>> GOOD MORNING, EVERYONE. WELCOME BACK TO THE SECOND DAY OF THE SECOND HUMAN PLACENTA PROJECT WORKSHOP. HOPE YOU HAD A GOOD EVENING LAST NIGHT AND THAT YOU WERE ABLE TO HAVE ENJOYABLE TIME AND I HOPE AS PART OF THAT TALK SOME GOOD PLACENTAL SCIENCE. THIS MORNING WE'LL BE HEARING FROM THE LEADERS OF THE BREAK OUT GROUPS GIVING THE HIGHLIGHTS FROM YESTERDAY'S DISCUSSIONS WHICH WERE QUITE ACTIVE AND INTERESTING ONES. AS YOU CAN SEE ON THE AGENDA THIS MORNING WE HAVE GIVEN 40 MINUTES FOR EACH OF THE TOPIC AREAS, IN GENERAL IT WILL BE ABOUT A 15 MINUTE PRESENTATION FOLLOWED BY 20, 25 MINUTES OF DISCUSSION ON EACH TOPIC BOTH FOR OTHERS WHO WERE IN THOSE BREAK-OUT GROUPS AND DEFINITELY FOR THOSE NOT IN THE BREAK-OUT GROUPS BUT WOULD LIKE TO BE PART OF THE DISCUSSIONS. AFTER THOSE FOUR AREAS WEAL HAVE A BLUE SKY GROUP DISCUSSION THAT GOES ACROSS ALL GROUPS AND BOUNDARIES, ET CETERA. BEFORE THAT A COUPLE OF ALERTS AND HOUSEKEEPING ITEMS. FIRST WE WANTED TO DO SOMETHING TO THANK ALL OF YOU WHO ACTUALLY GOT HERE ON TIME THIS MORNING. SO WE THOUGHT THE BEST WAY TO DO THAT IS OFFER YOU MONEY. SO IF I CAN PULL UP THE SLIDE, SOMEONE WILL TELL ME HOW TO PULL UP THE MONEY SLIDE. THERE WE GO. SOME OF YOU ASKED THIS, THIS IS ALSO UNDERSCORE OUR INTEREST IN PLACENTA NICHD DOES NOT GIN AND END WITH THE HUMAN PLACENTA PROJECT. THIS IS NOT PART OF HUMAN PLACENTA PROJECT, WE DON'T SEE THIS IT AS A PARTICULAR STEP TOWARDS THE ULTIMATE GOAL OF MOPTORRING PLACENTAL STRUCTURE AND FUNCTION IN REAL TIME IN THE HUMAN. HOWEVER WE SEE IT BEING INVALUABLE. AND WE ALSO SEE IT AS SOMETHING WHICH HAS RESPONSE DATE OF MAY 1st SO WE HOPE A NUMBER OF YOU HAVE BEEN ACTIVELY WORKING ON THIS, ANY OF YOU NOT YOU HAVE SOMETHING TO KEEP YOU BUSY THE NEXT COUPLE OF DAYS, THIS IS AGAIN TO UNDERSCORE THERE ARE LOTS OF THINGS YOU DO, IS JOHN LIKAS HERE YET? IF NOT MANY OF YOU PAID ATTENTION TO QUESTIONS YESTERDAY HERE, MET JOHN ALIKAS. HE'S THE PROGRAM OFFICER FOR THIS. IF YOU PURSUE OTHER PLACENTAL THOUGHTS YOU'RE UNCLEAR ABOUT WHETHER SOMETHING REALLY FALLS WITHIN THE HUMAN PLACENTA PROJECT OR NOT DAVID WINEBERG YOU MET REPETLY, YOU'LL AGAIN IN A MOMENT IS THE PERSON TO CONTACT ABOUT PART OF THE HUMAN PLACENTA PROJECT OR NOT. IF NOT, DAVID WILL STEER YOU TOWARDS THE RIGHT PROGRAM OFFICER AT NICHD, AND TALK ABOUT THAT. NOW SOME HOUSEKEEPING ANNOUNCEMENTS. WE ASK THOSE OF YOU WHO HAVE POSTERS IF YOU WOULD TO KEEP THEM ON DISPLAY THROUGH THE LUNCH HOUR SO PARTICIPANTS HAVE A FULL OPPORTUNITY TO LOOK AT THOSE. WE ALSO LIKE TO THANK EVERYBODY WHO HAS WRITTEN IDEAS ON THE IDEA BOARDS, GETTING FILLED WITH INTERESTING IDEAS, WE ASK YOU TO CONTINUE TO ADD TO WHAT HAS BEEN WRITTEN TO HELP US WITH OUR CONVERSATIONS THIS AFTERNOON SO THAT THOSE WILL BE OPEN UNTIL THE END OF THE LUNCH BREAK WHICH TIME WE'LL TAKE THEM DOWN AND START DIGESTING THOSE ALONG WITH OUR LUNCH IN THE AFTERNOON. IF YOU NEED TO ARRANGE A TAXI TO GET HOME THIS EVENING SO YOU CAN WORK ON YOUR APPLICATIONS, CHECK IN WITH THE REGISTRATION DESK DURING THE FIRST BREAK THIS MORNING SO THEY CAN FINALIZE ARRANGEMENTS FOR THE TAXIS. NOW, MY DELIGHT TO TURN IT BACK OVER TO THE AFORESAID DAVID WINEBERG. THAT WOULD BE YOU, DAVID. TOO BUSY RUNNING THE CONFERENCE TO RUN THE CONFERENCE. >> GOOD MORNING, FIRST WELCOME YOU BACK, THANK YOU FOR COMING. I WANT TO GO BACK TO OUR FAVORITE TOPIC. PHONES. TURNS OUT WE HAVE FOUND A PHONE. SO IF YOU FIND YOU'RE MISSING ONE AT THE FRONT DESK THEY CAN HELP YOU. SO THIS MORNING WE'RE GOING TO BE HAVING A DISCUSSION OF YOUR HARD WORK YESTERDAY, THE OUTPUT OF THAT AND GET THE WHOLE GROUP'S INPUT. SO WHAT WE WOULD LIKE TO DO IS ASK ALL THE GROUP LEADERS TO COME UP TO STAGE, WE HAVE