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ENGINEERING THAT CROSSES A RANGE

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OF DISCIPLINES, TO REALLY FOCUS

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ON DEVELOPING BREAK THROUGH

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TECHNOLOGIES TO ADVANCE

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HEALTHCARE. HE'S AUTHORED MORE

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THAN 500 PUBLICATIONS AND ALMOST

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200 U.S. PATENTS. HE'S FOUNDED

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SEVEN COMPANIES AND MADE GREAT

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STRIDES IN TRANSLATING THE

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SCIENTIFIC DISCOVERIES AND

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INNOVATIONS HIS TEAM HAS MADE

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INTO COMMERCIAL PRODUCTS, MANY

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OF WHICH ARE NOW EITHER IN

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CLINICAL TRIALS OR

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COMMERCIALIZED. DR. INGBAR IS

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MEMBER OF THE NATIONAL ACADEMY

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OF MEDICINE, CASHNAL ACADEMY OF

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-- NATIONAL ACADEMY OF

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ENGINEERING, AMERICAN INSTITUTE

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FOR AMERICAN BIOLOGICAL

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ENGINEERING AND THE AMERICAN

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ACADEMY OF ARTS AND SCIENCES. HE

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IS ALSO LISTED AMONG NATURE'S

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BIOTECHNOLOGIES TOP 20

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TRANSLATIONAL RESEARCHERS IN

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2012, 2019 AND 2020. SO REALLY

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PLEASED TO HAVE DR. INGBAR KICK

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OFF THIS SESSION. AND THE TITLE

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OF HIS TALK IS MODELING

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RESPIRATORY VIRAL INFECTIONS IN

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HUMAN LUNG CHIPS OVER TO YOU.

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>> THANK YOU SO MUCH. CAN
YOU

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SEE MY SCREEN IN

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>> SURE CAN.

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>> GREAT. THANK YOU FOR
THE

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OPPORTUNITY. WHAT I WOULD LIKE

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TO DO IS DESCRIBE TO YOU DRUG

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DISCOVERY THAT WE HAVE BEEN ABLE

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TO CARRY OUT OVER THE LAST

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COUPLE OF YEARS, IT'S BEEN

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ENABLED BY MODELING RESPIRATORY

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VIRUS INFECTIONS USING HUMAN

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LUNG CHIPS. WE HAVE WORKED FOR

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15 YEARS NOW CALLED HUMAN ORGAN

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ON CHIPS OR ORGAN CHIPS.  THESE

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ARE MICRODEVICES CONTAINING

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LIVING HUMAN CELLS THAT

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RECONSTITUTE ORGAN LEVEL

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STRUCTURE AND FUNCTIONS NOT

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CELLULAR TISSUE BUT ORGAN LEVEL

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FUNCTION THAT ARE CREATED WITH

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ORIGINALLY WITH MICROCHIP

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MANUFACTURING TECHNIQUES, CALLED

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ORGAN CHIPS. WE DEVELOPED THEM

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TO ACCELERATE DRUG DEVELOPMENT,

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REPLACE ANIMAL TESTING AND

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REPLACE PERSONALIZED MEDICINE.

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OUR FIRST CHIP WAS A LUNG CHIP,

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WE CALLED IT HUMAN BREATHING

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LUNG CHIP, IT IS A MODEL OF THE

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LUNG ALVEOLUS AND I WANT TO

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EMPHASIZE WE ARE T NO

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ENGINEERING THE WHOLE LUNG, THIS

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IS ARE LIVING THREE DIMENSIONAL

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CROSS SECTIONS FOR MAJOR

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FUNCTIONAL UNIT THE ALVEOLUS.

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THE NEXT VIDEO SHOWS HOW THIS

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WORKS. IT IS SIZE OF COMPUTER

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MEMORY STICK SHOWN AT THE TOP

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RIGHT. MADE OUT OF OPTICALLY

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CLEAR FLEXIBLE RUBBE RUBBER. IFU

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CUT IN CROSS SECTION THREE

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HOLLOW CHANNELS EACH LESS THAN A

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MILLIMETER WIDE.  THE MIDDLE ONE

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IS CUT INTO TOP AND BOTTOM WITH

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A POROUS MEMBRANE WITH EXTRA

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CELLULAR MATRIX. SO WE TAKE

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ALVEOLAR CELLS HUMAN CELLS ON

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TOP, HUMAN LUNG CAPILLARY CELLS

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ON THE BOTTOM, WE RECREATED THE

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ALVEOLAR CAPILLARY INTERFACE. 

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TRICK IS THAT WE HAVE SIDE

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CHAMBERS THAT ARE HOLLOW WE

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APPLY SUCTION, EVERYTHING IS

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FLEXIBLE AND ACTUALLY STRETCHES

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IN THE SAME RATE AND DEGREE AS

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WHEN WE BREATHE IN AND OUT.  WE

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CAN NOW FLOAT AIR OVER THE TOP

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TO HAVE AIR LIQUID INTERFACE,

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PUT CAPILLARY CELLS ON ALL FOUR

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SIDES AND FLOW MEDIUM WITH

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IMMUNE CELLS OR WHOLE BLOOD

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WITHOUT ANTI-COAGULANTS FOR

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SHORT TIMES. IF THIS WORKS MODEL

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ORGAN LEVEL RESPONSE IMAGINE YOU

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HAVE A BACTERIAL INFECTION OR

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VIRAL INFECTION THIS USUALLY IS

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A TISSUE TISSUE SIGNALING

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RESPONSE, SO EPITHELIAL CELLS

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PUT OUT CYTOKINES ACTIVATE

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ENDOTHELIUM, WHITE BLOOD CELLS

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THAT WERE JUST FALLING BEHIND

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STICK AND ROLL, MIGRATE ACROSS

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AND ENGULF THE BACTERIA. THAT'S

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BECAUSE THE CYTOKINES INDUCE THE

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ENDOTHREE LYNN TO PUT OUT

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ADHESION RECEPTORS.  THESE ARE

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FRESH WHITE BLOOD CELLS LABELED

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FLUORESCENTLY, YOU DON'T SEE THE

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ENDOTHELIUM, AND THE EPITHELIUM

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IS BEHIND THE SCREEN YOU CANNOT

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SEE. TO BEGIN WITH QUIESCENT,

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THEY FLOW BY, BACTERIA ON THE

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OTHER SIDE THERE IS SIGNALING

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RESPONSE, I CAM IS ON THE OTHER,

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THEY ARE PULLED OUT UNDER FLOW

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KNOWN THE INITIAL ADHESION IS

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SHEER STRESS DEPENDENT. AND NOW

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YOU CAN DO ANY IMAGING IN THE

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DEVICE YOU CAN DO OTHERWISE HERE

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IS ONE WHITE BLOOD CELL HERE

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BETWEEN TWO END HEELIAL CELLS,

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FINDS MATRIX PORE, MIGRATE OUT

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OF FOCUS TO THE OTHER SIDE, NOW

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YOU CAN SEE IT COMING OUT OF THE

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EPITHELIUM BY PHASE CONTRAST.

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NOW SHOW YOU THE WHITE BLOOD

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CELL IN RED, THE BACTERIA ARE

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LABELED IN GFP GREEN, WATCH THEM

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BEING ENGULFED SO YOU WATCHED

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THE ENTIRE HUMAN INFLAMMATORY

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RESPONSE IN THIS CHIP. MULTIPLE

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PUBLICATIONS WITH THIS CHIP BUT

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BASICALLY DEMONSTRATED PROOF OF

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PRINCIPLE FOR DISEASE MODELS, WE

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HAVE DONE PULMONARY EDEMA, THIS

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DRUG TOXICITY EVEN NOT SEEN IN

254
00:09:14,240 --> 00:09:15,920
ANIMALS, DRUG EFFICACY, WE

255
00:09:15,920 --> 00:09:17,480
DISCOVERED THERAPEUTIC TARGETS,

256
00:09:17,480 --> 00:09:19,400
AS A DRUG PHASE 2 CLINICAL

257
00:09:19,400 --> 00:09:21,240
TRIALS CAME OUT OF THE THIS WORK

258
00:09:21,240 --> 00:09:22,480
IN PART AND WE HAVE DELIVERED

259
00:09:22,480 --> 00:09:24,720
GENE THERAPIES ADENOVIRAL

260
00:09:24,720 --> 00:09:26,280
VECTORS ON THESE CHIPS. AND IN

261
00:09:26,280 --> 00:09:28,320
ADDITION TO IMMUNE CELLS WE HAVE

262
00:09:28,320 --> 00:09:29,920
INTEGRATED STROMAL FIBROBLASTS

263
00:09:29,920 --> 00:09:32,400
SO YOU CAN LOOK AT PULMONARY

264
00:09:32,400 --> 00:09:36,280
FIBROSIS WITH FUNDING FROM THE

265
00:09:36,280 --> 00:09:38,080
FDA. MULTIPLE AWARDS I WON'T GO

266
00:09:38,080 --> 00:09:41,160
INTO IN THIS TALK BUT IT REALLY

267
00:09:41,160 --> 00:09:42,320
REPRESENTED A PARADIGM SHIFT IN

268
00:09:42,320 --> 00:09:44,120
THE FIELD I THINK THAT PEOPLE

269
00:09:44,120 --> 00:09:47,440
RECOGNIZE THIS IS POSSIBLE. SO

270
00:09:47,440 --> 00:09:48,800
WE BUILD SOMETHING LIKE 20

271
00:09:48,800 --> 00:09:50,320
DIFFERENT ORGAN CHIPS BUT THE

272
00:09:50,320 --> 00:09:52,960
SECOND WE BUILT WAS A LUNG

273
00:09:52,960 --> 00:09:54,960
AIRWAY CHIP BECAUSE THE

274
00:09:54,960 --> 00:09:55,760
PHARMACEUTICAL COMPANIES WERE

275
00:09:55,760 --> 00:09:58,320
INTERESTED IN ASTHMA AND COPD,

276
00:09:58,320 --> 00:10:01,200
AND HERE WE TAKE PRIMARY HUMAN

277
00:10:01,200 --> 00:10:04,200
LUNG BRONCHIAL EPIHELIUM, HUMAN

278
00:10:04,200 --> 00:10:06,480
LUNG ENDOTHELIUM AND CULTURE IN

279
00:10:06,480 --> 00:10:09,120
AIR LIQUID INTERFACE AND NOW YOU

280
00:10:09,120 --> 00:10:11,240
HAVE INCREDIBLE BEAUTIFUL

281
00:10:11,240 --> 00:10:13,480
DIFFERENTIADIFFERENTIATION. YOUT

282
00:10:13,480 --> 00:10:14,560
FLUORESCENT PARTICLES AT THE

283
00:10:14,560 --> 00:10:18,400
RIGHT, YOU LOOK AT MUCOCILIARE

284
00:10:18,400 --> 00:10:19,960
CLEARANCE, THE SAME VELOCITY AS

285
00:10:19,960 --> 00:10:21,520
RO1 AT THE MOMENT, ALL THE CELL

286
00:10:21,520 --> 00:10:25,480
TYPES IN NORMAL RATIOS YOU GET

287
00:10:25,480 --> 00:10:27,840
NORMAL EPITHELIAL MORPHOLOGY. WE

288
00:10:27,840 --> 00:10:29,480
MADE CHIPS WITH CELLS FROM

289
00:10:29,480 --> 00:10:31,560
PATIENTS WITH DISEASES IN THIS

290
00:10:31,560 --> 00:10:33,360
CASE CHRONIC OBSTRUCTIVE

291
00:10:33,360 --> 00:10:34,840
PULMONARY DISEASE, COPD. WHAT

292
00:10:34,840 --> 00:10:35,920
BRINGS THE PATIENTS TO THE

293
00:10:35,920 --> 00:10:38,040
HOSPITAL USUALLY EXACERBATIONS

294
00:10:38,040 --> 00:10:40,040
BY BACTERIAL INFECTION VIRAL

295
00:10:40,040 --> 00:10:41,320
INFECTION OR CIGARETTE SMOKE AND

296
00:10:41,320 --> 00:10:43,360
THE FIRST THING WAS THAT WE CAN

297
00:10:43,360 --> 00:10:45,600
SHOW THAT YOU RETAIN THE THE

298
00:10:45,600 --> 00:10:47,240
COPD PHENOTYPE, NO IMMUNE CELLS

299
00:10:47,240 --> 00:10:48,800
HERE, MUST BE EPIGENETIC CHANGES

300
00:10:48,800 --> 00:10:51,520
IN THE EPITHELIUM IN TERMS OF

301
00:10:51,520 --> 00:10:54,480
DECREASE TOLL 3 R 4 RECEPTOR

302
00:10:54,480 --> 00:10:57,240
EXPRESSION. THEN IF YOU USE

303
00:10:57,240 --> 00:10:59,640
POLYVIRAL INFECTION OR LPS

304
00:10:59,640 --> 00:11:02,800
ENDOTOXIN ONLY THE COPD SHOW

305
00:11:02,800 --> 00:11:05,320
INCREASE RESPONSE TERMS OF IL 8

306
00:11:05,320 --> 00:11:08,000
OR MCSF SECRETION. WE BUILT A

307
00:11:08,000 --> 00:11:09,960
CIGARETTE SMOKING ROBOT THAT HAS

308
00:11:09,960 --> 00:11:13,120
LIGHTER FROM CAR AND REAL

309
00:11:13,120 --> 00:11:14,720
CIGARETTES MIMICKING SMOKING

310
00:11:14,720 --> 00:11:15,880
PARAMETERS REAL SMOKE NOT

311
00:11:15,880 --> 00:11:17,320
EXTRACT GOES TO AIR SPACE, AND

312
00:11:17,320 --> 00:11:19,640
JUST TO SHOW YOU COUPLE OF

313
00:11:19,640 --> 00:11:21,560
EXAMPLES LOOKING AT IL 8 YOU

314
00:11:21,560 --> 00:11:23,400
HAVE HEALTHY CHIPS CIGARETTE

315
00:11:23,400 --> 00:11:26,280
SMOKE EXPOSURE DOES NOTHING. IN

316
00:11:26,280 --> 00:11:28,800
COPD CHIPS IT DOUBLES. THE RIGHT

317
00:11:28,800 --> 00:11:30,840
YOU SEE TRANSCRIPTOMIC RESULTS

318
00:11:30,840 --> 00:11:34,360
WE DO -- WE HAVE DONE PROTEOMIC

319
00:11:34,360 --> 00:11:38,160
METABOLOMIC GLYCOMIC AND

320
00:11:38,160 --> 00:11:40,160
TRANSGENOMIC CHIPS ON THE RIGHT

321
00:11:40,160 --> 00:11:41,720
THEY ARE HEALTHY CHIPS FROM

322
00:11:41,720 --> 00:11:43,720
HEALTHY PATIENTS AFTER CIGARETTE

323
00:11:43,720 --> 00:11:45,960
SMOKE EXPOSURE. AT THE LEFT IS A

324
00:11:45,960 --> 00:11:47,120
PAST CLINICAL STUDY WITH HEALTHY

325
00:11:47,120 --> 00:11:48,920
PEOPLE WHO SMOKE CIGARETTES.

326
00:11:48,920 --> 00:11:50,840
WHAT YOU CAN SEE IS THAT THE TOP

327
00:11:50,840 --> 00:11:51,400
QUARTER VERSUS BOTTOM THREE

328
00:11:51,400 --> 00:11:53,760
QUARTERS ARE SIMILAR, WE GOT

329
00:11:53,760 --> 00:11:54,960
PUSH BACK BECAUSE OF VARIATION

330
00:11:54,960 --> 00:11:56,400
IN OUR CHIPS WAS LESS THAN THE

331
00:11:56,400 --> 00:11:59,800
PATIENT POPULATION. THEN WE

332
00:11:59,800 --> 00:12:01,800
REALIZE WE CAN DO MATCH

333
00:12:01,800 --> 00:12:03,160
COMPARATIVE MODELING IN THESE

334
00:12:03,160 --> 00:12:04,520
CHIPS MEANING A BETTER CLINICAL

335
00:12:04,520 --> 00:12:06,440
STUDY IN THE SENSE THAN REAL

336
00:12:06,440 --> 00:12:08,440
CLINICAL STUDY BECAUSE THESE

337
00:12:08,440 --> 00:12:10,680
GENES ARE DUE TO CIGARETTE SMOKE

338
00:12:10,680 --> 00:12:12,160
NOT FAMILY HISTORY, WORK

339
00:12:12,160 --> 00:12:13,360
ENVIRONMENT, ET CETERA.  THIS

340
00:12:13,360 --> 00:12:14,920
WAS PUBLISHED WITH A LITTLE

341
00:12:14,920 --> 00:12:17,280
COMMENTARY EXPLAINING THAT. TO

342
00:12:17,280 --> 00:12:18,880
GET TO THE POINT OF TODAY'S

343
00:12:18,880 --> 00:12:20,920
TALK, WHEN WE STARTED THIS THE

344
00:12:20,920 --> 00:12:21,920
IDEA WAS TO AXEL INVESTIGATE

345
00:12:21,920 --> 00:12:24,120
DRUG DEVELOPMENT BY REPLACING

346
00:12:24,120 --> 00:12:25,640
ANIMAL TEST E. CXFCG. CXFC BEWE

347
00:12:25,640 --> 00:12:26,680
REALIZED THESE CHIPS PROVIDE A

348
00:12:26,680 --> 00:12:28,000
WINDOW ON MOLECULAR SCALE

349
00:12:28,000 --> 00:12:29,280
ACTIVITIES INSIDE THE LIVING

350
00:12:29,280 --> 00:12:31,480
CELLS WITHIN A RELEVANT TISSUE

351
00:12:31,480 --> 00:12:33,760
AND ORGAN LEVEL CONTEXT. AND

352
00:12:33,760 --> 00:12:36,440
THAT'S THEY POTENTIALLY ENABLE

353
00:12:36,440 --> 00:12:37,840
MECHANISTIC INSIGHTS AND DRUG

354
00:12:37,840 --> 00:12:38,840
DISCOVERY AND AT THE SAME TIME

355
00:12:38,840 --> 00:12:40,680
PROVIDE EXPERIMENTALLY TEST

356
00:12:40,680 --> 00:12:42,040
PREDICTIONS WE HAVE, ALL THE

357
00:12:42,040 --> 00:12:46,720
HUMAN RELEVANT MODEL. ABOUT

358
00:12:46,720 --> 00:12:49,400
2017, WE WERE FUNDED BY DARPA

359
00:12:49,400 --> 00:12:51,440
AND NIH TO LEVERAGE OUR AIRWAY

360
00:12:51,440 --> 00:12:53,440
CHIPS TO DEVELOP MODELS OF VIRAL

361
00:12:53,440 --> 00:12:54,280
INFECTION AND THERE WAS GREAT

362
00:12:54,280 --> 00:12:55,760
INTEREST AT THAT TIME IN

363
00:12:55,760 --> 00:12:57,200
POTENTIAL PANDEMIC RESPIRATORY

364
00:12:57,200 --> 00:12:59,440
VIRUSES BUT THE FOCUS WAS ON

365
00:12:59,440 --> 00:13:01,680
INFLUENZA. SO WE TOOK OUR AIRWAY

366
00:13:01,680 --> 00:13:04,640
CHIP FOR EXAMPLE, THIS IS GFP

367
00:13:04,640 --> 00:13:07,560
LABELED H 1N 1 INFLUENZA AND YOU

368
00:13:07,560 --> 00:13:09,040
CAN WATCH CELLS INFECTED REAL

369
00:13:09,040 --> 00:13:12,640
TYPE ON THE CHIP. YOU CAN YOU

370
00:13:12,640 --> 00:13:14,200
HAVE BEAUTIFUL MORPHOLOGICAL

371
00:13:14,200 --> 00:13:17,680
READ OUTS OF INFECTION GFP VIRUS

372
00:13:17,680 --> 00:13:19,040
AT THE BOTTOM LEFT YOU LOSE

373
00:13:19,040 --> 00:13:21,880
JUNCTIONS, CILIA, YOU CAN SEE

374
00:13:21,880 --> 00:13:23,440
ENDOTHELIAL DAMAGE. WE DID

375
00:13:23,440 --> 00:13:25,480
DIFFERENT VIRAL STRAINS AND YOU

376
00:13:25,480 --> 00:13:27,720
CAN SEE VIRAL STRAIN DEPENDENT

377
00:13:27,720 --> 00:13:31,480
EFFECTS IN TERMS OF REPLICATION

378
00:13:31,480 --> 00:13:33,360
AND DIFFERENT VIRULENCE IS

379
00:13:33,360 --> 00:13:34,760
MIMICKED IN THESE CHIPS, THE

380
00:13:34,760 --> 00:13:36,040
SAME DIFFERENCES VIRULENCE YOU

381
00:13:36,040 --> 00:13:39,160
SEE IN PATIENTS BETWEEN H 1N 1

382
00:13:39,160 --> 00:13:41,800
AND H 5N 1, WE CAN BEGIN TO

383
00:13:41,800 --> 00:13:44,560
EXPLORE EFFECTS OF CO-MORBIDITY.

384
00:13:44,560 --> 00:13:46,880
SO WE DID THE SAME STUDY WITH

385
00:13:46,880 --> 00:13:49,120
COPD CHIPS AND SEE TENFOLD

386
00:13:49,120 --> 00:13:50,480
HIGHER INCREASE IN VIRAL

387
00:13:50,480 --> 00:13:52,120
REPLICATION COPD PATIENTS ARE

388
00:13:52,120 --> 00:13:53,480
MORE SENSITIVE TO INFLUENZA

389
00:13:53,480 --> 00:13:55,720
INFECTION. PERHAPS MOST

390
00:13:55,720 --> 00:13:57,400
IMPORTANTLY WE CAN MEASURE HOST

391
00:13:57,400 --> 00:13:59,280
RESPONSE TO INFECTION AND DRUGS

392
00:13:59,280 --> 00:14:01,880
IN TERMS OF WHAT IS A BASICALLY

393
00:14:01,880 --> 00:14:05,120
A CYTOKINE STORM USING COVID

394
00:14:05,120 --> 00:14:07,400
TERMS, THESE ARE IL 6 IP 10 AND

395
00:14:07,400 --> 00:14:10,000
FOUR OTHER CYTOKINES IN RESPONSE

396
00:14:10,000 --> 00:14:12,360
TO THREE TYPES OF INFLUENZA AND

397
00:14:12,360 --> 00:14:14,880
ONCE AGAIN THE CYTOKINE RESPONSE

398
00:14:14,880 --> 00:14:16,840
MATCHES THE DEGREE OF VIRULENCE

399
00:14:16,840 --> 00:14:18,080
SEEN IN PATIENTS. WE CAN DO

400
00:14:18,080 --> 00:14:19,400
IMMUNE CELL RECRUITMENT AND IN

401
00:14:19,400 --> 00:14:20,880
THIS CASE WE WATCHED IMMUNE

402
00:14:20,880 --> 00:14:22,760
CELLS MIGRATE INTO THE

403
00:14:22,760 --> 00:14:25,320
EPITHELIUM AND CLEAR THE VIRALLY

404
00:14:25,320 --> 00:14:26,360
INFECTED CELLS OVER COUPLE OF

405
00:14:26,360 --> 00:14:31,000
DAYS. THEN WE TESTED DRUGS SO

406
00:14:31,000 --> 00:14:33,560
TAMI FLU, THE MOST COMMON IS

407
00:14:33,560 --> 00:14:34,800
ANTI-INFLUENZA DRUG. WE SEE

408
00:14:34,800 --> 00:14:36,720
BEAUTIFUL IN ADDITION ON THE

409
00:14:36,720 --> 00:14:38,720
CHIPS, OVER THE SAME TWO DAYTIME

410
00:14:38,720 --> 00:14:40,640
COURSE THE FDA HAS APPROVED THIS

411
00:14:40,640 --> 00:14:44,600
DRUG IN PATIENTS. INTERESTINGLY

412
00:14:44,600 --> 00:14:49,080
WE ALSO CAN MODEL EVOLUTION OF

413
00:14:49,080 --> 00:14:50,880
VARIANTS OF CONCERN IF YOU LIKE

414
00:14:50,880 --> 00:14:53,080
ON THESE CHIPS. THIS STUDY WE

415
00:14:53,080 --> 00:14:54,640
TOOK A HUMAN AIRWAY CHIP WE

416
00:14:54,640 --> 00:14:56,880
INFECTED IT WITH INFLUENZA, AND

417
00:14:56,880 --> 00:14:59,360
WE GAVE IT A DRUG AT 90%

418
00:14:59,360 --> 00:15:02,440
EFFICACY LEVEL. IN THIS CASE WE

419
00:15:02,440 --> 00:15:05,960
DID AMANTADINE AND AFTER COUPLE

420
00:15:05,960 --> 00:15:07,800
OF DAYS WASHED THE DROPLETS AND

421
00:15:07,800 --> 00:15:09,920
PASSED TO AIR SPACE OF ANOTHER

422
00:15:09,920 --> 00:15:11,440
CHIP LIKE SOMEBODY WAS COUGHING

423
00:15:11,440 --> 00:15:12,520
HUMAN TO HUMAN TRANSMISSION. WE

424
00:15:12,520 --> 00:15:15,280
DID IT AGAIN AND AGAIN. WITH

425
00:15:15,280 --> 00:15:18,640
IMANTADINE IN EIGHT PASSAGES WE

426
00:15:18,640 --> 00:15:19,920
GOT RESISTANT VIRAL VAINS WHEN

427
00:15:19,920 --> 00:15:21,800
WE DID GENOME SEQUENCING WE

428
00:15:21,800 --> 00:15:22,880
IDENTIFIED ALL KNOWN MUTATIONS

429
00:15:22,880 --> 00:15:24,320
PUBLISHED IN THE LITERATURE

430
00:15:24,320 --> 00:15:26,320
BASED ON CLINICAL EXAMPLES

431
00:15:26,320 --> 00:15:28,960
PATIENTS BECAME RESISTANT.

432
00:15:28,960 --> 00:15:30,640
CLOSELY IDENTIFIED MULTIPLE

433
00:15:30,640 --> 00:15:33,160
MUTATIONS NEVER SEEN BEFORE. SO

434
00:15:33,160 --> 00:15:35,800
THIS COULD IDENTIFY VARIANTS OF

435
00:15:35,800 --> 00:15:37,800
CONCERN COMING DOWN THE PIKE FOR

436
00:15:37,800 --> 00:15:39,160
VACCINE AND THERAPEUTIC

437
00:15:39,160 --> 00:15:40,920
DEVELOPMENT. WE DID THIS WITH

438
00:15:40,920 --> 00:15:43,200
TAMI FLU, 25 OR 28 PASSAGES WE

439
00:15:43,200 --> 00:15:46,480
ALSO GOT RESISTANT VIRAL MUTANTS

440
00:15:46,480 --> 00:15:50,040
WHICH WAS TERRIFYING. NOW, THE

441
00:15:50,040 --> 00:15:52,560
REASON I SHOWED YOU THE COPD

442
00:15:52,560 --> 00:15:55,080
PAPER, THIS LAUNCHED US TO BEGIN

443
00:15:55,080 --> 00:15:57,120
TO LOOK AT DRAPERY PURPOSING FOR

444
00:15:57,120 --> 00:15:58,720
VIRAL -- DRUG REPURPOSES FOR

445
00:15:58,720 --> 00:16:00,240
VIRAL INFECTION. WE NOTICE

446
00:16:00,240 --> 00:16:03,960
UPREGULATION OF MULTIPLE SERENE

447
00:16:03,960 --> 00:16:05,760
PROTEASES AND ABOUT THESE ARE

448
00:16:05,760 --> 00:16:08,080
HOST SERENE PROTEASES TO TARGET

449
00:16:08,080 --> 00:16:10,200
HOST RATHER THAN VIRUS AND

450
00:16:10,200 --> 00:16:11,720
THERE'S BEEN SOME PAST WORK TO

451
00:16:11,720 --> 00:16:15,320
SUGGEST THAT SO WE TOOK TWO

452
00:16:15,320 --> 00:16:16,920
EXISTING DRUGS, ANTI-COAGULANT

453
00:16:16,920 --> 00:16:20,000
AND TRAZAWOL BOTH GENERAL

454
00:16:20,000 --> 00:16:21,640
PROTEASE INHIBITORS AND WE HAVE

455
00:16:21,640 --> 00:16:24,040
BEAUTIFUL INFECTION OF H 1N 1 H

456
00:16:24,040 --> 00:16:25,200
3N 2 BY BOTH OF THESE ON THE

457
00:16:25,200 --> 00:16:27,880
CHIPS.  BUT WHAT WAS REALLY

458
00:16:27,880 --> 00:16:32,800
EXCITING IS THAT WE CAN TAKE

459
00:16:32,800 --> 00:16:34,840
NAFAMOSTAT AND COMBINE IT WITH

460
00:16:34,840 --> 00:16:37,040
TAMIFLU AND DOUBLE TAMI FLU

461
00:16:37,040 --> 00:16:39,680
THERAPEUTIC WINDOW FROM 48 TO 96

462
00:16:39,680 --> 00:16:41,160
HOURS WHICH COULD HAVE REAL

463
00:16:41,160 --> 00:16:44,040
CLINICAL RELEVANCE GIVEN TAMI

464
00:16:44,040 --> 00:16:45,600
FLU IS ONLY APPROVED FOR 48

465
00:16:45,600 --> 00:16:47,640
HOURS. THIS IS WHEN COVID HIT

466
00:16:47,640 --> 00:16:51,880
END OF JANUARY 2020. I HAVE TWO

467
00:16:51,880 --> 00:16:53,680
VIROLOGISTS POST DOCS WHO ARE

468
00:16:53,680 --> 00:16:54,800
FROM CHINA FOLLOWING THIS ON

469
00:16:54,800 --> 00:16:56,760
SOCIAL MEDIA. WITHIN ONE DAY

470
00:16:56,760 --> 00:16:58,320
AFTER THE PUBLICATION OF THE

471
00:16:58,320 --> 00:17:00,400
GENOME SEQUENCING SARS COV-2 IN

472
00:17:00,400 --> 00:17:03,200
SCIENCE, THEY ENGINEERED A SARS

473
00:17:03,200 --> 00:17:05,960
COV-2 SPIKE PROTEIN EXPRESSING

474
00:17:05,960 --> 00:17:06,840
PSEUDOTYPE VIRUS BECAUSE WE ONLY

475
00:17:06,840 --> 00:17:09,440
HAVE A BSL 2 LAB. THEY ALSO HAD

476
00:17:09,440 --> 00:17:11,240
BEEN SEARCHING THROUGH THE

477
00:17:11,240 --> 00:17:12,720
LITERATURE TO QUICKLY MAYBE TAKE

478
00:17:12,720 --> 00:17:15,880
EXISTING APPROVED DRUG TO USE

479
00:17:15,880 --> 00:17:17,520
FOR THIS INCREDIBLE CLONALITY

480
00:17:17,520 --> 00:17:21,880
HAPPENING AT THAT TIME AND THEY

481
00:17:21,880 --> 00:17:22,680
IDENTIFIED 30 DRUGS SHOWN

482
00:17:22,680 --> 00:17:24,680
REPORTED ACTIVITIES AGAINST

483
00:17:24,680 --> 00:17:27,640
EBOLA, MRS OR SARS COVE 1 AND

484
00:17:27,640 --> 00:17:29,880
TESTED THEM IN PA CELL LINE THEY

485
00:17:29,880 --> 00:17:32,840
DID IN GRADUATE WORK THAT

486
00:17:32,840 --> 00:17:35,000
VIROLOGISTS USE LIVER CELL LINE

487
00:17:35,000 --> 00:17:36,200
ACTUALLY. AND YOU CAN SEE THE

488
00:17:36,200 --> 00:17:38,080
EIGHT DRUGS THAT SHOWED DOSE

489
00:17:38,080 --> 00:17:41,280
DEPENDENT INHIBITION IN THE LOW

490
00:17:41,280 --> 00:17:42,240
MICROMOLAR RANGE. THIS IS

491
00:17:42,240 --> 00:17:47,120
FEBRUARY OF 2020.

492
00:17:47,120 --> 00:17:47,720
HYDROXYCHLOROQUINE AND COLOR

493
00:17:47,720 --> 00:17:51,160
QUINN AMONG THESE EIGHT. WE THEN

494
00:17:51,160 --> 00:17:53,880
THOUGHT WE SHOULD TEST THESE IN

495
00:17:53,880 --> 00:17:57,400
OUR HUMAN LUNG AIRWAY CHIPS. I

496
00:17:57,400 --> 00:18:01,760
SHOULD NOTE H 287 OFTEN USED BY

497
00:18:01,760 --> 00:18:03,080
VIROLOGISTS HAVE NORMAL

498
00:18:03,080 --> 00:18:04,200
INTERFERON VIRUSES THAT'S WHY

499
00:18:04,200 --> 00:18:05,400
VIRUSES GROW WELL, THEY DON'T

500
00:18:05,400 --> 00:18:07,360
HAVE THE RIGHT RECEPTORS FOR

501
00:18:07,360 --> 00:18:10,120
CERTAIN VIRUSES LIKE SARS COV-2

502
00:18:10,120 --> 00:18:11,840
SO WE CONFIRMED THAT THE HUMAN

503
00:18:11,840 --> 00:18:13,240
LUNG AIRWAY CELLS WHEN

504
00:18:13,240 --> 00:18:14,440
DIFFERENTIATE HAVE HIGH LEVELS

505
00:18:14,440 --> 00:18:17,960
OF ACE 2 AND TMPRSS 2, PROTEASE

506
00:18:17,960 --> 00:18:21,480
AND RECEPTOR CRITICAL FOR COV 2

507
00:18:21,480 --> 00:18:23,360
INFECTION. WE CONFIRMED OUR

508
00:18:23,360 --> 00:18:25,800
PSEUDOTYPE VIRUS BINDS TO CILIA

509
00:18:25,800 --> 00:18:27,720
WHICH JUST WAS REPORTED IN VIVO

510
00:18:27,720 --> 00:18:30,200
IN LUNGS AS WELL. THIS IS ON OUR

511
00:18:30,200 --> 00:18:32,360
CHIPS TOP VIEW AND CROSS

512
00:18:32,360 --> 00:18:35,680
SECTIONAL VIEW. AND NOW WE

513
00:18:35,680 --> 00:18:37,000
INSTEAD OF BATHING THE CELL IN

514
00:18:37,000 --> 00:18:39,200
DRUG WE FLOW THE DRUG THROUGH AT

515
00:18:39,200 --> 00:18:41,120
CLINICALLY RELEVANT DOSE CMAX

516
00:18:41,120 --> 00:18:44,680
THROUGH THE CHIP. WE FIND

517
00:18:44,680 --> 00:18:45,640
HYDROXYCHLOROQUINE HAVE NO

518
00:18:45,640 --> 00:18:47,000
EFFECT NOR A NEW OTHER DRUGS

519
00:18:47,000 --> 00:18:48,800
TESTED IN CLINIC THAT WERE NOT

520
00:18:48,800 --> 00:18:50,280
EFFECTIVE. AND WE FOUND A COUPLE

521
00:18:50,280 --> 00:18:53,280
OF DRUGS THAT SHOWED MORE POTENT

522
00:18:53,280 --> 00:18:57,920
ACTIVITY WITH AMADAQUIN ANOTHER

523
00:18:57,920 --> 00:18:59,920
ANTI-MALARIA IN AFRICA FOR YEARS

524
00:18:59,920 --> 00:19:01,800
IN PARTICULAR KIDS WITH

525
00:19:01,800 --> 00:19:03,040
PROPHYLAXIS FOR MALARIA WAS

526
00:19:03,040 --> 00:19:08,600
SIGNIFICANTLY EFFECTI EFFECT EFE

527
00:19:08,600 --> 00:19:09,520
DATA I HAVE BEEN COMMUNICATING

528
00:19:09,520 --> 00:19:13,040
WITH PEOPLE AT GATES AND DARPA

529
00:19:13,040 --> 00:19:14,280
AND THIS TRIGGERED US TO GET

530
00:19:14,280 --> 00:19:17,040
FUNDING FROM DARPA TO DEVELOP A

531
00:19:17,040 --> 00:19:18,880
LARGER DRUG REPURPOSING PROGRAM

532
00:19:18,880 --> 00:19:20,360
THAT NOT ONLY LEVERAGE WHAT WE

533
00:19:20,360 --> 00:19:21,440
HAD DONE THERE BUT OTHER

534
00:19:21,440 --> 00:19:22,920
TECHNOLOGIES WE DEVELOPED IN MY

535
00:19:22,920 --> 00:19:25,680
LAB FOR DRUG REPURPOSING, ONE

536
00:19:25,680 --> 00:19:26,800
USING MOLECULAR DYNAMIC

537
00:19:26,800 --> 00:19:28,920
SIMULATION AN STRUCTURAL

538
00:19:28,920 --> 00:19:29,760
SIMILARITY AND STRUCTURE

539
00:19:29,760 --> 00:19:31,720
ACTIVITY RELATIONSHIPS WITH

540
00:19:31,720 --> 00:19:33,120
MEDICINAL CHEMISTRY. THE OTHER

541
00:19:33,120 --> 00:19:35,360
IS MACHINE LEARNING AND SORT OF

542
00:19:35,360 --> 00:19:37,480
NETWORK ANALYSIS COMPUTATIONAL

543
00:19:37,480 --> 00:19:40,560
PATHWAY CALLED NEMOCUT THAT

544
00:19:40,560 --> 00:19:42,000
STARTS WITH TRANSCRIPTOMIC DATA

545
00:19:42,000 --> 00:19:45,200
FOR PATIENTS, I WILL GO INTO

546
00:19:45,200 --> 00:19:46,720
MORE. THEY LINK ME --

547
00:19:46,720 --> 00:19:47,960
COLLABORATED WITH MATT FREEMAN,

548
00:19:47,960 --> 00:19:52,840
UNIVERSITY OF MARYLAND EXPERT IN

549
00:19:52,840 --> 00:19:56,440
CORONA VIRUS AND HAS BSL 3 AND

550
00:19:56,440 --> 00:19:59,200
TENANT OVER AT MOUNT SINAI WHO

551
00:19:59,200 --> 00:20:00,560
DEVELOPED HAMSTER SARS COV-2

552
00:20:00,560 --> 00:20:02,280
MODELS.  THE FIRST THING WE DID

553
00:20:02,280 --> 00:20:08,480
IS CONFIRM THAT AMODAAQUIN DOES

554
00:20:08,480 --> 00:20:10,760
AFFECT POTENTLY NATIVE SARS

555
00:20:10,760 --> 00:20:12,880
COV-2, METABOLITE HAS ACTIVITY.

556
00:20:12,880 --> 00:20:15,000
BEEN CONFIRMED THAT WE HAVE

557
00:20:15,000 --> 00:20:17,200
GREATER ACTIVITY IN HUMAN 8549

558
00:20:17,200 --> 00:20:19,600
CELLS EXPRESSING ACE 2 BUT THEN

559
00:20:19,600 --> 00:20:21,720
HE TESTED THE DRUG IN HAMSTER

560
00:20:21,720 --> 00:20:24,200
MODEL AND WHEN YOU CAN SEE HERE

561
00:20:24,200 --> 00:20:27,240
IS NOT HYDROXY COLOR QUINN,

562
00:20:27,240 --> 00:20:28,840
INHIBITS INFECTION BY SARS COV-2

563
00:20:28,840 --> 00:20:30,320
AND ADDED ONE DAY BEFORE

564
00:20:30,320 --> 00:20:32,680
INFECTION PROPHYLACTICICALLY

565
00:20:32,680 --> 00:20:35,480
POTENT INHIBITION FROM ANIMAL TO

566
00:20:35,480 --> 00:20:37,360
MAN MALL TRANSMISSION AND

567
00:20:37,360 --> 00:20:38,720
INHIBITS WHEN YOU START

568
00:20:38,720 --> 00:20:40,240
TREATMENT AFTERWARDS. IN PART

569
00:20:40,240 --> 00:20:41,280
THIS DATA THIS DRUG IS NOW IN

570
00:20:41,280 --> 00:20:42,840
CLINICAL TRIALS ACROSS 20 SITES

571
00:20:42,840 --> 00:20:48,360
IN AFRICA FOR COVID-19. MORE

572
00:20:48,360 --> 00:20:50,560
RECENTLY, WE DID WORK THAT WAS

573
00:20:50,560 --> 00:20:52,760
MORE MECHANISTIC FOCUSED, WE

574
00:20:52,760 --> 00:20:55,520
WERE LOOKING AT H 3N 2 INFLUENZA

575
00:20:55,520 --> 00:20:57,280
INFECTION BECAUSE WE FOUND THAT

576
00:20:57,280 --> 00:21:01,640
WAS A BETTER MODEL OF PNEUMONIA

577
00:21:01,640 --> 00:21:04,320
IF YOU LIKE AND CLOSER TO COV 2

578
00:21:04,320 --> 00:21:09,720
THAN COVID-19 THAN OTHER

579
00:21:09,720 --> 00:21:11,640
UNRELATED COLD VIRUSES THAT ARE

580
00:21:11,640 --> 00:21:14,920
CORONA VIRUS. AND MY POST DOC

581
00:21:14,920 --> 00:21:16,520
NOTICED DID EXPERIMENT DID WITH

582
00:21:16,520 --> 00:21:18,400
AND WITHOUT BREATHING MOTIONS IN

583
00:21:18,400 --> 00:21:21,320
THE ALVEOLUS CHIP AND HE FOUND

584
00:21:21,320 --> 00:21:24,200
THAT BREATHING SUPPRESSED VIRAL

585
00:21:24,200 --> 00:21:25,880
INFECTION DRAMATICALLY,

586
00:21:25,880 --> 00:21:27,280
PHYSIOLOGICAL BREATHING MOTIONS

587
00:21:27,280 --> 00:21:30,320
AND SUPPRESSED CYTOKINE

588
00:21:30,320 --> 00:21:31,400
INFLAMMATORY RESPONSE BASICALLY

589
00:21:31,400 --> 00:21:33,080
STIMULATED THE INNATE IMMUNE

590
00:21:33,080 --> 00:21:35,520
RESPONSE. WE DID SINGLE CELL RNA

591
00:21:35,520 --> 00:21:39,000
-- I'M SORRY, WE DID BOTH RNA

592
00:21:39,000 --> 00:21:40,720
SEQ AND HE NOTICED THERE WAS ONE

593
00:21:40,720 --> 00:21:43,520
GENE THAT CAME UP WITH BREATHING

594
00:21:43,520 --> 00:21:46,200
MORE THAN ANY OTHERS CALLED S

595
00:21:46,200 --> 00:21:48,560
100A 7 WHICH IS A LIGAND FOR THE

596
00:21:48,560 --> 00:21:50,400
RAGE RECEPTOR, THE RAGE WHICH IS

597
00:21:50,400 --> 00:21:52,600
THE RECEPTOR FOR ADVANCE

598
00:21:52,600 --> 00:21:53,800
GLYCATION PRODUCTS WHICH IS A

599
00:21:53,800 --> 00:21:57,160
MAJOR PLAYER IN INFLAMMATION,

600
00:21:57,160 --> 00:21:58,640
MOST HIGHLY EXPRESSED IN

601
00:21:58,640 --> 00:22:01,000
ALVEOLAR CELLS. SO WE RETAINED A

602
00:22:01,000 --> 00:22:03,200
DRUG A RAGE INHIBITOR AND

603
00:22:03,200 --> 00:22:04,640
INHIBITED THE CYTOKINE STORM IF

604
00:22:04,640 --> 00:22:06,840
YOU LIKE INDUCED BY VIRAL

605
00:22:06,840 --> 00:22:09,840
INFECTION IN THESE CHIPS. AND IT

606
00:22:09,840 --> 00:22:12,680
WAS IN PHASE 3 CLINICAL TRIALS,

607
00:22:12,680 --> 00:22:13,800
2000 PATIENTS COMPLETELY SAFE

608
00:22:13,800 --> 00:22:16,000
ORAL DRUG HIGHLY BIOAVAILABLE,

609
00:22:16,000 --> 00:22:18,560
IT WAS IN CLINICAL TRIALS FOR

610
00:22:18,560 --> 00:22:20,160
ALZHEIMER'S WHICH DID NOT HIT

611
00:22:20,160 --> 00:22:22,400
THE MARK BUT BASED ON THESE DATA

612
00:22:22,400 --> 00:22:24,560
AND EXTENSIVE LITERATURE

613
00:22:24,560 --> 00:22:28,400
SUPPORT, WE LICENSED THIS IP

614
00:22:28,400 --> 00:22:30,640
DISCOVERY TO CTEX PHARMA, THESE

615
00:22:30,640 --> 00:22:34,000
VERY DATA WERE INCLUDED IN IND

616
00:22:34,000 --> 00:22:35,600
APPLICATION INVATIONAL NEW DRUG

617
00:22:35,600 --> 00:22:37,520
APPLICATION TO THE FDA TO START

618
00:22:37,520 --> 00:22:39,320
COVID-19 TRIALS WHICH IS UNDER

619
00:22:39,320 --> 00:22:42,200
REVIEW RIGHT NOW. I MENTIONED

620
00:22:42,200 --> 00:22:45,600
THESE OTHER COMPUTATIONAL, WE

621
00:22:45,600 --> 00:22:47,880
USED A COMPUTATIONAL PIPELINE,

622
00:22:47,880 --> 00:22:50,320
WE DEVELOPED AT THE WYSS

623
00:22:50,320 --> 00:22:53,920
INSTITUTE TO STUDY THE SPIKE

624
00:22:53,920 --> 00:22:55,240
PROTEIN AND WHEN WE FOUND IS

625
00:22:55,240 --> 00:22:57,160
THAT IT HAS TO UNDERGO MAJOR

626
00:22:57,160 --> 00:22:58,400
OPENING SHOWN AT THE BOTTOM

627
00:22:58,400 --> 00:23:02,600
RIGHT IN THIS MOVIE, TO BIND TH

628
00:23:02,600 --> 00:23:04,120
2 -- MEDIATE FUSION WHEN IT

629
00:23:04,120 --> 00:23:05,800
BINDS TO ACE 2 RECEPTOR AND WE

630
00:23:05,800 --> 00:23:09,000
WERE ABLE TO IDENTIFY A

631
00:23:09,000 --> 00:23:09,880
CONSERVED SITE INSIDE THE

632
00:23:09,880 --> 00:23:13,800
MOLECULE THAT IS NOT INNATE SITE

633
00:23:13,800 --> 00:23:15,600
WHERE ANTIBODIES HIT THAT IS

634
00:23:15,600 --> 00:23:18,040
ALSO IN MANY OTHER CORONA VIRUS,

635
00:23:18,040 --> 00:23:20,760
ALL OTHER CORONA VIRUS THAT WE

636
00:23:20,760 --> 00:23:21,680
FELT IF WE CAN DESIGN MOLECULE

637
00:23:21,680 --> 00:23:23,440
TO HIT THAT SITE WE MIGHT BE

638
00:23:23,440 --> 00:23:28,360
ABLE TO INHIBIT INITIAL INFEC 

639
00:23:28,360 --> 00:23:30,440
INFECTION. WE USE THAT MODEL TO

640
00:23:30,440 --> 00:23:32,160
LOOK LIEU EXISTING APPROVED

641
00:23:32,160 --> 00:23:33,720
DRUGS TO SEE IF THERE'S ANY THAT

642
00:23:33,720 --> 00:23:34,760
BIND THAT SITE AND WE IDENTIFIED

643
00:23:34,760 --> 00:23:36,480
A COUPLE AND WE CAN SHOW THAT

644
00:23:36,480 --> 00:23:40,480
THEY INHIBIT THE SPIKE PROTEIN

645
00:23:40,480 --> 00:23:42,440
COV 2 SPIKE PROTEIN ENTRY. WE

646
00:23:42,440 --> 00:23:45,320
USE MEDICINAL CHEMISTRY TO

647
00:23:45,320 --> 00:23:48,160
DEVELOP NEWER VERSIONS OF THIS

648
00:23:48,160 --> 00:23:49,640
THAT WE HAVE SYNTHETIC ANALOG

649
00:23:49,640 --> 00:23:51,520
THAT ARE EVEN A LITTLE BIT MORE

650
00:23:51,520 --> 00:23:52,680
POTENT. THEN WE HAVE OPTIMIZED

651
00:23:52,680 --> 00:23:55,720
WITH FUNDING FROM NIH DARPA AND

652
00:23:55,720 --> 00:23:58,520
OPEN PHILANTHROPY AND WE NOW

653
00:23:58,520 --> 00:24:00,840
HAVE SYNTHETIC COMPOUNDS THAT

654
00:24:00,840 --> 00:24:03,520
INHIBIT ALL OF THE PSEUDOTYPE

655
00:24:03,520 --> 00:24:07,360
VIRUSES OF ALPHA BETA DELTA

656
00:24:07,360 --> 00:24:11,800
GAMMA OMICRON ALSO SARS COV 1

657
00:24:11,800 --> 00:24:14,800
AND MRSS, IT WORKS AGAINST

658
00:24:14,800 --> 00:24:18,920
NATIVE COV 2 IN BSL 3 LAB WITH

659
00:24:18,920 --> 00:24:21,040
150 NANOMOLAR IC 50 AND GREAT

660
00:24:21,040 --> 00:24:22,560
BIOAVAILABILITY SO WE ARE NOW

661
00:24:22,560 --> 00:24:24,600
MOVING THIS INTO ANIMAL EFFICACY

662
00:24:24,600 --> 00:24:26,280
STUDIES WITH THE HOPE OF HAVING

663
00:24:26,280 --> 00:24:29,400
ORAL PROPHYLACTIC IF YOU LIKE. 

664
00:24:29,400 --> 00:24:32,600
THE OTHER COMPUTATIONAL NETWORK

665
00:24:32,600 --> 00:24:35,840
ANALYSIS PREDICTION I

666
00:24:35,840 --> 00:24:38,560
MENTIONEDDED STARTS WITH

667
00:24:38,560 --> 00:24:40,920
TRANSCRIPTOMES FROM PATIENTS

668
00:24:40,920 --> 00:24:43,040
WITH COVID VERSUS HEALTHY. AND

669
00:24:43,040 --> 00:24:45,760
BASICALLY TRIES TO SEE WHAT

670
00:24:45,760 --> 00:24:47,880
GENES AND WHAT NETWORK

671
00:24:47,880 --> 00:24:49,720
TOPOLOGIES OR NETWORK

672
00:24:49,720 --> 00:24:52,400
RELATIONSHIPS HAVE TO CHANGE TO

673
00:24:52,400 --> 00:24:55,160
MAKE A DISEASE PHENOTYPE OR

674
00:24:55,160 --> 00:24:56,280
STATE SWITCH TO HEALTHY STATE.

675
00:24:56,280 --> 00:25:00,640
AND THEN IT LOOKS FOR DRUGS THAT

676
00:25:00,640 --> 00:25:02,640
HAVE KNOWN TRANSCRIPTIONAL

677
00:25:02,640 --> 00:25:04,320
SIGNATURES PUBLISHED IN

678
00:25:04,320 --> 00:25:05,880
DATABASES, GOES THROUGH THEM,

679
00:25:05,880 --> 00:25:07,120
AND ESSENTIALLY SEARCHES LIEU

680
00:25:07,120 --> 00:25:09,240
FOR DRUGS THAT ARE HIGHLY LIKELY

681
00:25:09,240 --> 00:25:11,320
TO REVERSE THAT STATE. WE FOUND

682
00:25:11,320 --> 00:25:13,760
DRUGS, THEY SHOWED EFFICACY

683
00:25:13,760 --> 00:25:16,120
AGAINST SARS COV-2 IN IN VITRO

684
00:25:16,120 --> 00:25:17,360
MODELS BUT ONE THING THAT CAME

685
00:25:17,360 --> 00:25:18,800
UP WAS THAT IT PREDICTED

686
00:25:18,800 --> 00:25:20,800
MULTIPLE STATINS WHICH IS LIKE

687
00:25:20,800 --> 00:25:24,040
ONE OF THE MOST POPULARLY USED

688
00:25:24,040 --> 00:25:26,280
DRUG AND SAFE DRUG, MULTIPLE

689
00:25:26,280 --> 00:25:30,600
STATINS WERE PREDICTED TO HAVE

690
00:25:30,600 --> 00:25:32,720
COVID REVERSING OR PROTECTING

691
00:25:32,720 --> 00:25:35,480
ACTIVITY, BUT THEY NOT ALL

692
00:25:35,480 --> 00:25:36,560
STATINS WERE THE SAME SUGGESTING

693
00:25:36,560 --> 00:25:39,400
THIS MIGHT NOT BE RELATED TO ITS

694
00:25:39,400 --> 00:25:41,720
KNOWN LIPID METABOLISM ACTIVITY.

695
00:25:41,720 --> 00:25:45,160
AND WE ALSO FOUND FOR EXAMPLE

696
00:25:45,160 --> 00:25:47,760
STATIN CAME UP AGAIN AND AGAIN.

697
00:25:47,760 --> 00:25:49,800
SIMVA STATIN DEMONSTRATED DIRECT

698
00:25:49,800 --> 00:25:52,680
INHIBITION OF SARS COV-2

699
00:25:52,680 --> 00:25:55,120
INFECTION IN VITRO AND EVEN

700
00:25:55,120 --> 00:25:56,120
INACTIVE METABOLITE HAD

701
00:25:56,120 --> 00:25:58,920
ACTIVITY. SO WE ARE UNCOVERING

702
00:25:58,920 --> 00:26:00,840
WE DO REPURPOSING ACTIVITIES

703
00:26:00,840 --> 00:26:02,600
THAT ARE NOT THE KNOWN TARGETS

704
00:26:02,600 --> 00:26:04,440
AND THIS HAS HAPPENED AGAIN AND

705
00:26:04,440 --> 00:26:06,320
AGAIN. NOW, RECENTLY WE

706
00:26:06,320 --> 00:26:09,520
COLLABORATED WITH MARIA SIROPTA

707
00:26:09,520 --> 00:26:11,880
AND OTHERS AT STANFORD WHO

708
00:26:11,880 --> 00:26:13,520
ANALYZED OVER 4,000 PATIENTS SO

709
00:26:13,520 --> 00:26:16,440
WE DID A RETROSPECTIVE ANALYSIS,

710
00:26:16,440 --> 00:26:18,440
INDEED WE CONFIRM THAT THERE ARE

711
00:26:18,440 --> 00:26:20,040
SIGNIFICANT DIFFERENCES BETWEEN

712
00:26:20,040 --> 00:26:23,080
DIFFERENT STATINS IF YOU LOOK IN

713
00:26:23,080 --> 00:26:27,360
RED HERE, TORVA STATIN AND SIMVA

714
00:26:27,360 --> 00:26:28,840
STATIN, DO PROTECT BUT OTHERS DO

715
00:26:28,840 --> 00:26:31,400
NOT. SO AGAIN THIS WAS

716
00:26:31,400 --> 00:26:33,360
ORIGINALLY COVERED BETWEEN

717
00:26:33,360 --> 00:26:35,040
COMPUTATIONAL APPROACH AND OUR

718
00:26:35,040 --> 00:26:38,080
IN VITRO MODELS. LASTLY, IN THE

719
00:26:38,080 --> 00:26:41,080
COURSE OF WORKING ON THE

720
00:26:41,080 --> 00:26:42,880
INTERFERON INFECTION WE CARRIED

721
00:26:42,880 --> 00:26:45,840
OUT STUDIES WITH A CRISPR SCREEN

722
00:26:45,840 --> 00:26:49,520
AND WE WERE ABLE TO IDENTIFY

723
00:26:49,520 --> 00:26:52,440
SHORT DUPLEX RNAs, ORIGINAL

724
00:26:52,440 --> 00:26:53,600
LIKING FOR LONG NON-CODING

725
00:26:53,600 --> 00:26:55,960
RNAs THAT ARE POTENT INDUCERS

726
00:26:55,960 --> 00:26:58,840
OF TYPE 1 INTERFERON LIKE

727
00:26:58,840 --> 00:27:01,040
INTERFERON BETHAT ARE PROTECTIVE

728
00:27:01,040 --> 00:27:02,240
INTERFERONS. AND FURTHER

729
00:27:02,240 --> 00:27:05,040
ANALYSIS REALIZE THAT WE WEREN'T

730
00:27:05,040 --> 00:27:06,560
WORKING THROUGH LONG NON-CODING

731
00:27:06,560 --> 00:27:08,640
RNAs, IT WAS ACTUALLY THE

732
00:27:08,640 --> 00:27:09,880
DUPLEX RNAs THEMSELVES HAD

733
00:27:09,880 --> 00:27:14,600
UNIQUE SEQUENCES THAT MADE THEM

734
00:27:14,600 --> 00:27:17,280
BASICALLY THE INTERFERON

735
00:27:17,280 --> 00:27:19,280
INDUCERS. HERE YOU CAN SEE

736
00:27:19,280 --> 00:27:21,400
INTERFERON BETA IN OUR CHIPS, WE

737
00:27:21,400 --> 00:27:26,280
CAN SHOW WITH THIS RNA 1, THIS

738
00:27:26,280 --> 00:27:29,000
IS 20 BASE PAIRS, VERY CHEAP TO

739
00:27:29,000 --> 00:27:30,800
SYNTHESIZE COMPLETELY, YOU HAVE

740
00:27:30,800 --> 00:27:33,640
30 FOLD INCREASE AND CLOSE TO 15

741
00:27:33,640 --> 00:27:36,120
FOLD INCREASE IN AIRWAY ALVEOLAR

742
00:27:36,120 --> 00:27:38,480
EPITHELIUM BUT MORE IMPORTANTLY,

743
00:27:38,480 --> 00:27:40,600
THIS ONE MOLECULE CAN BE USED TO

744
00:27:40,600 --> 00:27:43,880
INHIBIT INFLUENZA, H 1N 1 IN

745
00:27:43,880 --> 00:27:48,280
CHIPS, H 3N 2 INFLUENZA, SARS

746
00:27:48,280 --> 00:27:51,160
COV-2 WITH 4 LOG REDUCTION. MERS

747
00:27:51,160 --> 00:27:54,920
AND THE COMMON COLD VIRUS IN L

748
00:27:54,920 --> 00:27:57,760
63. WE HAVE CONFIRMED IN VIVO IN

749
00:27:57,760 --> 00:28:01,920
SARS COV-2 MOUSE MODEL, WE GET 3

750
00:28:01,920 --> 00:28:03,200
LOG REDUCTION USING THIS RNA,

751
00:28:03,200 --> 00:28:05,600
THIS IS ACTUALLY INTRAVENOUS

752
00:28:05,600 --> 00:28:07,640
INJECTION AND WE HAVE

753
00:28:07,640 --> 00:28:09,360
PRELIMINARY DATA WITH

754
00:28:09,360 --> 00:28:11,120
INTRATRACHEAL IN HAMSTERS BUT

755
00:28:11,120 --> 00:28:12,600
DELIVERY SYSTEM WASN'T OPTIMIZED

756
00:28:12,600 --> 00:28:14,520
BUT THIS LOOKS REALLY BEAUTIFUL.

757
00:28:14,520 --> 00:28:16,560
SO TO END, I THINK WHAT I WOULD

758
00:28:16,560 --> 00:28:17,760
LIKE TO COMMUNICATE IS THAT

759
00:28:17,760 --> 00:28:19,640
THESE HUMAN ORGAN CHIPS ARE MORE

760
00:28:19,640 --> 00:28:21,440
THAN POTENTIAL ANIMAL

761
00:28:21,440 --> 00:28:23,120
REPLACEMENTS AND THEY ARE AT A

762
00:28:23,120 --> 00:28:25,080
DIFFERENT LEVEL THAN ORGANOIDS.

763
00:28:25,080 --> 00:28:27,080
THEY MECHANISTIC DISCOVERY DRUG

764
00:28:27,080 --> 00:28:28,320
DISCOVERY TOOLS THAT PROVIDE NEW

765
00:28:28,320 --> 00:28:30,120
INSIGHT INTO PATHOPHYSIOLOGY

766
00:28:30,120 --> 00:28:32,320
THAT CAN BE COMBINED WITH

767
00:28:32,320 --> 00:28:33,840
ADVANCED ANALYTICAL TECHNIQUES.

768
00:28:33,840 --> 00:28:35,440
THEY CAN ENABLE RAPID DRUG

769
00:28:35,440 --> 00:28:37,000
REPURPOSING AND ACCELERATE

770
00:28:37,000 --> 00:28:38,400
DISCOVERY OF NOVEL THERAPEUTICS

771
00:28:38,400 --> 00:28:40,240
AS WELL. WITH THAT I HAVE TO

772
00:28:40,240 --> 00:28:42,040
DISCLOSE THAT I'M A MEMBER OF

773
00:28:42,040 --> 00:28:45,480
THE BOARD, CHAIR OF THE SAB AND

774
00:28:45,480 --> 00:28:47,520
EMULATE CELLS THESE CHIPS AND

775
00:28:47,520 --> 00:28:49,120
AUTOMATED INSTRUMENTS WORLDWIDE.

776
00:28:49,120 --> 00:28:50,760
AND I COULD NOT DO THIS WITHOUT

777
00:28:50,760 --> 00:28:52,120
INCREDIBLY INTERDISCIPLINARY

778
00:28:52,120 --> 00:28:54,280
TEAM AT THE WYSS INSTITUTE.

779
00:28:54,280 --> 00:28:55,240
PLEASE VISIT THE WEBSITE IF YOU

780
00:28:55,240 --> 00:28:56,800
WANT TO LEARN MORE. THANK YOU SO

781
00:28:56,800 --> 00:29:06,120
MUCH.

782
00:29:06,120 --> 00:29:08,360
>> THANK YOU, FASCINATING

783
00:29:08,360 --> 00:29:09,520
PRESENTATION. WE ARE COLLECTING

784
00:29:09,520 --> 00:29:10,520
QUESTIONS AND WILL HAVE

785
00:29:10,520 --> 00:29:12,640
DISCUSSION THIS AFTERNOON.

786
00:29:12,640 --> 00:29:13,920
SHIFTING GEARS NOW TO THE SECOND

787
00:29:13,920 --> 00:29:16,720
SPEAKER IN THE SESSION, LIKE TO

788
00:29:16,720 --> 00:29:21,040
INTRODUCE DR. LEE GEHRKE. DR.

789
00:29:21,040 --> 00:29:24,280
GEHRKE IS A HERMAN LF VON

790
00:29:24,280 --> 00:29:26,320
PROFESSOR OF HEALTH SCIENCES AND

791
00:29:26,320 --> 00:29:27,960
TECHNOLOGY AT THE MASSACHUSETTS

792
00:29:27,960 --> 00:29:31,520
INSTITUTE OF TECHNOLOGY. ALSO

793
00:29:31,520 --> 00:29:32,440
PROFESSOR OF MICROBIOLOGY AT

794
00:29:32,440 --> 00:29:35,400
HARVARD MEDICAL SCHOOL. DR.

795
00:29:35,400 --> 00:29:37,160
GEHRKE WAS BORN IN RAISED IN

796
00:29:37,160 --> 00:29:38,760
RURAL ILLINOIS BEFORE MOVING TO

797
00:29:38,760 --> 00:29:41,080
CLEVELAND, OHIO, TO ATTEND CASE

798
00:29:41,080 --> 00:29:42,400
WESTERN RESERVE UNIVERSITY FOR

799
00:29:42,400 --> 00:29:45,720
GRADUATE SCHOOL. FOLLOWING THAT

800
00:29:45,720 --> 00:29:47,280
HE DID A POST-DOCTORAL

801
00:29:47,280 --> 00:29:51,240
FELLOWSHIP AT MIT. DR. GEHRKE'S

802
00:29:51,240 --> 00:29:53,120
RESEARCH FOCUSED ON RNA FOR HIS

803
00:29:53,120 --> 00:29:54,800
ENTIRE CAREER AND MOST RECENTLY

804
00:29:54,800 --> 00:29:57,880
ON THE POSITIVE SENSE RNA

805
00:29:57,880 --> 00:30:01,280
VIRUSES AND PATHOGENESIS. DR.

806
00:30:01,280 --> 00:30:03,040
GEHRKE WAS ELECTED FELLOW OF THE

807
00:30:03,040 --> 00:30:03,680
AMERICAN INSTITUTE OF MEDICAL

808
00:30:03,680 --> 00:30:06,320
AND BIOLOGICAL ENGINEERING IN

809
00:30:06,320 --> 00:30:08,960
2021. AND AS A FELLOW OF THE

810
00:30:08,960 --> 00:30:10,360
AMERICAN ACADEMY OF MICROBIOLOGY

811
00:30:10,360 --> 00:30:13,680
IN 2022. DR. GEHRKE WILL BE

812
00:30:13,680 --> 00:30:16,000
SPEAKING ON DEFINING VIRAL

813
00:30:16,000 --> 00:30:18,200
PATHOGENESIS MECHANISMS USING

814
00:30:18,200 --> 00:30:20,800
HUMAN CEREBRAL ORGANOIDS. THANKS

815
00:30:20,800 --> 00:30:31,200
SO MUCH. OVER TO YOU.

816
00:30:33,400 --> 00:30:34,240
>> THANK YOU FOR THAT

817
00:30:34,240 --> 00:30:35,680
INVITATION.  ARE MY SLIDES

818
00:30:35,680 --> 00:30:36,720
VISIBLE, CAN YOU HEAR ME?

819
00:30:36,720 --> 00:30:39,840
>> ALL LOOKS GOOD.  THANK
YOU.

820
00:30:39,840 --> 00:30:42,680
>> FABULOUS. SO TODAY I
WANT TO

821
00:30:42,680 --> 00:30:43,480
TELL YOU ABOUT SOME OF THE WORK

822
00:30:43,480 --> 00:30:46,160
WE ARE DOING ON VIRAL

823
00:30:46,160 --> 00:30:48,240
PATHOGENESIS USING HUMAN

824
00:30:48,240 --> 00:30:53,640
CEREBRAL ORGANOID MODELS. I WILL

825
00:30:53,640 --> 00:30:58,080
START BY ADVANCING MY NEXT

826
00:30:58,080 --> 00:31:00,480
SLIDE. I WILL START BY SAYING

827
00:31:00,480 --> 00:31:03,520
THAT MY LAB IS REALLY A CONSUMER

828
00:31:03,520 --> 00:31:04,960
OF THIS TECHNOLOGY AND I WANT TO

829
00:31:04,960 --> 00:31:07,720
POINT OUT THE PEOPLE WHO HAVE

830
00:31:07,720 --> 00:31:11,920
REALLY BEEN PIONEERS IN

831
00:31:11,920 --> 00:31:12,960
DEVELOPING ORGANOID TECHNOLOGY.

832
00:31:12,960 --> 00:31:15,480
WE ARE USING TECHNIQUES THAT

833
00:31:15,480 --> 00:31:18,400
WERE PIONEERED BY MADELINE

834
00:31:18,400 --> 00:31:21,840
LANCASTER. WE ALSO HEARD FROM

835
00:31:21,840 --> 00:31:23,160
HANS CLEVER YESTERDAY ANOTHER

836
00:31:23,160 --> 00:31:24,800
PERSON WHO IS DONE A GREAT DEAL

837
00:31:24,800 --> 00:31:27,360
TO DEVELOP THIS TECHNOLOGY BUT

838
00:31:27,360 --> 00:31:30,000
TODAY I'M GOING TO TELL YOU

839
00:31:30,000 --> 00:31:31,360
ABOUT WORK WE HAVE DONE AND

840
00:31:31,360 --> 00:31:33,360
ABOUT THE LAST FIVE YEARS. SO IF

841
00:31:33,360 --> 00:31:35,560
ANY OF YOU ARE THINKING ABOUT

842
00:31:35,560 --> 00:31:36,880
USING ORGANOID SYSTEMS

843
00:31:36,880 --> 00:31:38,080
PARTICULARLY CEREBRAL ORGANOIDS

844
00:31:38,080 --> 00:31:41,360
I WANT TO TELL YOU ABOUT WHAT WE

845
00:31:41,360 --> 00:31:44,920
HAVE LEARNED IN USING THESE

846
00:31:44,920 --> 00:31:46,000
SYSTEMS, COMING FROM NEVER

847
00:31:46,000 --> 00:31:47,240
HAVING GROWN ONE UNTIL FIVE

848
00:31:47,240 --> 00:31:52,560
YEARS AGO. I THINK MANY PERHAPS

849
00:31:52,560 --> 00:31:55,280
ALL OF US ARE IN THIS WORKSHOP

850
00:31:55,280 --> 00:31:58,240
ARE INTERESTED IN STUDYING

851
00:31:58,240 --> 00:32:01,600
HALLWAYOLOGY. TO DO THAT IT IS

852
00:32:01,600 --> 00:32:02,920
NOT APPROPRIATE TO DO

853
00:32:02,920 --> 00:32:06,600
EXPERIMENTATION ON HUMANS. SO WE

854
00:32:06,600 --> 00:32:07,680
OFTEN TURN TO USING ANIMAL

855
00:32:07,680 --> 00:32:11,800
MODELS.  ANIMAL MODELS ARE

856
00:32:11,800 --> 00:32:13,280
EXTREMELY IMPORTANT, HAVE BEEN

857
00:32:13,280 --> 00:32:17,400
AND WILL CONTINUE TO BE

858
00:32:17,400 --> 00:32:20,040
IMPORTANT BUT THERE ARE EXAMPLES

859
00:32:20,040 --> 00:32:21,600
OF HOW ANIMAL MODELS DON'T

860
00:32:21,600 --> 00:32:24,600
COMPLETELY RECAPITULATE THE

861
00:32:24,600 --> 00:32:27,640
HUMAN BIOLOGY. AS A VIROLOGIST

862
00:32:27,640 --> 00:32:31,560
THERE ARE MANY VIRUSES FOR WHOM

863
00:32:31,560 --> 00:32:33,840
RODENTS ARE NOT NATURAL HOSTS.

864
00:32:33,840 --> 00:32:35,520
SO IN ORDER TO BE ABLE TO STUDY

865
00:32:35,520 --> 00:32:38,960
THEM IT IS NECESSARY TO USE MICE

866
00:32:38,960 --> 00:32:40,720
THAT HAVE THEIR SYSTEM FOR

867
00:32:40,720 --> 00:32:42,240
EXAMPLE KNOCKED OUT SO IT

868
00:32:42,240 --> 00:32:43,960
DOESN'T RECAPITULATE COMPLETELY

869
00:32:43,960 --> 00:32:46,280
SO WHAT WE WANT TO DO WAS TO

870
00:32:46,280 --> 00:32:50,560
FIND A SYSTEM THAT WAS A BRIDGE.

871
00:32:50,560 --> 00:32:54,960
A BRIDGE BETWEEN HUMAN BIOLOGY

872
00:32:54,960 --> 00:32:56,520
AND THE ANIMAL MODELS THAT'S

873
00:32:56,520 --> 00:33:01,320
WHEN WE STARTED USING ORGANOID

874
00:33:01,320 --> 00:33:03,680
SYSTEMS WE STUDY NEUROTROPIC

875
00:33:03,680 --> 00:33:04,920
VIRUSES SO WE WERE INTERESTED IN

876
00:33:04,920 --> 00:33:06,120
USING CEREBRAL ORGANOID

877
00:33:06,120 --> 00:33:08,800
TECHNOLOGY SO THE IMAGE IN THE

878
00:33:08,800 --> 00:33:13,440
CENTER HERE IS ONE OF A ORGANOID

879
00:33:13,440 --> 00:33:15,480
DERIVED FROM HUMAN PLURIPOTENT

880
00:33:15,480 --> 00:33:19,760
STEM CELLS.  SO THIS IS A SLIDE

881
00:33:19,760 --> 00:33:21,280
THAT'S ALREADY BEEN SHOWN IN A

882
00:33:21,280 --> 00:33:25,520
NUMBER OF CASES THROUGHOUT THIS

883
00:33:25,520 --> 00:33:27,960
WORKSHOP. WE CREATE THE

884
00:33:27,960 --> 00:33:29,240
ORGANOIDS IN PRETTY MUCH THE

885
00:33:29,240 --> 00:33:32,760
SAME WAY. FROM STARTING WITH

886
00:33:32,760 --> 00:33:34,960
STEM CELLS TO THE POINT WHERE WE

887
00:33:34,960 --> 00:33:37,760
DO ALL INFECTIONS TAKES 21 DAYS

888
00:33:37,760 --> 00:33:40,760
AND THE ORGANOIDS AT THAT POINT

889
00:33:40,760 --> 00:33:44,640
ARE ABOUT 2-MILLIMETERS IN

890
00:33:44,640 --> 00:33:46,320
DIAMETER. IF YOU SECTION THROUGH

891
00:33:46,320 --> 00:33:49,080
CEREBRAL ORGANOID IT LOOKS LIKE

892
00:33:49,080 --> 00:33:52,680
IMAGES THAT ARE BELOW HERE AT

893
00:33:52,680 --> 00:33:54,680
DAY 17, DAY 21 AND DAY 28. YOU

894
00:33:54,680 --> 00:33:56,280
CAN SEE THEY GROW, THESE ARE

895
00:33:56,280 --> 00:33:59,520
SAME SCALE.  ID WILL SHOW IMAGES

896
00:33:59,520 --> 00:34:03,360
THAT HAVE THIS TYPE OF STAINING

897
00:34:03,360 --> 00:34:04,360
AND SO THROUGHOUT THE ORGANOIDS

898
00:34:04,360 --> 00:34:07,000
YOU CAN SEE ROUND STRUCTURE WITH

899
00:34:07,000 --> 00:34:09,000
OPENING IN THE CENTER THESE ARE

900
00:34:09,000 --> 00:34:10,840
VENTRICLES RECAPITULATE LAYERING

901
00:34:10,840 --> 00:34:14,360
FOUND IN CORTEX.  THEY ARE

902
00:34:14,360 --> 00:34:18,560
SURROUNDED BY WITH SOX 2

903
00:34:18,560 --> 00:34:19,640
TRANSCRIPTION FACTOR. THEN YOU

904
00:34:19,640 --> 00:34:23,320
CAN ALSO SEE THE GREEN STAINING

905
00:34:23,320 --> 00:34:25,840
MAP 2 NEURONS BLUE STAINING IS

906
00:34:25,840 --> 00:34:29,920
DAPE. IF YOU WANT TO THINK ABOUT

907
00:34:29,920 --> 00:34:33,040
HOW THESE ORGANOIDS CORRELATE

908
00:34:33,040 --> 00:34:36,440
WITH DEVELOPMENT OF HUMAN BRAIN,

909
00:34:36,440 --> 00:34:37,800
LANCASTER PUT TOGETHER THIS

910
00:34:37,800 --> 00:34:41,400
SLIDE AND ON THE TOP HERE SHOWS

911
00:34:41,400 --> 00:34:43,600
THE TIMETABLE FOR DEVELOPMENT OF

912
00:34:43,600 --> 00:34:45,480
HUMAN BRAIN THROUGH FIRST AND

913
00:34:45,480 --> 00:34:47,080
SECOND AND THIRD TRIMESTERS AND

914
00:34:47,080 --> 00:34:50,080
THEN ON THE BOTTOM HERE IS

915
00:34:50,080 --> 00:34:52,280
DEVELOPMENT OF CEREBRAL

916
00:34:52,280 --> 00:34:55,040
ORGANOIDS FROM 20 TO 40 TO 60

917
00:34:55,040 --> 00:34:58,600
DAYS. IN THE CENTER THERE IS A

918
00:34:58,600 --> 00:34:59,520
COLOR GRAPH THAT SHOWS WHICH

919
00:34:59,520 --> 00:35:01,560
POINTS THERE'S BEST CORRELATION

920
00:35:01,560 --> 00:35:03,640
BETWEEN BIOLOGY OF THE ORGANOID

921
00:35:03,640 --> 00:35:05,680
AND THE HUMAN BRAIN. THAT IS IN

922
00:35:05,680 --> 00:35:08,040
THIS PURPLISH REGION RIGHT HERE.

923
00:35:08,040 --> 00:35:11,400
AND IN FACT WE DO OUR INFECTIONS

924
00:35:11,400 --> 00:35:15,960
TO STUDY VIRAL PATHOGENESIS FROM

925
00:35:15,960 --> 00:35:21,560
21 DAYS TO 41 DAYS.  SO THIS IS

926
00:35:21,560 --> 00:35:22,560
THE BIOLOGICAL PROBLEM WE ARE

927
00:35:22,560 --> 00:35:23,680
INTERESTED IN. WE ARE INTERESTED

928
00:35:23,680 --> 00:35:25,360
IN UNDERSTANDING HOW VIRUSES

929
00:35:25,360 --> 00:35:29,880
THAT ARE CLOSELY RELATED CAN

930
00:35:29,880 --> 00:35:31,240
CAUSE SUCH DIFFERENT PATHOLOGIES

931
00:35:31,240 --> 00:35:33,080
AND SOME MAKE PEOPLE SICK,

932
00:35:33,080 --> 00:35:35,280
OTHERS DON'T MAKE PEOPLE SICK.

933
00:35:35,280 --> 00:35:36,960
AND AN EXAMPLE OF THAT SHOWN IN

934
00:35:36,960 --> 00:35:42,920
THESE IMAGES IS HERE. ON THE

935
00:35:42,920 --> 00:35:45,240
LEFT IS THE MOCK INFECTED

936
00:35:45,240 --> 00:35:46,440
ORGANOID, THE PINK COLOR IS

937
00:35:46,440 --> 00:35:49,000
VENTRICLES THAT CONTAIN

938
00:35:49,000 --> 00:35:51,600
PROGENITOR CELLS ORAL PROGENITOR

939
00:35:51,600 --> 00:35:53,400
CELLS, GREEN IS NEURONS AND BLUE

940
00:35:53,400 --> 00:35:56,520
STAIN IS DAPE NUCLEI. HERE IS

941
00:35:56,520 --> 00:35:58,440
UNINFECTED. THIS IS ONE STRAIN

942
00:35:58,440 --> 00:36:01,640
OF ZIKA THAT IS I WOULD SAY A

943
00:36:01,640 --> 00:36:07,600
MILD PATHOGENESIS. THE ORGANOIDS

944
00:36:07,600 --> 00:36:09,240
RETAIN THEIR OVERALL STRUCTURE

945
00:36:09,240 --> 00:36:11,320
AND ONE CAN ALSO SEE THE

946
00:36:11,320 --> 00:36:15,120
VENTRICLES, THE WHITE DOTS HERE

947
00:36:15,120 --> 00:36:16,720
ARE VIRUS, OR VIRAL RNA, THEY

948
00:36:16,720 --> 00:36:18,920
ARE STAINED WITH AN ANTI-DOUBLE

949
00:36:18,920 --> 00:36:21,360
STRANDED RNA ANTIBODY. THEN WE

950
00:36:21,360 --> 00:36:24,000
GO TO THE SECOND STRAIN WHICH IS

951
00:36:24,000 --> 00:36:27,200
MORE PATHOGENIC. WHEN WE USE

952
00:36:27,200 --> 00:36:30,760
THIS VIRUS EVEN THOUGH IT IS 98%

953
00:36:30,760 --> 00:36:33,760
IDENTICAL TO THIS ONE HERE AT

954
00:36:33,760 --> 00:36:37,160
THE MOS LEVEL WE LOST A LOT OF

955
00:36:37,160 --> 00:36:40,880
VENTRICLE ARCHITECTURE, THE

956
00:36:40,880 --> 00:36:42,040
NEURONS HAVE BEEN DISRUPTED WE

957
00:36:42,040 --> 00:36:44,800
SEE CELL BODIES BUT WE DON'T SEE

958
00:36:44,800 --> 00:36:48,320
AXONS AND THEN WE GO TO THE

959
00:36:48,320 --> 00:36:50,240
THIRD VIRAL STRAIN ZIKA STRAIN

960
00:36:50,240 --> 00:36:52,480
WHICH IS VERY PATHOGENIC AND WE

961
00:36:52,480 --> 00:36:55,880
LOST COMPLETELY THE ORGANIZATION

962
00:36:55,880 --> 00:37:00,480
OF THE VENTRICLES THERE IS

963
00:37:00,480 --> 00:37:02,080
LITTLE MAP Q STAINING ON -- THAT

964
00:37:02,080 --> 00:37:05,200
CAN BE SEEN. SO ONE BIG

965
00:37:05,200 --> 00:37:06,440
ADVANTAGE OF THAT WE FIND USING

966
00:37:06,440 --> 00:37:08,080
THIS ORGANOID SYSTEM IS THAT WE

967
00:37:08,080 --> 00:37:09,840
CANNOT ONLY DO THE MOLECULAR

968
00:37:09,840 --> 00:37:12,880
BIOLOGY IN THE BIOCHEMISTRY ON

969
00:37:12,880 --> 00:37:15,280
THEM, BUT SEEING WHAT HAPPENS TO

970
00:37:15,280 --> 00:37:16,960
THE TISSUE, THIS IS A COMPLEX

971
00:37:16,960 --> 00:37:18,840
THREE DIMENSIONAL TISSUE, AND

972
00:37:18,840 --> 00:37:20,440
SEE WHAT HAPPENS TO THE

973
00:37:20,440 --> 00:37:22,520
ORGANIZATION OF THE INDIVIDUAL

974
00:37:22,520 --> 00:37:24,360
CELLS IS VERY IMPORTANT. SO NOW

975
00:37:24,360 --> 00:37:27,160
I WANT TO GIVE A FEW TIPS WE

976
00:37:27,160 --> 00:37:28,400
HAVE LEARNED SOMETIMES THE HARD

977
00:37:28,400 --> 00:37:30,400
WAY IN DOING EXPERIMENTATION

978
00:37:30,400 --> 00:37:32,120
USING CEREBRAL ORGANOIDS, AGAIN

979
00:37:32,120 --> 00:37:33,080
FOR ANYONE WHO IS IN THE

980
00:37:33,080 --> 00:37:34,200
AUDIENCE WHO MIGHT BE THINKING

981
00:37:34,200 --> 00:37:37,840
ABOUT ADOPTING THIS TECHNOLOGY I

982
00:37:37,840 --> 00:37:39,240
WOULD ENCOURAGE YOU TO DO SO.

983
00:37:39,240 --> 00:37:40,840
BUT I WANT TO TELL YOU ABOUT

984
00:37:40,840 --> 00:37:42,040
SOME OF THE THINGS WE HAVE

985
00:37:42,040 --> 00:37:46,000
LEARNED ALONG THE WAY. SO MY

986
00:37:46,000 --> 00:37:48,800
FIRST TIP IN USING CERTAIN

987
00:37:48,800 --> 00:37:50,320
ORGANOID OR ORGANOID MODELS IN

988
00:37:50,320 --> 00:37:52,120
GENERAL IS TO IDENTIFY STEM CELL

989
00:37:52,120 --> 00:37:56,760
COLLABORATOR. IN OUR CASE, WE --

990
00:37:56,760 --> 00:37:59,840
OUR COLLABORATOR IS RUDOLPH, A

991
00:37:59,840 --> 00:38:03,400
PIONEER IN THE STEM CELL FIELD,

992
00:38:03,400 --> 00:38:05,280
HE IS JUST ACROSS THE STREET

993
00:38:05,280 --> 00:38:06,400
FROM US AT THE WHITE HEAD

994
00:38:06,400 --> 00:38:08,560
INSTITUTE AND COLLABORATING WITH

995
00:38:08,560 --> 00:38:11,880
HIS LAB ON VIRUS INFECTION AND

996
00:38:11,880 --> 00:38:13,640
STEM CELLS HAS BEEN PRODUCTIVE

997
00:38:13,640 --> 00:38:16,200
BUT HAS BEEN ABSOLUTELY CRITICAL

998
00:38:16,200 --> 00:38:18,400
TO HAVE THEIR EXPERTISE AS STEM

999
00:38:18,400 --> 00:38:22,080
CELL BIOLOGISTS. THE REASON IS

1000
00:38:22,080 --> 00:38:23,880
THAT STEM CELLS AND STEM CELL

1001
00:38:23,880 --> 00:38:29,000
BIOLOGY IS BIG FIELD. IT IS

1002
00:38:29,000 --> 00:38:30,280
CHALLENGING FOR SOMEONE WHO IS

1003
00:38:30,280 --> 00:38:33,080
NOT A STEM CELL BIOLOGIST LIKE

1004
00:38:33,080 --> 00:38:35,520
ME TO ACQUIRE INFORMATION SO

1005
00:38:35,520 --> 00:38:37,520
QUICKLY THAT THIS CAN BE DONE

1006
00:38:37,520 --> 00:38:42,480
COMPLETELY INDEPENDENTLY. IT

1007
00:38:42,480 --> 00:38:45,040
DEFINITELY SHOWS IT IS A

1008
00:38:45,040 --> 00:38:45,960
CHALLENGE AND SOMETHING TO BE

1009
00:38:45,960 --> 00:38:47,640
VOIDED AS WORKING IN IN A VACUUM

1010
00:38:47,640 --> 00:38:48,800
AND DEVELOPING THESE THINGS

1011
00:38:48,800 --> 00:38:53,200
COMPLETELY ON YOUR OWN. PEOPLE

1012
00:38:53,200 --> 00:38:58,320
SKILLED CAN DO IT BUT YOU CAN DO

1013
00:38:58,320 --> 00:39:00,800
IT FASTER WITH GREATER

1014
00:39:00,800 --> 00:39:01,800
UNDERSTANDING IF YOU HAVE A

1015
00:39:01,800 --> 00:39:02,920
COLLEAGUE AND FINALLY STEM CELL

1016
00:39:02,920 --> 00:39:03,600
LABS HAVE SOME PIECES OF

1017
00:39:03,600 --> 00:39:05,440
EQUIPMENTNA ARE SPECIALIZED THAT

1018
00:39:05,440 --> 00:39:06,720
ARE VERY -- THAT ARE SPECIALIZED

1019
00:39:06,720 --> 00:39:07,840
VERY IMPORTANT. IN OUR CASE IT

1020
00:39:07,840 --> 00:39:11,440
IS NOT THIS ONE, THIS IS JUST A

1021
00:39:11,440 --> 00:39:12,960
PICTURE BUT STEM CELL LABS HAVE

1022
00:39:12,960 --> 00:39:14,920
LOW OXYGEN INCUBATORS THAT MY

1023
00:39:14,920 --> 00:39:17,240
LAB DOESN'T HAVE HAVE. AND THEYE

1024
00:39:17,240 --> 00:39:23,400
USED FOR KEEPING THE THEY ARE

1025
00:39:23,400 --> 00:39:25,760
USE TO KEEP THE STEM CELLS FROM

1026
00:39:25,760 --> 00:39:27,080
DIFFERENTIATING. THE SECOND TIP

1027
00:39:27,080 --> 00:39:29,760
IS TO USE HIGH QUALITIES

1028
00:39:29,760 --> 00:39:34,520
PLURIPOTENT STEM CELLS. THIS IS

1029
00:39:34,520 --> 00:39:36,240
REALLY THE FOUNDATION FOR

1030
00:39:36,240 --> 00:39:41,120
EVERYTHING DONE HER HERE. THIS E

1031
00:39:41,120 --> 00:39:42,720
OF GARBAGE IN AND OUT COULDN'T

1032
00:39:42,720 --> 00:39:45,120
BE MORE TRUE WHEN DOING THESE

1033
00:39:45,120 --> 00:39:48,160
PLURIPOTENT STEM CELL EXPERI 

1034
00:39:48,160 --> 00:39:50,360
EXPERIMENTS. THIS IS ALSO

1035
00:39:50,360 --> 00:39:53,120
CRITICAL FOR PRECISION, ACCURACY

1036
00:39:53,120 --> 00:39:53,920
REPRODUCIBILITY OF YOUR

1037
00:39:53,920 --> 00:39:56,240
EXPERIMENTS TO MAKE SURE YOU DO

1038
00:39:56,240 --> 00:39:59,280
EVERYTHING YOU CAN TO HAVE GOOD

1039
00:39:59,280 --> 00:40:01,040
STARTING AND WELL CHARACTERIZED

1040
00:40:01,040 --> 00:40:07,120
STARTING MATERIAL. AS WE HAVE

1041
00:40:07,120 --> 00:40:08,920
DONE THESE EXPERIMENTS YOU

1042
00:40:08,920 --> 00:40:10,320
ACQUIRE EXPERTISE AND NOTICE

1043
00:40:10,320 --> 00:40:12,720
THINGS THAT ARE WARNING SIGNS.

1044
00:40:12,720 --> 00:40:16,360
SO ON THE LEFT HERE IS AN

1045
00:40:16,360 --> 00:40:17,680
ORGANOID WE WOULD LIKE TO SEE ON

1046
00:40:17,680 --> 00:40:21,400
THE RIGHT THOUGH MAY NOT BE

1047
00:40:21,400 --> 00:40:22,920
OBVIOUS FIRST GLANCE WHY THIS IS

1048
00:40:22,920 --> 00:40:24,560
NOT ONE THAT WOULD WANT, WE

1049
00:40:24,560 --> 00:40:28,280
WOULD WANT. SO ON THE LEFT YOU

1050
00:40:28,280 --> 00:40:31,760
CAN SEE THE EMBRYO BODY HERE AND

1051
00:40:31,760 --> 00:40:35,200
THE CLEAR AREA AROUND THE

1052
00:40:35,200 --> 00:40:39,120
DEVELOPING EMBRYO BODY IS NEUTRA

1053
00:40:39,120 --> 00:40:41,640
GEL. T NOTICE ON THE RIGHT THAT

1054
00:40:41,640 --> 00:40:42,520
THERE ARE PROJECTIONS THAT ARE

1055
00:40:42,520 --> 00:40:46,360
GOING OUT INTO THE NATRIGEL.

