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GOOD AFTERNOON.

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WELCOME TO THE WEDNESDAY

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AFTERNOON LECTURE SERIES, MY

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NAME IS ALEXANDER ZALAZAR, AND I

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AM CHIEF OF THE NETWORK FUNCTION

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OF NISB OF NIAID AND TODAY I

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HAVE THE HONOR TO INTRODUCE

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TODAY'S WALS SPEAKER

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DR. ILEANA CRISTEA, BUT FIRST I

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HAVE SOME INFORMATION, THE CME

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CODE FOR TODAY IS 37953.

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I REPEAT, 37953.

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ALSO IF YOU CAN TELL THIS IS A

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HYBRID LECTURE IN WHICH SOME OF

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US ARE HERE AND THE VAST

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MAJORITY OF YOU ARE WATCHING NIH

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VIDEOCAST.

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THOSE THAT ARE REMOTE CAN STILL

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ASK QUESTIONS, CAN YOU DO SO BY

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CLICKING ON THE BUTTON JUST

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BELOW YOUR VIDEOCAST WINDOW THAT

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SAYS SEND LIVE FEEDBACK, CLICK

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ON THAT IN YOUR NAME, END

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QUESTION AND WE WILL RELAY TO

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DR. CRISTEA AT THE END OF HER

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LECTURE.

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CAN YOU SUBMIT QUESTIONS

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ANYTIME.

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PLEASE NOTE THAT TODAY'S LECTURE

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IS THE FINAL OF THIS WALS

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SEASON, WE'LL WILL TAKE A 2

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MONTH BREAK AND BEGIN A NEW

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SIEWZON ON SEPTEMBER 7th WHERE

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WE ARE JOINED BY DR. JILL

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[INDISCERNIBLE]OT TOPIC OF

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MICROBIAL DISEASE.

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OUR SPEAKER TODAY IS

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DR. ILEANA CRISTEA, SHE IS WITH

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THE LABORATORY CELLULAR

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MECHANISMS AT PRINCE ON TON

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UNIVERSITY, AS WELL AS

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MECHANISMS USED BY VIRUSES TO

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INHIBIT OR HIJOCK HOST CELL

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PROCESSES.

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HER LAB EMPLOYEES

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MULTIDISCIPLINARY APPROACHES

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INTEGRATING MOLECULAR VIROLOGY,

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MICROSCOPY, MASS

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SPECTROMETRY-BASED PROTEOMICS

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AND BIO-INFORMATICS.

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IN RECEIPT YEARS, SHE DEVELOPED

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SPACIAL AND TEMPORAL VITALS FOR

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HOST PROTEIN INTERACTIONS,

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BRIDGING DEVELOPMENT TO

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IMPORTANT FINDINGS IN BIOLOGY,

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FOR EXAMPLE HER LABORATORY HAS

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CONTRIBUTED TO THE EMERGENCE OF

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THE RESEARCH FIELD OF NUCLEIC

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DNA SENSING AND UNCOVERING

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MECHANISMS UNDERLYING MODELING

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AND ORGANELLE STUDY STRUCTURE

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FUNCTION RELATIONSHIPS DURING

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INFECTIONS, AND THEY HAVE

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DISCOVERED BROAD SPECTRUM

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ANTIVIRAL FACTORS.

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ILEANA RECEIVED HER MEDICAL

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DEGREE IN MACROCHEMMISTRY

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FOLLOWED BY A Ph.D. FROM

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MANCHESTER UNIVERSITY.

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AND SHE THEN PURSUED POST

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DOCTORAL WORK AT THE LABORATORY

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AT ROCKEFELLER UNIVERSITY.

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ILEANA JOINED PRINCETON

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UNIVERSITY IN 2008 AS ASSISTANT

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PROFESSOR AND BECAME ASSOCIATE

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PROFESSOR IN 2013 AND ATTAINED

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HER CURRENT POSITION IN TWEBT

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16.

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ELEANA IS VERY ACTIVE IN THE

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PROTEOMICS COMMUNITY.

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SHE'S THE PAST PRESIDENT OF THE

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HUMAN PROTEOME ORGANIZATION OF

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[INDISCERNIBLE], PAST CHEAR OF

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THE HUMAN PROTEOME PROJECT AND

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CHAIR OF THE INFECTIOUS DISEASE

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TEAM OF [INDISCERNIBLE] Ph.D.

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SHE HAS WORKED AT THE COLD

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SPRINGS LABORATORY FOR MORE THAN

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10 YEARS AND SENIOR EDITOR FOR

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END SYSTEMS, ASSOCIATE EDITOR

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FOR THE PROTEOME RESEARCH AND

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UNDER THE MOLECULAR SYSTEMS

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BIOLOGY AND MOLECULAR AND

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CELLULAR PROTEOMICS.

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EASE ALSO REYIPIENT OF MANY

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HONORS AND,A WARDS WHICH INCLUDE

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THE [INDISCERNIBLE] PRIZE FROM

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THE BRITISH MASS SPECTROMETRY

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SOCIETY, NIH NIDA AVAN GUARD

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ROAD FOR RESEARCH, HUMAN FRAN

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TEARS HUMAN INVESTIGATOR AWOORD,

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CAREER AWARD FROM ICS,

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[INDISCERNIBLE] SKOALAR AWARD

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AND THE MOST PROUDLY THE

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PRINCETON UNIVERSITY GRADUATE

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MOLECULAR AWARD.

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THE TITLE OF HER TALK TODAY IS

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VIRAL ORGANELLE REMODELING FOR

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HOST CELL BIOLOGY.

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ILEA, INA, WELCOME AND THANK YOU

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FOR BEING WITH US TODAY [

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APPLAUSE ]

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>> THANK YOU SO MUCH,
THANK YOU

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FOR THE VERY KIND INTRODUCTION

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AND THANK YOU FOR THE

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INVITATION, IT'S A GREAT

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PLEASURE TO BE HERE AND I THANK

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YOU ALL AND THE ORGANIZERS AND

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THANK YOU FOR BEING IN PERSON

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AND ALSO I THANK THOSE ONLINE

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FOR JOINING IN TODAY.

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I HAVE TO SAY IT'S SO GREAT TO

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BE IN PERSON FOR A SEMINAR IN 3D

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SO IT'S WAY HUGE DIFFERENCE AND

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GREAT HONOR TO BE HERE.

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SO AS YOU HEARD MY LAB IS AT

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PRINCETON IN THE DEPARTMENT OF

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BIOLOGY WHERE WE INDGREAT

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BIOLOGY WITH PROTEOMICS TO STUDY

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AT THE LEVEL OF HUMAN VIRUSES

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AND TODAY I SELECTED TO TELL YOU

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ABOUT SOME OF OUR SCIENTIFIC

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ADVENTURES DURING THE PANDEMIC

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THAT HAVE BROUGHT US TO BECOME

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QUITE INTERESTED AND REALLY

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FASCINATED WITH THIS CONCEPT OF

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DYNAMIC ORGANELLE REMODEL

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THAGOREAN HAPPENS DURING THE

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REPLICATION CYCLE OF VIRAL

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INFECTIONS SO I'LL TELL YOU MORE

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ABOUT THAT AND PUT THIS IN

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BROADER CONTEXT, BUT FIRST I

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WILL TELL YOU ABOUT MY

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DISCLOSURES, I AM THE FOUNDER

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AND CONFOUNDER OF A COMPANY THAT

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MAKES ANTIVIRAL TREATMENTS BY

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TARGETING SERIES POINTS TUEINS

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AND I'M ALSO A MEMBER OF

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SCIENTIFIC ADVISORY BOARD OF 908

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DEVICES WHICH IS A MASS

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SPECTROMETRY DEVICES, WHAT I

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WILL SPEAK ABOUT TODAY IS NOT

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CONTECTED TO THESE 2 COMPANIES

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BUT JUST TO LET YOU KNOW.

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ALL RIGHT, SO TO START WITH

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BROADER TOPIC, THE CELL IS

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DEPENDENTOT ABILITY OF THE VIRUS

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TO REMODEL ORGANELLES, SO IN

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OTHER WORDS THE CHANGES THAT CAN

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OCCUR IN ORGANELLE SHAPE AND

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COMPOSITION AND FUNCTION ARE

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ABSOLUTELY ESSENTIAL FOR THE

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VIRAL INFECTIONS, FOR THE VIRAL

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REPLICATION CYCLES AND 1

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IMPORTANT ILLUSTRATION OF THIS

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IS GIVEN BY INFECTION WITH HUMAN

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CYTOMEGALOW VIRUS, THIS IS A

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BETTER PERP ESTIMATE THAD VIRUS

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THAT IS WIDELY SPREAD, IT HAS A

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LARGE GENOME AND QUITE A LENGTHY

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REPLICATION CYCLE OF 4-5 DAYS,

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SO THIS HAS BOTH THE GENETIC

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CAPACITY AS WELL AS TIME TO

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INDUCE STRIKING CHANGES IN THE

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SUBCELLULAR ENVIRONMENT DURING

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ITSELF REPLICATION CYCLE SO FOR

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EXAMPLE FOR ENTRY, IT REMODELS

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THE PLASMA MEMBRANE, IT REMODELS

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CYTOSKELETON AND ENDOSTUDIES OF

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MULTIPLE ENDOCRINES AND THEN

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FOLLOWING IT'S NUCLEAR

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REPLICATION, THE VIRUS DISRUPTS

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THE PERIPHERY TO ALLOW THE VIRAL

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CAPSID TO EGRESS FROM THE

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NUCLEUS.

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LATER IN THE INFECTION, THE

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VIRUS MAKES A NEW ASSEMBLY, A

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SUBSET COMPARTMENT FORMED WITH

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GOLGI 'EM BRAINS AND SUBCELLS

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AND OVER HERE I WILL SHOW YOU

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THIS THAT I MENTIONED EARLIER.

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SO THE ASSEMBLY COMPARTMENT THAT

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MAKES NEW VIRAL PARTICLES THAT

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CONTAIN ENDOSTUDIES OF MULTIPLE

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ENDOCRINES IN THEM AND GOLGI

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MEMBRANES THAT ARE RESTRUCTURED

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AND LATER FOR EGRESS, ALSO IT

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HIJACKS TRAFFICKING PROCESSES,

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HOST TRAFFICKING PROCESSES,

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ANOTHER HALLMARK OF HSV

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INFECTION AND MITOCHONDRIAL

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INFECTION AND I WILL TELL YOU

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ABOUT THIS LATER IN THIS TALK,

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HOWEVER WHAT'S NOT FULLY

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UNDERSTOOD IS HOW THESE

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REMODELING EVENTS ARE CONNECTED

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TO SOME OF THE VIRAL

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PATHOLOGIES, SO INDUCED BY THIS

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VIRUS SO FOR EXAMPLE, CARDIAC

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DISEASE OR THE ONCOMODLATTORY

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PROPERTIES OF HCMV, HOWEVER,

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IT'S IMPORTANT TO NOTE

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NAREMODELLING IS NEEDED FOR ALL

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VIRUS, SO REGARD WILL OF GENOME

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SIZE, REPLICATION STRATEGIES,

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DIFFERENT CELL TROAPISMS, ALL

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VIRUSES ARE UNITED IN THEIR NEED

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FOR REGULATION OF AGER ANLE

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FUNCTION, ORGANELLE COMPOSITION

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AND SHAPE DURING THE REPLICATION

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CYCLE.

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SO FOR EXAMPLE, HSV 1, ALSO

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HERPES VIRUS ALSO REGULATES THE

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EGRESS OF THE VIRAL SID.

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AND ALSO [INDISCERNIBLE] THE

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CORONA VIRUS, LIKE OTHER BETA

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CORONA VIRUSES INDUCE REMODELING

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OF THE ER AND MAKES THE DOUBLE

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MEMBRANE FOR THE REPLICATION OF

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THESE VIRUS, SO NOW ALL THESE

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DYNAMIC MODELING EVENTS THAT

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OCCUR DURING INFECTION AND THIS

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IS SOMETHING WE HAVE FOCUSED ON

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IN RECENT YEARS.

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SO WE--WITH A QUESTION OF HOW

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AND WHY WHICH OF THESE PROCESSES

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ARE FOR THE BENEFIT OF VIRUS OR

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THE HOST AND IN ORDER TO

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UNDERSTAND THIS INFECTION

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INDUCED REWIRING OF HOST CELLS,

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WE HAVE MULTITUDE OF METHODS

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AVAILABLE FROM MOTE I DON'T

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MEANICS, FROM LIPID OMICS, AND

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TODAY I WILL TRY TO HIGHLIGHT

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SOME OF THE STRATEGIES WE HAVE

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USED OVER THE YEARS AND IN

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PARTICULAR IN MORE RECENT YEARS

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AND HOW WE HAVE LEARNED ABOUT

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THIS EPITHELIAL RACELLULAR

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REORGANIZATION FROM THESE

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DIFFERENT METHODS.

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SO WE HAVE STARTED INSHALLLY BY

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FOCUSING ON UNDERSTANDING THE

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VIRUS HOST PROTEIN INTERACTIONS

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THAT ARE DRIVING SOME OF THESE

256
00:10:04,615 --> 00:10:07,351
SIGNALING  CASCADES AND SOME OF

257
00:10:07,351 --> 00:10:09,387
THESE REMODELING EVENTS IN THE

258
00:10:09,387 --> 00:10:11,655
CELL.

259
00:10:11,655 --> 00:10:13,290
AND OF COURSE, WE HAVE SO MANY

260
00:10:13,290 --> 00:10:15,326
DIFFERENT APPROACHES WE CAN USE

261
00:10:15,326 --> 00:10:16,927
FOR STUDYING PROTEIN

262
00:10:16,927 --> 00:10:17,995
INTERACADEMIESS DURING AN

263
00:10:17,995 --> 00:10:21,599
INFECTION, WE CAN USE AFFINITY

264
00:10:21,599 --> 00:10:23,901
PURIFICATION, CROSS LINKING AND

265
00:10:23,901 --> 00:10:29,573
MANY PROTEIN MICROARRAYS AND

266
00:10:29,573 --> 00:10:30,775
THESE METHODS EVER ARE

267
00:10:30,775 --> 00:10:31,442
PROSCRIEDING US WITH AN

268
00:10:31,442 --> 00:10:35,813
OPPORTUNITY TO STUDY WITH A

269
00:10:35,813 --> 00:10:36,547
LOCAL PERSPECTIVE FOCUSED ON 1

270
00:10:36,547 --> 00:10:39,650
PROTEIN OF INTEREST AT A TIME OR

271
00:10:39,650 --> 00:10:41,018
FROM A GLOBAL PERSPECTIVE AND

272
00:10:41,018 --> 00:10:42,987
GIVEN OUR INTEREST IN ORGANELLE

273
00:10:42,987 --> 00:10:44,755
REMODELING, MORE AND MORE IN

274
00:10:44,755 --> 00:10:45,956
THESE RECENT YEARS WE BECAME

275
00:10:45,956 --> 00:10:48,526
FASCINATED BY THE IDEA OF TRYING

276
00:10:48,526 --> 00:10:49,927
TO CAPTURE IN 1 GOAL, WHAT

277
00:10:49,927 --> 00:10:52,830
HAPPENS IN THE CELL DURING

278
00:10:52,830 --> 00:10:54,432
INFECTION AND HOW THESE EVENTS

279
00:10:54,432 --> 00:10:55,866
COULD BE COORDINATED SO 1 METHOD

280
00:10:55,866 --> 00:10:59,904
I WANT TO HIGHLIGHT TODAY IS

281
00:10:59,904 --> 00:11:01,038
THIS THERMOCOAGULATION PROFILING

282
00:11:01,038 --> 00:11:02,206
AND I JUST TO TAKE YOU THROUGH

283
00:11:02,206 --> 00:11:05,976
THE APPROACH THIS METHOD, SO THE

284
00:11:05,976 --> 00:11:07,478
SAMPLE OF INTEREST WE HAVE USED

285
00:11:07,478 --> 00:11:08,813
THESE WITH CELLS AS WELL AS

286
00:11:08,813 --> 00:11:10,014
TISSUES, THE SAMPLE OF THIS

287
00:11:10,014 --> 00:11:15,386
INTEREST IS SUBJECTS TO

288
00:11:15,386 --> 00:11:17,421
INCREASING TEMPERATURES AND THEN

289
00:11:17,421 --> 00:11:19,790
QUANTITATIVE MASS SPECTROMETRY

290
00:11:19,790 --> 00:11:21,091
IS USED TO QUANTIFY SOLUBLE

291
00:11:21,091 --> 00:11:24,495
PROTEINS AT EACH OF THESE

292
00:11:24,495 --> 00:11:24,829
TEMPERATURES.

293
00:11:24,829 --> 00:11:29,667
IT IS READ OUT IS ACTUALLY AT

294
00:11:29,667 --> 00:11:31,168
COAGULATION CURVES AS THE

295
00:11:31,168 --> 00:11:32,803
TEMPERATURE INCREASES SO HOW DO

296
00:11:32,803 --> 00:11:37,575
WE LEARN FROM THIS ABOUT PROTEIN

297
00:11:37,575 --> 00:11:37,908
INTERACTIONS?

298
00:11:37,908 --> 00:11:39,810
WELL THE PRINCIPLE OF THIS IS

299
00:11:39,810 --> 00:11:42,112
THAT PROTEINS INTERACT WITH EACH

300
00:11:42,112 --> 00:11:44,348
OTHER ARE STABILIZING EACH OTHER

301
00:11:44,348 --> 00:11:46,283
AND THEY MAY HAVE STABILIZE EACH

302
00:11:46,283 --> 00:11:47,618
OTHER AN THE TEMPERATURE

303
00:11:47,618 --> 00:11:49,520
INCREASES AND THIS WORKS QUITE

304
00:11:49,520 --> 00:11:51,455
BEAUTIFULLY OR YOU CAN CAPTURE

305
00:11:51,455 --> 00:11:55,259
OR SCALE IT IN 1 GOING SAMPLE.