SEATS FROM YOU, WHAT WILL HAPPEN IS THERE WILL BE SHORT PRESENTATIONS BY THE GROUP LEADERS, TRY TO SHOOT FOR 15 MINUTES BUT WE HAVE A 40 MINUTE BLOCK AND WHAT WE WANT IS WE WANT TO HAVE DISCUSSION. WE HOPE THAT THOSE OF YOU IN THE AUDIENCE WILL CHALLENGE THINGS IF YOU HEAR THINGS THAT DON'T, DON'T MAKE SENSE OR YOU'RE CONCERNED ABOUT OR WE WANT TO HEAR WHEN YOU SAY THAT WE AGREE, IT SOUNDS LIKE THE RIGHT THING THAT WE SHOULD BE DOING SO WHAT WE WANT IS FOR YOU TO ACTIVELY ENGAGE, THAT'S THE BEST WAY TO MOVE IT FORWARD. SO IF GROUP LEADERS COULD COME UP, PLEASE. WE ARE RECORDING THIS AND SO IF YOU HAVE A QUESTION PLEASE USE THE MICROPHONE BECAUSE OTHERWISE IT WON'T BE RECORDED, WE WON'T BE ABLE TO CAPTURE YOUR QUESTIONS. JUST GIVE US A MOMENT, WE HAVE TO LOAD TWO PRESENTATIONS. >> NOW IS A GREAT TIME WHILE WE'RE DOING THIS TO LOOK AROUND AND SEE IF THERE'S ANYBODY THAT YOU HAVEN'T MET, THAT SEEMED TO WORK WELL YESTERDAY. FEEL FREE TO INTRODUCE YOURSELF TO SOMEBODY. TALK AMONG YOURSELVES. WE'RE ALMOST THERE. STOP TALKING. >> GOOD MORNING, EVERYONE. MY NAME IS SUSAN FISHER, I'M PRESENTING FOR THE PROTEOMICS DISCUSSION GROUP. ONE OF THE SESSIONS WAS LED BY LANCE LIOTTA AND I LED THE OTHER ONE. I APOLOGIZE FOR THE BULLET POINT NATURE OF THIS PRESENTATION, IT'S MORE BULLETS THAN SYNTHESIS BUT HOPEFULLY WE'LL GET TO MORE SYNTHESIS DURING THE PRESENTATION. YOU WILL ALSO NOTICE THAT SEVERAL OF THE POINTS ARE MADE MULTIPLE TIMES AND RATHER THAN TRY TO ELIMINATE REDUNDANCY WE DECIDED TO HAVE THOSE POINTS MADE MORE THAN ONE TIME BECAUSE WE THINK THEY'RE IMPORTANT. SO WE'LL GIVE -- THREE TIMES THAT YOU WILL THEE IT'S IMPORTANT AND REMEMBER IT. WHAT CAN WE DETECT AND HOW EARLY IN PREGNANCY CAN WE GET DETECTED? SO OUR GROUP DIVIDED THIS IN TO PRE-CON SECTION BECAUSE WE WERE THINKING PRE-CONCEPTION IS ALSO VERY IMPORTANT TIME, AND OF COURSE DURING THAT PERIOD WE CAN DETECT ENVIRONMENTAL CHEMICALS AND WE COULD DO PROTEOMICS AND METABALOMICS ON A VARIETY OF SAMPLES INCLUDING THOSE FROM IDS PATIENTS. POST CONCEPTION THE FIRST BULLET POINT IS GOING TO RISE OVER AND OVER GUN IN MY TALK. WE REALLY EVERYBODY FROM BOTH DISCUSSION SECTIONS THOUGHT WE NEEDED A NORMAL REFERENCE PROTEOME AND ME TAB -- METABALOME OVER GESTATION AND INCLUDING POST DELIVERY. WE TALK MEDIA SUCH AS PLASMA AND SERUM BUT WE ALSO THOUGHTED THIS SHOULD INCLUDE SAMPLES THAT ARE MUCH EASIER TO COLLECT BUT MORE CHALLENGING TO ANALYZE SUCH AS SALIVA, SWEAT AND URINE. FROM WITH REGARD TO TECHNICAL CHALLENGES YOU'LL SEE THAT WE OVERPOPULATED THE DIFFICULT TO OVERCOME CATEGORIES. THIS IS GOING TO BE A COMMON THEME WITH MY PRESENTATION. SO LIBRARIES AND REFERENCE STANDARDS, WE ALL THOUGHT THAT THE IMPORTANCE OF THESE SORT OF RESOURCES COULDN'T BE OVERSTATED. LIBRARIES WHO CAN GET SPECKTORAL LIBRARIES FOR MASS SPECTROMETRY BUT THE LIBRARIES ARE ESPECIALLY IMPORTANT FOR METABALOMICS. WHAT YOU SEE IN METABALOMICS IS WHAT YOU HAVE A REFERENCE STANDARD FOR BY THE MOST PART AND WE REALLY NEED TO HAVE THOSE LIBRARIES. SOME EXIST COMMERCIALLY BUT IF THEY BE ASSEMBLED IT WOULD BE AN INCREDIBLE RESOURCE SO HERE ARE THE DIFFICULTIES. SO STAMP -- SAMPLE STABILITY, PATIENT VARIABILITY, SO WE KNOW FROM MANY STUDIES PRESENTED YESTERDAY AND PUBLISHED THERE'S LOTS OF VARIABILITY. WE REALLY NEED BULLET PROOF SOPs FOR COLLECTING SAMPLES AND SOME OF THOSE EXIST AND SOME DON'T. DATA ANALYSIS IS A HUGE CHALLENGE WHEN COALESCING DATA AND STORAGE AS WE GET THESE HUGE DATA FILES FOR TO STORE THEM BECAUSE NO ONE WANTS TO THROW OUT THE DATA BUT STORAGE IS BECOMING INCREASINGLY AN ISSUE. WE ALSO WANT TO SHARE DATABASES. THIS IS MORE DIFFICULT THAN IT SOUNDS. THE OMIC PLATFORMS OFTEN DON'T TALK TO