1056
00:40:46,360 --> 00:40:48,440
THESE ARE HARRY ORGANOIDS. WE

1057
00:40:48,440 --> 00:40:50,120
DON'T WANT THESE AND WE LEARNED

1058
00:40:50,120 --> 00:40:52,120
THE HARD WAY THAT IF THE

1059
00:40:52,120 --> 00:40:54,200
ORGANOIDS HAVE THESE PROJECTIONS

1060
00:40:54,200 --> 00:40:57,640
IN THE NATRIGEL THEY HAVE

1061
00:40:57,640 --> 00:40:58,400
DIFFERENCE ADJUDICATED

1062
00:40:58,400 --> 00:40:59,760
PREMATURELY AND NOT USEFUL. SO

1063
00:40:59,760 --> 00:41:03,960
IF WE EVER SEE THIS KIND OF

1064
00:41:03,960 --> 00:41:05,520
ORGANOID IN OUR PREPS WE JUST

1065
00:41:05,520 --> 00:41:10,960
START OVER AGAIN. PREMATURE

1066
00:41:10,960 --> 00:41:11,760
DIFFERENTIATION OF THE

1067
00:41:11,760 --> 00:41:13,120
PLURIPOTENT STEM CELLS IS

1068
00:41:13,120 --> 00:41:16,520
SOMETHING ONE HAS TO KEEP IN

1069
00:41:16,520 --> 00:41:26,880
MIND, THIS IS WHERE

1070
00:42:00,360 --> 00:42:01,920
ORGANOIDS. AND YOU CAN

1071
00:42:01,920 --> 00:42:02,800
DIFFERENTIATE THE STEM CELLS

1072
00:42:02,800 --> 00:42:05,480
INTO THESE PROGENITORS AND THEN

1073
00:42:05,480 --> 00:42:07,600
FREEZE THEM AND STORE THEM FOR

1074
00:42:07,600 --> 00:42:09,760
UPCOMING EXPERIMENTS. IF YOU

1075
00:42:09,760 --> 00:42:11,960
HAVE A GREAT PREP OF THE NEURAL

1076
00:42:11,960 --> 00:42:13,680
PROGENITORS YOU CAN FOLLOW THEM

1077
00:42:13,680 --> 00:42:15,360
AND YOU CAN GROW THEM UP,

1078
00:42:15,360 --> 00:42:17,400
PASSAGE THEM FOR SEVEN OR EIGHT

1079
00:42:17,400 --> 00:42:19,120
PASSAGES. IF IT IS NOT A GREAT

1080
00:42:19,120 --> 00:42:20,520
PREP THEY WILL START TO

1081
00:42:20,520 --> 00:42:21,920
DIFFERENTIATE INTO OTHER

1082
00:42:21,920 --> 00:42:23,560
STRUCTURE WITHIN THE FIRST

1083
00:42:23,560 --> 00:42:24,960
PASSAGE. AND YOU LOSE THE

1084
00:42:24,960 --> 00:42:28,440
ABILITY TO GET ENOUGH CELLS TO

1085
00:42:28,440 --> 00:42:32,000
DO YOUR EXPERIMENT. HAVING GREAT

1086
00:42:32,000 --> 00:42:33,000
STARTING MATERIAL IS SO

1087
00:42:33,000 --> 00:42:38,920
IMPORTANT. ANTIBIOTIC. THERE'S

1088
00:42:38,920 --> 00:42:40,040
NOTHING THAT RUINS YOUR DAY MORE

1089
00:42:40,040 --> 00:42:41,840
THAN COMING IN IN THE MORNING

1090
00:42:41,840 --> 00:42:43,720
AND FINDING OUT THAT YOUR

1091
00:42:43,720 --> 00:42:47,520
CULTURES ARE CONTAMINATED. IN

1092
00:42:47,520 --> 00:42:50,560
THE CASE OF THE ORGANOID FIELD,

1093
00:42:50,560 --> 00:42:52,040
MOST OF THE PAPERS AND INDEED

1094
00:42:52,040 --> 00:42:54,120
THE MANUFACTURERS LIKE STEM CELL

1095
00:42:54,120 --> 00:42:59,240
TECHNOLOGIES DO NOT USE

1096
00:42:59,240 --> 00:43:03,000
ANTIBIOTICS. IN OUR WORK WE

1097
00:43:03,000 --> 00:43:05,200
GENERALLY -- LEAVE ANTIBIOTICS

1098
00:43:05,200 --> 00:43:09,400
OUT AS WELL. BUT THERE ARE CASES

1099
00:43:09,400 --> 00:43:10,560
WHEN YOU ARE TRAINING A NEW

1100
00:43:10,560 --> 00:43:12,120
PERSON, SOMEBODY NEW IS COMING

1101
00:43:12,120 --> 00:43:14,240
IN, THERE ARE A LOT OF

1102
00:43:14,240 --> 00:43:15,640
OPPORTUNITIES FOR CONTAMINATING

1103
00:43:15,640 --> 00:43:18,280
CULTURES PARTICULARLY IN

1104
00:43:18,280 --> 00:43:20,520
EMBEDDING STEP. SO WE HAVE USED

1105
00:43:20,520 --> 00:43:23,520
THEM AND WE HAVEN'T -- WE

1106
00:43:23,520 --> 00:43:25,560
HAVEN'T FOUND NEGATIVE EFFECTS

1107
00:43:25,560 --> 00:43:26,840
WITH CALLED STEM CELL

1108
00:43:26,840 --> 00:43:29,720
TECHNOLOGIES AND THEY SAY THAT

1109
00:43:29,720 --> 00:43:32,600
THEY DON'T RECOMMEND THE OUTWARD

1110
00:43:32,600 --> 00:43:34,160
USE OF ANTIBIOTICS HOWEVER THEY

1111
00:43:34,160 --> 00:43:35,960
USED THEM TRIED THEM AND HAVEN'T

1112
00:43:35,960 --> 00:43:40,960
SEEN ANY DELETERIOUS EFFECT. SO

1113
00:43:40,960 --> 00:43:43,120
THE BOTTOM LINE IS THAT I THINK

1114
00:43:43,120 --> 00:43:44,840
IT IS POSSIBLE TO USE THEM, WE

1115
00:43:44,840 --> 00:43:47,840
TRY TO AVOID IT WHENEVER WE CAN 

1116
00:43:47,840 --> 00:43:51,680
BUT WE HAVE NOT SEEN ANY

1117
00:43:51,680 --> 00:43:53,440
DELETERIOUS EFFECTS OF

1118
00:43:53,440 --> 00:43:55,000
ANTIBIOTICS. THE NEXT ONE HERE

1119
00:43:55,000 --> 00:43:58,120
IS BE GENTLE AND THIS IS -- THIS

1120
00:43:58,120 --> 00:44:01,320
COULD BE ONE'S LIFE MANTRA. BUT

1121
00:44:01,320 --> 00:44:06,200
IN TERMS OF DOING ORGANOIDS, IT

1122
00:44:06,200 --> 00:44:09,160
IS IMPORTANT AND WHEN

1123
00:44:09,160 --> 00:44:11,880
TRANSFERRING THESE FROM ONE

1124
00:44:11,880 --> 00:44:13,200
PLATE TO ANOTHER, YOU DON'T WANT

1125
00:44:13,200 --> 00:44:17,000
TO SUCK THEM UP INTO A NARROW

1126
00:44:17,000 --> 00:44:18,600
BOW BY PET TIP BECAUSE THEY ARE

1127
00:44:18,600 --> 00:44:22,040
FRAGILE, YOU WILL DAMAGE THEM SO

1128
00:44:22,040 --> 00:44:24,520
WE TAKE ONE PIPETTE TIP, CUT

1129
00:44:24,520 --> 00:44:29,840
THEM OFF WITH A CLEAN RAZOR AND

1130
00:44:29,840 --> 00:44:31,440
USE THOSE. THE GREEDY PART IS

1131
00:44:31,440 --> 00:44:32,840
WHEN YOU ARE TRANSFERRING INTO

1132
00:44:32,840 --> 00:44:34,720
LARGER DISHES FOR EXAMPLE YOU

1133
00:44:34,720 --> 00:44:37,320
WANT TO CHANGE MEDIA, WE WOULD

1134
00:44:37,320 --> 00:44:41,320
ADVISE TO RESIST THE TRYING TO

1135
00:44:41,320 --> 00:44:44,080
GET EVERY LAST MICROLITER OF

1136
00:44:44,080 --> 00:44:45,000
MEDIA OUT OF THE DISH BECAUSE

1137
00:44:45,000 --> 00:44:46,960
YOU ARE LIABLE TO DAMAGE THE

1138
00:44:46,960 --> 00:44:49,080
ORGANOIDS OR ALLOW THEM TO DRY

1139
00:44:49,080 --> 00:44:54,080
OUT BOTH OF WHICH WILL RUIN YOUR

1140
00:44:54,080 --> 00:44:55,840
EXPERIMENT. BOTTOM LINE HERE IS

1141
00:44:55,840 --> 00:44:59,400
THAT ONE HAS TO BE CAREFUL AND

1142
00:44:59,400 --> 00:45:01,160
PATIENT IN WORKING WITH THESE

1143
00:45:01,160 --> 00:45:02,360
ORGANOIDS. ANOTHER PROBLEM THAT

1144
00:45:02,360 --> 00:45:05,240
WE HAVE HAD FROM TIME TO TIME IS

1145
00:45:05,240 --> 00:45:08,240
THAT THESE ORGANOIDS WILL FUSE

1146
00:45:08,240 --> 00:45:10,640
IF THEY GET IN CONTACT WITH ONE

1147
00:45:10,640 --> 00:45:12,440
ANOTHER. IF THE ORGANOIDS GET

1148
00:45:12,440 --> 00:45:14,320
TOO CLOSE THEY WILL FUSE INTO

1149
00:45:14,320 --> 00:45:15,760
ANOTHER ORGANOID AND

1150
00:45:15,760 --> 00:45:18,400
UNFORTUNATELY WHEN THAT HAPPENS,

1151
00:45:18,400 --> 00:45:20,040
THEY USUALLY DON'T LOOK LIKE

1152
00:45:20,040 --> 00:45:21,720
THIS NICE ROUND ORGANOID, THEY

1153
00:45:21,720 --> 00:45:25,240
ARE VERY IRREGULAR IN SHAPE. WE

1154
00:45:25,240 --> 00:45:28,520
TRY TO AVOID THAT. SO WHAT WE DO

1155
00:45:28,520 --> 00:45:35,320
IS PUT THEM INTO 24 WELL PLATE

1156
00:45:35,320 --> 00:45:37,920
WELLS AND CULTURE THE ORGANOIDS

1157
00:45:37,920 --> 00:45:39,040
INDIVIDUALLY SO THEY DON'T HAVE

1158
00:45:39,040 --> 00:45:41,400
THE OPPORTUNITY TO DIFFUSE WITH

1159
00:45:41,400 --> 00:45:47,880
ONE ANOTHER.  SO THIS ONE IS

1160
00:45:47,880 --> 00:45:53,000
OBVIOUS BUT ONE NEEDS TO REDUCE

1161
00:45:53,000 --> 00:45:54,320
EXPERIMENTAL DELIVERY AND WE DO

1162
00:45:54,320 --> 00:45:56,680
THAT WITH DOING BATCH

1163
00:45:56,680 --> 00:45:57,840
EXPERIMENTS SO WE DO A LOT OF

1164
00:45:57,840 --> 00:45:59,080
VIRUS INFECTIONS SO WE TAKE A

1165
00:45:59,080 --> 00:46:01,440
GROUP OF ABOUT 15 TO 20

1166
00:46:01,440 --> 00:46:04,440
ORGANOIDS, PUT THEM INTO A SIX

1167
00:46:04,440 --> 00:46:07,480
WELL PLATE AND DO THE INFECTION

1168
00:46:07,480 --> 00:46:12,680
OF ALL THE ORGANOIDS AT ONCE.

1169
00:46:12,680 --> 00:46:14,480
THAT REALLY REDUCE IT IS

1170
00:46:14,480 --> 00:46:16,920
VARIABILITY IN EXPERIMENTS

1171
00:46:16,920 --> 00:46:19,680
OPPOSED TO TRYING TO TAKE THREE

1172
00:46:19,680 --> 00:46:21,400
OR FOUR ORGANOIDS AND INFECT

1173
00:46:21,400 --> 00:46:26,280
THEM SEPARATELY. THAT WOULD

1174
00:46:26,280 --> 00:46:27,760
CHARACTERIZE ANY EXPERIMENTAL

1175
00:46:27,760 --> 00:46:35,120
PROTOCOL THAT YOU ARE USING.  IF

1176
00:46:35,120 --> 00:46:36,440
YOU ARE DOING SECTIONS WE DO

1177
00:46:36,440 --> 00:46:37,800
SECTIONING TO SEE WHAT THE

1178
00:46:37,800 --> 00:46:39,200
ORIGINATION OF THE ORGANOIDS

1179
00:46:39,200 --> 00:46:42,280
LOOK LIKE. A HELPFUL SMALL TIP

1180
00:46:42,280 --> 00:46:44,120
IS USE GLUE OCT. THIS COMES IN A

1181
00:46:44,120 --> 00:46:46,440
NUMBER OF COLORS BUT THE

1182
00:46:46,440 --> 00:46:48,520
ORGANOIDS ARE VERY SMALL AND

1183
00:46:48,520 --> 00:46:50,720
WHITE AND YOU GET THEM INTO A

1184
00:46:50,720 --> 00:46:51,760
BLOCK IT IS VERY HARD TO SEE

1185
00:46:51,760 --> 00:46:53,240
THEM. SO THAT YOU KNOW WHERE TO

1186
00:46:53,240 --> 00:46:56,240
START CUTTING AND SO IF YOU USE

1187
00:46:56,240 --> 00:47:00,080
BLUE OCT THAT REALLY HELPS WITH

1188
00:47:00,080 --> 00:47:03,280
VISUALIZING THEM.  IF YOU WANT

1189
00:47:03,280 --> 00:47:05,200
TO DO SINGLE CELL RNA SEQ WE

1190
00:47:05,200 --> 00:47:09,160
HAVE DONE A LOT OF SINGLE CELL

1191
00:47:09,160 --> 00:47:11,840
RNA SEQ ON THESE ORGANOIDS

1192
00:47:11,840 --> 00:47:13,400
DISSOCIATING THE ORGANOIDS AND

1193
00:47:13,400 --> 00:47:15,280
RETAINING VIABILITY IS CRITICAL

1194
00:47:15,280 --> 00:47:18,280
AS IS TRUE FOR ANY SINGLE CELL

1195
00:47:18,280 --> 00:47:23,520
SEQ BUT WE FOUND THIS PARTICULAR

1196
00:47:23,520 --> 00:47:27,480
KIT, I DON'T WORK FOR THEM NOR

1197
00:47:27,480 --> 00:47:30,040
DO THEY GIVE ME ANYTHING BUT

1198
00:47:30,040 --> 00:47:31,560
THIS EM BRIEFED YOU BODY

1199
00:47:31,560 --> 00:47:33,920
DISSOCIATION KIT GAVE US THE

1200
00:47:33,920 --> 00:47:35,640
GREATEST VIABILITY OF CELLS WE

1201
00:47:35,640 --> 00:47:40,120
CAN CARRY FORWARD THEN INTO

1202
00:47:40,120 --> 00:47:43,280
SINGLE CELL SEQUENCING. SO TO

1203
00:47:43,280 --> 00:47:44,240
SUMMARIZE THESE POINTS WE LIKE

1204
00:47:44,240 --> 00:47:47,080
TO SEE AT THE END THE ORGANOIDS

1205
00:47:47,080 --> 00:47:49,160
ARE ROUND, BUT THEY CAN VARY BY

1206
00:47:49,160 --> 00:47:51,480
ABOUT TWOFOLD IN DIAMETER NO

1207
00:47:51,480 --> 00:47:56,120
MATTER HOW WE DO THE PREPS, THEY

1208
00:47:56,120 --> 00:47:58,080
HAVE APPROPRIATE -- WILL VARY

1209
00:47:58,080 --> 00:48:01,720
FROM SIZE BY FACTOR OF TWO. WE

1210
00:48:01,720 --> 00:48:04,720
GET USABLE ORGANOIDS 80 TO 90%

1211
00:48:04,720 --> 00:48:06,040
OF THE TIME, WHICH IS PRETTY

1212
00:48:06,040 --> 00:48:09,360
GOOD FOR THE TECHNOLOGY AND WE

1213
00:48:09,360 --> 00:48:14,680
DO BATCHES OF 300. THE 80 TO 90%

1214
00:48:14,680 --> 00:48:18,160
TIME WOULD NOT INCLUDE HAVING A

1215
00:48:18,160 --> 00:48:20,600
CONTAMINATION PROBLEM IN THE

1216
00:48:20,600 --> 00:48:21,920
LAB, THAT CAN BE FIXED AND IS

1217
00:48:21,920 --> 00:48:23,680
NOT INCLUDED IN THESE NUMBERS

1218
00:48:23,680 --> 00:48:26,760
BUT FOR JUST THE TECHNIQUE WE

1219
00:48:26,760 --> 00:48:29,800
CAN GET GOOD RESULTS WITH THE

1220
00:48:29,800 --> 00:48:32,160
ORGANOID PREPS QUITE OFTEN. SO

1221
00:48:32,160 --> 00:48:33,960
ONE OF THE VARIABLES THAT CAN

1222
00:48:33,960 --> 00:48:37,040
AFFECT OUTCOMES SOME OF THESE WE

1223
00:48:37,040 --> 00:48:38,840
SUSPECT WE DON'T REALLY HAVE

1224
00:48:38,840 --> 00:48:39,760
HARD DATA TO KNOW WHAT THE

1225
00:48:39,760 --> 00:48:41,600
PROBLEMS ARE BUT THE QUALITY OF

1226
00:48:41,600 --> 00:48:46,360
THE PLURIPOTENT STEM CELLS IS

1227
00:48:46,360 --> 00:48:48,120
ABSOLUTELY CRITICAL FOR GETTING

1228
00:48:48,120 --> 00:48:50,040
GOOD RESULTS. YOU WANT TO AVOID

1229
00:48:50,040 --> 00:48:51,280
CONTAMINATION AS I TOLD YOU

1230
00:48:51,280 --> 00:48:55,800
BELOW HERE. INFORMING THESE

1231
00:48:55,800 --> 00:48:58,000
ORGANOIDS THEY HAVE TO HAVE A

1232
00:48:58,000 --> 00:49:01,800
SOLID MATRIX AND THAT IS DONE BY

1233
00:49:01,800 --> 00:49:06,880
USING NATRIGEL AND THE LOTS OF

1234
00:49:06,880 --> 00:49:08,400
NATRI-- NATRIJELL VARY. THIS WAS

1235
00:49:08,400 --> 00:49:09,920
DISCUSSED BY LINDA GRIFFITHS

1236
00:49:09,920 --> 00:49:12,480
HANDS IS SOMETHING TO KEEP IN

1237
00:49:12,480 --> 00:49:15,160
MIND. MOST MEDIA WE USE IS MADE

1238
00:49:15,160 --> 00:49:17,000
COMMERCIALLY BY STEM CELL

1239
00:49:17,000 --> 00:49:17,800
TECHNOLOGIES, BUT THERE ARE

1240
00:49:17,800 --> 00:49:19,240
OTHER PARTS OF IT ONE HAS TO

1241
00:49:19,240 --> 00:49:21,680
MAKE IN THE LAB AND THERE CAN BE

1242
00:49:21,680 --> 00:49:23,400
VARIABILITY IN THOSE PREPS. THE

1243
00:49:23,400 --> 00:49:26,160
OTHER THING TO MENTION, IT IS IN

1244
00:49:26,160 --> 00:49:28,280
DEVELOPING EXPERTISE AND DOING

1245
00:49:28,280 --> 00:49:30,320
THIS THE LOWER THE AMOUNT OF

1246
00:49:30,320 --> 00:49:32,360
HANDLING YOU CAN DO WITH THESE

1247
00:49:32,360 --> 00:49:36,640
ORGANOIDS THE BETTER OFF. THEY

1248
00:49:36,640 --> 00:49:39,760
ARE FRIABLE, FRAGILE AND IF YOU

1249
00:49:39,760 --> 00:49:41,320
CAN MINIMIZE NUMBER OF STEPS YOU

1250
00:49:41,320 --> 00:49:43,720
WILL GET BETTER RESULTS. SO

1251
00:49:43,720 --> 00:49:48,200
COMING BACK THEN TO DRUGS AND

1252
00:49:48,200 --> 00:49:50,200
THESE ORGANOIDS, I HAVE

1253
00:49:50,200 --> 00:49:52,040
MENTIONED IN PREVIOUS SLIDE

1254
00:49:52,040 --> 00:50:02,520
INTEREST AND UNDERSTANDING HOW

1255
00:50:05,840 --> 00:50:08,440
THIS IS THE EXAMPLE WE SEE IN

1256
00:50:08,440 --> 00:50:09,720
THE SHY DA VIRUS STRAINS AND

1257
00:50:09,720 --> 00:50:11,600
PATHOGENIC VIRUSES THERE IS LOSS

1258
00:50:11,600 --> 00:50:15,800
OF THIS ORGANIZATION AND LOSS OF

1259
00:50:15,800 --> 00:50:16,760
NEURAL PROGENITOR CELLS. SO WE

1260
00:50:16,760 --> 00:50:20,200
HAVE BEEN LOOKING AT A FEW

1261
00:50:20,200 --> 00:50:23,800
COMPOUNDS THAT MIGHT AFFECT US

1262
00:50:23,800 --> 00:50:25,840
AND AFFECT THIS TECHNOLOGY AND

1263
00:50:25,840 --> 00:50:29,320
HELP US UNDERSTAND WHAT IS GOING

1264
00:50:29,320 --> 00:50:32,080
ON. SO THIS IS A SET OF

1265
00:50:32,080 --> 00:50:33,520
EXPERIMENTS WE DID, I'M SHOWING

1266
00:50:33,520 --> 00:50:36,920
YOU ADDITION O VITAMIN E THE

1267
00:50:36,920 --> 00:50:38,920
WHOLE ORGANOIDS ARE SHOWN AT THE

1268
00:50:38,920 --> 00:50:42,600
TOP AND THE BOXES ARE THE INSETS

1269
00:50:42,600 --> 00:50:44,280
SHOWING PICTURES, WITHOUT

1270
00:50:44,280 --> 00:50:47,120
TREATMENT. IN THE MOCK WE SEE

1271
00:50:47,120 --> 00:50:48,960
THESE NICE VENTRICLES AND

1272
00:50:48,960 --> 00:50:51,560
NEURONS, IF WE ADD VITAMIN E NOT

1273
00:50:51,560 --> 00:50:54,920
MUCH CHANGE. THE VENTRICLES

1274
00:50:54,920 --> 00:50:56,800
REMAIN INTACT. IF WE ADD THE

1275
00:50:56,800 --> 00:50:59,840
LEAST PATHOGENIC STRAIN NOW YOU

1276
00:50:59,840 --> 00:51:03,440
CAN SEE THE WHITE DOTS WHICH ARE

1277
00:51:03,440 --> 00:51:04,360
VIRUSES THAT ARE PRESENT IN

1278
00:51:04,360 --> 00:51:09,480
INFECTION. WE STILL SEE WELL

1279
00:51:09,480 --> 00:51:11,560
ORGANIZED VENTRICLES IN THE

1280
00:51:11,560 --> 00:51:13,400
VEHICLE AND THEN IF WE ADD

1281
00:51:13,400 --> 00:51:16,560
VITAMIN E. THERE IS SOME

1282
00:51:16,560 --> 00:51:20,120
IMPROVEMENT IN THE STRUCTURE BUT

1283
00:51:20,120 --> 00:51:22,520
WE DON'T SEE DISRUPTION TOO MUCH

1284
00:51:22,520 --> 00:51:24,040
OF THE VENTRICLES WITH THIS

1285
00:51:24,040 --> 00:51:28,280
VIRUS. IF WE GO TO MOST

1286
00:51:28,280 --> 00:51:30,000
PATHOGENIC VIRUS WE SEE HERE,

1287
00:51:30,000 --> 00:51:33,080
THIS IS THE WHOLE ORGANOID, WE

1288
00:51:33,080 --> 00:51:35,400
LOSE ALL THE ORGANIZED

1289
00:51:35,400 --> 00:51:38,640
VENTRICLES.  WE SEE SOME SOX 2

1290
00:51:38,640 --> 00:51:40,320
STAININGS, VERY LITTLE MAP 2

1291
00:51:40,320 --> 00:51:44,040
STAINING BUT IF WE ADD VITAMIN E

1292
00:51:44,040 --> 00:51:46,320
YOU CAN SEE IN THE WHOLE PICTURE

1293
00:51:46,320 --> 00:51:51,360
AT THE TOP HERE NOW WE SEE

1294
00:51:51,360 --> 00:51:52,640
VENTRICLES WHERE WE DIDN'T SEE

1295
00:51:52,640 --> 00:51:54,720
THEM HERE. AND WE CAN RESCUE

1296
00:51:54,720 --> 00:51:58,600
THIS PHENOTYPE BY ADDING SOME

1297
00:51:58,600 --> 00:52:06,040
VITAMIN E. SO WE THINK THIS IS A

1298
00:52:06,040 --> 00:52:06,840
GOOD MODEL SYSTEM UNDERSTANDING

1299
00:52:06,840 --> 00:52:10,840
HOW SOME OF THESE DRUGS WORK. TO

1300
00:52:10,840 --> 00:52:14,440
SUMMARIZE THEM WE PROPOSE

1301
00:52:14,440 --> 00:52:17,400
CEREBRAL ORGANOID MODELS A GOOD

1302
00:52:17,400 --> 00:52:19,680
BRIDGE BETWEEN HUMAN BIOLOGY AND

1303
00:52:19,680 --> 00:52:22,200
ANIMAL CELL MODELS AND PERMIT

1304
00:52:22,200 --> 00:52:25,960
EXPERIMENTATION IN A COMPLEX 3

1305
00:52:25,960 --> 00:52:28,160
DIMENSIONAL CELLULAR

1306
00:52:28,160 --> 00:52:29,720
ENVIRONMENT. IF ONE IS

1307
00:52:29,720 --> 00:52:31,920
INTERESTED IN USING THIS

1308
00:52:31,920 --> 00:52:34,360
TECHNOLOGY, MASTERING THE

1309
00:52:34,360 --> 00:52:35,560
FUNDAMENTALS, I WOULD SAY IS

1310
00:52:35,560 --> 00:52:36,920
VERY, VERY IMPORTANT SO YOU ARE

1311
00:52:36,920 --> 00:52:39,200
ALWAYS STARTING PARTICULARLY

1312
00:52:39,200 --> 00:52:41,880
WITH GOOD STARTING MATERIALS,

1313
00:52:41,880 --> 00:52:44,200
IPSCs OR HUMAN PLURIPOTENT

1314
00:52:44,200 --> 00:52:46,320
STEM CELLS, IN TERMS OF GETTING

1315
00:52:46,320 --> 00:52:50,240
GOOD REPRODUCIBLE RESULTS.  THIS

1316
00:52:50,240 --> 00:52:52,000
IS NOT A SLASH AND BURN

1317
00:52:52,000 --> 00:52:56,320
TECHNOLOGY. I WOULD SAY IT TAKES

1318
00:52:56,320 --> 00:52:57,960
TIME AND ACTION CARE IN HANDLING

1319
00:52:57,960 --> 00:53:00,480
THE ORGANOIDS IN ORDER TO BE

1320
00:53:00,480 --> 00:53:04,040
ABLE TO GET GOOD REPRODUCIBLE

1321
00:53:04,040 --> 00:53:05,800
DATA. FINALLY I CLOSE BY SAYING

1322
00:53:05,800 --> 00:53:07,440
THAT THESE ORGANOIDS WE BELIEVE

1323
00:53:07,440 --> 00:53:10,520
ARE REALLY GREAT MODELS FOR

1324
00:53:10,520 --> 00:53:14,800
LOOKING AT THE PATHOGENESIS OF

1325
00:53:14,800 --> 00:53:17,480
NEUROTROPIC RNA VIRUSES. SO I

1326
00:53:17,480 --> 00:53:18,760
WANT TO ACKNOWLEDGE THE PEOPLE

1327
00:53:18,760 --> 00:53:20,360
IN THE LAB WHO DID THE WORK ON

1328
00:53:20,360 --> 00:53:22,320
THE LEFT HERE. AND ON THE RIGHT

1329
00:53:22,320 --> 00:53:26,320
I WANT TO ACKNOWLEDGE OUR

1330
00:53:26,320 --> 00:53:28,320
COLLABORATOR IN THIS WORK AND

1331
00:53:28,320 --> 00:53:32,480
THEN OUR FUNDING IS HERE. THANK

1332
00:53:32,480 --> 00:53:34,360
YOU VERY MUCH FOR YOUR

1333
00:53:34,360 --> 00:53:36,000
ATTENTION. AT APPROPRIATE TIME I

1334
00:53:36,000 --> 00:53:37,040
WILL BE HAPPY TO ANSWER YES,

1335
00:53:37,040 --> 00:53:39,840
SIYEQUESTIONS.

1336
00:53:39,840 --> 00:53:41,560
>> EXCELLENT. THANK YOU SO
MUCH,

1337
00:53:41,560 --> 00:53:43,880
DR. GEHRKE. EXCELLENT

1338
00:53:43,880 --> 00:53:45,360
PRESENTATION. WE LOOK FORWARD TO

1339
00:53:45,360 --> 00:53:46,920
THE DISCUSSION OF QUESTIONS

1340
00:53:46,920 --> 00:53:49,960
COMING UP THIS AFTERNOON. NOW I

1341
00:53:49,960 --> 00:53:52,320
WOULD LIKE TO TURN TO OUR THIRD

1342
00:53:52,320 --> 00:53:57,640
SPEAKER, OF THE SESSION,

1343
00:53:57,640 --> 00:54:02,600
INTRODUCE DR. SASHI RAMANI,

1344
00:54:02,600 --> 00:54:03,200
ASSISTANT PROFESSOR DEPARTMENT

1345
00:54:03,200 --> 00:54:05,760
OF MOLECULAR VIROLOGY AND

1346
00:54:05,760 --> 00:54:07,400
MICROBIOLOGY AT BAYLOR COLLEGE

1347
00:54:07,400 --> 00:54:10,080
OF MEDICINE. MATERNAL AND CHILD

1348
00:54:10,080 --> 00:54:13,680
HEALTH WITH FOCUS ON GASTRO

1349
00:54:13,680 --> 00:54:14,600
INTESTINAL INFECTION AND

1350
00:54:14,600 --> 00:54:15,800
VACCINES.  SHE HAS EXPERIENCE

1351
00:54:15,800 --> 00:54:18,000
WORKING ON EPIDEMIOLOGY AND

1352
00:54:18,000 --> 00:54:22,640
PATHOGENESIS OF ROW D TA VIRUSES

1353
00:54:22,640 --> 00:54:24,080
AND NORA VIRUSES WITH THE GOAL

1354
00:54:24,080 --> 00:54:25,240
OF FACTORS THAT CONTRIBUTE TO

1355
00:54:25,240 --> 00:54:26,440
DISEASE SUSCEPTIBILITY AND

1356
00:54:26,440 --> 00:54:28,560
IDENTIFY MECHANISMS TO IMPROVE

1357
00:54:28,560 --> 00:54:30,200
IMMUNE RESPONSE AND TO

1358
00:54:30,200 --> 00:54:32,240
INFECTIOUS AGENTS AND VACCINE

1359
00:54:32,240 --> 00:54:34,760
DEVELOPMENT. WORK USING HUMAN

1360
00:54:34,760 --> 00:54:35,720
INTESTINAL ORGANOID CULTURES

1361
00:54:35,720 --> 00:54:38,960
FROM DIVERSE DONORS PROVIDES

1362
00:54:38,960 --> 00:54:41,000
PHYSIOLOGICALLY RELEVANT AND

1363
00:54:41,000 --> 00:54:41,840
GENETICALLY REPRESENTATIVE

1364
00:54:41,840 --> 00:54:43,600
SYSTEM TO UNDERSTAND HOST

1365
00:54:43,600 --> 00:54:44,760
PATHOGEN INTERACTIONS AT

1366
00:54:44,760 --> 00:54:46,440
MOLECULAR LEVEL AND ENABLES

1367
00:54:46,440 --> 00:54:48,200
PRE-CLINICAL TESTING OF

1368
00:54:48,200 --> 00:54:49,840
INTERVENTIONS THROUGH

1369
00:54:49,840 --> 00:54:51,200
COLLABORATIVE -- COLLABORATION

1370
00:54:51,200 --> 00:54:53,240
WITH INTERDISCIPLINARY GROUP OF

1371
00:54:53,240 --> 00:54:54,200
RESEARCHERS AND THROUGH

1372
00:54:54,200 --> 00:54:56,480
POPULATION STUDIES TO EVALUATE

1373
00:54:56,480 --> 00:54:59,480
FINDINGS IN HUMAN SUBJECTS. DR.

1374
00:54:59,480 --> 00:55:00,920
RAMANI'S WORK TAKES A BENCH TO

1375
00:55:00,920 --> 00:55:02,280
BEDSIDE APPROACH TO

1376
00:55:02,280 --> 00:55:04,200
UNDERSTANDING ENTERIC INFECTIOUS

1377
00:55:04,200 --> 00:55:05,480
DISEASE AND TODAY DR. RAMANI

1378
00:55:05,480 --> 00:55:07,240
WILL BE SPEAKING ON THE TOPIC OF

1379
00:55:07,240 --> 00:55:08,800
HUMAN INTESTINAL ORGANOIDS AS A

1380
00:55:08,800 --> 00:55:10,680
PLATFORM FOR TESTING ANTIVIRALS

1381
00:55:10,680 --> 00:55:21,080
TO HUMAN NOR ROW VIRUS.

1382
00:55:21,880 --> 00:55:23,080
>> THANK YOU, I WANT TO
THANK

1383
00:55:23,080 --> 00:55:24,360
THE ORGANIZERS FOR THE

1384
00:55:24,360 --> 00:55:25,600
INVITATION TO BE PARTS OF THIS

1385
00:55:25,600 --> 00:55:27,640
MEETING. I'M VERY EXCITED TO

1386
00:55:27,640 --> 00:55:28,760
SHARE WITH Y'ALL SOME OF OUR

1387
00:55:28,760 --> 00:55:32,600
WORK ON USING HUMAN INTESTINAL

1388
00:55:32,600 --> 00:55:34,840
ORGANOIDS AS A PLATFORM FOR

1389
00:55:34,840 --> 00:55:37,480
ANTIVIRAL TESTING FOR HUMAN

1390
00:55:37,480 --> 00:55:39,240
NOROVIRUS. AS A BRIEF INVESTOR

1391
00:55:39,240 --> 00:55:40,520
EWE OF WHAT IS TO COME IN THESE

1392
00:55:40,520 --> 00:55:43,000
20 MINUTES I WILL DO A QUICK

1393
00:55:43,000 --> 00:55:44,320
INTRODUCTION TO HUMAN NOROVIRUS

1394
00:55:44,320 --> 00:55:46,640
AND TALK ABOUT THE HISTORICAL

1395
00:55:46,640 --> 00:55:47,960
PERSPECTIVE ON CHALLENGES THAT

1396
00:55:47,960 --> 00:55:49,040
WE HAD WITH GROWING THIS VIRUS

1397
00:55:49,040 --> 00:55:54,480
IN THE LAB. AND HOW ANDROIDS ARE

1398
00:55:54,480 --> 00:55:56,000
USEFUL TO STUDY VIRAL

1399
00:55:56,000 --> 00:55:57,680
REPLICATION. IN THE CONTEXT OF

1400
00:55:57,680 --> 00:55:59,000
ANTIVIRAL, I WANT TO TELL YOU

1401
00:55:59,000 --> 00:56:00,440
PIPELINE WE HAVE IN THE LAB AND

1402
00:56:00,440 --> 00:56:03,640
WE WERE CHARGED WITH TALKING

1403
00:56:03,640 --> 00:56:04,560
ABOUT SOME OF THE CHALLENGES WE

1404
00:56:04,560 --> 00:56:06,520
FACE. SO I WILL TALK ABOUT SOME

1405
00:56:06,520 --> 00:56:08,200
CHALLENGES IN CYTOTOXICITY

1406
00:56:08,200 --> 00:56:10,160
ASSESSMENT THAT WE ENCOUNTER

1407
00:56:10,160 --> 00:56:11,480
DOING ANTIVIRUS STUDIES AND GIVE

1408
00:56:11,480 --> 00:56:13,400
UPDATES ON PROGRESS IN WHERE WE

1409
00:56:13,400 --> 00:56:15,920
ARE WITH TESTING DRUGS FOR

1410
00:56:15,920 --> 00:56:19,000
NOROVIRUS. AND I LIKE WHERE THE

1411
00:56:19,000 --> 00:56:21,960
ORGANOID FIELD IS MOVING, IN

1412
00:56:21,960 --> 00:56:23,600
TERMS OF DEVELOPING COMPLEX

1413
00:56:23,600 --> 00:56:24,840
CULTURES FOR INFECTIOUS DISEASE 

1414
00:56:24,840 --> 00:56:27,200
WITH THAT AS A AN INTRODUCTION

1415
00:56:27,200 --> 00:56:29,200
TO HUMAN NOROVIRUS. IT IS A

1416
00:56:29,200 --> 00:56:33,200
LEADING CAUSE OF THE GASTRO

1417
00:56:33,200 --> 00:56:35,240
ENTERITIS ACROSS ALL AGE GROUPS,

1418
00:56:35,240 --> 00:56:36,440
DIARRHEA, VOMITING, SOMETHING

1419
00:56:36,440 --> 00:56:37,960
YOU DO NOT WANT TO HAVE. IT HAS

1420
00:56:37,960 --> 00:56:40,200
A FAIRLY BROAD SPECTRUM OF

1421
00:56:40,200 --> 00:56:42,520
ILLNESS, IN THAT IF YOU TAKE

1422
00:56:42,520 --> 00:56:44,240
IMMUNOCOMPETENT HOST ACROSS ALL

1423
00:56:44,240 --> 00:56:46,440
AGES YOU SEE ACUTE -- PEOPLE GET

1424
00:56:46,440 --> 00:56:48,240
SICK AND SYMPTOMS RESOLVE IN A

1425
00:56:48,240 --> 00:56:50,760
COUPLE OF DAYS BUT WHEN YOU LOOK

1426
00:56:50,760 --> 00:56:52,000
AT IMMUNOCOMPROMISED PATIENTS

1427
00:56:52,000 --> 00:56:53,560
WHETHER CANCER PATIENTS OR

1428
00:56:53,560 --> 00:56:55,360
TRANSPLANT PATIENTS, INFECTIONS

1429
00:56:55,360 --> 00:56:58,160
ARE CHRONIC IN THAT NOROVIRUS

1430
00:56:58,160 --> 00:56:59,440
DIARRHEA CAN LAST YEARS AND YOU

1431
00:56:59,440 --> 00:57:01,000
CAN IMAGINE HOW THIS WOULD

1432
00:57:01,000 --> 00:57:02,800
AFFECT QUALITY OF LIFE OF THE

1433
00:57:02,800 --> 00:57:04,360
PERSON WHO ALREADY HAS A

1434
00:57:04,360 --> 00:57:08,000
CONDITION LIKE CANCER OR HAS HAD

1435
00:57:08,000 --> 00:57:10,040
M. IF YOU LOOK AT MORTALITY

1436
00:57:10,040 --> 00:57:11,520
BECAUSE OF THIS VIRUS IN

1437
00:57:11,520 --> 00:57:13,280
EXTREMES OF AGE GROUPS, SO YOUNG

1438
00:57:13,280 --> 00:57:14,760
CHILDREN AND OLDER ADULTS AND

1439
00:57:14,760 --> 00:57:17,400
THERE ARE ABOUT 200,000 DEATHS

1440
00:57:17,400 --> 00:57:19,320
ANNUALLY. SO ALL THIS TELLS YOU

1441
00:57:19,320 --> 00:57:22,000
HUMAN NOROVIRUS IS A PROBLEM A

1442
00:57:22,000 --> 00:57:25,560
BIG HEALTHCARE PROBLEM. THIS IS

1443
00:57:25,560 --> 00:57:28,040
REALLY EXPENSIVE VIRUS. IN THAT

1444
00:57:28,040 --> 00:57:33,960
IT IS ABOUT $60 MILLION PLUS $60

1445
00:57:33,960 --> 00:57:36,400
BILLION SPENT IN BECAUSE OF

1446
00:57:36,400 --> 00:57:38,920
NOROVIRUS AND MAJORITY OF THESE

1447
00:57:38,920 --> 00:57:40,280
COSTS COME FROM COSTS LIKE

1448
00:57:40,280 --> 00:57:42,080
PARENTS HAVING TO TAKE TIME OFF

1449
00:57:42,080 --> 00:57:43,720
WORK BECAUSE DAY CARE IS CLOSED

1450
00:57:43,720 --> 00:57:45,800
BECAUSE OF OUTBREAK OR HAVING TO

1451
00:57:45,800 --> 00:57:47,320
CLOSE RESTAURANT BECAUSE THERE

1452
00:57:47,320 --> 00:57:49,240
IS NOROVIRUS INFECTIONS AND YOU

1453
00:57:49,240 --> 00:57:50,800
HAVE TO SHUT DOWN THE

1454
00:57:50,800 --> 00:57:52,040
RESTAURANT, ET CETERA. AT THIS

1455
00:57:52,040 --> 00:57:54,080
POINT IN TIME THERE ARE NO

1456
00:57:54,080 --> 00:57:55,360
LICENSED VACCINES OR

1457
00:57:55,360 --> 00:57:56,360
THERAPEUTICS AND WE HAVE COME TO

1458
00:57:56,360 --> 00:57:58,080
THAT IN A MINUTE. AND I DID WANT

1459
00:57:58,080 --> 00:58:00,760
TO SAY THAT IN THE MEDIA

1460
00:58:00,760 --> 00:58:03,080
NOROVIRUS IS ALWAYS KNOWN AS THE

1461
00:58:03,080 --> 00:58:04,240
CRUISE SHIP VIRUS BUT IT IS MORE

1462
00:58:04,240 --> 00:58:05,640
THAN THAT. CRUISE SHIPS ACCOUNT

1463
00:58:05,640 --> 00:58:08,280
FOR A VERY SMALL PERCENTAGE OF

1464
00:58:08,280 --> 00:58:09,640
NOROVIRUSES CASES AND IN FACT

1465
00:58:09,640 --> 00:58:11,400
MAJORITY OF CASES COME FROM

1466
00:58:11,400 --> 00:58:12,440
HEALTHCARE FACILITIES,

1467
00:58:12,440 --> 00:58:13,760
RESTAURANTS, DAY CARES, ET

1468
00:58:13,760 --> 00:58:15,440
CETERA.  AND THE VEHICLE FOR

1469
00:58:15,440 --> 00:58:16,560
TRANSMISSION IS CONTAMINATED

1470
00:58:16,560 --> 00:58:19,840
FOOD AND WATER. SO SORRY TO

1471
00:58:19,840 --> 00:58:22,320
SPOIL YOUR LUNCH BUT LOTS OF

1472
00:58:22,320 --> 00:58:25,400
PEOPLE SAY IT IS FOODS, OYSTERS,

1473
00:58:25,400 --> 00:58:26,880
DELL LIVE MEAT CONDITION

1474
00:58:26,880 --> 00:58:28,720
CONTAMINATED WITH HUMAN

1475
00:58:28,720 --> 00:58:30,760
NOROVIRUS BUT ALSO IN

1476
00:58:30,760 --> 00:58:32,080
RECREATIONAL WATERS, YOU HEAR

1477
00:58:32,080 --> 00:58:33,400
STORIES OF THE ENTIRE FOOTBALL

1478
00:58:33,400 --> 00:58:38,640
TEAM COMING DOWN WITH NOROVIRUS.

1479
00:58:38,640 --> 00:58:41,200
AND PART OF THE REASON WHY WE

1480
00:58:41,200 --> 00:58:43,200
HAVE NOT HAD AN ANTIVIRAL OR

1481
00:58:43,200 --> 00:58:45,480
VACCINE FOR THIS VIRUS WAS THE

1482
00:58:45,480 --> 00:58:47,040
CHALLENGE IN STUDYING THIS VIRUS

1483
00:58:47,040 --> 00:58:50,400
IN THE LAB. SO THIS VIRUS, THE

1484
00:58:50,400 --> 00:58:52,840
FIRST KNOWN VIRAL CAUSE OF

1485
00:58:52,840 --> 00:58:54,400
GASTROENTERRYETIS WAS VISUALIZED

1486
00:58:54,400 --> 00:58:57,880
BY (INAUDIBLE) IN 1972 USING

1487
00:58:57,880 --> 00:58:59,840
CULTURES FROM ELEMENTARY SCHOOL

1488
00:58:59,840 --> 00:59:05,560
OUTBREAK IN NOR WALK OHIO IN

1489
00:59:05,560 --> 00:59:07,280
1968. WE STUDIED THIS VOICE FOR

1490
00:59:07,280 --> 00:59:08,360
DECADES SUMMARIZED BY THIS PAPER

1491
00:59:08,360 --> 00:59:11,160
THAT CAME OUT IN 2004 WHICH

1492
00:59:11,160 --> 00:59:12,960
LOOKED AT EFFORTS TO CULTIVATE

1493
00:59:12,960 --> 00:59:14,400
THIS VIRUS IN OVER 20 DIFFERENT

1494
00:59:14,400 --> 00:59:18,480
CELL LINES. THIS IS THE SUMMARY

1495
00:59:18,480 --> 00:59:20,680
-- THAT ALL CHANGED IN FIVE TO

1496
00:59:20,680 --> 00:59:21,920
SEVEN YEARS AGO WHEN DIFFERENT

1497
00:59:21,920 --> 00:59:25,040
MODELS OF THIS VIRUS BEGAN TO BE

1498
00:59:25,040 --> 00:59:27,760
DESCRIBED. WE DESCRIBE THE HUMAN

1499
00:59:27,760 --> 00:59:29,680
INTERESTAL ANDROID MODEL IN 2016

1500
00:59:29,680 --> 00:59:32,200
AND MORE RECENTLY ZEBRAFISH

1501
00:59:32,200 --> 00:59:33,680
MODEL. I WILL TALK ABOUT USING

1502
00:59:33,680 --> 00:59:36,440
ANDROIDS TO STUDY HUMAN

1503
00:59:36,440 --> 00:59:39,680
NOROVIRUS AS INTESTINAL FOR THIS

1504
00:59:39,680 --> 00:59:42,120
PATH GENERAL. TALKING BRIEF --

1505
00:59:42,120 --> 00:59:44,000
PATHOGEN. THIS AUDIENCE NEEDS NO

1506
00:59:44,000 --> 00:59:45,440
INTRODUCTION BUT IF YOU THINK

1507
00:59:45,440 --> 00:59:46,880
ABOUT ORGANOID CULTURE MS. THE

1508
00:59:46,880 --> 00:59:50,080
CONTEXT OF THE GUT YOU HAVE

1509
00:59:50,080 --> 00:59:52,040
TISSUE DERIVED CULTURES AND

1510
00:59:52,040 --> 00:59:53,200
CULTURES THAT COME FROM

1511
00:59:53,200 --> 00:59:56,240
PLURIPOTENT STEM CELLS.

1512
00:59:56,240 --> 00:59:59,480
PLURIPOTENT STEM CELLS HAVE A

1513
00:59:59,480 --> 01:00:00,960
STROMAL MESENCHYME, OUR EARLY

1514
01:00:00,960 --> 01:00:02,080
WORK SHOWS IN FACT THESE

1515
01:00:02,080 --> 01:00:03,840
CULTURES ARE NOT SUSCEPTIBLE TO

1516
01:00:03,840 --> 01:00:05,440
HUMAN NOROVIRUS INFECTION. SO IN

1517
01:00:05,440 --> 01:00:08,160
OUR LAB WHAT WE WORK WITH ARE

1518
01:00:08,160 --> 01:00:09,520
BASICALLY TISSUE DERIVED

1519
01:00:09,520 --> 01:00:12,360
CULTURES FROM INFANTS, ADULTS,

1520
01:00:12,360 --> 01:00:15,560
GOOD SPECIMENS WE ISOLATED

1521
01:00:15,560 --> 01:00:18,120
THESE, 3D STRUCTURE AND WE

1522
01:00:18,120 --> 01:00:23,200
PLAYED THEM AS MONOLAYERS ON 96

1523
01:00:23,200 --> 01:00:27,040
WELL PLATE. AS WE HEARD

1524
01:00:27,040 --> 01:00:28,960
YESTERDAY, IDENTIFY THIS

1525
01:00:28,960 --> 01:00:31,040
TECHNOLOGY, THESE REMARKABLE

1526
01:00:31,040 --> 01:00:33,080
CULTURES NOT TRANSFORMED TO

1527
01:00:33,080 --> 01:00:34,760
PASSAGE INDEFINITELY THEY HAVE

1528
01:00:34,760 --> 01:00:37,600
THE DIFFERENT EPITHELIAL CELL

1529
01:00:37,600 --> 01:00:39,400
TYPES. AND THEIR PHYSIOLOGICALLY

1530
01:00:39,400 --> 01:00:41,680
RESPONSIVE TO INFECTI INFECTIONN

1531
01:00:41,680 --> 01:00:42,680
MAKE THEM DIFFERENT INFECTIONS

1532
01:00:42,680 --> 01:00:45,200
OF THE GUT AND THEY DEEM

1533
01:00:45,200 --> 01:00:46,440
COMPLEXITY AND ORGANIZATION OF

1534
01:00:46,440 --> 01:00:51,920
THE EPITHELIUM THEY COME FROM.

1535
01:00:51,920 --> 01:00:55,520
SO WE SHOWED IN 2016 HIE SHOW

1536
01:00:55,520 --> 01:00:58,280
SUPPORT OF MULTIPLE VIRUSES. WE

1537
01:00:58,280 --> 01:01:01,600
TOOK TWO EXAMPLES A DOMINANT

1538
01:01:01,600 --> 01:01:04,040
STRAIN OF NOROVIRUS AND IT HAS

1539
01:01:04,040 --> 01:01:06,480
DIFFERENT PANDEMIC VARIANTS. IF

1540
01:01:06,480 --> 01:01:09,320
YOU LOOK AT THE RTPCR YOU SEE IN

1541
01:01:09,320 --> 01:01:12,560
THE LIGHT BLUE IS BINDING AND

1542
01:01:12,560 --> 01:01:14,440
HOW MUCH INFECTION VIRUSES

1543
01:01:14,440 --> 01:01:16,200
PRODUCE AT 72 HOURS AND YOU CAN

1544
01:01:16,200 --> 01:01:18,200
SEE HERE THAT THERE IS INCREASE

1545
01:01:18,200 --> 01:01:21,280
IN REPLICATION FROM ONE FOR ALL

1546
01:01:21,280 --> 01:01:25,600
THESE DIFFERENT VIRUSES WE LOOK

1547
01:01:25,600 --> 01:01:30,000
BY IMMUNOFLUORESCENCE STAINING

1548
01:01:30,000 --> 01:01:32,320
FOR THE CAPSID AND YOU CAN SEE

1549
01:01:32,320 --> 01:01:35,280
20% INFECTED CELLS, YOU CAN SEE

1550
01:01:35,280 --> 01:01:37,040
THAT ALSO IMMUNOFLUORESCENCE AND

1551
01:01:37,040 --> 01:01:40,160
IN SOME CASES WE WILL SEE

1552
01:01:40,160 --> 01:01:41,280
CYTOKINE EFFECTS. SO WE

1553
01:01:41,280 --> 01:01:43,680
ESSENTIALLY SHOWED REPLICATION

1554
01:01:43,680 --> 01:01:45,440
FOR A FEW VARIANTS, THE

1555
01:01:45,440 --> 01:01:49,080
PROTOTYPE VIRUS THAT CAME FROM

1556
01:01:49,080 --> 01:01:50,920
GP 1 STRAIN AND TWO OTHERS. AND

1557
01:01:50,920 --> 01:01:53,960
SINCE THEN WE HAVE GONE ON TO

1558
01:01:53,960 --> 01:01:55,720
EXPAND PROFILE OF NOROVIRUS. AND

1559
01:01:55,720 --> 01:01:57,920
WE HAVE DONE THIS BY WORKING

1560
01:01:57,920 --> 01:01:59,800
WITH MEDIA, TRAINING MEDIA

1561
01:01:59,800 --> 01:02:01,440
COMPOSITIONS AND WE WORK WITH

1562
01:02:01,440 --> 01:02:04,520
MAKING GENETICALLY QUANTIFIED

1563
01:02:04,520 --> 01:02:06,960
ORGANOIDS. COMPLEX EPIDEMIOLOGY,

1564
01:02:06,960 --> 01:02:09,000
THERE ARE MANY DIFFERENT GENOME

1565
01:02:09,000 --> 01:02:11,440
GROUPS, ONE GENOME GROUP WITHIN

1566
01:02:11,440 --> 01:02:14,280
GENOTYPES SOME GENOTYPES HAVE

1567
01:02:14,280 --> 01:02:15,440
VARIANTS, AS I MENTION THE

1568
01:02:15,440 --> 01:02:17,240
PREVIOUS SLIDE YOU HAVE PANDEMIC

1569
01:02:17,240 --> 01:02:18,720
VARIANTS THAT EVOLVE EVERY FEW

1570
01:02:18,720 --> 01:02:22,640
YEARS. SO NOW WE HAVE A FAIRLY

1571
01:02:22,640 --> 01:02:23,600
LARGE BATCH OF STRAINS AND WE

1572
01:02:23,600 --> 01:02:25,120
HAVE BEEN ABLE TO SHOW THAT

1573
01:02:25,120 --> 01:02:27,880
NOROVIRUS CAN GROW IN ALL

1574
01:02:27,880 --> 01:02:31,000
SEGMENTS OF THE INTESTINE,

1575
01:02:31,000 --> 01:02:34,080
DUODENUM, ILEUM BUT DOESN'T

1576
01:02:34,080 --> 01:02:35,200
REALLY GROW (INAUDIBLE). THE

1577
01:02:35,200 --> 01:02:37,600
OTHER REASON THESE CULTURES ARE

1578
01:02:37,600 --> 01:02:39,440
MULTIPLE STUDY NOROVIRUS IS THAT

1579
01:02:39,440 --> 01:02:42,160
THEY REFLECT THE HOST GENETIC

1580
01:02:42,160 --> 01:02:44,000
SUSCEPTIBILITY TO THE VIRUS. SO

1581
01:02:44,000 --> 01:02:45,880
AS EARLY AS THE '70s IT WAS

1582
01:02:45,880 --> 01:02:47,920
KNOWN A GENETIC SUSCEPTIBILITY

1583
01:02:47,920 --> 01:02:49,800
FACTOR FOR THIS VIRUS AND THAT

1584
01:02:49,800 --> 01:02:54,840
IS THE EXPRESSION OF FUNCTION OF

1585
01:02:54,840 --> 01:02:58,120
TRANSFERASE. PEOPLE HAVE

1586
01:02:58,120 --> 01:03:00,360
FUNCTION OF TRANSFERASE,

1587
01:03:00,360 --> 01:03:02,600
(INAUDIBLE) SUGARS IN MUCOSAL

1588
01:03:02,600 --> 01:03:03,960
SECRETIONS EPITHELIAL CELLS,

1589
01:03:03,960 --> 01:03:05,160
SECRET TORRS AND THEY ARE

1590
01:03:05,160 --> 01:03:06,520
SUSCEPTIBLE TO DIARRHEA AND

1591
01:03:06,520 --> 01:03:08,000
VOMITING BY MAJORITY OF THE

1592
01:03:08,000 --> 01:03:11,880
NOROVIRUSES.  ON THE OTHER HAND

1593
01:03:11,880 --> 01:03:13,840
IF YOU NON-SECRETER YOU DO NOT

1594
01:03:13,840 --> 01:03:15,560
GET INFECTED YOU DON'T BECOME

1595
01:03:15,560 --> 01:03:17,480
ILL WITH MOST VIRUSES. T WHAT

1596
01:03:17,480 --> 01:03:19,080
WAS INTERESTING WAS WHEN WE MADE

1597
01:03:19,080 --> 01:03:23,960
THE ORGANOIDS WE MADE ORGANOIDS

1598
01:03:23,960 --> 01:03:27,080
FROM ENTOIDS FROM SECRETERS.

1599
01:03:27,080 --> 01:03:31,040
ONLY GOT INFECT WITH THE G2 4

1600
01:03:31,040 --> 01:03:34,960
DOMINANT NOROVIRUS. NOT --

1601
01:03:34,960 --> 01:03:36,560
SUGGESTING THESE ORGANOIDS ARE

1602
01:03:36,560 --> 01:03:37,480
BEHAVING JUST LIKE WHAT YOU

1603
01:03:37,480 --> 01:03:40,400
WOULD EXPECT THEM TO IN TERMS OF

1604
01:03:40,400 --> 01:03:42,440
RETAINING GENETIC SUSCEPTIBILITY

1605
01:03:42,440 --> 01:03:44,680
PROFILE. WE TOOK THIS ONE STEP

1606
01:03:44,680 --> 01:03:48,000
FURTHER TO SEE HOW IMPORTANT IS

1607
01:03:48,000 --> 01:03:50,200
THE EXPRESSION OF GLYCANS SO WE

1608
01:03:50,200 --> 01:03:52,400
BASICALLY TOOK ONE SECRETER

1609
01:03:52,400 --> 01:03:55,400
ORGANOID AND ONE SECRET CRETEER

1610
01:03:55,400 --> 01:03:58,760
LINE AND MODIFY EXPRESSION OF

1611
01:03:58,760 --> 01:04:02,000
SUGAR EXPRESSI EXPRESSION. SO HU

1612
01:04:02,000 --> 01:04:04,160
HAVE A WILD TYPE SECRETER LINE,

1613
01:04:04,160 --> 01:04:06,880
WE KNOCKED OUT AND NO LONGER SEE

1614
01:04:06,880 --> 01:04:11,520
APICAL EXPRESSION OF THE GLYCAN

1615
01:04:11,520 --> 01:04:14,000
SHOWN, HERE YOU HAVE

1616
01:04:14,000 --> 01:04:16,440
NON-SECRETER LINE, THIS ONE WE

1617
01:04:16,440 --> 01:04:20,240
KNOCK IN FUT 2 GLYCAN

1618
01:04:20,240 --> 01:04:22,320
EXPRESSION. IT CHANGES THE

1619
01:04:22,320 --> 01:04:23,240
SUSCEPTIBILITY PATTERN OF

1620
01:04:23,240 --> 01:04:25,040
INFECTION SO YOU GO FROM A

1621
01:04:25,040 --> 01:04:26,680
SUSCEPTIBLE LINE TO COMPLETELY

1622
01:04:26,680 --> 01:04:28,280
RESISTANT LINE BUT YOU GO FROM

1623
01:04:28,280 --> 01:04:29,880
RESISTANT LINE TO A SUSCEPTIBLE

1624
01:04:29,880 --> 01:04:31,880
LINE. ALL THIS INDICATING THAT

1625
01:04:31,880 --> 01:04:33,480
THIS IS A REALLY GOOD MODEL FOR

1626
01:04:33,480 --> 01:04:36,480
US TO STUDY HUMAN NOROVIRUS.

1627
01:04:36,480 --> 01:04:37,720
WHICH BASICALLY MEANS YOU CAN

1628
01:04:37,720 --> 01:04:40,360
THEN USE THIS MODEL AS A

1629
01:04:40,360 --> 01:04:41,520
PLATFORM PRE-CLINICAL PLATFORM

1630
01:04:41,520 --> 01:04:43,280
FOR ANTIVIRAL TESTING. WE

1631
01:04:43,280 --> 01:04:44,960
STARTED WITH A FAIRLY SIMPLISTIC

1632
01:04:44,960 --> 01:04:47,440
APPROACH. WE TAKE NOROVIRUS

1633
01:04:47,440 --> 01:04:49,920
POSITIVE SUSPENSIONS WE ADD DRUG

1634
01:04:49,920 --> 01:04:53,640
OR NO DRUG TO HIV MONOLAYERS ON

1635
01:04:53,640 --> 01:04:55,040
96 WELL PLACE AND ASK TWO

1636
01:04:55,040 --> 01:04:57,680
QUESTIONS. IS THE DRUG CYTOTOXIC

1637
01:04:57,680 --> 01:05:00,360
AND IS THERE REPLICATION. AND WE

1638
01:05:00,360 --> 01:05:02,800
ASSESS THIS BY PATHWAY AND RTPCR

1639
01:05:02,800 --> 01:05:04,320
ASSAYS. WE LOOK AT DIFFERENT

1640
01:05:04,320 --> 01:05:07,160
CLASSES OF DRUGS. SO WE LOOK AT

1641
01:05:07,160 --> 01:05:08,520
MEDICINAL CHEMISTRY APPROACHES

1642
01:05:08,520 --> 01:05:11,040
FOR PROTEASE INHIBITORS.

1643
01:05:11,040 --> 01:05:13,480
NOROVIRUS IS A PROBLEM IN

1644
01:05:13,480 --> 01:05:15,440
IMMUNOCOMPROMISED PATIENTS SO

1645
01:05:15,440 --> 01:05:18,760
THERE ARE CERTAIN DRUGS USED FOR

1646
01:05:18,760 --> 01:05:19,760
ANECDOTALLY THEY WORK IN SOME

1647
01:05:19,760 --> 01:05:21,360
CASES DON'T WORK IN SOME CASES

1648
01:05:21,360 --> 01:05:23,760
WE WANT TO TEST THOSE DRUGS. WE

1649
01:05:23,760 --> 01:05:25,440
WANT TO SCREEN ANTIVIRAL

1650
01:05:25,440 --> 01:05:26,880
LIBRARIES AND MOST IMPORTANTLY

1651
01:05:26,880 --> 01:05:29,800
EXCITING FOR US IS BECAUSE WE

1652
01:05:29,800 --> 01:05:32,280
NOW HAVE MODEL SYSTEM FOR THIS

1653
01:05:32,280 --> 01:05:34,600
VIRUS, WE ARE NOW IN BIOLOGY AND

1654
01:05:34,600 --> 01:05:38,000
SO BASED ON NEUROBIOLOGY

1655
01:05:38,000 --> 01:05:39,320
FINDINGS CAN YOU IDENTIFY

1656
01:05:39,320 --> 01:05:40,760
COMPOUNDS USED TO TREAT

1657
01:05:40,760 --> 01:05:42,240
NOROVIRUS AND I SHOW YOU THE

1658
01:05:42,240 --> 01:05:46,960
DATA FOR ALL THESE. GOING TO

1659
01:05:46,960 --> 01:05:49,840
SHOW YOU DATA WITH FOUR HIV HIE

1660
01:05:49,840 --> 01:05:52,240
LINES J 2 AND J 4 AND

1661
01:05:52,240 --> 01:05:53,640
GENETICALLY MODIFIED LINES FOR

1662
01:05:53,640 --> 01:05:56,240
KNOCK OUTLINE ON THE J 2

1663
01:05:56,240 --> 01:05:58,280
BACKBONE AND KNOCK IN LINE ON

1664
01:05:58,280 --> 01:05:59,920
THE J 4 AND WE CHOSE THESE LINES

1665
01:05:59,920 --> 01:06:01,760
BECAUSE THESE LINES REALLY

1666
01:06:01,760 --> 01:06:03,240
SUPPORT BETTER REPLICATION OF

1667
01:06:03,240 --> 01:06:09,080
MANY HUMAN NOROVIRUSES.  WE WERE

1668
01:06:09,080 --> 01:06:11,600
LOOKING AT ASSAYS AND RT PCR.

1669
01:06:11,600 --> 01:06:13,360
WHEN WATERED DOING TRANSFERASE

1670
01:06:13,360 --> 01:06:14,240
WE HAVE AN INTERESTING

1671
01:06:14,240 --> 01:06:17,440
OBSERVATION. THIS IS WORK LED BY

1672
01:06:17,440 --> 01:06:19,680
A GRADUATE STUDENT IN THE GROUP,

1673
01:06:19,680 --> 01:06:21,360
MIRANDA NOTICED WHEN SHE GAVE

1674
01:06:21,360 --> 01:06:23,320
THESE DIFFERENT LINES SO FOUR

1675
01:06:23,320 --> 01:06:26,120
LINES HERE J 2 (INAUDIBLE) J 4

1676
01:06:26,120 --> 01:06:27,760
AND J 4 RAT THE BOTTOM, WHEN YOU

1677
01:06:27,760 --> 01:06:31,040
TAKE THESE LINES AND EITHER

1678
01:06:31,040 --> 01:06:33,280
LICENSE CONTROL OR TAKE THE --

1679
01:06:33,280 --> 01:06:36,600
IN OUR CASE DMSO OR A DRUG, I

1680
01:06:36,600 --> 01:06:37,920
WILL SHOW YOU IN A MINUTE, YOU

1681
01:06:37,920 --> 01:06:40,480
SEE THE STANDARD PROTOCOL WHICH

1682
01:06:40,480 --> 01:06:43,680
IS 30 MINUTES THE VALUES REALLY

1683
01:06:43,680 --> 01:06:47,440
AT LIMIT OF INFECTION SO 3 OR

1684
01:06:47,440 --> 01:06:48,760
HIGHER WHICH MEANS YOU DON'T GET

1685
01:06:48,760 --> 01:06:53,080
ACCURATE RESULTS WITH THOSE

1686
01:06:53,080 --> 01:06:54,880
VALUES. WE RECOMMEND YOU SHORTEN

1687
01:06:54,880 --> 01:06:56,560
THE TIME.  SHE SHORTENED THE

1688
01:06:56,560 --> 01:06:57,960
TIME TO 20 MINUTES 10 MINUTES

1689
01:06:57,960 --> 01:06:59,560
AND FIVE MINUTES.  IT IS ONLY AT

1690
01:06:59,560 --> 01:07:02,000
FIVE MINUTES YOU START TO SEE

1691
01:07:02,000 --> 01:07:04,760
SOME VALUES THAT ARE MORE LIKELY

1692
01:07:04,760 --> 01:07:08,280
TO BE WITHIN THE RANGE. WHEN YOU

1693
01:07:08,280 --> 01:07:10,400
USE THE (INAUDIBLE) TOXICITY THE

1694
01:07:10,400 --> 01:07:12,400
DATA IS STRIKING. I WANT TO SHOW

1695
01:07:12,400 --> 01:07:17,200
YOU DATA FROM TWO LINES. THE J 2

1696
01:07:17,200 --> 01:07:17,880
LINE WITH (INAUDIBLE) IF YOU

1697
01:07:17,880 --> 01:07:20,360
LOOK HERE AT THE 30 MINUTE TIME

1698
01:07:20,360 --> 01:07:23,760
POINT, DMSO LOOK LIKE THEY ARE

1699
01:07:23,760 --> 01:07:25,760
90% CYTOTOXIC WHICH WAS NOT THE

1700
01:07:25,760 --> 01:07:27,160
CASE WHEN YOU LOOK AT THE CELLS

1701
01:07:27,160 --> 01:07:29,440
UNDER THE MICROSCOPE. WHAT IS

1702
01:07:29,440 --> 01:07:31,000
INTERESTING ALSO IS THE TWO

1703
01:07:31,000 --> 01:07:32,160
LINES ARE VERY DIFFERENT FROM

1704
01:07:32,160 --> 01:07:36,760
EACH OTHER. SO THE J 4 FUT 2 FOR

1705
01:07:36,760 --> 01:07:39,240
EXAMPLE, LOOKS LIKE 30%

1706
01:07:39,240 --> 01:07:43,240
CYTOTOXIC, THE DRUG 80%

1707
01:07:43,240 --> 01:07:45,400
CYTOTOXIC. BUT IF YOU SHORT TN

1708
01:07:45,400 --> 01:07:48,320
ASSAY TO 5 MINUTE TIME. THERE IS

1709
01:07:48,320 --> 01:07:49,720
CYTOTOXICITY AND IF YOU DO

1710
01:07:49,720 --> 01:07:51,080
RELATIVE CYTOTOXICITY

1711
01:07:51,080 --> 01:07:52,880
CALCULATIONS THEY ARE GOING TO

1712
01:07:52,880 --> 01:07:54,040
BE QUITE DIFFERENT WITHIN

1713
01:07:54,040 --> 01:07:56,280
DIFFERENT TIME POINTS. SO THIS

1714
01:07:56,280 --> 01:07:58,160
GOT MIR DRAIN THINKING HOW DO

1715
01:07:58,160 --> 01:08:00,320
YOU MODIFY -- MIRANDA THINKING

1716
01:08:00,320 --> 01:08:02,880
ABOUT HOW TO MODIFY THE ASSAY

1717
01:08:02,880 --> 01:08:05,360
AND TAKE THIS THAT YOU USE FOR

1718
01:08:05,360 --> 01:08:07,120
THE ASSAY AND DILUTE THEM TO

1719
01:08:07,120 --> 01:08:08,800
FIGURE OUT WHERE YOU GET SOME

1720
01:08:08,800 --> 01:08:10,560
SORT OF LINEAR RANGE. ONCE AGAIN

1721
01:08:10,560 --> 01:08:13,280
THE DATA FROM FOUR LINES SHOWN

1722
01:08:13,280 --> 01:08:15,040
OVER HERE, 50 CALCULATIONS TO

1723
01:08:15,040 --> 01:08:17,560
FIND WHERE EXACTLY YOU HAVE END

1724
01:08:17,560 --> 01:08:18,800
POINTS AND YOU CAN SEE THE

1725
01:08:18,800 --> 01:08:19,800
DILUTION VARIES FOR THE

1726
01:08:19,800 --> 01:08:22,600
DIFFERENT LINES.  SO NOW WHEN

1727
01:08:22,600 --> 01:08:25,120
YOU CHOOSE THIS GOOD DILUTION

1728
01:08:25,120 --> 01:08:26,800
AND ASSAY YOUR RESULTS ARE

1729
01:08:26,800 --> 01:08:28,720
DIFFERENT. SO ONCE AGAIN DATA

1730
01:08:28,720 --> 01:08:33,560
FOR J 2 AND JFUT 2 WHAT YOU SEE

1731
01:08:33,560 --> 01:08:37,200
HERE IS THAT FOR THE J 2 LINE

1732
01:08:37,200 --> 01:08:39,840
DMSO IS 50% CYTOTOXIC. THE DRUG

1733
01:08:39,840 --> 01:08:43,040
IS 30%. FOR THE J 2 IT IS 5% AND

1734
01:08:43,040 --> 01:08:46,000
20%. THIS IS WHAT WE SEE UNDER

1735
01:08:46,000 --> 01:08:47,760
THE MICROSCOPE. AND WE DON'T SEE

1736
01:08:47,760 --> 01:08:48,880
BIG DIFFERENCE BETWEEN THE

1737
01:08:48,880 --> 01:08:51,920
DIFFERENT TIME POINTS. ALL THIS

1738
01:08:51,920 --> 01:08:53,600
TO SUGGEST THE THAT MODIFYING

1739
01:08:53,600 --> 01:08:56,080
THE ASSAY BY DILUTING MAYBE

1740
01:08:56,080 --> 01:08:56,880
SOMETHING IMPORTANT TO CONSIDER.

1741
01:08:56,880 --> 01:08:59,800
IN ADDITION, MIRANDA TESTED

1742
01:08:59,800 --> 01:09:03,680
OTHER COMMERCIALLY AVAILABLE

1743
01:09:03,680 --> 01:09:04,800
ASSAYS, TO SEE SHOULD WE BE

1744
01:09:04,800 --> 01:09:07,680
GOING FOR OTHER ASSAYS INSTEAD

1745
01:09:07,680 --> 01:09:09,800
OF LDH ASSAYS. I SHOW YOU DATA

1746
01:09:09,800 --> 01:09:12,360
HERE OF THE RESULTS WHICH IS

1747
01:09:12,360 --> 01:09:15,280
USED IN IMMUNOCOMPROMISED

1748
01:09:15,280 --> 01:09:16,800
PATIENTS AGAIN SOMETIMES WORK,

1749
01:09:16,800 --> 01:09:18,200
DOESN'T WORK SOMETIMES. WHAT YOU

1750
01:09:18,200 --> 01:09:20,840
SEE HERE IS LOOK AT DMSO

1751
01:09:20,840 --> 01:09:24,320
NON-CYTOTOXIC CONCENTRATION OR

1752
01:09:24,320 --> 01:09:26,160
CYTOTOXIC CONCENTRATION, THERE

1753
01:09:26,160 --> 01:09:29,160
IS A BIG DIFFERENCE BETWEEN LDH

1754
01:09:29,160 --> 01:09:30,520
ASSAYS IN DARK BLUE COMPARED TO

1755
01:09:30,520 --> 01:09:32,880
ALL THE OTHER ASSAYS AND THAT

1756
01:09:32,880 --> 01:09:34,200
HOLDS TRUE FOR BOTH LINES. 

1757
01:09:34,200 --> 01:09:35,480
IMPORTANTLY THAT'S JUST LOOKING

1758
01:09:35,480 --> 01:09:39,800
HERE AT THE J 4 FUT 2 LINE. THE

1759
01:09:39,800 --> 01:09:42,000
-- DOES SUGGEST 70% VIABLE.

1760
01:09:42,000 --> 01:09:43,960
UNDER THE MICROSCOPE OR FLOW

1761
01:09:43,960 --> 01:09:46,000
SIGH FOE METRICS IT IS 70% DEAD

1762
01:09:46,000 --> 01:09:48,560
SO ALL THIS IS TO TELL US THAT

1763
01:09:48,560 --> 01:09:50,840
WHEN YOU ARE USING MEDICINAL

1764
01:09:50,840 --> 01:09:53,000
ORGANOID CULTURES, WE MAY NEED

1765
01:09:53,000 --> 01:09:54,680
TO LOOK AT CYTOTOXICITY BY MORE

1766
01:09:54,680 --> 01:09:56,800
THAN ONE ASSAY AND WE NEED TO BE

1767
01:09:56,800 --> 01:09:59,920
VERY MINDFUL THAT THERE IS

1768
01:09:59,920 --> 01:10:02,720
VARIABILITY BETWEEN ENTROID

1769
01:10:02,720 --> 01:10:04,120
LINES. SO WE ARE TESTING

1770
01:10:04,120 --> 01:10:04,920
ANTIVIRALS AT THAT TIME SAME

1771
01:10:04,920 --> 01:10:06,600
TIME AND WE HAVE A PIPELINE FOR

1772
01:10:06,600 --> 01:10:08,320
ANTIVIRAL DESIGN AND DEVELOPMENT

1773
01:10:08,320 --> 01:10:10,400
IN TESTING. AS I MENTION WE CAN

1774
01:10:10,400 --> 01:10:12,400
DIVIDE WHAT WE DO IN A FEW

1775
01:10:12,400 --> 01:10:14,320
CATEGORIES AND I WILL SHOW YOU

1776
01:10:14,320 --> 01:10:15,200
EXAMPLESES OF ONES THAT WORK FOR

1777
01:10:15,200 --> 01:10:16,880
US.  AS A VIROLOGIST YOU ARE

1778
01:10:16,880 --> 01:10:18,560
INTERESTED IN PROTEASE AND

1779
01:10:18,560 --> 01:10:20,760
POLYMERASE INHIBITORS. THE --

1780
01:10:20,760 --> 01:10:22,720
SHOWN ON THE BOTTOM HERE, SO

1781
01:10:22,720 --> 01:10:26,880
HERE I HAVE TO SHOW WHEN YOU

1782
01:10:26,880 --> 01:10:29,200
GAVE (INAUDIBLE) VIRUS NOROVIRUS

1783
01:10:29,200 --> 01:10:30,880
YOU EVENTUALLY VARY

1784
01:10:30,880 --> 01:10:32,680
SIGNIFICANTLY REDUCE G1

1785
01:10:32,680 --> 01:10:34,320
REPLICATION IN A HOST DEPENDENT

1786
01:10:34,320 --> 01:10:38,080
MANNER. AS I MENTIONED, WE ARE

1787
01:10:38,080 --> 01:10:39,720
LOOMING WITH BIOLOGY, THAT GIVES

1788
01:10:39,720 --> 01:10:40,480
OPPORTUNITIES TO THINK ABOUT

1789
01:10:40,480 --> 01:10:41,520
REPURPOSING DRUGS, WHAT WE HEARD

1790
01:10:41,520 --> 01:10:44,360
IN THE FIRST TALK. SO WHEN WE

1791
01:10:44,360 --> 01:10:45,880
PUBLISH THE SCIENCE PAPER AND

1792
01:10:45,880 --> 01:10:49,000
LOOK AT VIRUS REPLICATION, WE

1793
01:10:49,000 --> 01:10:53,520
NOTICE THE GLOBALLY DOMINANT G2

1794
01:10:53,520 --> 01:10:55,080
4 STRAIN GO TO ANDROIDS WITHOUT

1795
01:10:55,080 --> 01:10:57,280
A PROBLEM BUT OTHER VIRUSES FOR

1796
01:10:57,280 --> 01:11:00,040
EXAMPLE IN G2 3 STRAIN YOU

1797
01:11:00,040 --> 01:11:04,880
REQUIRE BILE OR BILE ACID FOR

1798
01:11:04,880 --> 01:11:06,680
REPLICATION. REPLICATION IN THE

1799
01:11:06,680 --> 01:11:08,600
PRESENCE OF BILE. WHICH LED US

1800
01:11:08,600 --> 01:11:11,600
TO ASK IF YOU USE A BILE ACID

1801
01:11:11,600 --> 01:11:12,800
STRAIN WHAT HAPPENS? WE ACTUALLY

1802
01:11:12,800 --> 01:11:19,760
SEE THE BILE ACID SEQUENCE WITH

1803
01:11:19,760 --> 01:11:21,160
CHOLESTEROL STY RA MEAN INHIBITS

1804
01:11:21,160 --> 01:11:23,160
NOROVIRUS. SIMILARLY WE LEARNED

1805
01:11:23,160 --> 01:11:25,360
THAT WHEN YOU USE BILE OR BILE

1806
01:11:25,360 --> 01:11:28,320
ACID IN THIS CASE BILE ACID YOU

1807
01:11:28,320 --> 01:11:31,600
HAVE RAPID INCREASE IN

1808
01:11:31,600 --> 01:11:33,760
REGENERATION IN ENTROID

1809
01:11:33,760 --> 01:11:35,840
CULTURES, HAPPENS WITHIN TEN

1810
01:11:35,840 --> 01:11:39,040
MINUTES. YES GCDCA AND RED

1811
01:11:39,040 --> 01:11:40,080
STAINING, AND THIS IS IMPORTANT

1812
01:11:40,080 --> 01:11:42,280
FOR THE REPLICATION OF THIS

1813
01:11:42,280 --> 01:11:44,880
PARTICULAR VIRUS, G2, 3 VIRUS.

1814
01:11:44,880 --> 01:11:46,640
SO WHAT HAPPENS IF YOU USE

1815
01:11:46,640 --> 01:11:48,880
SOMETHING WHICH INHIBIT THE

1816
01:11:48,880 --> 01:11:51,000
CERAMIDE FORMATION. THIS IS

1817
01:11:51,000 --> 01:11:54,240
MEDIATED BY MILLENASE, SO WHEN

1818
01:11:54,240 --> 01:11:56,040
YOU USE INDIVIDUAL LIKE AIM TRIP

1819
01:11:56,040 --> 01:11:58,480
LIEN WHICH IS USED AS AN

1820
01:11:58,480 --> 01:12:00,040
ANTIDEPRESSANT BUT ALSO ACE

1821
01:12:00,040 --> 01:12:01,600
INHIBITOR YOU CAN SEE IT IS DOSE

1822
01:12:01,600 --> 01:12:04,200
DEPENDENT REDUCTION IN NOROVIRUS

1823
01:12:04,200 --> 01:12:05,960
REPLICATION. IN ADDITION TO ALL

1824
01:12:05,960 --> 01:12:07,120
THESE TARGETED APPROACHES YOU

1825
01:12:07,120 --> 01:12:09,960
WANT TO LOOK AT LIBRARIES AND

1826
01:12:09,960 --> 01:12:12,200
SCREEN LIBRARIES ANTIVIRALS. AS

1827
01:12:12,200 --> 01:12:14,160
AN EXAMPLE HERE I SHOW YOU DATA

1828
01:12:14,160 --> 01:12:18,000
WHICH CAME OUT OF A GROUP IN

1829
01:12:18,000 --> 01:12:20,160
JAPAN, DATA SCREEN 3626

1830
01:12:20,160 --> 01:12:21,720
COMPOUNDS USING HUMAN INTESTINAL

1831
01:12:21,720 --> 01:12:25,280
ANDROIDS AND IDENTIFY ANTIVIRAL

1832
01:12:25,280 --> 01:12:27,320
WHICH IS NOT CYTOTOXIC AND HAS

1833
01:12:27,320 --> 01:12:30,640
AAN INHIBITORY EFFECT ON HUMAN

1834
01:12:30,640 --> 01:12:32,400
NOROVIRUS REPLICATION. SO DID

1835
01:12:32,400 --> 01:12:34,000
THIS WITH MULTIPLE LINES AND

1836
01:12:34,000 --> 01:12:35,800
IDENTIFIED IT CAN INHIB

1837
01:12:35,800 --> 01:12:37,600
MULTIPLE NOROVIRUSES. SO WHAT I

1838
01:12:37,600 --> 01:12:40,360
WANT YOU TO TAKE AWAY FROM ALL

1839
01:12:40,360 --> 01:12:42,200
THIS IS HUMAN INTESTINAL

1840
01:12:42,200 --> 01:12:44,440
ANDROIDS ARE EXCELLENT MODEL FOR

1841
01:12:44,440 --> 01:12:45,440
PREVIOUSLY NON-COMPATIBLE

1842
01:12:45,440 --> 01:12:47,320
VIRUSES AND IMPORTANTLY IN THE

1843
01:12:47,320 --> 01:12:49,480
CONTEXT OF ANTIVIRAL, IT IS A

1844
01:12:49,480 --> 01:12:51,880
GREAT PRE-CLINICAL TOOL FOR DRUG

1845
01:12:51,880 --> 01:12:53,920
TESTING. BUT I THINK IT IS

1846
01:12:53,920 --> 01:12:55,480
IMPORTANT TO BE COGNIZANT OF THE

1847
01:12:55,480 --> 01:12:57,960
FACT THAT ORGANOIDS REALLY MIMIC

1848
01:12:57,960 --> 01:12:59,800
THE HOST VARIABILITY THAT IS

1849
01:12:59,800 --> 01:13:01,920
SEEN IN RESPONSE TO DRUGS. SO IF

1850
01:13:01,920 --> 01:13:05,960
YOU ARE USING THIS ANTIVIRAL YOU

1851
01:13:05,960 --> 01:13:07,560
WILL NEED TO CONSIDER TESTING

1852
01:13:07,560 --> 01:13:10,400
MULTIPLE LINES, AND THAT BRINGS

1853
01:13:10,400 --> 01:13:11,520
THE QUESTION WHAT IS A GOOD

1854
01:13:11,520 --> 01:13:12,560
NUMBER TO USE.  I DON'T THINK WE

1855
01:13:12,560 --> 01:13:14,680
REALLY HAVE A GOOD ANSWER AT

1856
01:13:14,680 --> 01:13:17,040
THIS POINT IN TIME. WE HAVE

1857
01:13:17,040 --> 01:13:18,040
LEARNED THROUGH OUR -- THAT IT

1858
01:13:18,040 --> 01:13:20,600
IS IMPORTANT TO EVALUATE

1859
01:13:20,600 --> 01:13:21,600
CYTOTOXICITY BY MULTIPLE

1860
01:13:21,600 --> 01:13:24,040
MEASURES AND YOU NEED TO

1861
01:13:24,040 --> 01:13:25,280
CONSIDER MODE OF ACTION IF YOU

1862
01:13:25,280 --> 01:13:27,400
KNOW IT FOR CHOOSING WHICH

1863
01:13:27,400 --> 01:13:29,480
CYTOTOXICITY TESTS YOU WILL USE.

1864
01:13:29,480 --> 01:13:31,920
YOU WILL NEED TO BE MINDFUL OF

1865
01:13:31,920 --> 01:13:33,400
VARIATION OVER TIME EVEN WITHIN

1866
01:13:33,400 --> 01:13:35,320
THE SAME LINE. WE TRY TO MAKE

1867
01:13:35,320 --> 01:13:36,360
THIS SAME NUMBER OF CELLS EVERY

1868
01:13:36,360 --> 01:13:38,560
TIME AND ALL THAT BUT STILL

1869
01:13:38,560 --> 01:13:39,320
VARIABILITY IN SOMETHING WE NEED

1870
01:13:39,320 --> 01:13:42,680
TO BE MINDFUL OF. WE ARE MOVING

1871
01:13:42,680 --> 01:13:44,880
TO USING 384 WELL PLATE ASSAYS

1872
01:13:44,880 --> 01:13:46,640
WHERE YOU CAN TEST MULTIPLE

1873
01:13:46,640 --> 01:13:47,880
ORGANOIDS MULTIPLE NOROVIRUS

1874
01:13:47,880 --> 01:13:49,520
STRAINS AND I THINK THAT IS

1875
01:13:49,520 --> 01:13:51,240
REALLY WHERE AT LEAST FOR THE

1876
01:13:51,240 --> 01:13:52,800
NOROVIRUS DRUG TESTING THE NEXT

1877
01:13:52,800 --> 01:13:53,960
STAGE WHERE YOU CAN USE TO COME

1878
01:13:53,960 --> 01:13:55,440
UP WITH COMPOUNDS THAT ARE

1879
01:13:55,440 --> 01:13:59,080
AFFECTIVE. FINALLY, BIG PICTURE

1880
01:13:59,080 --> 01:14:01,120
PERSPECTIVE. ALL THE LINES WE

1881
01:14:01,120 --> 01:14:03,040
WORK WITH NOW ARE EPITHELIAL

1882
01:14:03,040 --> 01:14:05,840
CELLS ONLY BUT OF COURSE THE

1883
01:14:05,840 --> 01:14:07,400
FACTORS ARE MORE COMPLEX THAN

1884
01:14:07,400 --> 01:14:10,680
THAT AND WE ARE ESTABLISHING

1885
01:14:10,680 --> 01:14:11,760
CO-CULTURES WITH CELLS AND

1886
01:14:11,760 --> 01:14:12,600
ORGANOIDS AND PLATFORMS WHERE

1887
01:14:12,600 --> 01:14:14,800
YOU CAN MIMIC THE INTESTINAL

1888
01:14:14,800 --> 01:14:17,160
GRADIENT AND MICROBIOME FOR

1889
01:14:17,160 --> 01:14:18,920
CULTURE STUDIES.  ALL THESE WILL

1890
01:14:18,920 --> 01:14:20,040
BEEN USEFUL FOR DRUG TESTING IN

1891
01:14:20,040 --> 01:14:22,360
THE FUTURE. SO WITH THAT I WANT

1892
01:14:22,360 --> 01:14:23,440
TO THANK EVERYBODY WHO HAS BEEN

1893
01:14:23,440 --> 01:14:29,480
PART OF THIS WORK. USE OF

1894
01:14:29,480 --> 01:14:31,080
ENTROIDS TO STUDY NOROVIRUSES,

1895
01:14:31,080 --> 01:14:33,160
THE WORK I SHOW YOU CAME FROM

1896
01:14:33,160 --> 01:14:37,560
RANDALL LOUIS A GRADUATE

1897
01:14:37,560 --> 01:14:40,000
STUDENT, SHE DID THE (INAUDIBLE)

1898
01:14:40,000 --> 01:14:42,960
WORK, BIOLOGY BASED DRUGS BY

1899
01:14:42,960 --> 01:14:44,760
VICTORIA AND THE ANTIVIRAL

1900
01:14:44,760 --> 01:14:49,320
LIBRARY STREAMING PAPER FROM

1901
01:14:49,320 --> 01:14:50,800
JAPAN. THANK YOU FOR YOUR

1902
01:14:50,800 --> 01:14:52,320
ATTENTION AND I LOOK FORWARD TO

1903
01:14:52,320 --> 01:14:53,800
YOUR QUESTIONS IN THE DISCUSSION

1904
01:14:53,800 --> 01:14:57,320
SESSION. THANK YOU.

1905
01:14:57,320 --> 01:14:59,240
>> THANK YOU SO MUCH, DR.

1906
01:14:59,240 --> 01:15:00,440
RAMANI. EXCELLENT PRESENTATION

1907
01:15:00,440 --> 01:15:01,480
AND ABSOLUTELY LOOK FORWARD TO

1908
01:15:01,480 --> 01:15:03,680
DISCUSSION LATER THIS AFTERNOON 

1909
01:15:03,680 --> 01:15:08,320
>> THANK YOU.

1910
01:15:08,320 --> 01:15:10,520
>> LOST COUNT I THINK WE
ARE AT

1911
01:15:10,520 --> 01:15:12,960
THE FOURTH SPEAKER OF THE

1912
01:15:12,960 --> 01:15:14,760
SESSION SO BEFORE OUR FIRST

1913
01:15:14,760 --> 01:15:16,680
BREAK. I WOULD LIKE TO INTRODUCE

1914
01:15:16,680 --> 01:15:20,720
DR. SARA CHERRY. DR. CHERRY IS A

1915
01:15:20,720 --> 01:15:22,120
PROFESSOR IN THE DEPARTMENT OF

1916
01:15:22,120 --> 01:15:23,000
PATHOLOGY AND LABORATORY

1917
01:15:23,000 --> 01:15:24,800
MEDICINE AT THE UNIVERSITY OF

1918
01:15:24,800 --> 01:15:26,280
PENNSYLVANIA AND IS A SCIENTIFIC

1919
01:15:26,280 --> 01:15:27,720
DIRECTOR OF THE HIGH LIEU PUT

1920
01:15:27,720 --> 01:15:29,640
SCREENING CORE AND DIRECTOR OF

1921
01:15:29,640 --> 01:15:31,160
THE CHEMOGENOMIC DISCOVERY

1922
01:15:31,160 --> 01:15:32,040
PROGRAM IN THE SCHOOL OF

1923
01:15:32,040 --> 01:15:36,480
MEDICINE THERE. SHE OBTAINED HER

1924
01:15:36,480 --> 01:15:38,080
BACHELOR'S DEGREE WORKING WITH

1925
01:15:38,080 --> 01:15:41,320
DR. PETER SCHULTZ AT BERKELEY,

1926
01:15:41,320 --> 01:15:43,040
HER Ph.D. WITH DAVID BALTIMORE

1927
01:15:43,040 --> 01:15:45,920
AT MIT AND POST-DOCTORAL

1928
01:15:45,920 --> 01:15:48,080
FELLOWSHIP WITH DR. PERRYMAN.

1929
01:15:48,080 --> 01:15:50,560
UPON STARTING HER LABORATORY AT

1930
01:15:50,560 --> 01:15:52,680
UPENN SHE HAS APPLIED HIGH LIEU

1931
01:15:52,680 --> 01:15:54,120
PUT SCREENING TECHNOLOGIES TO

1932
01:15:54,120 --> 01:15:55,920
KISS COVER MECHANISMS WHICH

1933
01:15:55,920 --> 01:16:00,240
VIRAL PATHOGENS HIJACK CELLULAR

1934
01:16:00,240 --> 01:16:03,880
MACHINERY EVADING DEFERENCES. 

1935
01:16:03,880 --> 01:16:05,520
SHE IDENTIFIED INNATE IMMUNITY

1936
01:16:05,520 --> 01:16:06,800
AND CELLULAR INTERACTIONS

1937
01:16:06,800 --> 01:16:07,840
BETWEEN VIRUSES AND CELLS

1938
01:16:07,840 --> 01:16:09,480
COMPARING AND CONTRASTING VIRAL

1939
01:16:09,480 --> 01:16:11,520
FAMILIES.  MORE RECENTLY SHE'S

1940
01:16:11,520 --> 01:16:12,920
UNCOVERED NEW INSIGHT TO THE

1941
01:16:12,920 --> 01:16:14,880
INNER PLAY BETWEEN METABOLIC

1942
01:16:14,880 --> 01:16:17,200
REGULATION, THE MICROBIOTA AND

1943
01:16:17,200 --> 01:16:18,680
IMMUNE DEFENSE. GIVEN THE

1944
01:16:18,680 --> 01:16:20,160
PANDEMIC HER LABORATORY HAS

1945
01:16:20,160 --> 01:16:21,360
APPLIED HER SCREENING PLATFORM

1946
01:16:21,360 --> 01:16:24,120
TO STUDY THE EMERGING CORONA

1947
01:16:24,120 --> 01:16:26,360
VIRUS SARS COV-2 IDENTIFY NEW

1948
01:16:26,360 --> 01:16:28,480
ANTIVIRALS, ACTIVE IN THE

1949
01:16:28,480 --> 01:16:30,840
RESPIRATORY TRACT. SHE UNCOVERED

1950
01:16:30,840 --> 01:16:31,720
ANTIVIRALS WITH DISTINCT

1951
01:16:31,720 --> 01:16:33,520
MECHANISMS OF ACTION INCLUDING

1952
01:16:33,520 --> 01:16:36,520
INNATE IMMUNE MODULATORS DIRECT

1953
01:16:36,520 --> 01:16:38,480
ACTING ANTIVIRALS AND HOST

1954
01:16:38,480 --> 01:16:40,400
DIRECTED ANTIVIRALS. BY

1955
01:16:40,400 --> 01:16:42,040
COMPARING ANTIVIRALS ACROSS

1956
01:16:42,040 --> 01:16:43,800
RELATED AND UNRELATED VIRUSES,

1957
01:16:43,800 --> 01:16:46,080
SHE IDENTIFIED SYNERGIES BETWEEN

1958
01:16:46,080 --> 01:16:47,440
ANTIVIRALS THAT MAY BE LEVERAGED

1959
01:16:47,440 --> 01:16:48,920
FOR COMBINATION THERAPIES IN THE

1960
01:16:48,920 --> 01:16:52,040
FUTURE. THE TITLE OF DR.

1961
01:16:52,040 --> 01:16:53,840
CHERRY'S TALK IS ANTIVIRAL

1962
01:16:53,840 --> 01:16:54,920
SCREENING PIPELINE AND LESSONS

1963
01:16:54,920 --> 01:16:57,960
LEARNED.  OVER TO YOU, DR.

1964
01:16:57,960 --> 01:17:02,240
CHERRY. 