306
00:11:55,259 --> 00:11:56,360
SO [INDISCERNIBLE] A POST DOC IN

307
00:11:56,360 --> 00:11:57,895
MY LAB WAS THE FIRST TO APPLY

308
00:11:57,895 --> 00:11:59,630
THIS METHOD TO VIRAL INFECTION

309
00:11:59,630 --> 00:12:02,500
AND HE APPLIED IT TO HCMV

310
00:12:02,500 --> 00:12:04,768
INFECTION AND THAL CASE, HE TOOK

311
00:12:04,768 --> 00:12:06,403
EXACTLY THIS APPROACH BUT

312
00:12:06,403 --> 00:12:07,204
INVESTIGATED SAMPLES AT

313
00:12:07,204 --> 00:12:08,138
DIFFERENT TIME POINTS OF

314
00:12:08,138 --> 00:12:12,309
INFECTION AND BY LOOKING AT THIS

315
00:12:12,309 --> 00:12:14,245
CO AGGREGATION PROTILE AS THE

316
00:12:14,245 --> 00:12:16,814
INFECTION PROGRESSED AND HOW

317
00:12:16,814 --> 00:12:17,515
THIS COAGULATION PROFILES

318
00:12:17,515 --> 00:12:19,817
CHANGE, WE COULD PREDICT WHICH

319
00:12:19,817 --> 00:12:20,818
INTERACTIONS ARE MAINTAINED

320
00:12:20,818 --> 00:12:23,020
DURING INFECTION, WHICH 1S ARE

321
00:12:23,020 --> 00:12:24,722
FORMED ONLY SPECIFICALLY AT A

322
00:12:24,722 --> 00:12:26,390
CERTAIN TIME POINT OF INFECTION,

323
00:12:26,390 --> 00:12:28,926
WHICH 1S ARE DISRUPTED AS THIS

324
00:12:28,926 --> 00:12:30,895
PROGRESSING AND MORE RECENTLY WE

325
00:12:30,895 --> 00:12:33,230
HAVE FURTHER DEVELOPED THIS

326
00:12:33,230 --> 00:12:35,332
APPROACH AND JOSHUA JUSTICE IN

327
00:12:35,332 --> 00:12:38,903
MY LAB APPLIED IT FOR STUDYING

328
00:12:38,903 --> 00:12:39,270
HSV1 INFECTION.

329
00:12:39,270 --> 00:12:40,404
TRAFFIC REED, THE Ph.D.

330
00:12:40,404 --> 00:12:42,206
STUDENT NOW HAS DEVELOPED

331
00:12:42,206 --> 00:12:44,275
MACHINE LEARNING ALGORITHMS AND

332
00:12:44,275 --> 00:12:45,342
FURTHER ADVANCED THIS APPROACH

333
00:12:45,342 --> 00:12:46,810
IN ORDER TO BE ABLE TO STUDY

334
00:12:46,810 --> 00:12:48,512
DIFFERENT TYPES OF PROTEIN

335
00:12:48,512 --> 00:12:49,813
CLASSES LIKE MEMBRANE BOUND

336
00:12:49,813 --> 00:12:51,348
PROTEINS AND PROTEINS THAT ARE

337
00:12:51,348 --> 00:12:52,683
HARDER TO DETECT NORMALLY, BUT I

338
00:12:52,683 --> 00:12:54,885
WANT TO KIND OF GIVE YOU AN IDEA

339
00:12:54,885 --> 00:12:56,253
OF WHAT WE CAN FIND WITH THIS

340
00:12:56,253 --> 00:12:56,587
METHOD.

341
00:12:56,587 --> 00:12:59,456
SO WE CAN OF COURSE MONITOR

342
00:12:59,456 --> 00:13:01,592
PROTEIN COMPLEXES THAT WE KNOW

343
00:13:01,592 --> 00:13:03,394
THAT THEY EXIST, FUNCTIONAL

344
00:13:03,394 --> 00:13:05,162
PROTEIN COMPLEXES THAT HAVE BEEN

345
00:13:05,162 --> 00:13:06,163
REPORTED SUCH AS THOSE THAT ARE

346
00:13:06,163 --> 00:13:09,133
IN THE DATABASE BUT SAME TIME

347
00:13:09,133 --> 00:13:10,200
YOU CAN UNCOVER DE NOVO

348
00:13:10,200 --> 00:13:11,835
INTERACTIONS THAT WERE NOT

349
00:13:11,835 --> 00:13:14,004
PREVIOUSLY KNOWN, EITHER VIRUS

350
00:13:14,004 --> 00:13:14,738
HOST OR HOST-HOST INTERACTIONS

351
00:13:14,738 --> 00:13:16,607
AND I WANT TO GIVE YOU 1 EXAMPLE

352
00:13:16,607 --> 00:13:22,613
FROM 1 OF OUR LONG STANDING

353
00:13:22,613 --> 00:13:23,948
INTERESTS AND WE HAVE LOOKED IN

354
00:13:23,948 --> 00:13:25,349
THIS LAB FOR OVER 14 YEARS AND

355
00:13:25,349 --> 00:13:26,917
HOW WE HAVE GAINED NEW

356
00:13:26,917 --> 00:13:29,954
INFORMATION BY APPLYING THIS

357
00:13:29,954 --> 00:13:31,689
THERMAL COAGULATION PROFILES TO

358
00:13:31,689 --> 00:13:34,825
THE CONCEPT OF NUCLEIC SENSING.

359
00:13:34,825 --> 00:13:37,294
SO UPON NUCLEIC REPLICATING

360
00:13:37,294 --> 00:13:42,633
VIRUSES SUCH AS HSV OR HSV1, IT

361
00:13:42,633 --> 00:13:44,234
TRAFFICS ALONG MICROTUBELES AND

362
00:13:44,234 --> 00:13:46,503
THE I HAVE RID CAPSID NUCLEAR

363
00:13:46,503 --> 00:13:49,506
PORE AND THE VIRAL DNA IS

364
00:13:49,506 --> 00:13:50,441
INSERTED INSIDE THE NUCLEUS

365
00:13:50,441 --> 00:13:51,775
HERE, THIS A MOMENT IN TIME THAT

366
00:13:51,775 --> 00:13:55,579
IS VERY IMPORTANT AND IS SORT OF

367
00:13:55,579 --> 00:13:57,648
DYNAMIC EVENTSA THE NUCLEIC

368
00:13:57,648 --> 00:13:59,249
PERIPHERY THAT ARE IMPORTANT

369
00:13:59,249 --> 00:14:00,718
HOST DEFENSE AGAINST VIRAL

370
00:14:00,718 --> 00:14:03,454
INFECTION AND IS CESSATION OF

371
00:14:03,454 --> 00:14:04,388
INNATE IMMUNE SIGNALING BY

372
00:14:04,388 --> 00:14:10,394
RECOGNITION OF THIS VIRAL DNA BY

373
00:14:10,394 --> 00:14:11,629
NUCLEAR DNA SENSORS AND SOME

374
00:14:11,629 --> 00:14:17,101
YEARS AGO WE CHARACTERIZED THIS

375
00:14:17,101 --> 00:14:18,669
PROTEIN 16 THAT BECAME THE FIRST

376
00:14:18,669 --> 00:14:20,471
KNOWN SENSOR SO VIRAL--HOST

377
00:14:20,471 --> 00:14:22,773
PROTEIN THAT'S ABLE TO RECOGNIZE

378
00:14:22,773 --> 00:14:25,342
VIRAL DNA IN THE NUCLEI IN

379
00:14:25,342 --> 00:14:26,810
INFECTED CELLS AND RECOGNIZE

380
00:14:26,810 --> 00:14:28,812
VIRAL DNA FROM OUR OWN CELL DNA

381
00:14:28,812 --> 00:14:32,449
IN THE SAME COMPARTMENT AND HERE

382
00:14:32,449 --> 00:14:34,585
YOU CAN SEE THE GREEN THAT GOES

383
00:14:34,585 --> 00:14:36,053
TO THE PERIPHERY UPON THE

384
00:14:36,053 --> 00:14:42,960
BINDING OF THE VIRAL CAPSID OF

385
00:14:42,960 --> 00:14:43,293
THE PERIPHERY.

386
00:14:43,293 --> 00:14:44,328
SO THIS WAS QUITE AN INTERESTING

387
00:14:44,328 --> 00:14:46,964
SORT OF TIME IN THIS FIELD OF

388
00:14:46,964 --> 00:14:48,365
DNA SENSING BUT THERE ARE SO

389
00:14:48,365 --> 00:14:50,000
MANY QUESTIONS REMAINING LIKE WE

390
00:14:50,000 --> 00:14:51,635
DO NOT UNDERSTAND HOW SIGNALING

391
00:14:51,635 --> 00:14:53,237
HAPPENS, THE DOWN STREAM OF THIS

392
00:14:53,237 --> 00:14:55,239
BINDING OF THIS TO VIRAL DNA OR

393
00:14:55,239 --> 00:14:57,908
EVEN WHAT MAKES THIS PROTEIN GO

394
00:14:57,908 --> 00:15:04,481
TO THE NUCLEIC PERIPHERY TO BIND

395
00:15:04,481 --> 00:15:06,450
TO VIRAL DNA.

396
00:15:06,450 --> 00:15:08,285
SO FROM THE PROFILES WE

397
00:15:08,285 --> 00:15:08,886
DISCOVERED THIS SENSOR VERY

398
00:15:08,886 --> 00:15:13,490
EARLY IN THE INFECTION INTERACTS

399
00:15:13,490 --> 00:15:17,594
WITH THE COMPLEX THAT HAS THE

400
00:15:17,594 --> 00:15:19,363
KINASE, AND DNA, PK AND THIS

401
00:15:19,363 --> 00:15:20,964
HAPPENS EARLY IN INFECTION, AND

402
00:15:20,964 --> 00:15:23,367
THIS IS CO AGREGATION AND IT'S

403
00:15:23,367 --> 00:15:28,806
LOST AS THE INFECTION PROGRESSES

404
00:15:28,806 --> 00:15:30,908
AND WE WENT ON AND OUR FINDINGS

405
00:15:30,908 --> 00:15:32,976
IN THE INTEREST OF TIME WE FIND

406
00:15:32,976 --> 00:15:35,779
THAT THESE CO LOCALIZE AT THE

407
00:15:35,779 --> 00:15:36,847
NUCLEAR PERIPHERY AND SITES OF

408
00:15:36,847 --> 00:15:39,216
VIRAL GENOME IN THE SPOGZ

409
00:15:39,216 --> 00:15:42,820
POSITION AND FURTHER MORE WE

410
00:15:42,820 --> 00:15:45,456
SHOW THAT IFI16 IS NEEDED FOR

411
00:15:45,456 --> 00:15:50,060
RECRUIT CRUDING THE DNA RESPONSE

412
00:15:50,060 --> 00:15:52,362
KINASE TO INCOMING VIRAL GENOMES

413
00:15:52,362 --> 00:15:53,297
AT THE NUCLEOTIDES CLER

414
00:15:53,297 --> 00:15:54,765
PERIPHERY AND THIS IS THE

415
00:15:54,765 --> 00:15:55,833
PHOSPHORYLATED FORM OF THE

416
00:15:55,833 --> 00:16:00,337
ACTIVATED FORM YOU SEE HERE.

417
00:16:00,337 --> 00:16:03,006
SO THIS RECRUITS THIS KINASE TO

418
00:16:03,006 --> 00:16:04,575
INCOMING GENOMES WE ASKED

419
00:16:04,575 --> 00:16:11,448
WHETHER THIS CAN BE A FEEDBACK

420
00:16:11,448 --> 00:16:13,851
LOOP, AND IF THIS IS A PEPTIDE,

421
00:16:13,851 --> 00:16:15,486
AND WE STUDY THIS

422
00:16:15,486 --> 00:16:16,954
PHOSPHORYLATION STATUS IN A

423
00:16:16,954 --> 00:16:17,821
MULTITUDE OF CONDITIONS EITHER

424
00:16:17,821 --> 00:16:20,357
WITH OR WOULD IT DNA INHIBITION

425
00:16:20,357 --> 00:16:23,494
WITH AND WITHOUT DNA DAMAGE

426
00:16:23,494 --> 00:16:24,695
INDUCING DNA DAMAGE BY TREATMENT

427
00:16:24,695 --> 00:16:27,664
WITH GLEEL CELLS O MICEIN AND

428
00:16:27,664 --> 00:16:29,199
WITH AND WITHOUT HSV INFECTION

429
00:16:29,199 --> 00:16:30,601
AT THESE EARLY TIME POINTS OF

430
00:16:30,601 --> 00:16:40,744
INFECTION AND WHAT WE FOUND IS

431
00:16:40,744 --> 00:16:46,583
INSIDE THAT AND IT

432
00:16:46,583 --> 00:16:49,086
PHOSPHORYLATES SPECIFICALLY THIS

433
00:16:49,086 --> 00:16:51,989
THREA9, THAT IS NEEDED FOR THIS

434
00:16:51,989 --> 00:16:53,857
AND THE HEME DO MAINS THAT BIND

435
00:16:53,857 --> 00:16:56,126
TO VIRAL DNA SO THIS RECRUITS

436
00:16:56,126 --> 00:16:58,495
DNA TO THE NUCLEOTIDES CLER

437
00:16:58,495 --> 00:17:03,033
PERIPHERY WHEN IT BECAME

438
00:17:03,033 --> 00:17:04,768
PHOSPHORYLATED AND THAT IS

439
00:17:04,768 --> 00:17:06,570
REQUIRED FOR THE ANTIVIRAL

440
00:17:06,570 --> 00:17:08,338
FUNCTIONS BECAUSE WHEN WE MUTATE

441
00:17:08,338 --> 00:17:13,043
THAT SIDE, THIS IS LESS ABLE TO

442
00:17:13,043 --> 00:17:15,145
INDUCE INTERFORON RESPONSE AND

443
00:17:15,145 --> 00:17:16,180
ANTIVIRAL CYTOKINE EXPRESSION

444
00:17:16,180 --> 00:17:17,581
UPON INFECTION AND IN AGREEMENT

445
00:17:17,581 --> 00:17:21,652
WITH THIS, IF WE INHIBIT DNAPK,

446
00:17:21,652 --> 00:17:23,954
WE OBSERVE INCREASED VIRAL

447
00:17:23,954 --> 00:17:29,326
TIGHTERS FOR HSV 1, SO SO WHAT

448
00:17:29,326 --> 00:17:31,862
THIS TECHNOLOGY ALLOWED US IS

449
00:17:31,862 --> 00:17:33,831
THE ELEGANCE DANCE BETWEEN THE

450
00:17:33,831 --> 00:17:37,835
SENSING AND DNA DAMAGE RESPONSE

451
00:17:37,835 --> 00:17:44,341
IN PARTICULAR DNA PK WHEREBY

452
00:17:44,341 --> 00:17:48,145
IFI16 GOES THROUGH THE DNA

453
00:17:48,145 --> 00:17:49,880
RECRUITS IT AND PHOSPHORYLATE

454
00:17:49,880 --> 00:17:57,554
ANDS THAT IMPORTANT FOR INDUCING

455
00:17:57,554 --> 00:17:58,722
INNATE IMMUNE SIGNALING.