EACH OTHER AND THEN THERE HAS TO BE A VERY PERSONAL WILLINGNESS TO SHARE DATA AND WE DECIDED ONE OF THE THEMES THAT FELL IN WITH THE OMICS OVER GESTATION WAS DEFINING ON AN INDIVIDUAL BASIS CHANGES IN THE METABALOME AND PROTEOME THAT HAPPENED OVER PREGNANCY. THINGS ARE HAPPENING RAPIDLY AND OFTENTIMES WE DON'T CAPTURE THAT IF WE JUST GET ONE OR TWO SAMPLES OVER GESTATION. WE ALSO NEED TO ASSEMBLE REALLY STERLING PATIENT INFORMATION, I THINK GOING BACK TO ORIGINAL CHARTS AND TRYING TO FERRET OUT THINGS LIKE BLOOD PRESSURE AND THINGS LIKE THAT ARE AMAZINGLY DIFFICULT, NOT VERY COST EFFECTIVE. WE THOUGHT ANOTHER CHALLENGE WAS A LOT OF FIRST AND FIRST TRIER SAMPLES AS SPECIALLY IF THE PLACENTA COME FROM PREGNANCIES WHICH WE DON'T KNOW WHAT THE OUTCOMES WOULD HAVE BEEN. THAT'S A MORE CHALLENGE. THAT MORE TECHNICAL LEVEL FUNCTIONAL PROTEOMICS AND LIGAND DEVELOPMENT FOR IMAGING. SO STILL IN THE THEME OF TECHNICAL CHALLENGES, WHAT'S THE NEXT BIG THING ON THE HORIZON? SO WE THOUGHT AGAIN THAT IT WOULD BE IMPORTANT TO BE ABLE TO MEASURE PROTEINS AND METABOLITES IN MEDIA OTHER THAN BLOOD AND PERHAPS URINE. ENRICHMENT TECHNOLOGIES FOR BOTH PROTEINS OR SUBSETS OF POST TRANSLATIONALLY MODIFIED PROTEINS AND METABOLITES WILL BE IMPORTANT BECAUSE SO MUCH EASIER TO ANALYZE SIMPLER FRACTIONS, TOP DOWN PROTEOMICS IN WHICH WE LOOK AT INTACT GLYCO PROTEINS TOGETHER WITH THEIR POST TRANSLATIONAL MODIFICATIONS. IS REALLY ON HORIZON AND DOABLE BUT TECHNOLOGIES ARE EXTREMELY CHALLENGING. I THINK WE CAME OVER AND OVER AGAIN TO THE MOLECULE WE ONLY ANALYZE A SMALL FRACTION BY ELISA, PROBABLY GLYCOSYLATION TELLS US MUCH ABOUT THE BIOLOGY OF PREGNANCY BUT WE DON'T KNOW ANYTHING ABOUT WHAT HAPPENS TO THE MOLECULE INTACT MOLECULE AND GLYCOSYLATION OVER PREGNANCY. WE THOUGHT PROTEIN PROTEIN INTERACTIONS WERE IMPORTANT TO STUDY BECAUSE OF POTENTIAL FOR YIELDING DRUGS AND ACTIVITIES. SINGLE MOLECULE DETECTION IS SO IMPORTANT BECAUSE IT ALLOWS FOCUS AND AMPLIFICATION TECHNOLOGIES IN THE WORKS SUCH AS PCR TIDE PLATFORMS FOR AMPLIFICATION OF PROTEINS. WITH REGARD TO TECHNOLOGIES THAT NEED TO BE DEVELOPED, WE SAVANTSLY THESE TESTS EVENTUALLY THESE TESTS TO BE DELIVERED IN THE FORM OF HIGHLY SENSITIVE MULTI-PLEX POINT OF CARE DEVICES WITH WITH THE RESULTS TRANSMITTED BY TELEMETRY. WE REALLY WANTED TO EMPHASIZE THE IMPORTANCE OF INTER-OMIC ANALYSIS, IN OTHER WORDS COALESCING DATA FROM MANY PLATFORMS, AND INTEGRATING THAT OMICS DATA WITH IMAGES WHICH VERY MUCH IN LINE WITH THE RFAs AND THE CONFERENCE AND NEW SENSORS WILL BE IMPORTANT. SO WHAT ARE THE KEY PRACTICAL CHALLENGES? WE STILL THINK THAT SHARING DATA SHARING AND SAMPLE SHARING ARE A PROBLEM, THESE SORTS OF THINGS CAN BE MANDATED BY RFAs, SO IN A WAY THEY'RE EASIER TO OVERCOME THAN SOME OF THE OTHER CHALLENGING, ALSO SYNCHRONIZING ANALYSES SO MANY INVOLVED IN CONSOR YUM ANALYSES VERY HARD TO STANDARDIZE AMONG LABS SO HAVING SOME ANALYSES CENTRALIZE IN LABS THAT HAVE PROVEN THEIR ABILITY TO DO THE ASSAYS WOULD REALLY BE A BENEFIT. THINGS THAT ARE DIFFICULT TO OVERCOME, I THINK WE ALL AWARE BUT MADE ANOTHER LIST. THIS INCLUDES SHARING IP. PRACTICAL TERMS IF PEOPLE HAVE THE MULTI-PLEX INDIVIDUAL PLATFORMS FOR ASSAYING SAMPLES FROM EVERY PREGNANT WOMAN IN THE US OVER PREGNANCY, THIS IS GOING TO BE A DIFFICULT IP CHALLENGE IN ORDER TO GET PEOPLE TO DONATE THAT TO THE COMMUNITY. PROCURING SAMPLES FROM PATIENTS ALONG WITH STANDARDIZED CLINICAL INFORMATION. THIS SOUNDS EASY BUT ALL OF US WHO TRIED TO DO IN THIS ROOM KNOW HOW EXCEEDINGLY DIFFICULT THIS IS. WE ALL FELT WE NEEDED LARGE AND DIVERSE COHORTS WITH LONGITUDINAL SAMPLES. OF COURSE, COST IS A HUGE ISSUE. BY ANALOGY WITH CANCER PROGRAM, THE CANCER