1965
01:17:02,240 --> 01:17:03,600
>> THANK YOU VERY MUCH,
ANN,

1966
01:17:03,600 --> 01:17:05,200
THANKS TO ORGANIZERS ALLOWING ME

1967
01:17:05,200 --> 01:17:05,920
TO PRESENCE THE WORK WE HAVE

1968
01:17:05,920 --> 01:17:09,000
BEEN DOING TO DEVELOP A PIPELINE

1969
01:17:09,000 --> 01:17:11,320
TO ALLOW US TO IDENTIFY NEW

1970
01:17:11,320 --> 01:17:15,240
ANTIVIRALS IN ORDER TO MOVE

1971
01:17:15,240 --> 01:17:16,600
THERAPEUTICS FORWARD POTENTIALLY

1972
01:17:16,600 --> 01:17:23,120
CLINICALLY.  SO AS WE ALL KNOW,

1973
01:17:23,120 --> 01:17:26,520
WE HAVE HAD MANY EMERGING AND

1974
01:17:26,520 --> 01:17:27,920
RE-EMERGING VIRUSES

1975
01:17:27,920 --> 01:17:30,560
HISTORICALLY, THIS IS A IMAGE

1976
01:17:30,560 --> 01:17:32,760
FROM THE GATES FOUNDATION THAT

1977
01:17:32,760 --> 01:17:34,920
CAPTURES MUCH OF OUR MORTALITY

1978
01:17:34,920 --> 01:17:37,800
PRIOR TO THE -- TO 2020 WHERE

1979
01:17:37,800 --> 01:17:40,240
MOSQUITOES AND MOSQUITO BORNE

1980
01:17:40,240 --> 01:17:41,840
ILLNESSES LEAD TO LARGE BURDEN

1981
01:17:41,840 --> 01:17:43,640
AND MY LAB HISTORICALLY STUDIED

1982
01:17:43,640 --> 01:17:46,240
THESE ARTHEROPOD VIRUSES. ALSO

1983
01:17:46,240 --> 01:17:47,680
KNOW THE WORLD IS GETTING

1984
01:17:47,680 --> 01:17:49,040
SMALLER MORE INTERACTIONS AND

1985
01:17:49,040 --> 01:17:52,160
MORE LIKELIHOOD OF NEW VIRUSES

1986
01:17:52,160 --> 01:17:53,920
ENTER INTO POPULATIONS AND OF

1987
01:17:53,920 --> 01:17:55,400
COURSE THE LAST FEW YEARS

1988
01:17:55,400 --> 01:17:57,640
THERE'S BEEN UNBELIEVABLE BURDEN

1989
01:17:57,640 --> 01:17:59,320
OF INFECTION AND MORTALITY DUE

1990
01:17:59,320 --> 01:18:03,120
TO COVID-19. SO WHAT WE ARE --

1991
01:18:03,120 --> 01:18:04,960
WHAT WE THINK, MANY HERE IN THIS

1992
01:18:04,960 --> 01:18:07,720
AUDIENCE THINK IS WE NEED MORE

1993
01:18:07,720 --> 01:18:10,520
ANTIVIRALS AGAIN SARS COV-2 BUT

1994
01:18:10,520 --> 01:18:12,120
ALSO ALL THE OTHER EMERGING AND

1995
01:18:12,120 --> 01:18:13,640
RE-EMERGING VIRUSES WHICH WE

1996
01:18:13,640 --> 01:18:16,200
HAVE VERY FEW ANTIVIRALS. SO WE

1997
01:18:16,200 --> 01:18:18,800
THINK OF ANTIVIRALS IS THREE

1998
01:18:18,800 --> 01:18:21,040
MAJOR CLASSES.  THERE'S THE

1999
01:18:21,040 --> 01:18:22,640
DIRECT ACTING ABOUT VIRALS WHICH

2000
01:18:22,640 --> 01:18:26,200
ARE LARGEST CATEGORY THAT BLOCK

2001
01:18:26,200 --> 01:18:28,080
VIRUS ITSELF, VIRAL ENZYME,

2002
01:18:28,080 --> 01:18:34,440
VIRAL ACTIVITY. THERE IS HOST

2003
01:18:34,440 --> 01:18:35,400
DIRECTED AB VIRALS REQUIRING

2004
01:18:35,400 --> 01:18:37,960
MACHINERY TO REPLICATE. YOUR

2005
01:18:37,960 --> 01:18:39,120
TARGET MACHINERY TO BLOCK

2006
01:18:39,120 --> 01:18:40,760
INFECTION. WE HAVE EXAMPLES FOR

2007
01:18:40,760 --> 01:18:43,320
ENTRY INHIBITORS. ANOTHER CLASS

2008
01:18:43,320 --> 01:18:45,200
OF ANTIVIRALS ARE THE ONES THAT

2009
01:18:45,200 --> 01:18:47,240
CAN MODULATE THE IMMUNE RESPONSE

2010
01:18:47,240 --> 01:18:49,320
AND I WILL TELL YOU TODAY ABOUT

2011
01:18:49,320 --> 01:18:50,080
ANTIVIRALS THAT WE HAVE BEEN

2012
01:18:50,080 --> 01:18:51,120
WORKING ON FROM ALL LEE

2013
01:18:51,120 --> 01:18:55,680
CATEGORIES. -- THREE CATEGORIES.

2014
01:18:55,680 --> 01:18:56,880
THE PIPELINE WE HAVE BEEN TRYING

2015
01:18:56,880 --> 01:18:58,720
TO IMPLEMENT IN SARS AND OTHER

2016
01:18:58,720 --> 01:19:00,680
VIRUSES IS THE FOLLOWING. SO WE

2017
01:19:00,680 --> 01:19:03,040
USE HIGH THROUGH PUT SCREENING

2018
01:19:03,040 --> 01:19:05,840
AND 384 WELL PLACE WHERE WE CAN

2019
01:19:05,840 --> 01:19:09,040
ADD CELLS THAT ADD DRUGS FROM

2020
01:19:09,040 --> 01:19:11,720
DRUG LIBRARIES USING ROBOTICS.

2021
01:19:11,720 --> 01:19:13,480
AND THEN WE CAN INFECT VIRUSES

2022
01:19:13,480 --> 01:19:17,680
SUCH AS SARS COV-2 AND OUR ASSAY

2023
01:19:17,680 --> 01:19:20,600
OF CHOICE USES MICROSCOPY, WE

2024
01:19:20,600 --> 01:19:23,120
HAVE AUTOMATED IMAGE ANALYSIS

2025
01:19:23,120 --> 01:19:26,080
THAT ALLOWS US TO LOOK AT WILD

2026
01:19:26,080 --> 01:19:28,320
TYPE VIRUSES STAINED WITH

2027
01:19:28,320 --> 01:19:30,680
ANTIBODIES AND ALLOWS US TO ALSO

2028
01:19:30,680 --> 01:19:32,280
LOOK AT CELL VIABILITY IN THE

2029
01:19:32,280 --> 01:19:34,040
SAME WELL. ALLOWING US TO FIND

2030
01:19:34,040 --> 01:19:36,280
THINGS THAT BLOCK INFECTION

2031
01:19:36,280 --> 01:19:40,760
WITHOUT CYTOTOXICITY UP FRONT IN

2032
01:19:40,760 --> 01:19:42,200
OUR SCREENS. WE GO ON TO

2033
01:19:42,200 --> 01:19:44,360
VALIDATE THE HITS FROM THE

2034
01:19:44,360 --> 01:19:45,800
PRIMARY SCREENS USING DOSE

2035
01:19:45,800 --> 01:19:46,760
RESPONSE STUDIES IN VARIETY OF

2036
01:19:46,760 --> 01:19:48,760
CELL TYPES AS WELL AS ORTHOGONAL

2037
01:19:48,760 --> 01:19:50,400
ASSAYS TO LOOK AT THE EFFICACY

2038
01:19:50,400 --> 01:19:51,800
BECAUSE WE AND MANY OTHERS THINK

2039
01:19:51,800 --> 01:19:55,800
THAT INHIBITORS HAVE TO BE

2040
01:19:55,800 --> 01:19:57,320
POTENT AND BLOCK INFECTION BY

2041
01:19:57,320 --> 01:19:59,320
MORE THAN A LOG TO HAVE

2042
01:19:59,320 --> 01:20:02,760
PHENOTYPES IN VIVO. WE HAVE BEEN

2043
01:20:02,760 --> 01:20:04,320
INCORN RATING PRIMARY CELL

2044
01:20:04,320 --> 01:20:08,120
MODELS INTO OUR PIPELINE AT THIS

2045
01:20:08,120 --> 01:20:11,720
POINT TO TRIAGE THOSE DRUGS THAT

2046
01:20:11,720 --> 01:20:13,560
MIGHT BE ACTIVE IN CULTURED CELL

2047
01:20:13,560 --> 01:20:15,760
LINES AND NOT IN VIVO. SO WE

2048
01:20:15,760 --> 01:20:18,480
HAVE BEEN USING LIQUID INTERFACE

2049
01:20:18,480 --> 01:20:19,640
CULTURES WHICH HAVE COME UP A

2050
01:20:19,640 --> 01:20:25,000
NUMBER OF TIMES WHERE THESE ARE

2051
01:20:25,000 --> 01:20:28,000
FULLY DIFFERENTIATED SILLIATED,

2052
01:20:28,000 --> 01:20:31,360
PRODUCE MUCOUS, AND WE FOUND FOR

2053
01:20:31,360 --> 01:20:34,840
SARS COV-2 THEY HAVE TO BE

2054
01:20:34,840 --> 01:20:36,840
CULTURES AND MORE THAN 8 DAYS

2055
01:20:36,840 --> 01:20:38,280
OLD. WE ARE USERS OF THIS

2056
01:20:38,280 --> 01:20:39,400
TECHNOLOGY NOT DEVELOPERS OF

2057
01:20:39,400 --> 01:20:40,360
THIS TECHNOLOGY AND SO WE HAVE

2058
01:20:40,360 --> 01:20:42,320
BEEN WORKING WITH NUMBER OF

2059
01:20:42,320 --> 01:20:45,280
COMPANIES TO UTILIZE THESE IN A

2060
01:20:45,280 --> 01:20:47,920
SYSTEMATIC WAY TO TEST SMALL

2061
01:20:47,920 --> 01:20:49,160
MOLECULES TO GET LIQUID

2062
01:20:49,160 --> 01:20:51,200
INTERFACE CULTURES FROM NASAL

2063
01:20:51,200 --> 01:20:54,320
EPITHELIUM, AND THE BRONCHIAL

2064
01:20:54,320 --> 01:20:55,800
EPITHELIUM FROM MATT TECH. IN

2065
01:20:55,800 --> 01:20:58,240
ADDITION AT PENN THERE IS A CORE

2066
01:20:58,240 --> 01:21:02,240
THAT PRODUCE HUMAN IPS DERIVED

2067
01:21:02,240 --> 01:21:03,960
CELLS, WE HAVE BEEN USING THIS

2068
01:21:03,960 --> 01:21:07,680
AS WELL. SO ONCE WE FIND DR.

2069
01:21:07,680 --> 01:21:09,240
DRUGS ACTIVE IN PRIMARY MODELS

2070
01:21:09,240 --> 01:21:10,520
TO DO MECHANISM STUDIES TO

2071
01:21:10,520 --> 01:21:13,160
UNDERSTAND HOW THEY MIGHT BE

2072
01:21:13,160 --> 01:21:15,480
ACTING, AS WELL AS TESTING THEM

2073
01:21:15,480 --> 01:21:16,920
ACROSS DIFFERENT VARIANTS AND

2074
01:21:16,920 --> 01:21:19,560
CORONA VIRUSES TO IDENTIFY

2075
01:21:19,560 --> 01:21:20,520
ANTIVIRALS THAT HAVE SOME

2076
01:21:20,520 --> 01:21:21,960
BREADTH. IN MANY ADDITION AS

2077
01:21:21,960 --> 01:21:29,200
MANY OF YOU KNOW THERE IS

2078
01:21:29,200 --> 01:21:30,960
CONCERN ABOUT MONOTHERAPY

2079
01:21:30,960 --> 01:21:32,720
BECAUSE VIRUSES CAN MUTATE HENCE

2080
01:21:32,720 --> 01:21:34,920
VARIANTS AND INCORPORATE

2081
01:21:34,920 --> 01:21:35,960
COMBINATION TESTING IN YOU ARE

2082
01:21:35,960 --> 01:21:38,200
PIPELINE TO SEE IF COMBINATIONS

2083
01:21:38,200 --> 01:21:40,800
OF DRUGS ARE ACTIVE AS WELL.  

2084
01:21:40,800 --> 01:21:41,880
COLLABORATION WITH A NUMBER OF

2085
01:21:41,880 --> 01:21:43,000
OUR COLLEAGUES WE HAVE MOVED

2086
01:21:43,000 --> 01:21:46,040
SOME OF THESE TESTS IN TO

2087
01:21:46,040 --> 01:21:47,960
PRE-CLINICAL MODELS, IN SMALL

2088
01:21:47,960 --> 01:21:49,560
ANIMALS, SUCH AS MICE WITH HOPES

2089
01:21:49,560 --> 01:21:51,120
THAT ONCE WE PASS ALL THESE

2090
01:21:51,120 --> 01:21:52,720
HURDLES WE CAN USE SOME OF THESE

2091
01:21:52,720 --> 01:21:57,120
DRUGS INTO CLINICAL TRIAL.  SO

2092
01:21:57,120 --> 01:21:59,560
TO START WITH HIGH THROUGH PUT

2093
01:21:59,560 --> 01:22:00,960
SCREENS, WE COME UP WITH NUMBER

2094
01:22:00,960 --> 01:22:02,840
OF LIBRARIES THAT WE HAVE BEEN

2095
01:22:02,840 --> 01:22:06,280
SCREENING. AS MANY AS YOU HAVE

2096
01:22:06,280 --> 01:22:08,160
HEARD ABOUT THE FASTEST WAY TO

2097
01:22:08,160 --> 01:22:09,680
GET MOVING IS TAKING DRUGS THAT

2098
01:22:09,680 --> 01:22:11,240
EXIST, THAT'S WHAT WE DID AS

2099
01:22:11,240 --> 01:22:13,000
WELL.  WE SCREENED 20,000 DRUGS

2100
01:22:13,000 --> 01:22:14,120
ARE FROM A VARIETY OF

2101
01:22:14,120 --> 01:22:17,320
REPURPOSING LIBRARIES INCLUDING

2102
01:22:17,320 --> 01:22:20,880
WORKING WITH NCATS TO LEVERAGE

2103
01:22:20,880 --> 01:22:24,600
THEIR LIBRARIES AS WELL. AS WITH

2104
01:22:24,600 --> 01:22:26,040
GATES FOUNDATION TO TEST THE

2105
01:22:26,040 --> 01:22:28,640
REFRAME LIBRARY. WE ARE ARE ALSO

2106
01:22:28,640 --> 01:22:29,720
INCORPORATING DIVERSITY

2107
01:22:29,720 --> 01:22:31,640
LIBRARIES BUT I'M NOT GOING TO

2108
01:22:31,640 --> 01:22:33,640
HAVE TIME TO TALK ABOUT THOSE

2109
01:22:33,640 --> 01:22:36,440
TODAY.  SO THE DRUG LIBRARY IS

2110
01:22:36,440 --> 01:22:38,200
ONE FACET OF HIGH THROUGH PUT

2111
01:22:38,200 --> 01:22:40,040
SCREEN BUT OTHER IS USED IN CELL

2112
01:22:40,040 --> 01:22:42,840
TYPES. SO AS YOU HAVE HEARD

2113
01:22:42,840 --> 01:22:44,560
EARLIER TODAY, IT IS CLEAR THIS

2114
01:22:44,560 --> 01:22:47,200
VIRUS CAN USE MULTIPLE MODES OF

2115
01:22:47,200 --> 01:22:51,040
ENTRY. EARLIER STUDIES USING HH

2116
01:22:51,040 --> 01:22:53,640
7 CELLS AND VIRILE CELLS AN

2117
01:22:53,640 --> 01:22:54,920
NON-RESPIRATORY CELLS SHOWED THE

2118
01:22:54,920 --> 01:22:56,320
VIRUS CAN ENTER CELLS THROUGH

2119
01:22:56,320 --> 01:22:57,800
ENDOCYTIC MECHANISM DEPENDENT ON

2120
01:22:57,800 --> 01:23:00,640
THE PH REQUIRED TO ACTIVATE

2121
01:23:00,640 --> 01:23:04,640
CAPSAICIN PROTEASES SO CAPSAICIN

2122
01:23:04,640 --> 01:23:07,080
INHIBITORS ARE ACTIVITY AS WELL

2123
01:23:07,080 --> 01:23:08,840
AS HYDROXYCHLOROQUINE AND

2124
01:23:08,840 --> 01:23:10,840
INHIBITOR INDICATIONS ARE ACTIVE

2125
01:23:10,840 --> 01:23:13,080
IN NON-RESPIRATORY CELLS. IN

2126
01:23:13,080 --> 01:23:14,640
CONTRAST WE KNOW ACTIVE IN

2127
01:23:14,640 --> 01:23:18,960
CERTAIN CONTEXT, TO TRIGGER

2128
01:23:18,960 --> 01:23:21,680
ENTRY IS NOT ACTIVE IN

2129
01:23:21,680 --> 01:23:23,680
ACTIVATORS ARE NOT ACTIVE IN

2130
01:23:23,680 --> 01:23:24,600
NON-RESPIRATORY CELLS BECAUSE

2131
01:23:24,600 --> 01:23:28,800
THEY DON'T EXPRESS TMPRSS 2. WE

2132
01:23:28,800 --> 01:23:30,840
HAVE SCREENED MANY CELL LINES TO

2133
01:23:30,840 --> 01:23:32,360
FIND RESPIRATORY CELL LINE

2134
01:23:32,360 --> 01:23:33,960
PERMISSIVE TO INFECTION

2135
01:23:33,960 --> 01:23:38,360
ENDOGENOUSLY AND WE CAME UPON

2136
01:23:38,360 --> 01:23:40,920
CELLS ROBUSTLY INFECTED IN CELL

2137
01:23:40,920 --> 01:23:42,240
CULTURE MODIFICATION. SO IN

2138
01:23:42,240 --> 01:23:45,720
THESE RESPIRATORY CELLS THE

2139
01:23:45,720 --> 01:23:49,640
CATHEPSIN CELLS ARE DEAD AND

2140
01:23:49,640 --> 01:23:50,640
TMPRSS 2 INHER TOES ARE ACTIVE

2141
01:23:50,640 --> 01:23:52,400
AND INHIBIT INFECTION AND THEY

2142
01:23:52,400 --> 01:23:54,720
ARE SO NON-TOXIC THE VIRUS WITH

2143
01:23:54,720 --> 01:23:56,400
GROW -- CELLS WITH GROW BETTER

2144
01:23:56,400 --> 01:23:57,760
IN THE PRESENCE OF THIS

2145
01:23:57,760 --> 01:24:01,080
INHIBITOR. I WANT TO POINT OUT

2146
01:24:01,080 --> 01:24:04,720
THE CELLS MANY PEOPLE USE TO

2147
01:24:04,720 --> 01:24:07,120
MODEL SARS COV-2 USES ENDOCYTIC

2148
01:24:07,120 --> 01:24:10,880
ENTRY AND NOT THE TMPRSS 2, THEY

2149
01:24:10,880 --> 01:24:14,000
ARE A BETTER MODEL FOR INDEED

2150
01:24:14,000 --> 01:24:15,320
ALL THE PRIMARY RESPIRATORY

2151
01:24:15,320 --> 01:24:18,680
CELLS THAT WE HAVE TESTED USE

2152
01:24:18,680 --> 01:24:20,440
TMPRSS 2 FOR ENTRY. SO IN THE

2153
01:24:20,440 --> 01:24:25,560
IPS DERIVED CELLS INTERFACE

2154
01:24:25,560 --> 01:24:26,880
CULTURES WE CAN BLOT INFECTION

2155
01:24:26,880 --> 01:24:29,200
AS MEASURED BY -- BLOCK

2156
01:24:29,200 --> 01:24:31,720
INFECTION MEASURED BY RTPCR.

2157
01:24:31,720 --> 01:24:32,880
ALSO IN OUR HAND THE VARIANTS

2158
01:24:32,880 --> 01:24:35,840
ARE DEPENDENT ON TMPRS 2 FOR

2159
01:24:35,840 --> 01:24:41,560
INFECTION, THESE ARE ICP USING

2160
01:24:41,560 --> 01:24:43,480
TMPRR 2 INHIBITOR TO INHIBIT ALL

2161
01:24:43,480 --> 01:24:48,000
THE VARIANTS WE TESTED TO DATE. 

2162
01:24:48,000 --> 01:24:50,360
THIS LED US TO USE THE CELLS FOR

2163
01:24:50,360 --> 01:24:52,520
THE CELL LINE OF CHOICE FOR OUR

2164
01:24:52,520 --> 01:25:00,200
INITIAL SCREENS. SO WHAT WE

2165
01:25:00,200 --> 01:25:02,840
FOUND EARLY ON IN THESE CELLS

2166
01:25:02,840 --> 01:25:05,720
AND IN OTHER RESPIRATORY MODELS

2167
01:25:05,720 --> 01:25:08,120
IS THAT THE INNATE IMMUNE SYSTEM

2168
01:25:08,120 --> 01:25:10,120
WHICH IS IMPORTANT TO INITIALLY

2169
01:25:10,120 --> 01:25:12,840
CONTROL INFECTION IS ACTUALLY

2170
01:25:12,840 --> 01:25:14,080
DELAYED ACTIVATION OF

2171
01:25:14,080 --> 01:25:16,120
INTERFERONS AND INNATE IMMUNITY

2172
01:25:16,120 --> 01:25:17,920
THE DELAYED UPON INFECTION WITH

2173
01:25:17,920 --> 01:25:20,600
SARS COV-2. SO WHILE MANY

2174
01:25:20,600 --> 01:25:24,520
VIRUSES INCLUDING INFLUENZA AND

2175
01:25:24,520 --> 01:25:26,520
RSV ACTIVATE EARLY TIME POINTS

2176
01:25:26,520 --> 01:25:28,320
POST INFECTION WE AND OTHERS

2177
01:25:28,320 --> 01:25:32,760
FOUND THAT SARS COV-2 ONLY

2178
01:25:32,760 --> 01:25:34,280
ACTIVATES INTERFERON IN THE

2179
01:25:34,280 --> 01:25:36,720
CELLS LATE TIME POINT POST

2180
01:25:36,720 --> 01:25:38,360
INFECTION. HOWEVER WHILE DELAYED

2181
01:25:38,360 --> 01:25:40,120
INDUCTION WE ALSO FOUND THAT

2182
01:25:40,120 --> 01:25:42,560
INTERFERONS CAN ROBUSTLY BLOCK

2183
01:25:42,560 --> 01:25:44,920
INFECTION IF TREATED BEFORE

2184
01:25:44,920 --> 01:25:47,000
INFECTION. YOU CAN SEE HERE WITH

2185
01:25:47,000 --> 01:25:48,760
INTERFERON BETA OR LAMBDA, YOU

2186
01:25:48,760 --> 01:25:51,960
CAN ROBUSTLY BLOCK INFECTION

2187
01:25:51,960 --> 01:25:54,680
MANY THESE 3 CELLS. GIVEN THAT

2188
01:25:54,680 --> 01:25:56,760
THE VIRUS SENSITIVE INTERFERONS

2189
01:25:56,760 --> 01:25:57,920
WE WERE WONDERING IF THERE'S

2190
01:25:57,920 --> 01:25:59,840
OTHER INNATE LIGANDS THAT MIGHT

2191
01:25:59,840 --> 01:26:02,440
BE ABLE TO HAVE ACTIVITY TO

2192
01:26:02,440 --> 01:26:05,240
BLOCK INFECTION. SO CREATE AD

2193
01:26:05,240 --> 01:26:07,320
LIBRARY WHAT ARE CALLED PAMS OR

2194
01:26:07,320 --> 01:26:09,760
PATHOGEN ASSOCIATED PATTERN TO

2195
01:26:09,760 --> 01:26:11,880
INNATE AGONISTS AND SCREEN FOR

2196
01:26:11,880 --> 01:26:14,120
ACTIVITY IN CAL 3 CELLS. SO WHAT

2197
01:26:14,120 --> 01:26:18,160
WE FOUND IS TWO OF THE LIGANDS

2198
01:26:18,160 --> 01:26:19,720
CYCLIC NUCLEOTIDES WERE QUITE

2199
01:26:19,720 --> 01:26:21,960
POTENT TO BLOCKING SARS COV-2

2200
01:26:21,960 --> 01:26:25,160
INFECTION IN CALU 3 CELLS. SO

2201
01:26:25,160 --> 01:26:26,720
THIS IS DOSE RESPONSE STUDIES WE

2202
01:26:26,720 --> 01:26:30,040
CAN SHOW THAT WE HAVE NICE DOSE

2203
01:26:30,040 --> 01:26:31,800
DEPENDENT ACTIVITY AND BY QPCR

2204
01:26:31,800 --> 01:26:33,840
WE CAN SEE WE CAN BLOCK

2205
01:26:33,840 --> 01:26:37,800
INFECTION. HOWEVER, EC 50s

2206
01:26:37,800 --> 01:26:39,880
HERE ARE ACTIVE BUT VERY HIGH

2207
01:26:39,880 --> 01:26:42,480
CONCENTRATIONS AND THAT IS

2208
01:26:42,480 --> 01:26:44,280
BECAUSE THESE DINUCLEOTIDES ARE

2209
01:26:44,280 --> 01:26:45,480
NOT CELL PERMEABLE. BECAUSE OF

2210
01:26:45,480 --> 01:26:47,160
THIS NUMBER OF PHARMA COMPANIES

2211
01:26:47,160 --> 01:26:48,880
DEVELOPED SMALL MOLECULES STAIN

2212
01:26:48,880 --> 01:26:51,120
AGONISTS SO WE RETAINED ONE

2213
01:26:51,120 --> 01:26:53,520
AGONIST AND WE FOUND THAT IT IS

2214
01:26:53,520 --> 01:26:55,600
POTENTLY ACTIVE IN CALU 3 CELLS

2215
01:26:55,600 --> 01:26:57,520
TO BLOCK INFECTION AND BLOCK

2216
01:26:57,520 --> 01:27:00,400
VIRAL REPLICATION BY THREE

2217
01:27:00,400 --> 01:27:02,840
ORDERS OF MAGNITUDE. NEXT WE

2218
01:27:02,840 --> 01:27:05,400
MOVE TO THE AIR LIQUID INTERFACE

2219
01:27:05,400 --> 01:27:06,920
CULTURE DESCRIBED IN THE

2220
01:27:06,920 --> 01:27:09,080
PIPELINE AND WE WORK WITH EMILY

2221
01:27:09,080 --> 01:27:10,840
AND MARK IN THESE STUDIES

2222
01:27:10,840 --> 01:27:13,040
OBTAINING CULTURES FROM MATT

2223
01:27:13,040 --> 01:27:15,160
TECH AND INFECT WITH SARS COV-2,

2224
01:27:15,160 --> 01:27:17,240
AND WE CAN REALLY POTENTLY BLOCK

2225
01:27:17,240 --> 01:27:20,200
VIRAL REPLICATION SHOWN BY

2226
01:27:20,200 --> 01:27:21,280
CONFOCAL MICROSCOPY IN THE

2227
01:27:21,280 --> 01:27:25,240
CENTER OR BY RTPCR ON THE RIGHT.

2228
01:27:25,240 --> 01:27:27,520
WHERE THESE -- THIS SMALL

2229
01:27:27,520 --> 01:27:29,240
MOLECULE LIGAND IS ACTIVE

2230
01:27:29,240 --> 01:27:32,200
AGAINST SARS COV-2. NEXT MOVE TO

2231
01:27:32,200 --> 01:27:34,280
ANIMAL MODEL COLLABORATION WITH

2232
01:27:34,280 --> 01:27:36,800
(INAUDIBLE) LAB WE INITIALLY USE

2233
01:27:36,800 --> 01:27:39,000
ANCESTRAL STRAIN OF SARS COV-2

2234
01:27:39,000 --> 01:27:41,680
AND INFECTED THE HUMAN

2235
01:27:41,680 --> 01:27:44,400
TRANSGENIC LINE CALLED K 18. IN

2236
01:27:44,400 --> 01:27:47,480
THIS CASE WE INTRANASALLY

2237
01:27:47,480 --> 01:27:49,840
DELIVERED THE LIGAND AND THEN

2238
01:27:49,840 --> 01:27:51,320
CHALLENGED INTRANASALLY WITH

2239
01:27:51,320 --> 01:27:52,680
SARS COV-2. WHAT WE CAN SEE IS

2240
01:27:52,680 --> 01:27:55,080
WE CAN PROTECT THE ANIMALS FROM

2241
01:27:55,080 --> 01:27:57,640
WEIGHT LOSS AND MORTALITY DUE TO

2242
01:27:57,640 --> 01:27:59,560
INFECTION, REALLY ROBUST

2243
01:27:59,560 --> 01:28:02,960
INHIBITION OF VIRAL REPLICATION

2244
01:28:02,960 --> 01:28:07,040
IN THE LUNGS. WE NEXT WANT TO

2245
01:28:07,040 --> 01:28:09,400
MOVE TO MORE RELEVANT MODEL

2246
01:28:09,400 --> 01:28:11,240
INFECTION SO AS MANY OF YOU

2247
01:28:11,240 --> 01:28:13,400
PROBABLY KNOW THE SOUTH AFRICAN

2248
01:28:13,400 --> 01:28:15,280
VARIANT INFECTS WILD TYPE, YOU

2249
01:28:15,280 --> 01:28:17,720
CAN USE THE MOUSE ACE 2 RECEPTOR

2250
01:28:17,720 --> 01:28:19,800
SO WE CAN USE THE SOUTH AFRICAN

2251
01:28:19,800 --> 01:28:21,960
VARIANT CHALLENGE WITH 129 WILD

2252
01:28:21,960 --> 01:28:25,240
TYPE MICE, IN THIS CASE THE

2253
01:28:25,240 --> 01:28:27,320
INFECTION IS LESS LETHAL SO WE

2254
01:28:27,320 --> 01:28:32,840
CAN ACTUALLY TREAT THE ANIMALS

2255
01:28:32,840 --> 01:28:34,920
WITH THIS MITIGATING WEIGHT LOSS

2256
01:28:34,920 --> 01:28:37,160
AND ATTENUATING VIRAL

2257
01:28:37,160 --> 01:28:38,240
REPLICATION, SUGGESTING WE CAN

2258
01:28:38,240 --> 01:28:40,160
GO FROM IN VITRO ASSAY ALL THE

2259
01:28:40,160 --> 01:28:41,760
WAY THROUGH PRE-CLINICAL MODELS

2260
01:28:41,760 --> 01:28:46,320
AND SHOW REALLY HIGH ACTIVITY.

2261
01:28:46,320 --> 01:28:48,240
AS I SAID WE HAVE SCREENED

2262
01:28:48,240 --> 01:28:50,880
20,000 DRUGS AT THIS POINT.

2263
01:28:50,880 --> 01:28:52,760
INCLUDING THOSE LIGANDS BUT MORE

2264
01:28:52,760 --> 01:28:54,240
CLASSICAL LIBRARIES THAT I

2265
01:28:54,240 --> 01:28:57,160
DESCRIBED EARLIER. SO FROM THESE

2266
01:28:57,160 --> 01:28:58,800
20,000 DRUGS WE THEN WENT ON TO

2267
01:28:58,800 --> 01:29:01,920
DO DOSE DEPENDENT STUDIES AND WE

2268
01:29:01,920 --> 01:29:05,760
VALIDATED 150 DRUGS THAT HAD

2269
01:29:05,760 --> 01:29:07,600
INDEXES AND QUITE ACTIVE. SO THE

2270
01:29:07,600 --> 01:29:09,280
TWO CATEGORIES THAT I WANT TO

2271
01:29:09,280 --> 01:29:13,560
MENTION NOW ARE THE NUCLEOSIDE

2272
01:29:13,560 --> 01:29:14,960
ANALOGS AND METABOLIC

2273
01:29:14,960 --> 01:29:17,920
INHIBITORS.  WE IDENTIFIED 16

2274
01:29:17,920 --> 01:29:19,800
NUCLEOSIDES THAT HAD ANTIVIRAL

2275
01:29:19,800 --> 01:29:21,760
ACTIVITY AND NUCLEOSIDE ANALOGS

2276
01:29:21,760 --> 01:29:24,040
ARE POTENT ANTIVIRALS, MANY CAN

2277
01:29:24,040 --> 01:29:26,680
BE INCORPORATED BY THE

2278
01:29:26,680 --> 01:29:28,400
POLYMERASE MEETING TO AFFECTING

2279
01:29:28,400 --> 01:29:30,080
THE VIRAL RNA REPLICATION. SO

2280
01:29:30,080 --> 01:29:32,680
SHOWN ON THE RIGHT HERE ARE THE

2281
01:29:32,680 --> 01:29:35,800
IC 50 CURVES OF CALU 3 TREAT

2282
01:29:35,800 --> 01:29:40,520
WITH REMDESIVIR, TO GO MEAN,

2283
01:29:40,520 --> 01:29:43,800
WHERE YOU CAN SEE THAT THEY HAVE

2284
01:29:43,800 --> 01:29:46,840
POTENT ACTIVITY IN THESE CELLS.

2285
01:29:46,840 --> 01:29:49,600
OF COURSE WE THEN TESTED THESE

2286
01:29:49,600 --> 01:29:53,200
SMALL MOLECULES IN MORE RELEVANT

2287
01:29:53,200 --> 01:29:56,440
CELL LINES SO WE TRIED -- WE

2288
01:29:56,440 --> 01:30:01,960
USED THE DERIVED 2 CELLS,

2289
01:30:01,960 --> 01:30:04,280
BRONCHIAL EPITHELIAL LINES FROM

2290
01:30:04,280 --> 01:30:06,200
MATTEK AND NASAL EPITHELIAL,

2291
01:30:06,200 --> 01:30:09,240
THIS IS LOOKING AT FOUR OF THOSE

2292
01:30:09,240 --> 01:30:12,120
ANALOGS WHERE YOU CAN SEE THAT

2293
01:30:12,120 --> 01:30:14,360
THEY ALL HAVE REMDESIVIR

2294
01:30:14,360 --> 01:30:16,880
ACTIVITY AGAINST ALL THESE LINES

2295
01:30:16,880 --> 01:30:18,040
AS DOES (INAUDIBLE) BUT THERE IS

2296
01:30:18,040 --> 01:30:20,800
MORE STRIKING DIFFERENCES

2297
01:30:20,800 --> 01:30:24,080
BETWEEN THE MAT TEK AND AIR

2298
01:30:24,080 --> 01:30:26,120
LIQUID INTERFACE CULTURE THAN

2299
01:30:26,120 --> 01:30:31,400
THE IA 2 AND CALU 3 TELLS WHERE

2300
01:30:31,400 --> 01:30:32,840
GUANINE HAVE NO ACTIVITY IN THE

2301
01:30:32,840 --> 01:30:34,360
AIR LIQUID INTERFACE MODELS,

2302
01:30:34,360 --> 01:30:36,200
AGAIN REALLY SUGGESTING THAT

2303
01:30:36,200 --> 01:30:38,560
GOING THROUGH THESE DIFFERENT

2304
01:30:38,560 --> 01:30:40,320
STEPS TO TRIAGE MOLECULES BEFORE

2305
01:30:40,320 --> 01:30:41,240
WE MOVE FORWARD IS REALLY

2306
01:30:41,240 --> 01:30:45,880
IMPORTANT. THE OTHER CLASS IN

2307
01:30:45,880 --> 01:30:47,560
THE PIE CHART THERE METABOLIC

2308
01:30:47,560 --> 01:30:50,080
INHIBITORS AND WE IDENTIFIED A

2309
01:30:50,080 --> 01:30:52,960
NUMBER OF BIOSYNTHESIS AND PIR

2310
01:30:52,960 --> 01:30:55,200
RENNE BIOSYNTHESIS INHIBITORS SO

2311
01:30:55,200 --> 01:30:58,160
THESE ARE SMALL MOLECULES

2312
01:30:58,160 --> 01:31:00,880
BLOCKING THE HOST WHILE BLOCKING

2313
01:31:00,880 --> 01:31:03,400
THE BIOSYNTHESIS, THE VIRUS ALSO

2314
01:31:03,400 --> 01:31:05,200
NEEDS TO USE FOR IT TO UNDERGO

2315
01:31:05,200 --> 01:31:06,960
RNA REPLICATION.  SO WE WERE

2316
01:31:06,960 --> 01:31:08,520
REALLY INTERESTED IN WHETHER OR

2317
01:31:08,520 --> 01:31:10,240
NOT WE CAN DO COMBINATION

2318
01:31:10,240 --> 01:31:12,200
THERAPIES, TO IDENTIFY SYNERGIES

2319
01:31:12,200 --> 01:31:13,280
BETWEEN DIFFERENT CLASSES OF

2320
01:31:13,280 --> 01:31:15,080
SMALL MOLECULES, TO POTENTIALLY

2321
01:31:15,080 --> 01:31:17,120
ALLOW FOR LOWER DOSES IN HIGHER

2322
01:31:17,120 --> 01:31:21,640
BARRIER TO RESISTANCE. SO WE

2323
01:31:21,640 --> 01:31:22,360
COMBINED THE PRIM DEAN

2324
01:31:22,360 --> 01:31:26,000
BIOSYNTHESIS INHIBITOR

2325
01:31:26,000 --> 01:31:27,440
BIOAVAILABLE WITH ORALLY

2326
01:31:27,440 --> 01:31:29,840
BIOAVAILABLE AND USING TWO BY

2327
01:31:29,840 --> 01:31:32,200
TWO MATRIX TESTING DOSE RESPONSE

2328
01:31:32,200 --> 01:31:34,440
BY DOSE RESPONSE, WE ARE ABLE TO

2329
01:31:34,440 --> 01:31:38,920
SHOW VERY POTENT SYNERGY AS

2330
01:31:38,920 --> 01:31:39,720
MEASURED BY BLISS ANALYSIS

2331
01:31:39,720 --> 01:31:40,960
BETWEEN THE TWO DRUGS SUGGESTING

2332
01:31:40,960 --> 01:31:42,320
THAT THERE MAYBE A REAL BENEFIT

2333
01:31:42,320 --> 01:31:45,480
TO COMBINING THESE TWO DIFFERENT

2334
01:31:45,480 --> 01:31:49,280
SMALL MOLECULE MECHANISMS IN

2335
01:31:49,280 --> 01:31:52,360
VIVO. ALSO ASK WHETHER OR NOT

2336
01:31:52,360 --> 01:31:54,760
THIS IS SPECIFIC TO (INAUDIBLE)

2337
01:31:54,760 --> 01:31:57,200
OR ALSO TRUE WITH REMDESIVIR,

2338
01:31:57,200 --> 01:31:59,280
ANOTHER NUCLEOSIDE ANALOG AND WE

2339
01:31:59,280 --> 01:32:01,440
WERE ABLE TO SHOW SYNERGY WITH

2340
01:32:01,440 --> 01:32:03,240
THE COMBINATION OF REMDESIVIR

2341
01:32:03,240 --> 01:32:06,160
AND BRECINAR ALSO SUGGESTING

2342
01:32:06,160 --> 01:32:08,080
THAT BY COMBINING NUCLEOSIDE

2343
01:32:08,080 --> 01:32:10,240
ANALOG WITH A BIOSYNTHETIC BLOCK

2344
01:32:10,240 --> 01:32:12,040
WE MAY SHOW REALLY GOOD ACTIVITY

2345
01:32:12,040 --> 01:32:18,840
IN VIVO. EARLIER I WANT TO POINT

2346
01:32:18,840 --> 01:32:21,640
OUT WE DID THESE WITH PAXLOVID

2347
01:32:21,640 --> 01:32:24,480
AND THE PROTEASE INHIBITOR AND

2348
01:32:24,480 --> 01:32:27,480
WHEN WE COMBINE THAT WE SEE

2349
01:32:27,480 --> 01:32:28,960
ACTIVITY NOT SYNERGY SUGGESTING

2350
01:32:28,960 --> 01:32:30,760
A GOOD COMBINATION TO USE FOR

2351
01:32:30,760 --> 01:32:34,000
POTENTIALLY MOVING FORWARD.  SO

2352
01:32:34,000 --> 01:32:35,320
THEN WE MOVED TO THE AIR LIQUID

2353
01:32:35,320 --> 01:32:38,320
INTERFACE MODELS, AND WITH

2354
01:32:38,320 --> 01:32:40,320
EPITHELIUM WE VALIDATED DOSING

2355
01:32:40,320 --> 01:32:41,640
OF THE CULTURES SO THIS

2356
01:32:41,640 --> 01:32:44,800
SOMETHING THAT MAYBE HASN'T COME

2357
01:32:44,800 --> 01:32:45,840
UP OFTEN BUT IT IS IMPORTANT TO

2358
01:32:45,840 --> 01:32:48,280
MAKE SURE THAT THE CULTURES ARE

2359
01:32:48,280 --> 01:32:52,920
HEALTHY AND ACTIVE WHEN TREATING

2360
01:32:52,920 --> 01:32:54,320
WITH THESE SMALL MOLECULES SO

2361
01:32:54,320 --> 01:32:56,840
THEY RUN ASSAYS INCLUDING TIERS

2362
01:32:56,840 --> 01:33:00,120
FREQUENCY AND TOXICITY AND

2363
01:33:00,120 --> 01:33:02,760
IDENTIFY CONCENTRATIONS THAT ARE

2364
01:33:02,760 --> 01:33:05,040
NOT AFFECTING THE VIABILITY AND

2365
01:33:05,040 --> 01:33:06,480
PERMEABILITY OF THE AIR LIQUID

2366
01:33:06,480 --> 01:33:08,600
INTERFACE CULTURES. SO THEN WE

2367
01:33:08,600 --> 01:33:11,040
TESTED THESE COMBINATIONS USING

2368
01:33:11,040 --> 01:33:12,640
THESE AIR LIQUID INTERFACE

2369
01:33:12,640 --> 01:33:16,720
CULTURES IN BOTH THE NASAL AND

2370
01:33:16,720 --> 01:33:18,560
BRONCHIAL MODELS. THIS IS A

2371
01:33:18,560 --> 01:33:20,240
LITTLE BUSY BUT YOU CAN SEE THAT

2372
01:33:20,240 --> 01:33:23,800
WHEN WE TREAT WITH THE 2801 WE

2373
01:33:23,800 --> 01:33:26,440
SEE A DOSE DEPENDENT CHANGE IN

2374
01:33:26,440 --> 01:33:28,680
REPLICATION WITH HIGHER DOSE WE

2375
01:33:28,680 --> 01:33:34,080
HAVE DECREASE IN PATIENT

2376
01:33:34,080 --> 01:33:35,880
COMPARED TO DIFFERENT DOSES AND

2377
01:33:35,880 --> 01:33:40,520
THAT IF WE THEN COMBINE LOWER

2378
01:33:40,520 --> 01:33:44,760
DOSE OF PIRAVIR WITH TWO

2379
01:33:44,760 --> 01:33:45,480
DIFFERENT BASSINET SINCE HUNDRED

2380
01:33:45,480 --> 01:33:48,640
TORRS WE SEE A VAST --

2381
01:33:48,640 --> 01:33:50,040
BIOSYNTHESIS, WE SEE REPLICATION

2382
01:33:50,040 --> 01:33:51,960
COMPARED TO DRUGS ALONE IN NASAL

2383
01:33:51,960 --> 01:33:54,160
CULTURES AS WELL AS BRONCHIAL

2384
01:33:54,160 --> 01:33:55,320
CULTURES SUGGESTING THAT AGAIN

2385
01:33:55,320 --> 01:33:57,320
THIS COMBINATION MIGHT BE

2386
01:33:57,320 --> 01:34:02,720
BENEFICIAL IN VIVO. THEN WE

2387
01:34:02,720 --> 01:34:04,200
COLLABORATE WITH MATT FREEMAN'S

2388
01:34:04,200 --> 01:34:06,520
LAB TESTED IN VIVO MODEL USING

2389
01:34:06,520 --> 01:34:09,480
THE SOUTH AFRICAN VARIANT WITH

2390
01:34:09,480 --> 01:34:11,040
NASAL CHALLENGE AND AGAIN YOU

2391
01:34:11,040 --> 01:34:15,040
CAN SEE HERE IF WE USE DIFFERENT

2392
01:34:15,040 --> 01:34:17,960
DOSES OF PIROVIR WE CAN HAVE

2393
01:34:17,960 --> 01:34:19,720
DOSE DEPENDENT REDUCTION IN

2394
01:34:19,720 --> 01:34:21,080
VIRAL REPLICATION AND WHEN WE

2395
01:34:21,080 --> 01:34:25,240
ADD BRECLINAR TO THE COMBINATION

2396
01:34:25,240 --> 01:34:27,800
THERAPY WE CAN REDUCE

2397
01:34:27,800 --> 01:34:30,120
REPLICATION AT EVERY

2398
01:34:30,120 --> 01:34:33,480
CONCENTRATION OF EIKD 2801 SO

2399
01:34:33,480 --> 01:34:34,560
INCREASE REDUCTION IN TITERS

2400
01:34:34,560 --> 01:34:38,840
COMPARED TO EITHER OF THE DRUGSS

2401
01:34:38,840 --> 01:34:41,360
ALONALONE. WE WERE EXCITED TO SE

2402
01:34:41,360 --> 01:34:42,800
NOT ONLY DO WE HAVE REDUCTION IN

2403
01:34:42,800 --> 01:34:44,360
TITERS WE SAW REDUCTION IN

2404
01:34:44,360 --> 01:34:46,200
INFLAMMATION, SO THIS IS FROM

2405
01:34:46,200 --> 01:34:49,800
THE LUNGS OF THE ANIMALS, EITHER

2406
01:34:49,800 --> 01:34:51,560
NOT TREATED WITH DRUGS WHERE YOU

2407
01:34:51,560 --> 01:34:53,720
CAN SEE THIS TERRIBLE

2408
01:34:53,720 --> 01:34:55,520
INFLAMMATION AND AIRWAYS LOOK

2409
01:34:55,520 --> 01:34:58,440
TERRIBLE IF WE TREAT WITH

2410
01:34:58,440 --> 01:35:00,480
PIROVIR ALONE YOU CAN SEE NOT A

2411
01:35:00,480 --> 01:35:02,400
COMPLETE RESTORATION OF THE

2412
01:35:02,400 --> 01:35:03,960
LUNGS AS YOU CAN SEE IN THE

2413
01:35:03,960 --> 01:35:06,200
UNAFFECTED ANIMALS BUT WE

2414
01:35:06,200 --> 01:35:09,120
COMBINE BREQLINAR WE CAN RESTORE

2415
01:35:09,120 --> 01:35:10,640
THE ARCHITECTURE BACK TO WILD

2416
01:35:10,640 --> 01:35:12,120
TYPE SUGGESTING THAT WE HAVE

2417
01:35:12,120 --> 01:35:14,960
BOTH DECREASE IN TITTEDDERS AND

2418
01:35:14,960 --> 01:35:18,200
INFLAMMATION COMBINATION. SO

2419
01:35:18,200 --> 01:35:19,600
MOVING FORWARD WE ARE SCREENING

2420
01:35:19,600 --> 01:35:21,040
MORE LIBRARIES DIVERSITY

2421
01:35:21,040 --> 01:35:23,280
LIBRARIES TO IDENTIFY NEW MATTER

2422
01:35:23,280 --> 01:35:26,040
AND POTENTIALLY NEW DIRECT

2423
01:35:26,040 --> 01:35:29,280
ACTING ANTIVIRALS THEN MOVING

2424
01:35:29,280 --> 01:35:31,160
PIPELINE TESTING AGAINST DIVERSE

2425
01:35:31,160 --> 01:35:33,040
CORONA VIRUSES IN PRIMARY CELL

2426
01:35:33,040 --> 01:35:34,520
MODELS AND MECHANISM OF ACTION

2427
01:35:34,520 --> 01:35:36,560
STUDIES IN ORDER TO BRING IT

2428
01:35:36,560 --> 01:35:42,000
BACK TO ANIMAL MODELS AND

2429
01:35:42,000 --> 01:35:45,320
POTENTIALLY -- MY LAB IS

2430
01:35:45,320 --> 01:35:46,560
STUDYING EMERGING AND

2431
01:35:46,560 --> 01:35:50,120
RE-EMERGING VIRUSES, LARGE

2432
01:35:50,120 --> 01:35:52,000
ARTHEROPOD BORN SO WE ARE

2433
01:35:52,000 --> 01:35:54,200
ACTUALLY NOW USING THIS KIND OF

2434
01:35:54,200 --> 01:35:56,880
MODEL TO DEVELOP A PIPELINE TO

2435
01:35:56,880 --> 01:35:59,120
SCREEN ALL MAJOR FAMILIES OF RNA

2436
01:35:59,120 --> 01:36:00,880
VIRUSES THAT ARE TRANSMITTED BY

2437
01:36:00,880 --> 01:36:03,840
DIVERSE ANIMALS TO HUMANS IN

2438
01:36:03,840 --> 01:36:05,640
NATURE. ALONG WITH THE

2439
01:36:05,640 --> 01:36:07,480
DEVELOPMENT OF THESE ANTIVIRAL

2440
01:36:07,480 --> 01:36:09,320
SCREENINGS STRATEGIES WE ARE

2441
01:36:09,320 --> 01:36:10,960
TRYING TO DEVELOP MORE WORK WITH

2442
01:36:10,960 --> 01:36:13,400
OTHERS TO OBTAIN MORE

2443
01:36:13,400 --> 01:36:15,320
SOPHISTICATED 3D MODELS OF

2444
01:36:15,320 --> 01:36:17,120
DIFFERENT CELL TYPES THESE

2445
01:36:17,120 --> 01:36:20,400
VIRUSES INFECT IN HUMAN SARS

2446
01:36:20,400 --> 01:36:21,480
PATHOGENS. I WOULD LIKE TO PACK

2447
01:36:21,480 --> 01:36:23,400
KNOW LEDGE MY LAB, AND THE HIGH

2448
01:36:23,400 --> 01:36:24,560
THROUGH PUT SCREENING CORE WHICH

2449
01:36:24,560 --> 01:36:25,760
REALLY FACILITATED ALL THESE

2450
01:36:25,760 --> 01:36:27,920
STUDIES OVER THE LAST TWO YEARS.

2451
01:36:27,920 --> 01:36:30,920
ANIMAL STUDIES COLLABORATORS AS

2452
01:36:30,920 --> 01:36:34,440
WELL AS FOLKS AT NCATS,

2453
01:36:34,440 --> 01:36:36,640
MEDICINES THE GATES FOUNDATION,

2454
01:36:36,640 --> 01:36:39,000
THAT IS FACILITATED STUDIES AS

2455
01:36:39,000 --> 01:36:43,120
WELL AS INDIVIDUALS AND DEVELOP

2456
01:36:43,120 --> 01:36:46,680
THESE MODELS THAT ALLOWED US TO

2457
01:36:46,680 --> 01:36:48,760
RAPIDLY IMPLEMENT THEM FOR OUR

2458
01:36:48,760 --> 01:36:52,720
ANTIVIRAL STUDIES. WITH THAT,

2459
01:36:52,720 --> 01:36:56,360
THANK YOU.

2460
01:36:56,360 --> 01:36:57,520
>> EXCELLENT. THANK YOU SO
MUCH,

2461
01:36:57,520 --> 01:36:59,960
DR. CHERRY, FOR A FANTASTIC TALK

2462
01:36:59,960 --> 01:37:02,080
AND TO THE PRIOR SPEAKERS

2463
01:37:02,080 --> 01:37:05,360
EARLIER IN THIS SESSION. SO WE

2464
01:37:05,360 --> 01:37:06,720
HAVE TWO MORE SPEAKERS TO GO AND

2465
01:37:06,720 --> 01:37:09,880
THEN THE QUESTION AND ANSWER

2466
01:37:09,880 --> 01:37:12,320
PERIOD AFTER LUNCH. BUT LIKE TO

2467
01:37:12,320 --> 01:37:15,400
TAKE A BRIEF BREAK, POLLS FOR

2468
01:37:15,400 --> 01:37:16,640
EATING INTO THE TIME A LITTLE

2469
01:37:16,640 --> 01:37:18,920
BIT BUT LIKE TO KEEP TO THE

2470
01:37:18,920 --> 01:37:20,520
SCHEDULE PLEASE AND RETURN FROM

2471
01:37:20,520 --> 01:37:23,160
BRIEF LUNCH BREAK AT 1:10 LOCAL

2472
01:37:23,160 --> 01:37:25,400
TIME. SO TEN AFTER HOUR WE WOULD

2473
01:37:25,400 --> 01:37:28,160
LIKE TO COME BACK AND FINISH OUT

2474
01:37:28,160 --> 01:37:29,960
SESSION 2. TWO MORE SPEAKERS AND

2475
01:37:29,960 --> 01:37:32,280
GET O THE QUESTIONS PERIOD. SO

2476
01:37:32,280 --> 01:37:33,800
ALSO BE PLEASE THINKING O YOUR

2477
01:37:33,800 --> 01:37:34,800
QUESTIONS AND FEEL FREE TO ADD

2478
01:37:34,800 --> 01:37:38,360
THEM TO THE Q&A CHAT BOX SO
WE

2479
01:37:38,360 --> 01:37:39,560
WILL BE SURE TO COVER THEM

2480
01:37:39,560 --> 01:37:41,600
DURING THAT DISCUSSION.  THANKS

2481
01:37:41,600 --> 01:37:43,640
AGAIN. SEE EVERYONE BACK AT 10

2482
01:37:43,640 --> 01:37:47,320
AFTER THE HOUR. 

2483
01:37:47,320 --> 01:37:50,120
>>I THIS I IT'S TIME TO RESUME

2484
01:37:50,120 --> 01:37:52,120
OUR SESSION 2 DISSECTIONS. SO

2485
01:37:52,120 --> 01:37:55,360
THANK YOU AGAIN TO THE PRIOR

2486
01:37:55,360 --> 01:37:58,200
FOUR SPEAKERS. I NOW LIKE TO

2487
01:37:58,200 --> 01:38:01,280
INTRODUCE OUR FIFTH SPEAKER FOR

2488
01:38:01,280 --> 01:38:04,040
THE SESSION, DR. EMILY LEE. DR.

2489
01:38:04,040 --> 01:38:05,800
LEE IS A STAFF SCIENTIST AND

2490
01:38:05,800 --> 01:38:08,920
FUNCTIONAL GROUP LEAD AT NCATS

2491
01:38:08,920 --> 01:38:11,200
NIH. DR. LEE JOINED THE EARLY

2492
01:38:11,200 --> 01:38:11,920
TRANSLATION BRANCH IN THE

2493
01:38:11,920 --> 01:38:13,760
DIVISION OF PRE-CLINICAL

2494
01:38:13,760 --> 01:38:16,520
INNOVATION AT NCATS IN 2019 AS

2495
01:38:16,520 --> 01:38:18,160
BIOLOGIST. DRAWING ON HER

2496
01:38:18,160 --> 01:38:20,400
DIVERSE BACKGROUND IN VIROLOGY

2497
01:38:20,400 --> 01:38:22,240
HIGH THROUGH PUT DRUG SCREENING

2498
01:38:22,240 --> 01:38:24,400
AND COMPLEX IN VITRO MODELS DR.

2499
01:38:24,400 --> 01:38:25,960
LEE LEADS ADVANCE MODELS AND

2500
01:38:25,960 --> 01:38:27,640
CELL DISCOVERY ASSAY GROUP

2501
01:38:27,640 --> 01:38:29,520
WITHIN THE ANTIVIRAL PROGRAM FOR

2502
01:38:29,520 --> 01:38:33,000
PANDEMICS. AS A POST-DOCTORAL

2503
01:38:33,000 --> 01:38:34,160
FELLOW IN THE THERAPEUTICS

2504
01:38:34,160 --> 01:38:36,280
BRANCH AT NCATS DR. LEE

2505
01:38:36,280 --> 01:38:37,560
DEVELOPED HIGH LIEU PUT ASSAYS

2506
01:38:37,560 --> 01:38:39,240
FOR ANTIVIRAL SCREENING AS WELL

2507
01:38:39,240 --> 01:38:41,000
AS RARE GENETIC DISEASES. DR.

2508
01:38:41,000 --> 01:38:43,360
LEE EARNED HER DOCTORAL DEGREE

2509
01:38:43,360 --> 01:38:44,800
IN CELL AND MOLECULAR BIOLOGY

2510
01:38:44,800 --> 01:38:46,160
FROM THE FLORIDA STATE

2511
01:38:46,160 --> 01:38:49,960
UNIVERSITY WHERE SHE WORKED WITH

2512
01:38:49,960 --> 01:38:52,200
HENLEY STUDYING HOST PATHOGEN

2513
01:38:52,200 --> 01:38:54,520
INTERACTIONS AND IDENTIFYING

2514
01:38:54,520 --> 01:38:56,000
POTENTIAL ANTIVIRAL COMPOUNDS

2515
01:38:56,000 --> 01:38:58,360
WITH A FOCUS ON FLAVI VIRUSES. 

2516
01:38:58,360 --> 01:38:59,720
HE CURRENT RESEARCH FOCUSES ON

2517
01:38:59,720 --> 01:39:01,760
DEVELOPING AND CHARACTERIZING

2518
01:39:01,760 --> 01:39:02,840
PHYSIOLOGICALLY RELEVANT CELL

2519
01:39:02,840 --> 01:39:04,800
BASED AND TISSUE ENGINEERED

2520
01:39:04,800 --> 01:39:06,400
PLATFORMS FOR VIRAL DISEASE

2521
01:39:06,400 --> 01:39:08,480
MODELING AND ANTIVIRAL DRUG

2522
01:39:08,480 --> 01:39:09,880
DISCOVERY. SHE AND HER TEAM ARE

2523
01:39:09,880 --> 01:39:10,920
CURRENTLY ENGAGED IN

2524
01:39:10,920 --> 01:39:12,120
COLLABORATIVE PROJECTS

2525
01:39:12,120 --> 01:39:14,920
PERTAINING TO HIGH IMPACT BLS 2

2526
01:39:14,920 --> 01:39:16,960
AND 3 VIRAL INFECTIONS INCLUDING

2527
01:39:16,960 --> 01:39:20,800
SARS COV-2. OF DR. LEE'S TEAM

2528
01:39:20,800 --> 01:39:22,560
WORKS CLOSE WITH MEMBERS OF THE

2529
01:39:22,560 --> 01:39:25,840
3D TISSUE BIBIOPRINTEDDING LAB

2530
01:39:25,840 --> 01:39:28,040
AT EARLY TRANSLATION BRANCH AT N

2531
01:39:28,040 --> 01:39:29,960
CATS AS WELL AS ACADEMIC

2532
01:39:29,960 --> 01:39:30,440
GOVERNMENT AND INDUSTRY

2533
01:39:30,440 --> 01:39:34,440
PARTNERS. SHE WILL BE SPEAKING

2534
01:39:34,440 --> 01:39:35,680
ON DEVELOPING MODELS FOR VIRAL

2535
01:39:35,680 --> 01:39:36,640
INFECTION AND DISEASE TO

2536
01:39:36,640 --> 01:39:38,680
INCORPORATE INTO THE DRUG

2537
01:39:38,680 --> 01:39:42,680
SCREENING PIPELINE. OVER TO YOU,

2538
01:39:42,680 --> 01:39:43,080
DR. LEE.

2539
01:39:43,080 --> 01:39:49,080
>> THANKS, DR. EAKIN.
GOING TO

2540
01:39:49,080 --> 01:39:50,680
PULL UP MY SCREEN. CAN YOU SEE

2541
01:39:50,680 --> 01:39:51,800
THE CORRECT SCREEN?

2542
01:39:51,800 --> 01:39:56,440
>> YES. LOOKS GREAT.

2543
01:39:56,440 --> 01:40:03,160
>> GREAT. LET ME PULL THIS
UP. 

2544
01:40:03,160 --> 01:40:04,040
THANK YOU FOR INTRODUCTION.

2545
01:40:04,040 --> 01:40:05,840
THANK YOU TO EVERYONE ATTENDING

2546
01:40:05,840 --> 01:40:08,480
THE ATM WORKSHOP TODAY.  I'M

2547
01:40:08,480 --> 01:40:09,920
HONORED TO SPEAK WITH Y'ALL

2548
01:40:09,920 --> 01:40:13,720
ABOUT SOME OF THE STRATEGIES WE

2549
01:40:13,720 --> 01:40:18,680
ARE TAKING ON 3D COMPLEX IN VIVO

2550
01:40:18,680 --> 01:40:23,280
MODELS.S. FOR INFECTIONS IN

2551
01:40:23,280 --> 01:40:25,360
DISEASE WITH THE GOAL OF

2552
01:40:25,360 --> 01:40:26,400
ENHANCING THE DRUG DEVELOPMENT

2553
01:40:26,400 --> 01:40:27,600
PIPELINE. I WILL START WITH WHO

2554
01:40:27,600 --> 01:40:30,360
WE R. THE IC AT THE NIH I WORK

2555
01:40:30,360 --> 01:40:33,320
IN IS NATIONAL CENTER FOR

2556
01:40:33,320 --> 01:40:35,280
TRANSLATION SCIENCES OR NCATS,

2557
01:40:35,280 --> 01:40:38,600
I'M A STAFF SCIENTIST MANY THE

2558
01:40:38,600 --> 01:40:40,640
3D LAB AND ALSO LEAD A SMALL

2559
01:40:40,640 --> 01:40:43,840
TEAM WITHIN THE SMALL TEAM APP.

2560
01:40:43,840 --> 01:40:47,040
MY TEAM IS LUCKY WE ARE A MIX OF

2561
01:40:47,040 --> 01:40:48,120
VIROLOGISTS, HIGH THROUGH PUT

2562
01:40:48,120 --> 01:40:49,680
SCIENTISTS AND TISSUE ENGINEERS

2563
01:40:49,680 --> 01:40:52,080
NESTLED TO LARGER GROUP OF DRUG

2564
01:40:52,080 --> 01:40:53,400
DISCOVERY AND HIGH THROUGH PUT

2565
01:40:53,400 --> 01:40:57,520
ASSAY SCIENTISTS MEDICINAL

2566
01:40:57,520 --> 01:41:02,680
CHEMIST, NAI TEAM AS WELL AS BY

2567
01:41:02,680 --> 01:41:04,240
LARGE GROUP OF TISSUE ENGINEERS

2568
01:41:04,240 --> 01:41:07,000
IN THE 3D TISSUE BIOPRINTING LAB

2569
01:41:07,000 --> 01:41:08,000
WE WORK AND COLLABORATE WITH

2570
01:41:08,000 --> 01:41:09,560
EVERY DAY ON DEVELOPING

2571
01:41:09,560 --> 01:41:10,840
UTILIZING TISSUE MODELS FOR

2572
01:41:10,840 --> 01:41:12,360
VIRAL INFECTION SO THE WORK WE

2573
01:41:12,360 --> 01:41:13,920
DO WOULDN'T BE POSSIBLE WITHOUT

2574
01:41:13,920 --> 01:41:15,640
THIS DIVERSE RANGE OF EXPERTISE

2575
01:41:15,640 --> 01:41:18,280
WORKING TOGETHER.  SO TO

2576
01:41:18,280 --> 01:41:21,040
UNDERSTAND WHAT AND WHY WE ARE

2577
01:41:21,040 --> 01:41:22,800
TALKING ABOUT WHAT WE ARE, IT IS

2578
01:41:22,800 --> 01:41:24,240
IMPORTANT TO KNOW THE GOALS OF

2579
01:41:24,240 --> 01:41:28,040
OUR TEAM. WE ARE PASSED

2580
01:41:28,040 --> 01:41:29,920
DEVELOPING 2D ANTIVIRAL

2581
01:41:29,920 --> 01:41:32,040
PLATFORMS AND 3D VIRAL ASSAYS

2582
01:41:32,040 --> 01:41:34,160
PER TIES UNDER APP HAVING

2583
01:41:34,160 --> 01:41:35,640
PANDEMIC OR AT LEAST SIGNIFICANT

2584
01:41:35,640 --> 01:41:37,600
OUTBREAK POTENTIAL. SO TO DO

2585
01:41:37,600 --> 01:41:39,760
THIS WE FIRST WORKED TO IDENTIFY

2586
01:41:39,760 --> 01:41:40,800
WHAT WOULD BE NECESSARY CELL

2587
01:41:40,800 --> 01:41:43,680
BASED AND TISSUE BASED MODELS

2588
01:41:43,680 --> 01:41:45,320
FOR EACH PRIORITY AREA OF

2589
01:41:45,320 --> 01:41:48,320
INTEREST AND THEN TAKE INTO

2590
01:41:48,320 --> 01:41:50,040
ACCOUNT FEASIBILITY WE DEVELOP

2591
01:41:50,040 --> 01:41:54,200
OR ADOPT HIGH THROUGH PUT

2592
01:41:54,200 --> 01:41:56,480
COMPATIBLE ANTI-ADJUVANT MODEL

2593
01:41:56,480 --> 01:41:59,320
CELL BASED MODELS THEN USE TO

2594
01:41:59,320 --> 01:42:02,200
SCREEN LARGE LIBRARIES TO

2595
01:42:02,200 --> 01:42:04,000
IDENTIFY ANTIVIRALS FOR THAT

2596
01:42:04,000 --> 01:42:05,120
FAMILY OF INTEREST IF POSSIBLE

2597
01:42:05,120 --> 01:42:07,440
WITH GOAL OF WORKING WITH NCATS

2598
01:42:07,440 --> 01:42:10,440
BIOCHEMICAL ASSAY TEAMS FOR

2599
01:42:10,440 --> 01:42:12,000
VALIDATE VIRAL TARGETS AND

2600
01:42:12,000 --> 01:42:14,000
MEDICINAL CHEMIST WHO IDENTIFY

2601
01:42:14,000 --> 01:42:16,800
POTENTIAL SMALL MOLECULE FOR

2602
01:42:16,800 --> 01:42:18,200
ANTIVIRAL DEVELOPMENT. SO WE ARE

2603
01:42:18,200 --> 01:42:20,240
IN PARALLEL DEVELOPING 3D TISSUE

2604
01:42:20,240 --> 01:42:21,480
MODELS WORKING WITH MEMBERS OF

2605
01:42:21,480 --> 01:42:24,280
THE 3D TISSUE BIOPRINTING LAB

2606
01:42:24,280 --> 01:42:26,240
WITH THE MODULAR COMPLEXITY WHEN

2607
01:42:26,240 --> 01:42:28,080
POSSIBLE FOR MODELING VIRAL

2608
01:42:28,080 --> 01:42:29,320
INFECTION AND VIRAL INDUCED

2609
01:42:29,320 --> 01:42:31,320
DISEASE SO THE GOAL IN OUTREACH

2610
01:42:31,320 --> 01:42:32,800
MODEL TO STUDY VIRAL INFECTION

2611
01:42:32,800 --> 01:42:35,440
AND DISEASE IS DRIVEN BY THE

2612
01:42:35,440 --> 01:42:36,320
UNDERSTANDING THAT FOR EACH

2613
01:42:36,320 --> 01:42:38,120
VIRUS THE COURSE OF INFECTION

2614
01:42:38,120 --> 01:42:39,760
VIRAL DISEASE IMPACT DIFFERENT

2615
01:42:39,760 --> 01:42:41,160
DESIRED TREATMENT STRATEGIES SO

2616
01:42:41,160 --> 01:42:43,360
FOR EXAMPLE FOR SOME VIRUSES WE

2617
01:42:43,360 --> 01:42:46,040
MAY REALLY ONLY NEED ANTIVIRALS

2618
01:42:46,040 --> 01:42:49,560
WHEREAS OTHERS WE MAY NEEDS TO

2619
01:42:49,560 --> 01:42:51,360
LOOK AT ANTI-MODULATORY DRUGS

2620
01:42:51,360 --> 01:42:53,920
FOR MEDIATING RESPONSE SYSTEMIC

2621
01:42:53,920 --> 01:42:58,240
DISEASE. SO WE HOPE THESE VIRAL

2622
01:42:58,240 --> 01:42:59,880
DISEASE MODELS TISSUE MODELS CAN

2623
01:42:59,880 --> 01:43:02,560
ENABLE US TO USE THESE MODELS TO

2624
01:43:02,560 --> 01:43:06,520
VALIDATE POTENTIAL THERAPEUTIC

2625
01:43:06,520 --> 01:43:08,040
FOR CLINICAL DEVELOPMENT AND

2626
01:43:08,040 --> 01:43:09,680
HAVE ON HAND LARGE BODY OF

2627
01:43:09,680 --> 01:43:12,120
INFORMATION WHEN MOLECULES OR OR

2628
01:43:12,120 --> 01:43:14,000
THERAPEUTICS MAY WORK FOR THE

2629
01:43:14,000 --> 01:43:15,440
PREPARATION OF NEXT EMERGING

2630
01:43:15,440 --> 01:43:17,160
VIRAL DISEASE FOR RAPID

2631
01:43:17,160 --> 01:43:18,600
EVALUATION. SO ALTHOUGH THERE

2632
01:43:18,600 --> 01:43:20,400
ARE MANY MODELS THAT WOULD LOVE

2633
01:43:20,400 --> 01:43:24,320
TO TALK TO YOU ABOUT TODAY VIRUS

2634
01:43:24,320 --> 01:43:25,320
TISSUE PRINTING LAB FOR TIME OF

2635
01:43:25,320 --> 01:43:27,240
THIS WORKSHOP I WILL BE FOCUSING

2636
01:43:27,240 --> 01:43:29,320
ON THREE EXAMPLES HOW WE ARE

2637
01:43:29,320 --> 01:43:31,880
TACKLING 3D MODELS FOR VIRAL

2638
01:43:31,880 --> 01:43:34,640
INFECTIONS IN THREE SECTIONS.  I

2639
01:43:34,640 --> 01:43:36,600
WILL HIGHLIGHT EXPERIENCE

2640
01:43:36,600 --> 01:43:39,600
WORKING WITH ALI LUNG MODELS,

2641
01:43:39,600 --> 01:43:42,960
FOR SARS COV-2 ANTIVIRAL

2642
01:43:42,960 --> 01:43:44,360
VALIDATION AND CHARACTERIZATIONS

2643
01:43:44,360 --> 01:43:46,280
OF THE MODEL WE FEEL WE CAN USE

2644
01:43:46,280 --> 01:43:47,960
FOR FURTHER THERAPEUTIC

2645
01:43:47,960 --> 01:43:49,120
EVALUATION AS REPRESENTATION OF

2646
01:43:49,120 --> 01:43:52,400
WHAT KIND OF MODEL WE MAY NEED

2647
01:43:52,400 --> 01:43:53,480
FORESTAY DIG DRUGS ANTIVIRALS

2648
01:43:53,480 --> 01:43:54,880
AND WHERE WE CAN GO WITH THESE

2649
01:43:54,880 --> 01:43:56,240
MODELS WHERE WE THINK WE CAN GO

2650
01:43:56,240 --> 01:43:59,120
WITH MODELS IN TERMS OF VIRAL

2651
01:43:59,120 --> 01:44:00,960
INFECTION DISEASE AND RELIABLE

2652
01:44:00,960 --> 01:44:06,240
READ OUTS. IN A SECOND I WILL

2653
01:44:06,240 --> 01:44:07,680
TALK MORPHINETYPIC MODEL SHOWING

2654
01:44:07,680 --> 01:44:09,080
EARLY STAGE VIRAL DISEASE

2655
01:44:09,080 --> 01:44:10,720
VASCULAR DAMAGE MODEL USING

2656
01:44:10,720 --> 01:44:13,640
DENGUE VIRUS IN A MULTI-CHIP

2657
01:44:13,640 --> 01:44:15,960
VASCULARIZED TISSUE MODEL AND

2658
01:44:15,960 --> 01:44:17,960
THIRD PART TALK ABOUT

2659
01:44:17,960 --> 01:44:19,880
REPURPOSING MODELS TO REITERATE

2660
01:44:19,880 --> 01:44:21,000
DISCUSSION THESE HUMAN BASE

2661
01:44:21,000 --> 01:44:22,640
TISSUE MODELS SHOULD BE

2662
01:44:22,640 --> 01:44:23,760
MULTI-PURPOSE AND MULTI-DISEASE

2663
01:44:23,760 --> 01:44:27,200
AND SO AS AN EXAMPLE WE CREATED

2664
01:44:27,200 --> 01:44:28,880
THE NEURONAL SPHERING MODELS

2665
01:44:28,880 --> 01:44:30,360
OVER YEARS FOR PURPOSE OF

2666
01:44:30,360 --> 01:44:31,680
MODELING NEUROLOGIC DISEASE SUCH

2667
01:44:31,680 --> 01:44:36,760
AS PARKINSON AND ALZHEIMER'S AND

2668
01:44:36,760 --> 01:44:38,520
THE IDEA EXPANDING USE OF THIS

2669
01:44:38,520 --> 01:44:39,760
MODELS TO VIRAL INFECTION SO

2670
01:44:39,760 --> 01:44:41,520
ALSO TOUCH BRIEFLY WHAT WE FEEL

2671
01:44:41,520 --> 01:44:43,080
IS NECESSARY FOR THE NEXT STEPS,

2672
01:44:43,080 --> 01:44:47,000
MAKE THIS MODEL MORE

2673
01:44:47,000 --> 01:44:48,200
REPRESENTATIVE FOR NEUROTROPIC

2674
01:44:48,200 --> 01:44:50,680
VIRAL INFECTION WHICH IS TO

2675
01:44:50,680 --> 01:44:51,440
FUNCTIONAL BLOOD BRAIN BARRIER

2676
01:44:51,440 --> 01:44:54,080
TO THE MODEL. SO START WITH

2677
01:44:54,080 --> 01:44:55,480
PANDEMIC A LOT OF US STARTED

2678
01:44:55,480 --> 01:44:58,640
WORKING TOGETHER TO GENERATE NEW

2679
01:44:58,640 --> 01:45:00,040
OR REPURPOSE EXISTING MODELS FOR

2680
01:45:00,040 --> 01:45:01,360
SARS COV-2 INFECTION. THE

2681
01:45:01,360 --> 01:45:04,040
STRATEGY WAS TO FOCUS ON THE

2682
01:45:04,040 --> 01:45:06,840
RESPIRATORY TRACT WHICH IS

2683
01:45:06,840 --> 01:45:08,320
IMPORTANT TO COVID WITH FOCUS ON

2684
01:45:08,320 --> 01:45:10,000
DIFFERENT AREAS OF DIFFERENT

2685
01:45:10,000 --> 01:45:14,720
CELL COMPOSITIONS INCLUDING THE

2686
01:45:14,720 --> 01:45:16,240
AIRWAY BRONCHIAL REGION AND

2687
01:45:16,240 --> 01:45:17,680
ALVEOLI SO WE WORKED IN VARIOUS

2688
01:45:17,680 --> 01:45:18,760
MODELS REPRESENTING DIFFERENT

2689
01:45:18,760 --> 01:45:20,480
LEVELS OF PHYSIOLOGICAL

2690
01:45:20,480 --> 01:45:23,880
COMPLEXITY RANGING FROM THE

2691
01:45:23,880 --> 01:45:27,080
SIMPLEST LUNG TRANSWELL ASH

2692
01:45:27,080 --> 01:45:27,800
LIQUID INTERFACE MODEL TO

2693
01:45:27,800 --> 01:45:29,600
CO-CULTURES OF PULMONARY CELL

2694
01:45:29,600 --> 01:45:31,480
TYPES TO BIOPRINTING OF VASCULAR

2695
01:45:31,480 --> 01:45:33,040
BED ALONG EPITHELIA TO

2696
01:45:33,040 --> 01:45:40,000
REPURPOSING THE 64 CHIP ORGANO

2697
01:45:40,000 --> 01:45:42,960
GRAPH PLATE TUMOR FOR

2698
01:45:42,960 --> 01:45:43,640
VASCULARIZED SPHEROIDS AND

2699
01:45:43,640 --> 01:45:46,920
AIRWAY OR ALVEOLAR EPITHELIAL

2700
01:45:46,920 --> 01:45:51,920
CELLS IN TOP OF PERFUSABLE

2701
01:45:51,920 --> 01:45:53,600
PULMONARY VASCULAR BED. WE HAVE

2702
01:45:53,600 --> 01:45:55,960
TO THINK ABOUT WHAT THE NEXT

2703
01:45:55,960 --> 01:45:57,960
STEPS WE WOULD TAKE WHAT ARE

2704
01:45:57,960 --> 01:46:00,240
ADDITIONAL CELL TYPES NECESSARY

2705
01:46:00,240 --> 01:46:01,360
TO ADD THERE IS TALK ABOUT

2706
01:46:01,360 --> 01:46:03,440
IMMUNE CELLS IN THIS WORKSHOP

2707
01:46:03,440 --> 01:46:07,200
AND WHAT READ OUTS WE NEED TO

2708
01:46:07,200 --> 01:46:09,000
EACH MODEL FOR REPRODUCIBLE

2709
01:46:09,000 --> 01:46:11,640
SYSTEMS FOR THESE TO REALLY BE

2710
01:46:11,640 --> 01:46:13,600
USED IN TRUE DRUG DISCOVERY

2711
01:46:13,600 --> 01:46:15,360
FASHION. IN ADDITION TO

2712
01:46:15,360 --> 01:46:17,160
IMPORTANCE OF CREATING UNBIASED

2713
01:46:17,160 --> 01:46:20,880
PARAMETERS USED BY ANY GROUP FOR

2714
01:46:20,880 --> 01:46:22,760
UNBIAS QCs THE MODELS

2715
01:46:22,760 --> 01:46:24,520
HOPEFULLY EVALUATING ANY

2716
01:46:24,520 --> 01:46:29,120
INFECTION OR DRUG  EFFICACY DATE

2717
01:46:29,120 --> 01:46:31,080
USE IN HOUSE MODELS FOR VIRUS,

2718
01:46:31,080 --> 01:46:33,840
SO WE MAKE OUR OWN IN HOUSE

2719
01:46:33,840 --> 01:46:38,400
SMALL AIRWAY AND ALVEOLAR 96

2720
01:46:38,400 --> 01:46:41,640
TRANSWELL MODEL AND PURCHASED

2721
01:46:41,640 --> 01:46:44,360
MATTEK AT ALVEOLAR MODELS SO

2722
01:46:44,360 --> 01:46:47,400
THESE CREATED BY PRIMARY LUNG

2723
01:46:47,400 --> 01:46:50,640
EPITHELIAL CELLS WITH OR WITHOUT

2724
01:46:50,640 --> 01:46:53,080
FIBROBLASTS ON TO TRANSWELL

2725
01:46:53,080 --> 01:46:55,680
MEMBRANE FORM EPITHELIAL LAYER

2726
01:46:55,680 --> 01:46:58,480
ON THE TOP AND MOVING CULTURE TO

2727
01:46:58,480 --> 01:47:00,080
AIR TO ALLOW THEMSELVES TO

2728
01:47:00,080 --> 01:47:02,160
MATURE, YOU SEE EMERGENCE OF

2729
01:47:02,160 --> 01:47:03,400
SEVERAL POPULATIONS IN THESE

2730
01:47:03,400 --> 01:47:05,160
MODELS IN THE AIRWAY YOU WILL

2731
01:47:05,160 --> 01:47:10,800
SEE POPULATION OF SILLIATED

2732
01:47:10,800 --> 01:47:11,640
CELLS, GOBLET CELLS AND

2733
01:47:11,640 --> 01:47:13,760
POPULATION CELLS ALVEOLAR TYPE

2734
01:47:13,760 --> 01:47:16,240
ONE AND TWO AND INTERMEDIATE

2735
01:47:16,240 --> 01:47:18,240
CELLS SO WE USE FOR VARIETY OF

2736
01:47:18,240 --> 01:47:20,240
INPEEKSES TO FOCUS ON SARS

2737
01:47:20,240 --> 01:47:21,640
COV-2, WHICH CASE FOR DRUG

2738
01:47:21,640 --> 01:47:24,880
SCREENING WE ADD MOLECULES TO

2739
01:47:24,880 --> 01:47:26,720
BASAL CHAMBER TO APICAL SIDE AND

2740
01:47:26,720 --> 01:47:29,080
MEASURE AMOUNT OF VIRAL

2741
01:47:29,080 --> 01:47:31,440
INFECTION ON THE TISSUE BY

2742
01:47:31,440 --> 01:47:32,640
DIRECT ANTIGEN STAINING FOR

2743
01:47:32,640 --> 01:47:34,760
BROWN CELLULAR MARKERS LOOK AT

2744
01:47:34,760 --> 01:47:36,040
TISSUE STRUCTURE MEASURE

2745
01:47:36,040 --> 01:47:37,680
SECRETED VIRUS, SECRETED

2746
01:47:37,680 --> 01:47:42,720
CYTOKINE CHEMOKINES AND DOING

2747
01:47:42,720 --> 01:47:44,040
SINGLE CELL RNA SEQ WORK IN

2748
01:47:44,040 --> 01:47:46,040
HEALTHY VERSUS INFECTED TISSUE

2749
01:47:46,040 --> 01:47:47,400
TO CHARACTERIZE DISEASE VERSUS

2750
01:47:47,400 --> 01:47:48,840
HEALTHY STATE AFTER SARS COV-2

2751
01:47:48,840 --> 01:47:53,600
INFECTION. SO YOU CAN SEE HERE

2752
01:47:53,600 --> 01:47:56,560
THAT THESE AIRWAY ALVEOLAR

2753
01:47:56,560 --> 01:47:57,760
TISSUES CELL MENTION WED ARE

2754
01:47:57,760 --> 01:48:00,760
USING THE TECH TISSUES IN THESE

2755
01:48:00,760 --> 01:48:02,520
NEXT FEW SLIDES SUPPORT

2756
01:48:02,520 --> 01:48:04,400
PRODUCTIVE INFECTION COV 2

2757
01:48:04,400 --> 01:48:06,400
MEASURING THE AMOUNT OF RELEASE

2758
01:48:06,400 --> 01:48:08,360
INFECTIOUS VIRAL PARTICLES AND

2759
01:48:08,360 --> 01:48:10,280
THAT VARIANCE DO HAVE DIFFERENT

2760
01:48:10,280 --> 01:48:12,480
INFECTIVITY OF THIS TISSUE SO WE

2761
01:48:12,480 --> 01:48:15,080
CAN LOOK WHETHER THERE ARE ANY

2762
01:48:15,080 --> 01:48:17,400
CELLULAR TROPISM COV 2 TISSUE

2763
01:48:17,400 --> 01:48:18,680
TYPES BY IMMUNOSTAINING AND WHAT

2764
01:48:18,680 --> 01:48:20,200
WE SEE IS PRIMARY TARGET IN

2765
01:48:20,200 --> 01:48:23,120
THESE BRONCHIAL TISSUES

2766
01:48:23,120 --> 01:48:24,600
SILLIATED CELLS, WHEN WE LOOK AT

2767
01:48:24,600 --> 01:48:28,640
VARIANCE OF ALPHA BETA GAMMA AND

2768
01:48:28,640 --> 01:48:32,280
DELTA SARS COV-2 ONE OF OUR

2769
01:48:32,280 --> 01:48:35,840
GOALS IS TO CHARACTERIZE ANY

2770
01:48:35,840 --> 01:48:38,840
TISSUES DEVELOPED AS MUCH AS

2771
01:48:38,840 --> 01:48:40,520
POSSIBLE BECAUSE PART OF OUR

2772
01:48:40,520 --> 01:48:42,120
MISSION IS ENABLE OTHER GROUPS

2773
01:48:42,120 --> 01:48:43,520
TO BE ABLE THE USE THESE

2774
01:48:43,520 --> 01:48:46,200
TECHNOLOGIES WITHOUT HAVING TO

2775
01:48:46,200 --> 01:48:47,640
REINVEST RESOURCES TO

2776
01:48:47,640 --> 01:48:49,760
RECHARACTERIZE THE SAME MODEL SO

2777
01:48:49,760 --> 01:48:52,640
BECAUSE OF THIS WE STARTED USING

2778
01:48:52,640 --> 01:48:54,400
SINGLE CELL RNA SEQ ON BOTH

2779
01:48:54,400 --> 01:48:56,200
HEALTHY AND DISEASE TISSUE AND

2780
01:48:56,200 --> 01:48:59,040
SHOWN HERE IS AN EXAMPLE LOOK AT

2781
01:48:59,040 --> 01:49:02,160
WHAT TISSUE VIRAL SPECIFIC

2782
01:49:02,160 --> 01:49:03,720
TRANSCRIPTOMIC PROFILES ARE IN

2783
01:49:03,720 --> 01:49:06,880
THAT WE OBSERVE IN AIRWAY VERSUS

2784
01:49:06,880 --> 01:49:09,480
ALVEOLAR ALI TISSUE MODEL IN

2785
01:49:09,480 --> 01:49:11,400
SARS COV-2 VERSUS HEALTHY

2786
01:49:11,400 --> 01:49:12,920
INFLUENZA INFECTION. BUT THE

2787
01:49:12,920 --> 01:49:15,520
PURPOSE OF WHETHER THIS CAN BE

2788
01:49:15,520 --> 01:49:17,120
LINKED TO DISEASE OBSERVED IN

2789
01:49:17,120 --> 01:49:20,520
VIVO WITH GOAL BEING WHEN WE

2790
01:49:20,520 --> 01:49:22,600
TEST THERAPEUTIC AGENT AGAINST

2791
01:49:22,600 --> 01:49:24,400
SARS COV-2 INFECTION DO WE GET

2792
01:49:24,400 --> 01:49:26,000
RETURN TO HEALTHY STATE VERSUS

2793
01:49:26,000 --> 01:49:29,440
DISEASE STATE.  SO THIS IS EARLY

2794
01:49:29,440 --> 01:49:31,040
WORK WE HAVE DONE IN STARTING TO

2795
01:49:31,040 --> 01:49:32,040
CHARACTERIZE DISEASE STATES IN

2796
01:49:32,040 --> 01:49:33,440
CONTEXT OF INFECTION AND I WON'T

2797
01:49:33,440 --> 01:49:35,240
GO INTO MUCH DETAIL BECAUSE OF

2798
01:49:35,240 --> 01:49:36,280
TIME BUT WHAT YOU CAN SEE HERE

2799
01:49:36,280 --> 01:49:38,120
IS THE TISSUE RESPONSE TO VIRAL

2800
01:49:38,120 --> 01:49:39,560
INFECTION IS DEPENDENT ON THE

2801
01:49:39,560 --> 01:49:41,600
VIRUS AND ON THE TISSUE TYPE.

2802
01:49:41,600 --> 01:49:44,240
AND AS AN EXAMPLE, THIS IS THE

2803
01:49:44,240 --> 01:49:46,480
EARLY WASHINGTON SARS COV-2

2804
01:49:46,480 --> 01:49:49,040
VARIANT YOU CAN SEE TISSUE

2805
01:49:49,040 --> 01:49:51,280
RESPONSE TO SARS COV-2 MORE

2806
01:49:51,280 --> 01:49:53,040
SUBTLE COMPARED TO INFLUENZA BUT

2807
01:49:53,040 --> 01:49:54,400
STILL GETTING CHANGES TO PROFILE

2808
01:49:54,400 --> 01:49:55,520
SO WE CAN START TO IDENTIFY

2809
01:49:55,520 --> 01:49:58,400
DIFFERENT PROFILES OBSERVED

2810
01:49:58,400 --> 01:49:59,880
BETWEEN DIFFERENT VIRUSES AND

2811
01:49:59,880 --> 01:50:01,440
THE TISSUE BETWEEN SAME VIRUS

2812
01:50:01,440 --> 01:50:03,000
AND DIFFERENT TISSUES AND WHAT

2813
01:50:03,000 --> 01:50:04,320
WE HOPE TO BE ABLE TO CREATE IS

2814
01:50:04,320 --> 01:50:05,640
A PANEL OF BIOMARKERS THAT WE

2815
01:50:05,640 --> 01:50:07,560
CAN USE TO EVALUATE SEVERE

2816
01:50:07,560 --> 01:50:08,680
DISEASE IN DIFFERENT TISSUES OF

2817
01:50:08,680 --> 01:50:13,040
THE RESPIRATORY TRACK. SO THIS

2818
01:50:13,040 --> 01:50:16,920
IS AN EXAMPLE, INTERESTED IN

2819
01:50:16,920 --> 01:50:19,240
INFECTION INFLAMMATORY RESPONSE

2820
01:50:19,240 --> 01:50:21,480
AIRWAY VERSUS ALVEOLAR ISSUES

2821
01:50:21,480 --> 01:50:23,720
THAT AFFECTS SEVERITY OF DISEASE

2822
01:50:23,720 --> 01:50:25,760
AND INFECTED INDIVIDUAL SO WE

2823
01:50:25,760 --> 01:50:27,800
LOOK AT PANEL LINKED TO DISEASE

2824
01:50:27,800 --> 01:50:33,000
IN COVID PATIENTS WE SEE HIGH

2825
01:50:33,000 --> 01:50:36,800
INDUCTION OF IP 10 PLURIPOTENT

2826
01:50:36,800 --> 01:50:40,920
CHEMOKINE. ALI TISSUE IN

2827
01:50:40,920 --> 01:50:42,680
PARTICULAR WE WERE OBSERVING A

2828
01:50:42,680 --> 01:50:45,320
HIGH INFECTION IN BOTH ALVEOLAR

2829
01:50:45,320 --> 01:50:47,680
EPITHELIAL CELLS AND WITH

2830
01:50:47,680 --> 01:50:49,240
CONTRIBUTION ENDOTHELIAL CELLS

2831
01:50:49,240 --> 01:50:54,200
AND FIBROBLASTS AS WELL.  SO WE

2832
01:50:54,200 --> 01:50:56,920
WANTED TO USE THE MODELS DURING

2833
01:50:56,920 --> 01:50:58,280
EARLY DAYS PANDEMIC. WE DIDN'T

2834
01:50:58,280 --> 01:51:00,600
HAVE ACCESS TO BSL 3 UNLIKE NOW

2835
01:51:00,600 --> 01:51:03,160
SO WE ARE LUCKY TO BE ABLE TO

2836
01:51:03,160 --> 01:51:04,800
COLLABORATE WITH DR. SARA CHERRY

2837
01:51:04,800 --> 01:51:10,400
AT UPENN WE HEARD SPEAK BEFORE

2838
01:51:10,400 --> 01:51:12,000
LUNCH, DR. CHERRY ARE WAS

2839
01:51:12,000 --> 01:51:14,280
WORKING WITH HUMAN CELL BASED

2840
01:51:14,280 --> 01:51:15,720
SCREENS AND TISSUE MOLES TO

2841
01:51:15,720 --> 01:51:17,280
UNCOVER DIFFERENCES IN ANTIVIRAL

2842
01:51:17,280 --> 01:51:18,480
ACTIVITY IN DIFFERENT HUMAN AND

2843
01:51:18,480 --> 01:51:23,960
NON-HUMAN CELL TYPES SO WE

2844
01:51:23,960 --> 01:51:26,080
STARTED WORKING WITH DR. CHERRY

2845
01:51:26,080 --> 01:51:28,000
PAIRING TISSUES MAYBE PREDICTIVE

2846
01:51:28,000 --> 01:51:29,320
AND WHETHER THIS HELPS NARROW

2847
01:51:29,320 --> 01:51:31,880
DOWN COMPOUNDS FOR FURTHER

2848
01:51:31,880 --> 01:51:33,760
EVALUATION IN ANIMAL MODELS

2849
01:51:33,760 --> 01:51:37,400
PRE-CLINICAL DEVELOPMENT. SO

2850
01:51:37,400 --> 01:51:38,680
THIS IS SHOWING SOME OF THE

2851
01:51:38,680 --> 01:51:41,920
DRUGS AND READ OUTS WE USE

2852
01:51:41,920 --> 01:51:46,320
RANGING FROM DIRECT VIRAL

2853
01:51:46,320 --> 01:51:47,560
ANTIGEN STAINS, QR PCR

2854
01:51:47,560 --> 01:51:48,960
PRODUCTION AND WHAT YOU CAN SEE

2855
01:51:48,960 --> 01:51:52,080
HERE IN THE BOTTOM RIGHT CORNER,

2856
01:51:52,080 --> 01:51:55,480
WE HAVE THE HYDROXYCHLOROQUINE,

2857
01:51:55,480 --> 01:52:00,000
EXPLORED EARLY ON IN THE

2858
01:52:00,000 --> 01:52:03,760
PANDEMIC DOESN'T WORK IN MODELS

2859
01:52:03,760 --> 01:52:04,800
DISCUSSED TODAY AND YESTERDAY

2860
01:52:04,800 --> 01:52:08,000
AND SUGGESTED BEFORE IT IS

2861
01:52:08,000 --> 01:52:09,360
POSSIBLE IF MODELS WERE

2862
01:52:09,360 --> 01:52:11,000
WIDESPREAD AND WIDESPREAD USE

2863
01:52:11,000 --> 01:52:12,720
EARLY ON DURING THE PANDEMIC WE

2864
01:52:12,720 --> 01:52:15,640
WOULD HAVE RECOGNIZED ANTS VIRAL

2865
01:52:15,640 --> 01:52:16,760
ACTIVITY MUCH EARLIER SO A KEY

2866
01:52:16,760 --> 01:52:18,080
TAKE AWAY FROM OUR EXPERIENCE IS

2867
01:52:18,080 --> 01:52:21,120
THAT WE NEED TO FULLY

2868
01:52:21,120 --> 01:52:22,040
CHARACTERIZE THESE MODELS EARLY

2869
01:52:22,040 --> 01:52:25,480
BEFORE THE NEXT VIRAL OUTBREAK

2870
01:52:25,480 --> 01:52:27,920
WITH BOTH DIRECT VIRAL INFECTION

2871
01:52:27,920 --> 01:52:28,920
READ OUT AND DISEASE

2872
01:52:28,920 --> 01:52:33,240
INFLAMMATORY READ OUTS, AND HAVE

2873
01:52:33,240 --> 01:52:36,880
THIS ACCESSIBLE FOR VIRAL FAMILY

2874
01:52:36,880 --> 01:52:38,920
AND TISSUES OF INTEREST IN THIS

2875
01:52:38,920 --> 01:52:40,240
CASE RESPIRATORY TRACK SO THE

2876
01:52:40,240 --> 01:52:41,600
NEXT VIRAL AGENT ARISES WE HAVE

2877
01:52:41,600 --> 01:52:44,600
THESE TISSUES AND TECHNIQUES IN

2878
01:52:44,600 --> 01:52:46,200
OUR TOOLBOX READY FOR

2879
01:52:46,200 --> 01:52:47,680
THERAPEUTICS EVALUATION SO THAT

2880
01:52:47,680 --> 01:52:50,280
WE CAN HAVE A MORE REAL TIME

2881
01:52:50,280 --> 01:52:52,440
RAPID IMPACT VIRAL THERAPEUTICS

2882
01:52:52,440 --> 01:52:57,040
BEING CONSIDERED FOR DEPLOYMENT 

2883
01:52:57,040 --> 01:52:58,520
SO FOR PART 2 OF MY TALK I WOULD

2884
01:52:58,520 --> 01:53:02,280
LIKE TO TALK ABOUT VIRAL INDUCED

2885
01:53:02,280 --> 01:53:02,880
DISEASE MODELING THIS IS AN

2886
01:53:02,880 --> 01:53:04,120
EXCEPTION OF THE FIRST PART

2887
01:53:04,120 --> 01:53:05,120
BECAUSE WE ARE INTERESTED IN IN

2888
01:53:05,120 --> 01:53:06,560
DIRECT INFECTION. SO WE ARE ALSO

2889
01:53:06,560 --> 01:53:08,160
LOOKING AT MORE SEVERE DISEASE

2890
01:53:08,160 --> 01:53:12,920
READ OUTS.  DENGUE VIRUS IS A

2891
01:53:12,920 --> 01:53:15,360
POSITIVE SENSE RNA VIRUS, POSES

2892
01:53:15,360 --> 01:53:18,360
A HUGE GLOBAL BURDEN EACH YEAR

2893
01:53:18,360 --> 01:53:19,880
WITH AROUND 400 MILLION CASES

2894
01:53:19,880 --> 01:53:22,480
ESTIMATED PER THE WORLD HEALTH

2895
01:53:22,480 --> 01:53:23,720
ORGANIZATION PER YEAR WORLDWIDE

2896
01:53:23,720 --> 01:53:25,720
WITH SEVERE DENGUE AFFECTING

2897
01:53:25,720 --> 01:53:27,640
SUBSET OF INDIVIDUALS THAT

2898
01:53:27,640 --> 01:53:33,960
RANGES DEPENDING ON AREA. SO AS

2899
01:53:33,960 --> 01:53:35,320
MENTIONED EARLIER OUR LAB WORKED

2900
01:53:35,320 --> 01:53:37,720
ON DEVELOPING BOTH AIRWAY

2901
01:53:37,720 --> 01:53:43,320
ALVEOLAR AND CHIP MODELS ORGANO

2902
01:53:43,320 --> 01:53:45,920
GRAPH PLATE GRAPH WHICH IS A 64

2903
01:53:45,920 --> 01:53:49,560
CHIP PROFUSE TISSUE MODEL THAT

2904
01:53:49,560 --> 01:53:51,760
USES HERE ON THE RIGHT TO INDUCE

2905
01:53:51,760 --> 01:53:54,000
FLOW IN THE MODEL. SO BECAUSE WE

2906
01:53:54,000 --> 01:53:56,360
KNOW THAT DENGUE VIRUS CAUSES

2907
01:53:56,360 --> 01:53:58,120
VASCULAR DAMAGE IN CASES OF

2908
01:53:58,120 --> 01:54:00,480
SEVERE DENGUE WE SOUGHT TO

2909
01:54:00,480 --> 01:54:02,240
MODIFY THE MODEL TO CREATE A

2910
01:54:02,240 --> 01:54:04,160
SIMPLER MODEL TO START FOR

2911
01:54:04,160 --> 01:54:07,200
STUDYING DENGUE INDUCED DAMAGE. 