456
00:17:58,722 --> 00:18:01,058
SO THIS IS 1 XVENL OF THE

457
00:18:01,058 --> 00:18:02,726
DYNAMIC PERIPHERY THAT ACTUALLY

458
00:18:02,726 --> 00:18:05,629
THE REPLODLING OF THE STRUCTURE

459
00:18:05,629 --> 00:18:07,130
OF THE NUCLEAR PERIPHERY IS

460
00:18:07,130 --> 00:18:08,665
LATER INFECTION WHEN IT HAS TO

461
00:18:08,665 --> 00:18:19,142
EGRESS FROM THE CELLS SO IN

462
00:18:22,379 --> 00:18:23,513
ADDITION TO LEARNING ABOUT

463
00:18:23,513 --> 00:18:26,750
PROTEIN INTERACTION, YOU CAN

464
00:18:26,750 --> 00:18:28,485
ACTUALLY LEARN ABOUT HOW

465
00:18:28,485 --> 00:18:29,286
INFECTION CHANGES THE PROPERTY

466
00:18:29,286 --> 00:18:31,188
OF A GIVEN PROTEIN, EITHER VIRAL

467
00:18:31,188 --> 00:18:34,024
OR HOST, AND WHETHER IT'S

468
00:18:34,024 --> 00:18:34,691
AGGREGATION PROFILE STARTS TO

469
00:18:34,691 --> 00:18:37,060
CHANGE AS THE INFECTION

470
00:18:37,060 --> 00:18:42,399
PROGRESSES, SO HERE IS LAMINE ON

471
00:18:42,399 --> 00:18:44,101
B INUNINFECTED CELLS POST TIME

472
00:18:44,101 --> 00:18:46,003
POINT INFECTION AND YOU SEE HOW

473
00:18:46,003 --> 00:18:49,039
THE THERMAL PROFILES, THERMAL

474
00:18:49,039 --> 00:18:50,540
AGGREGATION PROFILES AS THE

475
00:18:50,540 --> 00:18:51,808
TEMPERATURE INCREASES, THEY

476
00:18:51,808 --> 00:18:53,543
CHANGE WITH INFECTION AND THIS

477
00:18:53,543 --> 00:18:55,712
IS IN CONTRAST IF I SAY I SELECT

478
00:18:55,712 --> 00:18:57,147
AND THEN CHANGE AND SHOW A

479
00:18:57,147 --> 00:19:04,721
MEMBER OF THE CORE COMPLEX AND

480
00:19:04,721 --> 00:19:08,458
THE STATE IS FAIRLY STABLE OF

481
00:19:08,458 --> 00:19:09,126
THERMOAGGREGATION PROFILES FOR

482
00:19:09,126 --> 00:19:10,027
THE INFECTION AND FURTHER MORE

483
00:19:10,027 --> 00:19:12,129
IF WE TRY TO FIND OUT WHAT THIS

484
00:19:12,129 --> 00:19:14,965
CHANGE IN A PRO FILES MEANS IT

485
00:19:14,965 --> 00:19:15,666
ACTUALLY REPRESENTS THE

486
00:19:15,666 --> 00:19:17,367
DISRUPTION I SHOW YOU HERE AND

487
00:19:17,367 --> 00:19:19,403
ALSO ASSOCIATION WITH VIRAL

488
00:19:19,403 --> 00:19:22,172
PROTEINS THAT ARE CRITICAL IN

489
00:19:22,172 --> 00:19:22,873
THIS CAPSID EGRESS AND

490
00:19:22,873 --> 00:19:30,814
STABILITY, SO FOR EXAMPLE, LAMIN

491
00:19:30,814 --> 00:19:33,050
B1 HERE HAS SAME AGGREGATION

492
00:19:33,050 --> 00:19:37,087
WITH THIS PROTILE, THAT PLAYS A

493
00:19:37,087 --> 00:19:40,757
ROLE IN VIRION STABILITY, SO

494
00:19:40,757 --> 00:19:42,559
WHEN WE FURTHER INTEGRATED

495
00:19:42,559 --> 00:19:43,527
ANALYSIS OF POST MODIFICATION ON

496
00:19:43,527 --> 00:19:45,095
TOP OF THIS KNOWLEDGE OF

497
00:19:45,095 --> 00:19:46,496
INTERACTION, WE STARTED TO FIND

498
00:19:46,496 --> 00:19:53,603
OUT OTHER REGULATORY MECHANISMS

499
00:19:53,603 --> 00:19:55,138
THAT ARE CRITICAL FOR OR

500
00:19:55,138 --> 00:19:59,109
CHANGING THE STRUCTURE OF THE

501
00:19:59,109 --> 00:19:59,943
NUCLEAR PERIPHERY AND LAURA WHO

502
00:19:59,943 --> 00:20:06,249
WAS A Ph.D. STUDENT IN MY LAB,

503
00:20:06,249 --> 00:20:07,017
SHE DISCOVERED LYSEEN

504
00:20:07,017 --> 00:20:09,653
ACETYLATION THAT IS SHOWN ON B1,

505
00:20:09,653 --> 00:20:14,925
WHICH SHOWS WHEN B1 BECOMES

506
00:20:14,925 --> 00:20:15,892
ACETALATED, OF K134, THE

507
00:20:15,892 --> 00:20:17,995
INTEGRITY OF THE NUCLEUS IS

508
00:20:17,995 --> 00:20:19,329
RESTORED AND THE VIRUS IS NO

509
00:20:19,329 --> 00:20:25,335
LONGER TO CREATE THESE

510
00:20:25,335 --> 00:20:26,870
INFOLDINGS AND THIS RESULT

511
00:20:26,870 --> 00:20:28,338
INDEED SEQUESTRATION OF THE

512
00:20:28,338 --> 00:20:31,842
VIRAL DNA INSIDE THE NUCLEUS AND

513
00:20:31,842 --> 00:20:33,977
VIRAL CAPSID INSIDE THE NUCLEUS

514
00:20:33,977 --> 00:20:36,880
AND REDUCED VIRUS PARTICLES BOTH

515
00:20:36,880 --> 00:20:37,914
HERE INTRACELLULARLY AND EXTRA

516
00:20:37,914 --> 00:20:44,287
CELLULARLY AS SHOWN HERE.

517
00:20:44,287 --> 00:20:46,523
BUT WHAT THEY WERE ABLE TO SHOW

518
00:20:46,523 --> 00:20:47,891
IS MORE BROADLY RELEVANT SO

519
00:20:47,891 --> 00:20:49,760
FIRST OF ALL SHE SHOWED THAT

520
00:20:49,760 --> 00:20:53,196
DURING INFECTION OF HSV 1,

521
00:20:53,196 --> 00:20:54,631
ANOTHER NUCLEAR REPLICATING

522
00:20:54,631 --> 00:20:59,603
VIRUS AND ALPHA VIRUS.

523
00:20:59,603 --> 00:21:02,539
AGAIN OF THE NUCLEAR PERIPHERY

524
00:21:02,539 --> 00:21:08,311
OF THE LAMIN B1 PROTECTS THE

525
00:21:08,311 --> 00:21:09,212
INTEGRITY OF THE PERIPHERY AND

526
00:21:09,212 --> 00:21:10,647
DOES NOT OOH LOW TO PROGRESS

527
00:21:10,647 --> 00:21:11,214
FROM THE EGRESS.

528
00:21:11,214 --> 00:21:13,383
AND THEN SHE SHOWED THAT THIS IS

529
00:21:13,383 --> 00:21:14,484
BROADLY RELEVANT IN UNINFECTED

530
00:21:14,484 --> 00:21:16,920
CELLS AND A MECHANISM THAT CAN

531
00:21:16,920 --> 00:21:18,488
CONTROL DNA DAMAGE REPAIR CHOICE

532
00:21:18,488 --> 00:21:23,827
AND CELL CYCLE PROGRESSION.

533
00:21:23,827 --> 00:21:27,364
AND WHEN THIS IS ACETALATED,

534
00:21:27,364 --> 00:21:33,403
THIS PROMOTES INTRA LAMINAR

535
00:21:33,403 --> 00:21:34,771
INTERACTIONS AND THAT'S STRONGER

536
00:21:34,771 --> 00:21:37,774
BUT THAT LEADS THE CHROMA TEEN

537
00:21:37,774 --> 00:21:39,976
TO BE EXCLUDED FROM IT'S

538
00:21:39,976 --> 00:21:41,211
INTERACTIONS WITH THE LAMINA,

539
00:21:41,211 --> 00:21:42,746
IRPT ACTIONS THAT ARE REALLY

540
00:21:42,746 --> 00:21:47,918
CRITICAL FOR DNA DAMAGE REPAIR

541
00:21:47,918 --> 00:21:50,720
AND THEN SHE SHOWED THAT THAT

542
00:21:50,720 --> 00:21:52,022
LEADS TO IMPAIRED RECRUITMENT OF

543
00:21:52,022 --> 00:21:55,125
IMPORTANT DNA REPAIR PROTEINS TO

544
00:21:55,125 --> 00:21:58,295
DOUBLE STRANDED BREAK REPAIRS

545
00:21:58,295 --> 00:21:59,463
SUCH AS 53 BP1 IN PARTICULARLY

546
00:21:59,463 --> 00:22:03,233
AND THAT LEADS TO A SLOWER DNA

547
00:22:03,233 --> 00:22:10,740
REPAIR AND ALSO PERSISTENT CELL

548
00:22:10,740 --> 00:22:13,443
CYCLE ACTIVATION OF THE G1 TO S

549
00:22:13,443 --> 00:22:15,145
CONTROL AND PATHWAY CHOICE IN

550
00:22:15,145 --> 00:22:19,149
S-PHASE SO FOR HOMOLOGOUS

551
00:22:19,149 --> 00:22:20,217
RECOMBINATION VERSUS HOMOLOGOUS

552
00:22:20,217 --> 00:22:23,019
ENJOINING, SO IT'S AN EXAMPLE OF

553
00:22:23,019 --> 00:22:24,955
HOW BY STUDYING REMODELING EVENT

554
00:22:24,955 --> 00:22:26,256
DURING INFECTION, WE FOUND A

555
00:22:26,256 --> 00:22:28,692
MECHANISM THAT IS MORE BROADLY

556
00:22:28,692 --> 00:22:32,329
REGULATED AND IMPORTANT DURING

557
00:22:32,329 --> 00:22:34,164
CELL CYCLE PROGRESSION AND

558
00:22:34,164 --> 00:22:39,069
REGULATING THE CHOICE OF DNA

559
00:22:39,069 --> 00:22:41,104
PATHWAY, OF DNA REPAIR PATHWAY.

560
00:22:41,104 --> 00:22:43,640
OKAY, SO, I SHOWED YOU HOW WE

561
00:22:43,640 --> 00:22:45,609
ICE THE ISHT INTERACTION STUDIES

562
00:22:45,609 --> 00:22:48,445
EITHER TARGETED OR GLOBAL TO

563
00:22:48,445 --> 00:22:49,446
LEARN ABOUT DYNAMIC EVENTS THAT

564
00:22:49,446 --> 00:22:51,815
HAPPEN AS THE INFECTION

565
00:22:51,815 --> 00:22:52,582
PROGRESSES.

566
00:22:52,582 --> 00:22:54,251
BUT WE BECAME QUITE MORE AND

567
00:22:54,251 --> 00:22:56,920
MORE INTERESTED IN UNDERSTANDING

568
00:22:56,920 --> 00:22:58,021
REALLY STRUCTURE FUNCTION

569
00:22:58,021 --> 00:22:59,689
RELATIONSHIPS DURING VIRAL

570
00:22:59,689 --> 00:23:01,491
INFECTION, IN ORDER TO

571
00:23:01,491 --> 00:23:03,260
ACCOMPLISH THIS, WE TURNED SOME

572
00:23:03,260 --> 00:23:08,131
YEARS AGO TO SPATIAL PROTEOMICS.

573
00:23:08,131 --> 00:23:09,466
SO I WANT TO SHOW YOU WHERE WE

574
00:23:09,466 --> 00:23:10,567
STARTED AND WHERE WE ARE GOING

575
00:23:10,567 --> 00:23:12,502
NEXT AND I WILL FINISH WITH SOME

576
00:23:12,502 --> 00:23:13,637
WORK THAT IS NOT PUBLISHED AND

577
00:23:13,637 --> 00:23:15,071
THAT WILL TELL YOU ABOUT SOME OF

578
00:23:15,071 --> 00:23:17,807
THE NEW DIRECTIONS IN THE LAB.

579
00:23:17,807 --> 00:23:19,743
SO SOME YEARS AGO WE USED FACIAL

580
00:23:19,743 --> 00:23:22,512
PROT I DON'T MEANICS TO START TO

581
00:23:22,512 --> 00:23:23,380
UNDERSTAND WHAT ARE OTHER

582
00:23:23,380 --> 00:23:27,384
CHANGES THAT HAPPEN IN ORGANELLE

583
00:23:27,384 --> 00:23:28,685
COMPOSITION AND WHAT OTHER VIRAL

584
00:23:28,685 --> 00:23:30,554
PROTEINS THAT MAY BE TARGETING

585
00:23:30,554 --> 00:23:31,755
THESE DIFFERENT ORGANELLES IN

586
00:23:31,755 --> 00:23:33,723
ORDER TO INDUCE THESE CHANGES SO

587
00:23:33,723 --> 00:23:37,294
IN THIS CASE, WE INTEGRATED

588
00:23:37,294 --> 00:23:38,795
MICROSCOPY WHEN WE OBSERVE THE

589
00:23:38,795 --> 00:23:40,897
TIME POINTS WHEN WE OBSERVE THE

590
00:23:40,897 --> 00:23:42,432
STRUCTURAL CHANGES IN AGER ANLES

591
00:23:42,432 --> 00:23:45,402
AND THEN WE COMBINE THEM WITH

592
00:23:45,402 --> 00:23:46,703
ORGANELLE FRACTIONATION AND WE

593
00:23:46,703 --> 00:23:48,738
QUANTITATE THEM WITH MASS TECT

594
00:23:48,738 --> 00:23:50,240
ROMETRY AND THESE DIFFERENT

595
00:23:50,240 --> 00:23:51,474
ORGANELLE FRACTIONS AND USE

596
00:23:51,474 --> 00:23:52,442
THESE SUPER VISED MACHINE

597
00:23:52,442 --> 00:23:53,877
LEARNING TO START TO ASSIGN

598
00:23:53,877 --> 00:23:56,079
DIFFERENT HOSTS AND VIRAL

599
00:23:56,079 --> 00:23:57,681
PROTEINS, 2 DIFFERENT

600
00:23:57,681 --> 00:23:59,783
SUBCELLULAR COMPARTMENTS AS THE

601
00:23:59,783 --> 00:24:01,284
INFECTION PROGRESSES AND THIS IS

602
00:24:01,284 --> 00:24:03,954
REALLY EYE OPENING AT THE TIME,

603
00:24:03,954 --> 00:24:08,058
WE FOUND FRUNKZAL TRANSLOCATIONS

604
00:24:08,058 --> 00:24:09,192
FROM 1 COMPARTMENT TO ANOTHER,

605
00:24:09,192 --> 00:24:19,736
AND WE FOUND CHANGES IN THE AND

606
00:24:20,537 --> 00:24:24,107
1 UNEXPECTED FINDINGS AT THE

607
00:24:24,107 --> 00:24:26,409
TIME THAT ARE PEROX SEEM PROTEIN

608
00:24:26,409 --> 00:24:28,712
INCREASED IN ABUNDANCE DURING

609
00:24:28,712 --> 00:24:31,481
INFECTION AND THIS WAS A COMPANY

610
00:24:31,481 --> 00:24:37,020
TO--WE FOUND OUT BY USING

611
00:24:37,020 --> 00:24:44,094
MICROSCOPY BY A NUMBER OF AND

612
00:24:44,094 --> 00:24:45,962
ALSO THE STRUCTURE THAT WAS

613
00:24:45,962 --> 00:24:47,998
ALTERED DURING INFECTION, SO IN

614
00:24:47,998 --> 00:24:57,707
UNINFECTED CELLS YOU CAN SEE ON

615
00:24:57,707 --> 00:24:59,242
THE LEFT HAND THEY BECOME

616
00:24:59,242 --> 00:25:00,577
FRAGMENTED AND THE 1S THAT

617
00:25:00,577 --> 00:25:02,012
SURVIVE THEY ARE QUITE LARGE AND

618
00:25:02,012 --> 00:25:04,748
WE QUANTIFY THIS TO SHOW THAT

619
00:25:04,748 --> 00:25:06,416
THEY ARE ELONGATED AND CURVED

620
00:25:06,416 --> 00:25:11,921
AND BY INTEGRATED FURTHER,

621
00:25:11,921 --> 00:25:12,789
STRUCTURAL MICROSCOPY AND

622
00:25:12,789 --> 00:25:16,426
MATHEMATICAL MODELS WE LEARN HOW

623
00:25:16,426 --> 00:25:19,462
BIOGENESIS IS REGULATED IN

624
00:25:19,462 --> 00:25:21,998
MAMMALIAN CELLS AND BY USING

625
00:25:21,998 --> 00:25:23,166
PROTEOMICS AND FUNCTION WE

626
00:25:23,166 --> 00:25:25,335
ASSIGN THIS SO SPECIFICALLY WE

627
00:25:25,335 --> 00:25:27,570
FOUND THAT ENVELOPED VIRUSES

628
00:25:27,570 --> 00:25:30,173
SUCH AS HSV 1 INDUCED INCREASE

629
00:25:30,173 --> 00:25:31,741
NUMBER OF PEROXISOMES FOLLOWED

630
00:25:31,741 --> 00:25:34,811
BY CHANGES IN MORPHOLOGY, BUT

631
00:25:34,811 --> 00:25:41,384
THIS IS NOT DRIVEN BY INFECTION

632
00:25:41,384 --> 00:25:43,453
WITH NONENVELOPED VIRUSES, SO

633
00:25:43,453 --> 00:25:45,689
THIS IS REGULATED SO FIRST THE

634
00:25:45,689 --> 00:25:48,325
INFECTION, THE GROWTH AND

635
00:25:48,325 --> 00:25:50,226
INCREASE ABUNDANCE OF PEROXISOME

636
00:25:50,226 --> 00:25:52,395
PROTEINS FOR THE GROWTH AND

637
00:25:52,395 --> 00:25:52,929
VISION OF PEROXYSTUDIES OF

638
00:25:52,929 --> 00:25:55,999
MULTIPLE ENDOCRINE BY O GENESIS,

639
00:25:55,999 --> 00:26:01,705
WHILE LATER INFECTION THERE'S

640
00:26:01,705 --> 00:26:05,041
INCREASED ABUNDANCE OF

641
00:26:05,041 --> 00:26:05,775
PEROXISOME BIOGENESIS, SO THIS

642
00:26:05,775 --> 00:26:07,277
CHANGE IN STRUCTURE YOU SEE

643
00:26:07,277 --> 00:26:11,481
HERE, IT ACTIVATES THE SURFACE

644
00:26:11,481 --> 00:26:13,650
OF THE PEROXISOME AND THE

645
00:26:13,650 --> 00:26:15,652
PROTEINS THERE SUCH AS G-IMPACT

646
00:26:15,652 --> 00:26:17,387
THAT ARE CONTROLLING THE

647
00:26:17,387 --> 00:26:18,722
SYNTHESIS OF THESE LIPIDS THAT

648
00:26:18,722 --> 00:26:22,859
WE THEN SHOW TO BE IMPORTANT FOR

649
00:26:22,859 --> 00:26:23,993
THE SECONDARY ENVELOPEMENT SO

650
00:26:23,993 --> 00:26:26,162
THEY ARE INTEGRATED INSIDE THE

651
00:26:26,162 --> 00:26:28,298
VIRIONS AND THEY ARE CRITICAL

652
00:26:28,298 --> 00:26:30,967
FOR MAKING INFECTIOUS VIRAL

653
00:26:30,967 --> 00:26:32,635
PARTICLES AND IN AGREEMENT WITH

654
00:26:32,635 --> 00:26:38,408
THIS WE TOOK PATIENT WHO IS HAVE

655
00:26:38,408 --> 00:26:39,476
PEROXISOME DISORDERS AND FOUND

656
00:26:39,476 --> 00:26:41,344
THEY ARE RESISTANT TO INFECTION,

657
00:26:41,344 --> 00:26:43,813
SO THESE VIRUSES NEED THIS

658
00:26:43,813 --> 00:26:46,116
METABOLIC FUNCTION MUCH

659
00:26:46,116 --> 00:26:49,986
PEROXISOMES THAT ARE INTEGRATED

660
00:26:49,986 --> 00:26:51,921
IN THE VERRIONS SO THIS WAS

661
00:26:51,921 --> 00:26:53,757
UNEXPECTED AT THE TIME AND WAS

662
00:26:53,757 --> 00:26:55,525
IT A NEW OUTLOOK TO FUNCTIONS

663
00:26:55,525 --> 00:26:56,626
DURING INFECTION BECAUSE FOR

664
00:26:56,626 --> 00:27:00,096
OVER 10 YEARS WE KNEW THAT

665
00:27:00,096 --> 00:27:02,298
PEROXISOMES ARE IMPORTANT IN

666
00:27:02,298 --> 00:27:03,032
INNATE IMMUNE RESPONSES THEY

667
00:27:03,032 --> 00:27:06,035
HAVE MAPS AND ARE INVOLVE INDEED

668
00:27:06,035 --> 00:27:07,337
HOST DEFENSE IN INFECTION BUT

669
00:27:07,337 --> 00:27:09,706
NOW WE FOWBD THESE VIRUSES HAVE

670
00:27:09,706 --> 00:27:13,042
ACQUIRED MECHANISM TO TURN THIS

671
00:27:13,042 --> 00:27:14,978
INTO ANTIVIRAL ORGANELLE INTO A

672
00:27:14,978 --> 00:27:19,916
PROFILE ORGANELLE BY REGULATING

673
00:27:19,916 --> 00:27:21,151
LIPID SYNTHESIS, SO ALTOGETHER

674
00:27:21,151 --> 00:27:22,619
SHE'S STUDIES HAVE PAINTED FOR

675
00:27:22,619 --> 00:27:26,656
US A PICTURE OF THESE DYNAMIC

676
00:27:26,656 --> 00:27:27,157
STRUCTURURE FUNCTIONS

677
00:27:27,157 --> 00:27:29,125
RELATIONSHIPS AND WE WONDERED A

678
00:27:29,125 --> 00:27:31,060
FEW THINGS LIKE 1 CAN WE START

679
00:27:31,060 --> 00:27:33,296
MORE AND MORE TO UNDERSTAND WHAT

680
00:27:33,296 --> 00:27:34,931
IS THE FUNCTION, WHAT ARE THE

681
00:27:34,931 --> 00:27:36,566
FUNCTIONS OF THESE DIFFERENT

682
00:27:36,566 --> 00:27:37,634
STRUCTURES, HOW ARE A DRIVEN AND

683
00:27:37,634 --> 00:27:39,803
WHAT ARE THEIR FUNCTIONS BUT

684
00:27:39,803 --> 00:27:43,473
ALSO, ARE THEY--ARE THEY

685
00:27:43,473 --> 00:27:44,607
COORDINATED EVENTS.