GENOME ATLAS AND THE PROTEOMICS PROGRAMS. WE NEED THOSE LEVELS OF SUPPORT TO GET THE KIND OF INFORMATION THAT'S BEEN GENERATED IN THOSE PROGRAMS. MENTION DATA STORAGE BEFORE BUT I CAN'T MENTION IT ENOUGH SO I'M GOING TO MENTION IT AGAIN AND COALESCING DATA FROM DIFFERENT PLATFORMS AND DIFFERENT TECHNOLOGIES IS REALLY SUCH A CHALLENGE BUT WE HOPE TO MAKE PROGRESS. I THINK THAT COULD BE A REAL AREA OF CONTRIBUTION NOT JUST TO THE HPP BUT OTHER -- ANY OTHER NIH INITIATIVE. WHAT'S THE MAJOR STRENGTH OF OUR TECHNOLOGIES? THE PROTEOMICS FIELD HAS REALLY BENEFITED FROM SHOWING ESPECIALLY IN CANCER THE VALUE OF LIQUID BIOPSIES CIRCULATING TUMOR CELLS. PERHAPS WE CAN DO THE SAME FOR FETAL CELLS OR DNA OR RNA. NOW, WE KNOW FETAL CELLS IN MATERNAL BLOOD ARE FEW, ONE IN TEN TO THE SIX NUCLEATED CELLS, BUT ANALYZING EVEN RARE CELLS IS BECOMING MORE AND MORE OF A REALITY. WE DISCUSSED PAP SMEAR APPROACHES FOR OBTAINING SAMPLES OF PLACENTAL OR FETAL CELLS FROM THE CERVICAL REGION THROUGHOUT PREGNANCY. THE APPLICATION OF MULTIPLE REACTION MONITORING MASS SPECTROMETRY ASSAYS THAT ARE ALREADY OUT THERE IN CLINICAL LABS FOR ASSAYING ANOLYTES SO INSTEAD OF LOOKING AT ANTIBODY ANTIGEN INTERACTIONS WE'RE QUANTIFYING PEPTIDES SO IT'S AN ABSOLUTE QUANTITATION METHOD. THESE MASS SPEC ASSAYS ARE ALREADY BEING APPLIED AND IN ARTHRITIS, CANCER, THYROID STIMULATING HORMONE, ASSAYS SOME HCG AND PERSONAL METABOLIC MARKERS. IT WOULD BE INTERESTING TO APPLY THE ONES THAT ALREADY EXIST IN OTHER CLINICAL ASSAYS THROUGHOUT PREGNANCY. ARE THERE OTHER SYNERGIZING TECHNOLOGIES? I THINK THAT'S REALLY THE CORE OF WHAT WE WOULD WANT TO DO WITH THE METABALOMIC AND PROTEOMIC DATA. THAT'S THE TO COALESCE IT WITH OTHER DATA TYPES FROM OTHER PLATFORMS. EPIGENOMIC, GENOMIC TRANSCRIPTSOMIC DATA, AND BE ABLE TO COALESCE THOSE GRAND ALL ENCOMPASSING DATA SETS WITH IMAGING DATA, HOPEFULLY INCREASING THE SPECIFICITY OF ALL THE PLATFORMS AN HELPING US HAVE MORE BELIEF IN THE RESULTS OF OUR ASSAYS. IN THE END LIKE IN ANY OTHER SITUATION WHERE YOU'RE TRYING TO EVALUATE PATIENTS HAVING A BIOMARKER PANEL WOULD BE THE WAY TO GO AND KNOWING WHAT THOSE BIOMARKERS, SOME OF THOSE WE CAN ASSEMBLE TO PROTEIN PATHWAYS AND NETWORKS TO GET A BETTER UNDERSTANDING OF THE ROLE OF THESE MARKERS IN THE BIOLOGY OF NORMAL AND ABNORMAL PREGNANCIES. AND WE THOUGHT THAT IN THE END THAT HAVING MODEL SYSTEMS SUCH AS ANIMAL MODELS AND CULTURE MODELS FOR DISCOVERY OF PROTEINS METABOLITES INVOLVED IN PREGNANCY, AND IN THE VALIDATION OF THEIR FUNCTIONS WOULD BE IMPORTANT. SO WHAT ARE THE URGENT QUESTIONS? WE FELT THAT THE MOST URGENT QUESTION WHICH EMERGED IN BOTH OF OUR DISCUSSION GROUPS WAS WHAT IS THE NORMAL PROTEOME AND METABALOME OVER GESTATION. WE ALSO THOUGHT IT WAS URGENT, THIS GOES ALONG WITH THE ANNOUNCEMENT THAT WAS DISCUSSED AT THE BEGINNING OF THE CONFERENCE THIS MORNING, HUMAN OMICS ATLAS OF THE PLACENTA AND ALL THE CELL TYPES. WE E REALLY DON'T KNOW ENOUGH ABOUT NORMAL, IN COULD BE IN THE SAME VEIN AS THE FIRST BULLET POINT BEING COMPILED OVER GESTATION. AND HIGHER ORDER DATA SUCH AS PROTEIN FRAGMENTS PTMs AND PROTEIN PROTEIN INTERACTION AND THE EQUIVALENT OF METABOLITES IN WHICH THEY'RE ASSEMBLED TO THE PATHWAYS WE USED TO BE ALL FAMILIAR WITH AND EXPANDING EXPONENTIALLY. FETAL SEX IS ALSO VERY IMPORTANT. WE KNOW NOW THAT THERE'S SEX DIFFERENCES, BETTER CULTURE MODELS IN THE PLACENTA AND CLINICAL OUTCOMES BEYOND DELIVERY. I THINK ONE OF THE THINGS THAT POPS UP IN EVERYBODY'S GRANT REVIEW ARE ALWAYS POWER ANALYSES WHICH ARE SUPER CHALLENGING FOR EVERYONE, HOW DO WE POWER STUDIES CORRECTLY. THANK YOU FOR YOUR ATTENTION. [APPLAUSE] >> SO NOW IT'S OPEN FOR COMMENT, QUESTIONS, DISCUSSION, PLEASE