2912
01:54:07,200 --> 01:54:13,800
SO IMPORTANTLY, REASONS WE

2913
01:54:13,800 --> 01:54:17,120
SOUGHT TO USE THIS MODEL IS THAT

2914
01:54:17,120 --> 01:54:19,520
ONE, IT IS 64 CHIPS PER PLATE SO

2915
01:54:19,520 --> 01:54:22,160
WE CAN USE IT AND IT USES

2916
01:54:22,160 --> 01:54:24,600
IRONINGER SO WE CAN USE BSL 2

2917
01:54:24,600 --> 01:54:26,160
AND 3 CONTEXT AND IT IS

2918
01:54:26,160 --> 01:54:27,320
PROFUSABLE WHICH WILL ALLOW US

2919
01:54:27,320 --> 01:54:29,920
TO LOOK AT VIRAL EFFECTS ON

2920
01:54:29,920 --> 01:54:31,480
VESSEL WEAKNESS AND SHOWN HERE

2921
01:54:31,480 --> 01:54:33,280
ARE EXAMPLE PROFUSIONS AND GROUP

2922
01:54:33,280 --> 01:54:36,520
SMALL AIRWAY CHIP MODEL THAT

2923
01:54:36,520 --> 01:54:39,480
(INDISCERNIBLE) MADE IN THE LAB 

2924
01:54:39,480 --> 01:54:43,800
WE ARE SHOWING PROFUSION WITH 70

2925
01:54:43,800 --> 01:54:45,320
KD FLUORESCENT STRAND. WE ARE

2926
01:54:45,320 --> 01:54:48,120
OPTIMIZING THE TISSUE TO

2927
01:54:48,120 --> 01:54:48,880
MAINTAIN LARGE ENOUGH

2928
01:54:48,880 --> 01:54:49,920
CONNECTIONS BETWEEN THE LARGE

2929
01:54:49,920 --> 01:54:51,640
VESSELS AND MICROVASCULAR

2930
01:54:51,640 --> 01:54:53,160
NETWORK WHEN INCORPORATING

2931
01:54:53,160 --> 01:54:54,600
DIFFERENT EPITHELIAL LAYERS

2932
01:54:54,600 --> 01:54:56,360
BECAUSE THAT DOES IMPACT THE

2933
01:54:56,360 --> 01:54:57,440
VASCULATURE UNDERNEATH. SO WE

2934
01:54:57,440 --> 01:54:59,560
ARE DOING THIS AS WE EVALUATE

2935
01:54:59,560 --> 01:55:01,480
DIFFERENT CELL TYPES PERMISSIVE

2936
01:55:01,480 --> 01:55:03,520
TO DENGUE INFECTION. SO FOR OUR

2937
01:55:03,520 --> 01:55:06,160
FIRST PILOT STUDIES WE ARE USING

2938
01:55:06,160 --> 01:55:10,800
GFP EXPRESSING HUMAN PULMONARY

2939
01:55:10,800 --> 01:55:15,280
ENDOTHELIAL CELLS, WITH SEE

2940
01:55:15,280 --> 01:55:16,280
ENDOTHELIAL CELLS AND PAIR SITES

2941
01:55:16,280 --> 01:55:19,120
IN LOWER DENSITY LOWER CHAMBER

2942
01:55:19,120 --> 01:55:21,560
HYDRA GEL AND ALLOW THEM TO FORM

2943
01:55:21,560 --> 01:55:23,160
THIS NETWORK OVER TIME. BECAUSE

2944
01:55:23,160 --> 01:55:27,240
THEY ARE GFP WE CAN QC TISSUE

2945
01:55:27,240 --> 01:55:31,440
PLATE OVER TIME AND EXCLUDE

2946
01:55:31,440 --> 01:55:34,000
MONOLAYERS OR USE THE -- WE CAN

2947
01:55:34,000 --> 01:55:35,160
ALSO USE THE INFORMATION TO

2948
01:55:35,160 --> 01:55:36,480
INFORM US OF CHANGES IN THE

2949
01:55:36,480 --> 01:55:38,440
TISSUE RELATED TO INFECTION OR

2950
01:55:38,440 --> 01:55:41,000
SIMPLY RELATED TO AGING OF

2951
01:55:41,000 --> 01:55:42,840
TISSUES. SO SHOWN HERE ARE

2952
01:55:42,840 --> 01:55:45,360
REPRESENTATIVE IMAGES OF

2953
01:55:45,360 --> 01:55:46,800
MONITORING THE MICROVASCULAR

2954
01:55:46,800 --> 01:55:49,800
NETWORK DEVELOPMENT OVER TIME

2955
01:55:49,800 --> 01:55:51,360
FROM SEEDING UP UNTIL

2956
01:55:51,360 --> 01:55:53,160
MATURATION. BY USING THE

2957
01:55:53,160 --> 01:55:54,880
EPITHELIAL CELLS AND MON FORKING

2958
01:55:54,880 --> 01:55:57,080
THE SAME LEVEL FOR VIRAL INSULTS

2959
01:55:57,080 --> 01:55:59,720
IN THE BOTTOM WE ARE ABLE TO

2960
01:55:59,720 --> 01:56:01,720
OBSERVE MORPHOLOGICAL CHANGES IN

2961
01:56:01,720 --> 01:56:05,560
TISSUE AFTER RECOMBINANT DENGUE

2962
01:56:05,560 --> 01:56:08,400
TO THE CHANNEL IN VIRUS

2963
01:56:08,400 --> 01:56:09,600
EPITHELIAL LAYER QUANTIFY SHOWN

2964
01:56:09,600 --> 01:56:11,040
IN THE GRAPH IN THE LEFT AND WE

2965
01:56:11,040 --> 01:56:12,600
ARE CURRENTLY EXPLORING

2966
01:56:12,600 --> 01:56:14,360
ADDITIONAL PARAMETERS SUCH AS

2967
01:56:14,360 --> 01:56:16,560
VESSEL BRANCHING WEAKNESS AS

2968
01:56:16,560 --> 01:56:18,840
WELL AS ENDOTHELIAL DYSFUNCTION

2969
01:56:18,840 --> 01:56:20,880
SUCH AS SILL YAK ACID SECRETION.

2970
01:56:20,880 --> 01:56:22,880
I WILL NOTE HERE WE ARE USING A

2971
01:56:22,880 --> 01:56:26,560
DENGUE PERMISSIVE EPITHELIAL

2972
01:56:26,560 --> 01:56:29,000
LAYER OF EOSINOPHILS WHICH IS

2973
01:56:29,000 --> 01:56:30,880
IDEA WE USE THIS AS WE CREATE A

2974
01:56:30,880 --> 01:56:33,720
MODEL AND THEN SWITCH TO A

2975
01:56:33,720 --> 01:56:35,000
PRIMARY LINE.  SO AS I MENTION

2976
01:56:35,000 --> 01:56:37,000
WE ARE ALSO ACTIVELY SEEKING TO

2977
01:56:37,000 --> 01:56:38,960
REPURPOSE EXISTING MODELS FOR

2978
01:56:38,960 --> 01:56:42,200
THE PURPOSE OF VIRAL INFECTION

2979
01:56:42,200 --> 01:56:43,200
AND DISEASE MODELING, AND AS

2980
01:56:43,200 --> 01:56:44,640
DIVERSE RANGE OF TISSUES AS

2981
01:56:44,640 --> 01:56:46,520
NECESSARY FOR VIRUSES

2982
01:56:46,520 --> 01:56:49,320
PRIORITIZED UNDER ATP. SO WE

2983
01:56:49,320 --> 01:56:51,760
RECENTLY PUBLISHED A PRE-PRINT

2984
01:56:51,760 --> 01:56:56,320
DESCRIBING BRAIN REGION SPECIFIC

2985
01:56:56,320 --> 01:56:59,920
NEUROSPHERING MODEL WE MAKE IN

2986
01:56:59,920 --> 01:57:00,840
OUR LAB FOR DIFFERENT

2987
01:57:00,840 --> 01:57:03,800
NEUROLOGICAL DISEASE INCLUDING

2988
01:57:03,800 --> 01:57:04,520
ALZHEIMER'S DISEASE AND

2989
01:57:04,520 --> 01:57:08,360
PARKINSON. WE MAKE THESE

2990
01:57:08,360 --> 01:57:12,480
SPHEROIDS IN 3D PLACE USING IPSC

2991
01:57:12,480 --> 01:57:14,600
DIFFERENTIATED MATURED NEURONS

2992
01:57:14,600 --> 01:57:17,920
AND ASTROCYTES AND WE CAN ALTER

2993
01:57:17,920 --> 01:57:20,520
THE GLUTAMATERGIC GABAERGIC

2994
01:57:20,520 --> 01:57:22,360
NEURONS TO RATIOS REPORTED TO BE

2995
01:57:22,360 --> 01:57:23,480
PRESENT IN DIFFERENT BRAIN

2996
01:57:23,480 --> 01:57:25,640
REGIONS AND IMPORTANTLY WE CAN

2997
01:57:25,640 --> 01:57:27,560
SEE FUNCTIONAL SYNAPSES FORMING

2998
01:57:27,560 --> 01:57:30,880
LOOKS LIKE MY VIDEO IS NOT

2999
01:57:30,880 --> 01:57:35,720
PLAYING. THEN WE ALSO CAN SEE --

3000
01:57:35,720 --> 01:57:38,040
WE CAN ALSO USE KALIUMS IMAGING

3001
01:57:38,040 --> 01:57:40,480
TO SEE CORRESPONDING DIFFERENT

3002
01:57:40,480 --> 01:57:43,640
ACTIVITY PROFILES DEPENDING ON

3003
01:57:43,640 --> 01:57:44,920
RATIO OF NEURAL SUBTYPE

3004
01:57:44,920 --> 01:57:50,200
INCORPORATION. AN ADVANTAGE OF

3005
01:57:50,200 --> 01:57:52,080
USING CALCIUM ACTIVITY AS READ

3006
01:57:52,080 --> 01:57:53,840
OUT FOR THIS MODEL WE CAN LOOK

3007
01:57:53,840 --> 01:57:55,720
AT THE SAME SPHEREROID OVER TIME

3008
01:57:55,720 --> 01:57:58,800
BY TRANSDUCING EARLY ON DURING

3009
01:57:58,800 --> 01:58:01,600
MATURATION USING AN AAV VIRUS

3010
01:58:01,600 --> 01:58:03,520
ENCODING FOR GENETICALLY ENCODED

3011
01:58:03,520 --> 01:58:04,880
CALCIUM INDICATOR AND THEN

3012
01:58:04,880 --> 01:58:07,200
MEASURE AFFECTS OF DRUGS OR

3013
01:58:07,200 --> 01:58:10,120
INSULTS ON NEURONAL FIRING AND

3014
01:58:10,120 --> 01:58:12,560
THE SPHEROID USING A WHOLE PLATE

3015
01:58:12,560 --> 01:58:13,680
FLUORESCENCE IMAGING PLATE

3016
01:58:13,680 --> 01:58:14,920
READER OR LOOK MORE CLOSELY

3017
01:58:14,920 --> 01:58:17,760
USING AN AUTOMATED CONFOCAL

3018
01:58:17,760 --> 01:58:19,600
MICROSCOPE TO MEASURE INDIVIDUAL

3019
01:58:19,600 --> 01:58:20,880
AGENTS OF INTEREST AND NOT

3020
01:58:20,880 --> 01:58:22,320
CHANGES IN SYNCHRONIZATION OVER

3021
01:58:22,320 --> 01:58:24,440
TIME SO ON THE LEFT IS CONFOCAL

3022
01:58:24,440 --> 01:58:26,160
IMAGING AND ON THE RIGHT IS THE

3023
01:58:26,160 --> 01:58:28,080
FLUORESCENT IMAGING PLATE READER

3024
01:58:28,080 --> 01:58:33,640
THAT WE USE.  SO PROOF OF

3025
01:58:33,640 --> 01:58:35,440
CONCEPT WE EXPOSE THESE

3026
01:58:35,440 --> 01:58:39,440
SPHEROIDS TO SARS COV-2, WITHIN

3027
01:58:39,440 --> 01:58:41,040
ABLE TO DETECT ROBUST INFECTION

3028
01:58:41,040 --> 01:58:43,160
OF THE NEURONAL SPHEROID SHOWN

3029
01:58:43,160 --> 01:58:44,640
BY GREEN STAINING SIGNAL,

3030
01:58:44,640 --> 01:58:46,720
STAINING FOR THE SARS COV-2 KNEW

3031
01:58:46,720 --> 01:58:50,160
CLEAR CAPSID PROTEIN, BUT WHILE

3032
01:58:50,160 --> 01:58:55,000
SARS COV-2 IS LIKELY NOT TROPIC

3033
01:58:55,000 --> 01:58:56,760
VIRUS WE ARE GOING TO BE

3034
01:58:56,760 --> 01:58:58,840
EXPANDING THIS SO RECENTLY POST

3035
01:58:58,840 --> 01:59:00,640
DOC WITH EXPERIENCE IN

3036
01:59:00,640 --> 01:59:01,760
NEUROTROPIC VIRUSES SHE WILL BE

3037
01:59:01,760 --> 01:59:02,840
EXPANDING THIS MODEL TO A

3038
01:59:02,840 --> 01:59:05,400
VARIETY OF THE SL 2 LEVEL

3039
01:59:05,400 --> 01:59:07,240
NEUROTROPIC VIRUSES TO START

3040
01:59:07,240 --> 01:59:08,680
INVESTIGATING SHORT TERM VERSUS

3041
01:59:08,680 --> 01:59:12,880
LONG TERM CHANGES TO NEURON

3042
01:59:12,880 --> 01:59:15,080
SPHEREROID ACTIVITY AS WELL AS

3043
01:59:15,080 --> 01:59:17,720
SYNCHRONIZATION AS ONE OF THE

3044
01:59:17,720 --> 01:59:18,760
LIMITATIONS OF THE SYSTEM IS

3045
01:59:18,760 --> 01:59:20,680
HAVING ACCESS TO EQUIPMENT IN

3046
01:59:20,680 --> 01:59:22,160
APPROPRIATE BIOSAFETY LEVEL

3047
01:59:22,160 --> 01:59:23,960
SPACE SO THIS BRINGS UP ANOTHER

3048
01:59:23,960 --> 01:59:24,880
CRITICAL QUESTION ABOUT THIS

3049
01:59:24,880 --> 01:59:26,200
MODEL WHICH IS WHETHER WE CAN

3050
01:59:26,200 --> 01:59:29,560
USE THIS TO EVALUATE

3051
01:59:29,560 --> 01:59:31,440
NEUROTROPISM EMERGING VIRUSES,

3052
01:59:31,440 --> 01:59:34,360
WHICH I THINK TO DO THIS IN A

3053
01:59:34,360 --> 01:59:36,640
REPRESENTATIVE WAY WE MIGHT

3054
01:59:36,640 --> 01:59:40,600
FIRST VIRUS CAN INFECT NEURONAL

3055
01:59:40,600 --> 01:59:43,520
CELLS BUT THEN CHECK IF WE CAN

3056
01:59:43,520 --> 01:59:45,200
INCORPORATE BLOOD BRAIN BARRIER

3057
01:59:45,200 --> 01:59:48,960
INTO THIS MELD WE CAN EVALUATE

3058
01:59:48,960 --> 01:59:51,760
PAST BLOOD BRAIN BARRIER BBB

3059
01:59:51,760 --> 01:59:53,320
ACTS AS A BARRIER TO VIRAL

3060
01:59:53,320 --> 01:59:55,280
INFECTION IN THE BRAIN. TO WRAP

3061
01:59:55,280 --> 01:59:57,520
UP THIS TALK OUR ULTIMATE GOAL

3062
01:59:57,520 --> 02:00:00,840
TO FULLY CHARACTERIZE ISSUE IN

3063
02:00:00,840 --> 02:00:02,200
CONTEXT OF OUR OWN RANGE OF

3064
02:00:02,200 --> 02:00:06,360
INFECTION AS PRIORITIZE UNDER

3065
02:00:06,360 --> 02:00:10,320
ATP OF INTEREST. RANGING FROM

3066
02:00:10,320 --> 02:00:12,040
RESPIRATORY TRACK, BRAIN GUT

3067
02:00:12,040 --> 02:00:14,280
KIDNEY CARDIAC, WE STILL HAVE A

3068
02:00:14,280 --> 02:00:16,000
LONG WAY THE GO AND FOR THAT WE

3069
02:00:16,000 --> 02:00:18,080
HOPE TO COLLABORATE WITH EXPERTS

3070
02:00:18,080 --> 02:00:18,880
IN THE FIELD TO HELP SUPPORT

3071
02:00:18,880 --> 02:00:20,720
THESE CRITICAL EFFORTS AND

3072
02:00:20,720 --> 02:00:22,400
UTILIZING THE 3D TISSUE MODELS

3073
02:00:22,400 --> 02:00:25,120
FOR ANTIVIRAL RESEARCH FOR THE

3074
02:00:25,120 --> 02:00:29,280
BROADER SCIENTIFIC COMMUNITY. 

3075
02:00:29,280 --> 02:00:31,040
WITH THAT, I WOULD LIKE TO

3076
02:00:31,040 --> 02:00:32,400
HIGHLIGHT THE LARGE NUMBER OF

3077
02:00:32,400 --> 02:00:33,680
INDIVIDUALS INVOLVED IN THIS

3078
02:00:33,680 --> 02:00:34,800
WORK WITH INDIVIDUALS

3079
02:00:34,800 --> 02:00:37,440
SPECIFICALLY INVOLVED HERE

3080
02:00:37,440 --> 02:00:38,280
HIGHLIGHTED. AND LIKE TO SAY

3081
02:00:38,280 --> 02:00:41,040
THANK YOU TO THE WHOLE 3D LAB

3082
02:00:41,040 --> 02:00:43,160
AND ATP TEAM AND TO OUR

3083
02:00:43,160 --> 02:00:44,760
COLLABORATORS FOR ENABLING THIS

3084
02:00:44,760 --> 02:00:46,360
WORK. THANK YOU FOR YOUR TIME

3085
02:00:46,360 --> 02:00:50,440
AND LISTENING. 

3086
02:00:50,440 --> 02:00:53,520
>> THANK YOU SO MUCH FOR
THE

3087
02:00:53,520 --> 02:00:55,040
EXCELLENT TALK. LOOK FORWARD TO

3088
02:00:55,040 --> 02:00:56,440
COMING OUT AS PART OF THE

3089
02:00:56,440 --> 02:01:00,200
DISCUSSION IN A BIT.  NOW I WILL

3090
02:01:00,200 --> 02:01:03,160
TRANSITION OVER TO OUR FINAL

3091
02:01:03,160 --> 02:01:06,040
PRESENTATION OF THE SESSION 2

3092
02:01:06,040 --> 02:01:09,160
AND INTRODUCE DR. CALVIN KUO.

3093
02:01:09,160 --> 02:01:15,160
DR. KUO IS THE MAUREEN LILLS

3094
02:01:15,160 --> 02:01:16,080
DAMBROSIO PROFESSOR OF MEDICINE

3095
02:01:16,080 --> 02:01:16,880
STANFORD UNIVERSITY SCHOOL OF

3096
02:01:16,880 --> 02:01:17,920
MEDICINE.  HIS RESEARCH

3097
02:01:17,920 --> 02:01:20,360
INTERESTS INCLUDE MODELING OF

3098
02:01:20,360 --> 02:01:22,360
IMMUNITY AND PATHOGENS AND

3099
02:01:22,360 --> 02:01:25,280
CANCER IN 3D ORGANOID CULTURES

3100
02:01:25,280 --> 02:01:27,480
BIOLOGY OF INTESTINAL AND LUNG

3101
02:01:27,480 --> 02:01:30,160
STEM CELL POPULATIONS, AND

3102
02:01:30,160 --> 02:01:33,760
MOLECULAR REGULATION OF

3103
02:01:33,760 --> 02:01:35,040
ANGIOGENESIS AND THE BLOOD BRAIN

3104
02:01:35,040 --> 02:01:36,760
BARRIER. HE IS ELECTED MEMBER OF

3105
02:01:36,760 --> 02:01:38,600
ASSOCIATION OF AMERICAN

3106
02:01:38,600 --> 02:01:41,800
PHYSICIAN, AMERICAN SOCIETY FOR

3107
02:01:41,800 --> 02:01:43,520
CLINICAL INVESTIGATIONS AND THE

3108
02:01:43,520 --> 02:01:45,800
AAASS. TODAY HE WILL BE TALKING

3109
02:01:45,800 --> 02:01:47,560
TO US THE TITLE OF HIS TALK IS

3110
02:01:47,560 --> 02:01:49,880
USING ORGANOID MODELS OF TISSUE

3111
02:01:49,880 --> 02:01:52,000
RESIDENT IMMUNITY TO STUDY

3112
02:01:52,000 --> 02:01:55,680
INFECTIOUS DISEASESS. DR. KUO.

3113
02:01:55,680 --> 02:01:56,280
OVER TO YOU.

3114
02:01:56,280 --> 02:01:58,920
>> HOPEFULLY YOU CAN HEAR
ME.

3115
02:01:58,920 --> 02:02:00,480
LET ME TRY THE SHARE SCREEN

3116
02:02:00,480 --> 02:02:10,880
HERE. CAN YOU SEE THIS?

3117
02:02:11,560 --> 02:02:12,840
>> CURRENTLY I SEE YOUR
VIDEO

3118
02:02:12,840 --> 02:02:19,680
NOW.  NOT YOUR SLIDES.

3119
02:02:19,680 --> 02:02:20,840
>> VIDEO NOT SLIDES.

3120
02:02:20,840 --> 02:02:25,400
>> YEAH.  IS IT NOT JUST
ME?

3121
02:02:25,400 --> 02:02:31,200
>> YEAH WE CAN'T SEE THE
SLIDES

3122
02:02:31,200 --> 02:02:32,320
ABIGAIL, DO YOU WANT TO JUMP IN

3123
02:02:32,320 --> 02:02:32,680
AND HELP?

3124
02:02:32,680 --> 02:02:35,120
>> GIVE IT A GO.

3125
02:02:35,120 --> 02:02:37,320
>> HANG ON, I KNOW WHAT TO
DO. I

3126
02:02:37,320 --> 02:02:47,800
THINK. THAT SHOULD PROBABLY

3127
02:02:57,200 --> 02:03:00,840
WORK. GREAT. SO THANKS FOR THIS

3128
02:03:00,840 --> 02:03:03,080
KIND INVITATION AND I WOULD LIKE

3129
02:03:03,080 --> 02:03:05,200
TO TELL YOU ABOUT OUR RECENT

3130
02:03:05,200 --> 02:03:08,280
WORK IN ORGANOID MODELING OF

3131
02:03:08,280 --> 02:03:12,960
INFECTIOUS DISEASE AS WE KNOW

3132
02:03:12,960 --> 02:03:14,920
THERE IS DIFFERENT TYPES OF

3133
02:03:14,920 --> 02:03:15,640
ORGANOIDS, THERE IS WE

3134
02:03:15,640 --> 02:03:16,960
SPECIALIZE IN ADULT HUMAN

3135
02:03:16,960 --> 02:03:21,840
ORGANOID TYPE, NOT IPSC DERIVE

3136
02:03:21,840 --> 02:03:23,280
AND WE HAVE BEEN WORKING BOTH

3137
02:03:23,280 --> 02:03:25,240
ORGANOIDS THAT HAVE EPITHELIUM

3138
02:03:25,240 --> 02:03:27,680
ONLY AND THEN EPITHELIAL PLUS

3139
02:03:27,680 --> 02:03:29,400
STROMA, I WILL MENTION BOTH OF

3140
02:03:29,400 --> 02:03:31,720
THOSE TO YOU GUYS. STARTING WITH

3141
02:03:31,720 --> 02:03:34,520
EPITHELIAL ONLY ORGANOIDS, AS

3142
02:03:34,520 --> 02:03:37,280
YOU HEARD FROM EARLIER TALKS

3143
02:03:37,280 --> 02:03:38,920
THERE HAS BEEN A TREMENDOUS

3144
02:03:38,920 --> 02:03:39,760
EXPLOSION IN THE ABILITY TO

3145
02:03:39,760 --> 02:03:42,880
CULTURE ADULT HUMAN TISSUES. AS

3146
02:03:42,880 --> 02:03:44,640
ORGANOIDS.  THIS IS ONLY HALF OF

3147
02:03:44,640 --> 02:03:48,480
WHAT OUR LAB DOES SO IT IS

3148
02:03:48,480 --> 02:03:53,240
CLEARLY A ROBUST METHODOLOGY AND

3149
02:03:53,240 --> 02:03:54,960
WE PERTINENT TO THIS CONFERENCE

3150
02:03:54,960 --> 02:03:57,080
WE HAVE BEEN INTERESTED IN ADULT

3151
02:03:57,080 --> 02:03:59,440
DISTAL LUNG ORGANOIDS AT THE

3152
02:03:59,440 --> 02:04:01,080
TIME WE INITIATED THE PROJECT IT

3153
02:04:01,080 --> 02:04:04,080
WAS VERY DIFFICULT PREVIOUSLY TO

3154
02:04:04,080 --> 02:04:07,400
GROW HUMAN ALVEOLI IN A FEEDER

3155
02:04:07,400 --> 02:04:09,920
FREE CHEMICALLY DEFINED CLONAL

3156
02:04:09,920 --> 02:04:11,800
FASHION. SO WE STARTED WORKING

3157
02:04:11,800 --> 02:04:15,000
ON THIS SIX OR SEVEN YEARS AGO.

3158
02:04:15,000 --> 02:04:18,520
CAME UP WITH METHODOLOGIES TO

3159
02:04:18,520 --> 02:04:21,160
GROW BOTH THE ALVEOLAR

3160
02:04:21,160 --> 02:04:24,480
COMPONENTS AS WELL AS MORE BASAL

3161
02:04:24,480 --> 02:04:26,280
AIRWAY COMPONENTS AS CLONAL

3162
02:04:26,280 --> 02:04:30,440
ORGANOIDS AND YOU CAN SEE THE

3163
02:04:30,440 --> 02:04:33,160
SOLID MORE BASAL AIRWAY

3164
02:04:33,160 --> 02:04:35,520
ORGANOIDS AND THE CYSTIC

3165
02:04:35,520 --> 02:04:41,640
ALVEOLAR ORGANOIDS. THEN WORKING

3166
02:04:41,640 --> 02:04:44,440
WITH MANUEL LED BY M.D. Ph.D.

3167
02:04:44,440 --> 02:04:47,880
STUDENT, WE ALSO HAVE BEEN USING

3168
02:04:47,880 --> 02:04:51,520
THIS ROBUST SUSPENSION CULTURE

3169
02:04:51,520 --> 02:04:52,920
THAT MANUEL'S GROUP DEVISED THAT

3170
02:04:52,920 --> 02:04:57,360
CAN TURN ORGANOIDS INSIDE OUT.  

3171
02:04:57,360 --> 02:04:59,920
BASICALLY TAKE OUR ORGANOIDS

3172
02:04:59,920 --> 02:05:01,400
THAT HAVE HAD A LOT OF THE

3173
02:05:01,400 --> 02:05:02,520
DIFFERENTIATED CELLS ON THE

3174
02:05:02,520 --> 02:05:05,280
INTERIOR, WHY YOU ARE NOT SEEING

3175
02:05:05,280 --> 02:05:06,920
THE GREEN AND WHITE SIGNAL IN

3176
02:05:06,920 --> 02:05:08,160
SURFACE VIEW LEFT-HAND SIDE, YOU

3177
02:05:08,160 --> 02:05:10,440
CAN PUT THEM INTO SUSPENSION

3178
02:05:10,440 --> 02:05:11,600
CULTURE AND EVERT THE ORGANOIDS

3179
02:05:11,600 --> 02:05:13,280
LIKE A SOCK THAT IS THE WRONG

3180
02:05:13,280 --> 02:05:17,120
WAY IN THE LAUNDRY YOU GET

3181
02:05:17,120 --> 02:05:19,040
SILLIATED CELLS IN WHITE AND

3182
02:05:19,040 --> 02:05:22,320
GREEN CELLS INITIALLY INCITE --

3183
02:05:22,320 --> 02:05:25,000
INSIDE NOW ON THE OUTSIDE. THAT

3184
02:05:25,000 --> 02:05:25,960
WAS IMPORTANT BECAUSE IN OUR

3185
02:05:25,960 --> 02:05:28,480
ORGANOID IT IS ACE 2 RECEPTOR

3186
02:05:28,480 --> 02:05:30,280
WAS INTERIOR AND THESE ARE

3187
02:05:30,280 --> 02:05:33,920
APICAL IN ORGANOIDS WHEREAS IN

3188
02:05:33,920 --> 02:05:35,600
SUSPENSION CULTURE ACE 2 IN

3189
02:05:35,600 --> 02:05:38,040
GREEN IS ON THE OUTSIDE AND WE

3190
02:05:38,040 --> 02:05:41,920
WANTED TO USE THAT FOR INFECTION

3191
02:05:41,920 --> 02:05:44,120
STUDIES YOU CAN SEE THE

3192
02:05:44,120 --> 02:05:46,960
SILLIATED CELLS HERE IN THE

3193
02:05:46,960 --> 02:05:49,920
UNEVERTED SITUATION VERSUS NOW

3194
02:05:49,920 --> 02:05:53,440
AFTER E VERSION AND YOU CAN SEE

3195
02:05:53,440 --> 02:05:56,960
THTHE CILIARE ARE ON THE OUTSID.

3196
02:05:56,960 --> 02:05:59,840
THIS ALLOWED US TO BE ABLE TO DO

3197
02:05:59,840 --> 02:06:02,480
THESE INFECTIOUS STUDIES BY

3198
02:06:02,480 --> 02:06:05,120
ADDING SARS COV-2 TO THE

3199
02:06:05,120 --> 02:06:06,400
EXTERIOR OF THE NOW FLIPPED

3200
02:06:06,400 --> 02:06:07,960
ORGANOIDS, WONDERFUL

3201
02:06:07,960 --> 02:06:12,320
COLLABORATION WITH CATHERINE

3202
02:06:12,320 --> 02:06:13,160
BLISS, AND SO WE HAVE BEEN ABLE

3203
02:06:13,160 --> 02:06:18,400
TO DEMONSTRATE THAT NUCLEAR

3204
02:06:18,400 --> 02:06:20,080
CAPSID STAIN AND PLAQUE ASSAYS

3205
02:06:20,080 --> 02:06:22,760
AND ENVIRONMENT GENOMES DETECTED

3206
02:06:22,760 --> 02:06:24,640
WE HAVE BEEN ABLE TO SHOW THE

3207
02:06:24,640 --> 02:06:26,360
CLUB CELLS ARE A NOVEL CELL TYPE

3208
02:06:26,360 --> 02:06:27,560
INFECT AND OBVIOUSLY WE ARE

3209
02:06:27,560 --> 02:06:30,920
GETTING VERY ROBUST INFECTION OF

3210
02:06:30,920 --> 02:06:33,760
ALVEOLAR TYPE 2 ORGANOIDS. WE --

3211
02:06:33,760 --> 02:06:34,760
I THROUGH THIS IN BECAUSE WE

3212
02:06:34,760 --> 02:06:37,200
HAVE BEEN PLAYING AROUND WITH

3213
02:06:37,200 --> 02:06:37,800
MULTI-WELL SCREENING OF THESE

3214
02:06:37,800 --> 02:06:41,160
TYPES OF ORGANOIDS. MORE FOR

3215
02:06:41,160 --> 02:06:42,680
INFLUENZA ANTIVIRAL COMPOUNDS

3216
02:06:42,680 --> 02:06:44,720
BUT CERTAINLY ADAPTABLE TO OTHER

3217
02:06:44,720 --> 02:06:47,200
APPLICATIONS AS WELL I WOULD

3218
02:06:47,200 --> 02:06:50,200
SAY. AND WE CAN PLATE THESE IN

3219
02:06:50,200 --> 02:06:52,440
TO 96 WELL DISH, GET INFECTION,

3220
02:06:52,440 --> 02:06:56,880
THIS IS INFLUENZA H 1N 1 GFP

3221
02:06:56,880 --> 02:07:00,000
STRAIN SO YOU CAN SEE THE GFP

3222
02:07:00,000 --> 02:07:01,920
THEN WE CAN APPLY VARIOUS

3223
02:07:01,920 --> 02:07:03,480
ANTIVIRAL COMPOUNDS IN THIS

3224
02:07:03,480 --> 02:07:05,120
MULTI-WELL FORMAT AND GET

3225
02:07:05,120 --> 02:07:08,760
INHIBITION.  SO VERY POSSIBLE I

3226
02:07:08,760 --> 02:07:10,440
WOULD SAY TO TAKE THIS FIRST

3227
02:07:10,440 --> 02:07:14,320
GENERATION TYPE OF ORGANOID AND

3228
02:07:14,320 --> 02:07:17,760
PERFORM DRUG SCREENING. I WILL

3229
02:07:17,760 --> 02:07:20,440
SWITCH TO WORK ON EPITHELIAL

3230
02:07:20,440 --> 02:07:23,040
PLUS STROMAL ORGANOIDS.  THESE

3231
02:07:23,040 --> 02:07:25,880
ARE MORE COMPLEX AND HAVE I

3232
02:07:25,880 --> 02:07:29,040
WOULD SAY VERY HOLISTIC

3233
02:07:29,040 --> 02:07:30,480
REPRESENTATION OF THE TISSUE

3234
02:07:30,480 --> 02:07:33,760
MICROENVIRONMENT. WE HAVE BEEN

3235
02:07:33,760 --> 02:07:35,320
USING AIR INTERFACE YOU HAVE

3236
02:07:35,320 --> 02:07:38,040
HEARD ABOUT. IN MULTIPLE TALKS

3237
02:07:38,040 --> 02:07:43,160
BUT WE ARE DOING 3D AIR LIQUID

3238
02:07:43,160 --> 02:07:46,200
INTERFACE SO OUR INITIAL EFFORTS

3239
02:07:46,200 --> 02:07:50,480
STARTED WITH INTESTINE BACK IN

3240
02:07:50,480 --> 02:07:52,440
2009. I WILL SAY WE HAVE BEEN

3241
02:07:52,440 --> 02:07:57,440
MORE RECENT YEARS USING THIS FOR

3242
02:07:57,440 --> 02:07:59,640
CANCER CULTURES. THIS IS JUST A

3243
02:07:59,640 --> 02:08:01,720
WHOLE VARIETY OF DIFFERENT TYPES

3244
02:08:01,720 --> 02:08:05,600
OF TUMORS FROM ANATOMIC SITES WE

3245
02:08:05,600 --> 02:08:08,280
CAN GROW USING THIS TECHNIQUE. 

3246
02:08:08,280 --> 02:08:10,480
THE IMPORTANT THING IS THIS

3247
02:08:10,480 --> 02:08:11,600
METHODOLOGY, WE START OFF WITH

3248
02:08:11,600 --> 02:08:14,360
TISSUE FRAGMENTS NOT DISSOCIATED

3249
02:08:14,360 --> 02:08:17,120
CELLS SO WE PRESERVE

3250
02:08:17,120 --> 02:08:17,880
MICROENVIRONMENT WITHIN THE

3251
02:08:17,880 --> 02:08:22,560
FRAGMENTS WE ARE CULTURING. SO

3252
02:08:22,560 --> 02:08:25,000
IN YELLOW YOU CAN SEE THE CANCER

3253
02:08:25,000 --> 02:08:26,560
FIBROBLAST STROMA EMBEDDED

3254
02:08:26,560 --> 02:08:30,400
WITHIN THE TUMOR ORGANOID WITH

3255
02:08:30,400 --> 02:08:34,480
COLON PATIENT DERIVED ORGANOID. 

3256
02:08:34,480 --> 02:08:35,600
IMPORTANTLY THIS TYPE OF

3257
02:08:35,600 --> 02:08:38,240
TECHNIQUE PRESERVES RESIDENT

3258
02:08:38,240 --> 02:08:39,720
IMMUNE CELLS WITHOUT ANY

3259
02:08:39,720 --> 02:08:41,400
ARTIFICIAL RECONSTITUTION. THIS

3260
02:08:41,400 --> 02:08:43,720
IS A RENAL CELL CARCINOMA

3261
02:08:43,720 --> 02:08:46,360
ORGANOID WITH TUMOR CELLS IN

3262
02:08:46,360 --> 02:08:48,440
PINK AND TUMOR INFILTRATING

3263
02:08:48,440 --> 02:08:49,800
LYMPHOCYTES CD 3 MEMBRANE

3264
02:08:49,800 --> 02:08:52,560
STAINENING YELLOW. WE DIDN'T

3265
02:08:52,560 --> 02:08:53,920
RECONSTITUTE FROM PERIPHERAL

3266
02:08:53,920 --> 02:08:55,440
BLOOD THIS IS TISSUE RESIDENT OR

3267
02:08:55,440 --> 02:08:58,040
IE TUMOR RESIDENT FOR

3268
02:08:58,040 --> 02:09:00,680
LYMPHOCYTES ON THE LEFT AND

3269
02:09:00,680 --> 02:09:03,920
THESE ORANGE MACROPHAGES ON THE

3270
02:09:03,920 --> 02:09:06,440
RIGHT. SO WE CAN PRESERVE IN

3271
02:09:06,440 --> 02:09:10,120
SITU THE TISSUE RESIDENT

3272
02:09:10,120 --> 02:09:14,040
POPULATIONS SO THIS IS ALLOWS US

3273
02:09:14,040 --> 02:09:16,200
TO DO THINGS LIKE CHECK POINT

3274
02:09:16,200 --> 02:09:17,080
INHIBITORS AND TUMOR ORGANOIDS

3275
02:09:17,080 --> 02:09:20,000
AND GET THE TUMOR INFILTRATING

3276
02:09:20,000 --> 02:09:22,760
LYMPHOCYTES TO ATTACK TUMOR

3277
02:09:22,760 --> 02:09:24,280
CELLS. BUT I WANT TO SWITCH FROM

3278
02:09:24,280 --> 02:09:26,800
CANCER TO INFECTIOUS DISEASE.

3279
02:09:26,800 --> 02:09:29,400
WE CAN USE THE SAME TYPES OF

3280
02:09:29,400 --> 02:09:31,480
TECHNIQUES THAT HAVE ORGANOIDS

3281
02:09:31,480 --> 02:09:33,480
AND INTRINSIC IMMUNE CELLS

3282
02:09:33,480 --> 02:09:35,040
INFILTRATING IMMUNE CELLS AND

3283
02:09:35,040 --> 02:09:40,680
THEN ADD PATHOGENS. WE HAVE OF

3284
02:09:40,680 --> 02:09:42,320
COURSE POSTER CHILD IS SARS

3285
02:09:42,320 --> 02:09:44,640
COV-2 WE WANTED TO ESTABLISH

3286
02:09:44,640 --> 02:09:45,920
THESE TYPES OF LUNG ORGANOIDS

3287
02:09:45,920 --> 02:09:47,920
THAT HAVE PRIMARY EPITHELIAL

3288
02:09:47,920 --> 02:09:50,160
INFECTION BUT LOOK AT SECONDARY

3289
02:09:50,160 --> 02:09:51,760
IMMUNE ACTIVATION PARTICULARLY

3290
02:09:51,760 --> 02:09:54,120
ADAPTIVE RESPONSE OF T AND B

3291
02:09:54,120 --> 02:09:58,800
CELLS WITHIN THESE ORGANOIDS.  

3292
02:09:58,800 --> 02:09:59,920
SO OUR M.D. Ph.D. STUDENT HAS

3293
02:09:59,920 --> 02:10:02,360
BEEN LEADING THE CHARGE ON THIS

3294
02:10:02,360 --> 02:10:04,240
AND THIS HAS BEEN A VERY ROBUST

3295
02:10:04,240 --> 02:10:05,760
TECHNIQUE WITH THREE DIMENSIONAL

3296
02:10:05,760 --> 02:10:11,440
ALI NOT TWO, AND YOU CAN SEE THE

3297
02:10:11,440 --> 02:10:13,760
CONTINUED GROWTH OVER 180 DAYS.

3298
02:10:13,760 --> 02:10:17,680
AND BY HNE THERE'S ALL SORTS OF

3299
02:10:17,680 --> 02:10:20,400
ALVEOLAR AIR SACKS AND

3300
02:10:20,400 --> 02:10:21,760
BRONCHIOLAR STRUCTURE THAT ARE

3301
02:10:21,760 --> 02:10:24,120
APPARENT BY STAINING THERE IS

3302
02:10:24,120 --> 02:10:26,000
CLUB CELLS SILLIATED CELLS,

3303
02:10:26,000 --> 02:10:28,160
BASAL CELLS, WE HAVE BOTH

3304
02:10:28,160 --> 02:10:30,440
ALVEOLAR TYPE 1 AND 2 CELLS AND

3305
02:10:30,440 --> 02:10:32,840
DISTINCT DOMAINS. AND THE

3306
02:10:32,840 --> 02:10:34,440
ALVEOLAR TYPE 1 IN GREEN YOU CAN

3307
02:10:34,440 --> 02:10:38,040
SEE FORMING THESE ALVEOLAR HONEY

3308
02:10:38,040 --> 02:10:38,960
COMB STRUCTURE WITH SOME DEGREE

3309
02:10:38,960 --> 02:10:42,080
OF INTEGRATION OF ALVEOLAR TYPE

3310
02:10:42,080 --> 02:10:45,840
2 CELLS IN THEM BUT WE FIND AT 2

3311
02:10:45,840 --> 02:10:47,280
CELLS DO GROW OUTSIDE OF THE

3312
02:10:47,280 --> 02:10:50,840
ALVEOLI AS WELL. I WILL MS.

3313
02:10:50,840 --> 02:10:52,920
MENTION WE HAVE EXTENSIVE

3314
02:10:52,920 --> 02:10:54,160
ENDOTHELIAL NETWORKS WITHIN THE

3315
02:10:54,160 --> 02:10:56,120
ORGANOIDS.  THIS IS CD 31

3316
02:10:56,120 --> 02:11:00,000
STAINING YOU CAN SEE THAT THERE

3317
02:11:00,000 --> 02:11:01,680
IS VERY ARBORIZING TYPE OF

3318
02:11:01,680 --> 02:11:03,680
VASCULAR NETWORKS. NO PROFUSION

3319
02:11:03,680 --> 02:11:06,080
PER SE BUT IT WILL BE

3320
02:11:06,080 --> 02:11:07,120
INTERESTING TO BUILD IN

3321
02:11:07,120 --> 02:11:09,000
SUSTAINED PROLIFERATION WE CAN

3322
02:11:09,000 --> 02:11:11,600
SEE THE SF SUR FACT TIN PROTEIN

3323
02:11:11,600 --> 02:11:15,480
C DOMAIN IN WHITE HAS KI 67

3324
02:11:15,480 --> 02:11:17,880
POSITIVE CELLS WITHIN. P P AND

3325
02:11:17,880 --> 02:11:21,480
THEN WE ALSO HAVE MESENCHYMAL

3326
02:11:21,480 --> 02:11:26,840
STROMA. THIS IS STAINING IN RED

3327
02:11:26,840 --> 02:11:28,120
AND EPITHELIAL CELLS IN GREEN

3328
02:11:28,120 --> 02:11:29,520
BUT MORE IMPORTANTLY WE HAVE

3329
02:11:29,520 --> 02:11:33,360
IMMUNE CELLS, THIS IS CD 45

3330
02:11:33,360 --> 02:11:35,760
STAINING HEMATOPOIETIC MARKER.

3331
02:11:35,760 --> 02:11:38,400
WE ARE NOT RECONSTITUTING FROM

3332
02:11:38,400 --> 02:11:39,680
PERIPHERAL BLOOD THESE ARE

3333
02:11:39,680 --> 02:11:42,240
TISSUE RESIDENCE IMMUNE CELLS WE

3334
02:11:42,240 --> 02:11:43,600
PRESERVE BAKED INTO THE

3335
02:11:43,600 --> 02:11:46,440
ORGANOID. THEN WE CAN USE OUR

3336
02:11:46,440 --> 02:11:49,400
SUSPENSION CULTURE METHOD TO

3337
02:11:49,400 --> 02:11:51,400
EVERT VERY COMPLEX ORGANOID THAT

3338
02:11:51,400 --> 02:11:52,960
IS PROBABLY 10 TO 50 TIMES

3339
02:11:52,960 --> 02:11:55,480
LARGER THAN ORIGINAL EPITHELIAL

3340
02:11:55,480 --> 02:11:57,440
ONLY LUNG ORGANOIDS. WHEN WE DO

3341
02:11:57,440 --> 02:11:59,520
THAT IMMUNE CELLS CD 45 ARE

3342
02:11:59,520 --> 02:12:02,320
STILL PRESERVED WITHIN THE

3343
02:12:02,320 --> 02:12:04,640
ORGANOIDS. AND THE ACE 2 IN RED

3344
02:12:04,640 --> 02:12:09,600
WHICH WAS ORIGINALLY GRITTED

3345
02:12:09,600 --> 02:12:12,040
DIFFUSELY IS NOW EXTENDED ON THE

3346
02:12:12,040 --> 02:12:13,560
OUTSIDE IN A MORE ACCESSIBLE WAY

3347
02:12:13,560 --> 02:12:17,520
FOR INFECTION STUDIES.  SO BY

3348
02:12:17,520 --> 02:12:19,720
SINGLE RNA SEQUENCING OF LUNG

3349
02:12:19,720 --> 02:12:22,120
ORGANOIDS WE CAN FIND THAT ANY

3350
02:12:22,120 --> 02:12:24,760
EPITHELIAL COMPARTMENT THERE IS

3351
02:12:24,760 --> 02:12:25,520
TREMENDOUS DIVERSITY WITHIN

3352
02:12:25,520 --> 02:12:29,560
THESE ORGANOIDS CERTAINLY

3353
02:12:29,560 --> 02:12:31,880
ALVEOLAR TYPE 1 AND 2 CELLS,

3354
02:12:31,880 --> 02:12:33,440
PROLIFERATIVE ALVEOLAR TYPE 2

3355
02:12:33,440 --> 02:12:35,040
CELLS, BASAL CELLS,

3356
02:12:35,040 --> 02:12:38,680
PROLIFERATIVE BASAL CELLS.

3357
02:12:38,680 --> 02:12:40,320
FIBROBLASTS, ENDOTHELIAL CELLS,

3358
02:12:40,320 --> 02:12:41,640
BUT THEN ON THE IMMUNE SIDE OF

3359
02:12:41,640 --> 02:12:44,120
THE ORGANOIDS THERE IS A VERY

3360
02:12:44,120 --> 02:12:46,720
TREMENDOUS COMPLEXITY AS WELL

3361
02:12:46,720 --> 02:12:49,600
THAT EXTENDS NOT ONLY TO CD4 AND

3362
02:12:49,600 --> 02:12:53,240
CD8 T-CELLS BUT TREGS, THERE IS

3363
02:12:53,240 --> 02:12:55,360
MYELOID CELLS, MACROPHAGES,

3364
02:12:55,360 --> 02:12:57,360
THERE'S B CELLS AND PLASMA B

3365
02:12:57,360 --> 02:13:00,000
CELLS WE CAN ALSO DETECT NK

3366
02:13:00,000 --> 02:13:01,840
CELLS AND THERE IS ALSO TISSUE

3367
02:13:01,840 --> 02:13:04,400
RESIDENCY MARKERS WE CAN DETECT

3368
02:13:04,400 --> 02:13:06,520
AS WELL ON THE T-CELLS. SO VERY,

3369
02:13:06,520 --> 02:13:09,080
VERY HOLISTIC REPRESENTATION,

3370
02:13:09,080 --> 02:13:10,040
TREMENDOUS CELLULAR DIVERSITY

3371
02:13:10,040 --> 02:13:11,840
WITHIN THESE ADULT LUNG

3372
02:13:11,840 --> 02:13:14,960
ORGANOIDS. NO RECONSTITUTION.

3373
02:13:14,960 --> 02:13:19,480
THE TCR REPERTOIRE OF THE

3374
02:13:19,480 --> 02:13:21,280
ORIGINAL TISSUE MADE IN THE

3375
02:13:21,280 --> 02:13:22,400
ORGANOID INDUCE SINGLE CELL

3376
02:13:22,400 --> 02:13:24,520
SEQUENCING AND LOOK AT TCR ALPHA

3377
02:13:24,520 --> 02:13:27,400
BETA SEQUENCINGS IN THE CDR 3

3378
02:13:27,400 --> 02:13:29,040
REGENERAL, THE SAME -- REGION.

3379
02:13:29,040 --> 02:13:31,400
THE SAME CLONE TYPES EXPANDED IN

3380
02:13:31,400 --> 02:13:32,600
TISSUE ARE ALSO CLONALLY

3381
02:13:32,600 --> 02:13:35,600
EXPANDED IN THE ORGANOID. AND

3382
02:13:35,600 --> 02:13:37,040
THIS IS JUST A CORRELATION PLOT

3383
02:13:37,040 --> 02:13:38,840
BETWEEN THE TCR REPRESENTATION

3384
02:13:38,840 --> 02:13:40,600
BETWEEN ORGANOID AND TISSUE AND

3385
02:13:40,600 --> 02:13:44,160
WE SEE A LOT OF CCR 3 SEQUENCES

3386
02:13:44,160 --> 02:13:45,960
THAT MATCH PUBLIC DATABASE AND

3387
02:13:45,960 --> 02:13:48,160
RIGHT NOW RUNNING SAME SEQUENCE

3388
02:13:48,160 --> 02:13:52,360
ANALYSIS FOR SARS COV-2. SO HERE

3389
02:13:52,360 --> 02:13:54,440
BSL 3 AND THIS HAS BEEN A VERY

3390
02:13:54,440 --> 02:13:58,000
LARGE UNDERTAKING WITH FOLKS IN

3391
02:13:58,000 --> 02:14:00,120
MY LAB AND CATHERINE'S LAB,

3392
02:14:00,120 --> 02:14:01,760
REALLY DOING A LOT OF THESE

3393
02:14:01,760 --> 02:14:05,720
STUDIES IN BSL 3, AND INDEED WE

3394
02:14:05,720 --> 02:14:08,360
CAN CERTAINLY INFECT THESE VERY

3395
02:14:08,360 --> 02:14:09,560
COMPLEX LEVEL ORGANOIDS WITH

3396
02:14:09,560 --> 02:14:12,920
SARS COV-2 AND HERE THIS IS A

3397
02:14:12,920 --> 02:14:14,280
HIGH LEVEL OVERVIEW YOU CAN SEE

3398
02:14:14,280 --> 02:14:17,480
THE TRINITY OF THE SARS COV-2

3399
02:14:17,480 --> 02:14:19,040
INFECTION IN GREEN WITH NUCLEIC

3400
02:14:19,040 --> 02:14:20,640
CAPSID STAINING BUT THEN YOU

3401
02:14:20,640 --> 02:14:22,960
HAVE THE RED E CAD HEREIN LUNG

3402
02:14:22,960 --> 02:14:29,360
EPITHELIUM AND THE CD 45 LUNG

3403
02:14:29,360 --> 02:14:30,520
INTRINSIC HEMATOPOIETIC CELLS

3404
02:14:30,520 --> 02:14:31,880
PRESENT SO WE HAVE ALL THREE

3405
02:14:31,880 --> 02:14:35,440
COMPONENTS ALL TOGETHER. SO IF

3406
02:14:35,440 --> 02:14:37,680
THE EXTENT OF INFECTION THAT WE

3407
02:14:37,680 --> 02:14:39,640
SEE IN THE LUNG ALI ORGANOIDS IS

3408
02:14:39,640 --> 02:14:41,160
MUCH MORE EXTENSIVE THAN WHAT WE

3409
02:14:41,160 --> 02:14:44,840
WERE SEEING IN OUR LUNG

3410
02:14:44,840 --> 02:14:46,200
EPITHELIAL ONLY ORGANOIDS.  WE

3411
02:14:46,200 --> 02:14:48,000
CAN GET EXTREMELY SENSITIVE

3412
02:14:48,000 --> 02:14:49,320
INFECTION AS I SHOW YOU IN

3413
02:14:49,320 --> 02:14:51,360
SUBSEQUENT SLIDES. THEN ALSO

3414
02:14:51,360 --> 02:14:54,240
THIS SLIDE SHOWS THEE

3415
02:14:54,240 --> 02:14:55,200
DIFFERENCE BETWEEN THE SECOND

3416
02:14:55,200 --> 02:14:56,600
GENERATION ORGANOID ON THE LEFT

3417
02:14:56,600 --> 02:14:59,280
AND FIRST GENERATION ORGANOID ON

3418
02:14:59,280 --> 02:15:01,400
THE RIGHT. SO WE CAN DO VIRAL

3419
02:15:01,400 --> 02:15:04,280
STUDIES, THIS IS AN ANTIVIRAL

3420
02:15:04,280 --> 02:15:05,400
SCREENING CONFERENCE SO I

3421
02:15:05,400 --> 02:15:07,520
CONCLUDED LOTS OF DATA WITH

3422
02:15:07,520 --> 02:15:10,840
REMDESIVIR. THIS IS INDICATING

3423
02:15:10,840 --> 02:15:13,080
THAT WE CAN INDEED GET SARS

3424
02:15:13,080 --> 02:15:16,560
COV-2 REPLICATION WITH PLAQUE

3425
02:15:16,560 --> 02:15:19,800
FORMATION BUT THAT REMDESIVIR

3426
02:15:19,800 --> 02:15:21,320
RDV CAN STRONGLY INHIBIT THAT IN

3427
02:15:21,320 --> 02:15:26,840
PLAQUE ASSAYS. ALSO IF WE LOOK

3428
02:15:26,840 --> 02:15:30,440
AT CYTOKINE PRODUCTION BY QRT

3429
02:15:30,440 --> 02:15:37,560
PCR YOU CAN SEE THAT THE DARK

3430
02:15:37,560 --> 02:15:38,760
ORANGE OR BROWNISH BARS THESE

3431
02:15:38,760 --> 02:15:42,600
ARE SARS COV-2 INDUCED CYTOKINE

3432
02:15:42,600 --> 02:15:44,320
mRNA BUT THEN WITH RECOMMEND

3433
02:15:44,320 --> 02:15:46,240
DECEMBER VEER, THIS IS THE LIGHT

3434
02:15:46,240 --> 02:15:48,000
-- REMDESIVIR YOU CAN SEE

3435
02:15:48,000 --> 02:15:49,600
SIGNIFICANT INHIBITION OF

3436
02:15:49,600 --> 02:15:51,560
IMMUNOSTAINING LOTS OF

3437
02:15:51,560 --> 02:15:54,160
INTERFERONS TNF ALPHA, IL 6, ET

3438
02:15:54,160 --> 02:15:55,920
CETERA. WE CAN DO SAME WITH

3439
02:15:55,920 --> 02:15:57,720
LUMENEX. WE CAN TAKE CULTURE

3440
02:15:57,720 --> 02:16:00,400
SUPERNATANT THE ORGANOIDS AND

3441
02:16:00,400 --> 02:16:03,400
YOU CAN SEE THE STRONG

3442
02:16:03,400 --> 02:16:04,920
STIMULATION FOR INSTANCE WITH IL

3443
02:16:04,920 --> 02:16:06,640
6 FOR INSTANCE WITH SARS COV-2

3444
02:16:06,640 --> 02:16:09,000
BUT THEN WITH REMDESIVIR THIS

3445
02:16:09,000 --> 02:16:10,960
LIGHTER BROWN IS INHIBITION SO

3446
02:16:10,960 --> 02:16:13,160
WE CAN SEE AT PROTEIN LEVEL AS

3447
02:16:13,160 --> 02:16:16,440
WELL. WE CAN ALSO DO RNA

3448
02:16:16,440 --> 02:16:20,280
SEQUENCING AND LOOK AT A LOT OF

3449
02:16:20,280 --> 02:16:23,400
DIFFERENT GENES INHIBITED BY

3450
02:16:23,400 --> 02:16:25,920
REMDESIVIR, THAT IS ON THE GREEN

3451
02:16:25,920 --> 02:16:29,040
SHOWING THE REMDESIVIR INHIBITED

3452
02:16:29,040 --> 02:16:32,760
TYPES OF MESSENGER RNAs. SO

3453
02:16:32,760 --> 02:16:34,080
ONE ASPECT OF THIS IS THAT WE

3454
02:16:34,080 --> 02:16:35,720
CAN REALLY START TO TAKE THESE

3455
02:16:35,720 --> 02:16:38,360
INFECTIONS OUT TO LONGER TIME

3456
02:16:38,360 --> 02:16:40,800
POINTS. SO AT EARLY STAGE 3 DAYS

3457
02:16:40,800 --> 02:16:42,880
POST INFECTION YOU CAN SEE THERE

3458
02:16:42,880 --> 02:16:44,800
IS THE GREEN SARS COV-2 NUCLEIC

3459
02:16:44,800 --> 02:16:46,840
ACID SIGNAL, DOESN'T OVERLAP

3460
02:16:46,840 --> 02:16:48,600
WITH ANY KIND OF APOPTOTIC

3461
02:16:48,600 --> 02:16:51,640
SIGNAL WITH CASPASE 3, JUST RAN

3462
02:16:51,640 --> 02:16:53,320
COMELY DISTRIBUTED -- RANDOMLY

3463
02:16:53,320 --> 02:16:55,480
DISTRIBUTED TURN OVER WITHIN THE

3464
02:16:55,480 --> 02:16:57,120
ORGANOIDS BUT TEN DAYS POST

3465
02:16:57,120 --> 02:16:59,880
INFECTION WE CAN SEE SPREAD OF

3466
02:16:59,880 --> 02:17:03,080
THE INFECTION AND WITH THE GREEN

3467
02:17:03,080 --> 02:17:04,640
NUCLEIC CAPSID SIGNAL BUT NOW

3468
02:17:04,640 --> 02:17:06,400
THIS IS OVERLAPPING

3469
02:17:06,400 --> 02:17:07,240
SIGNIFICANTLY WITH CLEAVE

3470
02:17:07,240 --> 02:17:08,960
CASPASE 3 SO WE ARE STARTING TO

3471
02:17:08,960 --> 02:17:13,640
BE ABLE TO TAKE THIS TO AN END

3472
02:17:13,640 --> 02:17:15,960
STAGE TYPE OF DISEASE STATE.

3473
02:17:15,960 --> 02:17:17,520
THIS IS ANOTHER PICTURE AT TEN

3474
02:17:17,520 --> 02:17:18,840
DAYS POST INFECTION. YOU CAN SEE

3475
02:17:18,840 --> 02:17:22,640
THE TREMENDOUS SPREAD OF THE

3476
02:17:22,640 --> 02:17:25,480
SARS COV-2 NUCLEIC CAPSID SIGNAL

3477
02:17:25,480 --> 02:17:26,680
OVERLAPPING SUBSTANTIALLY WITH

3478
02:17:26,680 --> 02:17:30,000
THE CLEAVE CASPASE 3. SO AT

3479
02:17:30,000 --> 02:17:32,200
THESE LONGER TIME POINTS WE CAN

3480
02:17:32,200 --> 02:17:34,920
THEN START TO SEE IMMUNE

3481
02:17:34,920 --> 02:17:36,200
CHEMOTACKSIS TO THE INFECTED

3482
02:17:36,200 --> 02:17:38,600
AREA, THIS IS JUST THE SAME

3483
02:17:38,600 --> 02:17:39,560
IMAGE WITH DIFFERENT STAINS BUT

3484
02:17:39,560 --> 02:17:42,680
YOU CAN SEE THAT THE WHITE CD 45

3485
02:17:42,680 --> 02:17:45,160
CELLS START TO CHEMO TAX TO AREA

3486
02:17:45,160 --> 02:17:48,360
OF ACTIVE INFECTION. AND THEN WE

3487
02:17:48,360 --> 02:17:51,360
CAN START TO SEE SOME END STAGE

3488
02:17:51,360 --> 02:17:53,560
SEQUELAE. YOU CAN SEE SIN CITY

3489
02:17:53,560 --> 02:17:54,960
SHAH FORMATION WHICH IS STRICTLY

3490
02:17:54,960 --> 02:17:56,440
OBSERVED IN IF AUTOPSY

3491
02:17:56,440 --> 02:18:00,360
SPECIMENS. WITH MULTI-NUCLEATED

3492
02:18:00,360 --> 02:18:03,000
CELLS WITH INDICATED BY YELLOW

3493
02:18:03,000 --> 02:18:04,880
ARROWS.  ALSO WE START TO SEE A

3494
02:18:04,880 --> 02:18:09,080
LOT OF INDUCTION OF FIBROTIC

3495
02:18:09,080 --> 02:18:11,120
GENES, THIS IS BUNCH OF

3496
02:18:11,120 --> 02:18:12,760
DIFFERENT COLLAGEN GENES RNA

3497
02:18:12,760 --> 02:18:14,960
SEQUENCING, THIS IS LOG BASE 2

3498
02:18:14,960 --> 02:18:18,760
SO ZERO IS ONE FOLD AND SO THERE

3499
02:18:18,760 --> 02:18:21,280
IS SUBSTANTIAL INDUCTION THAT

3500
02:18:21,280 --> 02:18:22,720
SEEMS TO BE SOMEWHAT HIGHER AT

3501
02:18:22,720 --> 02:18:25,040
LATER TIME POINTS. SO

3502
02:18:25,040 --> 02:18:26,880
POTENTIALLY VERY INTERESTING FOR

3503
02:18:26,880 --> 02:18:31,400
STUDYING PASC TYPE OF SEQUELAE.

3504
02:18:31,400 --> 02:18:35,680
FOR SARS COV-2 THEN ON TO T-CELL

3505
02:18:35,680 --> 02:18:37,720
AND B CELL RESPONSES ADAPTIVE

3506
02:18:37,720 --> 02:18:39,320
RESPONSES WE SHOWED YOU A LOT OF

3507
02:18:39,320 --> 02:18:42,680
CYTOKINE INDUCTION MORE INNATE

3508
02:18:42,680 --> 02:18:44,160
AND THESE RESPONSES ARE OBSERVED

3509
02:18:44,160 --> 02:18:46,840
IN EPITHELIAL ONLY ORGANOIDS BUT

3510
02:18:46,840 --> 02:18:48,080
WE WANTED TO TAKE ADVANTAGE OF

3511
02:18:48,080 --> 02:18:50,000
HAVING ADAPTIVE IMMUNE

3512
02:18:50,000 --> 02:18:51,760
POPULATION T-CELLS AN B CELLS

3513
02:18:51,760 --> 02:18:55,200
AND ASSAY THOSE RESPONSES SO

3514
02:18:55,200 --> 02:18:59,000
THIS IS A ORGANOID FROM A

3515
02:18:59,000 --> 02:19:02,440
IMMUNIZED INDIVIDUAL AND WE DID

3516
02:19:02,440 --> 02:19:04,520
INFECTION AND THEN FACT SORTED

3517
02:19:04,520 --> 02:19:07,560
CD4 AND CD8 AND JUST SAW IF SARS

3518
02:19:07,560 --> 02:19:09,480
COV-2 INDUCE VARIOUS RESPONSES.

3519
02:19:09,480 --> 02:19:12,640
THIS IS NORMALIZED SO RATIO MORE

3520
02:19:12,640 --> 02:19:13,640
THAN ONE IS INDUCTION AND

3521
02:19:13,640 --> 02:19:15,640
THERE'S STRONG INDUCTION OF

3522
02:19:15,640 --> 02:19:18,920
INTERLEUKIN 2 AN TNF ALPHA.

3523
02:19:18,920 --> 02:19:20,080
THERE'S EVEN INDUCTION OF OTHER

3524
02:19:20,080 --> 02:19:22,160
THINGS AS WELL. THAT ARE JUST

3525
02:19:22,160 --> 02:19:23,960
OBSCURED BY THE SCALE, LIKE

3526
02:19:23,960 --> 02:19:26,600
INTERFERON GAMMA AND THE CD8 WE

3527
02:19:26,600 --> 02:19:29,000
CAN SEE CD 68 INDUCTION FOR

3528
02:19:29,000 --> 02:19:30,400
INSTANCE, EPITHELIAL CELLS YOU

3529
02:19:30,400 --> 02:19:33,320
CAN SEE DEGREE OF SARS GENOME

3530
02:19:33,320 --> 02:19:35,040
INCREASE IN EPITHELIUM BUT WE

3531
02:19:35,040 --> 02:19:37,560
ALSO SEE INTERFERON IN GCSF FOR

3532
02:19:37,560 --> 02:19:39,680
INSTANCE SO INDICATED ADAPTIVE

3533
02:19:39,680 --> 02:19:41,960
RESPONSES. WE HAVE ALSO BEEN

3534
02:19:41,960 --> 02:19:45,920
ABLE TO STIMULATE THE ORGANOIDS

3535
02:19:45,920 --> 02:19:48,840
WITH PEPTIDE MEGA POOLS OR MORE

3536
02:19:48,840 --> 02:19:52,480
SIMPLY SARS COV-2 SPIKE PROTEIN,

3537
02:19:52,480 --> 02:19:55,280
RECOMBINANT SPIKE PROTEIN. THERE

3538
02:19:55,280 --> 02:19:57,320
IS ANTIGEN MACHINERY IN THE

3539
02:19:57,320 --> 02:19:58,080
ORGANOIDS I DON'T HAVE TIME TO

3540
02:19:58,080 --> 02:19:59,800
TALK ABOUT BUT FEED THE ORGANOID

3541
02:19:59,800 --> 02:20:02,960
SPIKE PROTEIN AND OBSERVE VERY,

3542
02:20:02,960 --> 02:20:05,280
VERY INTERESTING THINGS LOOKING

3543
02:20:05,280 --> 02:20:07,640
AT ORGANOID UNVACCINATED

3544
02:20:07,640 --> 02:20:09,440
INDIVIDUALS VERSUS VACCINATED IF

3545
02:20:09,440 --> 02:20:13,280
WE FAX PURIFY CD4 AND LOOK AT IL

3546
02:20:13,280 --> 02:20:17,880
2 IN THE UNVACCINATED IN THIS

3547
02:20:17,880 --> 02:20:19,040
MAYBE GREENISH TYPE OF COLOR,

3548
02:20:19,040 --> 02:20:21,320
THERE IS VERY FEW RESPONSES BUT

3549
02:20:21,320 --> 02:20:23,080
THEN WITH VACCINATED

3550
02:20:23,080 --> 02:20:24,760
PARTICULARLY IF THE PATIENT HAS

3551
02:20:24,760 --> 02:20:28,080
BEEN VACCINATED RELATIVELY

3552
02:20:28,080 --> 02:20:30,400
RECENTLY, WE SEE HIGHER

3553
02:20:30,400 --> 02:20:31,760
INCREASES THAN IF THE PATIENT

3554
02:20:31,760 --> 02:20:33,400
WAS VACCINATED MORE IN THE

3555
02:20:33,400 --> 02:20:37,160
DISTANT PAST. OF COURSE ALL THIS

3556
02:20:37,160 --> 02:20:38,600
PAILS VERSUS THE UNVACCINATED

3557
02:20:38,600 --> 02:20:40,840
STATE SO WE ARE LOOKING AT KIND

3558
02:20:40,840 --> 02:20:44,280
OF A A RECALL TISSUE RESIDENT

3559
02:20:44,280 --> 02:20:46,400
MEMORY IMMUNITY THAT IS

3560
02:20:46,400 --> 02:20:48,840
VACCINATION DEPENDENT THAT IS

3561
02:20:48,840 --> 02:20:51,200
PRESENT WITHIN THESE LUNG

3562
02:20:51,200 --> 02:20:53,400
ORGANOIDS. CD8 SIMILAR THINGS WE

3563
02:20:53,400 --> 02:20:55,920
SEE A LOT OF STRONGER RESPONSES

3564
02:20:55,920 --> 02:20:58,240
IN VACCINATED VERSUS

3565
02:20:58,240 --> 02:21:01,720
UNVACCINATED. AND AGAIN WE CAN

3566
02:21:01,720 --> 02:21:03,160
SHOUT THIS OUT BY TIME SINCE

3567
02:21:03,160 --> 02:21:04,160
VACCINATION REALLY SUGGESTING

3568
02:21:04,160 --> 02:21:07,240
THE TISSUE RESIDENT IMMUNITY

3569
02:21:07,240 --> 02:21:09,000
WILL WANE WITH TIME. WE CAN ALSO

3570
02:21:09,000 --> 02:21:10,720
SEE SOME DIFFERENCES IN THE --

3571
02:21:10,720 --> 02:21:13,280
WITH AGE AS WELL. IF THE

3572
02:21:13,280 --> 02:21:16,720
PATIENTS ARE OLDER THAN THEIR

3573
02:21:16,720 --> 02:21:19,560
CD4 AND CD8 RESPONSES ARE LESS

3574
02:21:19,560 --> 02:21:22,080
VIGOROUS THAN IF THEY ARE

3575
02:21:22,080 --> 02:21:25,720
YOUNGER WITH CD4 AND CD8. ON TO

3576
02:21:25,720 --> 02:21:29,520
B CELLS, WE SEE THAT SARS COV-2

3577
02:21:29,520 --> 02:21:30,800
INDUCES SUBSTANTIAL

3578
02:21:30,800 --> 02:21:31,920
IMMUNOGLOBULIN GENE EXPRESSION

3579
02:21:31,920 --> 02:21:35,000
THAT IS SPANNING MULTIPLE

3580
02:21:35,000 --> 02:21:38,800
ISOTYPES. AGAIN, THIS IS VERY

3581
02:21:38,800 --> 02:21:39,800
SUBSTANTIAL INDUCTION OVER THE

3582
02:21:39,800 --> 02:21:44,640
BASELINE. AND THEN ALSO IF WE WE

3583
02:21:44,640 --> 02:21:46,600
ADD REMDESIVIR, SINGLE RNA

3584
02:21:46,600 --> 02:21:48,400
SEQUENCING WITH JUST SARS COV-2

3585
02:21:48,400 --> 02:21:50,480
INFECTION WE SEE DOUBLE POSITIVE

3586
02:21:50,480 --> 02:21:54,480
CELLS FOR CD 40 AND FOR INSTANCE

3587
02:21:54,480 --> 02:21:56,680
IMMUNOGLOBULIN ALPHA IGA GENES

3588
02:21:56,680 --> 02:21:58,200
EXPRESSION WHICH IS BEING

3589
02:21:58,200 --> 02:22:02,040
INDUCED BUT REMDESIVIR IS REALLY

3590
02:22:02,040 --> 02:22:03,800
SHUTTING THIS DOWN. FURTHERMORE

3591
02:22:03,800 --> 02:22:08,360
WE CAN LOOK AT SECRETION OF

3592
02:22:08,360 --> 02:22:10,040
ANTI-SARS COV-2 SPIKE

3593
02:22:10,040 --> 02:22:10,960
IMMUNOGLOBULIN SO WE ARE FEEDING

3594
02:22:10,960 --> 02:22:15,560
THE ORGANOIDS THE RECOMBINANT

3595
02:22:15,560 --> 02:22:17,960
SPIKE PROTEIN AND ACTIVATING

3596
02:22:17,960 --> 02:22:21,040
MEMORY B CELLS AND YOU CAN SEE

3597
02:22:21,040 --> 02:22:24,880
THIS IS NOT REALLY -- THIS IS --

3598
02:22:24,880 --> 02:22:27,480
THIS IS AN INFECTION SORRY. NOT

3599
02:22:27,480 --> 02:22:28,680
FEEDING THE PROTEIN BUT YOU CAN

3600
02:22:28,680 --> 02:22:31,720
SEE THERE IS INDUCTION OF

3601
02:22:31,720 --> 02:22:32,760
IMMUNOGLOBULIN PRODUCTION

3602
02:22:32,760 --> 02:22:35,360
AGAINST SARS COV-2 SPIKE AND WE

3603
02:22:35,360 --> 02:22:36,680
CAN SHUT THIS DOWN WITH

3604
02:22:36,680 --> 02:22:41,760
REMDESIVIR.  SO OF ALL WE HAVE A

3605
02:22:41,760 --> 02:22:43,120
HOLISTIC SYSTEM THAT HAS

3606
02:22:43,120 --> 02:22:44,240
EPITHELIUM STROMA TISSUE

3607
02:22:44,240 --> 02:22:47,120
RESIDENT IMMUNE CELLS, WE CAN

3608
02:22:47,120 --> 02:22:48,480
RECAPITULATE SENSITIVITY TO

3609
02:22:48,480 --> 02:22:52,760
ANTIVIRAL AGENTS, THE ADAPTIVE

3610
02:22:52,760 --> 02:22:55,120
IMMUNE RESPONSES ARE PRIOR SERA

3611
02:22:55,120 --> 02:22:57,640
POSITIVITY. WE CAN SHOW THIS

3612
02:22:57,640 --> 02:22:58,840
LOCALIZED IMMUNITY WANES OVER

3613
02:22:58,840 --> 02:23:03,680
TIME AND LASTLY, THESE ADAPTIVE

3614
02:23:03,680 --> 02:23:05,920
RESPONSES, THEY CAN BE INITIATED

3615
02:23:05,920 --> 02:23:06,960
AUTONOMOUSLY IN LUNG BECAUSE

3616
02:23:06,960 --> 02:23:09,120
LUNG ORGANOIDS DO NOT HAVE

3617
02:23:09,120 --> 02:23:11,320
PERIPHERAL LYMPHOID COMPONENT SO

3618
02:23:11,320 --> 02:23:13,680
WE CAN SHOW WE HAVE SUFFICIENCY

3619
02:23:13,680 --> 02:23:16,120
NECESSARY WITHIN THE LUNG FOR

3620
02:23:16,120 --> 02:23:17,360
ANTIGEN, INFECTION ANTIGEN

3621
02:23:17,360 --> 02:23:19,160
PRESENTATION, AND ADAPTIVE

3622
02:23:19,160 --> 02:23:21,640
MEMORY RESPONSES.  SO I WILL

3623
02:23:21,640 --> 02:23:22,440
STOP THERE AND THANK YOU VERY

3624
02:23:22,440 --> 02:23:29,960
MUCH.

3625
02:23:29,960 --> 02:23:33,080
>> FANTASTIC, DR. KUO.

3626
02:23:33,080 --> 02:23:34,200
APPRECIATE THAT TOUR DEFORCE

3627
02:23:34,200 --> 02:23:36,680
PRESENTATION. IF I CAN ASK ALL

3628
02:23:36,680 --> 02:23:38,880
SIX PANELISTS TO JOIN US ON

3629
02:23:38,880 --> 02:23:40,200
SCREEN, I THINK IT WOULD BE

3630
02:23:40,200 --> 02:23:47,160
GREAT TO KICK OFF THE Q&A

3631
02:23:47,160 --> 02:23:48,320
SESSION. THANKS FOR JOINING ON

3632
02:23:48,320 --> 02:23:51,240
VIDEO KEEPING US COMPANY. I

3633
02:23:51,240 --> 02:23:52,800
GUESS MAYBE I WILL GO TO -- A

3634
02:23:52,800 --> 02:23:56,480
QUICK REMINDER, PLEASE ENTER ANY

3635
02:23:56,480 --> 02:23:58,080
QUESTIONS YOU MIGHT HAVE FOR ANY

3636
02:23:58,080 --> 02:24:00,400
OF OUR SPEAKERS IN THIS SESSION

3637
02:24:00,400 --> 02:24:02,520
INTO THE Q&A BOX AND WE WILL
GET

3638
02:24:02,520 --> 02:24:06,760
TO THEM. PLEASE NOTE THAT OUR

3639
02:24:06,760 --> 02:24:08,560
SPEAKERS WERE VERY GENEROUS AND

3640
02:24:08,560 --> 02:24:10,080
EFFICIENT IN ANSWERING SOME OF

3641
02:24:10,080 --> 02:24:11,480
THE QUESTIONS THAT WERE POSTED

3642
02:24:11,480 --> 02:24:14,880
WILL IN WRITING SO BE SURE TO

3643
02:24:14,880 --> 02:24:16,680
FLIP TO ANSWERED TAB TO LOOK AT

3644
02:24:16,680 --> 02:24:18,760
THE RESPONSES IF YOU HAVE ANY

3645
02:24:18,760 --> 02:24:21,560
FOLLOW-UP OR OTHER QUESTIONS

3646
02:24:21,560 --> 02:24:23,360
RAISED PLEASE FEEL FREE TO TYPE

3647
02:24:23,360 --> 02:24:24,360
IN A NEW QUESTION AND WE WILL

3648
02:24:24,360 --> 02:24:26,680
CIRCLE BACK TO THAT. JUST WANT

3649
02:24:26,680 --> 02:24:28,480
TO HIGHLIGHT THE DIFFERENT TABS

3650
02:24:28,480 --> 02:24:32,280
IF YOU WILL FROM THAT Q&A
BOX.

3651
02:24:32,280 --> 02:24:33,720
TO KICK OFF I WILL LOOK THROUGH

3652
02:24:33,720 --> 02:24:37,200
WHAT IS IN THAT BOX FOR OPEN

3653
02:24:37,200 --> 02:24:39,240
QUESTIONS. ONE THIS IS FOR DR.

3654
02:24:39,240 --> 02:24:40,760
INGBAR, THANK YOU FOR THE TALK,

3655
02:24:40,760 --> 02:24:43,440
IT SEEMS THAT USING CHIPS FOR

3656
02:24:43,440 --> 02:24:46,200
EFFICACY AND REPURPOSING WILL --

3657
02:24:46,200 --> 02:24:47,880
WHERE THERE ARE EXISTING SAFETY

3658
02:24:47,880 --> 02:24:50,720
DATA MAYBE LOW HANGING FRUIT.

3659
02:24:50,720 --> 02:24:53,120
MORE LIKELY TO BE ACCEPTED FOR

3660
02:24:53,120 --> 02:24:55,360
REGULATORY SUBMISSIONS. CAN YOU

3661
02:24:55,360 --> 02:24:57,400
SEE CHIP DATA BEING USED IN LIEU

3662
02:24:57,400 --> 02:25:01,080
OF ANIMAL DATA FOR TESTING

3663
02:25:01,080 --> 02:25:03,000
TOXICITY OR DO WE NEED TO

3664
02:25:03,000 --> 02:25:05,000
RETHINK WHAT SAFETY QUESTIONS WE

3665
02:25:05,000 --> 02:25:05,880
ARE ASKING AND WHAT ANSWERS WE

3666
02:25:05,880 --> 02:25:06,080
NEED.

3667
02:25:06,080 --> 02:25:09,240
>> YEAH. WE HAVE A PAPER
IN

3668
02:25:09,240 --> 02:25:11,920
REVIEW, IN PRE-PRINT WITH

3669
02:25:11,920 --> 02:25:13,600
EMULATE COMPANY THAT MAKES THESE

3670
02:25:13,600 --> 02:25:16,360
CHIPS, WHERE THEY DID 800

3671
02:25:16,360 --> 02:25:18,000
DIFFERENT HUMAN LIVER CHIPS THAT

3672
02:25:18,000 --> 02:25:24,440
ARE ALIGNED BY PRIMARY HUMAN

3673
02:25:24,440 --> 02:25:27,720
HEPATOSITES PRIMARY LIVER

3674
02:25:27,720 --> 02:25:30,480
ENDOTHELIUM PRIMARY HUMAN AND

3675
02:25:30,480 --> 02:25:33,960
THEY TESTED 27 DRUGS. FOR DRUG

3676
02:25:33,960 --> 02:25:35,840
INDUCED LIVER INJURY. DRUGS

3677
02:25:35,840 --> 02:25:38,600
LISTED BY THE IQ CONSORTIUM

3678
02:25:38,600 --> 02:25:41,200
WHICH IS CONSORTIUM OF PHARMA

3679
02:25:41,200 --> 02:25:43,320
AND BIOTECH COMPANIES THEY

3680
02:25:43,320 --> 02:25:44,840
IDENTIFY THEY KNOW THE RESULTS

3681
02:25:44,840 --> 02:25:46,080
IN ANIMALS AND MOW THE RESULTS

3682
02:25:46,080 --> 02:25:49,280
IN HUMANS IN ABOUT 18 OF THOSE

3683
02:25:49,280 --> 02:25:51,080
ANIMALS WERE SAFE BUT THERE WAS

3684
02:25:51,080 --> 02:25:56,800
TOXICITY IN HUMANS AND THE NET

3685
02:25:56,800 --> 02:26:00,440
SUM WAS 780 CHIPS BUT NOW 800

3686
02:26:00,440 --> 02:26:03,200
WITH TWO DONOR, A THIRD DONOR.

3687
02:26:03,200 --> 02:26:05,360
80% SENSITIVITY AND 100%

3688
02:26:05,360 --> 02:26:07,320
SPECIFICITY. THAT IS 8 TIMES

3689
02:26:07,320 --> 02:26:09,640
BETTER THAN ANIMAL MODEL. SO WE

3690
02:26:09,640 --> 02:26:11,000
ARE HOPING THAT PEOPLE WILL

3691
02:26:11,000 --> 02:26:14,120
START USING THINGS LIKE THAT FOR

3692
02:26:14,120 --> 02:26:16,040
TOXICITY AS ONE EXAMPLE. THERE

3693
02:26:16,040 --> 02:26:18,960
IS ANOTHER COMPANY DOING KIDNEY

3694
02:26:18,960 --> 02:26:20,480
TOXICITY. BLANKING THE NAME OF

3695
02:26:20,480 --> 02:26:21,960
THE COMPANY BUT FOUND IT IS ALSO

3696
02:26:21,960 --> 02:26:25,680
MUCH BETTER THAN ANIMAL MODELS.

3697
02:26:25,680 --> 02:26:27,400
SO WE ARE APPROACHING A TIPPING

3698
02:26:27,400 --> 02:26:31,920
POINT BUT WE ARE NOT THERE YET. 

3699
02:26:31,920 --> 02:26:36,160
>> GREAT.  THANK YOU. SO
NEXT

3700
02:26:36,160 --> 02:26:39,360
QUESTION FROM THE BOX. AGAIN FOR

3701
02:26:39,360 --> 02:26:42,200
DR. INK BEAR. HAVE YOU DEVELOPED

3702
02:26:42,200 --> 02:26:44,360
LUNGS ON CHIPS FOR CYSTIC

3703
02:26:44,360 --> 02:26:46,720
FIBROSIS PATIENTS? AND HAVE YOU

3704
02:26:46,720 --> 02:26:48,400
TRIED TO EPIIF HE CAN THOSE WITH

3705
02:26:48,400 --> 02:26:50,040
BACTERIAL PATHOGENS?

3706
02:26:50,040 --> 02:26:53,920
>> WE PUBLISHED LAST YEAR
WORK

3707
02:26:53,920 --> 02:26:56,120
FUNDED BY CYSTIC FIBROSIS

3708
02:26:56,120 --> 02:26:57,640
FOUNDATION, WE GOT AIRWAY CELLS

3709
02:26:57,640 --> 02:26:59,400
FROM PATIENTS AND THE CHIPS

3710
02:26:59,400 --> 02:27:02,840
TOTALLY WE MAKE THE PHENOTYPE

3711
02:27:02,840 --> 02:27:05,080
INCREASE CILIA, THICKENED

3712
02:27:05,080 --> 02:27:07,600
MUCOUS, ALTERED EATING

3713
02:27:07,600 --> 02:27:09,840
FREQUENCY, INCREASE BASELINE

3714
02:27:09,840 --> 02:27:11,320
INFLAMMATORY STATE INCREASE

3715
02:27:11,320 --> 02:27:14,040
RECRUITMENT OF IMMUNE CELLS AND

3716
02:27:14,040 --> 02:27:21,720
WE GREW SINEMONAS. JOE THAT IS

3717
02:27:21,720 --> 02:27:22,000
PUBLISHED.

3718
02:27:22,000 --> 02:27:23,880
>> THANK YOU. FOLLOW-UP,
CURIOUS

3719
02:27:23,880 --> 02:27:25,320
WHETHER YOU -- I THINK YOU HAD

3720
02:27:25,320 --> 02:27:26,400
SHOWN IN YOUR TALK YOU LOOKED AT

3721
02:27:26,400 --> 02:27:29,240
THAT TIME COPD SAMPLES IN

3722
02:27:29,240 --> 02:27:31,760
COMPARE TO HEALTHY. WONDERED IF

3723
02:27:31,760 --> 02:27:33,560
YOU LOOK IN TERMS OF VIRAL

3724
02:27:33,560 --> 02:27:35,000
INFECTION OR PATHOGENESIS AND

3725
02:27:35,000 --> 02:27:38,680
WONDERING IF YOU LOOKED AT THAT

3726
02:27:38,680 --> 02:27:40,240
SMOKING IN PARALLEL WITH HEALTHY

3727
02:27:40,240 --> 02:27:42,040
TO SEE IF THERE'S ANY IMPACT ON

3728
02:27:42,040 --> 02:27:43,360
VIRAL INFECTIVITY OR

3729
02:27:43,360 --> 02:27:44,880
PATHOGENESIS. 

3730
02:27:44,880 --> 02:27:47,240
>> IT IS A MUCH MORE
COMPLEX

3731
02:27:47,240 --> 02:27:49,800
MODEL SYSTEM TO GET WORKING AND

3732
02:27:49,800 --> 02:27:52,200
WE DID THAT A COUPLE OF YEARS

3733
02:27:52,200 --> 02:27:54,240
AGO SO WE HAVE BE INTERESTING TO

3734
02:27:54,240 --> 02:27:56,800
SEE BUT WE HAVEN'T DONE THAT

3735
02:27:56,800 --> 02:27:56,960
ONE.

3736
02:27:56,960 --> 02:27:59,960
>> THANKS. NEXT I SEE HERE
IS

3737
02:27:59,960 --> 02:28:04,480
FOR DR. KUO. THE QUESTION IS CAN

3738
02:28:04,480 --> 02:28:06,080
THESE MORE COMPLEX LUNG

3739
02:28:06,080 --> 02:28:09,000
ORGANOIDS BE EXPANDED AND

3740
02:28:09,000 --> 02:28:12,680
CRYOPRESERVED LIKE THE MORE

3741
02:28:12,680 --> 02:28:16,880
CONVENTION PAL EPITHELIAL ONLY

3742
02:28:16,880 --> 02:28:19,200
ORGANOORGANOIDS?

3743
02:28:19,200 --> 02:28:20,800
>> I THINK SO. WE HAVEN'T
TRIED

3744
02:28:20,800 --> 02:28:22,880
THIS FOR THE MORE COMPLEX LUNG

3745
02:28:22,880 --> 02:28:25,680
ORGANOIDS.  FOR ANALOGOUS TUMOR

3746
02:28:25,680 --> 02:28:27,000
ORGANOIDS IT IS POSSIBLE. SO WE

3747
02:28:27,000 --> 02:28:30,680
ARE STARTING TO DO THIS WHAT WE

3748
02:28:30,680 --> 02:28:32,120
SUGGEST MARK AND WE DON'T HAVE A

3749
02:28:32,120 --> 02:28:34,000
LOT OF DATA YET BUT THINK IT IS

3750
02:28:34,000 --> 02:28:39,160
POSSIBLE.

3751
02:28:39,160 --> 02:28:45,760
>> NEXT FOR DR. KUO.
POLEDOR

3752
02:28:45,760 --> 02:28:48,440
WOULD YOU ELABORATE HOW YOU

3753
02:28:48,440 --> 02:28:50,360
SOURCE YOUR IMMUNE SPHEREROIDS

3754
02:28:50,360 --> 02:28:53,760
IN CULTURE THEM IN THE 3D ALI

3755
02:28:53,760 --> 02:28:55,640
ENVIRONMENT PRIOR TO

3756
02:28:55,640 --> 02:28:56,360
CHARACTERIZATION AND

3757
02:28:56,360 --> 02:28:57,680
PERTURBATION FROM THE MODEL? ARE

3758
02:28:57,680 --> 02:29:01,480
THEY REMOVED FROM PATIENT

3759
02:29:01,480 --> 02:29:03,800
BIOPSIES, HOW LONG TO MAINTAIN

3760
02:29:03,800 --> 02:29:04,040
INFECTION?