686
00:27:44,607 --> 00:27:50,613
ARE THESE ORGANELLE REMODELING

687
00:27:50,613 --> 00:27:53,583
EVENTS ACTUALLY WORKING TO

688
00:27:53,583 --> 00:27:55,185
INTRACELLULAR COMMUNICATION AND

689
00:27:55,185 --> 00:27:55,952
EVEN INTERCELLULAR

690
00:27:55,952 --> 00:27:56,286
COMMUNICATION.

691
00:27:56,286 --> 00:27:57,387
SO INDEED, THIS IS NOT PUBLISHED

692
00:27:57,387 --> 00:27:58,988
WHAT I WILL SHOW YOU NEXT BUT

693
00:27:58,988 --> 00:28:01,057
INDEED WE KNOW THAT ORGANELLES

694
00:28:01,057 --> 00:28:05,228
DON'T FUNCTION AS SEPARATE

695
00:28:05,228 --> 00:28:06,629
ENDITYS BUT THEY FORM THESE

696
00:28:06,629 --> 00:28:08,965
NETWORKS AND THIS IS

697
00:28:08,965 --> 00:28:10,166
ACCOMPLISHED BY MEMBRANE CONTEXT

698
00:28:10,166 --> 00:28:12,168
SITE PROTEINS THAT BRING

699
00:28:12,168 --> 00:28:14,103
ORGANELLES THAT TETHER

700
00:28:14,103 --> 00:28:16,139
ORGANELLES IN CLOSE PROXIMITY

701
00:28:16,139 --> 00:28:17,640
LIKE 10-30 NANO MEETS AND BY

702
00:28:17,640 --> 00:28:19,409
DOING THIS IT ALLOWS FOR

703
00:28:19,409 --> 00:28:21,044
TRANSFER OF BIOMOLECULES THAT,A

704
00:28:21,044 --> 00:28:22,278
LOWS THE RECRUITMENT OF

705
00:28:22,278 --> 00:28:24,047
DIFFERENT PROTEINS THAT ARE ALSO

706
00:28:24,047 --> 00:28:27,083
REGULATE THE FUNCTIONS OF THESE

707
00:28:27,083 --> 00:28:27,851
ORGANELLE-ORGANELLE CONTACTS AND

708
00:28:27,851 --> 00:28:31,020
HERE'S AN EXAMPLE OF 1 OF OUR

709
00:28:31,020 --> 00:28:33,523
MOVIES WHERE IN [INDISCERNIBLE]

710
00:28:33,523 --> 00:28:36,526
YOU SEE THE [INDISCERNIBLE] AND

711
00:28:36,526 --> 00:28:37,727
THEY SHOW THE MITOCHONDRIA AND

712
00:28:37,727 --> 00:28:39,829
THEY SHOW THE INTERACTIONS

713
00:28:39,829 --> 00:28:41,097
BETWEEN THESE ORGANELLES SO WE

714
00:28:41,097 --> 00:28:43,566
WONDER HOW DO VIRAL INFECTIONS

715
00:28:43,566 --> 00:28:44,767
CHANGE OR REGULATE PROTEINS

716
00:28:44,767 --> 00:28:46,035
DURING INFECTION AND WE PRO

717
00:28:46,035 --> 00:28:47,537
DICTED THAT MANY OF THE CHANGES

718
00:28:47,537 --> 00:28:50,607
THAT WE SEE IN THESE ORGANELLE

719
00:28:50,607 --> 00:28:53,343
STRUCTURE AND FUNCTION HAVE TO

720
00:28:53,343 --> 00:28:55,612
RELY ON THE REGULATION OF THESE

721
00:28:55,612 --> 00:28:56,846
MEMBRANE CONTEXT SIDE PROTEINS

722
00:28:56,846 --> 00:28:59,649
BUT WHAT WAS SURPRISING IS THAT

723
00:28:59,649 --> 00:29:01,751
MCS HAS NOT BEEN THE FOCUS OF

724
00:29:01,751 --> 00:29:04,187
STUDY DURING VIRAL INFECTION AND

725
00:29:04,187 --> 00:29:05,154
THIS IS PERHAPS, ALSO DRIVEN IN

726
00:29:05,154 --> 00:29:06,623
PART BY THE FACT THAT THESE ARE

727
00:29:06,623 --> 00:29:08,892
NOT EASY PROTEINS TO STUDY, THEY

728
00:29:08,892 --> 00:29:10,059
ARE MEMBRANE BOUND PROTEINS,

729
00:29:10,059 --> 00:29:12,862
MANY OF THEM ARE LOW ABUNDANCE

730
00:29:12,862 --> 00:29:14,497
PROTEINS, THEY ARE NOT--THERE

731
00:29:14,497 --> 00:29:15,398
ARE NO ANTIBODIES AVAILABLE FOR

732
00:29:15,398 --> 00:29:19,469
MANY OF THESE TO STUDY SO THIS

733
00:29:19,469 --> 00:29:20,703
PROBABLY HAS DRIVEN SOME OF THIS

734
00:29:20,703 --> 00:29:21,938
LACK OF KNOWLEDGE AND

735
00:29:21,938 --> 00:29:25,375
UNDERSTANDING THIS. 

736
00:29:25,375 --> 00:29:27,343
ALSO THE METHOD OF CHOICE FOR

737
00:29:27,343 --> 00:29:29,946
STUDYING CONTEXT SITES AND

738
00:29:29,946 --> 00:29:31,247
ORGANELLE CONTACT USUALLY

739
00:29:31,247 --> 00:29:32,482
PROVIDES THE OPPORTUNITY TO

740
00:29:32,482 --> 00:29:36,920
STUDY 1 TACT AT A TIME OR JUST A

741
00:29:36,920 --> 00:29:39,055
FEW SO WE ASKED CAN WE

742
00:29:39,055 --> 00:29:41,124
UNDERSTAND HOW THESE ORGANELLE

743
00:29:41,124 --> 00:29:43,660
REMODELING EVENTS ARE GLOBALLY

744
00:29:43,660 --> 00:29:45,628
REGULATED AND WHETHER NMCS

745
00:29:45,628 --> 00:29:47,096
PROTEINS PLAY A ROLE DURING

746
00:29:47,096 --> 00:29:48,264
VIRAL INFECTION AND THE WORK HAS

747
00:29:48,264 --> 00:29:51,501
BEEN DRIIVE BY THE SUPER

748
00:29:51,501 --> 00:29:52,802
TALENTED Ph.D. STUDENT WHO

749
00:29:52,802 --> 00:29:54,504
WORKED TOGETHER WITH HELEN AND

750
00:29:54,504 --> 00:29:55,071
[INDISCERNIBLE] IN MY LAB.

751
00:29:55,071 --> 00:29:58,908
SO IN ORDER TO DESIGN AN ASSAY

752
00:29:58,908 --> 00:30:00,944
TO MONITOR MCS PROTEINS MASS

753
00:30:00,944 --> 00:30:02,645
SPECTROMETRY IS IN A WAY IDEALLY

754
00:30:02,645 --> 00:30:03,947
SUITED FOR THAT AND THE REASON

755
00:30:03,947 --> 00:30:05,214
NEAR IS THAT THIS IS 1 OF THOSE

756
00:30:05,214 --> 00:30:07,083
CASES WHERE WE KNOW THAT PROTEIN

757
00:30:07,083 --> 00:30:08,384
ABUNDANCE IS DIRECTLY CONNECTED

758
00:30:08,384 --> 00:30:11,287
TO THE EXTENT OF CONTACT SO IN

759
00:30:11,287 --> 00:30:13,623
OTHER WORDS, THE LEVEL OF MCS IS

760
00:30:13,623 --> 00:30:15,491
REALLY CRITICAL FOR THE AMOUNT

761
00:30:15,491 --> 00:30:17,060
OF CONTACT BETWEEN ORGANELLES,

762
00:30:17,060 --> 00:30:19,128
SO THIS IS SHOWN HERE, LET'S SAY

763
00:30:19,128 --> 00:30:24,434
THE KNOCK DOWN OF THIS PROTEIN,

764
00:30:24,434 --> 00:30:25,868
PPR59P 51, WHEN YOU SEE HOW THAT

765
00:30:25,868 --> 00:30:30,106
IS BEING IMO TD DOWN YOU CAN SEE

766
00:30:30,106 --> 00:30:33,309
HOW IT AAFFECTS THE

767
00:30:33,309 --> 00:30:34,310
ER-MITOCHONDRIA.

768
00:30:34,310 --> 00:30:36,579
WHEN IT EXPANDS IT ENHANCES THE

769
00:30:36,579 --> 00:30:40,183
FACES OF THE INTERACTION BETWEEN

770
00:30:40,183 --> 00:30:41,484
MITOCHONDRIA AND ER.

771
00:30:41,484 --> 00:30:43,519
SO WE DECIDE TO TARGET A MASS

772
00:30:43,519 --> 00:30:45,488
SPECT ROMET RADIOY APPROACH THAT

773
00:30:45,488 --> 00:30:47,991
IS BASED ON PARALLEL REACTION

774
00:30:47,991 --> 00:30:49,359
MONITORING TO TRY TO DETECT THE

775
00:30:49,359 --> 00:30:53,796
PROTEINS IN HUMAN CELLS AND THIS

776
00:30:53,796 --> 00:30:55,832
WAS QUITE A LENGTHY PROCESS SO

777
00:30:55,832 --> 00:30:59,302
CAITLIN HAD TO MANUELLY CURATE A

778
00:30:59,302 --> 00:31:00,770
LIBRARY OF FUNCTIONALLY

779
00:31:00,770 --> 00:31:02,271
CHARACTERIZED MCS PROTEIN SO WE

780
00:31:02,271 --> 00:31:04,173
TOOK INTO ACCOUNT THEIR CELL

781
00:31:04,173 --> 00:31:05,875
TYPE SPECIFICITY, WE TOOK INTO

782
00:31:05,875 --> 00:31:07,710
ACCOUNT TETHERS AND INTERACTORS.

783
00:31:07,710 --> 00:31:13,249
AND THEN SHE HAD TO DESIGN A

784
00:31:13,249 --> 00:31:14,317
LIBRARY OF PARAMETERS THAT WOULD

785
00:31:14,317 --> 00:31:16,619
ALLOW US TO SPECIFICALLY DETECT

786
00:31:16,619 --> 00:31:18,921
ONLY THOSE PARTICULAR PROTEINS

787
00:31:18,921 --> 00:31:21,391
BY MASS SPECTROMETRY SO SHE FIND

788
00:31:21,391 --> 00:31:23,126
THE PARAMETERS AND UNIQUE

789
00:31:23,126 --> 00:31:24,827
PEPTIDES FOR THEIR DETECTION AND

790
00:31:24,827 --> 00:31:29,599
THOSE SPECTRA LIBRARY FOR ALL

791
00:31:29,599 --> 00:31:30,466
MCS PROTEINS.

792
00:31:30,466 --> 00:31:32,402
THIS IS WAY EASIER THAN DONE,

793
00:31:32,402 --> 00:31:33,703
THIS IS QUITE A LENGTHY PROCESS

794
00:31:33,703 --> 00:31:35,138
BUT WOONS WE HAD THIS WE COULD

795
00:31:35,138 --> 00:31:38,307
APPLY IT NOW TO MEASURE

796
00:31:38,307 --> 00:31:39,375
ABUNDANCES IN 1 GOAL

797
00:31:39,375 --> 00:31:40,343
SIMULTANEOUSLY ACROSS DIFFERENT

798
00:31:40,343 --> 00:31:42,612
TIME POINTS AND CONDITIONS AND

799
00:31:42,612 --> 00:31:45,381
USE THE INFORMATION TO INFER

800
00:31:45,381 --> 00:31:48,818
WHETHER NEW CONTACTS OR CHANGE

801
00:31:48,818 --> 00:31:50,687
CONTACTS BETWEEN ORGANELLES ARE

802
00:31:50,687 --> 00:31:52,355
OCCURRING SO OUR ASSAY SO FAR

803
00:31:52,355 --> 00:31:55,625
WHAT IT CAN DO IS SIMULTANEOUSLY

804
00:31:55,625 --> 00:31:57,760
DETECT 90% OF THE KNOWN MCSs

805
00:31:57,760 --> 00:32:01,764
AND THAT CONTAINS ALL MAJOR

806
00:32:01,764 --> 00:32:04,834
ORGANELLE INTERFACES INCLUDING

807
00:32:04,834 --> 00:32:05,468
PEROXISOME LIPID DROPMENTS AND

808
00:32:05,468 --> 00:32:09,472
ALL FUNCTIONS THAT ARE MEDIATED

809
00:32:09,472 --> 00:32:09,706
BY MCSs.

810
00:32:09,706 --> 00:32:11,674
SO ONCE WE HAD THE ASSAY WE OOH

811
00:32:11,674 --> 00:32:13,910
PLIED IT TO THE 4 VIRUSES I

812
00:32:13,910 --> 00:32:14,877
MENTIONED THESE 4 ENVELOPE

813
00:32:14,877 --> 00:32:21,217
VIRUSES WE STUDY IN THE LAB,

814
00:32:21,217 --> 00:32:26,589
ATMB, HSV1, AND THE INFLUENZA A

815
00:32:26,589 --> 00:32:28,491
AND HCOV-BET - CORONA VIRUS, SO

816
00:32:28,491 --> 00:32:31,894
EVERY COLUMN REP ARE'S SENTS AN

817
00:32:31,894 --> 00:32:33,863
MCS PROTEIN AND THEY ARE

818
00:32:33,863 --> 00:32:35,231
CLUSTERED ACCORDING TO THE

819
00:32:35,231 --> 00:32:36,432
ORGANELLE CONTACTS THAT THEY

820
00:32:36,432 --> 00:32:40,269
FACILITATE AND THESE ARE EXAMPLE

821
00:32:40,269 --> 00:32:42,305
ARE ER MITOCHONDRIA, THESE ARE

822
00:32:42,305 --> 00:32:44,707
ER-GOLGI AND SO ON AND EVERY ROW

823
00:32:44,707 --> 00:32:45,908
REPRESENTS A DIFFERENT TIME

824
00:32:45,908 --> 00:32:47,777
POINT OF INFECTION AND WHAT YOU

825
00:32:47,777 --> 00:32:50,012
CAN HOPEFULLY SEE, THE COLOR

826
00:32:50,012 --> 00:32:52,749
REPRESENTS CHANGES IN PROTEIN

827
00:32:52,749 --> 00:32:53,916
ABUNDANCE DURING--COMPARED TO

828
00:32:53,916 --> 00:32:54,851
INFECTED CELLS.

829
00:32:54,851 --> 00:32:57,653
SO WHAT CAN YOU MADLY SEE IS

830
00:32:57,653 --> 00:33:00,923
THAT ATMB INFECTION TRIGGERS

831
00:33:00,923 --> 00:33:02,458
GLOBAL UPREGULATION IN MCS

832
00:33:02,458 --> 00:33:03,826
PROTEIN ABUNDANCES AND WE HAVE

833
00:33:03,826 --> 00:33:05,461
AOBSERVED THIS AFTER INFECTION

834
00:33:05,461 --> 00:33:07,597
WITH THE LABORATORY STRAIN OF

835
00:33:07,597 --> 00:33:09,298
HCMV, AS WELL AS LOW PASSAGE

836
00:33:09,298 --> 00:33:11,134
STRAIN THAT HAS MORE CLINICAL

837
00:33:11,134 --> 00:33:11,934
RELEVANCE.

838
00:33:11,934 --> 00:33:13,636
THIS IS QUITE IN CONTRAST WITH

839
00:33:13,636 --> 00:33:18,307
CHANGES THAT HAPPEN DURING HSV 1

840
00:33:18,307 --> 00:33:20,510
INFECTION, INFLUENCE OR OC43.

841
00:33:20,510 --> 00:33:24,347
SO HSV 1 TRIGGERS MORE SUBTLE

842
00:33:24,347 --> 00:33:25,548
CHANGES BUT ALSO MORE DISCREET

843
00:33:25,548 --> 00:33:28,184
CHAIMPLES SO TO REGULATE CERTAIN

844
00:33:28,184 --> 00:33:38,661
MCS PROTEINS IN THE SPECIFIC

845
00:33:39,662 --> 00:33:39,962
MANNER.