USE THE MICROPHONE. >> I'M (INDISCERNIBLE) FROM (INAUDIBLE) UNIVERSITY. ONE OF THE PROBLEMS IS WHEN WE TAKE MEASUREMENTS A LOT OF TIME IT'S COMPLICATED BY WHAT A WOMAN EAT, HER METABOLIC CONDITION AND OTHER DISEASES HOW DO WE (INAUDIBLE) THAT OUT. WHEN YOU TALK ABOUT OTHER SYSTEM I FEEL LIKE WITH WE ARE TAKING BIOLOGICAL SAMPLES, WE'RE DEALING WITH A MIXTURE OF WHAT IS (INAUDIBLE) STILL CONDITIONS IN ONE OR TWO TYPE OF CELL AND HOW THEY RESPOND TO PREGNANCY. HOW DO WE SOLVE THAT IS MY QUESTION. >> COMMENT ON THAT. WE ARE USING VAGINAL SWABS ACTUALLY TO COLLECT FETAL CELLS FROM THE FETAL CELL, IN THE LOWER CERVIX. THEY ARE ACCUMULATING WITH MATERNAL CELLS IN A A -- APPROXIMATELY (INAUDIBLE) CELLS SO WHAT WE DO, THE GUY OVER THERE DEVELOPS TECHNOLOGY RECENTLY TO HIGHLY PURIFY THOSE CELLS IN CERVIX USING MAGNETIC BEAD SEPARATION NORMAL CELLS ARE THERE. THE TECHNICAL DIFFICULTY WAS TO GET THOSE CELLS (INAUDIBLE) WE ACHIEVEED THAT RECENTLY, WE HAVE 90 TO 95% PURITY OF CELLS, WE ARE EDUCATING CELLS. WE INVITE YOU DESCRIBE THE ABILITY OVER GESTATION (INAUDIBLE) I THINK IT FITS VERY NICELY WITH THE IDEAS AND WHAT WE WANT TO ACHIEVE WITH THE PLACENTA PROJECT. >> THERE'S A A LOT OF DISCUSSION ABILITY THIS TOPIC OF GETTING FETAL CELLS OR PLACENTAL CELLS BECAUSE WE CAN IDENTIFY THEM AS PLACENTAL BY SPECIFIC MARKERS AND THE MORE WE LEARN ABOUT THE PLACENTAL ATLAS WE CAN IDENTIFY SPECIFIC MARKERS ASSOCIATED WITH PLACENTAL CELLS COLLECT THEM, AND I THINK WE HEARD FROM A THOUSAND PLACENTAL CELLS CAN BE FOUND AND CALLED OUT AFTER SAMPLE FROM A CERVIX, YOU CAN DO THIS AT DIFFERENT TIME POINTS AND THE PROTEOMIC METHODS ARE ARE SENSITIVE ENOUGH TO LOOK AT THAT LOW NUMBER OF CELLS AND GET HUNDREDS OF END POINTS. SO WE THOUGHT IT WAS AN EXCITING WAY TO NON-INVASIVELY MONITOR LONGITUDINALLY OVER TIME WHAT'S HAPPENING IN THE PLACENTA. >> JEFF MURRAY, GATES -- AM I ON? JUSTIFY MURRAY GATES FOUNDATION, THANK YOU FOR HIGHLIGHTING THE IMPORTANCE OF DATA SHARING, BUT STRONGLY ARGUE THAT IT SHOULD BE IN THE HARD TO OVERCOME RATHER THAN THE EASY TO OVERCOME FILE, I THINK MANY PEOPLE HAVE STRUGGLED WITH THIS ISSUE, THERE ARE ENORMOUS ISSUES SURROUNDING WHAT IS THE CENTRAL SUPPORT FOR IT, THE METADATA THAT NEEDS TO BE ASSOCIATED, HOW IT'S STORED, HOW IT'S ACCESSED, WHO SCHMITZ IT, WHO MAINTAINS IT, WHO MANAGES IT AND I'M SURE MANY OF THE OTHER SPEAKERS TO COME WILL HIGHLIGHT THE IMPORTANCE BUT IT'S ABSOLUTELY CRITICAL TO THE SUCCESS OF THIS PROJECT AND NEEDS TO BE A PROMINENT FEATURE FROM THE GET GO. >> I THINK IF YOU GO BACK AND LOOK AT THE SLIDE THAT SOME PLACES THAT SHOWED UP IS EASY AND SOME PLACES THAT SHOWED UP IS DIFFICULT. I THINK THAT'S A REFLECTION AND EASY TO GET SOME PEOPLE -- JUST SHARE SOME KIND OF DATA. AS YOU SAID, EVEN IF THERE'S WILLINGNESS TO SHARE DATA, SOMETIMES THE FILES DON'T EVEN COALESCE OR TALK TO EACH OTHER, MAKING IT TECHNICALLY IMPOSSIBLE TO SHARE DATA SO IT'S A HUGE CHALLENGE. A LOT OF DATA ALREADY IS MAPPEDTORALLY PLACED WITHIN REPOSITORYIES. AT LEAST AS A FIRST STEP IN HOW TO COALESCE INFORMATION FROM DIFFERENT OMICS WHERE AT THE VERY MINIMUM YOU AT LEAST HAVE THE SAME GENE NAMES CAN BE DONE. BUT IT REQUIRES LEADERSHIP AN REQUIRES CENTRAL LEADERSHIP. AS TO THE ISSUE OF WHETHER OR NOT YOU CAN DEVELOP A GLOBAL ATLAS METABALOMICS PROTEOMICS FROM ABSOLUTELY NORMAL HEALTHY PREGNANCIES THAT WERE SERIALLY SAMPLED WITH HIGH-QUALITY CLINICAL DATA, THAT RESOURCE EXISTS WITHIN THE NIH NOW. THE STUDY WAS CALLED NEW MOMS TO BE. IF THE NIH REALLY WISHES TO PUSH THE COLLABORATIVE GROUP INTELLECTUAL PROPERTY, THAT SETS A BASELINE FOR FUTURE STUDIES TO LOOK FOR ABNORMALITIES DEFINE THE NORMAL FIRST, I WOULD SUGGEST THAT