3761
02:29:04,040 --> 02:29:07,600
>> EVERYTHING IS FROM
PATIENT

3762
02:29:07,600 --> 02:29:09,040
BIOPSIES BECAUSE THESE ARE

3763
02:29:09,040 --> 02:29:12,960
THEMSELVES CELL DIRECT

3764
02:29:12,960 --> 02:29:13,560
ORGANOIDS.

3765
02:29:13,560 --> 02:29:18,320
SO TYPICALLY SURGICAL RESECTIONS

3766
02:29:18,320 --> 02:29:21,480
FROM NORMAL MARGIN OF CANCER

3767
02:29:21,480 --> 02:29:22,560
PATIENTS OR FROM SOMETIMES

3768
02:29:22,560 --> 02:29:24,080
CHILDREN THERE IS VARIOUS TYPES

3769
02:29:24,080 --> 02:29:29,600
OF BIRTH DEFECTS FOR WHICH TH TE

3770
02:29:29,600 --> 02:29:32,680
IS A LUNG RESECTION THEN A

3771
02:29:32,680 --> 02:29:34,240
NORMAL REGION ASIDE FROM THE

3772
02:29:34,240 --> 02:29:37,880
EFFECT IS. AND RIGHT. WE CULTURE

3773
02:29:37,880 --> 02:29:39,120
ESTABLISH ORGANOIDS FIRST TO

3774
02:29:39,120 --> 02:29:43,000
MAKE SURE THEY ARE GROWING THEN

3775
02:29:43,000 --> 02:29:45,720
WE WILL FLIP THEM IN CULTURE TO

3776
02:29:45,720 --> 02:29:46,960
GET FOR INSTANCE THE ACE 2 TO

3777
02:29:46,960 --> 02:29:51,480
THE OUTSIDE THEN WE INFECT.

3778
02:29:51,480 --> 02:29:55,920
>> GREAT. THANK YOU. SO
THE NEXT

3779
02:29:55,920 --> 02:29:57,520
QUESTION IS FOR ANYONE, PLEASE

3780
02:29:57,520 --> 02:29:58,600
FEEL FREE TO SHOUT OUT IF YOU

3781
02:29:58,600 --> 02:30:02,040
HAVE A THOUGHT OR IDEA. SO TO

3782
02:30:02,040 --> 02:30:03,760
ALL THE SPEAKERS ARE YOU LOOKING

3783
02:30:03,760 --> 02:30:06,600
AT POPULATION VARIABILITY AND

3784
02:30:06,600 --> 02:30:07,640
SUSCEPTIBILITY TO ENVIRONMENTAL

3785
02:30:07,640 --> 02:30:08,960
CHEMICALS AND HOW THAT MIGHT

3786
02:30:08,960 --> 02:30:10,640
INFLUENCE THE VIRAL INFECTIONS

3787
02:30:10,640 --> 02:30:16,680
OR VICE VERSA? ANY THOUGHTS ON

3788
02:30:16,680 --> 02:30:23,640
THAT FOR THE SPEAKERS?

3789
02:30:23,640 --> 02:30:25,520
>> WE ARE DEFINITELY
LOOKING AT

3790
02:30:25,520 --> 02:30:26,320
POPULATION VARIABILITY NOT IN

3791
02:30:26,320 --> 02:30:28,040
THE CONTEXT OF CHEMICAL EXPOSURE

3792
02:30:28,040 --> 02:30:31,680
AT THIS POINT IN TIME BUT LOOK

3793
02:30:31,680 --> 02:30:33,400
AT DIFFERENT DONORS WHETHER FROM

3794
02:30:33,400 --> 02:30:34,760
CHILDREN OR ADULTS DEPENDING

3795
02:30:34,760 --> 02:30:35,720
CONTEXT OF WHAT YOU ARE

3796
02:30:35,720 --> 02:30:37,240
STUDYING. FOR EXAMPLE IN OUR

3797
02:30:37,240 --> 02:30:38,720
CASE OF NOROVIRUS INFECTION WE

3798
02:30:38,720 --> 02:30:42,840
LOOK AT SECRETERS NON-SECRETERS,

3799
02:30:42,840 --> 02:30:45,160
SO DEFINITELY CONSIDERING

3800
02:30:45,160 --> 02:30:46,640
POPULATION HETEROGENEITY BUT NOT

3801
02:30:46,640 --> 02:30:49,000
IN THE CONTEXT OF CATEGORY

3802
02:30:49,000 --> 02:30:52,120
(INAUDIBLE).

3803
02:30:52,120 --> 02:30:53,400
>> NO, THANK YOU FOR THAT.
I DID

3804
02:30:53,400 --> 02:30:55,520
REMEMBER IN YOUR TALK REMEMBER

3805
02:30:55,520 --> 02:30:56,800
CROSSED MY MIND, THERE MUST BE

3806
02:30:56,800 --> 02:30:59,160
-- IT MUST BE CHALLENGING TO GET

3807
02:30:59,160 --> 02:31:00,400
THAT BALANCE BETWEEN WANTING TO

3808
02:31:00,400 --> 02:31:02,160
SAMPLE THE BROAD POPULATION BUT

3809
02:31:02,160 --> 02:31:03,320
AT THE SAME TIME GENERATE THAT

3810
02:31:03,320 --> 02:31:06,160
SORT OF REPRODUCIBILITY FOR

3811
02:31:06,160 --> 02:31:07,280
SCREENING AND SO THOUGHT THAT

3812
02:31:07,280 --> 02:31:09,240
WAS INTERESTING POINT YOU RAISED

3813
02:31:09,240 --> 02:31:11,760
IN THAT REGARD. 

3814
02:31:11,760 --> 02:31:13,560
>> I THINK IT IS POINT IT
IS

3815
02:31:13,560 --> 02:31:14,680
LARGELY A CONVENIENCE, WE ARE

3816
02:31:14,680 --> 02:31:16,240
GETTING WHAT WE ARE GETTING OR

3817
02:31:16,240 --> 02:31:18,840
AT LEAST WHERE WE STARTED, MUCH

3818
02:31:18,840 --> 02:31:20,360
MORE MEDIAN SAMPLE, IT IS ONE OF

3819
02:31:20,360 --> 02:31:21,760
THE LINES WE HAVE GOT

3820
02:31:21,760 --> 02:31:23,440
CHARACTERIZED THEM AND DIVIDED

3821
02:31:23,440 --> 02:31:24,560
THEM INTO THE POPULATIONS WE

3822
02:31:24,560 --> 02:31:26,840
KNOW ARE RELEVANT FOR WHAT WE

3823
02:31:26,840 --> 02:31:29,720
ARE STUDYING. ASKING MORE

3824
02:31:29,720 --> 02:31:31,400
FORWARD WE ARE NOW GOING INTO

3825
02:31:31,400 --> 02:31:33,040
MORE SPECIFIC DISEASE.  WE WANT

3826
02:31:33,040 --> 02:31:35,160
TO STUDY THIS AND THEREFORE

3827
02:31:35,160 --> 02:31:36,800
WHICH GO TO WHATEVER ORGANOIDS

3828
02:31:36,800 --> 02:31:39,360
THAT ARE NECESSARY FOR AN AGE

3829
02:31:39,360 --> 02:31:41,160
GROUP OR PARTICULAR GENETIC

3830
02:31:41,160 --> 02:31:42,520
SUSCEPTIBILITY FACTOR. WE TAKE

3831
02:31:42,520 --> 02:31:45,600
THAT INTO CONSIDERATION.

3832
02:31:45,600 --> 02:31:47,480
>> ONE THING THAT IS
ALWAYS

3833
02:31:47,480 --> 02:31:48,920
BROUGHT UP WITH ORGANOIDS AND

3834
02:31:48,920 --> 02:31:52,760
ORGANS ON CHIPS IS VARIABILITY

3835
02:31:52,760 --> 02:31:55,560
ISSUES BECAUSE YOU DON'T HAVE

3836
02:31:55,560 --> 02:31:56,680
ESTABLISHED CELL LINE OR

3837
02:31:56,680 --> 02:31:59,960
ESTABLISHED ANIMAL MODEL BUT TO

3838
02:31:59,960 --> 02:32:01,920
ME THAT IS THE POWER, THAT IS

3839
02:32:01,920 --> 02:32:04,600
WHAT REAL CLINICAL TRIALS IS

3840
02:32:04,600 --> 02:32:05,800
ABOUT IS PATIENT TO PATIENT

3841
02:32:05,800 --> 02:32:09,960
VARIABILITY AND SO FORTH. SO WE

3842
02:32:09,960 --> 02:32:11,840
FOUND THAT WE USUALLY DO

3843
02:32:11,840 --> 02:32:13,360
MULTIPLE DONORS LIKE YOU HEARD.

3844
02:32:13,360 --> 02:32:15,800
THAT IS ONE AREA. BUT WE HAVEN'T

3845
02:32:15,800 --> 02:32:17,960
DONE IT FOR VIRAL INFECTION BUT

3846
02:32:17,960 --> 02:32:19,320
WE HAVE OTHER GRANTS WE ARE

3847
02:32:19,320 --> 02:32:21,720
WORKING ON FOR EXAMPLE VAGINA

3848
02:32:21,720 --> 02:32:23,760
AND CERVIX MODELS OF THE

3849
02:32:23,760 --> 02:32:26,920
MICROBIOME AND WE MADE CAUCASIAN

3850
02:32:26,920 --> 02:32:27,920
AFRICAN AMERICAN AND HISPANIC

3851
02:32:27,920 --> 02:32:30,760
AND THEY ARE DIFFERENT WHICH IS

3852
02:32:30,760 --> 02:32:33,080
INTERESTING. WE HAVE A GRANT ON

3853
02:32:33,080 --> 02:32:34,320
RADIATION COUNTER MEASURES FROM

3854
02:32:34,320 --> 02:32:37,600
FDA DOING MALE VERSUS FEMALE

3855
02:32:37,600 --> 02:32:38,920
BECAUSE IN CLINICAL TRIALS, NOT

3856
02:32:38,920 --> 02:32:41,160
COVERED EQUALLY IN A DIFFERENT

3857
02:32:41,160 --> 02:32:42,360
-- SO THAT IS A POWER OF THESE

3858
02:32:42,360 --> 02:32:46,720
BUT IT MAKE MORE DIFFICULT

3859
02:32:46,720 --> 02:32:47,840
BECAUSE YOU HAVE TO DO MORE

3860
02:32:47,840 --> 02:32:50,320
VARIABLES.

3861
02:32:50,320 --> 02:32:51,880
>> I WANT TO ASK A
QUESTION TO

3862
02:32:51,880 --> 02:32:55,280
FOLLOW-UP ON THAT. THERE WAS A

3863
02:32:55,280 --> 02:32:57,000
RESPONSE FOLLOW-UP TO QUESTION

3864
02:32:57,000 --> 02:33:00,040
DR. INGBAR RESPONDED TO. WHICH

3865
02:33:00,040 --> 02:33:02,360
IS IF YOU ARE WORKING WITH DRUG

3866
02:33:02,360 --> 02:33:03,760
INDUCED DISEASE AND YOU SAY YOU

3867
02:33:03,760 --> 02:33:07,040
HAVE THREE DONORS YOU INVESTED

3868
02:33:07,040 --> 02:33:09,520
GIVEN YOUR WORK WOULD SAY FDA --

3869
02:33:09,520 --> 02:33:10,920
IS THERE A CERTAIN EXPECTATION

3870
02:33:10,920 --> 02:33:12,800
THAT YOU SHOULD HAVE SIX DONORS

3871
02:33:12,800 --> 02:33:15,840
OR TEN DONORS, WHEN ARE WE

3872
02:33:15,840 --> 02:33:17,360
GETTING TO THAT NUMBER AS A

3873
02:33:17,360 --> 02:33:20,560
FIELD IN GENERAL?

3874
02:33:20,560 --> 02:33:22,480
>> MY FIRST INTERACTION
WITH THE

3875
02:33:22,480 --> 02:33:25,280
FDA PRETTY CONSISTENTLY EARLY

3876
02:33:25,280 --> 02:33:28,240
ON, FROM THOSE WHO ARE OPEN TO

3877
02:33:28,240 --> 02:33:30,040
THIS STUFF IS AS LONG AS YOU ARE

3878
02:33:30,040 --> 02:33:32,120
AS GOOD AS AN ANIMAL MODEL, OR

3879
02:33:32,120 --> 02:33:35,880
BETTER, WEIAL STATISTICAL

3880
02:33:35,880 --> 02:33:36,680
ROBUSTNESS AND IT IS HUMAN, THEY

3881
02:33:36,680 --> 02:33:38,680
REVIEW THAT AS A POSITIVE.

3882
02:33:38,680 --> 02:33:39,880
BECAUSE REALLY YOU ARE DEALING

3883
02:33:39,880 --> 02:33:42,120
WITH COMPETING WITH ANIMAL

3884
02:33:42,120 --> 02:33:44,120
MODELS WHERE THEY TOTALLY INBRED

3885
02:33:44,120 --> 02:33:46,520
YOU GET DIFFERENT RESULTS WITH

3886
02:33:46,520 --> 02:33:48,240
DIFFERENT BREEDS SO BUT THERE IS

3887
02:33:48,240 --> 02:33:50,760
NO DOUBT ONCE YOU START USING

3888
02:33:50,760 --> 02:33:52,320
THESE MODELS THE BIGGER

3889
02:33:52,320 --> 02:33:54,480
QUESTIONS COME UP. NOW -- CAN

3890
02:33:54,480 --> 02:33:56,480
YOU ONLY USE IT FOR MEN, OR CAN

3891
02:33:56,480 --> 02:33:58,800
YOU ONLY USE IT FOR CERTAIN AGE

3892
02:33:58,800 --> 02:34:01,760
GROUPS? SO THE FDA IS STILL NOT

3893
02:34:01,760 --> 02:34:03,200
CLEAR HOW TO HANDLE ALL THESE,

3894
02:34:03,200 --> 02:34:05,640
THEY ONLY DEAL WITH SAFETY. SO

3895
02:34:05,640 --> 02:34:08,920
IT IS DIFFERENT THAN THE

3896
02:34:08,920 --> 02:34:10,080
PHARMACEUTICAL BIOTECH INDUSTRY.

3897
02:34:10,080 --> 02:34:11,560
FROM THE CLINICAL SIDE THEY ARE

3898
02:34:11,560 --> 02:34:14,000
DIFFERENT CHALLENGES, YOU MIGHT

3899
02:34:14,000 --> 02:34:15,600
WANT PERSONALIZED MEDICINE SO IT

3900
02:34:15,600 --> 02:34:16,960
IS A LITTLE BIT UP IN THE AIR

3901
02:34:16,960 --> 02:34:20,520
BUT I DO THINK FOR SAFETY YOU

3902
02:34:20,520 --> 02:34:22,960
ARE COMPETING WITH ANIMAL MODELS

3903
02:34:22,960 --> 02:34:25,200
AND AS LONG AS IT IS HUMAN AND

3904
02:34:25,200 --> 02:34:28,680
IT IS -- YOU CAN REPLICATE

3905
02:34:28,680 --> 02:34:30,240
CLINICAL MIMICRY WITH THE MODEL,

3906
02:34:30,240 --> 02:34:32,400
THAT IS WHAT WE USE, DO WE SEE

3907
02:34:32,400 --> 02:34:40,640
THIS IN VIVO IN HUMANS CELL

3908
02:34:40,640 --> 02:34:45,000
POPULATIONS TOO. TO WHAT THAT

3909
02:34:45,000 --> 02:34:47,760
VALIDATION IS. HOW ARE YOU

3910
02:34:47,760 --> 02:34:49,880
VALIDATING THE MODEL SO IT IS

3911
02:34:49,880 --> 02:34:51,240
PROBABLY RELATIVE MAYBE A LITTLE

3912
02:34:51,240 --> 02:34:52,640
BIT NARROWER AREA LIKE YOU ARE

3913
02:34:52,640 --> 02:34:58,680
SAYING.

3914
02:34:58,680 --> 02:35:01,200
>> SO ANOTHER QUESTION ON
THE

3915
02:35:01,200 --> 02:35:03,520
BOX FOR SARA. TERRIFIC

3916
02:35:03,520 --> 02:35:06,160
PRESENTATION SARA WITH REGARD TO

3917
02:35:06,160 --> 02:35:08,440
THE NASAL VERSUS AIRWAY

3918
02:35:08,440 --> 02:35:09,440
PLATFORMS DO YOU SEE A

3919
02:35:09,440 --> 02:35:11,200
SYSTEMATIC DIFFERENCE IN VIRAL

3920
02:35:11,200 --> 02:35:12,440
REPLICATION RATES SUGGESTING

3921
02:35:12,440 --> 02:35:14,000
MORE RAPID REPLICATION IN LUNG

3922
02:35:14,000 --> 02:35:18,960
TISSUE VERSUS THE OTHER?

3923
02:35:18,960 --> 02:35:22,600
>> WE SEE SARS COV-2 REPLY
CASE

3924
02:35:22,600 --> 02:35:23,760
ROBUSTLY IN BOTH MODELS THOUGH

3925
02:35:23,760 --> 02:35:27,720
WHEN COMPARING ACROSS THE

3926
02:35:27,720 --> 02:35:28,760
VARIANTS THERE ARE SOME

3927
02:35:28,760 --> 02:35:32,560
DIFFERENCES IN PATHOGENESIS IN

3928
02:35:32,560 --> 02:35:34,200
THE DIFFERENT CULTURE SYSTEMS

3929
02:35:34,200 --> 02:35:35,680
WHERE THERE IS MORE TOXICITY FOR

3930
02:35:35,680 --> 02:35:36,800
VARIANTS IN ONE MODEL OR THE

3931
02:35:36,800 --> 02:35:39,040
OTHER. THEN IN TERMS OF THE DRUG

3932
02:35:39,040 --> 02:35:40,600
TREATMENT THERE IS CERTAINLY

3933
02:35:40,600 --> 02:35:42,600
DIFFERENCES IN EFFICACY BETWEEN

3934
02:35:42,600 --> 02:35:44,040
DIFFERENT CLASSES OF SMALL

3935
02:35:44,040 --> 02:35:46,400
MOLECULES, AND WHAT THAT MEANS

3936
02:35:46,400 --> 02:35:47,960
IS LESS CLEAR TO US BUT WE ARE

3937
02:35:47,960 --> 02:35:49,680
DOING EXPERIMENTS IN ANIMAL

3938
02:35:49,680 --> 02:35:51,520
MODELS COMPARING EFFICACY IN

3939
02:35:51,520 --> 02:35:55,600
NASAL EPITHELIUM VERSUS THE

3940
02:35:55,600 --> 02:35:57,480
LOWER RESPIRATORY TRACT SO WE

3941
02:35:57,480 --> 02:35:58,600
DON'T KNOW IF WE ARE MODELING

3942
02:35:58,600 --> 02:36:00,960
WELL OR NOT BUT THERE ARE

3943
02:36:00,960 --> 02:36:02,160
CERTAINLY DIFFERENCES BETWEEN

3944
02:36:02,160 --> 02:36:06,000
DIFFERENT TISSUES THAT MAY

3945
02:36:06,000 --> 02:36:07,960
REFLECT REALITY, JUST NOT SURE

3946
02:36:07,960 --> 02:36:11,360
YET BECAUSE WE HAVEN'T BEEN AS

3947
02:36:11,360 --> 02:36:17,520
SYSTEMATIC AS WE NEED TO BE.

3948
02:36:17,520 --> 02:36:19,360
>> THANK YOU. THERE IS A
TOPIC

3949
02:36:19,360 --> 02:36:20,760
IN THE ANSWER COLUMN NOW THAT

3950
02:36:20,760 --> 02:36:22,000
WENT ON IN THE CHAT THAT I

3951
02:36:22,000 --> 02:36:24,280
THOUGHT WAS REALLY WORTH

3952
02:36:24,280 --> 02:36:28,840
BRINGING UP UP. I THINK SASHA YU

3953
02:36:28,840 --> 02:36:31,480
RAISED IT BUT IT RAISES I GUESS

3954
02:36:31,480 --> 02:36:32,640
A QUESTION, I WILL READ YOUR

3955
02:36:32,640 --> 02:36:33,680
QUESTION SO YOU WORD IT BETTER

3956
02:36:33,680 --> 02:36:36,880
THAN I WAS TRYING TO. AND THAT

3957
02:36:36,880 --> 02:36:38,640
WAS TO DR. LEE TO KICK OFF THE

3958
02:36:38,640 --> 02:36:39,640
DISCUSSION BUT I THINK I WOULD

3959
02:36:39,640 --> 02:36:43,000
LIKE TO HEAR OTHERS CHIME IN AS

3960
02:36:43,000 --> 02:36:44,440
WELL. THE QUESTION OR COMMENT

3961
02:36:44,440 --> 02:36:45,920
WAS CURIOUS TO LEARN MORE ABOUT

3962
02:36:45,920 --> 02:36:48,040
YOUR THOUGHTS ON CHARACTERIZING

3963
02:36:48,040 --> 02:36:51,200
THE MODELS EARLY AND WHAT KIND

3964
02:36:51,200 --> 02:36:52,720
OF CHARACTERIZATION DO YOU THINK

3965
02:36:52,720 --> 02:36:55,320
IS IMPORTANT TO BE THOROUGH

3966
02:36:55,320 --> 02:36:57,280
ENOUGH. AGREE WOULD BE GREAT TO

3967
02:36:57,280 --> 02:36:58,800
HAVE WELL CHARACTERIZED MODELS

3968
02:36:58,800 --> 02:37:00,560
READY TO BE USED FOR DIFFERENT

3969
02:37:00,560 --> 02:37:03,080
INFECTIONS AND DISEASES, THIS

3970
02:37:03,080 --> 02:37:04,440
DEFINITE CAME UP IN MY THINKING

3971
02:37:04,440 --> 02:37:06,320
AS WELL AROUND THE SORT OF

3972
02:37:06,320 --> 02:37:08,960
PANDEMIC PREPAREDNESS MORE

3973
02:37:08,960 --> 02:37:10,440
BROADLY AND THINKING ABOUT HOW

3974
02:37:10,440 --> 02:37:15,480
DO WE PREPARE FOR THAT PATHOGEN

3975
02:37:15,480 --> 02:37:17,280
X REFLECTING BACK TO WHERE WE

3976
02:37:17,280 --> 02:37:19,080
WERE WITH SARS COV-2 WE ARE

3977
02:37:19,080 --> 02:37:20,400
FORTUNATE ACTUALLY THE

3978
02:37:20,400 --> 02:37:21,640
FOUNDATIONAL STUDIES WITH SARS

3979
02:37:21,640 --> 02:37:25,280
AND OTHER COMA VIRUSES THAT GAVE

3980
02:37:25,280 --> 02:37:26,640
CLUES WHETHER CELLS LINES TO USE

3981
02:37:26,640 --> 02:37:28,440
AND WE BUMPED ALONG SETTING UP

3982
02:37:28,440 --> 02:37:30,120
ASSAYS AND MODELS AND UNDERSTAND

3983
02:37:30,120 --> 02:37:32,480
CELL LINES BUT LOVE TO BE ABLE

3984
02:37:32,480 --> 02:37:35,400
TO DO IS INVEST MORE EFFORTS

3985
02:37:35,400 --> 02:37:36,520
DURING PEACETIME IF YOU WILL

3986
02:37:36,520 --> 02:37:41,240
ACROSS THE VIRAL FAMILIES THAT

3987
02:37:41,240 --> 02:37:43,760
MAY HAVE RELATED VIROS BE FUTURE

3988
02:37:43,760 --> 02:37:44,560
PROBLEM AND UNDERSTAND BASIC

3989
02:37:44,560 --> 02:37:46,600
FOUNDATIONAL WORK IN THAT SPACE

3990
02:37:46,600 --> 02:37:53,000
SO THAT WE A WE ARE BETTER TO

3991
02:37:53,000 --> 02:37:54,680
ACCELERATE RAPIDLY WHEN WE SEE A

3992
02:37:54,680 --> 02:37:57,800
PATHOGEN HIT OR RADAR. SO DR.

3993
02:37:57,800 --> 02:37:59,040
LEE IF YOU COULD KICK OFF EMILY

3994
02:37:59,040 --> 02:38:00,240
AND SHARE YOUR THOUGHTS HOW YOU

3995
02:38:00,240 --> 02:38:02,280
ARE SETTING UP TO TO PREPARE

3996
02:38:02,280 --> 02:38:03,760
FROM THAT AND LOVE TO HEAR

3997
02:38:03,760 --> 02:38:14,280
OTHERS HOW WE CAN DO THIS. FOR

3998
02:38:18,960 --> 02:38:21,160
THIS EXACT PURPOSE SO WE ARE

3999
02:38:21,160 --> 02:38:22,320
WORKING THROUGH DIFFERENT

4000
02:38:22,320 --> 02:38:24,040
MODELS, DIFFERENT VIRAL FAMILY,

4001
02:38:24,040 --> 02:38:25,480
DIFFERENT REPRESENTATIVE VIRUSES

4002
02:38:25,480 --> 02:38:27,080
IN THOSE FAMILIES AND STARTING

4003
02:38:27,080 --> 02:38:31,040
FROM THE VERY BASICS, STARTING

4004
02:38:31,040 --> 02:38:32,920
WITH WHAT ARE THE VIRAL KINETICS

4005
02:38:32,920 --> 02:38:35,760
IN THAT TISSUE WHAT IS CELLULAR

4006
02:38:35,760 --> 02:38:37,760
TROPISM IN THAT TISSUE, ARE WE

4007
02:38:37,760 --> 02:38:40,080
OBSERVING VIRAL PERSISTENCE,

4008
02:38:40,080 --> 02:38:41,320
LOOKING IN PARTICULAR IN THE GUT

4009
02:38:41,320 --> 02:38:45,520
FOR SARS COV-2, CAN WE ESTABLISH

4010
02:38:45,520 --> 02:38:47,080
PARAMETERS WHICH IS NOT EASY

4011
02:38:47,080 --> 02:38:48,560
CONTROL ANTIVIRAL HERPETIC FOR

4012
02:38:48,560 --> 02:38:50,080
BENCHMARKING FOR EVALUATING NEW

4013
02:38:50,080 --> 02:38:52,480
THERAPEUTICS IF POSSIBLE. THEN

4014
02:38:52,480 --> 02:38:55,000
IN TERMS OF VIRAL DISEASE WHICH

4015
02:38:55,000 --> 02:38:56,440
IS ALSO IMPORTANT TO LOOK AT WE

4016
02:38:56,440 --> 02:38:58,440
REALLY WANT TO BE ABLE TO

4017
02:38:58,440 --> 02:39:03,480
CHARACTERIZE TISSUES IN TERMS OF

4018
02:39:03,480 --> 02:39:05,520
HEALTHY UNINFECTED TISSUE VERSUS

4019
02:39:05,520 --> 02:39:07,200
VIRAL INFECTED TISSUE TO GET

4020
02:39:07,200 --> 02:39:08,400
IDEA WHAT READ OUTS WE SHOULD BE

4021
02:39:08,400 --> 02:39:11,760
USING TO EVALUATE THERAPEUTIC

4022
02:39:11,760 --> 02:39:13,480
EFFICACY BOTH DIRECTLY LOOKING

4023
02:39:13,480 --> 02:39:15,520
AT VIRAL INFECTION BUT THEN ALSO

4024
02:39:15,520 --> 02:39:17,040
AFFECTING THE TISSUE. SO WE ARE

4025
02:39:17,040 --> 02:39:19,640
TRYING TO LOOK AT MORPHOLOGICAL

4026
02:39:19,640 --> 02:39:21,120
READ OUTS, WE HAVE RECENTLY

4027
02:39:21,120 --> 02:39:23,120
STARTED USING SINGLE CELL RNA

4028
02:39:23,120 --> 02:39:26,760
SEQ SO WE HOPE TO MAKE THAT DATA

4029
02:39:26,760 --> 02:39:32,600
PUBLIC, AS WE GENERATE AND ALSO

4030
02:39:32,600 --> 02:39:35,040
HAVING FUNCTIONAL ASSAY AS WELL.

4031
02:39:35,040 --> 02:39:37,800
SO THIS IS A HUGE PROJECT THERE

4032
02:39:37,800 --> 02:39:40,200
IS A LOT OF PEOPLE INVOLVED AND

4033
02:39:40,200 --> 02:39:41,520
ALWAYS WELCOME COLLABORATORS TO

4034
02:39:41,520 --> 02:39:44,560
WORK WITH AS WELL TO TRY TO GET

4035
02:39:44,560 --> 02:39:47,560
THIS INFORMATION OUT FOR GENERAL

4036
02:39:47,560 --> 02:39:52,080
USE. 

4037
02:39:52,080 --> 02:39:53,440
>> I WAS GOING TO JUMP IN,
THIS

4038
02:39:53,440 --> 02:39:56,600
IS A REALLY IMPORTANT QUESTION

4039
02:39:56,600 --> 02:39:59,480
HOW WE PREPARE FOR THE NEXT

4040
02:39:59,480 --> 02:40:02,000
PANDEMIC WITH THESE MODELS. SO

4041
02:40:02,000 --> 02:40:05,000
IN OUR LABORATORY WITH WE ARE

4042
02:40:05,000 --> 02:40:06,960
INTERESTED IN THE QUESTION THAT

4043
02:40:06,960 --> 02:40:12,720
WAS ASKED TO ME BY MARK EARLIER,

4044
02:40:12,720 --> 02:40:14,400
WE WANT TO ESTABLISH BIOBANKS IN

4045
02:40:14,400 --> 02:40:17,080
THE ORGANOIDS THAT ARE

4046
02:40:17,080 --> 02:40:19,560
REPRESENTING DIFFERENT AGES

4047
02:40:19,560 --> 02:40:21,640
ETHNICITIES AND IN THE CASE OF

4048
02:40:21,640 --> 02:40:24,320
SARS VACCINATION STATUS, BECAUSE

4049
02:40:24,320 --> 02:40:26,320
WHEN WE SURVEY DIFFERENT

4050
02:40:26,320 --> 02:40:27,920
ORGANOIDS FOR ADAPTIVE IMMUNE

4051
02:40:27,920 --> 02:40:30,880
RESPONSE WE SAW VERY DIFFERENT

4052
02:40:30,880 --> 02:40:31,840
RESPONSES WHETHER PATIENT DONOR

4053
02:40:31,840 --> 02:40:33,400
HAS BEEN VACCINATED PREVIOUSLY

4054
02:40:33,400 --> 02:40:36,320
OR NOT.  SO THAT AUTOMATICALLY

4055
02:40:36,320 --> 02:40:40,480
SHOWS TREMENDOUS INTERPATIENT

4056
02:40:40,480 --> 02:40:44,760
VARIABILITY DEPENDING CERTAIN

4057
02:40:44,760 --> 02:40:48,200
CONCEPTS SO HAVING THESE

4058
02:40:48,200 --> 02:40:50,720
BIOBANKS AVAILABLE THAT SPAN

4059
02:40:50,720 --> 02:40:52,960
AGES ETHNICITY, VACCINATION

4060
02:40:52,960 --> 02:40:56,560
STATUS, ALONG WITH BLOOD BANKED

4061
02:40:56,560 --> 02:40:58,800
IN PARALLEL IS GOING TO BE VERY

4062
02:40:58,800 --> 02:41:02,240
IMPORTANT. SO THAT IS DEFINITELY

4063
02:41:02,240 --> 02:41:03,160
SOMETHING WE ARE INTERESTED IN

4064
02:41:03,160 --> 02:41:07,160
TRYING TO PURSUE WORKING WITH

4065
02:41:07,160 --> 02:41:07,640
Y'ALL.

4066
02:41:07,640 --> 02:41:09,560
>> SO WHAT ONE THING I
WOULD

4067
02:41:09,560 --> 02:41:11,320
ALSO MENTION IS THAT FOR MANY

4068
02:41:11,320 --> 02:41:16,640
EMERGING VIRUSES, WE DON'T KNOW

4069
02:41:16,640 --> 02:41:19,000
WHAT TROPISMS ARE THE VIRUSES

4070
02:41:19,000 --> 02:41:23,400
WHAT CELLS GET INFECTED.  AN

4071
02:41:23,400 --> 02:41:24,760
EXAMPLE IS TICK BORNE VIRUSES

4072
02:41:24,760 --> 02:41:26,640
BECOMING INCREASINGLY WORRISOME

4073
02:41:26,640 --> 02:41:28,760
BUT WE REALLY DON'T KNOW

4074
02:41:28,760 --> 02:41:30,000
ANYTHING ABOUT WHAT CELLS GET

4075
02:41:30,000 --> 02:41:35,440
INFECTED.  THAT IS A HUGE

4076
02:41:35,440 --> 02:41:36,760
OPPORTUNITY TO USE STEM CELL

4077
02:41:36,760 --> 02:41:37,960
DERIVED ORGANOIDS TO MAKE

4078
02:41:37,960 --> 02:41:43,160
VARIOUS ORGANOIDS AND TEST THEM.

4079
02:41:43,160 --> 02:41:47,440
FOR MANY ARTHEROPOD BORNE

4080
02:41:47,440 --> 02:41:49,600
VIRUSES DENDRITEICS DERMAL

4081
02:41:49,600 --> 02:41:50,720
DENDRITIC CELLS ARE MOST

4082
02:41:50,720 --> 02:41:53,360
IMPORTANT BUT THESE VIRUSES PAST

4083
02:41:53,360 --> 02:41:54,200
THROUGH OTHER TISSUES ON THE WAY

4084
02:41:54,200 --> 02:41:58,480
TO THE BRAIN. THERE IS FROM

4085
02:41:58,480 --> 02:41:59,320
TREMENDOUS OPPORTUNITY TO USE

4086
02:41:59,320 --> 02:42:01,520
STEM CELL DERIVED CELLS TO LOOK

4087
02:42:01,520 --> 02:42:03,320
AT EACH OF THESE DIFFERENT CELL

4088
02:42:03,320 --> 02:42:04,960
TYPES AND SEE OTHER DIFFERENCES

4089
02:42:04,960 --> 02:42:09,160
IN REPLICATION, DO VIRUSES

4090
02:42:09,160 --> 02:42:11,080
CHANGE, THIS KIND OF THING. SO A

4091
02:42:11,080 --> 02:42:12,000
LOT OF GOOD THINGS COULD BE

4092
02:42:12,000 --> 02:42:20,160
DONE.

4093
02:42:20,160 --> 02:42:22,080
>> GREAT. ONE THOUGHT
MAYBE YOUR

4094
02:42:22,080 --> 02:42:24,880
EXPERIENCE AND LOOKING ACROSS

4095
02:42:24,880 --> 02:42:26,840
THE BOARD AT DIFFERENT CELLS

4096
02:42:26,840 --> 02:42:32,480
DIFFERENT COMPLEXITY OF MODEL

4097
02:42:32,480 --> 02:42:33,520
ASSAYS, ONE OF THE THOUGHTS I

4098
02:42:33,520 --> 02:42:36,640
WAS HAVING IS FOR THAT UNKNOWN

4099
02:42:36,640 --> 02:42:38,160
PATHOGEN OR SURPRISE PATHOGEN

4100
02:42:38,160 --> 02:42:42,560
THAT COMES IN STARTING WITH MORE

4101
02:42:42,560 --> 02:42:46,880
COMPLEX MODEL ASSAYS BUT IT

4102
02:42:46,880 --> 02:42:47,920
MAKES SENSE AS YOU WERE SAYING

4103
02:42:47,920 --> 02:42:50,880
DR. GEHRKE BUT WONDERING IF

4104
02:42:50,880 --> 02:42:51,600
UNDERSTANDING THOSE SYSTEMS

4105
02:42:51,600 --> 02:42:54,440
ALLOW US TO THEN RETROSPECTIVE

4106
02:42:54,440 --> 02:42:56,080
BACK UP TO MORE SIMPLE CELL LINE

4107
02:42:56,080 --> 02:42:57,360
AND UNDERSTAND WHICH CELL LINES

4108
02:42:57,360 --> 02:42:58,640
WOULD BE BEST FOR WHAT TYPE OF

4109
02:42:58,640 --> 02:42:59,880
VIRAL FAMILIES AND THAT KIND OF

4110
02:42:59,880 --> 02:43:03,880
THING. AND WONDERING IF THERE IS

4111
02:43:03,880 --> 02:43:08,920
FOUNDATIONAL WORK TO BUILD THAT

4112
02:43:08,920 --> 02:43:09,520
TRANSLATION BETWEEN COMPLEX

4113
02:43:09,520 --> 02:43:11,160
SYSTEMS LEADING BACK TO VARIETY

4114
02:43:11,160 --> 02:43:13,440
OF MORE SIMPLE CELL ASSAY AND IF

4115
02:43:13,440 --> 02:43:15,080
THERE IS VALUE IN THAT OR IS

4116
02:43:15,080 --> 02:43:16,000
THAT DEFEATING THE PURPOSE OF

4117
02:43:16,000 --> 02:43:17,760
WHAT WAS GOING THROUGH MY MIND?

4118
02:43:17,760 --> 02:43:20,320
>> WE WORK WITH A LOT OF

4119
02:43:20,320 --> 02:43:21,360
DIFFERENT RNA VIRUSES IN MY LAB

4120
02:43:21,360 --> 02:43:23,920
AND WHAT WE HAVE BEEN TRYING TO

4121
02:43:23,920 --> 02:43:28,440
DO NOW IS DEVELOP CELL LINE

4122
02:43:28,440 --> 02:43:30,120
BASED MODEL CLOSE AS POSSIBLE TO

4123
02:43:30,120 --> 02:43:33,040
RELEVANT CELL TYPES IN VIVO

4124
02:43:33,040 --> 02:43:36,720
ASSAYS FOR THEM. SO WE HAVE

4125
02:43:36,720 --> 02:43:41,640
ASSAYS FOR HALF A DOZEN

4126
02:43:41,640 --> 02:43:43,520
FLAVIVIRUSES AND CORONA VIRUSES

4127
02:43:43,520 --> 02:43:47,560
AND MIX OF VIRUSES, IN A NUMBER

4128
02:43:47,560 --> 02:43:49,920
OF DIFFERENT CELL TYPES THAN WE

4129
02:43:49,920 --> 02:43:51,920
THINK ARE NOT VIRILE CELLS AND

4130
02:43:51,920 --> 02:43:54,200
NOT 3D MODELS BUT SOMETHING IN

4131
02:43:54,200 --> 02:43:55,760
BETWEEN TO REFLECT TISSUES THAT

4132
02:43:55,760 --> 02:44:00,360
ARE INFECTEDED. SO WE HAVE BLOOD

4133
02:44:00,360 --> 02:44:03,520
BRAIN BARRIER ENDOTHELIAL CELLS

4134
02:44:03,520 --> 02:44:06,240
VERSUS OTHER ENDOTHELIAL CELLS

4135
02:44:06,240 --> 02:44:07,560
AND THESE 3s ARE A GOOD MODEL

4136
02:44:07,560 --> 02:44:10,880
FOR THE RESPIRATORY EPITHELIUM

4137
02:44:10,880 --> 02:44:13,600
SO WE ARE TRYING TO COME UP WITH

4138
02:44:13,600 --> 02:44:15,280
A TOOLBOX DIFFERENT CELL TYPES

4139
02:44:15,280 --> 02:44:17,120
WE HAVE HIGH THROUGH PUT ASSAYS

4140
02:44:17,120 --> 02:44:19,120
SETS UP FOR DIFFERENT VIRUSES WE

4141
02:44:19,120 --> 02:44:20,640
HAVE HIGH THROUGH PUT ASSAYS SET

4142
02:44:20,640 --> 02:44:23,080
UP TO MIX AND MATCH RAPIDLY

4143
02:44:23,080 --> 02:44:24,760
BECAUSE WHEN SARS CAME OUT WE

4144
02:44:24,760 --> 02:44:26,200
TESTED EVERY CELL LINE WE CAN

4145
02:44:26,200 --> 02:44:28,880
BUY FROM ATCC AND THEN ENDED UP

4146
02:44:28,880 --> 02:44:32,280
ON CALU SO HOPEFULLY WE CAN HAVE

4147
02:44:32,280 --> 02:44:33,440
COUPLE OF HUNDRED CELL LINES IN

4148
02:44:33,440 --> 02:44:36,000
THE LAB AND FIGURE OUT WHAT IS

4149
02:44:36,000 --> 02:44:40,360
THE BEST MODEL FOR CELL TYPE IS

4150
02:44:40,360 --> 02:44:42,080
IMPORTANT. NEVER GOING TO BE THE

4151
02:44:42,080 --> 02:44:45,040
SAME AS 3D MODELS BUT AS SOMEONE

4152
02:44:45,040 --> 02:44:46,560
WHO IS A USER NOT A DEVELOPER,

4153
02:44:46,560 --> 02:44:49,040
IT IS HARD TO GET ACCESS TO

4154
02:44:49,040 --> 02:44:50,720
THESE MODELS, DIFFERENT LABS

4155
02:44:50,720 --> 02:44:52,240
DIFFERENT MODEL AND I'M NOT SURE

4156
02:44:52,240 --> 02:44:53,520
WHAT IS BETTER OR WORSE BETWEEN

4157
02:44:53,520 --> 02:44:55,120
THEM ACTUALLY WHICH IS PARTLY

4158
02:44:55,120 --> 02:44:56,480
WHY WE USE DIFFERENT MODELS FROM

4159
02:44:56,480 --> 02:44:59,840
DIFFERENT SOURCES, BUT I THINK

4160
02:44:59,840 --> 02:45:02,440
WE HAVE A LOT TO LEARN OR IF ALL

4161
02:45:02,440 --> 02:45:04,840
WE CAN DO IS START WITH 3D

4162
02:45:04,840 --> 02:45:06,000
MODELS IT IS HARD TO DO HIGH

4163
02:45:06,000 --> 02:45:09,080
THROUGH PUT SCREENING SO WE NEED

4164
02:45:09,080 --> 02:45:15,480
SOMETHING IN BETWEEN (INAUDIBLE)

4165
02:45:15,480 --> 02:45:17,680
>> GREAT. THANK YOU. ANY
OTHER

4166
02:45:17,680 --> 02:45:19,920
THOUGHTS ON THAT? BEFORE SHIFT

4167
02:45:19,920 --> 02:45:22,920
GEARS A LITTLE BIT?

4168
02:45:22,920 --> 02:45:24,800
>> MAY I ASK A FOLLOW-UP

4169
02:45:24,800 --> 02:45:25,080
QUESTION?

4170
02:45:25,080 --> 02:45:25,400
>> PLEASE.

4171
02:45:25,400 --> 02:45:27,960
>> I WAS WONDERING, IF
SARS

4172
02:45:27,960 --> 02:45:30,320
COV-2 IS A PRIME EXAMPLE FOR THE

4173
02:45:30,320 --> 02:45:33,680
MISSION WHERE YOU HAVE YOUR YOU

4174
02:45:33,680 --> 02:45:35,400
HAVE THE DIFFERENT CELL LINES,

4175
02:45:35,400 --> 02:45:37,000
YOU HAVE THE CELLS YOU HAVE 3D

4176
02:45:37,000 --> 02:45:38,520
MODELS AND CLINICAL EFFICACY

4177
02:45:38,520 --> 02:45:40,520
DATA SO ER TROUGH SPECKTIVELY

4178
02:45:40,520 --> 02:45:42,600
THINK HERE -- RETROSPECTIVELY

4179
02:45:42,600 --> 02:45:44,120
THINK HERE IS WHERE WE GET THE

4180
02:45:44,120 --> 02:45:44,840
CORRELATION AND USE THE

4181
02:45:44,840 --> 02:45:47,440
KNOWLEDGE TO INFORM US FOR THE

4182
02:45:47,440 --> 02:45:48,720
FUTURE. DO YOU ENVISION

4183
02:45:48,720 --> 02:45:50,920
SOMETHING LIKE THAT BASED ON

4184
02:45:50,920 --> 02:45:54,280
YOUR EXPERIENCE WITH SARS COV-2?

4185
02:45:54,280 --> 02:45:55,720
>> I PERSONALLY THINK IN
TERMS

4186
02:45:55,720 --> 02:45:58,040
OF THE CELL LINES THE CALU 3

4187
02:45:58,040 --> 02:46:01,560
CELLS ARE CLOSEST TO A LUNG BUT

4188
02:46:01,560 --> 02:46:03,400
THEY ARE NOT A LUNG SO BACKWARDS

4189
02:46:03,400 --> 02:46:06,760
I SHOWED YOU DATA MAYBE NOT VERY

4190
02:46:06,760 --> 02:46:09,920
CLEAR, THIS WAS ONLY 20 MINUTES

4191
02:46:09,920 --> 02:46:12,040
BUT WE HAVE DATA THREE APPROVED

4192
02:46:12,040 --> 02:46:14,880
DRUGS REMDESIVIR AND PAXLOVID

4193
02:46:14,880 --> 02:46:15,720
HAS ACTIVITY IN ALL THE MODELS

4194
02:46:15,720 --> 02:46:19,800
WE TESTED.  NOT ALL CELL LINES

4195
02:46:19,800 --> 02:46:24,080
BUT IN VIVO AND IN CALU SO I

4196
02:46:24,080 --> 02:46:26,080
THINK FOR THAT CLASS OF VIRUSES

4197
02:46:26,080 --> 02:46:29,120
I THINK A GOOD IN BETWEEN MODEL.

4198
02:46:29,120 --> 02:46:30,560
BUT FOR TRYING TO DEVELOP THESE

4199
02:46:30,560 --> 02:46:34,880
FOR OTHER VIRUSES, SO I THINK

4200
02:46:34,880 --> 02:46:38,960
FOR OTHER RESPIRATORY VIRUS VIRS

4201
02:46:38,960 --> 02:46:40,520
CALU IS GOOD BUT WE ARE

4202
02:46:40,520 --> 02:46:41,400
DEVELOPING THEM WHAT WE THINK

4203
02:46:41,400 --> 02:46:43,000
ARE AS GOOD AS THAT FOR OTHER

4204
02:46:43,000 --> 02:46:44,720
TISSUE TYPES AND I DON'T KNOW

4205
02:46:44,720 --> 02:46:47,400
THERE WILL BE ONE FOR EACH

4206
02:46:47,400 --> 02:46:55,080
TISSUE TYPE EVEN

4207
02:46:55,080 --> 02:46:57,280
>> I GUESS ANOTHER SORT OF
AREA

4208
02:46:57,280 --> 02:46:57,520
TOPIC --

4209
02:46:57,520 --> 02:46:58,320
>> CAN I --

4210
02:46:58,320 --> 02:47:00,120
>> PLEASE DO.

4211
02:47:00,120 --> 02:47:06,160
>> I THINK FOR RAPID
SCREENING

4212
02:47:06,160 --> 02:47:08,680
IT MAKES SENSE CALU 3 OR PEOPLE

4213
02:47:08,680 --> 02:47:10,960
NOW WORKING ON AUTOMATING

4214
02:47:10,960 --> 02:47:15,160
ORGANOIDS WHICH MAYBE BETTER.  

4215
02:47:15,160 --> 02:47:17,000
SO COULD BE ANOTHER WAY THE GET

4216
02:47:17,000 --> 02:47:19,960
TO NEXT STAGE. FROM OUR WORK WE

4217
02:47:19,960 --> 02:47:23,000
WERE LOOKING MORE HOST RESPONSE

4218
02:47:23,000 --> 02:47:24,880
RATHER THAN JUST GETTING VIRUS

4219
02:47:24,880 --> 02:47:27,000
TO GROW AND VIRUS INFECTION

4220
02:47:27,000 --> 02:47:28,560
MECHANISMS AND SO FORTH. JUST

4221
02:47:28,560 --> 02:47:29,320
BECAUSE WHEN YOU THINK ABOUT THE

4222
02:47:29,320 --> 02:47:32,680
EARLY DAYS OF COVID-19, IT WAS

4223
02:47:32,680 --> 02:47:34,840
REALLY THE CYTOKINE STORM IN THE

4224
02:47:34,840 --> 02:47:35,600
INFLAMMATORY RESPONSE THAT IS

4225
02:47:35,600 --> 02:47:39,120
KILLING PEOPLE. NOT THE INITIAL

4226
02:47:39,120 --> 02:47:40,920
INFECTIONS. SO YOU HAVE TO KEEP

4227
02:47:40,920 --> 02:47:43,200
THAT IN MIND TOO. WE NEED BOTH

4228
02:47:43,200 --> 02:47:46,720
ABSOLUTELY NEED BOTH. THAT IS

4229
02:47:46,720 --> 02:47:48,200
WHERE MORE COMPLEX MODELS COME

4230
02:47:48,200 --> 02:47:50,840
IN TRYING TO FIND HOST --

4231
02:47:50,840 --> 02:47:52,520
ANALYZE HOST RESPONSE AND FIND

4232
02:47:52,520 --> 02:47:58,800
MODULATORS. 

4233
02:47:58,800 --> 02:47:59,840
>> I AID GROW AND I REALLY

4234
02:47:59,840 --> 02:48:00,680
PERKED UP IN YOUR PRESENTATION

4235
02:48:00,680 --> 02:48:02,480
WHEN YOU WERE TALKING ABOUT I

4236
02:48:02,480 --> 02:48:04,720
THINK IT WAS THE RAGE INHIBITOR

4237
02:48:04,720 --> 02:48:07,280
THAT YOU PROFILED BECAUSE I

4238
02:48:07,280 --> 02:48:09,080
THINK TO THIS DAY WE HAVE A

4239
02:48:09,080 --> 02:48:11,400
COMPLETE GAP IN ABILITY TO

4240
02:48:11,400 --> 02:48:12,960
PRE-CLINICALLY ASSESS CANDIDATE

4241
02:48:12,960 --> 02:48:15,760
DRUGS FOR THAT SORT OF PHASE OF

4242
02:48:15,760 --> 02:48:17,360
DISEASE. AND THERE ARE A FEW --

4243
02:48:17,360 --> 02:48:20,600
WE WERE BASICALLY DOING OUR

4244
02:48:20,600 --> 02:48:22,600
ANIMAL MODELS WHO ARE IN

4245
02:48:22,600 --> 02:48:24,640
CLINICAL TRIALS FOR THOSE DURING

4246
02:48:24,640 --> 02:48:29,160
THE SARS COV-2 PANDEMIC FOR GOOD

4247
02:48:29,160 --> 02:48:30,480
REASON, THAT'S WHERE PEOPLE WERE

4248
02:48:30,480 --> 02:48:32,960
REALLY SUFFERING AND WE NEEDED

4249
02:48:32,960 --> 02:48:36,040
INTERVENTIONS. I THINK THAT WILL

4250
02:48:36,040 --> 02:48:39,600
BE NOT AN UNCOMMON SITUATION TO

4251
02:48:39,600 --> 02:48:41,920
BE IN FOR RESPIRATORY VIRAL

4252
02:48:41,920 --> 02:48:44,240
INFECTION. SO JUST LOVE TO HEAR

4253
02:48:44,240 --> 02:48:45,320
MORE ABOUT HOW MUCH WORK YOU

4254
02:48:45,320 --> 02:48:48,040
HAVE DONE IN THAT SPACE AND

4255
02:48:48,040 --> 02:48:49,280
PROFILING SOME OF THE KNOWN

4256
02:48:49,280 --> 02:48:51,360
CLINICAL CANDIDATES OR CLINICAL

4257
02:48:51,360 --> 02:48:53,280
DRUGS HITTING THAT MORE ARDS

4258
02:48:53,280 --> 02:48:55,600
TYPE PHASE OF INFECTION, HAVE

4259
02:48:55,600 --> 02:48:57,840
YOU LOOKED AT THOSE AND IS YOUR

4260
02:48:57,840 --> 02:49:00,480
SYSTEM RECAPITULATED IN CLINICAL

4261
02:49:00,480 --> 02:49:01,120
DATA THERE?

4262
02:49:01,120 --> 02:49:03,920
>> OUR FUNDING FROM DARPA
WAS

4263
02:49:03,920 --> 02:49:09,240
ONE YEAR AND ENDED A YEAR AGO. 

4264
02:49:09,240 --> 02:49:11,200
COMING TO AN END BUT THAT WAS ON

4265
02:49:11,200 --> 02:49:14,920
INFLUENZA FOR THE MOST PART. SO

4266
02:49:14,920 --> 02:49:16,560
WE HAVEN'T BUT YOU ARE

4267
02:49:16,560 --> 02:49:18,000
ABSOLUTELY RIGH RIGHT. WE HAVE

4268
02:49:18,000 --> 02:49:20,240
UNCOVERED A LOT OF INTERESTING

4269
02:49:20,240 --> 02:49:22,280
INSIGHTS INTO THE MCNISTIC

4270
02:49:22,280 --> 02:49:24,360
UNDERPINNINGS OF THAT --

4271
02:49:24,360 --> 02:49:25,280
MECHANISTIC UNDERPINNINGS OF

4272
02:49:25,280 --> 02:49:27,800
THAT BUT ONCE WE PICK THAT UP

4273
02:49:27,800 --> 02:49:29,040
ABOUT THE RAGE RECEPTOR YOU

4274
02:49:29,040 --> 02:49:32,160
START LOOKING AT THE LITERATURE

4275
02:49:32,160 --> 02:49:35,840
OUT THERE IT IS OVERWHELMINGLY

4276
02:49:35,840 --> 02:49:37,320
INDICATIVE IT PLAYS A CENTRAL

4277
02:49:37,320 --> 02:49:38,840
ROLE IN THIS PROCESS. I THINK

4278
02:49:38,840 --> 02:49:43,400
THIS IS COUNTERPOINTING OF RAPID

4279
02:49:43,400 --> 02:49:44,560
SCREENING, FOR JUST GOT TO

4280
02:49:44,560 --> 02:49:46,400
UNDERSTAND SOMETHING ABOUT THE

4281
02:49:46,400 --> 02:49:47,280
VERDICT YOU HAVE TO PROPAGATE

4282
02:49:47,280 --> 02:49:49,960
THE VIRUS TO STUDY THE VIRUS.

4283
02:49:49,960 --> 02:49:51,200
ABSOLUTELY NEED TO FIND WHAT

4284
02:49:51,200 --> 02:49:53,040
CELL LINES ARE RIGHT FOR THAT

4285
02:49:53,040 --> 02:49:56,240
AND THEN THE INITIAL ENTRY AND

4286
02:49:56,240 --> 02:49:57,560
DYNAMICS AND HOST RESPONSE WE

4287
02:49:57,560 --> 02:49:59,680
NEED ALL THOSE BUT CLOSER WE GET

4288
02:49:59,680 --> 02:50:02,880
TO HUMAN THE BETTER BECAUSE I

4289
02:50:02,880 --> 02:50:03,520
NOCIMON WILL PROBABLY TALK AT

4290
02:50:03,520 --> 02:50:06,640
THE END BUT JUST ANIMAL MODELS

4291
02:50:06,640 --> 02:50:11,840
WERE NOT OPTIMAL IN THIS ONE. 

4292
02:50:11,840 --> 02:50:14,240
>> AGREE. WE ARE GETTING
CLOSE

4293
02:50:14,240 --> 02:50:16,600
TO THE END BUT I WANTED TO PULL

4294
02:50:16,600 --> 02:50:18,800
-- ASK A FOLLOW-UP A LITTLE BIT

4295
02:50:18,800 --> 02:50:22,000
MORE ON I THINK SASHI YOU

4296
02:50:22,000 --> 02:50:23,800
MENTIONED IN YOUR TALK HAS A

4297
02:50:23,800 --> 02:50:26,960
NICE STORY HOW IT WAS IMPORTANT

4298
02:50:26,960 --> 02:50:30,800
TO IDENTIFY WHERE YOU WERE IN

4299
02:50:30,800 --> 02:50:34,000
THE END POINT ASSESSMENT AND HOW

4300
02:50:34,000 --> 02:50:36,280
SENSITIVE YOU WOULD BE TOWARD

4301
02:50:36,280 --> 02:50:38,880
TOXICITY OR CYTOTOXICITY TO GET

4302
02:50:38,880 --> 02:50:40,880
YOUR AND SENSITIVITY OF ASSAY TO

4303
02:50:40,880 --> 02:50:44,280
GET RELIABLE RESULTS. NICE

4304
02:50:44,280 --> 02:50:48,400
STORY, I WONDER FOR ALL THESE

4305
02:50:48,400 --> 02:50:50,400
SYSTEMS HOW BIG ISSUE ASSESSMENT

4306
02:50:50,400 --> 02:50:53,160
OF CYTOTOXICITY IS BECAUSE THAT

4307
02:50:53,160 --> 02:50:55,520
CERTAINLY IS AN ISSUE DOING

4308
02:50:55,520 --> 02:50:58,320
SIMPLE CELL SCREENING AND NOT

4309
02:50:58,320 --> 02:51:01,760
ONLY SURE YOU CAN DO A CYTOSOCK

4310
02:51:01,760 --> 02:51:04,400
AT THISTY SCREEN FOR THAT OVERT

4311
02:51:04,400 --> 02:51:06,280
CYTOTOX BUT MORE SUBTLE

4312
02:51:06,280 --> 02:51:08,840
INTERFERENCE OF CELLULAR

4313
02:51:08,840 --> 02:51:09,840
METABOLISM, THEREFORE GIVING YOU

4314
02:51:09,840 --> 02:51:11,560
A READ THAT LOOKS LIKE REDUCING

4315
02:51:11,560 --> 02:51:12,800
VIRAL LOAD I THINK IS AN

4316
02:51:12,800 --> 02:51:14,600
ARTIFACT THAT COMES UP ALL THE

4317
02:51:14,600 --> 02:51:15,960
TIME AND CELLS SCREENING AND I

4318
02:51:15,960 --> 02:51:18,440
WOULD IMAGINE THAT COULD BE ALSO

4319
02:51:18,440 --> 02:51:20,320
MAYBE EVEN MORE PROBLEMATIC IN

4320
02:51:20,320 --> 02:51:23,600
THESE MORE COMPLEX SYSTEMS,

4321
02:51:23,600 --> 02:51:25,520
WONDER WHAT FOLKS THINK OF THAT

4322
02:51:25,520 --> 02:51:26,400
STARTING WITH YOU TO ADDRESS

4323
02:51:26,400 --> 02:51:29,640
YOUR EXPERIENCE IN THAT SPACE. 

4324
02:51:29,640 --> 02:51:33,040
>> IT WAS A SURPRISE TO US
TO

4325
02:51:33,040 --> 02:51:34,760
SEE HOW MUCH VARIABILITY WAS

4326
02:51:34,760 --> 02:51:38,360
THERE AND HOW STANDARD PROTOCOL,

4327
02:51:38,360 --> 02:51:39,760
ANTIBODY USE OF PROTOCOL REALLY

4328
02:51:39,760 --> 02:51:41,280
DIDN'T WORK AS WELL IN OUR

4329
02:51:41,280 --> 02:51:43,800
HANDS. SO I DON'T THINK IT IS

4330
02:51:43,800 --> 02:51:44,960
REALLY WE ARE AT THE BEGINNING

4331
02:51:44,960 --> 02:51:46,760
OF THE LEARNING CURVE FOR THESE

4332
02:51:46,760 --> 02:51:48,440
THINGS AND CERTAINLY FOR US WE

4333
02:51:48,440 --> 02:51:52,200
APPRECIATE EACH OF OUR LINES ARE

4334
02:51:52,200 --> 02:51:53,200
QUITE DIFFERENT, THERE'S SOME

4335
02:51:53,200 --> 02:51:54,200
LINES WHICH ARE VERY DIFFERENT

4336
02:51:54,200 --> 02:51:57,480
FROM THE OTHERS, FOR EXAMPLE. SO

4337
02:51:57,480 --> 02:51:58,800
DOING TRANSCRIPTIONAL ANALYSIS

4338
02:51:58,800 --> 02:52:01,080
FOR EXAMPLE TRYING TO FIGURE OUT

4339
02:52:01,080 --> 02:52:02,720
WHAT IS DIFFERENT ABOUT THESE

4340
02:52:02,720 --> 02:52:06,360
LINES, IN SOME CASES WE HAVE

4341
02:52:06,360 --> 02:52:08,560
BUNCH OF SEQUENCE THE GENOME SO

4342
02:52:08,560 --> 02:52:10,400
THERE ARE DIFFERENCES IN DRUG

4343
02:52:10,400 --> 02:52:12,240
METABOLIZING ENZYMES IN GENERAL,

4344
02:52:12,240 --> 02:52:13,560
THOSE ARE ALL THE PLACES WHERE

4345
02:52:13,560 --> 02:52:16,360
WE ARE GOING TO BEGIN TO GET

4346
02:52:16,360 --> 02:52:17,600
ANSWERS WE DON'T HAVE PERMISSION

4347
02:52:17,600 --> 02:52:19,680
TO SEQUENCE GENOME FOR ALL OF

4348
02:52:19,680 --> 02:52:21,880
OUR CULTURES BUT I THINK THAT IS

4349
02:52:21,880 --> 02:52:24,520
WHERE WE ARE IN TERMS OF TRYING

4350
02:52:24,520 --> 02:52:25,920
TO UNDERSTAND WHY THERE ARE

4351
02:52:25,920 --> 02:52:32,640
DIFFERENCES.  ANY OTHER

4352
02:52:32,640 --> 02:52:34,160
PANELISTS HAVE EXPERIENCE IN

4353
02:52:34,160 --> 02:52:36,200
TRYING TO SORT THROUGH CYTOTOX

4354
02:52:36,200 --> 02:52:37,200
VERSUS ANTIVIRAL EFFECTS IN

4355
02:52:37,200 --> 02:52:39,120
THEIR SCREENING EFFORTS?

4356
02:52:39,120 --> 02:52:41,720
>> ONE NICE THING ABOUT
ORGAN

4357
02:52:41,720 --> 02:52:43,360
CHIPS IS WE CAN MEASURE

4358
02:52:43,360 --> 02:52:45,920
PHYSIOLOGICAL TOXICITIES LIKE

4359
02:52:45,920 --> 02:52:51,160
TISSUE BARRIER INTEGRITY,

4360
02:52:51,160 --> 02:52:54,040
CILIARE MOTION P PRODUCTION,

4361
02:52:54,040 --> 02:52:55,600
CYTOKINE PRODUCTION SO FORTH. SO

4362
02:52:55,600 --> 02:52:58,440
WE GET A LOT OF INFORMATION ON

4363
02:52:58,440 --> 02:53:03,720
THE SYSTEM MORE THAN JUST CELL

4364
02:53:03,720 --> 02:53:06,720
INJURY THE CYTOTOXICITIES ARE

4365
02:53:06,720 --> 02:53:12,120
RELATED TO PHARMACOKINETICS MOST

4366
02:53:12,120 --> 02:53:14,160
STATIC SYSTEMS IS BATHED IN

4367
02:53:14,160 --> 02:53:16,280
DRUGS FOR EXTENDED TIMES SO AS I

4368
02:53:16,280 --> 02:53:19,160
MENTION WE TRY TO USE WE USE C

4369
02:53:19,160 --> 02:53:22,160
MAX IN THESE STUDIES AT STEADY

4370
02:53:22,160 --> 02:53:24,080
RATE BUT WE MIMIC KNOWN PK

4371
02:53:24,080 --> 02:53:25,560
PROFILES IN OTHER PAPERS AND

4372
02:53:25,560 --> 02:53:34,040
THAT I THINK IS THE FUTURE.

4373
02:53:34,040 --> 02:53:35,600
>> IT IS REALLY IMPORTANT
TO

4374
02:53:35,600 --> 02:53:36,720
COME UP WITH GUIDELINES FOR

4375
02:53:36,720 --> 02:53:38,200
PEOPLE IN TERMS OF REPORTING AND

4376
02:53:38,200 --> 02:53:41,520
IN TERMS OF WHAT WE EXPECT. WE

4377
02:53:41,520 --> 02:53:42,760
HAVE TESTED DRUGS THAT PEOPLE

4378
02:53:42,760 --> 02:53:46,840
HAVE REPORTED IN OUR HANDS,

4379
02:53:46,840 --> 02:53:52,160
DIFFICULT TO INTERPRET.  SO IF

4380
02:53:52,160 --> 02:53:53,840
WE CAN COME UP WITH IDEAS FOR

4381
02:53:53,840 --> 02:53:54,760
THE COMMUNITY, THAT WOULD BE

4382
02:53:54,760 --> 02:53:56,400
GREAT.  NOT EVERYBODY CAN DO

4383
02:53:56,400 --> 02:53:57,760
EVERY ASSAY BUT MAYBE ASK PEOPLE

4384
02:53:57,760 --> 02:54:00,680
TO DO HANDFUL OF THINGS AND THAT

4385
02:54:00,680 --> 02:54:02,680
WAY WE CAN BE MORE SYSTEMATIC IN

4386
02:54:02,680 --> 02:54:09,440
INTERPRETING PHENOTYPES. 

4387
02:54:09,440 --> 02:54:11,880
>> GOOD POINT SARA.
WONDERING IF

4388
02:54:11,880 --> 02:54:13,480
SOMEWHERE ALONG THE LINES WE

4389
02:54:13,480 --> 02:54:14,840
HAVE DISCUSSIONS AND POSSIBLE

4390
02:54:14,840 --> 02:54:19,520
FOLLOW-UP WONDERING IF THERE WAS

4391
02:54:19,520 --> 02:54:23,120
ANY BENEFIT OF SETTING UP

4392
02:54:23,120 --> 02:54:25,560
STANDARDIZED REAGENTS, ACCESS TO

4393
02:54:25,560 --> 02:54:28,120
STANDARDIZED REAGENTS, DRUGS

4394
02:54:28,120 --> 02:54:28,760
OTHER CONTROL TYPE THINGS THAT

4395
02:54:28,760 --> 02:54:30,840
COULD BE USED ACROSS THE VARIOUS

4396
02:54:30,840 --> 02:54:33,720
MODELS AND ASSAYS TO NORMALIZE.

4397
02:54:33,720 --> 02:54:35,440
I THINK WE ALL EXPERIENCE THAT

4398
02:54:35,440 --> 02:54:37,120
WITH SARS COV-2, PEOPLE HAVING

4399
02:54:37,120 --> 02:54:38,040
SLIGHTLY DIFFERENT CHALLENGE

4400
02:54:38,040 --> 02:54:39,880
MATERIAL AND THINGS LIKE THAT

4401
02:54:39,880 --> 02:54:42,200
REALLY CHANGING OUTCOMES OR EVEN

4402
02:54:42,200 --> 02:54:43,360
DIFFERENT SUBTLE CELL LINES,

4403
02:54:43,360 --> 02:54:44,920
THINGS LIKE THAT SO WE SHOULD

4404
02:54:44,920 --> 02:54:46,200
PUT THAT ON OUR LIST OF THINGS

4405
02:54:46,200 --> 02:54:51,360
TO CAPTURE BECAUSE I THINK THERE

4406
02:54:51,360 --> 02:54:52,800
ARE MECHANISMS IN PLACE TO GET

4407
02:54:52,800 --> 02:54:55,800
IT DONE SOONER RATHER THAN IN A

4408
02:54:55,800 --> 02:54:57,040
PANIC THE WAY WE HAVE DONE THE

4409
02:54:57,040 --> 02:55:01,520
LAST COUPLE OF YEARS SOMETIMES. 

4410
02:55:01,520 --> 02:55:03,400
>> WE ARE DOING ASSAYS
LIKE

4411
02:55:03,400 --> 02:55:04,680
WHERE DO WE LOOK OR WHAT IS

4412
02:55:04,680 --> 02:55:07,560
RIGHT AND I DON'T THINK THERE IS

4413
02:55:07,560 --> 02:55:09,280
A RIGHT ANSWER BUT WE WANT TO BE

4414
02:55:09,280 --> 02:55:12,200
ABLE TO HAVE OPTIONS AND KNOW

4415
02:55:12,200 --> 02:55:13,440
THESE ARE WHAT IS REQUIRED IF

4416
02:55:13,440 --> 02:55:23,120
YOU DO WANT TO DO DRUG TESTING. 

4417
02:55:23,120 --> 02:55:25,480
>> WE ARE GETTING CLOSE TO
BREAK

4418
02:55:25,480 --> 02:55:26,720
TO BEFORE TURNING IT OVER I WANT

4419
02:55:26,720 --> 02:55:31,320
TO THANK ALL THE PANELISTS AND

4420
02:55:31,320 --> 02:55:32,400
SPEAKERS FOR SESSION 2, IT WAS

4421
02:55:32,400 --> 02:55:34,400
FANTASTIC. ALSO THANK YOU TO

4422
02:55:34,400 --> 02:55:35,200
PARTICIPANTS WRITING IN

4423
02:55:35,200 --> 02:55:37,400
QUESTIONS, IF YOU ARE FEELING

4424
02:55:37,400 --> 02:55:39,600
THIS DISCUSSION, VERY MUCH

4425
02:55:39,600 --> 02:55:40,480
APPRECIATE IT. THANK YOU SO

4426
02:55:40,480 --> 02:55:42,880
MUCH. OVER TO SARINE FOR

4427
02:55:42,880 --> 02:55:45,360
TRANSITIONING.

4428
02:55:45,360 --> 02:55:47,640
>> THANK YOU SO MUCH, ANN,
FOR A

4429
02:55:47,640 --> 02:55:51,480
WONDERFUL SESSION. AND ALL THE

4430
02:55:51,480 --> 02:55:52,960
SPEAKERS, CERTAINLY DID LIKE ALL

4431
02:55:52,960 --> 02:55:53,880
YOUR TALKS AND AMAZING

4432
02:55:53,880 --> 02:55:57,920
DISCUSSION. SO APPRECIATE Y'ALL.

4433
02:55:57,920 --> 02:56:02,800
SO NEXT WE WILL HAVE A BREAK

4434
02:56:02,800 --> 02:56:06,640
THEN RECONVENE AT 3 O'CLOCK FOR

4435
02:56:06,640 --> 02:56:10,480
SESSION 3 WHICH WILL BE ON USER

4436
02:56:10,480 --> 02:56:11,800
REPRODUCIBLE TREATING TISSUE

4437
02:56:11,800 --> 02:56:13,080
MODELS FROM DRUG DISCOVERY TO

4438
02:56:13,080 --> 02:56:14,400
DEVELOPMENT AND THAT WILL BE

4439
02:56:14,400 --> 02:56:16,760
CHAIRED BY DR. ROBERT JORDAN

4440
02:56:16,760 --> 02:56:18,280
FROM THE BILL AND MELINDA GATES

4441
02:56:18,280 --> 02:56:21,440
FOUNDATION. TIME FOR BREAK NOW

4442
02:56:21,440 --> 02:56:23,920
AND MEET AGAIN AT 3 O'CLOCK. 

4443
02:56:23,920 --> 02:56:27,360
THANK YOU VERY MUCH. 

4444
02:56:27,360 --> 02:56:28,960
>>WELCOME BACK. IT IS
THREE

4445
02:56:28,960 --> 02:56:30,720
O'CLOCK SO LET'S RESUME THE

4446
02:56:30,720 --> 02:56:36,720
WORKSHOP. NEXT IS SESSION 3,

4447
02:56:36,720 --> 02:56:40,040
GOING TO BE ON THE USE OF ROBUST

4448
02:56:40,040 --> 02:56:42,560
AND REPRODUCIBLE MODELS FROM

4449
02:56:42,560 --> 02:56:44,160
DRUG DISCOVERY TO DEVELOPMENT.

4450
02:56:44,160 --> 02:56:47,840
I'M SUPER EXCITED TO INTRODUCE

4451
02:56:47,840 --> 02:56:50,560
OUR CHAIR FOR THIS SESSION WHO

4452
02:56:50,560 --> 02:56:52,680
IS DR. ROBERT JORDAN, SENIOR

4453
02:56:52,680 --> 02:56:54,680
PROGRAM OFFICER AT THE BILL AND

4454
02:56:54,680 --> 02:56:59,520
MELINDA GATES FOUNDATION.  PRIOR

4455
02:56:59,520 --> 02:57:01,240
TO JOINING THE GATES FOUNDATION

4456
02:57:01,240 --> 02:57:01,840
ROBERT WAS VICE PRESIDENT OF

4457
02:57:01,840 --> 02:57:04,920
RESEARCH AND DEVELOPMENT AT MESA

4458
02:57:04,920 --> 02:57:06,560
VACCINES DEVELOPING LIVE

4459
02:57:06,560 --> 02:57:08,240
ATTENUATED VIRUS VACCINES FOR

4460
02:57:08,240 --> 02:57:10,120
RSV AND SARS COV-2 AS WELL AS

4461
02:57:10,120 --> 02:57:12,080
OTHER RESPIRATORY VIRUS

4462
02:57:12,080 --> 02:57:14,000
PATHOGEN. THANK YOU, ROBERT.

4463
02:57:14,000 --> 02:57:18,560
PASS THE BATON FOR YOU TO CHAIR.

4464
02:57:18,560 --> 02:57:20,280
>> WELCOME BACK TO SESSION
3.

4465
02:57:20,280 --> 02:57:23,800
THIS IS HAS BEEN A GREAT MEETING

4466
02:57:23,800 --> 02:57:25,160
SO FAR WE HAVE HEARD INTERESTING

4467
02:57:25,160 --> 02:57:28,440
RESEARCH ON 3D TISSUE MODELS TO

4468
02:57:28,440 --> 02:57:29,840
BETTER UNDERSTAND COMPLEX

4469
02:57:29,840 --> 02:57:33,520
BIOLOGY OF VIRUS HOST

4470
02:57:33,520 --> 02:57:34,680
INTERACTIONS AND HOW THEY CAN BE

4471
02:57:34,680 --> 02:57:36,440
USED TO FACILITATE DRUG

4472
02:57:36,440 --> 02:57:38,040
DISCOVERY AND DEVELOPMENT FOR

4473
02:57:38,040 --> 02:57:39,560
ANTIVIRALS AND UP COVER

4474
02:57:39,560 --> 02:57:42,560
INTERESTING PHENOTYPES THAT ARE

4475
02:57:42,560 --> 02:57:44,960
ASSOCIATED WITH ANTIVIRAL

4476
02:57:44,960 --> 02:57:48,440
DISCOVERY THAT AREN'T READILY

4477
02:57:48,440 --> 02:57:49,720
AVAILABLE IN 2D SYSTEMS, THERE'S

4478
02:57:49,720 --> 02:57:51,800
A LOT OF IMPORTANT INFORMATION

4479
02:57:51,800 --> 02:57:54,080
PRESENTED SO FAR. I THE GOAL OF

4480
02:57:54,080 --> 02:57:56,200
THIS SESSION IS TO LOOK AT

4481
02:57:56,200 --> 02:57:59,040
PRACTICAL ASPECTS OF 3D TISSUE

4482
02:57:59,040 --> 02:58:00,120
CULTURE MODELS IN DRUG DISCOVERY

4483
02:58:00,120 --> 02:58:01,800
AND DEVELOPMENT. SO LET ME

4484
02:58:01,800 --> 02:58:05,200
INTRODUCE OUR FIRST SPEAKER

4485
02:58:05,200 --> 02:58:09,360
TONIGHT, OUR FIRST SPEAKER IS

4486
02:58:09,360 --> 02:58:20,360
DR. NICOLE K ANY KLEINSTREUER H.

4487
02:58:23,160 --> 02:58:24,320
FEDERAL RESOURCE FOR

4488
02:58:24,320 --> 02:58:25,760
ALTERNATIVES TO ANIMAL TESTING.

4489
02:58:25,760 --> 02:58:28,840
ATH AT THE NICEATM SHE LEADS

4490
02:58:28,840 --> 02:58:30,320
DOMESTIC INTERNATIONAL EFFORTS

4491
02:58:30,320 --> 02:58:31,760
TO DEVELOP NOVEL TESTING

4492
02:58:31,760 --> 02:58:33,720
ANALYSIS STRATEGIES TO PROVIDE

4493
02:58:33,720 --> 02:58:36,240
RAPID MECHANISTIC AND HUMAN

4494
02:58:36,240 --> 02:58:37,840
RELEVANCE PREDICTIONS OF

4495
02:58:37,840 --> 02:58:40,240
POTENTIAL ENVIRONMENTAL HAZARDS.

4496
02:58:40,240 --> 02:58:44,880
DR. KLINESTREUER FOCUS FOCUSES

4497
02:58:44,880 --> 02:58:49,840
ON THE MATHEMATICAL MODELING OF

4498
02:58:49,840 --> 02:58:51,280
PERTURBATIONS AND ADVERSE

4499
02:58:51,280 --> 02:58:52,800
OUTCOMES. THE TITLE OF HEIFER

4500
02:58:52,800 --> 02:58:53,680
TALK IS CONNECTING AND

4501
02:58:53,680 --> 02:58:55,240
SUPPORTING THE TISSUE MODELING

4502
02:58:55,240 --> 02:58:58,040
COMMUNITY VIA NPSCORE GLOBAL

4503
02:58:58,040 --> 02:59:01,120
WORKING GROUP. NICOLE, THE FLOOR

4504
02:59:01,120 --> 02:59:02,360
IS YOURS.

4505
02:59:02,360 --> 02:59:08,760
>> PERFE PERFECT
KLEINSTREUER. T

4506
02:59:08,760 --> 02:59:10,200
YOU CAN SEE MY SCREEN IN THE

4507
02:59:10,200 --> 02:59:14,680
APPROPRIATE VIEW.  SO YEAH, I AM

4508
02:59:14,680 --> 02:59:17,520
AS I LEAVE NICEATM USUALLY HOW

4509
02:59:17,520 --> 02:59:22,160
WE SAY IT BUT I DO ACCEPT THE

4510
02:59:22,160 --> 02:59:24,920
FRIENDLY CASH MACHINE NICE ATM

4511
02:59:24,920 --> 02:59:26,160
PRONUNCIATION AS WELL. SO THIS

4512
02:59:26,160 --> 02:59:27,800
IS REALLY EXCITED TO TALK TO YOU

4513
02:59:27,800 --> 02:59:30,760
TODAY ABOUT THIS INITIATIVE THAT

4514
02:59:30,760 --> 02:59:33,640
WE PUT FORWARD OVER THE LAST TWO

4515
02:59:33,640 --> 02:59:35,720
YEARS NOW, THIS STARTED ABOUT

4516
02:59:35,720 --> 02:59:38,800
SIX MONTHS INTO THE PANDEMIC AND

4517
02:59:38,800 --> 02:59:39,960
I HAVE TO ABSOLUTELY START WITH

4518
02:59:39,960 --> 02:59:43,920
A SHOUT OUT TO MY CO-CHAIR ON

4519
02:59:43,920 --> 02:59:45,680
THIS WORKING GROUP ANTHONY

4520
02:59:45,680 --> 02:59:47,600
HOLMES SO A JOINT VENTURE

4521
02:59:47,600 --> 02:59:50,360
BETWEEN THE UK NC 3Rs TO, A

4522
02:59:50,360 --> 02:59:52,120
MALL CENTER REDUCTION REFINEMENT

4523
02:59:52,120 --> 02:59:53,920
AND REPLACEMENT OF ANIMAL

4524
02:59:53,920 --> 02:59:56,000
TESTING IN ENGLAND AND SO HE AND

4525
02:59:56,000 --> 02:59:57,960
I GOT TOGETHER ABOUT TWO YEARS

4526
02:59:57,960 --> 02:59:59,120
AGO AND DECIDED IT WAS TIME FOR

4527
02:59:59,120 --> 03:00:01,760
US TO TRY ARE TO CREATE THIS

4528
03:00:01,760 --> 03:00:05,320
NETWORK TO BRING THE COMMUNITY

4529
03:00:05,320 --> 03:00:07,000
TOGETHER ON FOLKS USING NPS

4530
03:00:07,000 --> 03:00:09,000
MODELS TO STUDY INFECTIOUS

4531
03:00:09,000 --> 03:00:10,000
DISEASE SPECIFICALLY COVID TO

4532
03:00:10,000 --> 03:00:14,840
PROVIDE A REALLY RESPONSIVE

4533
03:00:14,840 --> 03:00:16,840
EFFORT TO THE PANDEMIC MOTIVATED

4534
03:00:16,840 --> 03:00:19,680
BY THE FACT THAT THERE ARE NO

4535
03:00:19,680 --> 03:00:22,680
TRULY GOOD ANIMAL MODELS FOR

4536
03:00:22,680 --> 03:00:25,040
COVID DISEASE PRESENTATION AND

4537
03:00:25,040 --> 03:00:26,800
WE REALLY SAW IT AS AN

4538
03:00:26,800 --> 03:00:28,480
OPPORTUNITY TO HIGHLIGHT AND

4539
03:00:28,480 --> 03:00:32,160
INVESTIGATE THE UTILITY OF HUMAN

4540
03:00:32,160 --> 03:00:33,560
BIOLOGICALLY BASED

4541
03:00:33,560 --> 03:00:34,440
MICROPHYSIOLOGICAL SYSTEMS AND

4542
03:00:34,440 --> 03:00:36,400
PROVIDING INSIGHT INTO DISEASE

4543
03:00:36,400 --> 03:00:40,840
MECHANISMS AND TEST THERAPEUTICS

4544
03:00:40,840 --> 03:00:45,560
AND COORDINATE ACTIVITIES AROUND

4545
03:00:45,560 --> 03:00:47,800
MPS AND COVID-19 TO MAXIMIZE

4546
03:00:47,800 --> 03:00:49,880
HUMAN HEALTH AND ANIMAL WELFARE

4547
03:00:49,880 --> 03:00:52,440
IMPACTS OF THESE PLATFORMS. SO

4548
03:00:52,440 --> 03:00:53,880
FIRSTLY START WITH A LITTLE

4549
03:00:53,880 --> 03:00:56,080
BACKGROUND ABOUT THE WORKING

4550
03:00:56,080 --> 03:00:58,200
GROUP SO THE FOUNDING MEMBERS

4551
03:00:58,200 --> 03:01:01,720
ARE ON THE SCREEN HERE SO MYSELF

4552
03:01:01,720 --> 03:01:03,520
AND ANTHONY AND EXCELLENT

4553
03:01:03,520 --> 03:01:04,880
SUPPORT FROM NCATS NOT A

4554
03:01:04,880 --> 03:01:07,360
SURPRISE GIVEN THEIR TISSUE CHIP

4555
03:01:07,360 --> 03:01:09,200
CONSORTIUM ACTIVITIES. SO THEY

4556
03:01:09,200 --> 03:01:10,880
REALLY HELPED PUT US IN TOUCH

4557
03:01:10,880 --> 03:01:12,400
WITH ALL THE FOLKS THAT WERE

4558
03:01:12,400 --> 03:01:14,920
ALREADY GRANTEES UNDER THE NCATS

4559
03:01:14,920 --> 03:01:16,360
TISSUE CHIPS CONSORTIUM AND

4560
03:01:16,360 --> 03:01:17,480
RECEIVED SUPPLEMENTAL FUNDING

4561
03:01:17,480 --> 03:01:19,480
FOR DOING COVID-19 RESEARCH IN

4562
03:01:19,480 --> 03:01:21,640
THEIR PLATFORMS. AND THEN OF

4563
03:01:21,640 --> 03:01:23,880
COURSE WE ABSOLUTELY NEEDED TO

4564
03:01:23,880 --> 03:01:26,560
ENGAGE WITH NIAID AND MARK

4565
03:01:26,560 --> 03:01:29,880
WILLIAMS FROM D MID HAS BEEN A

4566
03:01:29,880 --> 03:01:32,320
FANTASTIC RESOURCE. THE U.S.

4567
03:01:32,320 --> 03:01:34,480
ARMY IS DOING REALLY EXCELLENT

4568
03:01:34,480 --> 03:01:36,480
WORK IN THE TISSUE CHIP SPACE

4569
03:01:36,480 --> 03:01:38,960
AND TYLER AND KYLE HAVE PROVIDED

4570
03:01:38,960 --> 03:01:40,560
QUITE LOT OF EXPERTISE AND

4571
03:01:40,560 --> 03:01:42,160
LEADERSHIP OF FOUNDING MEMBERS

4572
03:01:42,160 --> 03:01:44,000
OF THE THIS GROUP AS WELL. SO

4573
03:01:44,000 --> 03:01:47,600
WHO ARE OUR MEMBERSHIP? ONE OF

4574
03:01:47,600 --> 03:01:51,400
THE MAJOR OBJECTIVES WAS TO TRY

4575
03:01:51,400 --> 03:01:53,680
AND ENGAGE REGULATORY DECISION

4576
03:01:53,680 --> 03:01:55,240
MAKERS AND GOVERNMENT AGENCY AS

4577
03:01:55,240 --> 03:01:58,520
MUCH AS POSSIBLE TO START TO

4578
03:01:58,520 --> 03:02:01,600
UNDERSTAND WHAT ARE THE NEEDS IN

4579
03:02:01,600 --> 03:02:03,400
THIS TYPE OF SPACE, SO IN

4580
03:02:03,400 --> 03:02:05,160
INFECTIOUS DISEASE RESEARCH AND

4581
03:02:05,160 --> 03:02:06,760
LOOKING AT NEW THERAPEUTICS IN

4582
03:02:06,760 --> 03:02:08,800
UNDERSTANDING SAFETY AND

4583
03:02:08,800 --> 03:02:10,520
EFFICACY FROM A HUMAN BIOLOGY

4584
03:02:10,520 --> 03:02:12,200
BASED PERSPECTIVE AND GETTING

4585
03:02:12,200 --> 03:02:14,880
THAT FEEDBACK AND THAT DIALOGUE

4586
03:02:14,880 --> 03:02:18,000
WITH REGULATORS SO THAT THE MPS

4587
03:02:18,000 --> 03:02:19,800
COMMUNITY CAN BE BUILDING MODELS

4588
03:02:19,800 --> 03:02:21,680
AND DOING EXPERIMENTS THAT ARE

4589
03:02:21,680 --> 03:02:24,000
GOING TO PROVIDE INFORMATION

4590
03:02:24,000 --> 03:02:26,000
THAT IS VALUABLE TO REGULATORY

4591
03:02:26,000 --> 03:02:28,400
AUTHORITIES. SO WE HAVE

4592
03:02:28,400 --> 03:02:29,520
REPRESENTATIVES FROM DIVISIONS

4593
03:02:29,520 --> 03:02:31,600
BRANCHES OR CENTERS OF ALL OF

4594
03:02:31,600 --> 03:02:33,400
THE AGENCIES YOU SEE ON THE

4595
03:02:33,400 --> 03:02:35,520
SCREEN HERE OBVIOUSLY WE ARE

4596
03:02:35,520 --> 03:02:37,000
PRETTY U.S. CENTRIC BUT WE HAVE

4597
03:02:37,000 --> 03:02:39,720
HAD SOME REALLY GOOD INTERACTION

4598
03:02:39,720 --> 03:02:41,760
WITH EUROPEAN REGULATORS AS

4599
03:02:41,760 --> 03:02:44,120
WELL. WE HAVE QUITE A FEW

4600
03:02:44,120 --> 03:02:46,320
BIOTECH COMPANIES REPRESENTED,

4601
03:02:46,320 --> 03:02:47,680
SO THESE ARE SOME OF THESE ARE

4602
03:02:47,680 --> 03:02:49,280
SPIN OFFS TO SOME OF THESE

4603
03:02:49,280 --> 03:02:52,400
LARGER COMPANIES THAT HAVE

4604
03:02:52,400 --> 03:02:54,160
DEVELOPED MPS MODELS IN THEIR

4605
03:02:54,160 --> 03:02:56,520
OWN RIGHT AND COVERING A WIDE

4606
03:02:56,520 --> 03:03:00,200
VARIETY OF ORGANS. THEN WE HAVE

4607
03:03:00,200 --> 03:03:01,920
PARTICIPATION FROM LARGE

4608
03:03:01,920 --> 03:03:02,840
PHARMACEUTICAL COMPANIES THAT

4609
03:03:02,840 --> 03:03:04,480
ARE QUITE INTERESTED IN USING

4610
03:03:04,480 --> 03:03:07,560
THESE MPS PLATFORMS TO TEST

4611
03:03:07,560 --> 03:03:08,680
THINGS LIKE NEW THERAPEUTICS

4612
03:03:08,680 --> 03:03:12,040
THAT ARE IN THEIR PIPELINE. THEN

4613
03:03:12,040 --> 03:03:15,280
THE LARGEST CONTINGENT WE HAVE

4614
03:03:15,280 --> 03:03:16,800
REPRESENTATION FROM IS THE

4615
03:03:16,800 --> 03:03:18,800
ACADEMIC RESEARCHERS BECAUSE A

4616
03:03:18,800 --> 03:03:20,720
LOT OF THE CUTTING EDGE SCIENCE

4617
03:03:20,720 --> 03:03:23,640
AND LOT OF REALLY EXCITING WORK

4618
03:03:23,640 --> 03:03:26,320
IN MPS IS GOING ON IN ACADEMIC

4619
03:03:26,320 --> 03:03:28,880
LAB SO H IS JUST A SLIDE ONE OF

4620
03:03:28,880 --> 03:03:32,240
TWO SO WE HAVE GROUPS FROM ALL

4621
03:03:32,240 --> 03:03:34,640
OF THESE DIFFERENT INSTITUTIONS

4622
03:03:34,640 --> 03:03:37,640
REPRESENTED ON THE MPS CORE

4623
03:03:37,640 --> 03:03:40,480
WORKING GROUP. SOME -- QUITE FEW

4624
03:03:40,480 --> 03:03:42,520
MEMBERS HAVE PRESENTED IN THIS

4625
03:03:42,520 --> 03:03:44,280
WORKSHOP OVER LAST DAY AND A

4626
03:03:44,280 --> 03:03:46,280
HALF. THEN THIS IS OUR SECOND

4627
03:03:46,280 --> 03:03:49,520
SLIDE SHOWING AFFILIATIONS.

4628
03:03:49,520 --> 03:03:52,200
AGAIN REALLY INTERNATIONAL

4629
03:03:52,200 --> 03:03:55,720
PRESENCE SO NOT JUST EU AND U.S.

4630
03:03:55,720 --> 03:03:58,320
AND NORTH AMERICA AND UK BUT

4631
03:03:58,320 --> 03:03:59,640
ALSO WE HAVE REPRESENTATION FROM

4632
03:03:59,640 --> 03:04:04,400
ASIA, LATIN AMERICA AS WELL.

4633
03:04:04,400 --> 03:04:05,800
WHAT WERE THE OBJECTIVES

4634
03:04:05,800 --> 03:04:07,040
INFORMING THIS WORKING GROUP?

4635
03:04:07,040 --> 03:04:09,000
FIRST AND FOREMOST IT WAS TO

4636
03:04:09,000 --> 03:04:11,600
UNITE A SAFE SPACE FOR

4637
03:04:11,600 --> 03:04:15,480
COMMUNICATIONS AND ENGAGEMENT

4638
03:04:15,480 --> 03:04:18,560
AMONG RESEARCHERS TRYING TO

4639
03:04:18,560 --> 03:04:19,560
UNDERSTAND COVID DISEASE

4640
03:04:19,560 --> 03:04:21,160
MECHANISMS, TRYING TO COME UP

4641
03:04:21,160 --> 03:04:22,960
WITH PLATFORMSNA ARE MUCH MORE

4642
03:04:22,960 --> 03:04:26,360
HUMAN RELEVANT TO UNDERSTAND THE

4643
03:04:26,360 --> 03:04:29,840
PATHOPHYSIOLOGY AND TEST NEW

4644
03:04:29,840 --> 03:04:32,640
THERAPEUTICS TO RAISE THAT

4645
03:04:32,640 --> 03:04:35,200
AWARENESS OF MPS TECHNOLOGIES

4646
03:04:35,200 --> 03:04:37,000
AND UTILITY WITH RESPECT TO

4647
03:04:37,000 --> 03:04:38,480
COVID-19 BUT ALSO WITH RESPECT

4648
03:04:38,480 --> 03:04:41,040
TO FUTURE INFECTIOUS DISEASE

4649
03:04:41,040 --> 03:04:44,880
RESEARCH. TO TRY TO FACILITATE

4650
03:04:44,880 --> 03:04:47,600
CONNECTIONS BETWEEN FOLKS

4651
03:04:47,600 --> 03:04:48,880
DEVELOPING TECHNOLOGY AND END

4652
03:04:48,880 --> 03:04:51,320
USERS OF TECHNOLOGIES FROM A

4653
03:04:51,320 --> 03:04:52,480
PHARMACEUTICAL DRUG DEVELOPMENT

4654
03:04:52,480 --> 03:04:55,680
STANDPOINT OR FROM A SAFETY

4655
03:04:55,680 --> 03:04:56,920
ASSURANCE STANDPOINT REGULATORY

4656
03:04:56,920 --> 03:05:04,600
DECISION MAKING STAND POINT. I

4657
03:05:04,600 --> 03:05:05,840
TOUCHED THIS BUT ONE IMPORTANT

4658
03:05:05,840 --> 03:05:08,000
ASPECT IS TO HAVE DIALOGUE WITH

4659
03:05:08,000 --> 03:05:09,640
REGULAR REGULATORY AUTHORITY TO

4660
03:05:09,640 --> 03:05:13,960
UNDERSTAND NEEDS DECISION

4661
03:05:13,960 --> 03:05:18,600
CONTEXT, AND HOW MODELS ARE

4662
03:05:18,600 --> 03:05:19,560
CHARACTERIZED IN TERMS OF

4663
03:05:19,560 --> 03:05:20,640
PERFORMANCE AND READINESS

4664
03:05:20,640 --> 03:05:21,640
CRITERIAND USED TO SUPPORT

4665
03:05:21,640 --> 03:05:25,360
THINGS LIKE IND APPLICATIONS OR

4666
03:05:25,360 --> 03:05:27,040
DEMONSTRATIONS OF EFFICACY AND

4667
03:05:27,040 --> 03:05:29,600
SAFETY THAT MIGHT BE FIT FOR

4668
03:05:29,600 --> 03:05:33,680
REGULATORY CONTEXT AND USE.  