846
00:33:39,962 --> 00:33:44,267
AND OF COURSE THESE VIRUSES HAVE

847
00:33:44,267 --> 00:33:45,535
REPLICATION CYCLES THAT ARE MORE

848
00:33:45,535 --> 00:33:49,906
MATURE THAN THE CYCLE OF HCMV,

849
00:33:49,906 --> 00:34:00,449
SO WHAT CAN WE LEARN FROM THIS,

850
00:34:00,917 --> 00:34:03,186
WELL, AND THE FUNCTIONS THAT I

851
00:34:03,186 --> 00:34:05,054
TOLD YOU EARLIER, SOMETHING THAT

852
00:34:05,054 --> 00:34:07,323
WAS QUITE EVIDENT FROM OUR STUDY

853
00:34:07,323 --> 00:34:12,695
WAS THAT THE PROTEIN TEGHT ERS

854
00:34:12,695 --> 00:34:14,096
TO FACILITATE THESE, THESE 4

855
00:34:14,096 --> 00:34:16,499
PROTEINS LISTED HERE, THEY WERE

856
00:34:16,499 --> 00:34:19,202
ALL INCREASED IN ABUNDANCE

857
00:34:19,202 --> 00:34:21,337
DURING HCMV AND THAT MADE A LOT

858
00:34:21,337 --> 00:34:22,438
OF SENSE TO US BECAUSE IT'S

859
00:34:22,438 --> 00:34:27,844
KNOWN THAT THE ER CONTACT IS

860
00:34:27,844 --> 00:34:31,614
CRITICAL FOR SYNTHESIS AND THAT

861
00:34:31,614 --> 00:34:33,449
IS INITIATING THAT PEROXISOME

862
00:34:33,449 --> 00:34:35,718
AND IT WILL BE CONTINUED IN THE

863
00:34:35,718 --> 00:34:38,988
ER AND IT'S ALSO IMPORTANT FOR

864
00:34:38,988 --> 00:34:39,455
PEROXISOME GROWTH.

865
00:34:39,455 --> 00:34:41,691
SO WE ASKED WHETHER THE INCREASE

866
00:34:41,691 --> 00:34:44,493
THRA WE SEE IN PROTEIN CONTEXT

867
00:34:44,493 --> 00:34:46,062
HERE IN THEIR ABUNDANCE

868
00:34:46,062 --> 00:34:52,134
REPRESENT AN INCREASE IN ER,

869
00:34:52,134 --> 00:34:53,836
EROXISOME CONTACT AND IF IT

870
00:34:53,836 --> 00:34:54,370
HAPPENS DURING INFECTION.

871
00:34:54,370 --> 00:34:56,439
AND THAT WAS THE CASE.

872
00:34:56,439 --> 00:34:58,875
SO HERE IN UNINFECTED CELLS YOU

873
00:34:58,875 --> 00:35:00,476
CAN SEE THE ROUND CELL THAT I

874
00:35:00,476 --> 00:35:01,744
SHOWED YOU EARLIER ARE QUITE

875
00:35:01,744 --> 00:35:04,714
DYNAMIC AND THEY TRACK ALONG

876
00:35:04,714 --> 00:35:07,116
THESE ER TUBULES SHOWN HERE IN

877
00:35:07,116 --> 00:35:10,052
CYAN, HOWEVER AFTER INFECTION

878
00:35:10,052 --> 00:35:13,623
THEY BECOME MUCH MORE STABLY,

879
00:35:13,623 --> 00:35:14,991
QUITE LARGE PEROXISOMES AND THEY

880
00:35:14,991 --> 00:35:16,759
BECOME MUCH MORE STABLY ANCHORED

881
00:35:16,759 --> 00:35:19,128
ON THE ER MEMBRANE AS SHOWN

882
00:35:19,128 --> 00:35:19,395
HERE.

883
00:35:19,395 --> 00:35:23,666
AND WE WERE ABLE TO ALSO PERFORM

884
00:35:23,666 --> 00:35:26,702
REALLY--3D RECONSTRUCTION AND

885
00:35:26,702 --> 00:35:29,205
SHOW HOW PEROXISOMES HAVE

886
00:35:29,205 --> 00:35:30,640
INCREASED CONTACTS WITH ER

887
00:35:30,640 --> 00:35:33,242
MEMBRANES AND STABLING AS THE

888
00:35:33,242 --> 00:35:35,177
INFECTION PROGRESSES, SO WHAT'S

889
00:35:35,177 --> 00:35:37,179
THE MEANING OF THIS AND WHAT IS

890
00:35:37,179 --> 00:35:38,948
THE FUNCTION AND DOES THIS

891
00:35:38,948 --> 00:35:41,784
TETHER, IS THE TETHERING

892
00:35:41,784 --> 00:35:43,686
IMPORTANT FOR THE STRUCTURAL

893
00:35:43,686 --> 00:35:47,390
CHANGES I MENTIONED EARLIER WITH

894
00:35:47,390 --> 00:35:48,758
THE CURVED PEROXISOMES OR THE

895
00:35:48,758 --> 00:35:50,826
INCREASE IN THE NUMBERS.

896
00:35:50,826 --> 00:35:57,733
SO THE MAIN 2 TETHERS HERE ARE A

897
00:35:57,733 --> 00:36:01,203
CBD5 AND THEN THE ER FIRST OF

898
00:36:01,203 --> 00:36:05,474
ALL AS ECTOMYOSIN EXPECTED WE

899
00:36:05,474 --> 00:36:06,876
COMPARE PEROX ISOMES AND THIS IS

900
00:36:06,876 --> 00:36:09,245
JUST FOR INTEREST OF TAME SHOWN

901
00:36:09,245 --> 00:36:11,080
AT LATE TIME POINT OF INFECTION

902
00:36:11,080 --> 00:36:13,482
WE SEE THAT INCREASING MEMBRANE

903
00:36:13,482 --> 00:36:16,752
AREA AND INCREASING PEROXISOME

904
00:36:16,752 --> 00:36:17,219
NUMBERS.

905
00:36:17,219 --> 00:36:21,123
WHEN WE IMOWK DOWN ACDB 5 WE

906
00:36:21,123 --> 00:36:23,926
FIND THAT THE PEROXISOME NUMBERS

907
00:36:23,926 --> 00:36:26,295
ARE INCREASED SO SOMEHOW THIS IS

908
00:36:26,295 --> 00:36:28,698
A NEGATIVE FEEDBACK GROUP THAT

909
00:36:28,698 --> 00:36:30,700
WAS NOT PREVIOUSLY KNOWN BUT THE

910
00:36:30,700 --> 00:36:32,768
ABILITY OF THESE PEROXISOMES TO

911
00:36:32,768 --> 00:36:34,570
BECOMING LARGE IS LOST DURING

912
00:36:34,570 --> 00:36:38,407
INFECTION AND INDEED IF WE LOOK

913
00:36:38,407 --> 00:36:40,876
AT ACDB 5 LOCALIZATION WE FIND

914
00:36:40,876 --> 00:36:41,911
IT LOCALIZES SPECIFICALLY TO

915
00:36:41,911 --> 00:36:42,912
ENLARGE THESE TO INFECTION, IF

916
00:36:42,912 --> 00:36:44,847
YOU DO THE OPPOSITE EXPERIMENT

917
00:36:44,847 --> 00:36:48,184
AND WE OVEREXPRESS THIS TETHERED

918
00:36:48,184 --> 00:36:50,219
PROTEIN TO ICDB5, WE FIND THAT

919
00:36:50,219 --> 00:36:53,889
THE NUMBER OF PEROXISOME IS

920
00:36:53,889 --> 00:36:55,458
DECREASED BUT THE SIZE IS

921
00:36:55,458 --> 00:36:58,661
INCREASED, IT FORMS THE LARGE

922
00:36:58,661 --> 00:37:00,763
PEROXISOM, SOW THIS IS REQUIRED

923
00:37:00,763 --> 00:37:01,564
BUYER THE PROVIRAL CHANGES TO

924
00:37:01,564 --> 00:37:05,868
THE SIZES THAT I SHOWED YOU

925
00:37:05,868 --> 00:37:06,135
EARLIER.

926
00:37:06,135 --> 00:37:08,571
SO WE ALSO SHOWED THIS IS INDEED

927
00:37:08,571 --> 00:37:11,207
CONTRIBUTES TO THE VIRAL TITERS

928
00:37:11,207 --> 00:37:14,577
CHANGES WE SHOWED, WE REPORTED

929
00:37:14,577 --> 00:37:16,312
EARLIER FOR HCMB, AND WE FOUND

930
00:37:16,312 --> 00:37:20,349
THE SAME IS TRUE FOR INFLU

931
00:37:20,349 --> 00:37:27,690
FLUENZA A AND THE BETA CORONA

932
00:37:27,690 --> 00:37:29,291
VIRUS HCOV-O C43 SO THEY ALL

933
00:37:29,291 --> 00:37:34,296
NEEZ THE CONTACT IN ORDER TO

934
00:37:34,296 --> 00:37:35,331
CONTROL THEIR FUNCTIONS BUT I

935
00:37:35,331 --> 00:37:37,266
WANT TO SPEND KIND OF THE

936
00:37:37,266 --> 00:37:38,000
REMAINING FEW MINUTES I HAVE

937
00:37:38,000 --> 00:37:39,368
HERE ON SOMETHING NEW THAT WE

938
00:37:39,368 --> 00:37:41,837
DISCOVER THAT IS QUITE

939
00:37:41,837 --> 00:37:45,307
INTRIGUING AND IT'S BASED ON

940
00:37:45,307 --> 00:37:49,812
THIS OBSERVATION WE HAD ON ER

941
00:37:49,812 --> 00:37:51,514
MITOCHONDRIAL CONTACTS SO TO

942
00:37:51,514 --> 00:37:53,382
START BY PUTTING THIS IN BROADER

943
00:37:53,382 --> 00:37:54,817
CONTACTS WE HAVE BEEN INTERESTED

944
00:37:54,817 --> 00:37:56,685
IN THE REGULATION FOR A WHILE

945
00:37:56,685 --> 00:37:57,720
DURING INFECTION, AND IT'S VERY

946
00:37:57,720 --> 00:38:01,524
WELL KNOWN THAT MANY VIRUSES ARE

947
00:38:01,524 --> 00:38:02,758
CONTROLLING MITOCHONDRIAL

948
00:38:02,758 --> 00:38:03,759
FRAGMENTATION AND INFUSION

949
00:38:03,759 --> 00:38:06,128
DURING INFECTION IN ORDER TO

950
00:38:06,128 --> 00:38:08,264
CONTROL APOPTOSIS, IMMUNE

951
00:38:08,264 --> 00:38:09,965
SIGNALING AND ATP PRODUCTION.

952
00:38:09,965 --> 00:38:11,067
AND USUALLY INCREASED

953
00:38:11,067 --> 00:38:12,668
FRAGMENTATION THAT IS DRIVEN BY

954
00:38:12,668 --> 00:38:15,805
MANY VIRUSES IS CONNECTED WITH

955
00:38:15,805 --> 00:38:19,608
REDUCED ATP PRODUCTION, SO

956
00:38:19,608 --> 00:38:22,978
REDUCED BIOENERG JETTIC OUTPUT,

957
00:38:22,978 --> 00:38:25,781
HOWEVER HCMB INFECTION KIND OF

958
00:38:25,781 --> 00:38:29,885
PRESUNTS A CONUNDRUM, A PARADOX

959
00:38:29,885 --> 00:38:32,354
BECAUSE MITOCHONDRIA IS

960
00:38:32,354 --> 00:38:35,224
FRAGMENTED AFTER INFECTION WITH

961
00:38:35,224 --> 00:38:40,062
HCMB, HOWEVER SOMEHOW THEY ARE

962
00:38:40,062 --> 00:38:41,864
BIOLOGICALLY ENHANCED AND THE

963
00:38:41,864 --> 00:38:44,633
MECHANISMS REMAIN MYSTERIOUS AND

964
00:38:44,633 --> 00:38:50,940
SOMETHING WE NOTICED FROM OUR

965
00:38:50,940 --> 00:38:57,580
MCSN, ANDA PROTEINS ARE INNED AS

966
00:38:57,580 --> 00:39:00,916
THE INFECTIONS DONES AND THE

967
00:39:00,916 --> 00:39:02,685
TIME WHEN WE SEE AND ALSO WHEN

968
00:39:02,685 --> 00:39:06,222
WE SEE MANY CELLULAR CHANGES IN

969
00:39:06,222 --> 00:39:07,389
CELLULAR METABOLISM, INCREASED

970
00:39:07,389 --> 00:39:09,658
FLUX THROUGH GIVING--YOU COLSIS,

971
00:39:09,658 --> 00:39:11,460
INCREASED PHOSPHORYLATION, SO WE

972
00:39:11,460 --> 00:39:13,762
WONDERED WHETHER THESE CHANGES

973
00:39:13,762 --> 00:39:15,264
IN ER MITOCHONDRIAL CONTEXT,

974
00:39:15,264 --> 00:39:17,967
ACTUALLY SOMEHOW DRIVING THIS

975
00:39:17,967 --> 00:39:18,801
INCREASED--THIS INTERESTING

976
00:39:18,801 --> 00:39:20,736
PHENOTYPE THAT WE CAN'T EXPLAIN.

977
00:39:20,736 --> 00:39:22,538
BUT FIRST IN ORDER TO LOOK AT

978
00:39:22,538 --> 00:39:25,207
THIS, WE HAVE TO CONVINCE

979
00:39:25,207 --> 00:39:26,909
OURSELVES THAT CHANGES WE SEE

980
00:39:26,909 --> 00:39:29,712
HERE IN PROTEIN CONTACT, IN

981
00:39:29,712 --> 00:39:31,113
PROTEIN ABUNDANCES, ACTUALLY

982
00:39:31,113 --> 00:39:34,283
REFLECTS THE CHANGE IN

983
00:39:34,283 --> 00:39:36,418
ORGANELLE-ORGANELLE TON TACT.

984
00:39:36,418 --> 00:39:40,623
SO USING FLUORESCENT MICROSCOPY

985
00:39:40,623 --> 00:39:42,024
AND [INDISCERNIBLE] MICROSCOPY,

986
00:39:42,024 --> 00:39:45,494
WE MONITORED THE INTERACTION

987
00:39:45,494 --> 00:39:47,429
BETWEEN MITOCHONDRIA AND ER, AND

988
00:39:47,429 --> 00:39:49,098
WE NOTICED THIS INTERACTION THAT

989
00:39:49,098 --> 00:39:50,266
HAS BEEN PREPORTED MANY TIMES

990
00:39:50,266 --> 00:39:53,169
BEFORE IN WHICH THESE ER TUBULES

991
00:39:53,169 --> 00:39:55,004
ARE WEAVING ACROSS THE

992
00:39:55,004 --> 00:39:56,739
MITOCHONDRIA AND YOU CAN SEE

993
00:39:56,739 --> 00:40:00,042
THESE LITTLE CONSTRICTION SITES

994
00:40:00,042 --> 00:40:02,645
WHERE THE--ON MITOCHONDRIA WHERE

995
00:40:02,645 --> 00:40:06,782
THE MEMBRANE TUBULES ARE

996
00:40:06,782 --> 00:40:07,049
CROSSING.

997
00:40:07,049 --> 00:40:08,517
AND THIS IS A DYNAMIC

998
00:40:08,517 --> 00:40:10,653
INTERACTION AS YOU SEE HERE,

999
00:40:10,653 --> 00:40:12,421
HOWEVER, AFTER INFECTION, THE

1000
00:40:12,421 --> 00:40:15,090
INTERACTION CHANGES QUITE

1001
00:40:15,090 --> 00:40:17,059
STRIKINGLY, THE MITOCHONDRIA

1002
00:40:17,059 --> 00:40:18,260
BECOME ENCAPSULATED AND STABLY

1003
00:40:18,260 --> 00:40:21,197
IN THE ISHT ACTION WITH THE

1004
00:40:21,197 --> 00:40:25,234
MEMBRANES AND WHEN WE ALSO

1005
00:40:25,234 --> 00:40:28,304
LABELED AND THE OUTER MIGHT ON

1006
00:40:28,304 --> 00:40:29,672
CHOND RIA MEMBRANE, WE CAN

1007
00:40:29,672 --> 00:40:31,307
CONFIRM THAT THE CONTACT BETWEEN

1008
00:40:31,307 --> 00:40:32,608
THE MITOCHONDRIA AND THE ER IS

1009
00:40:32,608 --> 00:40:35,311
INCREASED BUT ALSO THIS IS

1010
00:40:35,311 --> 00:40:36,779
ASYMMETRIC, IT HAPPENS ON 1 SIDE

1011
00:40:36,779 --> 00:40:44,220
OF THE MITOCHONDRIA WHERE THE

1012
00:40:44,220 --> 00:40:45,454
CONTACT IS INCREASED SO THIS IS

1013
00:40:45,454 --> 00:40:48,190
QUITE DIFFERENT THAN THE DYNAMIC

1014
00:40:48,190 --> 00:40:49,425
TUBULE CROSSINGS THAT ARE

1015
00:40:49,425 --> 00:40:50,893
USUALLY REPORTED FOR THESE

1016
00:40:50,893 --> 00:40:54,763
INTERACTIONS AND PRESENTS A NEW

1017
00:40:54,763 --> 00:40:55,397
MITOCHONDRIAL ER CONTEXT

1018
00:40:55,397 --> 00:40:57,166
STRUCTURE THAT HAS NOT BEEN

1019
00:40:57,166 --> 00:40:59,602
REPORTED BEFORE, SO WE USE SUPER

1020
00:40:59,602 --> 00:41:00,769
RESOLUTION MICROSCOPY AND USE IT

1021
00:41:00,769 --> 00:41:01,670
TO GAIN BETTER UNDERSTANDING OF

1022
00:41:01,670 --> 00:41:03,872
WHAT WE ARE LOOKING AT, INDEED

1023
00:41:03,872 --> 00:41:09,511
WE FOUND THAT THE ER

1024
00:41:09,511 --> 00:41:10,346
FORMS--INCAPSULATES THE

1025
00:41:10,346 --> 00:41:11,747
MITOCHONDRIA IN LITTLE POCKETS

1026
00:41:11,747 --> 00:41:15,384
AND THIS IS TABLE AND ASYMMETRIC

1027
00:41:15,384 --> 00:41:19,888
MEMBRANE CAPSULATION, SO WE TURN

1028
00:41:19,888 --> 00:41:23,158
THIS STRUCTURE MENCs FOR

1029
00:41:23,158 --> 00:41:23,926
MITOCHONDRIA-ER ENCAPSULATIONS

1030
00:41:23,926 --> 00:41:25,060
AND WE MONITOR DURING THE

1031
00:41:25,060 --> 00:41:26,061
PROGRESSION OF INFECTION AND WE

1032
00:41:26,061 --> 00:41:30,199
NOTE THAD AS THE INFECTION

1033
00:41:30,199 --> 00:41:32,268
PROGRESSES, THIS CONTACT,

1034
00:41:32,268 --> 00:41:33,235
MENCs BECOME THE PRIMARY

1035
00:41:33,235 --> 00:41:35,371
CONTACT TYPE FOR ER MITOCHONDRIA

1036
00:41:35,371 --> 00:41:40,209
AND WE ALSO NOTICE THAT AS THESE

1037
00:41:40,209 --> 00:41:42,211
MENCs ARE FORMED THIS HAVE

1038
00:41:42,211 --> 00:41:44,546
INCREASED IN THIS STABLE TYPE OF

1039
00:41:44,546 --> 00:41:45,147
INTERACTION BETWEEN THESE 2

1040
00:41:45,147 --> 00:41:47,750
ORGANELLES AND THE DYNAMIC

1041
00:41:47,750 --> 00:41:50,953
INTERACTION PREVIOUSLY NOTICED

1042
00:41:50,953 --> 00:41:52,121
IS DECREASING.