YOU NEED A NEW MECHANISM, YOU NEED THE BEST BIOINFORMATICS PEOPLE ATTENDING THIS MEETING, MAYBE A COUPLE OF LEADERS FROM THE CENTERS THAT COLLECT THE DATA ALTHOUGH THE COLLECTION IS LARGELY A CLINICAL FUNCTION. THE ANALYSIS SHOULD BE CENTRALIZED, IT SHOULD BE AGREED UPON WHAT PLATFORM WOULD BE USED. TO ESTABLISH A BASELINE FOR THE HPP. THAT WOULD BE THE MOST EFFICIENT WAY TO DO THIS. >> WE CERTAINLY ARE ADVOCATING GOING OUT AND GETTING A BUNCH MORE SAMPLES THAT EXIST, FOR SURE NOT BUT THERE ARE LOTS OF CREDIBLY VALUABLE SAMPLES THAT DON'T EXIST YET SO IT WOULD BE HARD TO ARGUE THAT WE WANT TO PUT RESOURCES INTO REPLICATING WHAT WE ALREADY HAVE ARE. THERE'S SO MANY VALUABLE SAMPLES THAT WE NEED. I COULDN'T AGREE MORE, ON THE DATA ANALYSIS. MY GROUP FOR EXAMPLE PUT TOGETHER THE LEAD AND PUTTING TO THE HUMAN PROTEOME WHICH SOUNDS LIKE REALLY SIMPLE PROJECT. IN THE END WE HAD 300 TO 1,000 PROTEIN DECEMBER PENDING ON HOW YOU COUNTED THEM,. IT TOOK US A YEAR TO STRAIGHTEN OUT THE SPECK TRAM PROTEIN NAMES, JUST BECAUSE THE BIOINFORMATICS DOESN'T EXIST. EVEN THINGS THAT SOUND SIMPLE IF YOU GET THE RIGHT ADVICE FROM PEOPLE HAVE DONE IT, IT UNRAVELS INTO UNBELIEVABLE COMPLEX THETY. >> I'M CURIOUS THE QUESTION TOW WHO INTEGRATE IMAGING AND OMICS DATA. >> THERE'S DISCUSSION ABOUT THE IMPORTANCE OF DOING THAT, PARTICULARLY WHEN YOU HAVE A ULTRASOUND IMAGE FINDING THAT YOU'RE UNSURE OF, SUSPICIOUS FINDING OF A CHANGE, IF YOU COMBINE THAT WITH OMIC MARKER IN THE SAME PATIENT YOU MIGHT HAVE A HIGHER SPECIFICITY FOR DIAGNOSIS, AND INCREASE THE SPECIFICITY ON BOTH SIDES FOR THE BIOMARKER AS WELL AS IMAGING. BUT WE DID NOT DISCUSS HOW EXACTLY YOU WOULD MARY THOSE -- MARRY THOSE TWO OTHER THAN CORRELATION ANALYSIS. WE EMPHASIZE IN TERMS OF DATA ANALYSIS IN OUR DISCUSSION GROUP OVER AND OVER AGAIN, YOU DON'T WANT TO HAVE MEAN DIFFERENCES IN GROUP AND DO A T TEST, YOU WANT TO HAVE A ROCK CURVE SENSITIVITY AND SPECIFICITY FOR INDIVIDUAL PATIENTS, PARTICULARLY USING A PANEL OF MARKERS, YOU LOOK AT MORE THAN ONE MARKER GOING UP OR DOWN AS A REPRESENTATIVE OF A DISEASE STATE OR AS A RISK FACTOR THAT THEN CORRELATE WITH IMAGING. BUT EXACTLY HOW YOU WOULD COMBINE THE IMAGING WITH THE OMICS IS A REALLY IMPORTANT QUESTION. >> FIRST GLANCE OPPORTUNITIES WOULD BE TO IMPROVE THE SPECIFICITY OF IMAGING BECAME MORE MOLECULAR SPECIFIC PROTEOMICS IN GENERAL BECAME MORE SPATIALLY SPECIFIC PERHAPS MEET IN THE MIDDLE, THE OTHER IS TO DO SIGNIFICANT DATA REDUCTION IDENTIFY KEY VARIABLES IN EACH THAT COULD CORRELATE. >> RICH MILLER ROCHESTER. QUESTION FOR SUSAN PERHAPS KJERSTI AS WELL. I WOULD LIKE FOLLOW UP ON STAY''S COMMENT. WHAT DO WE HAVE IN THE NCS AND BIOPOSETORY TO IDENTIFY THE OVER 5,000 SUBJECTS COLLECTED, ONE MAY HAVE ADDITIONAL STORED SPECIMENS THAT MIGHT BE AFLIED LOOKING AT THESE OMICS QUESTION, ESPECIALLY WITH THE FOLLOW-UP OF THE CLINICAL DATA, I WAS LOOKING HERE FOR GIACOMO, I DIDN'T SEE HIM. BUT HE MAY HAVE A A THOUGHT OR ALAN OR OTHERS. BUT I SHARE THAT WITH SUSAN AND KJERSTI. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed >> YEAH, RICH, I KNOW WE TALKED ABOUT THIS BEFORE AND IT IS SUCH A GREAT RESOURCE THAT IT COULD BE LEVERAGED TO SUCH GREAT BENEFIT BY THE HPP. >> U.S. TO ECHO THAT IN THE DISCUSSION OF METABOLITES ONE THING THAT'S IMPORTANT TO REMEMBER IS WE GROUPING ALL METABOLITES OR HUMAN BACTERIAL METABOLITES? THOSE ARE DIFFERENT REFERENCE LIBRARIES, SLIGHTLY DIFFERENT TECHNIQUE CAN BE USED SO THINKING THROUGH METABOLITE WHAT DO WE MEAN? WHAT BECOMES IMPORTANT WE HAVE SPECIMENS THAT WE CAN ACCESS EXPAND THE DEPTHS OF METABOLITE AND HOW DO WE TRACE BACK TO THE SOURCE COMING FROM THE MOM, FETUS, THE META GENOME? WHAT IS