4669
03:05:33,680 --> 03:05:38,000
ALSO TO MAKE CONNECTIONS AND

4670
03:05:38,000 --> 03:05:41,320
HAVE PEOPLE HAVE ACCESS TO

4671
03:05:41,320 --> 03:05:42,160
PRE-CLINICAL DATA CLINICAL

4672
03:05:42,160 --> 03:05:44,040
TRIALS DATA AND ASSESS WHAT IS

4673
03:05:44,040 --> 03:05:48,240
THE VALUE OF INFORMATION GAINED

4674
03:05:48,240 --> 03:05:50,640
FROM MPS MODEL AND HOW THAT

4675
03:05:50,640 --> 03:05:54,440
COMPARES TO THE EXISTING GOLD

4676
03:05:54,440 --> 03:05:55,440
STANDARD AND ARE WE GETTING MORE

4677
03:05:55,440 --> 03:05:58,920
INSIGHT TO THE HUMAN BIOLOGY AND

4678
03:05:58,920 --> 03:06:01,680
THE HUMAN RESPONSE TO DISEASE

4679
03:06:01,680 --> 03:06:06,360
AND THERAPEUTICS IN SUPPORT OF

4680
03:06:06,360 --> 03:06:08,320
OBJECTIVES ON ANIMAL WELFARE AND

4681
03:06:08,320 --> 03:06:09,920
REDUCING REPLACING REFINING

4682
03:06:09,920 --> 03:06:12,160
ANIMAL TESTING. THREE Rs,

4683
03:06:12,160 --> 03:06:14,200
THERE HAVE BEEN A HUGE NUMBER OF

4684
03:06:14,200 --> 03:06:15,400
PUBLICATIONS THAT COME OUT IN

4685
03:06:15,400 --> 03:06:17,280
THIS FIELD OVER THE LAST TWO

4686
03:06:17,280 --> 03:06:18,960
YEARS. THE VERY END AT THE TOP I

4687
03:06:18,960 --> 03:06:20,520
WILL HIGHLIGHT OUR WEBSITE WHERE

4688
03:06:20,520 --> 03:06:22,640
YOU CAN FIND MORE INFORMATION

4689
03:06:22,640 --> 03:06:24,720
ABOUT THIS WORKING GROUP AND

4690
03:06:24,720 --> 03:06:27,320
ALSO FIND A SURVEY OF THE

4691
03:06:27,320 --> 03:06:28,640
LITERATURE SPECIFICALLY THE

4692
03:06:28,640 --> 03:06:32,280
LITERATURE ON MPS AND COVID

4693
03:06:32,280 --> 03:06:33,560
RESEARCH, CURRENT AS OF END OF

4694
03:06:33,560 --> 03:06:37,640
LAST YEAR. SO I CAN'T HIGHLIGHT

4695
03:06:37,640 --> 03:06:39,120
THE LARGE, LARGE NUMBER OF

4696
03:06:39,120 --> 03:06:40,160
PUBLICATIONS THAT HAVE COME OUT

4697
03:06:40,160 --> 03:06:42,920
IN THIS AREA OR FROM GROUP

4698
03:06:42,920 --> 03:06:43,920
MEMBERS SPECIFICALLY BUT I WANT

4699
03:06:43,920 --> 03:06:46,920
TO HIGHLIGHT A COUPLE OF

4700
03:06:46,920 --> 03:06:51,640
PUBLICATIONS ONE WAS A FEATURE

4701
03:06:51,640 --> 03:06:55,520
ARTICLE THAT WAS PUBLISHED IN

4702
03:06:55,520 --> 03:06:56,880
DRUG DISCOVERY THAT ANTHONY AND

4703
03:06:56,880 --> 03:07:00,040
I CO-AUTHORED TO TALK ABOUT THE

4704
03:07:00,040 --> 03:07:00,920
INTROINTRODUCE THE CORE WORKING

4705
03:07:00,920 --> 03:07:01,720
GROUP TO THE SCIENTIFIC

4706
03:07:01,720 --> 03:07:02,560
COMMUNITY BUT ALSO TALK ABOUT

4707
03:07:02,560 --> 03:07:05,120
THE CHALLENGES THAT ARE

4708
03:07:05,120 --> 03:07:07,560
AFFECTING THE UTILITY AND THE

4709
03:07:07,560 --> 03:07:11,640
ADOPTION OF MPS FOR SARS COV-2

4710
03:07:11,640 --> 03:07:13,480
RESEARCH AND DRUG DEVELOPMENT SO

4711
03:07:13,480 --> 03:07:15,920
WE SENT A SURVEY TO THE MPS FOR

4712
03:07:15,920 --> 03:07:17,240
WORKING GROUP MEMBERS AND ASKED

4713
03:07:17,240 --> 03:07:20,920
THEM TO SELECT THEIR TOP THREE

4714
03:07:20,920 --> 03:07:22,120
SCIENTIFIC PRACTICAL CHALLENGES

4715
03:07:22,120 --> 03:07:25,160
OR BARRIERS THAT ARE AFFECTING

4716
03:07:25,160 --> 03:07:29,160
THE USE OF MPS FOR SARS COV-2

4717
03:07:29,160 --> 03:07:31,840
AND COVID RESEARCH. SO YOU CAN

4718
03:07:31,840 --> 03:07:34,120
SEE SOME OF THE ANSWERS WE GOT

4719
03:07:34,120 --> 03:07:39,840
BACK ON THE SLIDE HERE. SO THE

4720
03:07:39,840 --> 03:07:41,960
TOP CHALLENGE FROM SCIENTIFIC

4721
03:07:41,960 --> 03:07:43,800
STANDPOINT WAS INCORPORATING

4722
03:07:43,800 --> 03:07:47,520
HOST IMMUNE AND CORE IMMUNE

4723
03:07:47,520 --> 03:07:48,840
COMPONENTS FOLLOWED BY THINGS

4724
03:07:48,840 --> 03:07:51,600
LIKE PERFORMANCE CRITERIA, THEN

4725
03:07:51,600 --> 03:07:53,920
ACCESS TO TISSUES, AND ACCESS TO

4726
03:07:53,920 --> 03:07:56,760
TISSUE AND CELL SOURCES. BOTH

4727
03:07:56,760 --> 03:07:59,520
NORMAL HUMAN TISSUES DISEASED

4728
03:07:59,520 --> 03:08:01,440
HUMAN TISSUES AND THERE WERE

4729
03:08:01,440 --> 03:08:03,520
SOME OTHER CHALLENGES THAT WERE

4730
03:08:03,520 --> 03:08:07,080
TECHNICAL IN NATURE LIKE PBMS

4731
03:08:07,080 --> 03:08:10,120
DRUG BINDING AND OTHERS THAT

4732
03:08:10,120 --> 03:08:14,920
WERE MORE I THINK PRACTICAL IN

4733
03:08:14,920 --> 03:08:16,960
NATURE, DARE I SAY PHILOSOPHICAL

4734
03:08:16,960 --> 03:08:18,440
IN TERMS OF LACK OF CONFIDENCE

4735
03:08:18,440 --> 03:08:21,760
IN MODELS OR WARENESS OF THE

4736
03:08:21,760 --> 03:08:23,560
MODEL AND CONTEXT OF USE. ON THE

4737
03:08:23,560 --> 03:08:26,680
PRACTICAL CHALLENGES SIDE THERE

4738
03:08:26,680 --> 03:08:30,240
WAS AGAIN ISSUES AROUND RESOURCE

4739
03:08:30,240 --> 03:08:32,640
ALLOTMENT SO FUNDING BY FAR, THE

4740
03:08:32,640 --> 03:08:34,120
NUMBER ONE ISSUE BUT ALSO ACCESS

4741
03:08:34,120 --> 03:08:36,800
TO BSL 3 FACILITIES, THE ABILITY

4742
03:08:36,800 --> 03:08:40,640
TO WORK WITH LIVE VIRUS REQUIRES

4743
03:08:40,640 --> 03:08:42,920
YOU HAVE THIS BIOSAFETY LEVEL OF

4744
03:08:42,920 --> 03:08:44,600
THREE OR FOUR AND THOSE ARE NOT

4745
03:08:44,600 --> 03:08:45,960
ONLY CHALLENGING TO FIND BUT

4746
03:08:45,960 --> 03:08:47,520
ALSO CHALLENGING TO WORK IN EVEN

4747
03:08:47,520 --> 03:08:50,520
ONCE YOU HAVE ACCESS TO THEM. SO

4748
03:08:50,520 --> 03:08:53,560
SOME OF THESE CHALLENGES THAT WE

4749
03:08:53,560 --> 03:08:54,880
ACCUMULATED FROM THESE SURVEY OF

4750
03:08:54,880 --> 03:08:56,560
OUR MEMBERSHIP ARE BEING

4751
03:08:56,560 --> 03:08:58,360
ADDRESSED BY INTERACTION AND

4752
03:08:58,360 --> 03:09:02,400
DISCUSSION AMONG OUR MEMBERSHIP.

4753
03:09:02,400 --> 03:09:04,040
AND BY SPECIFIC PROJECTS WE

4754
03:09:04,040 --> 03:09:05,120
SUPPORT THROUGH THIS WORK GROUP

4755
03:09:05,120 --> 03:09:06,480
I WILL TALK ABOUT A LITTLE BIT

4756
03:09:06,480 --> 03:09:07,840
LATER. THE OTHER PUBLICATION I

4757
03:09:07,840 --> 03:09:09,360
WANT TO HIGHLIGHT BUT WON'T

4758
03:09:09,360 --> 03:09:10,400
SPEND MUCH TIME ON BECAUSE YOU

4759
03:09:10,400 --> 03:09:12,200
ARE HEAR MORE ABOUT THIS WORK

4760
03:09:12,200 --> 03:09:17,920
LATER IN THIS SESSION FROM

4761
03:09:17,920 --> 03:09:18,560
THOMAS HARTUNG BUT THOUGHT IT

4762
03:09:18,560 --> 03:09:21,520
WAS A NICE PUBLICATION THAT WAS

4763
03:09:21,520 --> 03:09:23,720
AN ILLUSTRATION HOW MPS ARE

4764
03:09:23,720 --> 03:09:28,320
ABSOLUTELY CRITICAL RESOURCE FOR

4765
03:09:28,320 --> 03:09:31,200
COVID-19 RESEARCH AND IN THIS

4766
03:09:31,200 --> 03:09:32,560
CASE PARTNER WITH THE JOHNS

4767
03:09:32,560 --> 03:09:35,520
HOPKINS GROUP AND NIAID

4768
03:09:35,520 --> 03:09:38,440
RESEARCHERS TO DO SURVEY OF THE

4769
03:09:38,440 --> 03:09:40,440
LITERATURE OF ORIGINAL RESEARCH

4770
03:09:40,440 --> 03:09:44,280
ON SARS COV-2 NEUROTROPISM.

4771
03:09:44,280 --> 03:09:46,760
USING BRAIN ORGANOID MODELS. I

4772
03:09:46,760 --> 03:09:48,360
WON'T SPOIL WHAT THOMAS IS GOING

4773
03:09:48,360 --> 03:09:50,280
TO TELL YOU BUT WE ALSO LOOKED

4774
03:09:50,280 --> 03:09:54,080
AT SYMPTOMS OF COVID-19 PATIENTS

4775
03:09:54,080 --> 03:09:55,400
ASSOCIATED WITH CENTRAL NERVOUS

4776
03:09:55,400 --> 03:09:56,760
SYSTEM AND THEN FROM THAT

4777
03:09:56,760 --> 03:09:58,680
SUGGESTED WHAT THE KEY

4778
03:09:58,680 --> 03:10:01,560
MECHANISMS OF SO CALLED

4779
03:10:01,560 --> 03:10:03,760
NEUROCOVID MIGHT BE IN TERMS OF

4780
03:10:03,760 --> 03:10:06,800
HOW INFECTION IN THE BRAIN MIGHT

4781
03:10:06,800 --> 03:10:09,480
LEAD TO ALTER NEUROCHEMICAL

4782
03:10:09,480 --> 03:10:12,280
LANDSCAPE, ALTER BEHAVIOR, OTHER

4783
03:10:12,280 --> 03:10:12,960
NEUROLOGICAL END POINTS.

4784
03:10:12,960 --> 03:10:15,000
SO THE PROJECTS THAT ARE FUNDED

4785
03:10:15,000 --> 03:10:17,840
DIRECTLY UNDER THE MPS CORE

4786
03:10:17,840 --> 03:10:20,880
WORKING GROUP ARE TWOFOLD. ONE

4787
03:10:20,880 --> 03:10:22,240
IS COLLABORATION BETWEEN MY

4788
03:10:22,240 --> 03:10:28,200
GROUP DOD AND NIAID. THAT IS

4789
03:10:28,200 --> 03:10:29,520
ESTABLISHING ORGAN ON CHIP

4790
03:10:29,520 --> 03:10:31,320
TECHNOLOGY AT THE NIAID

4791
03:10:31,320 --> 03:10:34,080
INTEGRATED RESEARCH FACILITY

4792
03:10:34,080 --> 03:10:36,760
WHICH HAS BEEN IN ANIMAL SHOPS A

4793
03:10:36,760 --> 03:10:38,000
VERY STRONG NON-HUMAN PRIMATE

4794
03:10:38,000 --> 03:10:40,080
PROGRAM AND OTHER ANIMAL MODELS,

4795
03:10:40,080 --> 03:10:41,640
BUT NOW FOR THE FIRST TIME THEY

4796
03:10:41,640 --> 03:10:46,520
HAVE MPS IN HOUSE AND THEY ARE

4797
03:10:46,520 --> 03:10:47,880
CONDUCTING THIS INITIAL PROOF OF

4798
03:10:47,880 --> 03:10:49,640
CONCEPT STUDY THAT WILL ALLOW

4799
03:10:49,640 --> 03:10:51,280
SIDE BY SIDE EVALUATION OF LOW

4800
03:10:51,280 --> 03:10:52,800
AND HIGH COMPLEXITY MODELS ANDLY

4801
03:10:52,800 --> 03:10:55,880
TALK ABOUT THAT IN MORE DETAIL

4802
03:10:55,880 --> 03:10:59,840
THEN THE MPS DATABASE IS A

4803
03:10:59,840 --> 03:11:02,920
WEB-BASED RESOURCE SUPPORTED BY

4804
03:11:02,920 --> 03:11:04,600
NCATS TO ACCELERATE DEVELOPMENT

4805
03:11:04,600 --> 03:11:07,160
AND APPLICATION OF MPS FOR BOTH

4806
03:11:07,160 --> 03:11:09,320
BASIC RESEARCH AND DRUG

4807
03:11:09,320 --> 03:11:11,760
DEVELOPMENT SAFETY AND EFFICACY.

4808
03:11:11,760 --> 03:11:15,000
SO WE HAVE PARTNERED WITH THOSE

4809
03:11:15,000 --> 03:11:17,960
DEVELOPERS TO PROVIDE ADDITIONAL

4810
03:11:17,960 --> 03:11:19,800
SUPPLEMENTARY FUNDING TO EXPAND

4811
03:11:19,800 --> 03:11:22,160
THE PLATFORM AND INCLUDE

4812
03:11:22,160 --> 03:11:23,560
COVID-19 DISEASE PORTAL. I WILL

4813
03:11:23,560 --> 03:11:25,160
SHOW YOU WHAT THAT LOOKS LIKE IN

4814
03:11:25,160 --> 03:11:30,320
A SECOND. SO FIRST THE NIAID

4815
03:11:30,320 --> 03:11:33,920
COLLABORATION. ESTABLISHING THE

4816
03:11:33,920 --> 03:11:39,160
LUNG CHIP TECHNOLOGY AT THE IRF

4817
03:11:39,160 --> 03:11:41,400
AND THEN DOING SOME EXPERIMENTS

4818
03:11:41,400 --> 03:11:44,080
IN BOTH BSL 2 AND 4 ENVIRONMENTS

4819
03:11:44,080 --> 03:11:45,760
STARTING WITH SOME SYNTHETIC

4820
03:11:45,760 --> 03:11:50,480
HUMAN DERIVED ANTIBODIES THAT

4821
03:11:50,480 --> 03:11:52,120
DEMONSTRATED EFFICACY POTENCY

4822
03:11:52,120 --> 03:11:54,800
AGAINST SARS COV-2 ENTERING

4823
03:11:54,800 --> 03:11:55,880
HUMAN CLINICAL TRIALS IN EUROPE

4824
03:11:55,880 --> 03:12:00,880
AND CANADA. BEING ABLE TO DO

4825
03:12:00,880 --> 03:12:01,760
THIS SIDE BY SIDE EVALUATION OF

4826
03:12:01,760 --> 03:12:03,440
LOW AND HIGH COMPLEXITY MODELS

4827
03:12:03,440 --> 03:12:08,480
BY COMPARING TYPICAL IN VITRO

4828
03:12:08,480 --> 03:12:10,760
CELL CULTURE LIKE VIRO CELLS

4829
03:12:10,760 --> 03:12:13,120
WITH MPS MODELS WITH ANIMAL

4830
03:12:13,120 --> 03:12:15,160
MODELS LIKE THE GOLDMAN HAMSTER

4831
03:12:15,160 --> 03:12:18,120
WITH HUMAN DATA FROM CLINICAL

4832
03:12:18,120 --> 03:12:21,920
TRIALS, TO UNDERSTAND WHAT IS

4833
03:12:21,920 --> 03:12:23,200
VALUE OF INFORMATION GAINED FROM

4834
03:12:23,200 --> 03:12:28,200
USING THESE MORE HUMAN RELEVANT

4835
03:12:28,200 --> 03:12:31,480
MPS PLATFORMS. THEN THE MPS KB

4836
03:12:31,480 --> 03:12:34,960
IS NOW CALLED BIOSTATISTICS

4837
03:12:34,960 --> 03:12:36,400
ANALYTIC PLATFORM, PART OF THEIR

4838
03:12:36,400 --> 03:12:39,720
GRANT FROM NCATS OR FUNDING FROM

4839
03:12:39,720 --> 03:12:41,600
NCATS INCLUDES COMMERCIALIZATION

4840
03:12:41,600 --> 03:12:42,720
PHASE SO MY UNDERSTANDING IS

4841
03:12:42,720 --> 03:12:46,280
THAT IT WILL CONTINUE TO BE FREE

4842
03:12:46,280 --> 03:12:47,760
OF ACCESS TO CERTAIN CUSTOMERS

4843
03:12:47,760 --> 03:12:50,760
LIKE ACADEMIC AND GOVERNMENT

4844
03:12:50,760 --> 03:12:52,880
INSTITUTIONS BUT FOR THINGS LIKE

4845
03:12:52,880 --> 03:12:54,520
LARGE PHARMACEUTICAL COMPANIES

4846
03:12:54,520 --> 03:12:56,760
THAT ARE DEVELOPING COMMERCIAL

4847
03:12:56,760 --> 03:12:59,200
VERSION THAT WILL ALLOW YOU TO

4848
03:12:59,200 --> 03:13:01,840
DO WORK CONFIDENTIALLY BEHIND A

4849
03:13:01,840 --> 03:13:03,640
FIREWALL AND IT IS PHENOMENAL

4850
03:13:03,640 --> 03:13:04,920
RESOURCE, IF YOU HAVEN'T CHECKED

4851
03:13:04,920 --> 03:13:09,880
IT OUT I ENCOURAGE YOU TO DO SO.

4852
03:13:09,880 --> 03:13:11,920
THERE ARE NOT ONLY IS THERE

4853
03:13:11,920 --> 03:13:13,920
INFORMATION ABOUT DIFFERENT MPS

4854
03:13:13,920 --> 03:13:16,320
MODELS AND UTILITY AND DIFFERENT

4855
03:13:16,320 --> 03:13:18,040
PROJECTS AND EXPERIMENTS

4856
03:13:18,040 --> 03:13:21,240
ONGOING, THERE IS ALSO

4857
03:13:21,240 --> 03:13:22,720
COMPUTATIONAL TOOLS AND WORK

4858
03:13:22,720 --> 03:13:24,880
FLOWS YOU CAN APPLY TO YOUR OWN

4859
03:13:24,880 --> 03:13:26,240
DATA SO YOU CAN LOOK AT THINGS

4860
03:13:26,240 --> 03:13:30,400
LIKE REPRODUCIBILITY ANALYSES,

4861
03:13:30,400 --> 03:13:32,520
RUN PHYSIOLOGICALLY BASED

4862
03:13:32,520 --> 03:13:34,040
PHARMACOKINETIC MODELS TO

4863
03:13:34,040 --> 03:13:37,160
UNDERSTAND ADME AND TOX AND LOOK

4864
03:13:37,160 --> 03:13:41,480
AT COMPARING SIDE BY SIDE WITH

4865
03:13:41,480 --> 03:13:43,080
OTHER EXPERIMENTS TARGETING

4866
03:13:43,080 --> 03:13:44,840
BIOLOGY OR MECHANISMS INTERESTED

4867
03:13:44,840 --> 03:13:46,360
IN QUERYING. THERE IS AGAIN

4868
03:13:46,360 --> 03:13:49,520
DIFFERENT LEVELS OF SECURITY SO

4869
03:13:49,520 --> 03:13:51,200
YOU CAN LOAD DATA AND

4870
03:13:51,200 --> 03:13:52,680
INFORMATION ABOUT MODEL SYSTEM

4871
03:13:52,680 --> 03:13:53,920
AND KEEP COMPLETELY CONFIDENTIAL

4872
03:13:53,920 --> 03:13:55,960
TO YOURSELF OR YOUR GROUP OR

4873
03:13:55,960 --> 03:13:57,240
SELECT GROUP OF COLLABORATORS OR

4874
03:13:57,240 --> 03:14:02,400
MAKE IT PUBLICLY AVAILABLE. SO

4875
03:14:02,400 --> 03:14:04,280
IT IS A TREMENDOUS RESOURCE. WE

4876
03:14:04,280 --> 03:14:10,160
FUNDED THE DEVELOPMENT OF

4877
03:14:10,160 --> 03:14:12,280
COVID-19 DISEASE WITHIN THE

4878
03:14:12,280 --> 03:14:15,160
BIOSTATISTICS ANALYTICS

4879
03:14:15,160 --> 03:14:17,960
PLATFORM, THAT HAS LOTS OF

4880
03:14:17,960 --> 03:14:19,720
INFORMATION ON IT SO LINKS TO

4881
03:14:19,720 --> 03:14:21,040
RESULTS OF DIFFERENT LITERATURE

4882
03:14:21,040 --> 03:14:22,480
SEARCHES, LINKS TO EXPERIMENTAL

4883
03:14:22,480 --> 03:14:24,440
MODELS THAT ARE ALREADY BEING

4884
03:14:24,440 --> 03:14:28,000
USED FOR COVID-19 DISEASE

4885
03:14:28,000 --> 03:14:29,560
RESEARCH SPANNING THAT WHOLE

4886
03:14:29,560 --> 03:14:33,360
RANGE FROM IN VITRO TO IN VIVO,

4887
03:14:33,360 --> 03:14:36,680
RESOURCES THAT IN TERMS OF

4888
03:14:36,680 --> 03:14:39,880
ACTUAL SUPPLIES YOU NEED TO

4889
03:14:39,880 --> 03:14:40,760
PURCHASE, DIRECT LINKS TO

4890
03:14:40,760 --> 03:14:43,000
INVENTORY TORRS, COMPARING TO

4891
03:14:43,000 --> 03:14:45,440
COMPUTATIONAL MODEL OUTPUTS,

4892
03:14:45,440 --> 03:14:48,200
PRE-CLINICAL DATA, CLINICAL

4893
03:14:48,200 --> 03:14:49,320
DATA, ET CETERA. OUR MEMBERS

4894
03:14:49,320 --> 03:14:52,240
HAVE ACCESS TO A PRIVATE PORTAL

4895
03:14:52,240 --> 03:14:55,640
THAT ALLOWS YOU TO IDENTIFY

4896
03:14:55,640 --> 03:14:58,600
OTHER RESEARCHERS THAT ARE

4897
03:14:58,600 --> 03:15:00,320
WORKING IN THE SAME AREA SO THE

4898
03:15:00,320 --> 03:15:03,520
SAME TISSUE TYPE OF INTEREST OR

4899
03:15:03,520 --> 03:15:06,120
SAME PLATFORM OR MAYBE HAVE BSL

4900
03:15:06,120 --> 03:15:08,400
3 OR 4 FACILITIES AVAILABLE AND

4901
03:15:08,400 --> 03:15:11,200
THIS IS A PRIVATE PORTAL ONLY

4902
03:15:11,200 --> 03:15:12,000
ACCESSIBLE TO WORK GROUP

4903
03:15:12,000 --> 03:15:13,840
MEMBERS. THE MOST RECENT THING

4904
03:15:13,840 --> 03:15:17,280
WE HAVE DONE IS PROVIDED

4905
03:15:17,280 --> 03:15:18,680
ADDITIONAL FUNDING ON TOP OF

4906
03:15:18,680 --> 03:15:21,200
THAT TO CREATE A PORTAL FOR

4907
03:15:21,200 --> 03:15:22,440
INDUCED PLURIPOTENT STEM CELLS.

4908
03:15:22,440 --> 03:15:25,160
THAT WAS ONE CHALLENGE

4909
03:15:25,160 --> 03:15:27,760
IDENTIFIED IN OUR MEMBER SURVEY,

4910
03:15:27,760 --> 03:15:31,760
ACCESS TO IPSCs AND ACCESS TO

4911
03:15:31,760 --> 03:15:33,640
INFORMATION ABOUT IPSCs SO

4912
03:15:33,640 --> 03:15:38,880
WELL CHARACTERIZED CELLS. HERE

4913
03:15:38,880 --> 03:15:41,440
WE HAVE INFORMATION AND LINKS ON

4914
03:15:41,440 --> 03:15:44,560
HOW TO OBTAIN CELLS, WHAT ARE

4915
03:15:44,560 --> 03:15:45,840
CHARACTERISTICS, HOW TO USE THEM

4916
03:15:45,840 --> 03:15:48,440
PROTOCOLS ET CETERA, SO

4917
03:15:48,440 --> 03:15:50,720
CURRENTLY WITHIN THE IPSC PORTAL

4918
03:15:50,720 --> 03:15:52,160
FOR EACH INSTANCE WE HAVE THE

4919
03:15:52,160 --> 03:15:53,880
DIFFERENT CHARACTERISTICS LIKE

4920
03:15:53,880 --> 03:15:56,960
THE DIFFERENTIATION, LEVEL AND

4921
03:15:56,960 --> 03:15:58,920
STATUS AND PHENOTYPES, THE

4922
03:15:58,920 --> 03:16:01,840
PATIENT PROFILES WITH CELLS

4923
03:16:01,840 --> 03:16:08,760
DERIVED FROM, SOURCE OF CELLS

4924
03:16:08,760 --> 03:16:10,280
PROTOCOLLINGS AND ESTABLISHED

4925
03:16:10,280 --> 03:16:13,400
APPLICATION SO WE HAVE NUMBER OF

4926
03:16:13,400 --> 03:16:16,720
RESOURCES AVAILABLE THIS IS THE

4927
03:16:16,720 --> 03:16:18,880
MAIN WEBSITE ON THE NICE ATM

4928
03:16:18,880 --> 03:16:28,240
HOME PAGE TO ACCESS WE HAD

4929
03:16:28,240 --> 03:16:29,880
SATELLITE TISSUE SHIP CONSORTIUM

4930
03:16:29,880 --> 03:16:31,360
MEETING AND FULL RECORDING IS

4931
03:16:31,360 --> 03:16:33,960
AVAILABLE SO REALLY TREMENDOUS

4932
03:16:33,960 --> 03:16:38,320
PRESENTATIONS, FROM OUR MEMBERS.

4933
03:16:38,320 --> 03:16:41,040
WE ALSO HAVE INTERNAL WEBINARS

4934
03:16:41,040 --> 03:16:44,800
NOT MADE PUBLICLY AVAILABLE BUT

4935
03:16:44,800 --> 03:16:47,000
INTENDED TO CONNECT RESEARCHERS

4936
03:16:47,000 --> 03:16:50,000
TOGETHER AND TROUBLESHOOT

4937
03:16:50,000 --> 03:16:53,840
HANDSOME APPROXIMATE FOLKS MAYBE

4938
03:16:53,840 --> 03:16:54,560
ENCOUNTERING, ALSO A

4939
03:16:54,560 --> 03:16:55,240
DISTRIBUTION LIST FOR THAT

4940
03:16:55,240 --> 03:16:58,240
PURPOSE. MY GROUP IS WE HAVE

4941
03:16:58,240 --> 03:16:59,800
EXPERTS IN VALIDATION OF

4942
03:16:59,800 --> 03:17:03,400
ALTERNATIVES AND WE HAVE OTHER

4943
03:17:03,400 --> 03:17:06,240
MEMBERS EXPERT IN THAT SPACE, SO

4944
03:17:06,240 --> 03:17:10,120
HAPPY TO HELP PROVIDE STUDY

4945
03:17:10,120 --> 03:17:10,920
DESIGN SUPPORT, DISTRIBUTE

4946
03:17:10,920 --> 03:17:11,800
INFORMATION ON FUNDING

4947
03:17:11,800 --> 03:17:14,120
MECHANISMS AND TRYING TO ENGAGE

4948
03:17:14,120 --> 03:17:15,680
AS MUCH AS POSSIBLE WITH

4949
03:17:15,680 --> 03:17:19,480
REGULATORY DECISION MAKERS. ONE

4950
03:17:19,480 --> 03:17:20,960
REALLY EXCITING ACTIVITY WE

4951
03:17:20,960 --> 03:17:24,240
PARTICIPATED IN AT THE END OF

4952
03:17:24,240 --> 03:17:26,960
LAST YEAR THROUGH SIMON FUNNELL

4953
03:17:26,960 --> 03:17:29,240
AND WHO WAS TRYING TO ENGAGE TO

4954
03:17:29,240 --> 03:17:30,840
IDENTIFY MPS RESEARCHERS THAT

4955
03:17:30,840 --> 03:17:33,040
MIGHT BE READY TO HIT THE GROUND

4956
03:17:33,040 --> 03:17:34,680
RUNNING TO START DOING

4957
03:17:34,680 --> 03:17:36,480
EXPERIMENTS ON VARIANTS OF

4958
03:17:36,480 --> 03:17:39,120
CONCERN. PROVIDING THIS AGILE

4959
03:17:39,120 --> 03:17:41,120
RESPONSE NETWORK WHERE THEY

4960
03:17:41,120 --> 03:17:42,480
COULD GO THROUGH WHO

4961
03:17:42,480 --> 03:17:44,360
DISTRIBUTION NETWORK AND GET THE

4962
03:17:44,360 --> 03:17:45,520
VARIANTS OF CONCERN AND

4963
03:17:45,520 --> 03:17:47,160
IMMEDIATELY TEST THEM AS THEY

4964
03:17:47,160 --> 03:17:51,040
ARISE AND EMERGE. THEN THEY

4965
03:17:51,040 --> 03:17:54,160
ALREADY MENTIONED MPS DB

4966
03:17:54,160 --> 03:17:54,960
BIOSTATISTICS PORTAL IS

4967
03:17:54,960 --> 03:17:55,840
FANTASTIC AND ON THEIR WEBSITE

4968
03:17:55,840 --> 03:17:58,200
THEY HAVE A NUMBER OF TRAINING

4969
03:17:58,200 --> 03:17:59,440
RESOURCES AVAILABLE THAT

4970
03:17:59,440 --> 03:18:03,360
ENCOURAGE YOU TO CHECK OUT.  SO

4971
03:18:03,360 --> 03:18:04,440
I WILL STOP THERE, THANK YOU FOR

4972
03:18:04,440 --> 03:18:07,080
YOUR TIME AND SAY IF YOU ARE NOT

4973
03:18:07,080 --> 03:18:09,680
A MEMBER OF THE MPS CORE WORK

4974
03:18:09,680 --> 03:18:10,520
GROUP ALWAYSOR AND WOULD LIKE TO

4975
03:18:10,520 --> 03:18:12,320
BE YOU DON'T HAVE TO ACTIVELY DO

4976
03:18:12,320 --> 03:18:14,680
COVID OR SARS COV-2 RESEARCH IN

4977
03:18:14,680 --> 03:18:17,640
MPS TO BE MEMBER, YOU CAN SIMPLY

4978
03:18:17,640 --> 03:18:20,160
BE DOING MPS RESEARCH OR JUST DO

4979
03:18:20,160 --> 03:18:21,320
COVID RESEARCH OR JUST BE

4980
03:18:21,320 --> 03:18:22,840
INTERESTED IN GETTING INTO THIS

4981
03:18:22,840 --> 03:18:25,720
SPACE. HAPPY TO HAVE YOU PLEASE

4982
03:18:25,720 --> 03:18:34,400
REACH OUT. THANKS.

4983
03:18:34,400 --> 03:18:35,840
>> THANK YOU VERY MUCH,
NICOLE,

4984
03:18:35,840 --> 03:18:36,880
WONDERFUL TALK. REALLY

4985
03:18:36,880 --> 03:18:38,520
INTERESTING INFORMATION AND SURE

4986
03:18:38,520 --> 03:18:39,320
THERE WILL BE PLENTY OF

4987
03:18:39,320 --> 03:18:40,080
QUESTIONS AT THE END OF THE

4988
03:18:40,080 --> 03:18:45,560
SESSION. OUR NEXT SPEAKER IS EVI

4989
03:18:45,560 --> 03:18:49,800
STRUBLE WHO IS A RESEARCH

4990
03:18:49,800 --> 03:18:51,920
PHARMACOLOGIST DERIVATIVES

4991
03:18:51,920 --> 03:18:52,880
BRANCH DIVISION OF PLASMA

4992
03:18:52,880 --> 03:18:55,160
PROTEIN THERAPEUTICS OFFICE OF

4993
03:18:55,160 --> 03:18:58,520
TISSUE CENTER FOR EVALUATION

4994
03:18:58,520 --> 03:18:59,640
BIOLOGICS AND RESEARCH AT THE

4995
03:18:59,640 --> 03:19:00,400
U.S. FOOD AND DRUG

4996
03:19:00,400 --> 03:19:03,600
ADMINISTRATION.  Ph.D. IN

4997
03:19:03,600 --> 03:19:04,800
BIOPHYSICS FROM JOHNS HOPKINS

4998
03:19:04,800 --> 03:19:05,520
UNIVERSITY POST-DOCTORAL

4999
03:19:05,520 --> 03:19:06,640
TRAINING AT THE NATIONAL

5000
03:19:06,640 --> 03:19:09,840
INSTITUTE OF STANDARDS AND

5001
03:19:09,840 --> 03:19:11,560
TECHNOLOGY. SHE IS RESEARCH

5002
03:19:11,560 --> 03:19:13,680
PHARMACOLOGIST AT CBER FDA SHE

5003
03:19:13,680 --> 03:19:16,120
PERFORMS REGULATORY

5004
03:19:16,120 --> 03:19:17,320
APPLICATIONS, AND ADDITIONALLY

5005
03:19:17,320 --> 03:19:20,960
RELATED RESEARCH.  AS A RESEARCH

5006
03:19:20,960 --> 03:19:25,400
SCIENTIST DR. STRUBLE EXAMINES

5007
03:19:25,400 --> 03:19:27,400
ANIMAL SAFETY DRUGS DURING

5008
03:19:27,400 --> 03:19:29,920
PREGNANPREGNANCY. RECENT WORK ON

5009
03:19:29,920 --> 03:19:32,280
THERAPIES FOR ZEKA VIRAL

5010
03:19:32,280 --> 03:19:34,240
INFECTION. THE TITLE OF HER TALK

5011
03:19:34,240 --> 03:19:36,080
TODAY IS MICROPHYSIOLOGICAL

5012
03:19:36,080 --> 03:19:39,280
SYSTEMS FOR EVALUATING IGG

5013
03:19:39,280 --> 03:19:41,280
ANTIVIRALS DURING PREGNANCY.  

5014
03:19:41,280 --> 03:19:42,400
EVI. 

5015
03:19:42,400 --> 03:19:48,000
>> THANK YOU. THANK YOU
FOR THE

5016
03:19:48,000 --> 03:19:49,680
INVITATION TO TALK. LET ME SHARE

5017
03:19:49,680 --> 03:20:00,200
MY SCREEN. DO YOU SEE MY SLIDES

5018
03:20:01,160 --> 03:20:01,760
SM

5019
03:20:01,760 --> 03:20:04,360
>> YOU NEED TO SHIFT TO SO
WE

5020
03:20:04,360 --> 03:20:06,040
CAN SEE -- YOU ARE IN PRESENTER

5021
03:20:06,040 --> 03:20:08,240
MODE SO WE SEE THE PRESENTER

5022
03:20:08,240 --> 03:20:08,480
MODE.

5023
03:20:08,480 --> 03:20:18,760
>> UNDERSTAND. OKAY.

5024
03:20:18,760 --> 03:20:24,560
>> I THINK YOU CAN SWAP ON
THAT

5025
03:20:24,560 --> 03:20:24,760
BUT --

5026
03:20:24,760 --> 03:20:28,520
>> IF YOU GO BACK TO SHARE

5027
03:20:28,520 --> 03:20:32,040
POWERPOINT AGAIN, YOU CAN DO IT

5028
03:20:32,040 --> 03:20:41,400
FROM THERE.  CLICK NEW SHARE,

5029
03:20:41,400 --> 03:20:48,040
FROM THERE

5030
03:20:48,040 --> 03:20:48,840
>> IS IT BETTER?

5031
03:20:48,840 --> 03:20:59,320
>> NO, GO BACK TO
POWERPOINT

5032
03:21:00,520 --> 03:21:08,360
AGAIN. YOUR INTERFACE IS

5033
03:21:08,360 --> 03:21:12,600
DIFFERENDIFFERENT. DOWN AT THE M

5034
03:21:12,600 --> 03:21:15,680
NEXT TO THREE DOTS, WHAT THAT

5035
03:21:15,680 --> 03:21:16,880
ONE?

5036
03:21:16,880 --> 03:21:18,200
>> HIDE PRESENTER VIEW?

5037
03:21:18,200 --> 03:21:24,440
>> DON'T DO THAT. NEXT TO
LEFT

5038
03:21:24,440 --> 03:21:25,880
OVER. WHAT IS THAT ONE?

5039
03:21:25,880 --> 03:21:30,240
>> THAT IS SUBTITLE.

5040
03:21:30,240 --> 03:21:33,000
>> INITIALLY IS ON TOP,
THE

5041
03:21:33,000 --> 03:21:33,280
SECOND --

5042
03:21:33,280 --> 03:21:34,720
>> USUALLY ON TOP

5043
03:21:34,720 --> 03:21:36,440
>> SO PROBABLY HIDDEN
BEHIND

5044
03:21:36,440 --> 03:21:46,600
THAT BAR.

5045
03:21:50,880 --> 03:21:53,800
>> STOP SHARING AND I WILL
MOVE

5046
03:21:53,800 --> 03:22:01,200
IT TO GET PRESENTER SCREEN.

5047
03:22:01,200 --> 03:22:03,400
>> SORRY I CAN'T SEE WHAT
THE

5048
03:22:03,400 --> 03:22:08,440
BUTTON IS IS. ARE YOU ON A MAC?

5049
03:22:08,440 --> 03:22:12,480
>> NO. THE THE WEB
INTERFACE OF

5050
03:22:12,480 --> 03:22:23,160
ZOOM? TH SO SHARE SCREEN AGAIN. 

5051
03:22:36,120 --> 03:22:37,840
NEED TO GO BACK OVER -- OKAY

5052
03:22:37,840 --> 03:22:44,440
FROM HERE WE JUST NEED TO

5053
03:22:44,440 --> 03:22:47,520
>> IF YOU HOVER ON TOP
RIGHT

5054
03:22:47,520 --> 03:22:50,840
NEXT TO SHOW TASK BAR HOVER TO

5055
03:22:50,840 --> 03:22:55,600
THE RIGHT USUALLY UNDER THAT

5056
03:22:55,600 --> 03:23:01,040
BAR. ONE THING WE CAN ALSO DO

5057
03:23:01,040 --> 03:23:02,680
ABIGAIL, DO YOU HAVE SLIDES SO

5058
03:23:02,680 --> 03:23:03,400
PERHAPS YOU CAN ADVANCE?

5059
03:23:03,400 --> 03:23:06,760
>> SHE DOESN'T. INVOLVE TO
HAVE

5060
03:23:06,760 --> 03:23:12,520
IN PRESENTER, I CAN HAVE IT IN

5061
03:23:12,520 --> 03:23:13,000
REGULAR VIEW.

5062
03:23:13,000 --> 03:23:14,520
>> PRESENTATION VIEW IS
WHAT IT

5063
03:23:14,520 --> 03:23:16,320
IS FOR NORMALLY CALLED IN POWER

5064
03:23:16,320 --> 03:23:26,880
POINT. I'M SORRY ANY ATTENDEES.

5065
03:23:31,440 --> 03:23:32,880
>> THERE WE GO.

5066
03:23:32,880 --> 03:23:36,680
>> I'M SORRY, ABOUT THIS

5067
03:23:36,680 --> 03:23:39,120
TECHNICAL DIFFICULTIES. I WAS

5068
03:23:39,120 --> 03:23:41,560
ASKED TO TALK ABOUT SOME OF OUR

5069
03:23:41,560 --> 03:23:42,320
WORK WE HAVE BEEN PERFORMING

5070
03:23:42,320 --> 03:23:45,640
TOWARDS DEVELOPING A

5071
03:23:45,640 --> 03:23:47,280
MICROPHYSIOLOGICAL SYSTEM, ONE

5072
03:23:47,280 --> 03:23:48,640
GROUP WE HAVE BEEN DUB IN

5073
03:23:48,640 --> 03:23:50,720
COLLABORATION WITH CENTER FOR

5074
03:23:50,720 --> 03:23:52,640
TOX LOGICAL RESEARCH IS MY

5075
03:23:52,640 --> 03:23:54,960
COLLABORATOR AND THIS IS A NEW

5076
03:23:54,960 --> 03:23:58,520
WORD DOING THIS ABOUT YEAR AND A

5077
03:23:58,520 --> 03:24:02,400
HALF OR SO IN ADDITION TO TIE

5078
03:24:02,400 --> 03:24:05,200
INTO THAT TALK ABOUT THE WAY WE

5079
03:24:05,200 --> 03:24:09,680
THINK AT THE FDA IN OUR BRANCH

5080
03:24:09,680 --> 03:24:13,320
AND OUR DIVISION ABOUT UTILITY

5081
03:24:13,320 --> 03:24:14,480
OF SUCH MOSHING PHYSIOLOGICAL

5082
03:24:14,480 --> 03:24:17,000
EXPERIMENTS WHEN WE REVIEW

5083
03:24:17,000 --> 03:24:21,880
ANIMAL DATA. I'M SORRY,

5084
03:24:21,880 --> 03:24:23,400
PRE-CLINICAL DATA FOR MAKING

5085
03:24:23,400 --> 03:24:27,800
REGULATORY DECISIONS.  SO

5086
03:24:27,800 --> 03:24:30,920
DISCLAIMER THOUGH MY SLIDES HAVE

5087
03:24:30,920 --> 03:24:32,960
BEEN CLEAR WHATEVER I SAID

5088
03:24:32,960 --> 03:24:35,640
VERBALLY IS ANY BEST JUDGMENT

5089
03:24:35,640 --> 03:24:38,680
AND DOES NOT BIND THE FDA. SO WE

5090
03:24:38,680 --> 03:24:41,640
ARE TALKING ANTIVIRALS, IT IS

5091
03:24:41,640 --> 03:24:43,000
NORMAL TALK ABOUT INFECTIONS AND

5092
03:24:43,000 --> 03:24:45,640
INFECTIONS ARE SOMETHING THAT

5093
03:24:45,640 --> 03:24:47,320
CAN HAPPEN DURING PREGNANCY AND

5094
03:24:47,320 --> 03:24:49,560
PREGNANT WOMEN ARE VERY

5095
03:24:49,560 --> 03:24:50,920
SUSCEPTIBLE TO INFECTION THEY

5096
03:24:50,920 --> 03:24:54,720
CAN RESULT IN MATERNAL AND FETAL

5097
03:24:54,720 --> 03:24:56,520
TOXICITY HERE I LIST SOME

5098
03:24:56,520 --> 03:24:57,120
INFECTIONS THAT ARE OF

5099
03:24:57,120 --> 03:25:00,400
RELEVANCE.   especially the

5100
03:25:00,400 --> 03:25:04,440
health of the baby.  The fetal

5101
03:25:04,440 --> 03:25:08,600
and developmental issues can

5102
03:25:08,600 --> 03:25:14,160
occur via direct infection of

5103
03:25:14,160 --> 03:25:15,200
babies but also through

5104
03:25:15,200 --> 03:25:18,040
infection of the placenta and

5105
03:25:18,040 --> 03:25:22,400
the problems that arise such as

5106
03:25:22,400 --> 03:25:26,480
decrease nutrient oxygen

5107
03:25:26,480 --> 03:25:28,280
transport presence of reservoir

5108
03:25:28,280 --> 03:25:34,280
for infection and et cetera.  

5109
03:25:34,280 --> 03:25:40,560
The -- what so the antibody

5110
03:25:40,560 --> 03:25:42,000
treatment and antibody

5111
03:25:42,000 --> 03:25:46,960
therapeutics can be used during

5112
03:25:46,960 --> 03:25:50,280
pregnancy for to bomb cat such

5113
03:25:50,280 --> 03:25:51,320
infections and here is a table

5114
03:25:51,320 --> 03:25:53,760
of some examples of antibodies

5115
03:25:53,760 --> 03:25:55,360
that are being used, or can be

5116
03:25:55,360 --> 03:25:57,760
used or are being studied for

5117
03:25:57,760 --> 03:26:01,720
use, during pregnancy for viral

5118
03:26:01,720 --> 03:26:03,600
infections. I subdivided the

5119
03:26:03,600 --> 03:26:08,360
table here in two categories.

5120
03:26:08,360 --> 03:26:09,840
One antibodies that are

5121
03:26:09,840 --> 03:26:13,640
indicated for pregnancy. For

5122
03:26:13,640 --> 03:26:14,960
indications such as further

5123
03:26:14,960 --> 03:26:16,160
prevention of transmission of

5124
03:26:16,160 --> 03:26:19,040
infection, that includes

5125
03:26:19,040 --> 03:26:21,040
cytomegalovirus, hepatitis B

5126
03:26:21,040 --> 03:26:23,520
HIV, there is an example of

5127
03:26:23,520 --> 03:26:25,080
antibody cocktail that is

5128
03:26:25,080 --> 03:26:29,040
studied for the prevention of

5129
03:26:29,040 --> 03:26:31,040
Zika neurological damage in

5130
03:26:31,040 --> 03:26:33,960
macaques.  Rhesus macaques but

5131
03:26:33,960 --> 03:26:37,400
in addition to this group there

5132
03:26:37,400 --> 03:26:41,760
is another subgroup that

5133
03:26:41,760 --> 03:26:43,480
includes antibodies not approved

5134
03:26:43,480 --> 03:26:54,000
for pregnancy per se but there

5135
03:26:55,040 --> 03:26:57,240
include treatment for eBola and

5136
03:26:57,240 --> 03:27:00,120
SARS COV-2 and for such

5137
03:27:00,120 --> 03:27:02,080
antibodies the prescribing

5138
03:27:02,080 --> 03:27:04,280
information as well as the fact

5139
03:27:04,280 --> 03:27:08,160
sheet or EUA clearly state that

5140
03:27:08,160 --> 03:27:09,720
the antibody treatment should

5141
03:27:09,720 --> 03:27:12,000
not be held to pregnancy women

5142
03:27:12,000 --> 03:27:22,560
-- pregnant women due to if risk

5143
03:27:23,800 --> 03:27:26,640
benefit ratio is -- these

5144
03:27:26,640 --> 03:27:29,720
therapies have the same time

5145
03:27:29,720 --> 03:27:31,840
line and drug development as

5146
03:27:31,840 --> 03:27:34,560
other drugs. I'm showing this is

5147
03:27:34,560 --> 03:27:37,200
the linear array, we are forward

5148
03:27:37,200 --> 03:27:39,840
moving type of development which

5149
03:27:39,840 --> 03:27:41,880
we very well know is not such.

5150
03:27:41,880 --> 03:27:46,240
So for example, the clinical

5151
03:27:46,240 --> 03:27:47,560
trials, can be ongoing in

5152
03:27:47,560 --> 03:27:50,280
healthy volunteers while

5153
03:27:50,280 --> 03:27:52,800
pre-clinical studies in for

5154
03:27:52,800 --> 03:27:54,320
example to support use

5155
03:27:54,320 --> 03:27:55,320
susceptible population can be

5156
03:27:55,320 --> 03:28:02,640
ongoing.  Because yes talking

5157
03:28:02,640 --> 03:28:04,040
microphysiological systems, in

5158
03:28:04,040 --> 03:28:07,480
vitro systems that can be used

5159
03:28:07,480 --> 03:28:08,360
in this part of the

5160
03:28:08,360 --> 03:28:10,200
developmental process, in the

5161
03:28:10,200 --> 03:28:11,320
pre-clinical non-clinical

5162
03:28:11,320 --> 03:28:13,120
assessment. The purpose of this

5163
03:28:13,120 --> 03:28:14,720
pre-clinical assessment is of

5164
03:28:14,720 --> 03:28:16,520
course to provide data to

5165
03:28:16,520 --> 03:28:17,280
support initiation of the

5166
03:28:17,280 --> 03:28:20,600
clinical trials.  This type of

5167
03:28:20,600 --> 03:28:22,280
data falls into two buckets. 

5168
03:28:22,280 --> 03:28:24,760
One is to provide evidence of

5169
03:28:24,760 --> 03:28:26,000
activity in targeting the viral

5170
03:28:26,000 --> 03:28:28,440
disease. And by definition these

5171
03:28:28,440 --> 03:28:32,440
studies are performed with in

5172
03:28:32,440 --> 03:28:37,360
the presence of viral agent via

5173
03:28:37,360 --> 03:28:40,600
live virus or suitable

5174
03:28:40,600 --> 03:28:43,120
surrogate. These studies are

5175
03:28:43,120 --> 03:28:44,600
often we call them proof of

5176
03:28:44,600 --> 03:28:46,360
concept or Pharmacodynamic

5177
03:28:46,360 --> 03:28:49,480
studies not only aimed to show

5178
03:28:49,480 --> 03:28:51,920
the activity but most

5179
03:28:51,920 --> 03:28:54,720
importantly they need 'ally dose

5180
03:28:54,720 --> 03:28:58,320
to biologic activity. So they

5181
03:28:58,320 --> 03:29:01,280
are aimed to identify those

5182
03:29:01,280 --> 03:29:03,200
activity -- dose activity

5183
03:29:03,200 --> 03:29:04,720
relationship. On the other hand,

5184
03:29:04,720 --> 03:29:07,400
the other bucket of studies is

5185
03:29:07,400 --> 03:29:09,800
study that show evidence for

5186
03:29:09,800 --> 03:29:13,440
safety, these are toxicology

5187
03:29:13,440 --> 03:29:15,320
studies and most often not

5188
03:29:15,320 --> 03:29:16,080
always these studies are

5189
03:29:16,080 --> 03:29:20,480
performed in healthy animals. In

5190
03:29:20,480 --> 03:29:22,720
general there's no in vitro

5191
03:29:22,720 --> 03:29:25,320
alternatives or substitutions

5192
03:29:25,320 --> 03:29:28,760
for these general toxicity

5193
03:29:28,760 --> 03:29:30,600
studies, however, in vitro

5194
03:29:30,600 --> 03:29:31,040
studies are.

5195
03:29:31,040 --> 03:29:32,200
PROKED FOR SPECIFIC ASPECT OF

5196
03:29:32,200 --> 03:29:34,000
TOXICITY AND SAFETY AND I WILL

5197
03:29:34,000 --> 03:29:35,920
HOPEFULLY HIGHLIGHT ONE OR TWO

5198
03:29:35,920 --> 03:29:38,880
OF THOSE IN MY SUBSEQUENT

5199
03:29:38,880 --> 03:29:43,240
SLIDES. BUT I WOULD LIKE TO

5200
03:29:43,240 --> 03:29:46,160
MENTION HERE THAT WE ENCOURAGE

5201
03:29:46,160 --> 03:29:50,280
USE OF CLEAR PRINCIPLES WHEN

5202
03:29:50,280 --> 03:29:53,160
DESIGNING THESE TOXICITY

5203
03:29:53,160 --> 03:29:56,600
STUDIES. PROOF OF CONCEPT

5204
03:29:56,600 --> 03:30:00,200
PHARMACO DYNAMIC STUDIES

5205
03:30:00,200 --> 03:30:01,760
PHARMACODYNAMIC STUDIES ARE

5206
03:30:01,760 --> 03:30:03,240
CALLED POTENCY ASSAYS, THEY

5207
03:30:03,240 --> 03:30:06,400
PROVIDE A QUANTITATIVE MEASURE

5208
03:30:06,400 --> 03:30:09,080
OF THE ACTIVITY AS LINKED AND

5209
03:30:09,080 --> 03:30:10,160
DEPENDENT ON THE MECHANISM OF

5210
03:30:10,160 --> 03:30:18,080
ACTION. ICH QCB LAYS OUT THEY

5211
03:30:18,080 --> 03:30:19,760
ARE -- THESE TYPES OF ASSAYS CAN

5212
03:30:19,760 --> 03:30:24,480
BE IN VIVO INRY VITRO OR

5213
03:30:24,480 --> 03:30:28,520
BIOASSAYS. FOR ANTIVIRALS

5214
03:30:28,520 --> 03:30:31,000
INCLUDING ANTIVIRAL ANTIBODIES,

5215
03:30:31,000 --> 03:30:34,640
IS NEUTRALIZATION ASSAY. THAT IS

5216
03:30:34,640 --> 03:30:38,960
MOST OFTEN IN VITRO ASSAY,

5217
03:30:38,960 --> 03:30:40,400
SOMETIMES WE SEE BY AND LARGE

5218
03:30:40,400 --> 03:30:45,200
THESE ASSAYS ARE IN VITRO AND

5219
03:30:45,200 --> 03:30:48,680
THESE SCHEMATIC ON THE RIGHT

5220
03:30:48,680 --> 03:30:52,040
THAT/MY COLLEAGUE OFFICE OF

5221
03:30:52,040 --> 03:30:57,080
VACCINES, DR. WISE, YOU CAN SEE

5222
03:30:57,080 --> 03:31:00,080
THAT THIS ASSAY CAN BE PERFORMED

5223
03:31:00,080 --> 03:31:04,920
WITH WHOLE VIRUS IN THE CASE OF

5224
03:31:04,920 --> 03:31:06,960
SARS COV THEY HAVE TO BE

5225
03:31:06,960 --> 03:31:11,800
PERFORMED UNDER BSL 3

5226
03:31:11,800 --> 03:31:13,360
CONDITIONS, BUT ALSO IT IS IN

5227
03:31:13,360 --> 03:31:15,440
OTHER CASES TO OVERCOME THIS

5228
03:31:15,440 --> 03:31:18,440
CHALLENGE SO THE VIRUS CAN BE

5229
03:31:18,440 --> 03:31:24,720
USED. AND -- (INAUDIBLE) CAN BE

5230
03:31:24,720 --> 03:31:27,200
OF DIFFERENT KINDS BUT THEY HAVE

5231
03:31:27,200 --> 03:31:28,840
THE ADVANTAGE WHEN VIRUS IS

5232
03:31:28,840 --> 03:31:31,360
PSEUDO VIRUS IS USED, THIS

5233
03:31:31,360 --> 03:31:36,680
ASSAYS COULD BE PERFORMED UNDER

5234
03:31:36,680 --> 03:31:39,160
BSL 2 CONDITIONS. HOWEVER, WE

5235
03:31:39,160 --> 03:31:43,560
OFTEN REQUEST AND REQUIRE THAT

5236
03:31:43,560 --> 03:31:46,400
THE DATA FROM ASSAYS THAT ARE

5237
03:31:46,400 --> 03:31:48,400
PERFORMED WITH PSEUDO VIRUS BE

5238
03:31:48,400 --> 03:31:50,400
CORRELATED TO THE DATA FROM

5239
03:31:50,400 --> 03:31:54,760
ASSAYS PERFORMED WITH ACTUAL

5240
03:31:54,760 --> 03:31:56,600
CLINICAL ISOLATE OR INFECTIOUS

5241
03:31:56,600 --> 03:32:02,880
VIRUS. SO IN VITRO UTILIZATION

5242
03:32:02,880 --> 03:32:04,000
ASSAYS HAVE ADVANTAGES AND DRAW

5243
03:32:04,000 --> 03:32:07,560
BACKS AND THE ADVANTAGES ARE

5244
03:32:07,560 --> 03:32:10,120
OBVIOUS, LONG HISTORY, MANY

5245
03:32:10,120 --> 03:32:12,880
OPTIONS, PLAQUE NEUTRALIZATION

5246
03:32:12,880 --> 03:32:15,160
ASSAY, ET CETERA. ANOTHER

5247
03:32:15,160 --> 03:32:16,400
IMPORTANT POINT HERE IS THAT FOR

5248
03:32:16,400 --> 03:32:18,560
THIS ASSAY THEY ARE AUTOMATABLE,

5249
03:32:18,560 --> 03:32:22,000
THEY CAN BE USED ROUTINELY FOR

5250
03:32:22,000 --> 03:32:23,200
EXAMPLE MICRONEUTRALIZATION

5251
03:32:23,200 --> 03:32:25,200
ASSAY. THEY CAN DERIVE ACTIVITY

5252
03:32:25,200 --> 03:32:27,040
CONCENTRATION RELATIONSHIP AS I

5253
03:32:27,040 --> 03:32:29,200
ALREADY MENTION AND THEY ALSO DO

5254
03:32:29,200 --> 03:32:31,840
NOT INCLUDE USE OF ANIMALS. 

5255
03:32:31,840 --> 03:32:35,560
HOWEVER THE DRAWING BACKS ALSO

5256
03:32:35,560 --> 03:32:38,280
ARE CLEAR, SIMPLIFIED MODELS,

5257
03:32:38,280 --> 03:32:40,600
THEY ARE A SNAP SHOT IN TIME, WE

5258
03:32:40,600 --> 03:32:42,720
DON'T USUALLY GET KINETIC

5259
03:32:42,720 --> 03:32:44,520
INFORMATION WITH THESE ASSAYS.

5260
03:32:44,520 --> 03:32:46,840
ALSO WE DON'T USUALLY GET ORGAN

5261
03:32:46,840 --> 03:32:48,200
CONCENTRATION INFORMATION. WE

5262
03:32:48,200 --> 03:32:51,000
GET CELL LEVEL BUT ORGAN

5263
03:32:51,000 --> 03:32:53,200
CONCENTRATION. AND CONVERTING

5264
03:32:53,200 --> 03:32:56,840
ACTIVE CONCENTRATION, IC 19s

5265
03:32:56,840 --> 03:32:59,640
TO DOSE CAN BE CHALLENGE

5266
03:32:59,640 --> 03:33:02,200
ESPECIALLY FOR MORE COMPLICATED

5267
03:33:02,200 --> 03:33:04,760
SITUATIONS SUCH AS PREGNANCY.

5268
03:33:04,760 --> 03:33:07,960
AND WE VIEW MICROPHYSIOLOGICAL

5269
03:33:07,960 --> 03:33:12,280
SYSTEMS AS A BRIDGE BETWEEN IN

5270
03:33:12,280 --> 03:33:16,120
VITRO AND IN VIVO, NOTHING NEW

5271
03:33:16,120 --> 03:33:24,080
HERE BUT ALSO THE ADVANTAGES OF

5272
03:33:24,080 --> 03:33:25,280
MICROPHYSIOLOGICAL SYSTEMS ARE

5273
03:33:25,280 --> 03:33:28,760
CLEAR VERSUS SINGLE CELL

5274
03:33:28,760 --> 03:33:33,440
NEUTRALIZATION ASSAY. SO WE

5275
03:33:33,440 --> 03:33:36,120
DECIDED, MYSELF AND COLLABORATOR

5276
03:33:36,120 --> 03:33:39,760
DECIDED TO FOCUS OUR EFFORT

5277
03:33:39,760 --> 03:33:43,640
DEVELOPING A PLACENTA IPS FOR

5278
03:33:43,640 --> 03:33:46,320
SEVERAL REASONS ONE BECAUSE WE

5279
03:33:46,320 --> 03:33:50,400
SAW THERE IS A NEED PLACENTA IS

5280
03:33:50,400 --> 03:33:52,920
IMPORTANT ORGAN CRITICAL FOR

5281
03:33:52,920 --> 03:33:54,160
HEALTH OF THE PREGNANT MOTHER

5282
03:33:54,160 --> 03:33:57,840
AND FETUS. THERE IS -- IT IS

5283
03:33:57,840 --> 03:34:02,760
ALSO AN ORGAN NOT VERY WELL

5284
03:34:02,760 --> 03:34:10,440
STUDIED AND USED BECAUSE -- THAT

5285
03:34:10,440 --> 03:34:15,120
ACTUALLY IT IS A MISSING THAT

5286
03:34:15,120 --> 03:34:17,880
ACTUALLY IS AN AREA THAT NEEDS

5287
03:34:17,880 --> 03:34:20,640
TO BE IMPROVED. PLACENTA IS

5288
03:34:20,640 --> 03:34:21,960
ACCEPTABLE TO -- SUSCEPTIBLE TO

5289
03:34:21,960 --> 03:34:23,720
INFECTION AND DAMAGE AND WE

5290
03:34:23,720 --> 03:34:27,200
DECIDED TO USE ZIKA AS A CASE

5291
03:34:27,200 --> 03:34:28,720
STUDY BECAUSE IT WOULD ALLOW US

5292
03:34:28,720 --> 03:34:32,560
TO LOOK AT THE PATHOYENSIS OF

5293
03:34:32,560 --> 03:34:35,600
PLACENTA INFECTION IN GENERAL AS

5294
03:34:35,600 --> 03:34:40,440
WELL AS LOOK INTO A SPECIFIC

5295
03:34:40,440 --> 03:34:44,720
THEORETICAL CONCERN, WORRIED

5296
03:34:44,720 --> 03:34:47,120
ABOUT, WHAT IS KNOWN AS ANTIBODY

5297
03:34:47,120 --> 03:34:52,200
ENHANCEMENT WHICH IS SHOWN IN

5298
03:34:52,200 --> 03:34:57,200
VITRO SYSTEM OF ANIMAL. FINALLY

5299
03:34:57,200 --> 03:35:00,080
MODELING A PLACENTA IN A IN

5300
03:35:00,080 --> 03:35:03,920
VITRO MPS WOULD BE USEFUL TO

5301
03:35:03,920 --> 03:35:07,920
ALSO LOOK AT THE ANTIBODY

5302
03:35:07,920 --> 03:35:11,360
TRANSFER WHICH IS ANOTHER THING

5303
03:35:11,360 --> 03:35:12,960
UNIQUE FOR ANTIBODIES WHEN THEY

5304
03:35:12,960 --> 03:35:15,080
ARE USED IN PREGNANCY AND CAN

5305
03:35:15,080 --> 03:35:20,760
AFFECT THEIR PK AND PD FOR THE

5306
03:35:20,760 --> 03:35:22,440
PREGNANT WOMAN. IN DEVELOPING

5307
03:35:22,440 --> 03:35:28,360
OUR THREE DIMENSIONAL WE FIRST

5308
03:35:28,360 --> 03:35:33,200
DECIDED TO LOOK AT THE ACTUAL

5309
03:35:33,200 --> 03:35:35,120
WHAT ARE THE CELL TYPES AND WHAT

5310
03:35:35,120 --> 03:35:38,040
THAT TYPE OF STRUCTURE WE ARE

5311
03:35:38,040 --> 03:35:45,640
TRYING TO WE DECIDED TO MODEL

5312
03:35:45,640 --> 03:35:47,760
THE VILLAS.  HERE IS A SCHEMATIC

5313
03:35:47,760 --> 03:35:50,840
OF A FIRST TRIMESTER

5314
03:35:50,840 --> 03:35:53,400
DIFFERENTIATED ALVEOLUS, THIS

5315
03:35:53,400 --> 03:35:58,280
HAS MULTIPLE CELL TYPES, IN THE

5316
03:35:58,280 --> 03:36:01,920
OTHER PART, THETROPE BLAST WHICH

5317
03:36:01,920 --> 03:36:10,360
IN CIRCLES OR ENCLOSES A

5318
03:36:10,360 --> 03:36:14,800
MESENCHYMEA, FETAL VESSELS ARE

5319
03:36:14,800 --> 03:36:19,120
ALSO EMBEDDED. GIVEN THAT THIS

5320
03:36:19,120 --> 03:36:22,480
STRUCTURE IS QUITE COMPLEX, WE

5321
03:36:22,480 --> 03:36:24,320
TOOK A STEP WISE APPROACH IN OUR

5322
03:36:24,320 --> 03:36:27,560
MODELING. SO WE DECIDED TO BUILD

5323
03:36:27,560 --> 03:36:29,680
PLACENTAL MEMBRANE BARRIERS ON A

5324
03:36:29,680 --> 03:36:32,960
TRANSWELL THAT CONTAIN ONLY A

5325
03:36:32,960 --> 03:36:34,800
MONOCULTURES THEN GO TO

5326
03:36:34,800 --> 03:36:35,920
CO-CULTURES AND THEN BUILD

5327
03:36:35,920 --> 03:36:37,320
TOWARDS A MICROPHYSIOLOGICAL

5328
03:36:37,320 --> 03:36:40,960
SYSTEM. THAT CONTAINS MULTIPLE

5329
03:36:40,960 --> 03:36:42,800
CELL TYPES. SO FOR MONOCULTURES

5330
03:36:42,800 --> 03:36:45,960
WE FOCUSED ON CARDIO SARCOMA

5331
03:36:45,960 --> 03:36:48,200
CELLS OF TRIPLE BLAST ORIGINS,

5332
03:36:48,200 --> 03:36:52,000
IN VIVO INJECT THREE CELL LINES

5333
03:36:52,000 --> 03:36:53,720
WHICH FORMS POLARIZE ISORRIZED

5334
03:36:53,720 --> 03:36:55,440
LAYERS IN MEMBRANE. THESE CELLS

5335
03:36:55,440 --> 03:37:01,680
SHOWN HERE IN THIS SCHEMATIC

5336
03:37:01,680 --> 03:37:03,760
SEMIPERMEABLE MEMBRANE CAN

5337
03:37:03,760 --> 03:37:08,280
SEPARATE IN APICAL CHAMBER WHICH

5338
03:37:08,280 --> 03:37:11,840
WE CAN CALL THE MATERNAL BLOOD

5339
03:37:11,840 --> 03:37:15,880
IF YOU WILL AS A MODEL OF THE

5340
03:37:15,880 --> 03:37:18,640
COMPARTMENT AND THIS CHAMBER IS

5341
03:37:18,640 --> 03:37:21,600
SEPARATED FROM BASAL LATERAL

5342
03:37:21,600 --> 03:37:23,920
CHAMBER WITH WHAT WOULD BE

5343
03:37:23,920 --> 03:37:25,280
EQUIVALENT OF THE FETAL

5344
03:37:25,280 --> 03:37:32,280
COMPARTMENT. WE FIRST BEFORE WE

5345
03:37:32,280 --> 03:37:37,880
EMBARKED IN MAKING THIS MEMBRANE

5346
03:37:37,880 --> 03:37:39,640
ON TRANSWELL WE LOOK AT THE

5347
03:37:39,640 --> 03:37:44,560
ABILITY OF CELL LINES TO BE

5348
03:37:44,560 --> 03:37:45,920
SUBSEQUENT TO ZIKA INFECTION AND

5349
03:37:45,920 --> 03:37:48,560
WE SHOWED HERE IS A SIMPLE

5350
03:37:48,560 --> 03:37:51,600
KINETIC INFECTION KINETICS OF

5351
03:37:51,600 --> 03:37:55,200
BIGGER CELLS INJECT THREE CELLS

5352
03:37:55,200 --> 03:37:56,320
MAY HAVE SAME WAY SUSCEPTIBLE TO

5353
03:37:56,320 --> 03:37:58,520
INFECTION AND SAW SIMILAR

5354
03:37:58,520 --> 03:38:00,840
KINETICS TO VIRAL CELLS. IN

5355
03:38:00,840 --> 03:38:06,040
ADDITION ADDING ANTI-ZIKA

5356
03:38:06,040 --> 03:38:09,280
FLAVIVIRUS ANTIBODIES BLOCK

5357
03:38:09,280 --> 03:38:12,840
INFECTION. SO THEN WE WENT TO

5358
03:38:12,840 --> 03:38:14,080
BUILDING THESE MEMBRANE OR

5359
03:38:14,080 --> 03:38:19,400
GROWING THESE BARRIERS AND

5360
03:38:19,400 --> 03:38:20,280
MONITOR THEIR GROWTH AND

5361
03:38:20,280 --> 03:38:22,160
ACTIVITY BY LOOKING AT

5362
03:38:22,160 --> 03:38:23,400
INTERSELECTIVE RESISTANCE AS

5363
03:38:23,400 --> 03:38:27,120
WELL AS THE PERMEABLE --

5364
03:38:27,120 --> 03:38:30,480
PERMEABILITY OF SMALL MOLECULE

5365
03:38:30,480 --> 03:38:33,960
TO SEE THAT THIS MEMBRANES ARE

5366
03:38:33,960 --> 03:38:35,160
IN FACT CONFLUENT AND HAVE LOW

5367
03:38:35,160 --> 03:38:45,880
PERMEABILITY. SUBSEQUENTLY WE

5368
03:38:45,880 --> 03:38:48,760
ADDED IN THE APICAL CHAMBER

5369
03:38:48,760 --> 03:38:52,120
EITHER ZIKA VIRUS WITH OR

5370
03:38:52,120 --> 03:38:54,520
WITHOUT ANTIBODY TARGETING ZIKA.

5371
03:38:54,520 --> 03:38:59,280
WE LOOKED AT THE ABILITY OF

5372
03:38:59,280 --> 03:39:01,280
ANTIBODY TO PASSAGE THROUGH THIS

5373
03:39:01,280 --> 03:39:03,280
BARRIER, INDEED WE DID SEE

5374
03:39:03,280 --> 03:39:06,040
ANTIBODY PASSAGE FROM CAN THE

5375
03:39:06,040 --> 03:39:09,480
BASAL LATERAL CHAMBERS.  IN A

5376
03:39:09,480 --> 03:39:13,680
ADDITION SAME WAS TRUE FOR ZIKA

5377
03:39:13,680 --> 03:39:17,080
IT COULD PASS THROUGH BARRIERS,

5378
03:39:17,080 --> 03:39:21,520
ADDING ANTIBODY DECREASED THE

5379
03:39:21,520 --> 03:39:23,080
AMOUNT OF ANTIBODY VIRUS WE

5380
03:39:23,080 --> 03:39:26,120
COULD DETECT IN BASAL

5381
03:39:26,120 --> 03:39:26,760
COMPARTMENT SO USING THESE

5382
03:39:26,760 --> 03:39:29,000
BARRIERS WE DID NOT SEE

5383
03:39:29,000 --> 03:39:32,120
ENHANCEMENT OF INFECTION. THE

5384
03:39:32,120 --> 03:39:38,160
NEXT STEP BUILDING CO-CULTURE

5385
03:39:38,160 --> 03:39:40,240
USING DIFFERENT CELLS IN

5386
03:39:40,240 --> 03:39:42,840
ADDITION TOP VIVO OR THREE

5387
03:39:42,840 --> 03:39:47,320
TRIPLE BLAST WE ADDED

5388
03:39:47,320 --> 03:39:49,200
FIBROBLASTS IN THE APE AL

5389
03:39:49,200 --> 03:39:52,800
MEMBRANE AS WELL AS ENDOTHELIAL

5390
03:39:52,800 --> 03:39:54,920
CELLS HUMAN UMBILICAL VEIN

5391
03:39:54,920 --> 03:39:57,480
ENDOTHELIAL CELLS MANY THE

5392
03:39:57,480 --> 03:40:01,480
OPPOSING SIDE WE PERFORMED

5393
03:40:01,480 --> 03:40:06,160
SIMILAR EXPERIMENTS AS BEFORE,

5394
03:40:06,160 --> 03:40:07,520
FIRST AS CERTAINING THESE

5395
03:40:07,520 --> 03:40:09,960
MEMBRANES DID IN FACT GROW AND

5396
03:40:09,960 --> 03:40:14,000
CONTAIN MULTIPLE CELL TYPES, BY

5397
03:40:14,000 --> 03:40:15,920
HNE STAINING AND SPECIFIC

5398
03:40:15,920 --> 03:40:21,320
MARKERS FOR THESE CELL LINES. 

5399
03:40:21,320 --> 03:40:23,560
THEN ADDED IGG IN APICAL

5400
03:40:23,560 --> 03:40:24,960
COMPARTMENT AND LOOKED FOR

5401
03:40:24,960 --> 03:40:27,000
PASSAGE IN BASAL COMPARTMENT AND

5402
03:40:27,000 --> 03:40:30,800
INDEED WE DID SEE SOME ALBEIT

5403
03:40:30,800 --> 03:40:34,800
SMALL AMOUNT OF IGG PASSAGE.

5404
03:40:34,800 --> 03:40:35,960
THIS IS MY DATA PRESENTATION WE

5405
03:40:35,960 --> 03:40:38,480
ARE IN THE PROCESS OF COMPLETING

5406
03:40:38,480 --> 03:40:42,040
AND ANALYZING THE DATA WITH

5407
03:40:42,040 --> 03:40:45,800
VIRUS BUT I WOULD LIKE TO SHOW

5408
03:40:45,800 --> 03:40:50,000
YOU WHERE WE WANT TO GO AND TO

5409
03:40:50,000 --> 03:40:52,800
BE IN THIS MPS SPACE. WE ARE

5410
03:40:52,800 --> 03:40:58,880
HOPING TO BUILD A RICH

5411
03:40:58,880 --> 03:41:03,360
COMPARTMENT MPS COMPARTMENT 1

5412
03:41:03,360 --> 03:41:06,440
REPLICATE PLACENTAL BARRIER

5413
03:41:06,440 --> 03:41:11,120
CONTAIN THIS MIX CELLS THEN WE

5414
03:41:11,120 --> 03:41:14,160
WOULD ADD IN THERE VIRUS AND IGG

5415
03:41:14,160 --> 03:41:17,920
OR IGM AGAIN ZIKA VIRUS,

5416
03:41:17,920 --> 03:41:19,440
COMPARTMENT 2 WOULD BE

5417
03:41:19,440 --> 03:41:22,160
EQUIVALENT OF THE FETAL

5418
03:41:22,160 --> 03:41:25,600
COMPARTMENT, IT WOULD CONTAIN

5419
03:41:25,600 --> 03:41:30,080
TISSUE SUSCEPTIBLE TO ZIKA

5420
03:41:30,080 --> 03:41:32,680
INFECTION SUCH AS NEUROSPHERE,

5421
03:41:32,680 --> 03:41:36,520
THE OUTCOMES IS TO MONITOR

5422
03:41:36,520 --> 03:41:38,880
PLACENTAL TOXICITY METABOLIC

5423
03:41:38,880 --> 03:41:40,320
FUNCTION, TRANSCYTOSIS,

5424
03:41:40,320 --> 03:41:43,640
INFLAMMATORY SIGNALING

5425
03:41:43,640 --> 03:41:45,320
MOLECULES, WE LOOK AT SIMILAR

5426
03:41:45,320 --> 03:41:49,240
END POINTS SUCH AS IN ADDITION

5427
03:41:49,240 --> 03:41:53,400
TO THAT, THE POTENTIAL FOR

5428
03:41:53,400 --> 03:41:54,800
INCREASE INFECTION IN THE

5429
03:41:54,800 --> 03:41:59,120
PRESENCE OF ANTIBODY SPECIFIC

5430
03:41:59,120 --> 03:42:03,120
CONCERN HAS BEEN RAISED. I WANT

5431
03:42:03,120 --> 03:42:07,800
TO CONCLUDE WITH A FEW THOUGHTS,

5432
03:42:07,800 --> 03:42:11,800
GENERAL THOUGHTS ON

5433
03:42:11,800 --> 03:42:13,560
MICROPHYSIOLOGICAL SYSTEMS AND

5434
03:42:13,560 --> 03:42:16,880
WHERE WE SEE THEM IN THE

5435
03:42:16,880 --> 03:42:18,160
REGULATORY SPACE AND UTILITY CAN

5436
03:42:18,160 --> 03:42:23,960
BE. SO AS I ALREADY MENTIONED,

5437
03:42:23,960 --> 03:42:25,240
WE THINK THAT THEY HAVE GREAT

5438
03:42:25,240 --> 03:42:26,880
POTENTIAL TO CHARACTERIZE

5439
03:42:26,880 --> 03:42:29,800
ACTIVITY AND MEASURE POTENCY OF

5440
03:42:29,800 --> 03:42:32,360
THIS ANTIVIRAL IGGs BECAUSE

5441
03:42:32,360 --> 03:42:34,680
THEY ARE USEFUL TO ASSESS THE

5442
03:42:34,680 --> 03:42:36,920
ORGAN TISSUE SPECIFIC ACTIVITY

5443
03:42:36,920 --> 03:42:39,000
AND WHEN COMBINED WITH

5444
03:42:39,000 --> 03:42:41,080
PHARMACOKINETIC OR -- AND

5445
03:42:41,080 --> 03:42:42,920
PHARMACODYNAMIC MODELING IT CAN

5446
03:42:42,920 --> 03:42:47,720
BE HELPFUL TO RELATE THOSE --

5447
03:42:47,720 --> 03:42:49,800
SYSTEMIC DOSE IV OR SUB Q TO

5448
03:42:49,800 --> 03:42:53,680
ORGAN CONCENTRATION THAT WOULD

5449
03:42:53,680 --> 03:42:57,400
BE POTENT AND EFFICACIOUS. HOW

5450
03:42:57,400 --> 03:43:00,440
FAR, REGULAR LA -- HOWEVER,

5451
03:43:00,440 --> 03:43:03,160
REGULATORY EXPECTATION IS THIS

5452
03:43:03,160 --> 03:43:05,600
AUSSIE IS PERFORMED BASED ON ONE

5453
03:43:05,600 --> 03:43:06,960
SCIENTIFIC PRINCIPLES AND BE

5454
03:43:06,960 --> 03:43:09,080
QUALIFIED AND THE QUALIFICATION

5455
03:43:09,080 --> 03:43:11,600
USUALLY ARE GOING TO ENTER INTO

5456
03:43:11,600 --> 03:43:15,600
PICTURE IN PHASE 2 AND PHASE 3

5457
03:43:15,600 --> 03:43:18,600
STUDIES, BECAUSE THAT IS WHERE

5458
03:43:18,600 --> 03:43:23,360
MORE SUSCEPTIBLE POPULATION

5459
03:43:23,360 --> 03:43:26,480
DISEASE WOULD BE ENTERING

5460
03:43:26,480 --> 03:43:28,240
CLINICAL TRIALS. THEN ANOTHER

5461
03:43:28,240 --> 03:43:31,520
AREA WHERE SUCH MPS COULD BE

5462
03:43:31,520 --> 03:43:36,400
ALSO USEFUL WOULD BE IN THE

5463
03:43:36,400 --> 03:43:38,640
SPECIFIC CONCERNS SUCH AS

5464
03:43:38,640 --> 03:43:40,680
ANTIBODY DEPENDENT ENHANCEMENT

5465
03:43:40,680 --> 03:43:42,720
AS WELL AS FOR EXAMPLE PLACENTAL

5466
03:43:42,720 --> 03:43:44,840
TRANSFER OF THERAPEUTIC

5467
03:43:44,840 --> 03:43:49,000
ANTIBODIES. WE SEE THIS TYPE OF

5468
03:43:49,000 --> 03:43:53,400
UTILITY TO BE MORE USEFUL IN THE

5469
03:43:53,400 --> 03:43:55,000
EARLY STAGE OF DEVELOPMENT SUCH

5470
03:43:55,000 --> 03:43:55,800
AS CANDIDATE SELECTION, ET

5471
03:43:55,800 --> 03:44:04,200
CETERA.  I ALSO WANT TO IN

5472
03:44:04,200 --> 03:44:06,600
CLOSING TWO SUMMARY SLIDES THAT

5473
03:44:06,600 --> 03:44:08,680
ARE DUALLY NOT MY -- ACTUALLY

5474
03:44:08,680 --> 03:44:10,360
NOT MY SLIDES, I TOOK THIS FIRST

5475
03:44:10,360 --> 03:44:13,200
TABLE FROM A REVIEW PUBLISHED

5476
03:44:13,200 --> 03:44:15,680
THIS YEAR THAT CAME OUT OF A

5477
03:44:15,680 --> 03:44:20,560
WORKSHOP BETWEEN FDA AND

5478
03:44:20,560 --> 03:44:22,680
INDUSTRY ON NEW TECHNOLOGY USED

5479
03:44:22,680 --> 03:44:26,120
FOR REGULATORY APPLICATION. SOME

5480
03:44:26,120 --> 03:44:27,760
BIG IDEAS OR IMPORTANT IDEAS

5481
03:44:27,760 --> 03:44:31,680
THAT I UNDERLINE IN THIS TABLE

5482
03:44:31,680 --> 03:44:35,120
ARE SOME QUESTIONS WE NEED

5483
03:44:35,120 --> 03:44:39,600
ANSWERED OR ASK OURSELVES BEFORE

5484
03:44:39,600 --> 03:44:42,240
SUBMITTING DATA THAT HAS BEEN

5485
03:44:42,240 --> 03:44:44,000
DERIVED FROM NEW TECHNOLOGY. SO

5486
03:44:44,000 --> 03:44:48,400
ONE IMPORTANT QUESTION WOULD BE

5487
03:44:48,400 --> 03:44:51,680
IS THIS DATA ANSWERING

5488
03:44:51,680 --> 03:44:53,200
FUNDAMENTAL DRUG DEVELOPMENT

5489
03:44:53,200 --> 03:44:54,920
QUESTIOQUESTIONS. I HAVE UNANSWD

5490
03:44:54,920 --> 03:44:56,080
QUESTIONS WE ARE ANSWERING BY

5491
03:44:56,080 --> 03:45:00,520
USING THIS NEW TECHNOLOGY. 

5492
03:45:00,520 --> 03:45:02,560
PREDICTIVE OF THE EFFECT THAT I

5493
03:45:02,560 --> 03:45:08,400
HAVE EXPECTED TO BE IN VIVO. HAS

5494
03:45:08,400 --> 03:45:11,720
THE VALIDITY BEEN SHOWN,

5495
03:45:11,720 --> 03:45:14,200
ACCURACY AND SPECIFICITY OF THE

5496
03:45:14,200 --> 03:45:18,840
METHOD. FINALLY, THE SLIDE WAS

5497
03:45:18,840 --> 03:45:21,720
TAKEN FROM A PRESENTATION DR.

5498
03:45:21,720 --> 03:45:24,120
JANET WEEKCOCK PRINCIPLE DEPUTY

5499
03:45:24,120 --> 03:45:28,800
DIRECTOR GAVE AT THE ANNUAL

5500
03:45:28,800 --> 03:45:30,480
MEETING OF THE COLLEGE OF

5501
03:45:30,480 --> 03:45:32,640
TOXICOLOGY, IT IS AN EXCELLENT

5502
03:45:32,640 --> 03:45:34,200
TALK, ENCOURAGE EVERYBODY TO GET

5503
03:45:34,200 --> 03:45:38,600
THE PRESENTATION FROM THE FDA

5504
03:45:38,600 --> 03:45:42,160
WEBSITE. THE POINT OF THE

5505
03:45:42,160 --> 03:45:45,360
SUMMARY, MAIN POINT IS FDA AND

5506
03:45:45,360 --> 03:45:48,880
WORLDWIDE REGULATORS WILL

5507
03:45:48,880 --> 03:45:50,480
INCORPORATE NEW TESTING

5508
03:45:50,480 --> 03:45:53,440
METHODOLOGIES. IF SOME STANDARDS

5509
03:45:53,440 --> 03:45:58,800
ARE MET. THE SECOND POINT IS

5510
03:45:58,800 --> 03:46:01,440
THAT WHEN SUCH DATA IS INTENDED

5511
03:46:01,440 --> 03:46:03,560
TO REPLACE AN EXISTING TEST OR

5512
03:46:03,560 --> 03:46:10,600
TO SUPPORT SAFETY THE BIAS IS

5513
03:46:10,600 --> 03:46:15,120
VERY HIGH HOWEVER IT IS VERY

5514
03:46:15,120 --> 03:46:18,440
IMPORTANT FIRST NEW TECHNOLOGY

5515
03:46:18,440 --> 03:46:23,640
TO DEFINE THE CONTEXT OF USE.

5516
03:46:23,640 --> 03:46:24,840
THIS MEANS HAVING A CLEAR IDEA

5517
03:46:24,840 --> 03:46:26,760
WHAT IS THE UNMET NEED AND

5518
03:46:26,760 --> 03:46:28,880
IMPROVEMENT THAT THE NEW

5519
03:46:28,880 --> 03:46:31,840
TECHNOLOGY IS GOING TO BRING TO

5520
03:46:31,840 --> 03:46:36,120
THE FLOOR. FINALLY, AFTER

5521
03:46:36,120 --> 03:46:38,000
CONTEXT USE IS CLEAR, THE

5522
03:46:38,000 --> 03:46:41,160
DEVELOPER CAN QUALIFY THE METHOD

5523
03:46:41,160 --> 03:46:42,720
FOR ITS USE AFTER QUALIFIED

5524
03:46:42,720 --> 03:46:45,640
METHOD CAN BE USED FOR OTHER

5525
03:46:45,640 --> 03:46:48,400
PURPOSES WITHOUT ADDITIONAL

5526
03:46:48,400 --> 03:46:50,320
DEMONSTRATION OF ITS

5527
03:46:50,320 --> 03:46:52,000
PERFORMANCE. THAT CONCLUDES MY

5528
03:46:52,000 --> 03:46:53,480
TALK I WOULD LIKE TO ACKNOWLEDGE

5529
03:46:53,480 --> 03:46:55,200
MY COLLEAGUES AT THE DIVISION OF

5530
03:46:55,200 --> 03:46:57,360
PLASMA PROTEIN THERAPEUTICS AS

5531
03:46:57,360 --> 03:47:02,040
WELL AS PEOPLE WHO PERFORM THIS

5532
03:47:02,040 --> 03:47:05,200
WORK, THEY ARE BOTH NOT WITH ME

5533
03:47:05,200 --> 03:47:06,880
ANY MORE, I'M LOOKING FOR A POST

5534
03:47:06,880 --> 03:47:08,480
DOC IF YOU KNOW ANYBODY OR

5535
03:47:08,480 --> 03:47:09,560
ANYBODY IS INTERESTED TO BRING

5536
03:47:09,560 --> 03:47:13,280
THIS PROJECT FORWARD PLEASE SEND

5537
03:47:13,280 --> 03:47:15,720
ME AN EMAIL.  ACKNOWLEDGING MY

5538
03:47:15,720 --> 03:47:17,920
COLLABORATOR DAYTON WHO

5539
03:47:17,920 --> 03:47:19,280
PERFORMED STUDIES, MY OTHER

5540
03:47:19,280 --> 03:47:22,800
COLLABORATOR MARIA RIOS WHO IS

5541
03:47:22,800 --> 03:47:27,280
OUR ZIKA EXPERT, KYUNG SUNG FROM

5542
03:47:27,280 --> 03:47:29,200
FDA ALTERNATIVE METHODS WORKING

5543
03:47:29,200 --> 03:47:30,640
GROUP AND PERINATAL HEALTH

5544
03:47:30,640 --> 03:47:31,480
CENTER OF EXCELLENCE FOR

5545
03:47:31,480 --> 03:47:33,760
FUNDING. I WILL TAKE QUESTIONS.

5546
03:47:33,760 --> 03:47:43,000
THANK YOU.

5547
03:47:43,000 --> 03:47:44,800
>> THANK YOU, EVI. NICE
TALK.

5548
03:47:44,800 --> 03:47:46,280
GET TO QUESTIONS AT THE END. I

5549
03:47:46,280 --> 03:47:48,200
WOULD LIKE TO INTRODUCE THE NEXT

5550
03:47:48,200 --> 03:47:53,920
SPEAKER DR. THOMAS HARTUNG. DR.

5551
03:47:53,920 --> 03:47:56,800
HARTUNG IS THE (INAUDIBLE) CHAIR

5552
03:47:56,800 --> 03:47:58,400
FOR EVIDENCE BASED TOXICOLOGY IN

5553
03:47:58,400 --> 03:47:59,560
THE DEPARTMENT OF ENVIRONMENTAL

5554
03:47:59,560 --> 03:48:01,360
HEALTH AND ENGINEERING JOHNS

5555
03:48:01,360 --> 03:48:03,040
HOPKINS BLOOMBERG SCHOOL OF

5556
03:48:03,040 --> 03:48:06,320
HEALTH PUBLIC HEALTH IN

5557
03:48:06,320 --> 03:48:08,800
BALTIMORE. DR. HARTUNG HOLDS

5558
03:48:08,800 --> 03:48:13,280
NUMBER OF JOINT APPOINTMENTS

5559
03:48:13,280 --> 03:48:15,360
INCLUDING APPOINTMENT AS

5560
03:48:15,360 --> 03:48:18,240
PROFESSOR PHARMACOLOGY

5561
03:48:18,240 --> 03:48:18,920
TOXICOLOGY UNIVERSITY OF

5562
03:48:18,920 --> 03:48:20,560
(INAUDIBLE) IN GERMANY, ALSO

5563
03:48:20,560 --> 03:48:21,840
DIRECTOR OF CENTER FOR

5564
03:48:21,840 --> 03:48:23,960
ALTERNATIVES TO ANIMAL TESTING

5565
03:48:23,960 --> 03:48:26,400
OR THE CABOT PROGRAM FOR BOTH

5566
03:48:26,400 --> 03:48:28,000
UNIVERSITIES. HOSTS SECRETARY OF

5567
03:48:28,000 --> 03:48:29,960
EVIDENCE BASED TOXICOLOGY

5568
03:48:29,960 --> 03:48:33,800
COLLABORATION AND MANAGES

5569
03:48:33,800 --> 03:48:36,680
CREATIVE COST PRACTICE, CULTURE

5570
03:48:36,680 --> 03:48:38,760
PRACTICE, TOXICOLOGY

5571
03:48:38,760 --> 03:48:41,040
DEVELOPMENTAL NEUROTOX TOXICITY

5572
03:48:41,040 --> 03:48:44,800
AND MICROPHYSIOLOGICAL SYSTEMS.