1043
00:41:52,121 --> 00:41:57,393
SO WE THEREFORE ASK WHAT ARE THE

1044
00:41:57,393 --> 00:41:58,827
ER MITOCHONDRIAL MCS PROTEINS

1045
00:41:58,827 --> 00:42:01,497
THAT ARE LOCALIZING TO THE

1046
00:42:01,497 --> 00:42:04,199
MENCs, AND WHAT IS THE

1047
00:42:04,199 --> 00:42:04,667
STRUCTURAL FORMATION.

1048
00:42:04,667 --> 00:42:06,869
SO WE LOOK AT THE MASS

1049
00:42:06,869 --> 00:42:08,103
SPECTROMETRY DATA ISSUES THE 2

1050
00:42:08,103 --> 00:42:10,606
THAT ARE BETWEEN THESE CONTACT

1051
00:42:10,606 --> 00:42:12,408
WERE THE TETHERING COMPLEX THAT

1052
00:42:12,408 --> 00:42:19,848
IS FORMED BY PTP151 AND VAP-B

1053
00:42:19,848 --> 00:42:26,855
AND THIS IS KNOWN TO BE IN

1054
00:42:26,855 --> 00:42:28,657
CA-FLUX, AND BIOENERGETICS AND

1055
00:42:28,657 --> 00:42:32,561
AUTOPHAGY, SO WE LOOK AT THESE

1056
00:42:32,561 --> 00:42:35,030
PARTNERS AS THE INFECTION

1057
00:42:35,030 --> 00:42:36,632
PROGRESSES AND THAT ALLOWS US TO

1058
00:42:36,632 --> 00:42:38,267
DISCOVER THE FORMALITY OF THIS

1059
00:42:38,267 --> 00:42:41,403
AND WE FOUND MENCs ARE FORMED

1060
00:42:41,403 --> 00:42:47,009
AND ABOUT 48 HOURS POST

1061
00:42:47,009 --> 00:42:48,510
INFECTION, THEN PTPIP51 IS AT 72

1062
00:42:48,510 --> 00:42:52,448
HOURS POST INFECTION AND BOTH OF

1063
00:42:52,448 --> 00:42:55,751
THESE PROTEINS, VAP-B AND

1064
00:42:55,751 --> 00:42:57,252
PTPIP51 ARE LOCALIZATIONOT 1

1065
00:42:57,252 --> 00:42:59,722
SIDE OF THE MITOCHONDRIA AND WE

1066
00:42:59,722 --> 00:43:01,690
FURTHER VALIDATED THIS

1067
00:43:01,690 --> 00:43:03,125
INTERACTION USING PROXIMITY

1068
00:43:03,125 --> 00:43:04,626
LIGATION ASSAY TO CONFIRM THE

1069
00:43:04,626 --> 00:43:06,028
INTERACTION AND ALSO OBSERVE THE

1070
00:43:06,028 --> 00:43:07,796
INTERACTION FOR THE ENDOGENOUS

1071
00:43:07,796 --> 00:43:11,033
PROTEINS AND WE COULD SEE HOW

1072
00:43:11,033 --> 00:43:12,835
LATENT INFECTION THIS ACTUALLY

1073
00:43:12,835 --> 00:43:14,169
HAPPENS.

1074
00:43:14,169 --> 00:43:16,271
SO SINCE PTPIP51 WAS THE LAST 1

1075
00:43:16,271 --> 00:43:19,675
RECRUITED TO THIS, SO MENCs

1076
00:43:19,675 --> 00:43:22,778
FORM AND THEN VAP-B AND THEN

1077
00:43:22,778 --> 00:43:23,746
PTPIP51 AND WE ASKED THE

1078
00:43:23,746 --> 00:43:25,614
FUNCTION OF THIS IS TO USE THIS

1079
00:43:25,614 --> 00:43:27,783
WE USE THE ASSAY WE DEVELOPED

1080
00:43:27,783 --> 00:43:29,385
RECENTLY IN THE LAB AND THIS WAS

1081
00:43:29,385 --> 00:43:31,420
DEVELOPED BY MICHELLE KENNEDY A

1082
00:43:31,420 --> 00:43:32,588
VERY TALENTED STUDENT IN THE

1083
00:43:32,588 --> 00:43:32,788
LAB.

1084
00:43:32,788 --> 00:43:35,891
AS I TOLD YOU EARLIER THESE

1085
00:43:35,891 --> 00:43:36,992
VIRUSES ISSUES HERPES VIRUSES

1086
00:43:36,992 --> 00:43:38,961
ARE REALLY LARGE, THEY HAVE

1087
00:43:38,961 --> 00:43:40,062
LARGE GENOMES WE LACK ANTIBODIES

1088
00:43:40,062 --> 00:43:42,631
FOR MOST OF THESE VIRAL PROTEINS

1089
00:43:42,631 --> 00:43:45,868
SO DETECTING THEM AND

1090
00:43:45,868 --> 00:43:47,102
QUANTIFYING THEM AND ACCURATELY

1091
00:43:47,102 --> 00:43:49,471
DURING INFECTION IS NOT TRIVIAL

1092
00:43:49,471 --> 00:43:53,275
SO MICHELLE HAS DEVELOPED THIS

1093
00:43:53,275 --> 00:43:54,543
TARGETED MASS SPECTROMETRY ASSAY

1094
00:43:54,543 --> 00:43:56,111
TO DETECT THE MAJORITY OF THE

1095
00:43:56,111 --> 00:43:59,782
PROI DON'T MEANS OF THESE

1096
00:43:59,782 --> 00:44:01,850
VIRUSES, HCMV, AND KSHV AND SHE

1097
00:44:01,850 --> 00:44:03,585
SHOWED THAT SHE CAN CAPTURE WILL

1098
00:44:03,585 --> 00:44:06,255
TEMPORAL EXPRESSION OF VIRAL

1099
00:44:06,255 --> 00:44:06,789
GENE EXPRESSION, SHE CAN

1100
00:44:06,789 --> 00:44:08,490
PROJECTION  MONITOR

1101
00:44:08,490 --> 00:44:10,592
THE TEMPORAL DRUGS OR SMALL MOLL

1102
00:44:10,592 --> 00:44:12,561
COWLS OR GENETIC PROTURBATIONS

1103
00:44:12,561 --> 00:44:14,062
AND TOGETHER WITH TOM KRISTI WE

1104
00:44:14,062 --> 00:44:15,597
SHOWED THAT WE,A MRI THIS NOT

1105
00:44:15,597 --> 00:44:17,566
ONLY TO CELL CULTURE BUT ALSO

1106
00:44:17,566 --> 00:44:19,568
ANIMAL MODELS OF INFECTION, SO

1107
00:44:19,568 --> 00:44:21,203
THEREFORE WE USED OUR HCMV

1108
00:44:21,203 --> 00:44:23,539
VERSION OF THIS,A SAY, BUT THIS

1109
00:44:23,539 --> 00:44:28,610
TIME TO OUR CONDITION OF PTPIP51

1110
00:44:28,610 --> 00:44:29,978
KNOCK DOWN TO FIND OUT THE

1111
00:44:29,978 --> 00:44:34,049
FUNCTIONAL CONSEQUENCE OF THIS

1112
00:44:34,049 --> 00:44:34,583
RECRUITMENT OF PTPIP51.

1113
00:44:34,583 --> 00:44:38,187
SO WE FOUND THE CONTROL KNOCK

1114
00:44:38,187 --> 00:44:40,589
DOWN AND THE PTPIP51 KNOCK DOWN

1115
00:44:40,589 --> 00:44:43,559
AND YOU ARE LOOKING AT FEW VIRAL

1116
00:44:43,559 --> 00:44:45,661
PROTEINS ILLUSTRATED HERE AND WE

1117
00:44:45,661 --> 00:44:49,498
FOUND THAT THIS--THE KNOCK DOWN

1118
00:44:49,498 --> 00:44:51,166
OF PTPIP51 DOES NOT IMPACT THE

1119
00:44:51,166 --> 00:44:53,302
EXPRESSION OF EARLY VIRAL GENES

1120
00:44:53,302 --> 00:44:55,804
BUT RATHER DECREASES THE LEVELS

1121
00:44:55,804 --> 00:44:57,372
OF DELAYED EARLY AND DELAYED

1122
00:44:57,372 --> 00:44:59,975
VIRAL PROTEINS SO PROTEINS THAT

1123
00:44:59,975 --> 00:45:00,976
SYNTHESIZE AROUND 48 AND 72

1124
00:45:00,976 --> 00:45:02,244
HOURS POST INFECTION.

1125
00:45:02,244 --> 00:45:05,047
AND THIS DECREASE IN VIRAL

1126
00:45:05,047 --> 00:45:07,516
PROTEIN LEVELS INDEED LEADS TO

1127
00:45:07,516 --> 00:45:09,918
AN OVERHUNDRED FOLD DECREASE IN

1128
00:45:09,918 --> 00:45:11,587
VIRUS TITER AND THIS IMPACT ON

1129
00:45:11,587 --> 00:45:15,791
THE VIRUS TIGHTER IS MAINTAINED

1130
00:45:15,791 --> 00:45:16,391
OVER TIME.

1131
00:45:16,391 --> 00:45:20,229
SO ALTOGETHER WHAT WE NOW

1132
00:45:20,229 --> 00:45:23,532
UNDERSTAND IS THAT PROTEIN

1133
00:45:23,532 --> 00:45:27,369
PTPIP51 INCREASE IN ABUNDANCE IN

1134
00:45:27,369 --> 00:45:30,839
INFECTION AND ACCUMULATING

1135
00:45:30,839 --> 00:45:38,714
ASSIMETRICALLY THE MENCs AND

1136
00:45:38,714 --> 00:45:40,315
IT'S CONTECTING TO INFECTION.

1137
00:45:40,315 --> 00:45:44,219
SO I JUST TOLD YOU PTPIP51 IS

1138
00:45:44,219 --> 00:45:45,821
PROVIRAL, SUPPORTING VIRAL

1139
00:45:45,821 --> 00:45:47,589
PRODUCTION BUT TURNS OUT THAT

1140
00:45:47,589 --> 00:45:49,825
THE TEMPERRALLITY IS ABSOLUTELY

1141
00:45:49,825 --> 00:45:50,959
KEY AND THIS IS SOMETHING

1142
00:45:50,959 --> 00:45:52,427
SURPRISING AT THE TIME AND MADE

1143
00:45:52,427 --> 00:45:56,265
SENSE TO US SO IF WE PREMATURELY

1144
00:45:56,265 --> 00:45:57,466
INCREASE ER MITOCHONDRIAL

1145
00:45:57,466 --> 00:45:59,668
CONTACT IT TURNS OUT THIS IS

1146
00:45:59,668 --> 00:46:04,506
ANTIVIRAL, IT'S NOT PROVIRAL, IF

1147
00:46:04,506 --> 00:46:06,742
WE SET THIS INTERACTION TOO

1148
00:46:06,742 --> 00:46:08,911
EARLY IT'S NOT DOING WHAT WE

1149
00:46:08,911 --> 00:46:12,180
THOUGHT IT WOULD DO SO FOR

1150
00:46:12,180 --> 00:46:13,715
EXAMPLE, THIS BRINGS TOGETHER

1151
00:46:13,715 --> 00:46:15,684
EARLIER INFECTION AND WE SEE

1152
00:46:15,684 --> 00:46:17,352
CONCENTRATION DEPENDENT AND

1153
00:46:17,352 --> 00:46:18,554
DECREASE VIRUS PROTUKS, SO FEW

1154
00:46:18,554 --> 00:46:21,823
QUESTION, FIRST OF ALL WHY IS IT

1155
00:46:21,823 --> 00:46:25,127
PROVIRAL ONLY LATENT INFECTION,

1156
00:46:25,127 --> 00:46:26,495
ONLY AFTER 48 HOURS WHEN THIS

1157
00:46:26,495 --> 00:46:28,297
CONTACT, THE FORMATION OF THIS

1158
00:46:28,297 --> 00:46:30,599
CONTACT IS ONLY PROVIRAL LATENT

1159
00:46:30,599 --> 00:46:31,934
INFECTION AND WE THINK THAT IT'S

1160
00:46:31,934 --> 00:46:33,936
BECAUSE IT NEEDS THE WRITE

1161
00:46:33,936 --> 00:46:37,172
CONTEXT, IT NEEDS THE

1162
00:46:37,172 --> 00:46:37,973
MITOCHONDRIAL FRAGMENTATION TO

1163
00:46:37,973 --> 00:46:39,608
OCCUR CAN AND IT NEEDS THE

1164
00:46:39,608 --> 00:46:41,243
LOCALIZATION OF THE FACTORS TO

1165
00:46:41,243 --> 00:46:41,743
THE MITOCHONDRIA.

1166
00:46:41,743 --> 00:46:43,779
SO FROM THE PATTIAL PROTEOMICS

1167
00:46:43,779 --> 00:46:47,749
STUDY I MENTIONED EARLIER, I

1168
00:46:47,749 --> 00:46:50,485
TOLD YOU WE FOUND OUT WHICH 1S

1169
00:46:50,485 --> 00:46:51,853
LOCALIZE TO PRODUCE ORGANELLES

1170
00:46:51,853 --> 00:46:52,821
TO INDUCE THESE CHANGES AND WE

1171
00:46:52,821 --> 00:47:00,562
FOUND THIS IS THE WORK OF

1172
00:47:00,562 --> 00:47:02,030
CORA BETSINGER IN MY LAB, SHE

1173
00:47:02,030 --> 00:47:03,498
PUBLISHED THIS LAST YEAR, BUT WE

1174
00:47:03,498 --> 00:47:06,735
FOUND OUT THAT THIS LOCALIZED TO

1175
00:47:06,735 --> 00:47:08,437
THE MITOCHONDRIA AND BY USING

1176
00:47:08,437 --> 00:47:10,806
LIVE CELL METABOLIC ASSAYS, SEA

1177
00:47:10,806 --> 00:47:14,209
HORSE ASSAY, SHE SHOWED THAT

1178
00:47:14,209 --> 00:47:16,612
VIRAL PROTEIN IS NECESSARY AND

1179
00:47:16,612 --> 00:47:17,379
SUFFICIENT TO INCREASE

1180
00:47:17,379 --> 00:47:18,747
PHOSPHORYLATION AND WE THINK

1181
00:47:18,747 --> 00:47:25,053
THIS IS ACTUALLY DOWN STREAM OF

1182
00:47:25,053 --> 00:47:28,857
THE MAIN FORMATION WHEN PUL13 IS

1183
00:47:28,857 --> 00:47:29,358
LOCALIZED THERE.

1184
00:47:29,358 --> 00:47:31,126
AND SHE ASKED HOW IS THIS

1185
00:47:31,126 --> 00:47:32,427
ACCOMPLISHING THIS AND TO DO

1186
00:47:32,427 --> 00:47:35,364
THIS SHE ANALYZE THE TEMPORAL

1187
00:47:35,364 --> 00:47:35,831
INTERACTIONS, PROTEIN

1188
00:47:35,831 --> 00:47:37,633
INTERFERON-GAMMA T-CELL ACTIONS

1189
00:47:37,633 --> 00:47:39,368
AS THE PROTEIN PROGRESSES AND

1190
00:47:39,368 --> 00:47:41,303
SHE USED THE PROGRAM COMPUTATION

1191
00:47:41,303 --> 00:47:45,941
PLATFORM THAT WE DEVELOPED A FEW

1192
00:47:45,941 --> 00:47:47,576
YEARS AGO CALLED INTERVISTA, AND

1193
00:47:47,576 --> 00:47:50,846
SHE INFECTED THESE CELLS WITH

1194
00:47:50,846 --> 00:47:53,615
THE PROTEIN, PERFORMED AN

1195
00:47:53,615 --> 00:47:54,249
AFFINITY PURIFICATION DURING

1196
00:47:54,249 --> 00:47:55,717
DIFFERENT TIMES OF INFECTION AND

1197
00:47:55,717 --> 00:47:59,421
USED THIS TO VISUALIZE THESE

1198
00:47:59,421 --> 00:48:00,922
INTERACTIONS AND SHE FOUND THAT

1199
00:48:00,922 --> 00:48:06,728
48 HOURS POST INFECTION, WHEN WE

1200
00:48:06,728 --> 00:48:10,232
SEE MENC FORMATION, UL13 GOES

1201
00:48:10,232 --> 00:48:11,967
THROUGH THE REMODELING

1202
00:48:11,967 --> 00:48:15,437
COMPLEXES, AND USING SUPER

1203
00:48:15,437 --> 00:48:16,571
RESOLUTION MICROSCOPY, PUL13 IS

1204
00:48:16,571 --> 00:48:20,709
SUFFICIENT TO CHANGE THE

1205
00:48:20,709 --> 00:48:22,411
ARCHITECTURE OF THE CRISTACE

1206
00:48:22,411 --> 00:48:24,012
STRUCTURE AND THE SURFACE AND

1207
00:48:24,012 --> 00:48:25,080
VOLUME OF THIS.