IT COMING FROM? THOSE ARE CRITICALLY IMPORTANT QUESTIONS MOVING FORWARD. AND YOU'RE ABSOLUTELY CORRECT, WHAT DO WE HAVE (INAUDIBLE) AND HOW DO WE AVOID DUPLICATING AN REINVENTING THE WHEEL? >> BRIAN COX CAN UNIVERSITY OF TORONTO. I DON'T KNOW -- I DON'T THINK ANYONE HERE CAN ADDRESS THIS ASIDE FROM MEMBERS FROM THE NIH THEMSELVES BUT I FINE IT IRONIC WITH WE HAVE SECTIONS DISCUSSING PROTEOMICS WHEN HIPPOCANCELLED THE PEPTIDE READ ARCHIVE, WITH THE SHORT READ ARCHIVE AND GEOREPOSITORY FOR ARRAY DATA SO THEY STARTED TO COLLECT DATA IN THERE, TO THAT REPOSITORY AND SIX MONTHS LATER GOT AN EMAIL TO SAY IT WAS CANCELED DUE TO BUDGET CUTS. THOSE RESOURCES THAT YOU HAVE MAINTAINED LIKE GEO AND SHORT DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed READ ARCHIVE ARE INVALUABLE IN KEEPING THAT THERE. AND ANOTHER CONCERN I HAVE IS AS A FOREIGNER, WHEN YOU RUN UP AGAINST FUNDING CEILINGS AND YOU THREATEN TO REMOVE THE LARGE RESOURCE THAT THE BIOINFORMATIC RESOURCE AND INFORMATION RESOURCE IT HAD, I DON'T SEE ANOTHER GLOBALLY MIRRORED SITES OF GEOREPOSITORY, THERE'S ARRAY EXPRESSED IN EUROPE, THE SHORT READ ARCHIVES IN PUBMED AND OTHER RESOURCES, I THINK THERE NEEDS TO BE A BETTER GLOBAL RESOURCE OF THESE INFORMATICS SOURCES SO THAT WE DON'T LOSE IT AND MAYBE THEN SORT OF SPREAD THE COSTS AROUND. BECAUSE I CAN'T BELIEVE THE AMERICANS ARE SO GENEROUS TO MAINTAIN THIS MASSIVE INFRASTRUCTURE THAT THE ENTIRE WORLD USES AND IT REALLY NEEDS TO BE A MORE GLOBAL EFFORT. >> I THINK I KNOW THAT YOU'RE WELL AWARE, BRIAN, I THINK FOR THE FIRST TIME I HAVE BEEN IN MASS SPECTROMETRY FOR OVER 30 YEARS AND FOR THE FIRST TIME PEOPLE ARE TALKING ABOUT THROWING AWAY DATA. IT'S BECAUSE YOU CAN -- LIKE EVERY OTHER PLATFORM BUT PERHAPS EXPONENTIALLY LARGER, THE FILES THAT ARE GENERATED IN MASS SPECTROMETERS NOW, WE WANT TO SAVE OUR DATA, THEY'RE PHENOMENALLY IMPORTANT LIBRARIES BUT WHERE ARE WE GOING TO PUT IT? AND FOR THE MOST PART THIS IS ON THE INDIVIDUAL HERE. IT'S A HUGE ISSUE FOR US, THERE'S SOME RESOURCES LIKE TRANCHE AT THE UNIVERSITY OF MICHIGAN BUT THERE ARE -- IT FEELS LIKE TRANCHE HAS ONE FOOT ON AND -- DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed >> ROCHESTER. THIS QUESTIONS GOES MORE TO EVERYBODY HEAR MORE ABOUT LATER. TRANSCRIPTOMEICS, PROTEOMICS,OMICS, GETTING ENOUGH EVERYTHING IN ONE PLACENTA, MANY PLATFORMS REQUIRE PRESENTATION OF THE TISSUE IN DIFFERENT WAY, THERE'S NOT A ONE SIZE FIT ALL THING. WITH THE PROJECT 18 STUDY, ET CETERA. STUDY DESIGN ACROSS MULTIPLE TIME POINTS FOR ALL OF THESE WILL BE MORE POWERFUL THAN A GROUP HERE THAT GOT X AND GROUP HERE THAT GOT Y AND TRY AN CORRELATE THOSE TOGETHER WITH DIFFERENCE PHENOTYPIC OUTCOMES AT THE END. >> I MENTION IN MY PRESENTATION OUT THERE THAT PRESERVE ALL THE CATEGORIES AND MOLECULES INCLUDING POST TRANSLATIONAL MODIFICATION AND THE HISTOLOGY OF THE TISSUE, DEVELOPED UNDER NIH FUNDING. THEY ALSO ALLOW FOR VERY FINELY DETAILED LASER INFRARED MICRODISSECTION, IT DOESN'T DAMAGE THE TISSUE, IT PRESERVES ENZYMATIC FUNCTION. SO IT'S POSSIBLE NOW TO TAKE THAT ADVANCE AND APPLY IT TO THE PLACENTA IN A WAY THAT'S NEVER BEEN BEFORE POSSIBLE FOR BOTH LOOKING AT GENOMICS AND PROTEOMICS IN THE SAME MICROENVIRONMENT SPACE OF THE PLACENTA SAMPLES. ON THE OTHER HAND WHEN WE DISCUSS THIS AT OUR GROUP MEETING, ONE POINT WAS THAT THE PLACENTA AT THE END ALL ALONG THE WAY. WHAT WE LOOK ATLANTA THE END MAY HAVE NOTHING TO DO WITH WHAT'S EARLY ON. NEVERTHELESS THERE ARE SOME DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed REALLY EXCITING NEW TECHNOLOGIES ADVANCES FOR LOOK AT TISSUE THAT DIDN'T EXIST A COUPLE OF YEARS AGO. >> JUST TO ADD ON TO THAT, ONE OF THE THINGS THAT