5573
03:48:44,800 --> 03:48:55,040
DR. HARTUNG'S

5574
03:49:13,120 --> 03:49:21,000
>> TECHNOLOGY AT HOPKINS
AND

5575
03:49:21,000 --> 03:49:21,640
LICENSED BUT I SEE A FEW OTHERS

5576
03:49:21,640 --> 03:49:22,240
SO TAKE PLEASE EVERYTHING I'M

5577
03:49:22,240 --> 03:49:25,080
DOING WITH A GRAIN OF SALT. I

5578
03:49:25,080 --> 03:49:30,360
SEE BRING THE RABBIT TO THE

5579
03:49:30,360 --> 03:49:31,800
GROUND AND THESE WONDERFUL

5580
03:49:31,800 --> 03:49:32,840
TECHNOLOGIES TO ACTUAL USE.  

5581
03:49:32,840 --> 03:49:35,120
COMING JUST FROM A MOST EXCITING

5582
03:49:35,120 --> 03:49:36,720
EVENT IN THE MICROPHYSIOLOGICAL

5583
03:49:36,720 --> 03:49:39,720
SYSTEMS LAST WEEK, WE METAPHOR

5584
03:49:39,720 --> 03:49:42,840
THE FIRST TIME AND DID TWO

5585
03:49:42,840 --> 03:49:47,160
COHORTS AND SUSIE FITZPATRICK

5586
03:49:47,160 --> 03:49:51,280
FROM FDA. 52 ORGANIZATIONS

5587
03:49:51,280 --> 03:49:52,560
TEAMED UP AND THIS IS THE BRAIN

5588
03:49:52,560 --> 03:49:57,520
CHILD FROM NCATS, INTO THIS REAL

5589
03:49:57,520 --> 03:49:58,720
WORLD SUMMIT SO THIS IS

5590
03:49:58,720 --> 03:50:01,480
TECHNOLOGY WHICH IS BECOMING

5591
03:50:01,480 --> 03:50:02,160
SCIENTIFIC DISCIPLINE OF ITS

5592
03:50:02,160 --> 03:50:08,480
OWN. OUR OWN CONTRIBUTION STARTS

5593
03:50:08,480 --> 03:50:13,320
IN 2016 WHEN WE WERE ONLY THE

5594
03:50:13,320 --> 03:50:15,440
THIRD OR FOURTH GROUP TO USE

5595
03:50:15,440 --> 03:50:18,440
BRAIN ORGANICS BECAUSE THE MINI

5596
03:50:18,440 --> 03:50:20,400
BRAINS AT THE TIME MASS PRODUCE

5597
03:50:20,400 --> 03:50:24,880
THEM SO THEY ACTUALLY COULD DO

5598
03:50:24,880 --> 03:50:26,280
THINGS SOUGHT SOUTH OF THESE IN

5599
03:50:26,280 --> 03:50:31,720
-- WHICH ARE IDENTICAL IN

5600
03:50:31,720 --> 03:50:37,280
CERTAIN COMPOSITION,INGS FROM

5601
03:50:37,280 --> 03:50:38,400
INDUCED PLURIPOTENT STEM CELLS. 

5602
03:50:38,400 --> 03:50:39,280
YOU CAN DO THEM FROM DIFFERENT

5603
03:50:39,280 --> 03:50:40,240
GENETIC BACKGROUNDS FOR THIS

5604
03:50:40,240 --> 03:50:46,160
REASON YOU CAN ALSO MANIPULATE

5605
03:50:46,160 --> 03:50:47,440
EXPANSE TO NEURONAL PRECURSOR

5606
03:50:47,440 --> 03:50:50,480
CELLS IN 2D AND COMING AS CELL

5607
03:50:50,480 --> 03:50:53,800
SUSPENSION ON THIS, THEY ARE

5608
03:50:53,800 --> 03:50:55,160
(INDISCERNIBLE) EACH OF THESE

5609
03:50:55,160 --> 03:50:57,680
SIX WELL PLACE GETS US BETWEEN

5610
03:50:57,680 --> 03:51:01,520
600 AND 1,200 BRAIN ORGANOIDS.

5611
03:51:01,520 --> 03:51:03,040
SO A VERY EFFICIENT WAY OF

5612
03:51:03,040 --> 03:51:07,560
PRODUCING THEM.  THERE ARE A LOT

5613
03:51:07,560 --> 03:51:10,960
OF INTERESTING FEATURES, SHOW

5614
03:51:10,960 --> 03:51:12,160
BIT MORE ABOUT THIS IN A SECOND.

5615
03:51:12,160 --> 03:51:15,560
THEY ARE SPONTANEOUS

5616
03:51:15,560 --> 03:51:19,600
ELECTROPHYSIOLOGICALLY ACTIVE

5617
03:51:19,600 --> 03:51:20,240
AND UNDERGO VARIETY OF PROCESSES

5618
03:51:20,240 --> 03:51:30,720
WHICH ARE TYPICAL FOR NEURAL

5619
03:51:35,680 --> 03:51:37,520
DEVELOPMENT. FOR EXAMPLE,

5620
03:51:37,520 --> 03:51:38,120
MYELINATION IS A KEY FEATURE YOU

5621
03:51:38,120 --> 03:51:38,720
MIGHT SEE HERE, THE LAYERS OF

5622
03:51:38,720 --> 03:51:39,320
OLIGODENDROCYTES AROUND AXONS,

5623
03:51:39,320 --> 03:51:40,000
40% AXONS ARE MYELINATED AND YOU

5624
03:51:40,000 --> 03:51:41,520
CAN SEE THE RESPECTEDTIVE

5625
03:51:41,520 --> 03:51:43,400
PUBLICATIONS AND EDITS ARTICLES

5626
03:51:43,400 --> 03:51:44,840
FOR THOSE WHO MIGHT BE

5627
03:51:44,840 --> 03:51:45,840
INTERESTED TO RETRIEVE THESE

5628
03:51:45,840 --> 03:51:49,880
PAPERS.  THESE OLIGODENDROCYTES

5629
03:51:49,880 --> 03:51:52,240
WE CAN FOLLOW BECAUSE WE BROUGHT

5630
03:51:52,240 --> 03:51:58,400
FLOW CYTOMETRY IS WE SEE

5631
03:51:58,400 --> 03:51:59,000
PRE-OLIGODENDROCYTES, YOU CAN

5632
03:51:59,000 --> 03:52:02,440
STAIN THE BASIC PROTEIN TO MORE

5633
03:52:02,440 --> 03:52:04,120
MATURE OLIGODENDROCYTES SO IT IS

5634
03:52:04,120 --> 03:52:07,120
REALLY VERY NICE POPULATION

5635
03:52:07,120 --> 03:52:08,720
OFTEN ABOUT 10% OF THE CELLS WE

5636
03:52:08,720 --> 03:52:12,920
ARE SEEING. WE ALSO DO HAVE

5637
03:52:12,920 --> 03:52:16,320
OTHER CELLS, IF ASTROCYTES YOU

5638
03:52:16,320 --> 03:52:18,240
CAN FOLLOW WITH TIP OF YOUR

5639
03:52:18,240 --> 03:52:19,360
MARKERS. THE ONLY CELL THE BASE

5640
03:52:19,360 --> 03:52:21,760
MODEL IS LACKING IS THE

5641
03:52:21,760 --> 03:52:25,440
MICROGLIA BECAUSE MICROGLIA IS

5642
03:52:25,440 --> 03:52:27,960
INVADING CELL TYPE, IT COMES

5643
03:52:27,960 --> 03:52:31,200
FROM THE EGG YOLK FROM YOLK SACK

5644
03:52:31,200 --> 03:52:34,520
OF EMBRYO DEVELOPMENT. IT IS

5645
03:52:34,520 --> 03:52:36,800
PRESENT HERE. MEANTIME WE HAVE

5646
03:52:36,800 --> 03:52:37,840
DEVELOPED TECHNOLOGIES AND

5647
03:52:37,840 --> 03:52:40,480
COLLABORATION ALSO WITH THE

5648
03:52:40,480 --> 03:52:47,800
DEPARTMENT OF DEFENSE. FROM IPC

5649
03:52:47,800 --> 03:52:48,880
DERIVED MICROGROWIA WE CAN

5650
03:52:48,880 --> 03:52:53,480
INTEGRATE TO BRAIN ORGANOID ON

5651
03:52:53,480 --> 03:52:56,480
THE RESPECTIVE SLIDE.  THIS IS A

5652
03:52:56,480 --> 03:52:58,000
VERY -- TOOL, A MODEL YOU CAN

5653
03:52:58,000 --> 03:53:00,240
USE FOR MODELING VARIOUS

5654
03:53:00,240 --> 03:53:03,200
DISEASES I LIKE TO CALL THEM

5655
03:53:03,200 --> 03:53:05,240
MICROPATHOPHYSIOLOGICAL MODELS.

5656
03:53:05,240 --> 03:53:06,160
FIRST INTERESTED IN

5657
03:53:06,160 --> 03:53:16,640
DEVELOPMENTAL NEUROTOXICITY,

5658
03:53:19,840 --> 03:53:20,760
CHEMICALS AND OTHERS LINKED TO

5659
03:53:20,760 --> 03:53:21,520
AUTISM DRAMATIC I INCREASE THE

5660
03:53:21,520 --> 03:53:22,120
OVER LAST DEGAD. ALLOWS US TO

5661
03:53:22,120 --> 03:53:22,600
LOOK INTO DEMYELINATION,

5662
03:53:22,600 --> 03:53:23,240
REMYELINATION, VARIOUS DISEASES

5663
03:53:23,240 --> 03:53:25,760
WHICH ARE AFFECTING THIS, WE ARE

5664
03:53:25,760 --> 03:53:27,800
STUDYING GENE ENVIRONMENT,

5665
03:53:27,800 --> 03:53:29,200
DETECTION OF DISEASES BY

5666
03:53:29,200 --> 03:53:31,200
BRINGING IN RISK GENES FOR

5667
03:53:31,200 --> 03:53:34,680
EXAMPLE, VARIOUS TYPES OF NEW

5668
03:53:34,680 --> 03:53:35,840
NEURODEGENERATIVE DISEASE FROM

5669
03:53:35,840 --> 03:53:38,640
ALZHEIMERS TO PARKINSON TO

5670
03:53:38,640 --> 03:53:40,880
LATERAL SCLEROSIS, WE HAVE

5671
03:53:40,880 --> 03:53:42,720
GRAFTED THEM IN GLIOBLASTOMA.

5672
03:53:42,720 --> 03:53:45,760
THIS IS THE TOPIC TODAY, WE RUN

5673
03:53:45,760 --> 03:53:46,680
VARIOUS INFECTION MODELS IN

5674
03:53:46,680 --> 03:53:53,600
THIS. THIS STARTED IN 2018 BUT

5675
03:53:53,600 --> 03:53:56,360
PUBLISHED ON THE FACT THAT YOU

5676
03:53:56,360 --> 03:54:00,160
COULD INFECT BOTH ZIKA AND

5677
03:54:00,160 --> 03:54:07,600
DENGUE VIRUS, WE INCLUDED ALSO

5678
03:54:07,600 --> 03:54:09,760
MICROGLIA, NOT YET CDNF

5679
03:54:09,760 --> 03:54:11,800
MICROGLIA BUT MICROGLIA LIN LINE

5680
03:54:11,800 --> 03:54:17,360
SHOW INFLAMMATORY RESPONSESK SEE

5681
03:54:17,360 --> 03:54:18,960
DAMAGE TO NEURONS DUE TO RELEASE

5682
03:54:18,960 --> 03:54:20,560
OF CYTOKINES AND OTHERS SO YOU

5683
03:54:20,560 --> 03:54:22,040
CAN MODEL INFLAMMATORY PROCESSES

5684
03:54:22,040 --> 03:54:24,240
HERE. MORE RECENTLY, WE

5685
03:54:24,240 --> 03:54:27,120
PUBLISHED ON JC VIRUS, JC VIRUS

5686
03:54:27,120 --> 03:54:31,440
IS A VIRUS ASSOCIATED WITH HIV

5687
03:54:31,440 --> 03:54:34,560
INFECTION, IT IS NOT POSSIBLE TO

5688
03:54:34,560 --> 03:54:37,640
PROPAGATE VIRUS IN 2D CULTURE

5689
03:54:37,640 --> 03:54:40,040
NORMALLY, BUT HERE IN THE HIGH

5690
03:54:40,040 --> 03:54:44,000
DENSITY, OF THE 3D ORGANOID,

5691
03:54:44,000 --> 03:54:46,160
ABOUT 1,000 TIMES DENSER THAN 2D

5692
03:54:46,160 --> 03:54:47,280
CULTURE THERE IS POSSIBILITY TO

5693
03:54:47,280 --> 03:54:49,920
DO SO. WHAT IS INTERESTING OF

5694
03:54:49,920 --> 03:54:51,600
THE INFECTED CELLS ON THE

5695
03:54:51,600 --> 03:54:53,280
PICTURES BELOW ACTUALLY NOT

5696
03:54:53,280 --> 03:54:54,960
NEURONS BUT THE OLIGODENDROCYTES

5697
03:54:54,960 --> 03:54:57,480
AND THE ASTROCYTES OF THE

5698
03:54:57,480 --> 03:55:00,960
SYSTEM. SO THIS IS PUBLISHED IN

5699
03:55:00,960 --> 03:55:04,120
FEBRUARY THIS YEAR.  SO THEN THE

5700
03:55:04,120 --> 03:55:08,040
COVID PANDEMIC STARTED, IT

5701
03:55:08,040 --> 03:55:08,840
BECAME CLEAR QUICKLY THAT

5702
03:55:08,840 --> 03:55:12,840
DEPENDING ON THE COHORT YOU LOOK

5703
03:55:12,840 --> 03:55:15,840
UP TO 60% SHOW SOME TIME OF

5704
03:55:15,840 --> 03:55:18,840
NEUROLOGIC SYMPTOMS. VARIOUS

5705
03:55:18,840 --> 03:55:20,520
KINDS OF COLORFUL SPECTRUM OF

5706
03:55:20,520 --> 03:55:26,000
DISEASE FROM STROKE TO BRAIN

5707
03:55:26,000 --> 03:55:29,720
VARIOUS TYPE OF PSYCHOSIS

5708
03:55:29,720 --> 03:55:31,640
ENENCEPHALITIS. EVERYTHING HAS

5709
03:55:31,640 --> 03:55:33,920
BEEN REPORTED.  ENCEPHALITIS. SO

5710
03:55:33,920 --> 03:55:36,200
IN MARCH OF 2020 I GAVE A

5711
03:55:36,200 --> 03:55:37,560
PRESENTATION AND ASKED CAN THE

5712
03:55:37,560 --> 03:55:44,280
BRAIN BE INFECTED. BECAUSE IT

5713
03:55:44,280 --> 03:55:45,440
WAS A OBVIOUS POSSIBILITY. SOME

5714
03:55:45,440 --> 03:55:48,440
OF THE CORONA VIRUS IS UNKNOWN

5715
03:55:48,440 --> 03:55:50,400
NEUROTROPIC BUT IT WAS NOT KNOWN

5716
03:55:50,400 --> 03:55:52,000
FOR (INAUDIBLE) AT THE TIME.

5717
03:55:52,000 --> 03:55:53,280
QUIZ EASIER POST THAN ANSWERED

5718
03:55:53,280 --> 03:55:55,920
BUT THE RICH ENVIRONMENT IN

5719
03:55:55,920 --> 03:55:57,720
HOPKINS ALLOWED US TO PARTNER

5720
03:55:57,720 --> 03:56:03,760
WITH SOME INFECTIOUS DISEASE

5721
03:56:03,760 --> 03:56:06,040
PEOPLE CORRY WOOD AND TEAM

5722
03:56:06,040 --> 03:56:07,360
AFFECTED BRAIN ORGANOIDS.  THIS

5723
03:56:07,360 --> 03:56:10,600
WAS I THINK THE FIRST PICTURE

5724
03:56:10,600 --> 03:56:12,600
ACTUALLY OF HUMAN NEURON

5725
03:56:12,600 --> 03:56:14,080
INFECTED WITH SARS COV-2. YOU

5726
03:56:14,080 --> 03:56:17,440
CAN SEE THE RED DOTS EACH

5727
03:56:17,440 --> 03:56:18,960
REPRESENTING ONE VIRUS PARTICLE,

5728
03:56:18,960 --> 03:56:21,760
PARTICULARLY LARGE IN THIS CASE,

5729
03:56:21,760 --> 03:56:23,360
THIS GOT A LOT OF INTEREST,

5730
03:56:23,360 --> 03:56:24,600
FINANCIAL TIMES REPORTED ON IT

5731
03:56:24,600 --> 03:56:30,520
IN MAY OF 2020. 200 LAY PRESS

5732
03:56:30,520 --> 03:56:33,080
JOURNALS FOLLOWED AND OTHER

5733
03:56:33,080 --> 03:56:34,280
OUTLETS REPORTED ON THIS AND WE

5734
03:56:34,280 --> 03:56:37,720
WERE ACTUALLY ABLE TO FIRST

5735
03:56:37,720 --> 03:56:39,920
DESCRIBE IN THE PEER REVIEW

5736
03:56:39,920 --> 03:56:44,320
PAPER IN JUNE OF 2020, THIS IS

5737
03:56:44,320 --> 03:56:46,640
IN EFFECT NEUROTROPIC VIRUS.

5738
03:56:46,640 --> 03:56:49,680
PART OF THIS WAS SHOWING THAT

5739
03:56:49,680 --> 03:56:55,520
THE NECESSARY SARS 2 INHIBITOR

5740
03:56:55,520 --> 03:56:57,920
INHIBIT -- SARS 2 RECEPTOR FOUND

5741
03:56:57,920 --> 03:56:59,560
IN THE BRAIN FROM EARLY STAGES

5742
03:56:59,560 --> 03:57:06,720
OF NEURONAL PRECURSOR CELLS

5743
03:57:06,720 --> 03:57:08,240
ONWARDS. WE DID SHOW PRESENCE OF

5744
03:57:08,240 --> 03:57:11,160
VIRUS IN CELL -- DIFFERENT CELLS

5745
03:57:11,160 --> 03:57:12,880
AND ALSO REPLICATION BY PCR AND

5746
03:57:12,880 --> 03:57:17,360
CONFOCAL MICROSCOPY.  NICOLE

5747
03:57:17,360 --> 03:57:18,880
REFERRED TO THIS JOINT PAPER

5748
03:57:18,880 --> 03:57:22,120
ABOUT A YEAR LATER WE LOOKED

5749
03:57:22,120 --> 03:57:25,640
INTO THE SCIENTIFIC LITERATURE

5750
03:57:25,640 --> 03:57:26,520
AND HOW DOES THIS STAND NOW,

5751
03:57:26,520 --> 03:57:28,360
THIS WAS REALLY A VERY EARLY

5752
03:57:28,360 --> 03:57:30,640
FINDING. YOU HAVE TO RECALL, IN

5753
03:57:30,640 --> 03:57:36,080
MANY APRIL OF 2020, IN THE

5754
03:57:36,080 --> 03:57:38,520
LITERATURE WILL IS NO ANIMAL

5755
03:57:38,520 --> 03:57:40,080
MODEL FOR COVID AND MANY

5756
03:57:40,080 --> 03:57:42,480
CLINICAL DEVELOPMENTS HAD TO GO

5757
03:57:42,480 --> 03:57:45,520
INTO HUMAN TRIALS IN JUNE JUST

5758
03:57:45,520 --> 03:57:47,520
SAFETY TESTING DATA, NOT

5759
03:57:47,520 --> 03:57:48,640
EFFICACY BECAUSE NO ANIMAL MODEL

5760
03:57:48,640 --> 03:57:51,640
WAS THERE.  IT WAS AROUND SPRING

5761
03:57:51,640 --> 03:57:55,600
OF 2020 THIS TYPE OF MODELS ARE

5762
03:57:55,600 --> 03:57:56,960
DELIVERING, SHOWING VARIOUS

5763
03:57:56,960 --> 03:57:58,320
ORGAN CONTRIBUTIONS WHICH

5764
03:57:58,320 --> 03:58:00,120
ACTUALLY MAKE COVID SUCH A

5765
03:58:00,120 --> 03:58:02,760
DEADLY COLORFUL DISEASE. WHICH

5766
03:58:02,760 --> 03:58:04,760
ARE NOT REPRODUCIBLE UNTIL NOW

5767
03:58:04,760 --> 03:58:09,960
IN ANY ANIMAL MODEL. IF LEADING

5768
03:58:09,960 --> 03:58:12,280
TO LUNG INFECTION AT LEAST NOT

5769
03:58:12,280 --> 03:58:16,120
FROM TODAY ANY MAJOR CNS

5770
03:58:16,120 --> 03:58:19,120
CONTRIBUTION OF THE DISEASE.  SO

5771
03:58:19,120 --> 03:58:20,720
JUST TO SHOW YOU A LITTLE BIT OF

5772
03:58:20,720 --> 03:58:22,960
THESE EXPERIMENTS WHICH HAVE

5773
03:58:22,960 --> 03:58:28,120
BEEN PUBLISHED THE NEWS

5774
03:58:28,120 --> 03:58:32,040
RELATIVELY SMALL OF OPEN VIRUS

5775
03:58:32,040 --> 03:58:35,080
IN THE CELL SIX HOURS EXPOSURE

5776
03:58:35,080 --> 03:58:37,560
THEN WE DID WASH AND WE STUDIED

5777
03:58:37,560 --> 03:58:42,520
THE COPY NUMBER OF THE RNA OF

5778
03:58:42,520 --> 03:58:45,440
VIRUS IN THE LYSATE SUPERNATANT.

5779
03:58:45,440 --> 03:58:46,840
AND WE DID LOOK FOR THE VIRUS

5780
03:58:46,840 --> 03:58:48,920
ALSO IN STAINING FOR BOTH THE

5781
03:58:48,920 --> 03:58:54,560
SPIKE OF THE M PROTEIN. YOU CAN

5782
03:58:54,560 --> 03:58:59,400
SEE THIS VIRUSES HERE, INFECTED

5783
03:58:59,400 --> 03:59:01,200
CELLS ARE SOME NOT VERY MANY

5784
03:59:01,200 --> 03:59:05,200
CELLS BUT FOUND THROUGHOUT THE

5785
03:59:05,200 --> 03:59:06,280
ORGANOID. YOU CAN DO CERTAIN

5786
03:59:06,280 --> 03:59:13,240
COUNTER STAINS.  THIS IS NOW THE

5787
03:59:13,240 --> 03:59:18,160
SPIKE PROTEIN. IT IS NOT

5788
03:59:18,160 --> 03:59:20,120
CO-LOCALIZING WITH GFAP WHICH IS

5789
03:59:20,120 --> 03:59:21,960
THE AMOUNT OF ASTROCYTES SO NOT

5790
03:59:21,960 --> 03:59:23,760
THE ASTROCYTES POPULATION WHICH

5791
03:59:23,760 --> 03:59:30,120
IS INFECTED HERE.  WE THINK SOME

5792
03:59:30,120 --> 03:59:31,240
TYPES OF NEURONS BEING INFECTED 

5793
03:59:31,240 --> 03:59:34,600
I HOPE YOU CAN SEE THIS TYPE OF

5794
03:59:34,600 --> 03:59:37,240
PICTURES WHICH IS SHOWING A CELL

5795
03:59:37,240 --> 03:59:40,800
WE INTERPRET BEING SPACE LYSED

5796
03:59:40,800 --> 03:59:43,120
SO INFECTION PROPAGATING THE

5797
03:59:43,120 --> 03:59:46,640
VIRUS SET FREE. AND ABLE TO

5798
03:59:46,640 --> 03:59:50,080
INFECT FURTHER CELLS. IN THE

5799
03:59:50,080 --> 03:59:52,360
PATHOLOGY YOU CAN FIND THESE

5800
03:59:52,360 --> 03:59:54,720
CELLS AND YOU CAN SEE THE

5801
03:59:54,720 --> 03:59:56,720
CHANGES ENORMOUS AMOUNT OF

5802
03:59:56,720 --> 03:59:58,480
DIVERSITY CONDENSED CHROMATIN ON

5803
03:59:58,480 --> 03:59:59,560
THE RIGHT WHERE THE MOCK

5804
03:59:59,560 --> 04:00:00,760
INFECTION IS NOT SHOWING THIS

5805
04:00:00,760 --> 04:00:06,880
TYPE OF STRUCTURE.  THIS IS THE

5806
04:00:06,880 --> 04:00:08,880
PCR RESULTS ON THE LEFT FOR CELL

5807
04:00:08,880 --> 04:00:14,400
LYSATE.  YOU CAN SEE IN THESE

5808
04:00:14,400 --> 04:00:16,200
TOTAL 64 HOURS YOU SEE 3500 FOLD

5809
04:00:16,200 --> 04:00:17,960
INCREASE IN COPIES OF THE VIRUS

5810
04:00:17,960 --> 04:00:22,440
OVER LYSATE AND IN SUPERNATANT,

5811
04:00:22,440 --> 04:00:25,200
SO IT IS NOT ONLY PRODUCED IN

5812
04:00:25,200 --> 04:00:27,280
THE CELLS AND REPLICATING BUT

5813
04:00:27,280 --> 04:00:31,680
ALSO SET FREE FROM THE ORGANOID.

5814
04:00:31,680 --> 04:00:34,920
THIS IS AGAIN REVIEW PAPER,

5815
04:00:34,920 --> 04:00:38,560
WHICH NICOLE TOUCHED ON, IT IS

5816
04:00:38,560 --> 04:00:40,720
SHOWING MORE THAN TEN GROUPS

5817
04:00:40,720 --> 04:00:42,520
MEANTIME SHOWN INDEED

5818
04:00:42,520 --> 04:00:43,120
MICROPHYSIOLOGICAL SYSTEMS OF

5819
04:00:43,120 --> 04:00:44,640
THE BRAIN CAN BE INFECTED WITH

5820
04:00:44,640 --> 04:00:48,280
THIS VIRUS.  STUDYING DIFFERENT

5821
04:00:48,280 --> 04:00:52,560
ASPECTS SHOWN HERE. WE SUMMARIZE

5822
04:00:52,560 --> 04:00:54,720
CLINICAL DATA, THEY ARE VERY

5823
04:00:54,720 --> 04:00:56,080
MUCH IN LINE THAT THERE IS SOME

5824
04:00:56,080 --> 04:01:00,320
INFECTION OF THE BRAIN BUT NOT

5825
04:01:00,320 --> 04:01:01,440
PERMANENT INFECTION BUT

5826
04:01:01,440 --> 04:01:02,440
PERSISTENT INFECTION OF THE

5827
04:01:02,440 --> 04:01:04,120
SYSTEM. THESE ARE SOME OF THE

5828
04:01:04,120 --> 04:01:07,960
PAPERS, SUMMARIZE BY OTHERS SO

5829
04:01:07,960 --> 04:01:10,040
MEANTIME THERE IS SOLID

5830
04:01:10,040 --> 04:01:15,920
LITERATURE ON NEURONAL INFECTION

5831
04:01:15,920 --> 04:01:24,000
BY SARS COV-2. THIS IS THE SLIDE

5832
04:01:24,000 --> 04:01:25,120
SHOWING NO CONSENSUS ON HOW

5833
04:01:25,120 --> 04:01:26,960
EFFECTS ON THE BRAIN BEING

5834
04:01:26,960 --> 04:01:29,320
PRODUCED, PROBABLY DIFFERENT

5835
04:01:29,320 --> 04:01:32,720
MECHANISMS. OBVIOUSLY IN SEVERE

5836
04:01:32,720 --> 04:01:33,960
COVID OF THE ENTIRE BODY WHICH

5837
04:01:33,960 --> 04:01:35,120
HAS AFFECT ON FUNCTIONING OF

5838
04:01:35,120 --> 04:01:37,240
BRAIN, THE CYTOKINE STORM, THE

5839
04:01:37,240 --> 04:01:38,320
PENETRATION THROUGH THE BLOOD

5840
04:01:38,320 --> 04:01:41,760
BRAIN BARRIER SUGGESTED BY SOME,

5841
04:01:41,760 --> 04:01:45,480
BUT NOT CONCLUSIVELY SHOWN.  

5842
04:01:45,480 --> 04:01:47,600
THERE IS SOME SUGGESTION

5843
04:01:47,600 --> 04:01:49,320
OLFACTSRY NERVE MIGHT BE

5844
04:01:49,320 --> 04:01:51,120
POSSIBLE THAT RETRO GRADE

5845
04:01:51,120 --> 04:01:53,920
INFECTION OF BRAIN CAN TAKE

5846
04:01:53,920 --> 04:01:57,000
PLACE. MAINLY HYPERCORRELATION

5847
04:01:57,000 --> 04:01:58,240
ISCHEMIA AND VASOCONVICTION

5848
04:01:58,240 --> 04:02:01,600
WHICH LEADS TO REDUCED OXYGEN

5849
04:02:01,600 --> 04:02:05,360
WHICH IS ACTING ON THE BRAIN.

5850
04:02:05,360 --> 04:02:06,440
THERE HAVE BEEN CLEAR EVIDENCE

5851
04:02:06,440 --> 04:02:09,120
IN PATIENTS OF VIRUS IN CELLS

5852
04:02:09,120 --> 04:02:13,320
VIRUS IN THE CELL SPINAL FLUID,

5853
04:02:13,320 --> 04:02:16,240
AND ANTIBODY PRODUCTION WHICH

5854
04:02:16,240 --> 04:02:18,560
SEEMS TO BE FOR BRAIN INFECTION,

5855
04:02:18,560 --> 04:02:21,160
AND NOT IMMUNIZATION.  WE ARE

5856
04:02:21,160 --> 04:02:23,840
CONTINUING TO WORK ON THIS

5857
04:02:23,840 --> 04:02:26,000
TOPICS TO IDENTIFY WHY THIS

5858
04:02:26,000 --> 04:02:28,440
SUBPOPULATION INFECTED WHAT

5859
04:02:28,440 --> 04:02:30,560
AREAS OF THE CELLS WE HAVE

5860
04:02:30,560 --> 04:02:31,920
PROLONGED INFECTION SCENARIO

5861
04:02:31,920 --> 04:02:35,040
WORKING ON BLOOD BRAIN BARRIER

5862
04:02:35,040 --> 04:02:37,040
ASPECT AND MOST INTERESTED ALSO

5863
04:02:37,040 --> 04:02:38,320
STUDY INFLAMMATORY COMPONENT AS

5864
04:02:38,320 --> 04:02:40,880
THIS IS A RISK FACTOR FOR

5865
04:02:40,880 --> 04:02:43,080
VARIOUS DISEASES AS YOU KNOW FOR

5866
04:02:43,080 --> 04:02:48,560
OTHER NEUROTROPIC INFECTIONS.  

5867
04:02:48,560 --> 04:02:50,120
SEW ONE QUESTION WE ARE

5868
04:02:50,120 --> 04:02:52,160
INTERESTED IN IS THIS POSITIVELY

5869
04:02:52,160 --> 04:02:53,360
IMPACTING ON NEURAL DEVELOPMENT

5870
04:02:53,360 --> 04:02:56,800
ON AUTISM? BECAUSE THE BABIES OF

5871
04:02:56,800 --> 04:02:58,040
PANDEMIC ARE NOT YET OLD ENOUGH

5872
04:02:58,040 --> 04:03:03,840
TO REALLY ASSESS THIS AUTISM IS

5873
04:03:03,840 --> 04:03:05,240
DIAGNOSED BETWEEN 2 AND 3

5874
04:03:05,240 --> 04:03:07,440
SOMETIMES AS LATE AS 8 YEARS OF

5875
04:03:07,440 --> 04:03:11,520
PAGE. GOOD NEWS HERE IS THAT OUR

5876
04:03:11,520 --> 04:03:13,600
PRELIMINARY DATA KNOW THE EARLY

5877
04:03:13,600 --> 04:03:16,720
BRAIN DEVELOPMENT WHICH IS

5878
04:03:16,720 --> 04:03:19,520
VULNERABLE ASK WE BE INFECTED

5879
04:03:19,520 --> 04:03:21,880
VIRUS IS NOT PROPAGATING AS YOU

5880
04:03:21,880 --> 04:03:24,360
CAN SEE IN THE FIVE WEEK OLD

5881
04:03:24,360 --> 04:03:28,880
BRAIN, HERE IN BLACK, WHILE

5882
04:03:28,880 --> 04:03:33,200
EIGHT WEEK OLD ARE SHOWING

5883
04:03:33,200 --> 04:03:34,760
PROGRESSIVE INFECTION FURTHER

5884
04:03:34,760 --> 04:03:36,840
INCREASE VIRUS AMONG SO THIS IS

5885
04:03:36,840 --> 04:03:38,800
ALREADY SOME TYPE OF HOMOFUL

5886
04:03:38,800 --> 04:03:40,880
SCIENCE NEURAL DEVELOPMENT IS

5887
04:03:40,880 --> 04:03:42,280
NOT AS MUCH AND ACTUALLY THERE

5888
04:03:42,280 --> 04:03:44,880
IS MARKERS OF NEURAL DEVELOPMENT

5889
04:03:44,880 --> 04:03:47,080
BY PCR SHOW THAT THERE IS NO

5890
04:03:47,080 --> 04:03:49,280
MAJOR CHANGE IN COMPARTMENT OF

5891
04:03:49,280 --> 04:03:52,200
CELLS DUE TO INFECTION SO WE ARE

5892
04:03:52,200 --> 04:03:54,960
QUITE HOPEFUL THAT THIS IS NOT

5893
04:03:54,960 --> 04:03:58,240
STRONG IMPACTING. SO IN SUMMARY

5894
04:03:58,240 --> 04:03:59,960
OF THESE PARTS THIS IS A

5895
04:03:59,960 --> 04:04:02,640
STANDARDIZED HUMAN 3D MODEL

5896
04:04:02,640 --> 04:04:04,960
DEVELOPED FROM STEM CELLS, GLIAL

5897
04:04:04,960 --> 04:04:08,960
CELLS MYELINATION AND MICRO--

5898
04:04:08,960 --> 04:04:11,320
WHICH CAN BE EDIT GENETIC

5899
04:04:11,320 --> 04:04:12,520
BACKGROUNDS BUT INTRODUCE RISK

5900
04:04:12,520 --> 04:04:14,360
GENES REPAIR INCLUDE REPORTER

5901
04:04:14,360 --> 04:04:16,480
GENES LIKE THE ONE FOR

5902
04:04:16,480 --> 04:04:17,760
OLIGODENDROCYTES. INFECTION

5903
04:04:17,760 --> 04:04:18,760
OTHER DISEASES CAN BE MODELED

5904
04:04:18,760 --> 04:04:20,880
AND WE ARE VERY MUCH INTERESTED

5905
04:04:20,880 --> 04:04:22,040
IN GENE ENVIRONMENT INTERACTIONS

5906
04:04:22,040 --> 04:04:25,800
IN THE MODEL. FUNCTIONAL ASSAYS

5907
04:04:25,800 --> 04:04:28,240
ARE POSSIBLE NEURITE OUTGROWTH

5908
04:04:28,240 --> 04:04:32,440
EEG, EVEN HAVE THREE DIMENSIONAL

5909
04:04:32,440 --> 04:04:33,920
EEG TYPE OF ELECTROPHYSIOLOGY

5910
04:04:33,920 --> 04:04:37,560
AND MOST RECENTLY INTERESTED IN

5911
04:04:37,560 --> 04:04:39,600
IMPLEMENTING COGNITIVE FUNCTION,

5912
04:04:39,600 --> 04:04:42,840
ORGANOID INTELLIGENCE. I WOULD

5913
04:04:42,840 --> 04:04:46,360
LIKE TO SAY A FEW WORDS TIME

5914
04:04:46,360 --> 04:04:49,440
REMAINING. BIOLOGICAL MODELS ARE

5915
04:04:49,440 --> 04:04:50,640
MODEL, THEY CAN GIVE RISE TO

5916
04:04:50,640 --> 04:04:53,880
MANY DIFFERENT ASSAYS.  AND FROM

5917
04:04:53,880 --> 04:04:55,600
MY UNDERSTANDING WHAT THE

5918
04:04:55,600 --> 04:04:57,120
DISCUSSION IS ABOUT IS ACTUALLY

5919
04:04:57,120 --> 04:04:59,600
ABOUT ASSAYS AND WE HAVE TO

5920
04:04:59,600 --> 04:05:02,000
REALLY ESTABLISH WHAT ARE LIMITS

5921
04:05:02,000 --> 04:05:03,680
OF THE DETECTION LIMITS OF

5922
04:05:03,680 --> 04:05:04,880
QUANTIFICATION, WHAT IS THE

5923
04:05:04,880 --> 04:05:08,600
DYNAMIC RANGE OF THESE ASSAYS WE

5924
04:05:08,600 --> 04:05:09,800
CAN ESTABLISH THAT DEFINE

5925
04:05:09,800 --> 04:05:13,440
REASONABLE BIOMARKERS POINT OF

5926
04:05:13,440 --> 04:05:17,080
INTEREST. THIS REQUIRES A LOT OF

5927
04:05:17,080 --> 04:05:19,520
THINKING MOVING MODEL TO

5928
04:05:19,520 --> 04:05:20,760
SOMETHING ELSE. WE ARE WORKING

5929
04:05:20,760 --> 04:05:22,120
AT THE MOMENT ALSO ON FREEZING

5930
04:05:22,120 --> 04:05:25,520
BRAIN ORGANOIDS AND THE

5931
04:05:25,520 --> 04:05:26,760
DIFFERENCE BETWEEN WHAT YOU SEE

5932
04:05:26,760 --> 04:05:30,720
HERE IS JUST ONE WAS KEPT IN

5933
04:05:30,720 --> 04:05:34,320
CULTURE, OTHER WAS FROZEN AND

5934
04:05:34,320 --> 04:05:37,760
FORM AD FEW DAYS LATER. WE STILL

5935
04:05:37,760 --> 04:05:40,200
SEE THAT THEY ARE FLUFFY BUT

5936
04:05:40,200 --> 04:05:41,600
SHOW NEURITE OUTGROWTH AND WE

5937
04:05:41,600 --> 04:05:43,360
ARE LOOKING LEK ROW PHYSIOLOGY

5938
04:05:43,360 --> 04:05:45,400
TO OPTIMIZE PROCESS --

5939
04:05:45,400 --> 04:05:46,160
ELECTROPHYSIOLOGY TO OPTIMIZE

5940
04:05:46,160 --> 04:05:49,280
THE PROCESSES. THIS IS TO REALLY

5941
04:05:49,280 --> 04:05:50,920
HAVE AN OPPORTUNITY TO SEND THEM

5942
04:05:50,920 --> 04:05:52,040
OUT, AT ROOM TEMPERATURE WE CAN

5943
04:05:52,040 --> 04:05:53,840
SEND THEM OUT AND CERTAIN CASES

5944
04:05:53,840 --> 04:05:56,080
SEVEN DAYS OF TRANSPORT DID NOT

5945
04:05:56,080 --> 04:05:57,520
DAMAGE THEM, THEY CAN BE USED

5946
04:05:57,520 --> 04:05:59,240
FOR FURTHER EXPERIMENTS. SO FOR

5947
04:05:59,240 --> 04:06:02,120
EXAMPLE, WE ARE DELIVERING BRAIN

5948
04:06:02,120 --> 04:06:06,520
ORGANOIDS FOR RABIES RESEARCH IN

5949
04:06:06,520 --> 04:06:08,040
BELGIUM AND AUSTRALIA FOR

5950
04:06:08,040 --> 04:06:11,120
COGNITIVE FUNCTION. AND WOULD BE

5951
04:06:11,120 --> 04:06:12,360
TO BRING THEM ALSO IN OTHER

5952
04:06:12,360 --> 04:06:15,600
ENVIRONMENTS OF RESEARCH. I

5953
04:06:15,600 --> 04:06:17,720
WOULD LIKE TO SAY FEW WORDS ON

5954
04:06:17,720 --> 04:06:20,880
QUALITY. I'M ONE OF THE

5955
04:06:20,880 --> 04:06:22,880
PROPOINTS OF CELL CULTURE

5956
04:06:22,880 --> 04:06:25,800
PRACTICES IN VITRO REPORTING

5957
04:06:25,800 --> 04:06:27,120
STANDARDS, AND VALIDATION,

5958
04:06:27,120 --> 04:06:28,880
HAVING THE VALIDATION BODY OF

5959
04:06:28,880 --> 04:06:31,400
THE EUROPEAN COMMISSION. AS

5960
04:06:31,400 --> 04:06:35,600
APPEARS IN 1996, I WANT TO BE

5961
04:06:35,600 --> 04:06:40,880
SHORT PUBLISHED IN 2005 AS A

5962
04:06:40,880 --> 04:06:41,760
GUIDANCE FROM EUROPEAN

5963
04:06:41,760 --> 04:06:44,080
COMMISSION. WE TEAMED UP IN

5964
04:06:44,080 --> 04:06:45,760
2015, THIS GUIDANCE DOESN'T

5965
04:06:45,760 --> 04:06:48,000
INCLUDE STEM CELL MODELS,

5966
04:06:48,000 --> 04:06:49,120
MICROPHYSIOLOGICAL SYSTEMS, SO

5967
04:06:49,120 --> 04:06:51,120
WE TEAMED UP WITH VARIOUS

5968
04:06:51,120 --> 04:06:53,280
ORGANIZATIONS AND HAD TWO

5969
04:06:53,280 --> 04:06:55,280
WORKSHOPS AND THESE ARE WORKSHOP

5970
04:06:55,280 --> 04:06:56,680
REPORTS, WHICH ARE AVAILABLE IN

5971
04:06:56,680 --> 04:06:59,840
THE MEANTIME AND WE THEN FINALLY

5972
04:06:59,840 --> 04:07:01,800
PUBLISHED IN JANUARY OF THIS

5973
04:07:01,800 --> 04:07:04,640
YEAR GUIDANCE DOCUMENT OF 350

5974
04:07:04,640 --> 04:07:07,520
COMMENTS FROM STAKEHOLDERS MORE

5975
04:07:07,520 --> 04:07:08,840
THAN 100 DIFFERENT STAKEHOLDERS

5976
04:07:08,840 --> 04:07:11,160
COMMENTING ON THIS AND THIS IS

5977
04:07:11,160 --> 04:07:12,720
NOW NEW GUIDANCE DOCUMENT AND WE

5978
04:07:12,720 --> 04:07:14,240
ARE ENTERING DISSEMINATION PHASE

5979
04:07:14,240 --> 04:07:15,520
TRYING TO CONVINCE FUNDING

5980
04:07:15,520 --> 04:07:16,840
BODIES AND JOURNALS TO ACCEPT

5981
04:07:16,840 --> 04:07:21,920
THIS AS A NEW STANDARD.  WE ALSO

5982
04:07:21,920 --> 04:07:25,800
INITIATED ALREADY WORK TOWARDS

5983
04:07:25,800 --> 04:07:29,680
REPORTING BECAUSE WE

5984
04:07:29,680 --> 04:07:31,000
REPRODUCIBILITY PROBLEMS IN OUR

5985
04:07:31,000 --> 04:07:34,320
FIELD ARE NOT DUE TO US BUT

5986
04:07:34,320 --> 04:07:35,960
BETTER REPORT E BAD REPORTING

5987
04:07:35,960 --> 04:07:37,840
AND DIFFICULT TO REPRODUCE.  WE

5988
04:07:37,840 --> 04:07:40,000
HAVE SOME EXAMPLES LIKE THE IN

5989
04:07:40,000 --> 04:07:41,400
VITRO TOXICOLOGY FEMME PLATE,

5990
04:07:41,400 --> 04:07:42,520
THIS IS ONGOING AND HOPE TO

5991
04:07:42,520 --> 04:07:44,840
EXTEND TO MICROPHYSICAL GENETIC

5992
04:07:44,840 --> 04:07:45,880
SYSTEMS. WITH THIS I WOULD LIKE

5993
04:07:45,880 --> 04:07:51,320
TO CLOSE. USING (INDISCERNIBLE)

5994
04:07:51,320 --> 04:07:53,760
VERY SUITING QUOTE, THE

5995
04:07:53,760 --> 04:07:55,640
DIFFICULTY LIES NOT IN THE NEW

5996
04:07:55,640 --> 04:07:57,000
IDEAS BUT ESCAPING FROM THE OLD

5997
04:07:57,000 --> 04:07:59,240
ONES.  THANK YOU VERY MUCH.

5998
04:07:59,240 --> 04:08:01,920
>> THANK YOU VERY MUCH,
THAT WAS

5999
04:08:01,920 --> 04:08:03,320
WONDERFUL TALK. VERY INTERESTING

6000
04:08:03,320 --> 04:08:07,960
TOPIC. I LOOK FORWARD TO GETTING

6001
04:08:07,960 --> 04:08:09,080
THE QUESTIONS AT THE END OF THE

6002
04:08:09,080 --> 04:08:12,000
PRESENTATIONS.  I WOULD LIKE TO

6003
04:08:12,000 --> 04:08:15,840
INTRODUCE OUR LAST SPEAKER FOR

6004
04:08:15,840 --> 04:08:23,760
THIS SESSION. DR. ROSADO

6005
04:08:23,760 --> 04:08:27,440
OLIVIERI, VICE PRESIDENT OF

6006
04:08:27,440 --> 04:08:32,000
RUMIVIRO. DR. ROSADO RECEIVED

6007
04:08:32,000 --> 04:08:33,800
STEM CELL BIOLOGY FROM HARVARD

6008
04:08:33,800 --> 04:08:35,480
MEDICAL SCHOOL AND MIT

6009
04:08:35,480 --> 04:08:38,160
POST-DOCTORAL RESEARCH WITH DR.

6010
04:08:38,160 --> 04:08:40,360
(INAUDIBLE) AT ROCKEFELLAR

6011
04:08:40,360 --> 04:08:42,280
UNIVERSITY. HE DEVELOPED AN

6012
04:08:42,280 --> 04:08:43,880
INNOVATIVE STEM CELL BASED

6013
04:08:43,880 --> 04:08:47,480
PLATFORM TO TRACK INFECTION BY

6014
04:08:47,480 --> 04:08:48,680
RESPIRATORY VIRUSES AND IDENTIFY

6015
04:08:48,680 --> 04:08:50,520
THERAPEUTIC FOR COVID-19 AND IN

6016
04:08:50,520 --> 04:08:52,720
COLLABORATION WITH DR. CHARLIE

6017
04:08:52,720 --> 04:08:56,160
RICE. HE ALSO SPEARHEADED

6018
04:08:56,160 --> 04:08:59,000
CREATION OF RUMIVIRO WHICH IS

6019
04:08:59,000 --> 04:09:00,720
FIRST IN CLASS BROAD SPECTRUM

6020
04:09:00,720 --> 04:09:01,360
ANTIVIRAL THERAPEUTICS FOR

6021
04:09:01,360 --> 04:09:03,000
RESPIRATORY VIRUSES AND VIRUS

6022
04:09:03,000 --> 04:09:05,640
INDUCED ACUTE KIDNEY INJURY. THE

6023
04:09:05,640 --> 04:09:08,160
TITLE OF HIS TALK TODAY IS

6024
04:09:08,160 --> 04:09:09,600
STANDARDIZE HUMAN MINI ORGAN ON

6025
04:09:09,600 --> 04:09:11,120
MICROCHIPS TO IDENTIFY ANTIVIRAL

6026
04:09:11,120 --> 04:09:13,840
THERAPEUTICS AT SCALE. THE FLOOR

6027
04:09:13,840 --> 04:09:17,120
IS ALL YOURS.

6028
04:09:17,120 --> 04:09:18,400
>> THANK YOU. THANK YOU SO
MUCH

6029
04:09:18,400 --> 04:09:20,280
FOR THE ORGANIZERS FOR INVITING

6030
04:09:20,280 --> 04:09:22,560
ME TO SUCH AN IMPORTANT FORUM,

6031
04:09:22,560 --> 04:09:24,680
TODAY IT IS MY PLEASURE TO TELL

6032
04:09:24,680 --> 04:09:26,640
YOU ABOUT OUR COMPANY RUMIVIRO

6033
04:09:26,640 --> 04:09:28,160
AND HOW WE ARE USING A

6034
04:09:28,160 --> 04:09:29,600
PSEUDOAPPROACH TO WHAT'S

6035
04:09:29,600 --> 04:09:30,720
DESCRIBED MANY TIMES WITH STEM

6036
04:09:30,720 --> 04:09:37,440
CELL BASED MODELS TO RECAPITATE

6037
04:09:37,440 --> 04:09:40,120
LATE BUT THIS TIME FULLY

6038
04:09:40,120 --> 04:09:41,480
STANDARDIZED APPROACHES TO

6039
04:09:41,480 --> 04:09:42,880
DERIVE ORGANS TO IDENTIFY

6040
04:09:42,880 --> 04:09:43,880
UNDEVELOPED THERAPEUTICS OF

6041
04:09:43,880 --> 04:09:47,680
SCALE. OF COURSE THE WAY WE DO

6042
04:09:47,680 --> 04:09:49,960
OUR WORK IS THE FACT THAT

6043
04:09:49,960 --> 04:09:53,600
BECAUSE OF THE HUGE BURDEN VIRUS

6044
04:09:53,600 --> 04:09:56,920
ON GLOBAL HEALTH NOT ONLY COVID

6045
04:09:56,920 --> 04:09:58,320
PANDEMIC BUT WITH MANY OTHER

6046
04:09:58,320 --> 04:09:59,960
VIRUSES INCLUDING RESPIRATORY

6047
04:09:59,960 --> 04:10:02,520
VIRUS AS WELL AS MANY OTHERS

6048
04:10:02,520 --> 04:10:03,960
THAT STILL COST A LARGE FRACTION

6049
04:10:03,960 --> 04:10:06,600
OF HUMAN DISEASE. THE MAIN

6050
04:10:06,600 --> 04:10:07,560
CHALLENGE WITH VIRUSES IN

6051
04:10:07,560 --> 04:10:09,840
GENERAL IS THAT FOR MANY OF

6052
04:10:09,840 --> 04:10:11,600
THEM, THERE IS COMPLETE ABSENCE

6053
04:10:11,600 --> 04:10:13,240
OF TREATMENT OR VACCINES AND

6054
04:10:13,240 --> 04:10:14,600
EVEN WHEN THERE ARE VACCINES FOR

6055
04:10:14,600 --> 04:10:16,560
MANY -- FOR SOME THERE IS ALWAYS

6056
04:10:16,560 --> 04:10:20,640
THESE ISSUES OF EMERGENCE OF NEW

6057
04:10:20,640 --> 04:10:23,200
VARIANTS WHOSE RES ISTANT

6058
04:10:23,200 --> 04:10:25,680
MUTATIONS IN SYSTEMS AGAIN

6059
04:10:25,680 --> 04:10:27,880
CURRENT -- THIS HIGHLIGHTS THE

6060
04:10:27,880 --> 04:10:29,840
NEED FOR NOVEL ANTIVIRAL DRUG

6061
04:10:29,840 --> 04:10:31,600
DISCOVERY PARADIGM THAT CAN LEAD

6062
04:10:31,600 --> 04:10:33,480
TO NEW THERAPEUTIC STUDIES TO

6063
04:10:33,480 --> 04:10:38,880
TACKLE VIRUSES THAT ARE MAY

6064
04:10:38,880 --> 04:10:40,680
CAUSE PANDEMIC, THIS WHERE I

6065
04:10:40,680 --> 04:10:43,000
THINK MODELS MAY PLAY A BIG ROLE

6066
04:10:43,000 --> 04:10:46,240
IN THE NEAR FUTURE. I THINK THE

6067
04:10:46,240 --> 04:10:47,480
CHALLENGE WITH ANTIVIRAL DRUG

6068
04:10:47,480 --> 04:10:50,040
DEVELOPMENT IS THE EFFORTS THAT

6069
04:10:50,040 --> 04:10:52,640
HAVE BEEN DEPLOYED ARE ACTUALLY

6070
04:10:52,640 --> 04:10:54,800
TARGET BASE WHERE DRUG IS

6071
04:10:54,800 --> 04:10:56,200
DEVELOPED AGAINST SPECIFIC VIRAL

6072
04:10:56,200 --> 04:10:58,080
TARGET OR HOST FACTOR, AND THE

6073
04:10:58,080 --> 04:11:00,800
CHALLENGE WITH THIS IS THAT

6074
04:11:00,800 --> 04:11:03,520
TARGETS ARE JUST A FEW AND HOST

6075
04:11:03,520 --> 04:11:05,400
FACTORS ARE TYPICALLY ELUSIVE

6076
04:11:05,400 --> 04:11:07,080
FOR MANY VIRUSES THAT ARE OF

6077
04:11:07,080 --> 04:11:09,960
CONCERN SO THERE IS A QUESTION

6078
04:11:09,960 --> 04:11:11,640
AS TO HOW SPECIFIC TARGET FOR

6079
04:11:11,640 --> 04:11:12,800
THERAPEUTIC DEVELOPMENT AND HOW

6080
04:11:12,800 --> 04:11:15,320
DO YOU PRIORITIZE THEM. ON THE

6081
04:11:15,320 --> 04:11:17,480
OTHER END OF THE SPECTRUM YOU

6082
04:11:17,480 --> 04:11:20,440
CAN THINK ABOUT SUB BASE

6083
04:11:20,440 --> 04:11:22,560
APPROACHES FOR NON-KINASE CELLS

6084
04:11:22,560 --> 04:11:26,040
HAS A WAY OF IDENTIFYING

6085
04:11:26,040 --> 04:11:27,440
ANTIVIRAL ACTIVITY AGAINST

6086
04:11:27,440 --> 04:11:29,080
VIRUSES, AND I THINK THE

6087
04:11:29,080 --> 04:11:31,760
CHALLENGE HERE IS THE FIELD HAS

6088
04:11:31,760 --> 04:11:33,200
ADOPTED THE CANCER CELL LINES AS

6089
04:11:33,200 --> 04:11:35,240
STANDARD FOR TESTING

6090
04:11:35,240 --> 04:11:38,320
THERAPEUTICS IN PRE-CLINICAL

6091
04:11:38,320 --> 04:11:39,920
ASSAYS, IN DRUG DISCOVERY AND

6092
04:11:39,920 --> 04:11:41,480
DRUG TESTING PARADIGMS. THE

6093
04:11:41,480 --> 04:11:45,240
ISSUE WITH THIS IS THAT THESE

6094
04:11:45,240 --> 04:11:47,440
CELL LINES LACK ORGAN FACILITY

6095
04:11:47,440 --> 04:11:49,480
AND WE HAVE HIGHLIGHTED MANY

6096
04:11:49,480 --> 04:11:51,240
TIMES DURING THE LAST FEW DAYS

6097
04:11:51,240 --> 04:11:55,200
THEY ALSO DISPLAY KEY

6098
04:11:55,200 --> 04:11:58,280
DIFFERENCES IN BIOPATHWAYS.

6099
04:11:58,280 --> 04:12:00,320
IMPORTANT CHALLENGE REALLY

6100
04:12:00,320 --> 04:12:01,720
IMPORTANT SPECIFICALLY IN

6101
04:12:01,720 --> 04:12:03,720
CONCEPT OF COVID-19 WHERE MANY

6102
04:12:03,720 --> 04:12:06,880
DRUGS WE ARE IDENTIFIED IN DRUG

6103
04:12:06,880 --> 04:12:07,680
REPURPOSING EFFORTS YOU HAVE

6104
04:12:07,680 --> 04:12:10,480
SEEP THESE CELL LINES ENDED UP

6105
04:12:10,480 --> 04:12:12,520
FAILING CLINICAL TRIALS DUE TO

6106
04:12:12,520 --> 04:12:14,400
NON-PHYSICAL MECHANISM OF ACTION

6107
04:12:14,400 --> 04:12:15,520
AS IT WAS HIGHLIGHTED IN THIS

6108
04:12:15,520 --> 04:12:19,760
RECENT STUDY BY THE GROUP OUT OF

6109
04:12:19,760 --> 04:12:23,360
UCSF. THIS AGAIN HIGHLIGHTS THE

6110
04:12:23,360 --> 04:12:26,480
NEED FOR NEW NOVEL TISSUE BASE

6111
04:12:26,480 --> 04:12:28,600
MODELS FOR NOT ONLY ANTIVIRAL

6112
04:12:28,600 --> 04:12:31,240
TESTING BUT ALSO ANTIVIRAL DRUG

6113
04:12:31,240 --> 04:12:34,440
DISCOVERY. TODAY I WANT TO TELL

6114
04:12:34,440 --> 04:12:36,240
YOU ABOUT HOW WE PROPOSE TO

6115
04:12:36,240 --> 04:12:39,920
REACH THAT (AUDIO GAP) AND

6116
04:12:39,920 --> 04:12:42,080
APPROACH THE GENERATE TARGET

6117
04:12:42,080 --> 04:12:43,560
TISSUE FROM STEM CELLS

6118
04:12:43,560 --> 04:12:45,720
SUSCEPTIBLE TO INFECTION HOW

6119
04:12:45,720 --> 04:12:49,000
THIS MANY ORGANS DERIVED FROM

6120
04:12:49,000 --> 04:12:50,160
PATIENT LIKE RESPONSES TO VIRAL

6121
04:12:50,160 --> 04:12:52,440
INFECTION. AND HOW WE CAN ALSO

6122
04:12:52,440 --> 04:12:56,000
PERFORM HIGHLY QUANTITATIVE AND

6123
04:12:56,000 --> 04:12:56,960
STANDARDIZE HIGH LIEU PUT SCALE

6124
04:12:56,960 --> 04:12:58,720
AND I THINK WHAT IS REALLY

6125
04:12:58,720 --> 04:13:01,000
UNIQUE ABOUT THIS APPROACHES ARE

6126
04:13:01,000 --> 04:13:04,440
NOW FOR THE FIRST TIME WE CAN

6127
04:13:04,440 --> 04:13:06,000
REALLY PLAY HOST VIRAL

6128
04:13:06,000 --> 04:13:09,120
INTERACTIONS AT CENTER OF DRUG

6129
04:13:09,120 --> 04:13:09,680
DISCOVERY DRUG DEVELOPMENT

6130
04:13:09,680 --> 04:13:16,320
PIPELINE. DRUG DISCOVERY WE ARE

6131
04:13:16,320 --> 04:13:18,720
NOW UTILIZING A NEW ERA OF

6132
04:13:18,720 --> 04:13:20,600
CLINICAL MODELS BY COMBINING A

6133
04:13:20,600 --> 04:13:23,640
HIGH THROUGH PUT UNBIASED

6134
04:13:23,640 --> 04:13:24,960
APPROACH THAT IS THE BEST MANNER

6135
04:13:24,960 --> 04:13:26,480
TO DISCOVER NEW MECHANISM OF

6136
04:13:26,480 --> 04:13:29,720
ACTION AND ALSO NEW THERAPEUTIC

6137
04:13:29,720 --> 04:13:30,800
HYPOTHESIS, AND COMBINE THAT

6138
04:13:30,800 --> 04:13:32,400
WITH DERIVATION OF SYNTHETIC

6139
04:13:32,400 --> 04:13:35,000
HUMAN TISSUE WHICH YOU HAVE

6140
04:13:35,000 --> 04:13:36,240
HIGHLIGHTED MANY TIMES LAST TWO

6141
04:13:36,240 --> 04:13:38,840
DAYS AS BEING THE BEST CLINICAL

6142
04:13:38,840 --> 04:13:40,000
MODS OF HUMAN PHYSIOLOGY BUT

6143
04:13:40,000 --> 04:13:42,280
ALSO THE BEST PREDICTORS OF

6144
04:13:42,280 --> 04:13:46,120
HUMAN EFFICACIES.

6145
04:13:46,120 --> 04:13:47,680
(INDISCERNIBLE) ALLOWS US TO

6146
04:13:47,680 --> 04:13:51,360
BUILD THE RIGHT TISSUE, WE DO

6147
04:13:51,360 --> 04:13:53,320
THAT WITH MICROPATENT TECHNOLOGY

6148
04:13:53,320 --> 04:13:56,200
THAT ALLOWS US TO STANDARDIZE

6149
04:13:56,200 --> 04:13:57,360
TRANSITION WITH STEM CELLS, WE

6150
04:13:57,360 --> 04:13:59,920
DO SO BY CREATING THOUSANDS OF

6151
04:13:59,920 --> 04:14:03,040
STEM CELLS IN THIS BY EMBRYONIC

6152
04:14:03,040 --> 04:14:05,800
STEM CELLS IPSCs THAT WE CAN

6153
04:14:05,800 --> 04:14:08,240
GROW ON VERY WELL DESIGNED

6154
04:14:08,240 --> 04:14:11,840
SPECIFIC SIZE MORPHOLOGIES, THIS

6155
04:14:11,840 --> 04:14:15,360
IS WHAT IS KEY TO OUR APPROACH

6156
04:14:15,360 --> 04:14:16,960
BECAUSE IT IS MANY SOMETHING YOU

6157
04:14:16,960 --> 04:14:18,800
CANNOT DO TO THE EXTENT STEM

6158
04:14:18,800 --> 04:14:23,160
CELL CULTURES THAT ARE VARIABLE

6159
04:14:23,160 --> 04:14:29,160
AND HIGHLY (INAUDIBLE) IN NAT 

6160
04:14:29,160 --> 04:14:30,320
NATURE. ANOTHER (INAUDIBLE)

6161
04:14:30,320 --> 04:14:32,080
WORKING WITH THIS UTILIZATION

6162
04:14:32,080 --> 04:14:33,960
APPROACH WE HAVE ALSO SHOWN THAT

6163
04:14:33,960 --> 04:14:38,400
WHEN STEM CELL IS DIFFERENTIATE

6164
04:14:38,400 --> 04:14:40,400
UNDER THIS COLONIES THEY

6165
04:14:40,400 --> 04:14:43,120
DIFFERENTIATE ON ORGANOIDS TO

6166
04:14:43,120 --> 04:14:44,840
CREATE COMPLEX TISSUES AND YOU

6167
04:14:44,840 --> 04:14:46,680
WILL SEE IN MY TALK LATER TODAY

6168
04:14:46,680 --> 04:14:49,680
THAT THESE TISSUES ARE --

6169
04:14:49,680 --> 04:14:55,840
SELF-ORGANIZE INTO CLOSE TO MY

6170
04:14:55,840 --> 04:14:57,360
MIMICKING HUMAN COUNTER PARTS.

6171
04:14:57,360 --> 04:14:59,800
THIS I LIGHT HOW THESE

6172
04:14:59,800 --> 04:15:02,600
APPROACHES NOT ONLY ALLOWS US TO

6173
04:15:02,600 --> 04:15:04,080
STANDARDIZE THE SUBSTANTIAL

6174
04:15:04,080 --> 04:15:05,560
DIFFERENTIATION BUT ALLOWS US TO

6175
04:15:05,560 --> 04:15:11,280
GENERATE SELF-ORGANIZED ORGANS

6176
04:15:11,280 --> 04:15:12,360
THAT RESEMBLE HUMAN COUNTER

6177
04:15:12,360 --> 04:15:18,920
PART.  THIS IS AN IMPORTANT STEP

6178
04:15:18,920 --> 04:15:20,040
TOWARD DEPLOYMENT OF THESE

6179
04:15:20,040 --> 04:15:21,520
MODELS FOR DRUG DISDVRRY BECAUSE

6180
04:15:21,520 --> 04:15:23,400
AS WE HAVE DISCUSS MANY TIME

6181
04:15:23,400 --> 04:15:26,920
THROUGH THE ORGANOID HAVE BEEN

6182
04:15:26,920 --> 04:15:28,080
REALLY IMPORTANT FOR SO MANY

6183
04:15:28,080 --> 04:15:29,680
DIFFERENT ASPECTS OF VIRAL

6184
04:15:29,680 --> 04:15:32,360
DISEASE BUT RIALITY IS THEY ARE

6185
04:15:32,360 --> 04:15:34,040
NOT -- REALITY IS THEY ARE NOT

6186
04:15:34,040 --> 04:15:36,160
WELL ENOUGH FOR DRUG DISCOVERY

6187
04:15:36,160 --> 04:15:38,160
LARGE SCALE AS WE HAVE ASSESSED

6188
04:15:38,160 --> 04:15:39,360
MANY TIMES AND THE REASON FOR

6189
04:15:39,360 --> 04:15:48,240
THAT IS THAT THESE VARIABLE,

6190
04:15:48,240 --> 04:15:50,440
THEY ALLOW US TO PERFORM TARGET

6191
04:15:50,440 --> 04:15:53,440
OF ANY GIVEN TISSUE BECAUSE THIS

6192
04:15:53,440 --> 04:15:56,000
IS MICROPATENT TECHNOLOGY THIS

6193
04:15:56,000 --> 04:15:58,240
ALLOWS THOUSANDS OF MINI ORGANS

6194
04:15:58,240 --> 04:16:02,240
IN PARALLEL IN DOING SO WE CAN

6195
04:16:02,240 --> 04:16:10,560
CREATE LARGE APPROACHES TO

6196
04:16:10,560 --> 04:16:13,960
DEFINE SET OF QUANTITATIVE

6197
04:16:13,960 --> 04:16:17,480
FENTYPICS A ASSOCIATED WITH ANY

6198
04:16:17,480 --> 04:16:21,200
GIVEN DISEASE, AND (INAUDIBLE)

6199
04:16:21,200 --> 04:16:26,400
ALLOWS US TO STREAM LARNING

6200
04:16:26,400 --> 04:16:28,560
CLINICAL RESCUE IN GIVEN DISEASE

6201
04:16:28,560 --> 04:16:33,200
ASSOCIATED PHENOTYPIC SIGNATURE 

6202
04:16:33,200 --> 04:16:35,840
ANOTHER ASPECT OF OUR WORK HAS

6203
04:16:35,840 --> 04:16:38,320
BEEN REALLY IMPORTANT IS THAT WE

6204
04:16:38,320 --> 04:16:40,120
TRULY TAKE VERSATILITY OF STEM

6205
04:16:40,120 --> 04:16:43,360
CELLS BECAUSE NOW WE CAN THINK

6206
04:16:43,360 --> 04:16:45,280
APPLYING THIS TO ANY ORGAN AND

6207
04:16:45,280 --> 04:16:47,120
TISSUE IN OUR BODY AND TISSUES

6208
04:16:47,120 --> 04:16:49,200
THAT ARE HIGHLY SUSCEPTIBLE TO

6209
04:16:49,200 --> 04:16:53,080
INFECTION. TODAY I'M -- ALSO

6210
04:16:53,080 --> 04:16:54,920
NEXT FEW MINUTES ON THE

6211
04:16:54,920 --> 04:16:57,840
(INAUDIBLE) SYSTEM WE DEPLOYED

6212
04:16:57,840 --> 04:16:59,320
TO STUDY VIRAL INFECTION IN THE

6213
04:16:59,320 --> 04:17:03,160
LUNG. WE ALSO HAVE ACCESSING

6214
04:17:03,160 --> 04:17:05,960
DEVELOPMENTS TO DERIVE TISSUES

6215
04:17:05,960 --> 04:17:08,800
OF THE LIVER KIDNEY AS WELL AS

6216
04:17:08,800 --> 04:17:10,480
BRAIN, WILL ALLOW US TO NOT ONLY

6217
04:17:10,480 --> 04:17:13,720
MODEL INFECTION BY THIS PERSON,

6218
04:17:13,720 --> 04:17:15,480
SPECIFIC ORGAN TISSUE CONTEXT

6219
04:17:15,480 --> 04:17:19,640
BUT ALSO POTENTIALLY IDENTIFY

6220
04:17:19,640 --> 04:17:21,000
THERAPEUTIC AT SCALE FOR ANY OF

6221
04:17:21,000 --> 04:17:27,400
THESE VIRUSES.  HIGHLIGHTS HOW

6222
04:17:27,400 --> 04:17:28,560
THIS PLATFORM ASSESS TISSUE THAT

6223
04:17:28,560 --> 04:17:30,000
IS HIGHLY REPRODUCIBLE AND

6224
04:17:30,000 --> 04:17:34,480
AMENABLE TO HIGH THROUGH PUT IN

6225
04:17:34,480 --> 04:17:38,560
MANY DIFFERENT DISEASE CONTEXT. 

6226
04:17:38,560 --> 04:17:41,120
TODAY THIS WORK WAS REALLY

6227
04:17:41,120 --> 04:17:42,520
STARTED BECAUSE OF THE PANDEMIC

6228
04:17:42,520 --> 04:17:46,920
WHEN I WAS POST-DOC AT

6229
04:17:46,920 --> 04:17:48,680
ROCKEFELLAR UNIVERSITY IN

6230
04:17:48,680 --> 04:17:50,920
COLLABORATION -- WHEN WE STARTED

6231
04:17:50,920 --> 04:17:51,560
THE PANDEMIC -- WHEN THE

6232
04:17:51,560 --> 04:17:53,160
PANDEMIC STARTED WE WANTED TO

6233
04:17:53,160 --> 04:17:54,200
DEVELOP MODEL SYSTEM THAT WILL

6234
04:17:54,200 --> 04:17:57,920
ALLOW US TO GENERATE MINI LUNG

6235
04:17:57,920 --> 04:18:00,040
TISSUE IN STANDARDIZED WAY, AND

6236
04:18:00,040 --> 04:18:02,000
WE CAME UP WITH HISTORICAL DATA

6237
04:18:02,000 --> 04:18:05,520
THAT I ALLOWS US TO GENERATE

6238
04:18:05,520 --> 04:18:06,440
MICROPARTICLES THAT DISTRIBUTE

6239
04:18:06,440 --> 04:18:09,680
TISSUE STRUCTURES, THAT CONTAIN

6240
04:18:09,680 --> 04:18:13,280
TWO TISSUE TYPES INCLUDING

6241
04:18:13,280 --> 04:18:15,200
AIRWAY CELLS ALVEOLAR CELLS FORM

6242
04:18:15,200 --> 04:18:17,520
IN THIS CONTINUOUS EPITHELIA

6243
04:18:17,520 --> 04:18:20,640
STRUCTURE FORMING ON TOP OF THE

6244
04:18:20,640 --> 04:18:23,280
-- WAS FASCINATING ABOUT THIS

6245
04:18:23,280 --> 04:18:26,120
APPROACH IS THIS PROCESS TAKES

6246
04:18:26,120 --> 04:18:28,360
13 DAYS.  ANOTHER ASPECT OF THIS

6247
04:18:28,360 --> 04:18:30,080
WORK IS THAT WE HAVE SHOWN THIS

6248
04:18:30,080 --> 04:18:34,320
TISSUES ARE CLOSELY MANIPULATING

6249
04:18:34,320 --> 04:18:35,880
HOW TISSUES LOOK LIKE IN

6250
04:18:35,880 --> 04:18:40,120
PATIENTS ORGANS AND JUST TO

6251
04:18:40,120 --> 04:18:42,040
ILLUSTRATE DIAGRAM HOW ANY HUMAN

6252
04:18:42,040 --> 04:18:44,520
LOOKS LIKE AND I HOPE YOU CAN

6253
04:18:44,520 --> 04:18:47,800
APPRECIATE HUMAN PATIENTS ALSO

6254
04:18:47,800 --> 04:18:49,560
HAVE SAME STRUCTURE WITH SAME

6255
04:18:49,560 --> 04:18:51,560
PROXIMAL DISTAL ORGANIZATION OF

6256
04:18:51,560 --> 04:18:54,480
AIRWAY ALVEOLAR CELLS. THIS

6257
04:18:54,480 --> 04:18:56,560
HIGHLIGHT IT IS UTILITY OF OUR

6258
04:18:56,560 --> 04:18:59,360
PLATFORM TO NOT ONLY GET ACCESS

6259
04:18:59,360 --> 04:19:00,840
TO PHYSIOLOGICAL LUNG TISSUE BUT

6260
04:19:00,840 --> 04:19:04,440
ALSO TISSUES THAT ARE MIMICKING

6261
04:19:04,440 --> 04:19:05,880
HUMAN COUNTER PARTS IN BOTH

6262
04:19:05,880 --> 04:19:08,320
TISSUE COMPLEXITY AND TISSUE

6263
04:19:08,320 --> 04:19:12,440
MORPHOLOGY.  WE -- IT STARTED TO

6264
04:19:12,440 --> 04:19:16,840
DEVELOP ASSAYS ABOUT US TO

6265
04:19:16,840 --> 04:19:20,360
REALLY -- BY SARS COV-2 THIS IS

6266
04:19:20,360 --> 04:19:23,080
INITIALLY WE EFFICIENT DERIVED

6267
04:19:23,080 --> 04:19:25,440
ISOLATE OF SARS COV-2. WE SAW

6268
04:19:25,440 --> 04:19:27,000
THIS SYSTEM WAS HIGHLY

6269
04:19:27,000 --> 04:19:28,360
SUSCEPTIBLE TO SARS COV-2

6270
04:19:28,360 --> 04:19:31,640
INFECTION AS YOU CAN SEE HERE IN

6271
04:19:31,640 --> 04:19:34,560
THIS MICROGRAPH TO

6272
04:19:34,560 --> 04:19:36,320
REPRESENTATIVE -- WE DON'T SEE

6273
04:19:36,320 --> 04:19:39,400
INFECTION IN BOTH ALVEOLAR

6274
04:19:39,400 --> 04:19:41,440
AIRWAY CELLS. THIS PLATFORM IS

6275
04:19:41,440 --> 04:19:44,840
TRULY UNABLE TO HIGH RESOLUTION

6276
04:19:44,840 --> 04:19:46,040
CONFOCAL IMAGING YOU CAN SEE

6277
04:19:46,040 --> 04:19:50,640
HERE IN THIS VIDEO WHERE WE CAN

6278
04:19:50,640 --> 04:19:54,640
TRACK CELL TISSUE WITHIN A

6279
04:19:54,640 --> 04:19:57,320
MINUTENY, BECAUSE IN THE

6280
04:19:57,320 --> 04:20:00,320
MICROBIOME WE CAN TRACK IN MANY

6281
04:20:00,320 --> 04:20:04,160
THOUSANDS OF PARALLEL AND

6282
04:20:04,160 --> 04:20:07,560
IDENTIFY THE DISEASE FEATURE

6283
04:20:07,560 --> 04:20:09,680
WITH INFECTION BY VIRUS IN THIS

6284
04:20:09,680 --> 04:20:14,040
CASE SARS COV-2. WE WERE REALLY

6285
04:20:14,040 --> 04:20:15,520
EXCITED ABOUT THIS HE CAN

6286
04:20:15,520 --> 04:20:17,560
TECHNOLOGY, WE WANTED ASSAYS

6287
04:20:17,560 --> 04:20:19,000
THAT WOULD ALLOW US TO PERFORM

6288
04:20:19,000 --> 04:20:21,160
HIGHLY QUANTITATIVE AANALYSIS OF

6289
04:20:21,160 --> 04:20:23,600
SPECIFIC PROCESSES OF THE VIRAL

6290
04:20:23,600 --> 04:20:28,640
LIFE CYCLE, WE WERE LOOKING AT

6291
04:20:28,640 --> 04:20:31,840
VIRUS IDENTIFY POTENTIALLY TUSH

6292
04:20:31,840 --> 04:20:34,120
SHOE SPECIFIC DIFFERENCES IN

6293
04:20:34,120 --> 04:20:35,520
ACTIVITY TO INFECTION BETWEEN

6294
04:20:35,520 --> 04:20:37,840
AIRWAY ALVEOLAR CELLS WE SAW

6295
04:20:37,840 --> 04:20:40,200
THAT ALVEOLAR CELLS ARE MORE

6296
04:20:40,200 --> 04:20:41,760
SUSCEPTIBLE TO INFECTION THAN

6297
04:20:41,760 --> 04:20:43,360
AIRWAY CELLS, WE ALSO DEVELOPED

6298
04:20:43,360 --> 04:20:45,720
ASSAYS THAT ALLOWS US TO LOOK AT

6299
04:20:45,720 --> 04:20:48,440
REPLICATION TRANSMISSION OF

6300
04:20:48,440 --> 04:20:49,840
VIRUS, THIS TRANSMISSION

6301
04:20:49,840 --> 04:20:50,960
PARAMETER WE SEE INCREASE IN

6302
04:20:50,960 --> 04:20:52,560
NUMBER OF INFECTED CELLS OVER

6303
04:20:52,560 --> 04:20:55,280
TIME. WE SEE REFLECTS AFTER

6304
04:20:55,280 --> 04:20:56,400
REPLICATION OF VIRUS IN LUNG

6305
04:20:56,400 --> 04:21:04,120
TISSUE.  WE CAN QUANTIFY HIGH

6306
04:21:04,120 --> 04:21:07,800
LEVELS OF APOPTOSIS IN ACUTE

6307
04:21:07,800 --> 04:21:08,920
PHASE OF BOTH INFECTION AND

6308
04:21:08,920 --> 04:21:12,320
TRANSMISSION. THIS IS REALLY THE

6309
04:21:12,320 --> 04:21:15,320
MOST -- SORRY ABOUT THAT. THIS

6310
04:21:15,320 --> 04:21:17,800
IS NOT TO ONLY RECAPITULATE

6311
04:21:17,800 --> 04:21:20,720
ENTIRE LIFE CYCLE OF THE VIRUS

6312
04:21:20,720 --> 04:21:22,240
BUT ALSO APPLY HIGHLY

6313
04:21:22,240 --> 04:21:24,440
QUANTITATIVE ANALYSIS THAT

6314
04:21:24,440 --> 04:21:27,240
ALLOWS US TO REALLY QUANTIFY

6315
04:21:27,240 --> 04:21:32,200
EVERY STEP INDIVIDUALLY.  IN

6316
04:21:32,200 --> 04:21:35,760
MANY LUNGS CYTOKINES. OF COURSE

6317
04:21:35,760 --> 04:21:38,680
OUR WE ARE EXCITED BECAUSE THIS

6318
04:21:38,680 --> 04:21:42,200
IS IS -- SUN STATISTIC

6319
04:21:42,200 --> 04:21:44,480
PHYSIOLOGICAL RESPONSES WE ARE

6320
04:21:44,480 --> 04:21:45,720
INTERESTED IN UNDERSTANDING

6321
04:21:45,720 --> 04:21:48,520
WHETHER THIS SYSTEM WAS

6322
04:21:48,520 --> 04:21:51,800
RECAPITULATED IN ASSOCIATED WITH

6323
04:21:51,800 --> 04:21:53,160
COVID (INAUDIBLE) AND DO THEY

6324
04:21:53,160 --> 04:21:55,000
PERFORM GENE EXPRESSION ANALYSIS

6325
04:21:55,000 --> 04:21:58,240
AND COMPARISONS WITH POSTMORTEM

6326
04:21:58,240 --> 04:21:59,960
TISSUE OF COVID PATIENTS THIS

6327
04:21:59,960 --> 04:22:02,920
COHORT OF ALMOST 40 PATIENTS,

6328
04:22:02,920 --> 04:22:08,200
THAT DIED BECAUSE OF COVID. H

6329
04:22:08,200 --> 04:22:10,120
THIS IS LUNG TISSUE RECOVERED

6330
04:22:10,120 --> 04:22:16,760
FROM THEM.  WE ARE LOOKING AT

6331
04:22:16,760 --> 04:22:19,720
CORRELATION, BETWEEN OUR MODEL

6332
04:22:19,720 --> 04:22:22,600
AND PATIENT SAMPLES AND WHAT WE

6333
04:22:22,600 --> 04:22:24,240
SAW IS THAT AMONG TOP EXPRESSED

6334
04:22:24,240 --> 04:22:27,480
GENES YOU CAN SEE HERE IN THE

6335
04:22:27,480 --> 04:22:31,080
HEAT MAP, THERE IS HIGH

6336
04:22:31,080 --> 04:22:34,280
CORRELATION BETWEEN GENES IN

6337
04:22:34,280 --> 04:22:37,120
LUNG BIOPSY INFECTED LUNG BIOPSY

6338
04:22:37,120 --> 04:22:38,360
COMPARED TO INFECTED LUNG WHERE

6339
04:22:38,360 --> 04:22:41,080
YOU SEE GENES HAVE SIMILAR

6340
04:22:41,080 --> 04:22:47,520
EXPRESSION PATTERNS. ALSO

6341
04:22:47,520 --> 04:22:49,560
INTERESTING IN CELL LINES

6342
04:22:49,560 --> 04:22:50,880
RECAPITULATED THESE GENES DO NOT

6343
04:22:50,880 --> 04:22:53,320
CHANGE IN EXPRESSION OF -- TO

6344
04:22:53,320 --> 04:22:55,960
INFECTION IN SIMILAR WAY. TO

6345
04:22:55,960 --> 04:22:59,080
TALK -- TAKE A STEP FURTHER WE

6346
04:22:59,080 --> 04:23:01,520
PERFORM ANALYSIS TO LOOK AT

6347
04:23:01,520 --> 04:23:04,320
ENRICHMENT OF THIS PATIENT

6348
04:23:04,320 --> 04:23:05,480
ASSOCIATED GENE EXPRESSION

6349
04:23:05,480 --> 04:23:09,600
POLYMERS. WE FOUND THAT OUR

6350
04:23:09,600 --> 04:23:11,960
MINIMUM (INAUDIBLE) DISPLAY HIGH

6351
04:23:11,960 --> 04:23:13,200
ENRICHMENT FOR THESE ENGINE

6352
04:23:13,200 --> 04:23:14,280
EXPRESSION PROGRAMS CORRELATED

6353
04:23:14,280 --> 04:23:20,600
WITH COVID-19 IN PATIENTS. THIS

6354
04:23:20,600 --> 04:23:21,920
SOMETHING NOT RECAPITULATED

6355
04:23:21,920 --> 04:23:25,640
USING STANDARD CELL LINES,

6356
04:23:25,640 --> 04:23:33,000
APOLOGIZE FOR TYPO, WE DIDN'T

6357
04:23:33,000 --> 04:23:35,640
ENRICHMENT OF GENE EXPRESSION

6358
04:23:35,640 --> 04:23:37,720
PROGRAMS, THIS IS DEMONSTRATING

6359
04:23:37,720 --> 04:23:39,600
THAT OUR PLATFORM ANALYSIS TO

6360
04:23:39,600 --> 04:23:44,520
CLOSELY MIMIC PATIENT LIKE COVID

6361
04:23:44,520 --> 04:23:46,240
RESPONSES, IN A WAY UNPARALLEL

6362
04:23:46,240 --> 04:23:50,080
TO ANY OTHER CELL BASE RESEARCH

6363
04:23:50,080 --> 04:23:52,680
TOOL THAT ARE PLOYED AS STANDARD

6364
04:23:52,680 --> 04:23:54,200
AND THERE IS PRE-CLINICAL

6365
04:23:54,200 --> 04:23:55,320
TESTING OF PRE-CLINICAL

6366
04:23:55,320 --> 04:24:02,560
VALIDATION OF COMPOUNDS.  WE

6367
04:24:02,560 --> 04:24:03,720
HAVE ACCESS TO A SYSTEM THAT WE

6368
04:24:03,720 --> 04:24:06,800
CAN USE TO INTERROGATE HOST

6369
04:24:06,800 --> 04:24:08,400
TARGETS CRITICAL FOR (INAUDIBLE)

6370
04:24:08,400 --> 04:24:12,640
WE ARE EXCITED ABOUT MINING DATA

6371
04:24:12,640 --> 04:24:14,760
FROM CRISPER SCREENS THAT

6372
04:24:14,760 --> 04:24:17,880
IDENTIFY GENES ESSENTIAL FOR

6373
04:24:17,880 --> 04:24:20,960
INFECTION BY SARS COV-2 OR ALSO

6374
04:24:20,960 --> 04:24:22,760
ENDEMIC CORONA VIRUS HERE

6375
04:24:22,760 --> 04:24:24,920
COLLABORATING WITH CHARLIE RICE

6376
04:24:24,920 --> 04:24:26,240
WHERE WE ROOK AT GENES THAT

6377
04:24:26,240 --> 04:24:27,400
IDENTIFY ESSENTIAL GENES FOR

6378
04:24:27,400 --> 04:24:32,200
SARS COV-2 AND WE TRIED TO

6379
04:24:32,200 --> 04:24:35,120
VALIDATE WHICH OF THEM HAD WORK

6380
04:24:35,120 --> 04:24:36,600
RELATED INFECTION IN THE

6381
04:24:36,600 --> 04:24:39,040
NEURONAL SYSTE SYSTEM. WE FOUNDE

6382
04:24:39,040 --> 04:24:41,240
GENE THAT WAS HIGHLY CORRELATED

6383
04:24:41,240 --> 04:24:43,440
WITH SARS COV-2 NOT ONLY IN THE

6384
04:24:43,440 --> 04:24:44,840
LUNG SYSTEM BUT ALSO IN PATIENT

6385
04:24:44,840 --> 04:24:48,240
SAMPLES WE SAW THAT WAS HIGHLY

6386
04:24:48,240 --> 04:24:49,800
UPREGULATED FROM SARS COV-2

6387
04:24:49,800 --> 04:24:52,920
INFECTION. AND NOW THIS GENE WAS

6388
04:24:52,920 --> 04:24:57,960
INTERESTING AS A DRUGGABLE

6389
04:24:57,960 --> 04:25:00,280
TARGET, THERE ARE -- WE ARE

6390
04:25:00,280 --> 04:25:02,000
EXCITED ABOUT USING OUR MODEL TO

6391
04:25:02,000 --> 04:25:04,480
TEST WHETHER THERAPEUTICS AND

6392
04:25:04,480 --> 04:25:06,000
ACTIVITY WOULD HAVE ANY EFFECT

6393
04:25:06,000 --> 04:25:08,200
ON SARS COV-2 INFECTION IN THE

6394
04:25:08,200 --> 04:25:10,760
LUNGS AND REALLY THAT WAS

6395
04:25:10,760 --> 04:25:13,320
FASCINATING TO FIND INHIBITOR OF

6396
04:25:13,320 --> 04:25:18,160
THIS GENE DEMONSTRATED POTENT

6397
04:25:18,160 --> 04:25:19,720
INDIVIDUAL INHIBITORY ACTIVITY

6398
04:25:19,720 --> 04:25:22,360
AGAINST SARS COV-2 IN OUR ASSAY 

6399
04:25:22,360 --> 04:25:27,680
AGAIN THIS CLEARLY HIGHLIGHTS

6400
04:25:27,680 --> 04:25:29,120
GENETICS BUT ALSO DRUGS GIVEN ON

6401
04:25:29,120 --> 04:25:31,520
TESTING APPROACHES CAN BE USED

6402
04:25:31,520 --> 04:25:33,720
TO DISCOVER NEW HOST BASE

6403
04:25:33,720 --> 04:25:35,320
MECHANISM OF ACTION THAT

6404
04:25:35,320 --> 04:25:40,200
ACTUALLY ARE FOCUSING ON TARGET

6405
04:25:40,200 --> 04:25:41,560
THAT HOST RESPONDS PRODUCING

6406
04:25:41,560 --> 04:25:47,840
VIRAL INFECTION. E O WE WANTED

6407
04:25:47,840 --> 04:25:52,480
TO TRANSFER THIS TO HIGH PUT

6408
04:25:52,480 --> 04:25:59,480
SETTING SO WE TRANSFER TO 96 AND

6409
04:25:59,480 --> 04:26:00,720
384 WELL PLACE WHERE EVERY WELL

6410
04:26:00,720 --> 04:26:03,360
OF THE MULTI-WELL PLATE CONTAIN

6411
04:26:03,360 --> 04:26:05,560
TENS OF QUANTITIES OF LUNG

6412
04:26:05,560 --> 04:26:08,000
TISSUE HIGHLY SUSCEPTIBLE TO

6413
04:26:08,000 --> 04:26:09,920
VIRUS INFECTION. SARS COV-2 AS

6414
04:26:09,920 --> 04:26:11,360
PROOF OF CONCEPT FOR TESTING

6415
04:26:11,360 --> 04:26:14,960
THIS PLATFORM, WE COLLABORATED

6416
04:26:14,960 --> 04:26:16,960
WITH (INAUDIBLE) WILSON LAB AT

6417
04:26:16,960 --> 04:26:17,960
ROCKEFELLAR UNIVERSITY WHERE WE

6418
04:26:17,960 --> 04:26:20,400
WANTED TO TEST MONOCLONAL

6419
04:26:20,400 --> 04:26:22,600
ANTIBODIES ISOLATED FROM

6420
04:26:22,600 --> 04:26:23,640
CONVALESCENT PLASMA

6421
04:26:23,640 --> 04:26:29,000
PUBLICATIONS. HERE IS ONE OF

6422
04:26:29,000 --> 04:26:30,480
ANTIBODIES 121 WHICH IS

6423
04:26:30,480 --> 04:26:32,360
CURRENTLY IN CLINICAL TRIALS AT

6424
04:26:32,360 --> 04:26:35,480
THIS POINT, THAT SHOW PROMISING

6425
04:26:35,480 --> 04:26:37,320
POTENT ANTIVIRAL NEUTRALIZING

6426
04:26:37,320 --> 04:26:39,480
ACTIVITY AGAINST SARS COV-2 IN

6427
04:26:39,480 --> 04:26:42,160
OUR MINIMUM ASSAY. WE CAN

6428
04:26:42,160 --> 04:26:44,280
BECAUSE THIS IS HIGH THROUGH PUT

6429
04:26:44,280 --> 04:26:45,640
ASSAY WE CAN NOW PERFORM HIGHLY

6430
04:26:45,640 --> 04:26:48,200
QUANTITATIVE ANALYSIS IN THIS

6431
04:26:48,200 --> 04:26:50,240
CASE ANTIBODY POTENCY AND

6432
04:26:50,240 --> 04:26:51,800
EFFICACY, YOU CAN THINK OF USING

6433
04:26:51,800 --> 04:26:53,320
THIS HIGH THROUGH PUT PLATFORM

6434
04:26:53,320 --> 04:26:56,760
TO ALSO TEST POTENTIALLY OTHER

6435
04:26:56,760 --> 04:26:57,600
CANDIDATE ANTIVIRAL

6436
04:26:57,600 --> 04:27:05,080
THERAPEUTICS. JUST DEMONSTRATE

6437
04:27:05,080 --> 04:27:06,120
THIS PLATFORM, I WANT TO SPEND

6438
04:27:06,120 --> 04:27:08,960
TIME SHOWING YOU THE PLATFORM

6439
04:27:08,960 --> 04:27:13,680
WHERE WE SEE THAT DEMONSTRATES

6440
04:27:13,680 --> 04:27:14,800
HIGH SENSITIVITY TO LEVEL OF

6441
04:27:14,800 --> 04:27:16,960
SARS COV-2 INFECTION SO WE SEE

6442
04:27:16,960 --> 04:27:19,960
IN THIS SOLUTION ASSAY, THE

6443
04:27:19,960 --> 04:27:23,440
ASSAY THE DATA WAS VERY ROBUST

6444
04:27:23,440 --> 04:27:25,200
AND IN THIS CASE CORRESPONDS TO

6445
04:27:25,200 --> 04:27:26,920
SINGLE ORGAN SO QUANTIFYING MANY

6446
04:27:26,920 --> 04:27:30,360
AT A TIME.  WHEN WE LOOK AT

6447
04:27:30,360 --> 04:27:31,480
SEQUENCE SCORES BETWEEN POSITIVE

6448
04:27:31,480 --> 04:27:36,280
AND NEGATIVE CONTROLS WE SEE

6449
04:27:36,280 --> 04:27:38,520
WEIGHTED .5. WE ALSO SERVE

6450
04:27:38,520 --> 04:27:41,280
COEFFICIENT VARIANT LESS THAN

6451
04:27:41,280 --> 04:27:42,600
20% WITH ASSAY METRICS THAT

6452
04:27:42,600 --> 04:27:46,120
SPEAKS A LOT AS TO THE ASSAY

6453
04:27:46,120 --> 04:27:49,080
STANDARDIZATION OF THIS ASSAY.