1208
00:48:25,080 --> 00:48:27,349
SO THIS REPRESENTS THE FIRST

1209
00:48:27,349 --> 00:48:30,585
VIRAL PROTEIN THAT CO MODULATE

1210
00:48:30,585 --> 00:48:32,854
THAT CAN LOCALIDES AND THE

1211
00:48:32,854 --> 00:48:34,356
STRUCTURE OF MITOCHONDRIA BY

1212
00:48:34,356 --> 00:48:38,960
ITSELF TO IN ORDER TO INCREASE

1213
00:48:38,960 --> 00:48:39,895
BIOINNER GENETICS.

1214
00:48:39,895 --> 00:48:43,732
SO I TOLD YOU THAT THIS POST

1215
00:48:43,732 --> 00:48:44,633
VIRAL FUNCTION HAPPENINGS LATE

1216
00:48:44,633 --> 00:48:45,901
IN INFECTION AND WHY WE THINK IT

1217
00:48:45,901 --> 00:48:46,968
HAPPENS BUT LASTLY IF WE COME

1218
00:48:46,968 --> 00:48:49,237
BACK TO THIS IDEA THAT IF WE

1219
00:48:49,237 --> 00:48:51,106
TETHER THIS EARLIER, SUDDENLY

1220
00:48:51,106 --> 00:48:52,407
THIS BECOMES ANTIVIRAL, THE

1221
00:48:52,407 --> 00:48:53,508
QUESTION IS WHY DOES THAT

1222
00:48:53,508 --> 00:48:53,875
HAPPEN.

1223
00:48:53,875 --> 00:48:56,745
AND WELL, IN USING THE SYNTHETIC

1224
00:48:56,745 --> 00:49:00,615
TETHER WE FOUND THAT IF

1225
00:49:00,615 --> 00:49:02,284
ER-MITOCHONDRIA ARE FORCED TO

1226
00:49:02,284 --> 00:49:03,752
INTERACTION TO EARLY AND

1227
00:49:03,752 --> 00:49:06,221
MAINTAIN AS A STABLE INTERACTION

1228
00:49:06,221 --> 00:49:11,326
TOO EARLY, IT ACTIVATES STING

1229
00:49:11,326 --> 00:49:13,428
AND THEREBY ACTIVATES THE TTK,

1230
00:49:13,428 --> 00:49:16,665
AND SIGNALING KASP A R CASE AND

1231
00:49:16,665 --> 00:49:17,265
INDUCES CYTOKINE EXPRESSION.

1232
00:49:17,265 --> 00:49:23,238
SO IN AGREEMENT WITH THE

1233
00:49:23,238 --> 00:49:24,439
ACTIVATION OF THIS BROAD HOST

1234
00:49:24,439 --> 00:49:26,441
DEFENSE MECHANISM, WE SEE THE

1235
00:49:26,441 --> 00:49:27,509
TETHER FORCING THIS INTERACTION

1236
00:49:27,509 --> 00:49:29,745
EARLY ON, ALSO DECREASES THE

1237
00:49:29,745 --> 00:49:31,847
VIRUS TITER FOR HSV 1 AND

1238
00:49:31,847 --> 00:49:33,782
INFLUENZA A IN A CONCENTRATION

1239
00:49:33,782 --> 00:49:34,783
DEPENDENT MANNER FOR THIS DATA

1240
00:49:34,783 --> 00:49:37,919
AND THIS IS PERHAPS WHY FOR

1241
00:49:37,919 --> 00:49:40,155
THESE VIRUSES THAT HAVE MUCH

1242
00:49:40,155 --> 00:49:41,890
SHORTER REPLICATION CYCLES WE

1243
00:49:41,890 --> 00:49:43,592
SEE THAT EARLY IN INFECTION THEY

1244
00:49:43,592 --> 00:49:47,863
IMMEDIATELY START TO DOWN

1245
00:49:47,863 --> 00:49:49,231
REGULATE THE ER-MITOCHONDRIAIAL

1246
00:49:49,231 --> 00:49:50,065
CONTACT PROTEIN OTHERWISE THEY

1247
00:49:50,065 --> 00:49:52,768
WOULD FORCE THIS TO HAPPEN WHEN

1248
00:49:52,768 --> 00:49:59,141
INDUCED SIGNALING. 

1249
00:49:59,141 --> 00:50:00,842
OKAY, SO WITH THAT I TOLD YOU

1250
00:50:00,842 --> 00:50:02,477
HOW THESE ARE TEMPORALLY

1251
00:50:02,477 --> 00:50:04,079
RESTRUCTURED AND HOW THE

1252
00:50:04,079 --> 00:50:05,447
TEMPORALITY OF THE MCS

1253
00:50:05,447 --> 00:50:06,481
REGULATION IS CRITICAL AND HOW

1254
00:50:06,481 --> 00:50:08,917
WE HAVE DISCOVERED THIS NEW

1255
00:50:08,917 --> 00:50:12,154
STRUCTURE OF MITOCHONDRIA ER

1256
00:50:12,154 --> 00:50:13,655
ENCAPSULATION THAT WE

1257
00:50:13,655 --> 00:50:14,723
DEMONSTRATE THAD IS NECESSARY

1258
00:50:14,723 --> 00:50:22,597
FOR VIRUS PRODUCTION AND IT'S A

1259
00:50:22,597 --> 00:50:23,398
PRO VIRAL.

1260
00:50:23,398 --> 00:50:24,900
AND HOW THIS REMODEL SUGGEST

1261
00:50:24,900 --> 00:50:27,035
QUITE BROADER IT'S QUITE GLOBAL

1262
00:50:27,035 --> 00:50:28,103
DURING ATV INFECTION AND WE

1263
00:50:28,103 --> 00:50:29,971
DEVELOP THIS ASSAY TOO BE ABLE

1264
00:50:29,971 --> 00:50:32,507
TO MONITOR ALL THESE MCSs IN

1265
00:50:32,507 --> 00:50:35,410
THE SAME TIME AND HOW--THIS

1266
00:50:35,410 --> 00:50:36,645
ALLOWED US TO FIND VIRUS

1267
00:50:36,645 --> 00:50:38,713
SPECIFIC AS WELL AS SHARED MCS

1268
00:50:38,713 --> 00:50:43,118
WIRING EVENT SUCH AS

1269
00:50:43,118 --> 00:50:48,523
ER-PEROXISOME INN TACT.--CONTAC.

1270
00:50:48,523 --> 00:50:51,159
SO WITH THAT I WILL THANK THE

1271
00:50:51,159 --> 00:50:52,828
PEOPLE I HIGHLIGHTED TODAY, THE

1272
00:50:52,828 --> 00:50:54,329
COLLAB RETIREDDORS, FUNDING AND

1273
00:50:54,329 --> 00:50:55,130
MY PHENOMENAL LAB AND I WANT TO

1274
00:50:55,130 --> 00:50:57,032
THANK YOU IF ARE YOUR ATTENTION

1275
00:50:57,032 --> 00:51:00,735
AND AGAIN THE HONOR FOR INVITING

1276
00:51:00,735 --> 00:51:10,045
ME HERE TODAY.

1277
00:51:10,045 --> 00:51:10,846
[ APPLAUSE ]

1278
00:51:10,846 --> 00:51:11,680
>> OKAY, THANK YOU.

1279
00:51:11,680 --> 00:51:15,851
ANYONE'S FREE TO USE THE MICs

1280
00:51:15,851 --> 00:51:18,753
IN 

1281
00:51:18,753 --> 00:51:19,487
IN THE AISLES.

1282
00:51:19,487 --> 00:51:20,856
I DO MY BEST TO READ THEM FOR

1283
00:51:20,856 --> 00:51:21,056
YOU.

1284
00:51:21,056 --> 00:51:25,493
THIS CAME IN EARLY IN YOUR

1285
00:51:25,493 --> 00:51:26,728
LECTURE.

1286
00:51:26,728 --> 00:51:27,095
>> SURE.

1287
00:51:27,095 --> 00:51:29,097
>> BASICALLY THE--THIS IS
FROM

1288
00:51:29,097 --> 00:51:30,932
SOMEONE HERE, [INDISCERNIBLE],

1289
00:51:30,932 --> 00:51:32,734
BASICALLY THE TEMPERATURE IS

1290
00:51:32,734 --> 00:51:35,837
CHANGED WITH AIR COMSUMPTION

1291
00:51:35,837 --> 00:51:36,504
ESPECIALLY HIGH TEMPERATURE, DID

1292
00:51:36,504 --> 00:51:39,007
YOU CHANGE TD CULTURE CONDITION

1293
00:51:39,007 --> 00:51:41,610
ESPECIALLY OXYGEN AND CO-2

1294
00:51:41,610 --> 00:51:42,043
COMSUMPTION?

1295
00:51:42,043 --> 00:51:44,913
>> OKAY, SO THIS PROBABLY
REFERS

1296
00:51:44,913 --> 00:51:45,847
TO THE THERMOCOAGULATION

1297
00:51:45,847 --> 00:51:47,282
PROFILES WHERE THE PRINCIPLE IS

1298
00:51:47,282 --> 00:51:48,617
THAT YOU'RE DIN'RE INDUCE

1299
00:51:48,617 --> 00:51:49,384
THANKSGIVING AG DPREIGATION OF

1300
00:51:49,384 --> 00:51:51,453
THE PROTEIN BECAUSE YOU'RE

1301
00:51:51,453 --> 00:51:52,087
INCREASING THE TEMPERATURE.

1302
00:51:52,087 --> 00:51:54,122
OF COURSE AT THAT TIME YOU'RE

1303
00:51:54,122 --> 00:51:55,190
JUST SIMPLY AGGREGATING THE

1304
00:51:55,190 --> 00:51:56,458
PROTEIN, YOU'RE NOT TRYING TO

1305
00:51:56,458 --> 00:52:03,031
PRESERVE THE CELL FUNCTIONS IN A

1306
00:52:03,031 --> 00:52:04,432
CELL IT'S MAINLY TO AGGREGATE

1307
00:52:04,432 --> 00:52:12,073
THE PROTEIN AND SEE WHICH

1308
00:52:12,073 --> 00:52:12,974
PROTEIN-PROTEIN INTERACTIONS BUT

1309
00:52:12,974 --> 00:52:13,808
SOMETHING THAT'S VERY NICE

1310
00:52:13,808 --> 00:52:15,510
QUESTION BECAUSE SOMETHING THAT

1311
00:52:15,510 --> 00:52:17,812
WE HAVE ACTUALLY DONE IS NOW TO

1312
00:52:17,812 --> 00:52:21,750
REVISIT A FEW THINGS FOR THAT

1313
00:52:21,750 --> 00:52:22,717
WORK FLOW IN PARTICULAR THE

1314
00:52:22,717 --> 00:52:26,288
TEMPERATURES THAT ARE NEED IN

1315
00:52:26,288 --> 00:52:27,889
ORDER TO GET THOSE CURVES AND WE

1316
00:52:27,889 --> 00:52:30,392
FIND THAT YOU DO NOT NEED TO GO

1317
00:52:30,392 --> 00:52:31,359
THAT HIGH IN TEMRATURE IN

1318
00:52:31,359 --> 00:52:33,528
ORDER TO BE IN THE SWEET SPOT

1319
00:52:33,528 --> 00:52:37,032
WHERE YOU BEST PREDICT

1320
00:52:37,032 --> 00:52:37,866
COAGULATION PROFILES AND ALSO

1321
00:52:37,866 --> 00:52:40,268
MANY PROTEINS AS YOU PROBABLY

1322
00:52:40,268 --> 00:52:42,604
GUESS THIS IS COMPUTATIONALLY

1323
00:52:42,604 --> 00:52:43,171
INTENSIVE, RIGHT?

1324
00:52:43,171 --> 00:52:44,973
SO MANY PROTEINS DO NOT BEHAVE

1325
00:52:44,973 --> 00:52:46,741
VERY WELL AND THEY ARE HAVING

1326
00:52:46,741 --> 00:52:48,677
CURVES IN ALL DIFFERENT DREKS

1327
00:52:48,677 --> 00:52:51,146
AND AGGREGATING PROTEINS OR

1328
00:52:51,146 --> 00:52:52,914
MEMBRANE BOUND PROTEINS DO NOT

1329
00:52:52,914 --> 00:52:55,784
BEHAVE WELL, SO TRAVIS IN MY LAB

1330
00:52:55,784 --> 00:52:57,018
HAS LICENSED BUFFER CONDITIONS

1331
00:52:57,018 --> 00:52:58,386
TO TRY TO CAPTURE MORE AND MORE

1332
00:52:58,386 --> 00:53:00,755
OF THE PROTEOME BUT HE ALSO HAS

1333
00:53:00,755 --> 00:53:05,760
TESTED EXPERIMENTALLY AND ALSO

1334
00:53:05,760 --> 00:53:06,461
COMPUTATIONALLY MONITORS WHAT

1335
00:53:06,461 --> 00:53:08,063
ARE THE TEMPERATURES SO WE NEED

1336
00:53:08,063 --> 00:53:10,265
ONLY 5 TEMPERATURES IN ORDER TO

1337
00:53:10,265 --> 00:53:11,700
GET REALLY GREAT INFORMATION

1338
00:53:11,700 --> 00:53:12,600
ABOUT AGGREGATION CURVES AND

1339
00:53:12,600 --> 00:53:17,739
THIS  BRINGS IT INTO DIFFERENT

1340
00:53:17,739 --> 00:53:19,174
TEMPERATURES IN TERMS OF

1341
00:53:19,174 --> 00:53:20,175
MULTIPLEXING THIS AND MAKING IT

1342
00:53:20,175 --> 00:53:21,142
MUCH FASTER.

1343
00:53:21,142 --> 00:53:23,511
BUT HE ALSO DEVELOPED THEE

1344
00:53:23,511 --> 00:53:25,113
MACHINE ALGORITHMS FOR BETTER

1345
00:53:25,113 --> 00:53:27,582
ANALYZING THE DATA.

1346
00:53:27,582 --> 00:53:27,849
YES.

1347
00:53:27,849 --> 00:53:30,819
SNRS I HAVE 2 QUESTIONS, 1 IS TO

1348
00:53:30,819 --> 00:53:31,886
THE LAMINA ACETYLATION, DO YOU

1349
00:53:31,886 --> 00:53:33,922
KNOW THE ENZYME THAT DOES IT?

1350
00:53:33,922 --> 00:53:39,361
IS IT A SPECIFIC ACETYLATION OR?

1351
00:53:39,361 --> 00:53:41,296
>> SO WE ONLY VERY LITTLE
TABLED

1352
00:53:41,296 --> 00:53:42,163
FOR THE MOMENT.

1353
00:53:42,163 --> 00:53:43,665
SO I CAN TELL YOU WHAT WE KNOW

1354
00:53:43,665 --> 00:53:46,501
SO FAR, SO IT SEEMS LIKE P300

1355
00:53:46,501 --> 00:53:48,236
ARE THE STILL TRANSFER ACE THAT

1356
00:53:48,236 --> 00:53:52,374
DOES THAT, FOR THE

1357
00:53:52,374 --> 00:53:55,543
DEACETYLATION, WE TESTED WITH

1358
00:53:55,543 --> 00:53:58,046
HBACK INHIBITORS AND WE STARTED

1359
00:53:58,046 --> 00:54:01,416
TO LOOK AT CERTUEINS 1 AND 6 AND

1360
00:54:01,416 --> 00:54:02,617
WE NOTICE THAD 6 IS GOING TO THE

1361
00:54:02,617 --> 00:54:03,251
PERIPH RADIOY AND THEREFORE IS

1362
00:54:03,251 --> 00:54:06,221
KIND OF AT THE RIGHT TIME AND

1363
00:54:06,221 --> 00:54:07,322
PLACE TO TRY TO DEACETALATE THAT

1364
00:54:07,322 --> 00:54:09,824
BUT WE HAVE NOT YET LOOKED INTO

1365
00:54:09,824 --> 00:54:18,299
THAT TO VALIDATE IT.

1366
00:54:18,299 --> 00:54:21,703
>> BECAUSE THIS COULD BE
MAB

1367
00:54:21,703 --> 00:54:22,103
EPIGENETICCULATED

1368
00:54:22,103 --> 00:54:22,470
THERAPEUTICALLY.

1369
00:54:22,470 --> 00:54:24,372
>> YES, YES, AND AS WE ALL
KNOW

1370
00:54:24,372 --> 00:54:25,807
THEY ARE RESTING THE CELL SITE,

1371
00:54:25,807 --> 00:54:29,277
SO THEY ARE REPLICATING THE THIS

1372
00:54:29,277 --> 00:54:30,845
G1 S SO IT'S PERFECT FOR THE

1373
00:54:30,845 --> 00:54:32,714
HOST MACHINERY TO BE IMPRESSED

1374
00:54:32,714 --> 00:54:34,949
BUT NOT FOR HOST REPLICATION TOO

1375
00:54:34,949 --> 00:54:35,550
HAPPEN, RIGHT?