6454
04:27:49,080 --> 04:27:50,520
ON HIGH THROUGH PUT SCALE. WE

6455
04:27:50,520 --> 04:27:53,520
HAVE ALSO DEPLOYED PLATFORM TO

6456
04:27:53,520 --> 04:27:55,200
START TESTING AND IDENTIFYING

6457
04:27:55,200 --> 04:27:58,600
CANDIDATE THERAPEUTICS

6458
04:27:58,600 --> 04:27:59,400
PARTICULAR VIRUSES DEMON

6459
04:27:59,400 --> 04:28:01,680
INVESTIGATING SHOWING YOU OUR

6460
04:28:01,680 --> 04:28:02,960
RECENT RESULTS WITH OUR WORK

6461
04:28:02,960 --> 04:28:10,160
WITH RSV SHOWING YOU HEAT MAP OF

6462
04:28:10,160 --> 04:28:10,840
COMPOUND TREATED WELL PLATE WITH

6463
04:28:10,840 --> 04:28:11,640
(INAUDIBLE) ON THE OUTSIDE AND

6464
04:28:11,640 --> 04:28:15,240
YOU CAN CLEARLY IDENTIFY VERY

6465
04:28:15,240 --> 04:28:16,920
POTENT ACTIVITY AGAINST RSV, NOW

6466
04:28:16,920 --> 04:28:19,560
YOU CAN REPEAT THE PROCESS WITH

6467
04:28:19,560 --> 04:28:24,320
THOUSANDS AND THOUSANDS OF

6468
04:28:24,320 --> 04:28:27,520
COMPOUNDS, EVEN IDENTIFY THOSE

6469
04:28:27,520 --> 04:28:31,000
THAT HAVE VERY POTENT INHIBITION

6470
04:28:31,000 --> 04:28:33,320
ACTIVITY AGAINST RSV IN THIS

6471
04:28:33,320 --> 04:28:36,000
CASE WE WERE EXCITED ABOUT THIS

6472
04:28:36,000 --> 04:28:39,160
19 COMPOUNDS DEMONSTRATED

6473
04:28:39,160 --> 04:28:40,760
INHIBITOR ACTIVITY AGAINST RSV

6474
04:28:40,760 --> 04:28:45,880
GREATER THAN 80%. THIS CREATES

6475
04:28:45,880 --> 04:28:47,800
FOR US TO STREAM LARGE CLINICAL

6476
04:28:47,800 --> 04:28:51,280
LIBRARIES TO IDENTIFY ANTIVIRAL

6477
04:28:51,280 --> 04:28:52,320
THERAPEUTICS FOR CANDIDATE

6478
04:28:52,320 --> 04:28:57,160
VIRUSES AS WELL. EXCITING PART

6479
04:28:57,160 --> 04:28:59,560
OF OUR WORK IS HAS THE ABILITY

6480
04:28:59,560 --> 04:29:02,200
TO (INAUDIBLE) VIRUSES BECAUSE

6481
04:29:02,200 --> 04:29:05,000
ALSO CONTAINS OLDER VIRUSES AND

6482
04:29:05,000 --> 04:29:09,000
WE HAVE SHOWN THIS ARE

6483
04:29:09,000 --> 04:29:09,880
SUSCEPTIBLE TO INFECTION BY

6484
04:29:09,880 --> 04:29:12,600
OTHER ENDEMIC VIRUSES HERE AS

6485
04:29:12,600 --> 04:29:17,360
WELL AS RSV, SOME INFLUENZA AND

6486
04:29:17,360 --> 04:29:23,880
THIS AGAIN IS DIAGNOSTIC AND

6487
04:29:23,880 --> 04:29:25,480
RECAPITULATE INFECTION BY ANY

6488
04:29:25,480 --> 04:29:29,040
GIVEN VIRUS, THINK ABOUT

6489
04:29:29,040 --> 04:29:36,520
DEVELOPING HIGH THROUGH PUT DRUG

6490
04:29:36,520 --> 04:29:37,080
DISCOVERY CAMPAIGN GIVEN THE

6491
04:29:37,080 --> 04:29:38,600
HIGH THROUGH PUT ASPECT OF OUR

6492
04:29:38,600 --> 04:29:42,600
WORK. WE ARE TAKING THIS

6493
04:29:42,600 --> 04:29:46,040
APPROACH FURTHER. WE ARE EXCITED

6494
04:29:46,040 --> 04:29:46,640
(INAUDIBLE) IN HOUSE DISCOVERY

6495
04:29:46,640 --> 04:29:48,120
PROGRAMS WE ARE ACTIVELY USING

6496
04:29:48,120 --> 04:29:50,600
THE SYSTEM TO IDENTIFY BROAD

6497
04:29:50,600 --> 04:29:52,080
SPECTRUM ANTIVIRALS FOR

6498
04:29:52,080 --> 04:29:55,560
RESPIRATORY VIRAL INFECTION AND

6499
04:29:55,560 --> 04:29:57,840
THAT IS FOR ALL MAJOR CLASSES OF

6500
04:29:57,840 --> 04:30:00,000
VIRUS PREFERENTIALLY IN THE LUNG

6501
04:30:00,000 --> 04:30:02,480
AND WE ARE TAKING UP PLATFORM TO

6502
04:30:02,480 --> 04:30:04,880
IDENTIFY BROAD SPECTRUM

6503
04:30:04,880 --> 04:30:06,440
ANTIVIRUS FOR ACUTE INJURY, THIS

6504
04:30:06,440 --> 04:30:08,160
IS HIGHLIGHTING THE ACTIVITY OF

6505
04:30:08,160 --> 04:30:10,760
3D TISSUE MODELS AND FULLY

6506
04:30:10,760 --> 04:30:12,800
STANDARDIZED THAT CAN ENABLE

6507
04:30:12,800 --> 04:30:16,280
IDENTIFICATION OF NEW THERAPY

6508
04:30:16,280 --> 04:30:18,600
BASED ON TISSUE TARGETED HOST

6509
04:30:18,600 --> 04:30:21,040
BASE THERAPEUTICS. WITH THAT I

6510
04:30:21,040 --> 04:30:21,840
WOULD LIKE TO SUMMARIZE WHAT I

6511
04:30:21,840 --> 04:30:25,680
PRESENTED SO FAR, AS I SAID THE

6512
04:30:25,680 --> 04:30:28,000
MAIN MUTATIONS ARE CLEARLY OF

6513
04:30:28,000 --> 04:30:30,560
ANTIVIRAL DEVELOPMENT IS LACK OF

6514
04:30:30,560 --> 04:30:31,720
STANDARDIZE PHYSIOLOGICAL

6515
04:30:31,720 --> 04:30:35,720
MODELS. I TOLD YOU HOW MANY

6516
04:30:35,720 --> 04:30:37,080
ORGANS IN GENERAL OFFER LIMITED

6517
04:30:37,080 --> 04:30:39,880
ACCESS TO STANDARDIZE PATIENT

6518
04:30:39,880 --> 04:30:42,360
LIKE TISSUE WE CAN USE TO MODEL

6519
04:30:42,360 --> 04:30:44,680
INFECTION LIKE VIRUSES AND AT

6520
04:30:44,680 --> 04:30:46,600
THE SAME TIME PERFORM HIGHLY

6521
04:30:46,600 --> 04:30:49,400
QUANTITATIVE ANALYSIS OF NOT

6522
04:30:49,400 --> 04:30:53,000
ONLY SPECIFIC PROCESSES OF VIRAL

6523
04:30:53,000 --> 04:30:54,240
PROCESSES OF THE VIRAL LIFE

6524
04:30:54,240 --> 04:30:57,080
CYCLE BUT ALSO TEST THERAPEUTICS

6525
04:30:57,080 --> 04:30:58,680
AND HOW THEY CAN MEDIATE THESE

6526
04:30:58,680 --> 04:31:01,680
PROCESSES. I ALSO TOLD YOU ABOUT

6527
04:31:01,680 --> 04:31:03,560
HOW THIS HIGH THROUGH PUT

6528
04:31:03,560 --> 04:31:05,280
PLATFORM IS HIGHLY SENSITIVE AND

6529
04:31:05,280 --> 04:31:10,120
CAN BE USED TO IDENTIFY

6530
04:31:10,120 --> 04:31:10,920
CANDIDATE ANTIVIRAL AGAINST

6531
04:31:10,920 --> 04:31:12,160
PARTICULAR VIRUS. THIS CLEARLY

6532
04:31:12,160 --> 04:31:17,280
HIGHLIGHTS HOW THIS MODEL WILL

6533
04:31:17,280 --> 04:31:19,320
ENABLE IDENTIFICATION OF FIRST

6534
04:31:19,320 --> 04:31:22,160
IN CLASS MOLECULES FOR VARIOUS

6535
04:31:22,160 --> 04:31:23,680
VIRUSES, BASED ON THIS

6536
04:31:23,680 --> 04:31:25,040
STANDARDIZED 3D TISSUE MODEL.

6537
04:31:25,040 --> 04:31:26,800
WITH THAT I WOULD LIKE TO END MY

6538
04:31:26,800 --> 04:31:28,640
TALK AND LOOKING FORWARD TO OUR

6539
04:31:28,640 --> 04:31:38,240
Q&A SESSION. THANK YOU.

6540
04:31:38,240 --> 04:31:38,720
>> THANK YOU VERY MUCH.

6541
04:31:38,720 --> 04:31:39,720
FANTASTIC TALK. I WOULD LIKE TO

6542
04:31:39,720 --> 04:31:43,520
ASK SPEAKERS TO TURN ON CAMERAS

6543
04:31:43,520 --> 04:31:45,440
AND THEIR MICROPHONES. WE HAVE

6544
04:31:45,440 --> 04:31:48,520
15 MINUTES FOR Q&A. I WILL
START

6545
04:31:48,520 --> 04:31:53,680
WITH THE QUESTION FROM AUDIENCE

6546
04:31:53,680 --> 04:31:54,880
FOR THOMAS. WHAT DO YOU THINK

6547
04:31:54,880 --> 04:31:56,600
ABOUT THE FACT THAT THERE IS NO

6548
04:31:56,600 --> 04:31:58,280
INTERFERON RESPONSE IN THE BRAIN

6549
04:31:58,280 --> 04:32:06,560
ORGANOIDS AFTER SARS COV-2

6550
04:32:06,560 --> 04:32:17,040
INFECTION? THOMAS, THAT IS A

6551
04:32:23,480 --> 04:32:24,400
QUESTION FOR YOU THE BRAIN

6552
04:32:24,400 --> 04:32:25,080
ORGANOID SYSTEMS. QUESTION FROM

6553
04:32:25,080 --> 04:32:27,000
THE AUDIENCE ABOUT THE LACK OF

6554
04:32:27,000 --> 04:32:30,360
INTERFERON RESPONSE. AFTER SARS

6555
04:32:30,360 --> 04:32:35,040
COV-2 INFECTION. THAT IMPACT

6556
04:32:35,040 --> 04:32:37,360
RATTLE YOU ARE SEEING OR IS THAT

6557
04:32:37,360 --> 04:32:40,880
PART OF DOES THAT IMPACT THE

6558
04:32:40,880 --> 04:32:43,600
NATURAL PHYSIOLOGY OF INFECTION?

6559
04:32:43,600 --> 04:32:46,080
>> I CANNOT SPEAK TO THIS
FROM

6560
04:32:46,080 --> 04:32:50,320
-- NOT ADDRESS THIS ISSUE. THERE

6561
04:32:50,320 --> 04:32:55,600
IS OBVIOUSLY NO INTERFERON

6562
04:32:55,600 --> 04:32:57,680
PRODUCING CELL MEASURE, BUT WE

6563
04:32:57,680 --> 04:33:01,880
HAVE ANOTHER CONTEXT ALSO

6564
04:33:01,880 --> 04:33:05,160
LYMPHOCYTIC CELLS AND SEPSIS

6565
04:33:05,160 --> 04:33:06,480
MODELS AND POSSIBLE ALSO TO

6566
04:33:06,480 --> 04:33:08,800
ENGAGE OTHER CELL TYPES WHICH

6567
04:33:08,800 --> 04:33:11,480
MIGHT INVADE AND CONTRIBUTE

6568
04:33:11,480 --> 04:33:13,280
THIS. I MIGHT BE COMPLETELY OFF

6569
04:33:13,280 --> 04:33:18,920
THIS IS NOT MY AREA OF RESEARCH 

6570
04:33:18,920 --> 04:33:22,720
>> NEXT QUESTION FROM THE

6571
04:33:22,720 --> 04:33:24,760
AUDIENCE, COMPARED TO AIR LIQUID

6572
04:33:24,760 --> 04:33:26,480
INTERFACE MODEL HAVE YOU ALSO

6573
04:33:26,480 --> 04:33:28,200
VALIDATED THE OTHER CELL

6574
04:33:28,200 --> 04:33:32,760
COMPONENTS? YOUR MODEL?

6575
04:33:32,760 --> 04:33:33,680
SILLIATION AND MUCOUS

6576
04:33:33,680 --> 04:33:34,080
PRODUCTION?

6577
04:33:34,080 --> 04:33:36,640
>> WE DID AND I DIDN'T
HAVE TIME

6578
04:33:36,640 --> 04:33:39,440
TO DISCUSS IN DETAIL, RNA

6579
04:33:39,440 --> 04:33:42,720
SEQUENCING AND HOW IDENTIFY THE

6580
04:33:42,720 --> 04:33:46,040
CELL TYPES IN THESE LUNGS, WE

6581
04:33:46,040 --> 04:33:47,960
FOUND CELL TYPES IN AIRWAY

6582
04:33:47,960 --> 04:33:51,120
COMPARTMENT MOSTLY CELLS MOSTLY

6583
04:33:51,120 --> 04:33:53,800
CELLS THAT HAVE CILIA OPPOSED TO

6584
04:33:53,800 --> 04:33:57,880
THE APICAL SITE AND THERE IS

6585
04:33:57,880 --> 04:34:01,640
THREE MAJOR CELL TYPES IN STEM

6586
04:34:01,640 --> 04:34:06,520
CELL LIKE THAT WAS IDENTIFY IN

6587
04:34:06,520 --> 04:34:09,120
TISSUE AS WELL AS WELL AS EARLY

6588
04:34:09,120 --> 04:34:12,840
TYPE 1 AND 2 PNEUMOCYTE SO THOSE

6589
04:34:12,840 --> 04:34:14,280
ARE THE BEST WORK WE HAVE DONE

6590
04:34:14,280 --> 04:34:16,880
AND THOSE MUCOUS CELLS MUCOUS

6591
04:34:16,880 --> 04:34:17,680
PLUCKS IS SOMETHING WE HAVEN'T

6592
04:34:17,680 --> 04:34:19,600
DONE AND WE DON'T HAVE A LOT OF

6593
04:34:19,600 --> 04:34:21,480
CELLS AND A LOT OF MUCOUS CELLS

6594
04:34:21,480 --> 04:34:22,600
IN OUR MODEL SYSTEM WHICH IS OF

6595
04:34:22,600 --> 04:34:28,520
COURSE LIMITATION BUT WE DO HAVE

6596
04:34:28,520 --> 04:34:33,040
USUAL SUSPECTS THE MAJOR

6597
04:34:33,040 --> 04:34:40,800
(INAUDIBLE) IN THE LUNG SYSTEM. 

6598
04:34:40,800 --> 04:34:44,880
ONE AREA I WAS INTERESTED IN IS

6599
04:34:44,880 --> 04:34:46,360
WHAT ARE SOME OF THE WHAT ARE

6600
04:34:46,360 --> 04:34:48,680
TECHNICAL REGULATORY HURDLES FOR

6601
04:34:48,680 --> 04:34:51,200
ADOPTING THESE 3D CULTURE MODEL

6602
04:34:51,200 --> 04:34:55,200
SYSTEMS AND DRUG DEVELOPMENT?

6603
04:34:55,200 --> 04:34:57,560
EVI AND I IN NICOLE MIGHT BE

6604
04:34:57,560 --> 04:34:59,000
ABLE TO ADDRESS THIS BASED ON

6605
04:34:59,000 --> 04:35:00,200
YOUR EXPERIENCES. 

6606
04:35:00,200 --> 04:35:09,840
>> I'LL DEFER TO EVI. 
BEING THE

6607
04:35:09,840 --> 04:35:11,400
I DO A LOT OF WORK IN SUPPORT OF

6608
04:35:11,400 --> 04:35:13,080
REGULATORY AGENCIES.  PLEASE GO

6609
04:35:13,080 --> 04:35:14,400
I MED THEN I WILL ADD MY

6610
04:35:14,400 --> 04:35:18,080
THOUGHTS. 

6611
04:35:18,080 --> 04:35:23,040
>> SO IN TERMS OF HURDLES,
I CAN

6612
04:35:23,040 --> 04:35:24,760
ONLY TALK ABOUT WHAT WE SEE IN

6613
04:35:24,760 --> 04:35:26,680
OUR BRANCH AND OUR DIVISION.

6614
04:35:26,680 --> 04:35:31,720
FIRST I HAVEN'T SEEN MANY OF

6615
04:35:31,720 --> 04:35:35,520
THESE INNOVATIONS TO SUPPORT OUR

6616
04:35:35,520 --> 04:35:36,240
PRODUCT.  HAVE NOT MADE IT DOWN

6617
04:35:36,240 --> 04:35:37,960
THROUGH THE REGULATORY PATH. I

6618
04:35:37,960 --> 04:35:45,520
DON'T KNOW WHAT THE HURDLE IS. 

6619
04:35:45,520 --> 04:35:47,040
MAYBE THE THINKING IS WE DON'T

6620
04:35:47,040 --> 04:35:49,600
HAVE ACCEPTANCE OR THE

6621
04:35:49,600 --> 04:35:51,400
CAPABILITY OF REVIEWING THIS

6622
04:35:51,400 --> 04:35:53,440
DATA, I AM NOT SURE. BUT AGAIN I

6623
04:35:53,440 --> 04:35:56,960
WILL SAY THAT WE HAVE SEEN MUCH

6624
04:35:56,960 --> 04:36:07,520
OF THIS. ALSO ORB POINT IS -- WE

6625
04:36:07,520 --> 04:36:10,520
TEND TO NEUTRALIZATION ASSAYS

6626
04:36:10,520 --> 04:36:13,360
HAVE BEEN TRADITIONALLY USED AND

6627
04:36:13,360 --> 04:36:22,640
WE HAVE ACCEPTED THEM AS GOOD

6628
04:36:22,640 --> 04:36:23,600
INDICATION OF ACTIVITY BUT FOR

6629
04:36:23,600 --> 04:36:25,040
-- AS MORE AND MORE

6630
04:36:25,040 --> 04:36:27,280
SOPHISTICATED AND MORE

6631
04:36:27,280 --> 04:36:33,480
COMPLICATED PRODUCTS ARE COMING

6632
04:36:33,480 --> 04:36:34,160
AND BEING DEVELOPED WE MAYBE

6633
04:36:34,160 --> 04:36:41,600
NEED TO KNOW MORE AND SEE MORE. 

6634
04:36:41,600 --> 04:36:43,760
THE OTHER THING IS, AS WAS OFTEN

6635
04:36:43,760 --> 04:36:46,360
DISCUSSED IN CONTEXT OF SARS

6636
04:36:46,360 --> 04:36:52,200
COV-2, IS THE FACT THAT FOR SOME

6637
04:36:52,200 --> 04:36:52,960
EMERGING VIRAL DISEASE THE

6638
04:36:52,960 --> 04:36:59,760
ANIMAL MODELS ARE NOT THERE. AND

6639
04:36:59,760 --> 04:37:02,240
BECAUSE IN THIS CASE

6640
04:37:02,240 --> 04:37:03,880
MICROPHYSIOLOGICAL SET UP WOULD

6641
04:37:03,880 --> 04:37:06,320
BE A REPLACEMENT, WOULD BE A

6642
04:37:06,320 --> 04:37:15,040
TEST THAT IS MORE APPLICABLE TO

6643
04:37:15,040 --> 04:37:19,600
THE SITUATION SO IN THAT

6644
04:37:19,600 --> 04:37:22,160
SCENARIO WE WOULD ENCOURAGE SUCH

6645
04:37:22,160 --> 04:37:32,680
STUDIES TO COME IN THE DOOR.  I

6646
04:37:37,200 --> 04:37:39,160
AGREE. BUT ALSO THERE IS A

6647
04:37:39,160 --> 04:37:41,120
DISCONNECT AT MOMENT. LAST WEEK

6648
04:37:41,120 --> 04:37:42,840
I WAS AT THIS INCREDIBLE MEETING

6649
04:37:42,840 --> 04:37:44,880
THE TEAM FROM JOHNS HOPKINS

6650
04:37:44,880 --> 04:37:48,120
HELPED CO-ORGANIZE OR ORGANIZED

6651
04:37:48,120 --> 04:37:50,400
AND HELPED BY OTHER INSTITUTIONS

6652
04:37:50,400 --> 04:37:52,800
AS WELL, MICROPHYSIOLOGICAL

6653
04:37:52,800 --> 04:37:55,000
SYSTEM WORLD SUMMIT AND THERE

6654
04:37:55,000 --> 04:37:57,400
WAS INCREDIBLE SCIENCE BEING

6655
04:37:57,400 --> 04:37:58,840
PRESENCED. THERE IS A LITTLE BIT

6656
04:37:58,840 --> 04:38:00,800
OF DISCONNECT BETWEEN REALLY

6657
04:38:00,800 --> 04:38:02,560
EXCITING CUTTING EDGE SCIENCE

6658
04:38:02,560 --> 04:38:07,840
AND THE SORT OF REAL GROUNDED IN

6659
04:38:07,840 --> 04:38:09,160
REALITY PRACTICALITY NEEDS OF

6660
04:38:09,160 --> 04:38:13,440
REGULATORY DECISION MAKERS. SORT

6661
04:38:13,440 --> 04:38:17,000
OF ONE OF THE PIECES OF FEEDBACK

6662
04:38:17,000 --> 04:38:18,720
WE GOT WHEN WE THROUGH THE CORE

6663
04:38:18,720 --> 04:38:21,320
WORKING GROUP LEADERSHIP OF THAT

6664
04:38:21,320 --> 04:38:23,120
GROUP MET WITH EUROPEAN

6665
04:38:23,120 --> 04:38:24,520
REGULATORS PARTICULARLY WITH

6666
04:38:24,520 --> 04:38:25,760
EUROPEAN MEDICINE AUTHORITY AND

6667
04:38:25,760 --> 04:38:27,840
THE SAFETY WORKING PARTY WAS

6668
04:38:27,840 --> 04:38:30,840
SORT OF THE NEED TO HAVE MODELS

6669
04:38:30,840 --> 04:38:34,840
LIKE THE FOCUS INITIALLY FOR

6670
04:38:34,840 --> 04:38:37,720
ESTABLISHING REGULATORY UTILITY,

6671
04:38:37,720 --> 04:38:41,400
AND CONFIDENCE, SHOULD BE ON

6672
04:38:41,400 --> 04:38:51,840
SIMPLE SINGLE ORGAN MODEL

6673
04:38:53,000 --> 04:38:53,760
APPLIED TO SAFETY PHARMACOLOGY

6674
04:38:53,760 --> 04:38:54,320
END POINTS RATHER THAN THESE

6675
04:38:54,320 --> 04:38:54,920
MUCH MORE COMPLICATED BUT VERY

6676
04:38:54,920 --> 04:38:55,560
SEXY BODIES ON A CHIP, MULTIPLE

6677
04:38:55,560 --> 04:38:56,200
DIFFERENT TISSUES, DAISY CHAINED

6678
04:38:56,200 --> 04:38:57,360
TOGETHER TO REPEAT SIX MONTH

6679
04:38:57,360 --> 04:38:59,000
DOSE STUDIES ALL REALLY EXCITING

6680
04:38:59,000 --> 04:39:02,160
AND NEEDED TO MOVE THE FIELD

6681
04:39:02,160 --> 04:39:02,800
FORWARD BUT YOU CAN'T START WITH

6682
04:39:02,800 --> 04:39:06,080
THAT. IN MANY TERMS OF

6683
04:39:06,080 --> 04:39:06,840
REGULATORY CONSIDERATIONSS.

6684
04:39:06,840 --> 04:39:07,280
ACCEPTANCE.

6685
04:39:07,280 --> 04:39:09,480
I WILL SAY THERE WAS A EXAMPLE

6686
04:39:09,480 --> 04:39:10,920
THAT WAS PRESENTED LAST WEEK

6687
04:39:10,920 --> 04:39:14,800
WHERE THE FIRST IND APPLICATION

6688
04:39:14,800 --> 04:39:18,880
SUPPORTED EXCLUSIVELY BY TISSUE

6689
04:39:18,880 --> 04:39:21,200
CHIP DATA WAS SUBMITTED

6690
04:39:21,200 --> 04:39:23,440
SUCCESSFULLY TO THE FDA AND

6691
04:39:23,440 --> 04:39:24,520
PERHAPS THOMAS CAN EXPAND ON

6692
04:39:24,520 --> 04:39:30,600
THAT A LITTLE BIT. 

6693
04:39:30,600 --> 04:39:36,560
>> IMPORTANT -- THERE THE
FIRST

6694
04:39:36,560 --> 04:39:41,320
EXAMPLES HAS BEEN ABLE TO

6695
04:39:41,320 --> 04:39:41,880
SUPPORT (INAUDIBLE) THERE'S

6696
04:39:41,880 --> 04:39:46,240
OTHER CASES WHERE DERISKING OF

6697
04:39:46,240 --> 04:39:49,840
SUBSTANCES TOOK PLACE IN FORM OF

6698
04:39:49,840 --> 04:39:51,680
INVESTIGATIVE TOXICOLOGY AND

6699
04:39:51,680 --> 04:39:53,560
THINGS COULD BE CONTINUED. BUT

6700
04:39:53,560 --> 04:39:56,560
AT THE MOMENT WE HAVE A

6701
04:39:56,560 --> 04:39:57,360
SITUATION WHICH IS -- THERE IS

6702
04:39:57,360 --> 04:40:00,520
NOT REALLY -- NOBODY -- VERY FEW

6703
04:40:00,520 --> 04:40:03,080
CAN OVERSEE WHAT IT IS PRODUCING

6704
04:40:03,080 --> 04:40:05,280
BECAUSE SO MUCH (INAUDIBLE) THEY

6705
04:40:05,280 --> 04:40:08,880
NEED TO IDENTIFY SRI STANDARDS

6706
04:40:08,880 --> 04:40:12,800
WHAT IS THE TO GO MODELS

6707
04:40:12,800 --> 04:40:14,560
ROBUSTLY AVAILABLE ALSO DEPEND

6708
04:40:14,560 --> 04:40:18,800
ON WHAT IS COMMERCIALLY

6709
04:40:18,800 --> 04:40:20,120
AVAILABLE BECAUSE THIS IS WAY OF

6710
04:40:20,120 --> 04:40:21,360
STANDARDIZATION. WE DON'T HAVE A

6711
04:40:21,360 --> 04:40:24,320
SITUATION WHERE EACH AND EVERY

6712
04:40:24,320 --> 04:40:26,440
MODEL CAN BE VALIDATED BY EACH

6713
04:40:26,440 --> 04:40:27,680
AND EVERY COMPANY WHO WANTS TO

6714
04:40:27,680 --> 04:40:29,840
USE IT SO WE NEED THE MASTER

6715
04:40:29,840 --> 04:40:34,320
FILES, THE BEST PRACTICES CREATE

6716
04:40:34,320 --> 04:40:35,320
SOMETHING BOTH USERS AND

6717
04:40:35,320 --> 04:40:39,040
REGULATORS CAN RELATE TO IN THE

6718
04:40:39,040 --> 04:40:43,120
END. IT IS THE VALIDATION. THIS

6719
04:40:43,120 --> 04:40:46,000
IS WHAT WILL BE REQUIRED. THESE

6720
04:40:46,000 --> 04:40:47,080
ASSAYS HAVE SO COMPLEX YOU DON'T

6721
04:40:47,080 --> 04:40:49,880
WANT TO PRODUCE A FILE FOR THE

6722
04:40:49,880 --> 04:40:52,200
FDA EVERY TIME YOU WANT TO

6723
04:40:52,200 --> 04:40:56,240
SUPPORT AN APPLICATION. 

6724
04:40:56,240 --> 04:40:58,240
>> THIS IS A GREAT
DISCUSSION

6725
04:40:58,240 --> 04:40:59,920
FROM MY EXPERIENCE TOO, THERE IS

6726
04:40:59,920 --> 04:41:03,320
FLEXIBILITY FROM THE REGULATORY

6727
04:41:03,320 --> 04:41:04,800
AGENCIESND EVALUATING ASSAYS AS

6728
04:41:04,800 --> 04:41:06,320
LONG AS WELL VALIDATED WITH

6729
04:41:06,320 --> 04:41:10,960
STANDARDS AND CONTROLS AND VERY

6730
04:41:10,960 --> 04:41:13,640
SPECIFICATIONS YOU POINT OUT FOR

6731
04:41:13,640 --> 04:41:17,000
REGULATORY PURPOSES. THERE IS

6732
04:41:17,000 --> 04:41:18,320
HESITANCE FROM THE INDUSTRY TO

6733
04:41:18,320 --> 04:41:19,440
TAKE ON THAT RESPONSIBILITY.

6734
04:41:19,440 --> 04:41:21,440
THERE ARE OTHER EASIER WAYS TO

6735
04:41:21,440 --> 04:41:23,680
GET THAT DATA OR MORE STANDARD

6736
04:41:23,680 --> 04:41:27,320
WAYS TO GET THAT DATA, THAT IS

6737
04:41:27,320 --> 04:41:29,440
PREFERRED PATH BUT AS YOU SAY

6738
04:41:29,440 --> 04:41:32,560
THOMAS, IF THERE ARE SOME ASSAYS

6739
04:41:32,560 --> 04:41:36,320
THAT HAVE BEEN MORE WELL

6740
04:41:36,320 --> 04:41:37,040
CHARACTERIZED, VALIDATED FOR

6741
04:41:37,040 --> 04:41:40,320
SPECIFIC USE PURPOSES, PERHAPS

6742
04:41:40,320 --> 04:41:43,960
HAVING IT EITHER -- GO AHEAD. 

6743
04:41:43,960 --> 04:41:47,600
>> THE INDUSTRY HAS TO
COME

6744
04:41:47,600 --> 04:41:49,400
TOGETHER AND FORM CONSORTIA TO

6745
04:41:49,400 --> 04:41:51,640
JOIN BECAUSE IT IS MORE

6746
04:41:51,640 --> 04:41:54,440
EXPENSIVE AND DIFFICULT TO

6747
04:41:54,440 --> 04:41:58,080
EVALUATE THESE SYSTEMS AND ALSO

6748
04:41:58,080 --> 04:42:00,640
FEEDBACK TO THE WHAT IS NEEDED

6749
04:42:00,640 --> 04:42:03,440
AND DIFFERENT WEAKNESSES.  THERE

6750
04:42:03,440 --> 04:42:06,480
IS TREMENDOUS -- I HAVE NEVER

6751
04:42:06,480 --> 04:42:07,720
SEEN SOMETHING LIKE WHAT THE FDA

6752
04:42:07,720 --> 04:42:12,120
IS DOING WITH MPS. THE DOOR WITH

6753
04:42:12,120 --> 04:42:14,200
THE ICELAND PROGRAM FOR

6754
04:42:14,200 --> 04:42:17,120
QUALIFICATION. WHICH HAS TO BE

6755
04:42:17,120 --> 04:42:19,440
TRIED. WE IMMEDIATE THE FIRST

6756
04:42:19,440 --> 04:42:21,120
MPS TO GO THROUGH PROCESS TO SEE

6757
04:42:21,120 --> 04:42:23,320
IF THIS FEASIBLE, WAY OF

6758
04:42:23,320 --> 04:42:26,640
CREATING THE TRUST WHICH IS

6759
04:42:26,640 --> 04:42:29,800
REQUIRED. THE ONLY THING WORD

6760
04:42:29,800 --> 04:42:36,640
DRUG DEVELOPMENT IS FDA, VERY

6761
04:42:36,640 --> 04:42:37,520
SIMPLE, 4.3% OF THE WORLD

6762
04:42:37,520 --> 04:42:40,000
POPULATION BUT WE CONSUME 48% OF

6763
04:42:40,000 --> 04:42:43,480
ALL DRUGS MARKETED IN THE WORLD

6764
04:42:43,480 --> 04:42:45,520
AND 64% WHAT IS SOLD ON THE

6765
04:42:45,520 --> 04:42:47,320
PATENT SO PHARMA COMPANIES LOOK

6766
04:42:47,320 --> 04:42:52,040
FOR FDA DOING. THIS IS WHY

6767
04:42:52,040 --> 04:42:54,160
ATTITUDE IS SUCH BREAK THROUGH

6768
04:42:54,160 --> 04:43:02,200
FOR ADOPTING EARLY.

6769
04:43:02,200 --> 04:43:04,640
>> VERY GOOD POINT. THANK
YOU,

6770
04:43:04,640 --> 04:43:08,840
NICOLE. YOU BRING BACK VERY GOOD

6771
04:43:08,840 --> 04:43:13,200
POINT. THE FACT THAT THE

6772
04:43:13,200 --> 04:43:15,520
INDUSTRY NEEDS TO FORM THIS

6773
04:43:15,520 --> 04:43:17,640
CONSORTIA AND HAVE THIS DRUG, WE

6774
04:43:17,640 --> 04:43:20,520
HAVE EXPERIENCE AND USE THEM

6775
04:43:20,520 --> 04:43:24,120
BEFORE IN SARS COV-2 WAS

6776
04:43:24,120 --> 04:43:26,440
EXCELLENT EXAMPLE. AND MASTER

6777
04:43:26,440 --> 04:43:30,560
FILES GET WISE USE AND HELPED

6778
04:43:30,560 --> 04:43:32,200
ASSAY AS REVIEWERS OF THESE

6779
04:43:32,200 --> 04:43:35,160
APPLICATIONS AND HELP COMPANIES

6780
04:43:35,160 --> 04:43:37,080
EXAMINING THINGS FORWARD. I

6781
04:43:37,080 --> 04:43:41,920
THINK THAT IS A SPACE THAT COULD

6782
04:43:41,920 --> 04:43:43,640
BE FURTHER EXPLORED AND WORKED

6783
04:43:43,640 --> 04:43:44,920
ON.

6784
04:43:44,920 --> 04:43:46,800
>> IT IS ALSO IMPORTANT TO

6785
04:43:46,800 --> 04:43:51,200
CONSIDER THE FACT THAT THERE IS

6786
04:43:51,200 --> 04:43:52,200
OBVIOUSLY CONTEXT OF USE IS

6787
04:43:52,200 --> 04:43:53,520
ESSENTIALLY THE MOST IMPORTANT

6788
04:43:53,520 --> 04:43:56,480
THING WHEN VALIDATING AN

6789
04:43:56,480 --> 04:43:58,000
APPROACH AND WHEN SCIENTIFIC

6790
04:43:58,000 --> 04:43:59,040
CONFIDENCE AND THERE IS A

6791
04:43:59,040 --> 04:44:01,360
DIFFERENT BAR BETWEEN

6792
04:44:01,360 --> 04:44:01,960
DEMONSTRATING EFFICACY AND

6793
04:44:01,960 --> 04:44:06,440
DEMONSTRATING SAFETY.  AT THE

6794
04:44:06,440 --> 04:44:11,920
MOMENT THERE IS TREMENDOUS

6795
04:44:11,920 --> 04:44:12,480
OPPORTUNITY IN THE EFFICACY

6796
04:44:12,480 --> 04:44:13,080
SPACE, SPARLY AS EVIDENCED BY

6797
04:44:13,080 --> 04:44:13,680
EVI'S TALK AND THE TALKS I SAW

6798
04:44:13,680 --> 04:44:14,840
LAST WEEK PARTICULARLY WORK

6799
04:44:14,840 --> 04:44:16,040
BEING DONE BY ROCHE AND OTHER

6800
04:44:16,040 --> 04:44:18,680
COMPANIES, IN MANY THE BIOLOGICS

6801
04:44:18,680 --> 04:44:20,360
SPACE. SO MANY NEW MOLECULES

6802
04:44:20,360 --> 04:44:21,800
COMING OUT ARE BIOLOGICS AND

6803
04:44:21,800 --> 04:44:24,640
THEY SIMPLY DO NOT HAVE

6804
04:44:24,640 --> 04:44:26,120
NON-HUMAN TARGETS. THEY JUST

6805
04:44:26,120 --> 04:44:27,520
DON'T HAVE THE OPTION OF USING

6806
04:44:27,520 --> 04:44:31,880
AN ANIMAL MODEL TO TEST THEM

6807
04:44:31,880 --> 04:44:34,200
BECAUSE THE ANIMAL SPECIES

6808
04:44:34,200 --> 04:44:38,160
DOESN'T POSSESS THE TARGET

6809
04:44:38,160 --> 04:44:39,600
ENGINEERED FOR. SO I THINK THAT

6810
04:44:39,600 --> 04:44:45,440
IS AN AREA WHERE THERE IS REALLY

6811
04:44:45,440 --> 04:44:46,800
EXCITING OPPORTUNITY AND

6812
04:44:46,800 --> 04:44:49,960
ABSOLUTE REQUIREMENT TO USE

6813
04:44:49,960 --> 04:44:54,680
HUMAN BASED SYSTEMS TO ADDRESS

6814
04:44:54,680 --> 04:44:57,520
THOSE PARTICULAR BIOLOGICS.

6815
04:44:57,520 --> 04:44:59,120
>> I CAN ONLY SUSPECT IT
IS

6816
04:44:59,120 --> 04:45:00,680
REALLY EFFICACY TESTING THAT'S

6817
04:45:00,680 --> 04:45:02,880
THE COMPETITION OF IDEAS WHERE

6818
04:45:02,880 --> 04:45:08,080
THE BETTER MODEL IS USED BY THE

6819
04:45:08,080 --> 04:45:13,000
MORE TECHNOLOGY COMPANIES. THE

6820
04:45:13,000 --> 04:45:13,960
AREA SHOOT IN THE FOOT IF YOU

6821
04:45:13,960 --> 04:45:14,720
ARE USING IN ADDITION TO WHAT

6822
04:45:14,720 --> 04:45:17,440
YOU HAVE TO DO, YOU CAN ONLY

6823
04:45:17,440 --> 04:45:18,080
LOSE INNOCENCE AND THEN YOU HAVE

6824
04:45:18,080 --> 04:45:21,080
TO FOLLOW-UP AND DELAY WHATEVER

6825
04:45:21,080 --> 04:45:23,160
PROCESS. THERE ARE THESE MODELS

6826
04:45:23,160 --> 04:45:26,360
SHINE VERY EARLY STAGE OF

6827
04:45:26,360 --> 04:45:29,880
INVESTIGATIVE TOXICOLOGY OF

6828
04:45:29,880 --> 04:45:38,160
TARGET EVALUATION AND FOR

6829
04:45:38,160 --> 04:45:38,760
DIVERTS PHIING ANIMAL STUDIES

6830
04:45:38,760 --> 04:45:39,320
YOU WANT TO -- DIVERSIFYING

6831
04:45:39,320 --> 04:45:39,960
ANIMAL STUDIES YOU WANT TO SHOW

6832
04:45:39,960 --> 04:45:40,520
IT IS NOT RELEVANT SO IT IS

6833
04:45:40,520 --> 04:45:41,120
TOXICOLOGY BUT NOT REGULATORY

6834
04:45:41,120 --> 04:45:41,440
TOXICOLOGISTS.

6835
04:45:41,440 --> 04:45:42,360
>> SO I WOULD JUST MAKE A
LITTLE

6836
04:45:42,360 --> 04:45:44,800
PUSH BACK HERE FOR IN TERMS OF

6837
04:45:44,800 --> 04:45:49,600
DATA SAFETY DATA. OF COURSE THE

6838
04:45:49,600 --> 04:45:52,640
VIRUS IS VERY HIGH BUT WE DON'T

6839
04:45:52,640 --> 04:45:57,840
HAVE TO USE THEM FOR ALL END

6840
04:45:57,840 --> 04:45:58,760
POINTS IF WE HAVE SPECIFIC WELL

6841
04:45:58,760 --> 04:46:04,120
DEFINED END POINTS FOR ANIMALS

6842
04:46:04,120 --> 04:46:04,720
FULFILLING ALL THE INFORMATION.

6843
04:46:04,720 --> 04:46:06,760
BY DOING THAT IT IS NOT THAT WE

6844
04:46:06,760 --> 04:46:09,600
ARE SHOWING DEVELOPMENT, IN FACT

6845
04:46:09,600 --> 04:46:11,640
THE MORE UNCOMFORTABLE US AS

6846
04:46:11,640 --> 04:46:15,560
REGULATORS ARE WITH A PRODUCT

6847
04:46:15,560 --> 04:46:16,480
THAT IS GOING TO -- THE SLOWER

6848
04:46:16,480 --> 04:46:20,640
THE STUDY WILL BE BECAUSE THE

6849
04:46:20,640 --> 04:46:27,880
CLINICAL TRIAL DESIGN WILL BE

6850
04:46:27,880 --> 04:46:28,480
IMPACTED, IT WILL HAVE SAFETY

6851
04:46:28,480 --> 04:46:35,200
MEASURES, WILL HAVE ONE PATIENT

6852
04:46:35,200 --> 04:46:35,840
AT A TIME. SO THERE WOULD BE THE

6853
04:46:35,840 --> 04:46:39,440
MORE UNKNOWNS WE HAVE THE MORE

6854
04:46:39,440 --> 04:46:43,760
UNCOMFORTABLE WE ARE. THE SLOWER

6855
04:46:43,760 --> 04:46:44,400
THE MORE SAFETY MEASURES WE HAVE

6856
04:46:44,400 --> 04:46:46,800
TO PUT IN PLACE JUST TO MAKE

6857
04:46:46,800 --> 04:46:47,440
SURE THAT THE SAFETY OF CLINICAL

6858
04:46:47,440 --> 04:46:49,920
TRIAL PARTICIPANTS IS BEING

6859
04:46:49,920 --> 04:46:59,440
ENSURED. SO IF DATA FROM A

6860
04:46:59,440 --> 04:47:01,560
SYSTEM VALIDATED, THAT IS WE

6861
04:47:01,560 --> 04:47:05,440
KNOW THAT IS BRINGING OUT END

6862
04:47:05,440 --> 04:47:07,320
POINT AND OUTCOMES THAT ARE

6863
04:47:07,320 --> 04:47:08,080
PREDICTIVE OF HUMAN OUTCOMES

6864
04:47:08,080 --> 04:47:11,080
THEN THAT WOULD ACTUALLY HELP TO

6865
04:47:11,080 --> 04:47:11,760
THE CLINICAL DEVELOPMENT IN MY

6866
04:47:11,760 --> 04:47:16,520
OPINION.

6867
04:47:16,520 --> 04:47:18,240
>> I WANT TO TAKE THE LAST

6868
04:47:18,240 --> 04:47:21,360
MINUTE COUPLE OF QUESTIONS FOR

6869
04:47:21,360 --> 04:47:23,320
EDWIN. THE ONE QUESTION, IT IS A

6870
04:47:23,320 --> 04:47:24,960
BEAUTIFUL SYSTEM FOR SCREENING. 

6871
04:47:24,960 --> 04:47:26,880
WHAT IS THE THROUGH PUT FOR

6872
04:47:26,880 --> 04:47:29,120
THAT, HOW MANY COMPOUNDS COULD

6873
04:47:29,120 --> 04:47:30,840
YOU SCREEN PER MONTH OR WEEK?

6874
04:47:30,840 --> 04:47:34,000
>> I THINK THAT IT IS UP
TO

6875
04:47:34,000 --> 04:47:35,240
DEFINITELY RIGHT NOW THE MOST WE

6876
04:47:35,240 --> 04:47:38,320
HAVE DONE IS BASICALLY -- TEN

6877
04:47:38,320 --> 04:47:40,240
PLACE OVER TIME BUT WE CAN SET

6878
04:47:40,240 --> 04:47:42,560
UP TO HOW MANY YOU WANT TO DO

6879
04:47:42,560 --> 04:47:46,520
ACTUALLY AND THEN RIGHT NOW IT

6880
04:47:46,520 --> 04:47:48,000
IS VERY WELL SCALABLE IT IS NOT

6881
04:47:48,000 --> 04:47:49,160
REALLY A LIMITATION AT THIS

6882
04:47:49,160 --> 04:47:55,360
POINT. WE DO THE ASSAYS HAVE 384

6883
04:47:55,360 --> 04:47:58,160
WELL PLATE ACCESS SO HIGHLY

6884
04:47:58,160 --> 04:48:01,360
SCALABLE WE HAVE MORE THAN 50

6885
04:48:01,360 --> 04:48:02,720
PATIENTS SO FEW ROUNDS OF

6886
04:48:02,720 --> 04:48:07,280
SCREENING BUT MOST PART HIGHLY

6887
04:48:07,280 --> 04:48:09,440
HIGH THROUGH PUT AND VERY WELL

6888
04:48:09,440 --> 04:48:10,440
SCALABLE AS WELL.

6889
04:48:10,440 --> 04:48:12,840
>> AND ALWAYS HIGH CONTENT

6890
04:48:12,840 --> 04:48:13,680
IMAGING OR DO YOU HAVE FURTHER

6891
04:48:13,680 --> 04:48:14,280
READ OUTS?

6892
04:48:14,280 --> 04:48:16,840
>> IT IS HIGH CONTENT
IMAGING,

6893
04:48:16,840 --> 04:48:21,640
CONFOCAL BASED IMAGING ACTUALLY.

6894
04:48:21,640 --> 04:48:24,720
IT IS BOTH IN NOT ONLY INFECTION

6895
04:48:24,720 --> 04:48:29,560
LEVELS BUT ALSO IN SITU LOOK AT

6896
04:48:29,560 --> 04:48:31,840
COMPOUNDS THAT NOT ONLY BENEFITS

6897
04:48:31,840 --> 04:48:34,480
IN TERMS OF DEREDUCING VIRAL

6898
04:48:34,480 --> 04:48:36,080
LOAD BUT RESCUING PATHOLOGY IN

6899
04:48:36,080 --> 04:48:38,960
LUNG TISSUE. WE DO THAT BY USING

6900
04:48:38,960 --> 04:48:42,720
THE COMPUTATIONAL BASE AND TO

6901
04:48:42,720 --> 04:48:43,840
DEFINE THOSE WE DON'T SEE

6902
04:48:43,840 --> 04:48:46,080
MEASURES YET. 

6903
04:48:46,080 --> 04:48:47,880
>> THAT SHOULD COVER OTHER

6904
04:48:47,880 --> 04:48:49,040
QUESTIONS FOR YOU IN THE OPEN

6905
04:48:49,040 --> 04:48:51,120
BOX IF YOU WANT TO ANSWER

6906
04:48:51,120 --> 04:48:52,960
OFFLINE. WE ARE OUT OF TIME. I

6907
04:48:52,960 --> 04:48:55,640
WILL TURN THE MEETING BACK TO

6908
04:48:55,640 --> 04:48:57,560
SARINE. THANK YOU, ALL SPEAKERS 

6909
04:48:57,560 --> 04:48:59,120
THIS HAS BEEN A WONDERFUL

6910
04:48:59,120 --> 04:48:59,680
SESSION. THANK YOU FOR THIS

6911
04:48:59,680 --> 04:49:00,760
GREAT DISCUSSION AFTERWARDS. 

6912
04:49:00,760 --> 04:49:01,200
APPRECIATE IT.

6913
04:49:01,200 --> 04:49:03,960
>> THANK YOU.

6914
04:49:03,960 --> 04:49:06,400
>> THANK YOU SO MUCH,
ROBERT RO,

6915
04:49:06,400 --> 04:49:07,640
FOR CHAIRING THE WONDERFUL

6916
04:49:07,640 --> 04:49:08,800
SESSION AGAIN, I WOULD LIKE TO

6917
04:49:08,800 --> 04:49:10,360
THANK AGAIN THE SPEAKERS OF THE

6918
04:49:10,360 --> 04:49:11,920
SESSION AND THE WONDERFUL

6919
04:49:11,920 --> 04:49:13,400
CONVERSATION AND DISCUSSION THAT

6920
04:49:13,400 --> 04:49:17,440
WAS REALLY EXCITING. OKAY. SO WE

6921
04:49:17,440 --> 04:49:22,720
ARE AT THE FINAL SESSION. SUPER

6922
04:49:22,720 --> 04:49:25,560
EXCITED TO INVITE BACK DR. SIMON

6923
04:49:25,560 --> 04:49:27,680
FUNNELL OUR KEYNOTE SPEAKER FROM

6924
04:49:27,680 --> 04:49:31,640
THE UK HEALTH SECURITY AGENCY.

6925
04:49:31,640 --> 04:49:38,800
DR. NICOLE KLEINSTREUER FROM

6926
04:49:38,800 --> 04:49:39,400
ENVIRONMENTAL HEALTH SCIENCES

6927
04:49:39,400 --> 04:49:41,280
AND SARA CHERRY FROM UNIVERSITY

6928
04:49:41,280 --> 04:49:44,120
OF PENNSYLVANIA, EXCITED TO HEAR

6929
04:49:44,120 --> 04:49:46,640
ABOUT DISCUSSIONS AND

6930
04:49:46,640 --> 04:49:47,240
PERSPECTIVES ON THE CHALLENGES

6931
04:49:47,240 --> 04:49:50,440
AHEAD.  THE FLOOR IS YOURS. 

6932
04:49:50,440 --> 04:49:53,520
>> THANKS. WHAT I DO IS I
ASK

6933
04:49:53,520 --> 04:49:57,360
YOU FOR YOUR SLIDE FROM THE

6934
04:49:57,360 --> 04:49:58,120
FIRST SESSION WHERE YOU

6935
04:49:58,120 --> 04:49:59,520
INTRODUCED THE WORKSHOP AND I

6936
04:49:59,520 --> 04:50:04,320
JUST WANTED TO SHARE YOUR SLIDE

6937
04:50:04,320 --> 04:50:05,480
TO TALK ABOUT WHAT YOU STATED

6938
04:50:05,480 --> 04:50:07,800
WERE OBJECTIVES. I THINK WE DID

6939
04:50:07,800 --> 04:50:11,960
A GOOD JOB COVERING TODAY. AND

6940
04:50:11,960 --> 04:50:20,440
YESTERDAY. YOUR SLIDE. 

6941
04:50:20,440 --> 04:50:22,440
>> IDE SEE IN PRESENTER
MODE. 

6942
04:50:22,440 --> 04:50:32,960
HAPPY TO SHARE IF YOU WOULD LIKE

6943
04:50:50,920 --> 04:50:52,600
TALKING AVAILABILITY OF TISSUE

6944
04:50:52,600 --> 04:50:53,560
MODELS AND CHALLENGES IN

6945
04:50:53,560 --> 04:50:54,680
BUILDING THEM IN TERMS OF

6946
04:50:54,680 --> 04:50:56,360
UTILITY AND LIMITATIONS HOW THEY

6947
04:50:56,360 --> 04:50:58,320
CAN BE USED IN DRUG DISCOVERY

6948
04:50:58,320 --> 04:51:01,160
DEVELOPMENT WITH THE PROS AND

6949
04:51:01,160 --> 04:51:02,680
CONS, WHAT WE THINK GUIDES LINES

6950
04:51:02,680 --> 04:51:03,840
AND CONSIDERATIONS MAYBE FOR

6951
04:51:03,840 --> 04:51:08,280
DEVELOPING ROBUST REPRODUCIBLE

6952
04:51:08,280 --> 04:51:11,120
MODELS. AND THEN TALK ABOUT

6953
04:51:11,120 --> 04:51:12,560
AFFORDABILITY ACCESSIBILITY AND

6954
04:51:12,560 --> 04:51:17,600
TRANSFERABILITY OF THESE MODELS.

6955
04:51:17,600 --> 04:51:18,600
COVER THAT MUCH ABOUT THE

6956
04:51:18,600 --> 04:51:20,960
ADVANTAGE AND DISADVANTAGE OF 3D

6957
04:51:20,960 --> 04:51:22,760
MODELS OTHER THAN TO PRETTY MUCH

6958
04:51:22,760 --> 04:51:24,960
ALL AGREE THERE ARE MAJOR

6959
04:51:24,960 --> 04:51:29,240
ADVANTAGES BUT I THINK THERE ARE

6960
04:51:29,240 --> 04:51:30,520
LIMITATIONS PERSONALLY AS USER

6961
04:51:30,520 --> 04:51:34,080
IT IS DIFFICULT TO ADOPT THESE

6962
04:51:34,080 --> 04:51:35,960
AND FIGURE OUT THE DIFFERENCES

6963
04:51:35,960 --> 04:51:40,000
ACROSS THE PLATFORMS BUT I

6964
04:51:40,000 --> 04:51:45,080
THOUGHT THAT ACCESS AND SIMON

6965
04:51:45,080 --> 04:51:46,400
WANTED TO TALK A LITTLE BIT

6966
04:51:46,400 --> 04:51:47,640
ABOUT SOME ASPECTS OF THIS SO

6967
04:51:47,640 --> 04:51:49,240
I'M GOING TO TURN IT OVER TO HIM

6968
04:51:49,240 --> 04:51:56,280
NOW.

6969
04:51:56,280 --> 04:51:58,400
>> THANK YOU, ALSO THANK
YOU TO

6970
04:51:58,400 --> 04:52:00,240
NSP CORE GROUP WHO INTRODUCED ME

6971
04:52:00,240 --> 04:52:06,160
TO THIS DAZZLING ARRAY OF TALKS

6972
04:52:06,160 --> 04:52:09,960
THE LAST TWO DAYS.  SESSION 1, 2

6973
04:52:09,960 --> 04:52:12,360
AND 3 TOGETHER FORM WHAT I TRIED

6974
04:52:12,360 --> 04:52:19,080
TO DESCRIBE AS A SCIENCE, THAT

6975
04:52:19,080 --> 04:52:20,120
TRAIN HAS LEFT THE STATION AND

6976
04:52:20,120 --> 04:52:23,360
I'M PLEASED TO BE ON THE LAST

6977
04:52:23,360 --> 04:52:26,520
CARRIAGE. WHEN WE TALK

6978
04:52:26,520 --> 04:52:27,600
REGULATORY ACCEPTANCE OF THE

6979
04:52:27,600 --> 04:52:34,760
DATA BEING GENERATED, WHEN WE

6980
04:52:34,760 --> 04:52:37,560
SAW SLIDE OF REQUIREMENTS AND

6981
04:52:37,560 --> 04:52:39,800
THE WHETHER THE POINT SHE PUT

6982
04:52:39,800 --> 04:52:41,640
YOU WANT -- BULLET POINTS SHE

6983
04:52:41,640 --> 04:52:43,400
PUT UP WE CAN TAKE AWAY FROM THE

6984
04:52:43,400 --> 04:52:45,120
BULLET POINTS. MY PERCEPTION IS

6985
04:52:45,120 --> 04:52:48,280
SARS COV-2 AS TRAGIC AS IT HAS

6986
04:52:48,280 --> 04:52:53,160
BEEN FOR THE PLANET, IT HAS

6987
04:52:53,160 --> 04:52:54,120
ACTUALLY BEEN A GIFT FOR THIS

6988
04:52:54,120 --> 04:52:56,080
TYPE OF TECHNOLOGY. WHEN WE

6989
04:52:56,080 --> 04:53:00,320
REFLECT HOW ANIMAL MODELS HAVE

6990
04:53:00,320 --> 04:53:04,120
DELIVERED AND ARGUABLY THE

6991
04:53:04,120 --> 04:53:07,440
HAMSTER HAS BEEN VERY HELPFUL

6992
04:53:07,440 --> 04:53:09,760
BECAUSE THERE IS NOT ENOUGH

6993
04:53:09,760 --> 04:53:12,600
NON-HUMAN PRIMATES WITH DATA

6994
04:53:12,600 --> 04:53:16,880
THAT WE NEED WHEN WE THINK ABOUT

6995
04:53:16,880 --> 04:53:21,400
OMICRON AND BA 2, BA 4, BA 5

6996
04:53:21,400 --> 04:53:24,560
CURRENT CIRCULATING STRENGTH,

6997
04:53:24,560 --> 04:53:26,880
THESE VIRUSES ARE DIFFERENT THAN

6998
04:53:26,880 --> 04:53:31,640
THE PROTOTYPE VIRUS. WE CAN'T --

6999
04:53:31,640 --> 04:53:33,400
ANYBODY TRIES TO GROW BA 2 BA 4

7000
04:53:33,400 --> 04:53:38,640
OR 5 THEY STRUGGLE WITH THAT.

7001
04:53:38,640 --> 04:53:42,840
THEY ALWAYS USE STEM CELL WHICH

7002
04:53:42,840 --> 04:53:44,040
HAS A PLASMA WITHIN IT, WHICH

7003
04:53:44,040 --> 04:53:46,720
HAS (INAUDIBLE) AND WHENEVER WE

7004
04:53:46,720 --> 04:53:48,480
GROW VIRUS IN THAT CELL LINE

7005
04:53:48,480 --> 04:53:52,120
THEY TEND TO BE TRUE TO THE

7006
04:53:52,120 --> 04:53:54,080
ISOLATES. BUT I KNOW OTHERS HAVE

7007
04:53:54,080 --> 04:53:57,520
USED OTHER CELL LINES BUT

7008
04:53:57,520 --> 04:53:58,880
VARIOUS HAVE BEEN A GIFT TO US

7009
04:53:58,880 --> 04:54:00,200
BECAUSE WE HAVE BEEN ABLE GROW

7010
04:54:00,200 --> 04:54:03,040
OMICRON IN THOSE CELLS IN A WAY

7011
04:54:03,040 --> 04:54:04,880
WE COULDN'T DO SO BUT AT THE END

7012
04:54:04,880 --> 04:54:08,200
OF THE DAY IT IS STILL A CELL,

7013
04:54:08,200 --> 04:54:09,520
AT HEART OF THE ISSUE OF

7014
04:54:09,520 --> 04:54:10,960
ANTIVIRAL DRUG DEVELOPMENT IS

7015
04:54:10,960 --> 04:54:13,200
GETTING THE RIGHT VIRUS TO START

7016
04:54:13,200 --> 04:54:14,440
WITH. YOU CAN HAVE THE BEST

7017
04:54:14,440 --> 04:54:15,960
SYSTEM ON THE PLANET IF YOU PUT

7018
04:54:15,960 --> 04:54:18,840
IN A VIRUS, ANY WAY COMPROMISE

7019
04:54:18,840 --> 04:54:21,120
FROM THE ACTUAL TARGETS YOU HAS

7020
04:54:21,120 --> 04:54:23,800
-- YOU WERE AT BAD START. WHEN

7021
04:54:23,800 --> 04:54:25,720
WE THINK ABOUT OMICRON IT IS

7022
04:54:25,720 --> 04:54:28,680
ALSO REI CAN LOUSE TO SHOW ANY

7023
04:54:28,680 --> 04:54:30,360
CLINICAL SIZE AT ALL UNLIKE

7024
04:54:30,360 --> 04:54:33,960
HUMAN YOU WILL SEE A NUMBER OF

7025
04:54:33,960 --> 04:54:35,360
CLINICAL SITES, SO WHEN WE THINK

7026
04:54:35,360 --> 04:54:37,960
COMPARING TO THE GOLD STANDARD,

7027
04:54:37,960 --> 04:54:42,840
WHICH IS ONE BULLET POINT ON THE

7028
04:54:42,840 --> 04:54:47,840
SLIDE, THEY MAY BE A GIFT. SO

7029
04:54:47,840 --> 04:54:51,600
STRAIGHT AWAY YOU WANTED TO --

7030
04:54:51,600 --> 04:54:53,680
THEY KNOW THAT AND THEY HAVE

7031
04:54:53,680 --> 04:54:55,000
GREAT APPETITE TO ACCEPT THIS

7032
04:54:55,000 --> 04:54:57,400
KIND OF DATA AND THE OTHER GIFT

7033
04:54:57,400 --> 04:55:00,680
WAS THE PAPER I DESCRIBED,

7034
04:55:00,680 --> 04:55:04,600
YESTERDAY AND REFERRED TO AGAIN

7035
04:55:04,600 --> 04:55:08,160
TODAY ABOUT HYDROXYCHLOROQUINE

7036
04:55:08,160 --> 04:55:11,200
AND HEMATONIB, THESE DRUGS ARE

7037
04:55:11,200 --> 04:55:13,520
DIFFICULT COURSES TO THE

7038
04:55:13,520 --> 04:55:14,200
COMMUNITY BECAUSE THEY

7039
04:55:14,200 --> 04:55:16,000
CONSOLIDATE MPS AS A MEDICAL

7040
04:55:16,000 --> 04:55:19,640
TOOL IN THE QUEST FOR ANTIVIRALS

7041
04:55:19,640 --> 04:55:21,920
AND WHEN I THINK ABOUT WHAT SARA

7042
04:55:21,920 --> 04:55:24,600
HAS PRESENTED, WHAT CALVIN

7043
04:55:24,600 --> 04:55:27,880
PRESENTED, WHAT -- THERE'S SO

7044
04:55:27,880 --> 04:55:29,800
MANY TALKS HERE, THAT GIVES ME

7045
04:55:29,800 --> 04:55:31,040
INSPIRATION THAT YOU CAN VERY

7046
04:55:31,040 --> 04:55:33,520
QUICKLY PUTTING TO A REGULATORY

7047
04:55:33,520 --> 04:55:35,720
PACKAGE ACCEPTABLE BY THE FDA

7048
04:55:35,720 --> 04:55:37,800
BASED ON THE DEFICIENCIES OF THE

7049
04:55:37,800 --> 04:55:40,240
CURRENT GOLD STANDARD WHICH MAY

7050
04:55:40,240 --> 04:55:41,680
NO LONGER WORK FOR SOME OF THESE

7051
04:55:41,680 --> 04:55:47,720
VARIANTS.  I DON'T WANT TO TAKE

7052
04:55:47,720 --> 04:55:49,520
UP ALL 20 MINUTES BUT SAW

7053
04:55:49,520 --> 04:55:50,960
WONDERFUL QUOTATIONS IN SOME OF

7054
04:55:50,960 --> 04:55:53,560
THE SLIDES, ONE FROM EINSTEIN

7055
04:55:53,560 --> 04:55:55,680
SAYING WITHIN ANY CRISIS THERE'S

7056
04:55:55,680 --> 04:55:57,040
OPPORTUNITIES WHERE WE ARE THERE

7057
04:55:57,040 --> 04:56:00,280
NOW WITH SARS COV-2 AND I SAW

7058
04:56:00,280 --> 04:56:01,720
ANOTHER QUOTE SAYING THE

7059
04:56:01,720 --> 04:56:03,160
DIFFICULTY OF FUTURE TECHNOLOGY

7060
04:56:03,160 --> 04:56:04,520
IS NOT ACCEPTANCE OF THE NEW BUT

7061
04:56:04,520 --> 04:56:07,080
THE RESISTANCE TO REJECT THE

7062
04:56:07,080 --> 04:56:09,520
OLD. THAT IS ONE OF THE -- THAT

7063
04:56:09,520 --> 04:56:11,880
I DO THINK THERE'S -- WITHIN THE

7064
04:56:11,880 --> 04:56:15,720
FDA TO UNDERSTAND THESE ISSUES

7065
04:56:15,720 --> 04:56:17,280
SO I THINK THAT I WILL STOP

7066
04:56:17,280 --> 04:56:20,760
THERE AND ALLOW SARA AND NICOLE

7067
04:56:20,760 --> 04:56:22,720
TO TALK IN THE MINUTES THAT

7068
04:56:22,720 --> 04:56:28,120
REMAIN IN THIS DISCUSSION. 

7069
04:56:28,120 --> 04:56:31,320
>> THANKS, SIMON. I WILL
WEIGH

7070
04:56:31,320 --> 04:56:35,720
IN AS FAR AS MY 30,000-FOOT VIEW

7071
04:56:35,720 --> 04:56:38,160
PERSPECTIVE FROM THE WORK THAT

7072
04:56:38,160 --> 04:56:39,600
THE EXCELLENT TALKS WE HAVE

7073
04:56:39,600 --> 04:56:41,120
HEARD THE LAST DAY AND A HALF.

7074
04:56:41,120 --> 04:56:43,720
AND WHERE THIS FIELD IS GOING

7075
04:56:43,720 --> 04:56:46,520
AND SPECIFICALLY FROM

7076
04:56:46,520 --> 04:56:48,600
PERSPECTIVE OF STARTING THE

7077
04:56:48,600 --> 04:56:49,640
QUALIFY SYSTEMS FOR SPECIFIC

7078
04:56:49,640 --> 04:56:52,000
CONTEXT AND USE AND GAINS MORE

7079
04:56:52,000 --> 04:56:53,960
ACCEPTANCE AS I HAVE MENTIONED I

7080
04:56:53,960 --> 04:56:56,480
FULLY AGREE THAT WHILE

7081
04:56:56,480 --> 04:56:59,040
INCREDIBLY TRAGIC THE COVID

7082
04:56:59,040 --> 04:57:01,400
PANDEMIC HAS PROVIDED JUST AN

7083
04:57:01,400 --> 04:57:02,920
OUTSTANDING OPPORTUNITY TO

7084
04:57:02,920 --> 04:57:04,920
REALLY STRESS TEST THESE SYSTEMS

7085
04:57:04,920 --> 04:57:06,840
AND SHOW HOW USEFUL THEY ARE AND

7086
04:57:06,840 --> 04:57:10,120
HOW IMPORTANT THEY ARE, IN

7087
04:57:10,120 --> 04:57:12,720
PROVIDING US HUMAN RELEVANT

7088
04:57:12,720 --> 04:57:14,320
INSIGHT INTO THE PATHOPHYSIOLOGY

7089
04:57:14,320 --> 04:57:19,200
AND DISEASE MECHANISMS PLATFORMS

7090
04:57:19,200 --> 04:57:21,160
FOR THERAPEUTIC TREATMENT BUT

7091
04:57:21,160 --> 04:57:24,440
STEPPING BACK THINKING MORE

7092
04:57:24,440 --> 04:57:26,520
GENERALLY ABOUT MPS AND HOW WE

7093
04:57:26,520 --> 04:57:29,920
GET TO REGULATORY ACCEPTANCE AND

7094
04:57:29,920 --> 04:57:32,160
ABILITY TO TRULY HAVE THAT

7095
04:57:32,160 --> 04:57:34,200
SCIENTIFIC CONFIDENCE TO RELY ON

7096
04:57:34,200 --> 04:57:35,920
THE DATA THOSE SYSTEMS ARE

7097
04:57:35,920 --> 04:57:37,800
PROVIDING, I THINK THERE IS BEEN

7098
04:57:37,800 --> 04:57:40,240
MANY INSTANCES OF MEETINGS VERY

7099
04:57:40,240 --> 04:57:42,520
USEFUL MEETINGS WHERE DEVELOPERS

7100
04:57:42,520 --> 04:57:46,440
AND END USERS IN PHARMA DRUG

7101
04:57:46,440 --> 04:57:47,760
DEVELOPMENT SPACE AND REGULATORS

7102
04:57:47,760 --> 04:57:49,120
COME TOGETHER AND DISCUSS

7103
04:57:49,120 --> 04:57:51,800
QUALIFICATION CRITERIA AND

7104
04:57:51,800 --> 04:57:53,200
REGULATORY NEEDS, AROUND

7105
04:57:53,200 --> 04:57:54,880
COMPARISON THE EXISTING DATA AND

7106
04:57:54,880 --> 04:57:58,080
SPECIFIC END POINTS BUT THERE IS

7107
04:57:58,080 --> 04:58:01,200
NO CONSENSUS TO WHAT THAT LOOKS

7108
04:58:01,200 --> 04:58:05,800
LIKE SO I THINK WE ARE MOVING

7109
04:58:05,800 --> 04:58:09,280
TOWARD THAT SPACE. AS WE ENGAGE

7110
04:58:09,280 --> 04:58:10,720
MORE AND MORE WITH REGULATORY

7111
04:58:10,720 --> 04:58:11,760
AUTHORITY IN THE U.S. IN EUROPE

7112
04:58:11,760 --> 04:58:14,240
IN ASIA. AND DEVELOP

7113
04:58:14,240 --> 04:58:17,920
QUALIFICATION CRITERIA, THE

7114
04:58:17,920 --> 04:58:19,400
IQMPS AFFILIATE IS ONE OF THE

7115
04:58:19,400 --> 04:58:23,720
WORLDWIDE LEADERS IN THIS SPACE,

7116
04:58:23,720 --> 04:58:25,640
THERE IS A NICE EXAMPLE

7117
04:58:25,640 --> 04:58:30,880
PUBLISHED ON LIVER CHIP,

7118
04:58:30,880 --> 04:58:32,040
QUALIFICATION CRITERIA AND

7119
04:58:32,040 --> 04:58:35,040
STANDARD COMPOUND SETS FROM MY

7120
04:58:35,040 --> 04:58:38,600
PERSPECTIVE HELPING TO LEAD

7121
04:58:38,600 --> 04:58:39,360
VALIDATION ORGANIZATION

7122
04:58:39,360 --> 04:58:42,800
REFERENCE COMPOUNDS ARE PRETTY

7123
04:58:42,800 --> 04:58:44,520
CRITICAL IN TERMS OF BEING ABLE

7124
04:58:44,520 --> 04:58:46,840
TO DEMONSTRATE THE SYSTEM IS

7125
04:58:46,840 --> 04:58:48,280
REPRODUCELY ROBUSTLY GIVING YOU

7126
04:58:48,280 --> 04:58:49,600
THE INFORMATION YOU EXPECT SO

7127
04:58:49,600 --> 04:58:50,520
YOU CAN HAVE CONFIDENCE WHEN YOU

7128
04:58:50,520 --> 04:58:54,040
ARE TESTING SOMETHING NEW AND

7129
04:58:54,040 --> 04:58:55,080
UNKNOWN THAT YOU CAN TRUST THAT

7130
04:58:55,080 --> 04:58:58,080
DATA AN INTERPRET THOSE RESULTS

7131
04:58:58,080 --> 04:59:00,720
SO I THINK THAT THERE -- WE

7132
04:59:00,720 --> 04:59:04,880
REALLY NEED TO HAVE MORE GLOBAL

7133
04:59:04,880 --> 04:59:06,920
INTERACTIONS AMONG DIFFERENT

7134
04:59:06,920 --> 04:59:07,960
REGULATORY AUTHORITIES AND

7135
04:59:07,960 --> 04:59:12,480
METHOD DEVELOPERS TO ESTABLISH

7136
04:59:12,480 --> 04:59:13,840
STANDARD COMPOUNDS, THOSE

7137
04:59:13,840 --> 04:59:16,240
QUALIFICATION CRITERIA THAT ARE

7138
04:59:16,240 --> 04:59:20,680
TARGET ORGANS SPECIFIC. SO THAT

7139
04:59:20,680 --> 04:59:23,680
IS ONE THING TO SEE MORE

7140
04:59:23,680 --> 04:59:28,400
EMPHASIS PUT ON. IT IS NOT

7141
04:59:28,400 --> 04:59:32,800
ADEQUATELY RECOGNIZED HOW MUCH

7142
04:59:32,800 --> 04:59:33,520
OPPORTUNITY FROM THERE IS FOR

7143
04:59:33,520 --> 04:59:34,080
COMPANIES AND TECHNOLOGY

7144
04:59:34,080 --> 04:59:39,440
DEVELOPERS TO EBB GAUGE WITH THE

7145
04:59:39,440 --> 04:59:41,400
FDA THROUGH THE ICAM PROGRAM FOR

7146
04:59:41,400 --> 04:59:43,520
SURE BUT REACHING OUT TO THE FOR

7147
04:59:43,520 --> 04:59:44,840
EXAM FELONY THE ALTERNATIVE

7148
04:59:44,840 --> 04:59:47,080
METHODS WORK -- EXAMPLE, THE

7149
04:59:47,080 --> 04:59:48,640
ALTERNATIVE METHODS WORKING

7150
04:59:48,640 --> 04:59:50,040
GROUP AT THE FDA AND STARTING A

7151
04:59:50,040 --> 04:59:51,720
DIALOGUE. THERE ARE MANY CENTERS

7152
04:59:51,720 --> 04:59:56,520
NOT JUST CBER BUT CDER VERY

7153
04:59:56,520 --> 04:59:59,160
ENGAGED IN THE SPACE AND VERY

7154
04:59:59,160 --> 05:00:01,280
INTERESTED IN GETTING

7155
05:00:01,280 --> 05:00:04,480
SUBMISSIONS OF DATA RELYING ON

7156
05:00:04,480 --> 05:00:06,120
MPS, THAT ARE TARGETED FOR

7157
05:00:06,120 --> 05:00:07,720
SPECIFIC CONTEXT OF CRUISE BUT

7158
05:00:07,720 --> 05:00:12,520
IF I HAVE LEARNED ANYTHING IN

7159
05:00:12,520 --> 05:00:14,800
THE LAST TEN YEARS WITH NICEATM

7160
05:00:14,800 --> 05:00:17,800
IT IS THE ABSOLUTE IMPORTANCE OF

7161
05:00:17,800 --> 05:00:20,720
ENGAGING WITH YOUR END USERS

7162
05:00:20,720 --> 05:00:21,840
PARTICULARLY REGULATORY DECISION

7163
05:00:21,840 --> 05:00:24,040
MAKERS FROM DAY ONE, HAVING THAT

7164
05:00:24,040 --> 05:00:28,040
BE A CONSTANT ITERATIVE CYCLE OF

7165
05:00:28,040 --> 05:00:31,080
COMMUNICATION SO THAT YOU ARE

7166
05:00:31,080 --> 05:00:32,800
DEVELOPING METHODS TARGETED

7167
05:00:32,800 --> 05:00:35,640
TOWARDS THEIR NEEDS AND YOU ARE

7168
05:00:35,640 --> 05:00:37,640
UNDERSTANDING THEIR DECISION

7169
05:00:37,640 --> 05:00:39,880
CONTEXT AS GOING THROUGH THE

7170
05:00:39,880 --> 05:00:42,600
PROCESS OF DEVELOPMENT AND

7171
05:00:42,600 --> 05:00:44,400
QUALIFICATION AND ESTABLISHING

7172
05:00:44,400 --> 05:00:46,200
CONFIDENCE IN THOSE NEW

7173
05:00:46,200 --> 05:00:48,520
APPROACH. BUT I THINK THE SAME

7174
05:00:48,520 --> 05:00:51,280
IS ALSO TRUE WITH I MENTION WE

7175
05:00:51,280 --> 05:00:53,600
HAD A MEETING WITH EUROPEAN

7176
05:00:53,600 --> 05:00:56,600
MEDICINE AGENCY, THEY HAVE THE

7177
05:00:56,600 --> 05:00:59,360
INNOVATION TASK FORCE, SO THEY

7178
05:00:59,360 --> 05:01:00,440
HAVE SAFETY WORKING PARTY AND

7179
05:01:00,440 --> 05:01:03,320
THE INNOVATION TASK FORCE AND

7180
05:01:03,320 --> 05:01:07,200
THIS SAFE HARBOR PROGRAM WHERE

7181
05:01:07,200 --> 05:01:10,520
THERE IS GUIDANCE ON HOW THESE

7182
05:01:10,520 --> 05:01:12,160
DIFFERENT ROUTES OF

7183
05:01:12,160 --> 05:01:12,760
COMMUNICATION CAN BE -- WHERE

7184
05:01:12,760 --> 05:01:14,000
YOU CAN GET REGULATORY ADVICE ON

7185
05:01:14,000 --> 05:01:16,960
THE UTILITY AND VALIDITY OF

7186
05:01:16,960 --> 05:01:18,320
MODELS AND DATA GENERATED AND

7187
05:01:18,320 --> 05:01:19,920
COMPARE ALONGSIDE DATA GENERATED

7188
05:01:19,920 --> 05:01:23,280
IN TRADITIONAL STUDIES.  SO

7189
05:01:23,280 --> 05:01:24,480
THERE IS GUIDANCE HOW TO ACCESS

7190
05:01:24,480 --> 05:01:26,360
THOSE ROUTES BUT WHAT WE HEAR IS

7191
05:01:26,360 --> 05:01:30,840
THE UPTAKE IS VERY LOW SO THERE

7192
05:01:30,840 --> 05:01:35,440
IS FACTORS THAT CONTRIBUTE TO

7193
05:01:35,440 --> 05:01:38,320
THAT, LACK OF AWARENESS AROUND

7194
05:01:38,320 --> 05:01:38,840
OPPORTUNITIES, CONCERNS

7195
05:01:38,840 --> 05:01:40,480
MISPLACED OR NOT THAT IF

7196
05:01:40,480 --> 05:01:41,720
DISCUSSIONS ARE NOT FAVORABLE

7197
05:01:41,720 --> 05:01:47,640
THAT MIGHT COUNT AGAINST THEM

7198
05:01:47,640 --> 05:01:49,080
BUT HELPING SOCIALIZE

7199
05:01:49,080 --> 05:01:49,840
DISSEMINATE THAT INFORMATION

7200
05:01:49,840 --> 05:01:50,760
ABOUT OPPORTUNITIES TO ENGAGE

7201
05:01:50,760 --> 05:01:54,320
WITH REGULATORY AUTHORITIES, AND

7202
05:01:54,320 --> 05:01:57,760
GET DIALOGUE GOING AND GET THAT

7203
05:01:57,760 --> 05:01:59,160
ADVICE, IN A SAFE HARBOR WAY IS

7204
05:01:59,160 --> 05:01:59,840
HELPFUL IN MOVING THE FIELD

7205
05:01:59,840 --> 05:02:03,240
FORWARD.  THAT IS MY PIECE, I

7206
05:02:03,240 --> 05:02:06,080
WILL STOP THERE.

7207
05:02:06,080 --> 05:02:09,280
>> I THINK THAT THAT IS
RIGHT,

7208
05:02:09,280 --> 05:02:12,400
FROM THE END STAGE, REGULATORY

7209
05:02:12,400 --> 05:02:14,000
AGENCIES IS REALLY IMPORTANT BUT

7210
05:02:14,000 --> 05:02:20,760
I ALSO THINK THAT IT IS HELPFUL

7211
05:02:20,760 --> 05:02:22,240
TO ENGAGE MORE OF THE USER BASE

7212
05:02:22,240 --> 05:02:27,600
TO THIS COMMUNITY AND HAVE MORE

7213
05:02:27,600 --> 05:02:28,320
ACCESSIBILITY TO YOUR

7214
05:02:28,320 --> 05:02:29,280
(INAUDIBLE) FOR EXAMPLE, THE

7215
05:02:29,280 --> 05:02:30,840
ONLY WAY I START TO UTILIZE

7216
05:02:30,840 --> 05:02:35,600
THESE MODEL IS COLLABORATE WITH

7217
05:02:35,600 --> 05:02:40,320
NCATS AND WITH GATES FOUNDATION

7218
05:02:40,320 --> 05:02:41,640
WHO FACILITATED THE ABILITY NOT

7219
05:02:41,640 --> 05:02:42,920
ONLY TO ACCESS MODEL BUT LEARN

7220
05:02:42,920 --> 05:02:44,280
HOW TO USE THEM. SO I REALLY

7221
05:02:44,280 --> 05:02:46,960
THINK THAT THAT IS A REAL GAP,

7222
05:02:46,960 --> 05:02:51,320
IT IS CHALLENGING FOR

7223
05:02:51,320 --> 05:02:53,360
VIROLOGISTS TO ACCESS THEM SO

7224
05:02:53,360 --> 05:02:57,720
THE VIROLOGISTS BRING DRUGS

7225
05:02:57,720 --> 05:02:58,720
FORWARD, NOT ACTIVE BECAUSE THEY

7226
05:02:58,720 --> 05:03:00,280
ARE USING FLAWED MODELS SO IF WE

7227
05:03:00,280 --> 05:03:03,720
CAN STEP BACK AND BRING SOME OF

7228
05:03:03,720 --> 05:03:06,280
THESE MODELS MORE EASILY TO

7229
05:03:06,280 --> 05:03:07,640
REGULAR SCIENTISTS THEN I THINK

7230
05:03:07,640 --> 05:03:10,520
WE WOULD BE BRINGING FORWARD

7231
05:03:10,520 --> 05:03:12,280
MORE DRUGS THAT WOULD ULTIMATELY

7232
05:03:12,280 --> 05:03:13,160
BE ACTIVE, HOPING TO.

7233
05:03:13,160 --> 05:03:15,840
COUP WITH STRATEGIES.  TO MAKE

7234
05:03:15,840 --> 05:03:16,920
ACCESSIBLE AND UNDERSTANDABLE

7235
05:03:16,920 --> 05:03:18,240
WITH MORE TO THE STANDARDIZATION

7236
05:03:18,240 --> 05:03:28,360
TO MAKE IT EASIER. 

7237
05:03:28,360 --> 05:03:29,760
>> YESTERDAY SOMEONE ASKED
ME A

7238
05:03:29,760 --> 05:03:32,760
QUESTION WHAT IMMUNE CELLS ARE

7239
05:03:32,760 --> 05:03:34,360
INTRODUCED INTO

7240
05:03:34,360 --> 05:03:35,160
MICROPHYSIOLOGICAL SYSTEMS AND

7241
05:03:35,160 --> 05:03:38,040
TODAY WE HEARD ABOUT THAT. AND

7242
05:03:38,040 --> 05:03:40,040
EFFICACY AS WELL. WE HEARD ABOUT

7243
05:03:40,040 --> 05:03:43,280
NUTRIENTS BEING INTRODUCED,

7244
05:03:43,280 --> 05:03:45,960
INTRODUCE WHOLE BLOOD INTO THE

7245
05:03:45,960 --> 05:03:50,160
CHANNEL WHICH IS A COMPLEX SET

7246
05:03:50,160 --> 05:03:51,720
FOR PERIPHERAL BLOOD AND WE

7247
05:03:51,720 --> 05:03:55,480
HEARD FROM CALVIN ABOUT TISSUE

7248
05:03:55,480 --> 05:03:57,240
RESIDENT T-CELLS, THAT IS A HOT

7249
05:03:57,240 --> 05:03:59,560
TOPIC BECAUSE THAT IS DIFFICULT

7250
05:03:59,560 --> 05:04:03,240
TO MEASURE IN THE FIELD. I WANT

7251
05:04:03,240 --> 05:04:05,600
TO REFLECT ON THE GOLD -- OLD

7252
05:04:05,600 --> 05:04:07,600
WAY OF DOING THINGS. THE OLD WAY

7253
05:04:07,600 --> 05:04:09,920
IS PERHAPS TO USE CELL LINES

7254
05:04:09,920 --> 05:04:11,800
MAYBE INSECTS AND THEN MOVE UP

7255
05:04:11,800 --> 05:04:13,760
TO SMALL ANIMALS LIKE MICE AN

7256
05:04:13,760 --> 05:04:19,280
RATS HAMSTERS AND THEN ENTER NHP

7257
05:04:19,280 --> 05:04:22,080
FOR FINAL DATA SET AND FOR

7258
05:04:22,080 --> 05:04:29,360
SELECT AGENTS. MAYBE THE SORT

7259
05:04:29,360 --> 05:04:32,040
SYSTEMS SARA AND THE AMAZING

7260
05:04:32,040 --> 05:04:34,800
LAST SPEAKER WAS TALKING ABOUT

7261
05:04:34,800 --> 05:04:39,240
IN TERMS OF SCREENING THOUSANDS

7262
05:04:39,240 --> 05:04:43,640
OF DRUGS IS A VERY USEFUL

7263
05:04:43,640 --> 05:04:46,520
PRELIMINARY SCREENING MODE THEN

7264
05:04:46,520 --> 05:04:49,240
WHEN WE GET INTO PHASE 1 STUDY

7265
05:04:49,240 --> 05:04:50,880
WE CAN LEVERAGE PHASE 1 STUDIES

7266
05:04:50,880 --> 05:04:52,440
IN A WAY THAT I HADN'T THOUGHT

7267
05:04:52,440 --> 05:04:58,440
OF AND THAT IS TO TAKE A PHASE 1

7268
05:04:58,440 --> 05:05:03,320
STUDY TAKE BLOOD BUT ALSO TAKE A

7269
05:05:03,320 --> 05:05:05,760
SMALL BRUSH OR BIOPSY TO SEE

7270
05:05:05,760 --> 05:05:06,760
TISSUE BIOLOGY I DON'T KNOW SHY

7271
05:05:06,760 --> 05:05:11,360
THAT INCLUDES T-CELL -- RESIDENT

7272
05:05:11,360 --> 05:05:12,720
T-CELLS, SO MAYBE TOGETHER THAT

7273
05:05:12,720 --> 05:05:16,360
IS FORMIDABLE DOUBLE ACT INITIAL

7274
05:05:16,360 --> 05:05:17,880
SCREENING AND THEN ACTUAL PHASE

7275
05:05:17,880 --> 05:05:21,880
1 STUDY. MAYBE THE -- THIS

7276
05:05:21,880 --> 05:05:23,480
CONFERENCE IS ABOUT SPECIFICALLY

7277
05:05:23,480 --> 05:05:24,600
ANTIVIRALS AND WE HAVE

7278
05:05:24,600 --> 05:05:25,720
INEVITABLY ANTIVIRALS WILL

7279
05:05:25,720 --> 05:05:26,960
INCLUDE DRUGS WHICH STIMULATE

7280
05:05:26,960 --> 05:05:29,880
THE IMMUNE SYSTEM OR ACT AS IF

7281
05:05:29,880 --> 05:05:31,520
THEY ARE PART OF IT BUT MAYBE

7282
05:05:31,520 --> 05:05:35,920
THE LOW HANGING FRUIT IS A DRUG

7283
05:05:35,920 --> 05:05:38,600
WHICH DOES WORK IN HUMANSES BUT

7284
05:05:38,600 --> 05:05:42,360
JUST CAN'T WORK IN AN ANIMAL. SO

7285
05:05:42,360 --> 05:05:44,080
YOU ARE A WINNER THERE BECAUSE

7286
05:05:44,080 --> 05:05:45,000
THERE IS NOT GOLD STANDARD. 

7287
05:05:45,000 --> 05:05:48,000
THIS IS WHAT WE HAVE AND THEN

7288
05:05:48,000 --> 05:05:52,400
YOU CAN SAY YOU CAN RELEVERAGE

7289
05:05:52,400 --> 05:05:57,040
HYDROXYCHLOROQUINE FORRY IN THAT

7290
05:05:57,040 --> 05:05:58,040
SOMETHING LIEU THE REGULATORY

7291
05:05:58,040 --> 05:06:00,720
PATHWAY AND BUILD ON IT WHICH IS

7292
05:06:00,720 --> 05:06:03,280
MORE COMPLICATED THAN WAS TRYING

7293
05:06:03,280 --> 05:06:04,920
TO ARTICULATE YESTERDAY BUT THE

7294
05:06:04,920 --> 05:06:05,920
DIVERSITY MODELS I HEARD ABOUT

7295
05:06:05,920 --> 05:06:07,040
TODAY AND OBVIOUSLY REALLY

7296
05:06:07,040 --> 05:06:09,120
REGRET NOT HAVING BEEN ABLE TO

7297
05:06:09,120 --> 05:06:10,360
ATTEND THE CONFERENCE COUPLE OF

7298
05:06:10,360 --> 05:06:12,040
WEEKS AGO BECAUSE CLEARLY THERE

7299
05:06:12,040 --> 05:06:16,080
ARE MANY SOLUTIONS IN THE MST

7300
05:06:16,080 --> 05:06:18,880
CORE HUB WHICH WILL ANSWER

7301
05:06:18,880 --> 05:06:21,440
QUESTIONS THAT WILL EVOLVE AS WE

7302
05:06:21,440 --> 05:06:22,800
HIT VARIOUS REGULATORY

7303
05:06:22,800 --> 05:06:25,480
CHALLENGES. AND I DON'T SAY THE

7304
05:06:25,480 --> 05:06:27,240
HURDLES, I SAY THEY ARE

7305
05:06:27,240 --> 05:06:29,120
CHALLENGES.  I THINK WE WILL

7306
05:06:29,120 --> 05:06:30,680
MAKE MISTAKES ALONG THE WAY BUT

7307
05:06:30,680 --> 05:06:33,080
AS I SAID BEFORE IN ANSWERING

7308
05:06:33,080 --> 05:06:33,840
QUESTIONS FROM YESTERDAY A

7309
05:06:33,840 --> 05:06:35,200
MISTAKE OR FAILURE IS AN

7310
05:06:35,200 --> 05:06:38,720
OPPORTUNITIES TO IMPROVE. SO

7311
05:06:38,720 --> 05:06:42,480
LET'S NOT BE DOWN HEARTED ABOUT

7312
05:06:42,480 --> 05:06:43,200
FAILURE BECAUSE IT IS THE SPACE

7313
05:06:43,200 --> 05:06:45,120
TO MOVE FORWARD. I CAN SEE

7314
05:06:45,120 --> 05:06:46,240
SUCCESS IN WHAT I HAVE HEARD

7315
05:06:46,240 --> 05:06:50,200
ABOUT ESPECIALLY SESSION 2 AND 3

7316
05:06:50,200 --> 05:06:52,320
TODAY, MIND BOGGLING AND SO

7317
05:06:52,320 --> 05:06:54,000
HAPPY TO HAVE BEEN INVITED TO

7318
05:06:54,000 --> 05:06:55,560
PRESENT AND ATTEND SO I WILL

7319
05:06:55,560 --> 05:07:04,360
STOP THERE.

7320
05:07:04,360 --> 05:07:07,360
>> ALL RIGHT, THANK YOU
VERY

7321
05:07:07,360 --> 05:07:08,880
MUCH SARA, NICOLE, SIMON FOR THE

7322
05:07:08,880 --> 05:07:10,560
WONDERFUL WRAP UP OF THIS REALLY

7323
05:07:10,560 --> 05:07:13,000
EXCITING TWO DAYS. I HAVE ONE

7324
05:07:13,000 --> 05:07:19,520
FINAL SLIDE TO SHARE. IT IS A

7325
05:07:19,520 --> 05:07:24,720
THANK YOU SLIDE.  SO I WOULD

7326
05:07:24,720 --> 05:07:27,360
LIKE TO WRAP UP TODAY BY TAKING

7327
05:07:27,360 --> 05:07:29,080
EVERYONE THE CHAIRS THE

7328
05:07:29,080 --> 05:07:31,680
ORGANIZER, THE SPEAKERS, F

7329
05:07:31,680 --> 05:07:35,600
WONDERFUL TWO DAYS, THANKS

7330
05:07:35,600 --> 05:07:36,720
ATTENDEES AND THANK FOR EVERYONE

7331
05:07:36,720 --> 05:07:39,280
FOR ATTENDING. HOPEFULLY YOU

7332
05:07:39,280 --> 05:07:40,280
LEARNED A LOT AND THIS WAS

7333
05:07:40,280 --> 05:07:43,400
REALLY BENEFICIAL TO YOU AND FOR

7334
05:07:43,400 --> 05:07:46,400
YOUR RESEARCH. WE DO LIKE TO GET

7335
05:07:46,400 --> 05:07:50,320
YOUR FEEDBACK SO I KNOW ABIGAIL

7336
05:07:50,320 --> 05:07:52,160
MESSAGED ALREADY, SHE WILL REACH

7337
05:07:52,160 --> 05:07:53,480
OUT TO EVERYONE WITH THE

7338
05:07:53,480 --> 05:07:55,160
FEEDBACK LINK, I BELIEVE IT IS

7339
05:07:55,160 --> 05:07:57,040
IN THE CHAT, SHE ALREADY SENT IT

7340
05:07:57,040 --> 05:07:59,280
TO YOU ALL AND SHE WILL ALSO

7341
05:07:59,280 --> 05:08:01,440
EMAIL EVERYONE WITH THE FEEDBACK

7342
05:08:01,440 --> 05:08:04,880
SO PLEASE PROVIDE FEEDBACK WITH

7343
05:08:04,880 --> 05:08:07,600
LOTS OF -- WHAT YOU THINK WE DID

7344
05:08:07,600 --> 05:08:10,360
RIGHT AND WHERE WE CAN IMPROVE.

7345
05:08:10,360 --> 05:08:13,680
I ALSO INVITE EVERYONE TO

7346
05:08:13,680 --> 05:08:15,680
CONNECT WITH US SO WITH THE --

7347
05:08:15,680 --> 05:08:18,120
WITH OUR PROGRAM THE ASSAY

7348
05:08:18,120 --> 05:08:19,960
GUIDANCE MANUAL PROGRAM AND

7349
05:08:19,960 --> 05:08:21,760
HOPEFULLY ATTEND FUTURE

7350
05:08:21,760 --> 05:08:23,400
WORKSHOPS WE RUN, SO AGAIN ON

7351
05:08:23,400 --> 05:08:25,440
BEHALF OF THE ASSAY GUIDANCE

7352
05:08:25,440 --> 05:08:28,600
MANUAL PROGRAM, THANK YOU, VERY

7353
05:08:28,600 --> 05:08:32,080
MUCH FOR ATTENDING FOR SPEAKING

7354
05:08:32,080 --> 05:08:34,360
AND WITH THIS I WOULD LIKE TO

7355
05:08:34,360 --> 05:08:35,800
ADJOURN TODAY. YOU ALL HAVE A

7356
05:08:35,800 --> 05:08:46,280
WONDERFUL EVENING. THANK YOU.