1376
00:54:35,550 --> 00:54:37,419
SO IT MAKES SENSE THAT THE

1377
00:54:37,419 --> 00:54:40,922
ACETYLATION THAT WE SEE IT IN

1378
00:54:40,922 --> 00:54:42,190
UNINFECTED CELLS IS THE SAME,

1379
00:54:42,190 --> 00:54:43,591
AND THE SECOND QUESTION IS TO

1380
00:54:43,591 --> 00:54:46,194
TETHERING, THE LAST TOPIC, DO

1381
00:54:46,194 --> 00:54:48,229
YOU THINK IT'S MORE GENERAL

1382
00:54:48,229 --> 00:54:49,831
PHENOMENON OR IT CAN HAPPEN IN

1383
00:54:49,831 --> 00:54:53,068
ALL INFECTIONS OR EVEN WHATEVER

1384
00:54:53,068 --> 00:54:55,403
PERTURBATIONS THE CELLS ARE AT

1385
00:54:55,403 --> 00:54:57,238
AND AND IF SO, BECAUSE IT CAN--I

1386
00:54:57,238 --> 00:54:59,874
WAS THINKING IT CAN AFFECT OTHER

1387
00:54:59,874 --> 00:55:02,744
KINDS OF EXPERIMENTS SO FOR

1388
00:55:02,744 --> 00:55:04,112
EXAMPLE CELLULAR LOCALIZATION

1389
00:55:04,112 --> 00:55:05,980
EXPERIMENTS CAN BE CHANGED

1390
00:55:05,980 --> 00:55:08,316
BECAUSE OF THAT AND NOT BECAUSE

1391
00:55:08,316 --> 00:55:09,717
THE PROTEIN ACTUALLY CHANGED THE

1392
00:55:09,717 --> 00:55:11,052
LOCALIZATION, THEY CAN LOOK LIKE

1393
00:55:11,052 --> 00:55:11,419
THAT.

1394
00:55:11,419 --> 00:55:13,388
>> SO I THINK IT MAKES SO
MUCH

1395
00:55:13,388 --> 00:55:15,356
SENSE AND I'LL COME BACK TO THE

1396
00:55:15,356 --> 00:55:16,191
PARTICULAR TETHERING AND TELL

1397
00:55:16,191 --> 00:55:17,959
YOU WHY I THINK IT MAY OR MAY

1398
00:55:17,959 --> 00:55:21,329
NOT BE BUT IT MAKES SO MUCH

1399
00:55:21,329 --> 00:55:22,931
SENSE FOR MEMBRANE CONTEXT SITE

1400
00:55:22,931 --> 00:55:24,499
PROTEINS TO BE REGULATED DURING

1401
00:55:24,499 --> 00:55:26,000
INFECTION BECAUSE IF WE THINK

1402
00:55:26,000 --> 00:55:28,336
ABOUT IT, IT'S SO CRITICAL

1403
00:55:28,336 --> 00:55:29,904
PROTEINS FOR INTRACELLULAR

1404
00:55:29,904 --> 00:55:30,772
COMMUNICATION FOR THESE VERY

1405
00:55:30,772 --> 00:55:35,176
FAST SIGNAL THAGOREAN WE SEE IN

1406
00:55:35,176 --> 00:55:35,543
RESPONSES.

1407
00:55:35,543 --> 00:55:38,780
SO WHEN WE LOOK AT ALL THOSE

1408
00:55:38,780 --> 00:55:39,781
STRUCTURAL CHANGES, IT'S

1409
00:55:39,781 --> 00:55:40,615
IMPOSSIBLE FOR THE EARTH

1410
00:55:40,615 --> 00:55:42,884
STRUCTURE LIKE THAT NOT TO

1411
00:55:42,884 --> 00:55:43,785
IMMEDIATELY INFLUENCE ITS

1412
00:55:43,785 --> 00:55:45,587
ENVIRONMENT AND ALSO COMMUNICATE

1413
00:55:45,587 --> 00:55:47,589
THAT, AND WHAT BETTER WAY THAN

1414
00:55:47,589 --> 00:55:48,423
DIRECT CONTEXT BETWEEN

1415
00:55:48,423 --> 00:55:51,659
ORGANELLES THAT CAN QUICKLY MOVE

1416
00:55:51,659 --> 00:55:57,098
SMALL MOLECULES OR RECRUIT

1417
00:55:57,098 --> 00:55:57,398
PROTEINS.

1418
00:55:57,398 --> 00:56:02,670
I'VE BEEN FOR A WHILE FASCINATED

1419
00:56:02,670 --> 00:56:06,774
WITH THE MECHANO RESPONSES AND

1420
00:56:06,774 --> 00:56:08,576
THAT HAPPEN DURING INFECTION AND

1421
00:56:08,576 --> 00:56:10,311
THOSE ARE CLEARLY INVOLVED HERE

1422
00:56:10,311 --> 00:56:10,578
AS WELL.

1423
00:56:10,578 --> 00:56:12,313
NOW COMING BACK TO THE TETHER,

1424
00:56:12,313 --> 00:56:15,450
DEPENDING ON WHICH, SO FOR THE

1425
00:56:15,450 --> 00:56:17,018
MENCs, FOR THESE STRUCTURES, I

1426
00:56:17,018 --> 00:56:19,220
ACTUALLY THINK THAT THIS IS

1427
00:56:19,220 --> 00:56:21,356
PROBABLY FAIRLY SPECIFIC, SO IF

1428
00:56:21,356 --> 00:56:25,994
WE JUST INDUCE MITOCHONDRIAL

1429
00:56:25,994 --> 00:56:27,929
FRAGMENTATION, OR IF WE PERTURB

1430
00:56:27,929 --> 00:56:30,698
THE ER FUNCTIONS WE DO NOT SEE

1431
00:56:30,698 --> 00:56:32,967
MENCs FORMING SO WE THINK THAT

1432
00:56:32,967 --> 00:56:35,970
THIS IS ACTUALLY HAVING TO DO

1433
00:56:35,970 --> 00:56:38,239
WITH THAT REALLY INTERESTING

1434
00:56:38,239 --> 00:56:39,541
PHENOTYPES OF MITOCHONDRIA BEING

1435
00:56:39,541 --> 00:56:42,844
FRAGMENTED BUT BEING STILL

1436
00:56:42,844 --> 00:56:44,779
BIOGENETICALLY ENHANCED SO WE

1437
00:56:44,779 --> 00:56:46,848
NOW SHOW AND HAVE PRELIMINARY

1438
00:56:46,848 --> 00:56:50,018
DATA THAT WE THINK THAT S&P

1439
00:56:50,018 --> 00:56:55,823
PROTECTING THE MITOCHONDRIA AND

1440
00:56:55,823 --> 00:56:56,357
PERHAPS DECREASING MIGHT O

1441
00:56:56,357 --> 00:56:57,358
PHAGEY AND THE WORK OF OTHERS SO

1442
00:56:57,358 --> 00:57:03,097
THIS IS THE WORK OF WILL AND

1443
00:57:03,097 --> 00:57:04,632
CAITLIN COOK SO I DO NOT THINK

1444
00:57:04,632 --> 00:57:07,101
THAT IT WILL BE RELEVANT TO ALL

1445
00:57:07,101 --> 00:57:08,503
VIRAL INFECTIONS BECAUSE OF

1446
00:57:08,503 --> 00:57:10,572
THIS, HOWEVER, WE NOW HAVE

1447
00:57:10,572 --> 00:57:12,240
EVIDENCE THAT IT'S RELEVANT IN

1448
00:57:12,240 --> 00:57:12,674
OTHER CIRCUMSTANCES.

1449
00:57:12,674 --> 00:57:16,678
WE THINK THAT IT'S RELEVANT IN

1450
00:57:16,678 --> 00:57:17,512
CERTAIN NEUROGERONTOLOGYSTS

1451
00:57:17,512 --> 00:57:18,780
GENRATIVE DISEASES BUT IT'S ALSO

1452
00:57:18,780 --> 00:57:20,181
RELEVANT IN CANCER, ISY SO WE

1453
00:57:20,181 --> 00:57:24,485
LOOK AT CANCER CELLS BECAUSE

1454
00:57:24,485 --> 00:57:28,323
THEY TRIGGER A SIMILAR CHANGE IN

1455
00:57:28,323 --> 00:57:29,857
CELLULAR METABOLISM LIKE HCMB SO

1456
00:57:29,857 --> 00:57:32,794
WE DO SEE THAT MENCs DO FORM

1457
00:57:32,794 --> 00:57:33,061
THERE.

1458
00:57:33,061 --> 00:57:34,596
>> SO THE MEMBRANE IS A

1459
00:57:34,596 --> 00:57:41,236
PHENOMENON, THANK YOU FOR THIS

1460
00:57:41,236 --> 00:57:41,603
INSPIRING TALK.

1461
00:57:41,603 --> 00:57:42,770
>>  COUPLE MORE THIS, IS
FROM

1462
00:57:42,770 --> 00:57:44,038
DR. [INDISCERNIBLE] AT THE NIH,

1463
00:57:44,038 --> 00:57:46,407
MIGHT BE RELATED TO THAT.

1464
00:57:46,407 --> 00:57:48,876
COULD THE I HAVE RUGS DNA

1465
00:57:48,876 --> 00:57:51,346
BINDING PROTEIN RECOGNIZE DNA

1466
00:57:51,346 --> 00:57:53,114
ENDS WITHOUT TELEOR MERES, DO

1467
00:57:53,114 --> 00:57:57,185
THE SAME PROTEINS RECOGNIZE

1468
00:57:57,185 --> 00:57:58,086
CIRCULAR VIRAL DNA,.

1469
00:57:58,086 --> 00:57:58,820
>> SO THAT'S REALLY
INTERESTING

1470
00:57:58,820 --> 00:57:59,754
AND I DON'T KNOW, THIS IS

1471
00:57:59,754 --> 00:58:01,789
PROBABLY REFERRING TO THE DNA

1472
00:58:01,789 --> 00:58:04,092
SENSING STORY, THE NUCLEAR DNA

1473
00:58:04,092 --> 00:58:09,097
SENSING AND HOW--YES,--AND HOW

1474
00:58:09,097 --> 00:58:11,499
THESE HOST PROTEIN I516

1475
00:58:11,499 --> 00:58:13,601
RECOGNIZES VIRAL DNA INSTEAD OF

1476
00:58:13,601 --> 00:58:15,336
HOST DNA AND 1 THING I CAN SAY,

1477
00:58:15,336 --> 00:58:17,905
WE HAVE DONE THIS BUT THIS WAS

1478
00:58:17,905 --> 00:58:20,141
DONE INVITRO WHEN WE LOOKED AT

1479
00:58:20,141 --> 00:58:23,177
CIRCULAR DNA VERSUS LINEAR DNA,

1480
00:58:23,177 --> 00:58:26,481
WE WERE SPECULATING IT WOULD

1481
00:58:26,481 --> 00:58:27,815
ATTACHED TO LINEAR BECAUSE IT

1482
00:58:27,815 --> 00:58:29,651
WOULD DAMAGE DNA BUT WE FIND IT

1483
00:58:29,651 --> 00:58:31,419
BINDS TO BOTH CIRCULAR AND

1484
00:58:31,419 --> 00:58:33,521
LINEAR IN A SIMILAR FASHION, WE

1485
00:58:33,521 --> 00:58:39,894
HAVE SINCE THEN DONE OUR CHP-SEQ

1486
00:58:39,894 --> 00:58:41,529
AND ATTACH SEQ AND BYPASSEDS IN

1487
00:58:41,529 --> 00:58:43,564
A SEQUENCING MANNER AND IT'S

1488
00:58:43,564 --> 00:58:46,267
KNOWN ALREADY THAT IT'S--SO THE

1489
00:58:46,267 --> 00:58:49,437
PYRENE DOMAIN HAS ALL THIS BASIC

1490
00:58:49,437 --> 00:58:50,705
RESIDUES AND WE FOUND CERTAIN

1491
00:58:50,705 --> 00:58:57,145
RESIDUES THAT CAN BE MUTATED AND

1492
00:58:57,145 --> 00:59:00,515
WE FOUND HOW THOSE ARE

1493
00:59:00,515 --> 00:59:02,383
POLYMERIZED AND HOW THEY BIND TO

1494
00:59:02,383 --> 00:59:02,984
VIRAL DNA.

1495
00:59:02,984 --> 00:59:04,385
YEAH, THAT ARE SO MANY THINGS TO

1496
00:59:04,385 --> 00:59:07,789
SAY THERE, SO YOU CAN STOP ME

1497
00:59:07,789 --> 00:59:08,523
WHEN YOU WANT.

1498
00:59:08,523 --> 00:59:10,024
>> WELL MAYBE WE CAN SNEAK
IN 1

1499
00:59:10,024 --> 00:59:12,226
MORE BEFORE WE CLOSE THIS, IS

1500
00:59:12,226 --> 00:59:17,865
FROM RON GERMANE AT THE NIH

1501
00:59:17,865 --> 00:59:20,702
HERE, YOU SHOWED THAT MENC FORM

1502
00:59:20,702 --> 00:59:21,836
EARLY BEFORE THE ADHESIVE

1503
00:59:21,836 --> 00:59:23,071
INTERACTIONS WITH THE PROTEINS

1504
00:59:23,071 --> 00:59:25,907
THAT CONTRIBUTE TO VIRUS

1505
00:59:25,907 --> 00:59:27,775
REPLICATION, WHAT ALLOWS

1506
00:59:27,775 --> 00:59:30,345
FORMATION OF MENC THAT INVOLVES

1507
00:59:30,345 --> 00:59:31,746
MEMBRANE TO MEMBRANE INTERACTION

1508
00:59:31,746 --> 00:59:33,948
OF ORGANELLES BUT NOT THE

1509
00:59:33,948 --> 00:59:37,085
MOLECULAR PAIR YOU MENTIONED AS

1510
00:59:37,085 --> 00:59:38,086
CRITICAL FOR ER MIGHT O CONTACT.

1511
00:59:38,086 --> 00:59:39,854
SO CAN YOU PLEASE
REPEAT THAT

1512
00:59:39,854 --> 00:59:41,089
BECAUSE I MISSED THE BEGINNING

1513
00:59:41,089 --> 00:59:48,629
SO IT'S ABOUT THE MENCs,. 

1514
00:59:48,629 --> 00:59:49,630
AND--SIT'S FINE, YES.

1515
00:59:49,630 --> 00:59:51,799
YES, OKAY, SO YOU SHOW
THAT

1516
00:59:51,799 --> 00:59:54,669
MENC FORM EARLY BEFORE THE

1517
00:59:54,669 --> 00:59:58,272
ADHESIVE INTERACTION WITH THE

1518
00:59:58,272 --> 01:00:01,242
PROTEIN THAT CONTRIBUTES TO

1519
01:00:01,242 --> 01:00:01,642
VIRAL REPLICATION.

1520
01:00:01,642 --> 01:00:03,010
>> YES, SO IT'S FORM BIDE
MANY

1521
01:00:03,010 --> 01:00:03,778
PROTEINS SO REMEMBER THE HEAT

1522
01:00:03,778 --> 01:00:06,114
MAP AND I SHOWED HOW MANY OF

1523
01:00:06,114 --> 01:00:08,282
THEM ARE KNOWN TO INFORM THAT

1524
01:00:08,282 --> 01:00:09,717
THE ER MITOCHONDRIAL CONTACT BUT

1525
01:00:09,717 --> 01:00:11,719
THEN THE PROTEINS, THE VAP-B, I

1526
01:00:11,719 --> 01:00:13,354
THINK THAT'S WHAT THE QUESTION

1527
01:00:13,354 --> 01:00:15,690
REFERS TO AND PTPIP51 ARE

1528
01:00:15,690 --> 01:00:16,057
RECRUITED THERE.

1529
01:00:16,057 --> 01:00:22,630
IF YOU LOOK AT PTPIP51 IT'S

1530
01:00:22,630 --> 01:00:24,665
DISTRIBUTED, DIFFUSED AND

1531
01:00:24,665 --> 01:00:27,101
RELOCALLIZED IT GOES TO THE

1532
01:00:27,101 --> 01:00:28,269
TETHERING WITH VAP-B APPROXIMATE

1533
01:00:28,269 --> 01:00:30,905
HOW IT'S LOCALIZED ON THE

1534
01:00:30,905 --> 01:00:34,609
MITOCHONDRIA, SO, AND THAT'S

1535
01:00:34,609 --> 01:00:35,743
KNOWN--THAT'S NOT KNOWN FOR

1536
01:00:35,743 --> 01:00:37,845
INFECTION OR NOT KNOWN THAT IT

1537
01:00:37,845 --> 01:00:39,847
HAPPENS IN A SYMMETRIC THING AND

1538
01:00:39,847 --> 01:00:40,681
THAT RELOCALLIZATION IS KNOWN TO

1539
01:00:40,681 --> 01:00:42,417
BE IMPORTANT FOR THE FORMATION

1540
01:00:42,417 --> 01:00:43,851
OF THIS TETHERING COMPLEX AND

1541
01:00:43,851 --> 01:00:45,153
THERE ARE OTHER PROTEINS THAT

1542
01:00:45,153 --> 01:00:49,557
EARLIER ON ARE BRING THESE 2

1543
01:00:49,557 --> 01:00:51,159
ORGANELLES IN CONTACT THAT ARE

1544
01:00:51,159 --> 01:00:56,564
INCREASE NOTHING ABUNDANCE AS I

1545
01:00:56,564 --> 01:00:57,298
SHOWED THERE.

1546
01:00:57,298 --> 01:00:58,099
>> MAYBE--CLOSE THIS OUT?

1547
01:00:58,099 --> 01:01:01,803
>> THANK YOU FOR ALL THOSE
GREAT

1548
01:01:01,803 --> 01:01:02,069
QUESTIONS.

1549
01:01:02,069 --> 01:01:03,404
>> THANK YOU VERY MUCH
ILEANA

1550
01:01:03,404 --> 01:01:05,440
FOR THE GREAT TALK, I AM SURE IT

1551
01:01:05,440 --> 01:01:07,341
WILL BE INSPIRING FOR A LOT

1552
01:01:07,341 --> 01:01:11,179
PEOPLE AND THANK YOU VERY MUCH

1553
01:01:11,179 --> 01:01:13,514
FOR COMING AND AND WONDERFUL

1554
01:01:13,514 --> 01:01:15,683
ATTENDANCE IN PERSON AND ONLINE.

1555
01:01:15,683 --> 01:01:17,251
THANK YOU SO MUCH.

1556
01:01:17,251 --> 01:01:18,186
THANK YOU AGAIN.

1557
01:01:18,186 --> 01:01:28,396
[APPLAUSE ]