I REALLY BENEFITED PROJECT MEETING THE CLINICAL TEAM ON IT GENERATING 300 HARD CORE REFERENCE META GENOMES MULTIPLE P BODY SITES, ALL PUBLISHED. WE USE CLINICAL CRITERIA TO ENROLL SAMPLE, ET CETERA AND WE WERE EXTREMELY RIGOROUS ABOUT WHAT WE CALLED REFERENCE. AND THEN WE HAD A NUMBER OF DEMONSTRATION PROJECTS THAT $170 MILLION, ABOUT 16 MILLION SO WHEN YOU'RE TALKING ABOUT EARLIER ABOUT WHAT DO YOU DO FUNDING COMPUTATIONAL TOOLS THE AGREEMENT WAS ALL THOSE TOOLS WOULD BE CROWD SOURCED AND TO THIS DAY THE THINGS WE USE FOR MICROBIOME RESEARCH FUNDED BY THE HMP ARE CROWD SOURCE TOOLS FREE AND PUBLICLY AVAILABLE. WHEN WE HAVE THAT REFERENCE COHORT, THAT HARD CORE WE LITERALLY HAD TWO PHYSICIANS SAMPLING EVERY ONE OF THOSE 300 SUBJECTS SO WE HAD MINIMAL VARIABLE, WE HAD STANDARDS SOPs WERE ONLY ALLOWED TO USE VERY CERTAIN SOAPS AND SHAMPOOS AND WE NORMALIZED EVERYTHING WE COULD AND THEN USE THE DEMONSTRATION PROJECTS, AS WAY TO DIVE INTO THE MEDICINE IN BIOLOGY. WHERE THEY REPLICATED HARD CORE THAT'S PART OF WHAT YOU GET AT, HOW DO WE WITH CREATE THAT REFERENCE AND COMPARE EVERYTHING TO IT? DR. GUTS MAKER TALKED EXPERIENCE IN THE HUMAN GENOME PROJECT, WITH PEOPLE THAT WE USED PROCESS AND WE LOOK AT WHERE WE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed DEPOSITED THAT BECAUSE WE DID HAVE CLINICAL METADATA, THINGS THAT WERE POTENTIALLY IDENTIFIED, HAVE TO GO BACK TO DB GAP. ANYBODY THAT USED DB GAP, IS AN INTEREST PROCESS, AND YOU HAVE A A LOT OF DONE DOING IT, IT'S A VERY SECURE WAY AND WE WHEN BACK AND CARRIED OUR PATIENTS, OUR SUBJECTS, HOW DID YOU FEEL IF WE TOLD YOU IT WAS SECURE AND WE GUARANTEED IT'S SECURE. THEY FELT GOOD ABOUT PARTICIPATING IN A PROJECT, THEY DIDN'T CARE AS MUCH ABOUT HOW EASY WAS IT FOR PEOPLE TO MOVE DATA FROM ONE LAB TO THE NEXT. THEY CARED ABOUT THE FACT THAT THEIR DAYTIME AND INFORMATION WAS SECURE BUT WE HAVE TO TAKE INTO ACCOUNT SOME OF OUR PATIENT PREFERENCES. AS WE'RE THINKING THROUGH HOW WE SHARE DATA AND HOW WE DEPOSIT IT BACK. >> THIS MAY APPLY WHAT ARE ARE WE DOING WITH PROTEOMICS? WHAT ANALYSIS ARE WE GOING TO DO? JUST GET THE PROTEOMICS ANALYSIS, WITH THE DATA THAT WE ALREADY HAVE AT THE QUESTION AND CONCERN EVERYONE HAD IS THAT THE CONVECTIONAL PROTEOMICS IN THE PAST IS NOT SENSITIVE ENOUGH AND EVEN IS LOOK THE SAME HIGH ABUNDANCE PROTEINS, WE CAN NOW SAY THAT IN THE FUTURE WE CAN LOOK AT MUCH MORE LOWER ABUNDANCE PROTEINS AND REALLY GET INTO THE IMPORTANT PROTEINS INVOLVED IN CELL SIGNALING THAT WE COULDN'T SEE BEFORE. RATHER THAN LOOKING AT INDIVIDUAL PROTEINS OR DO CORRELATION WE CAN SEE UPSTREAM AND DOWNSTREAM ACTIVATED AND THAT GIVES US AN IDEA OF THE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WHOLE PATHWAY. THERE WAS A GOODIES CUSHION ABOUT JUST DOING FISHING EXPEDITIONS LOOKING FOR SURVEYS OF PROTEINS WE NEED TO DO HYPOTHESIS-H BASED COMBINE THAT WITH HYPOTHESIS BASE LOOK AT SPECIFIC CLASSES OF PROTEINS INVOLVED IN WHAT WE THINK ARE IMMUNE REGULATION OR HYPOXIA MUCH MOVE SENSITIVE LEVEL THAN BEFORE SO I THINK THAT'S A VERY GOOD POINT. WE TALKED ABOUT MOVING IN TERMS OF THE ATLAS OF THE PLACENTA, NOT JUST A GROUND-UP PLACENTA PROTEOME OR GENOME BUT DOING AN ANTIBODY ATLAS, THERE SAN ANTIBODYPEDIA, IT'S A CONSORTIUM OF ANTIBODIES THAT WAS SUPPORTED BY A A GENEROUS DONOR WHERE THEY DID A ANTIBODY PROTEOME MAP OF THE ALL BODY TISSUES THOUSANDS OF VALIDATED ANTIBODIES IN DIFFERENT EPITOPES OF PROTEIN EXIST THAT APPLY TO THE DIFFERENT CELLS IN THE PLACENTA. AND PERHAPS IN A DIFFERENT DISEASE CONDITIONS I THINK THAT WOULD BE AT LEAST GOING IN THE DIRECTION OF MORE FUNCTIONAL PRO YOM AT THE ANTIBODY IMAGING LEVEL. >> WE HAVE TIME FOR THE LAST TWO SPEAKERS TO ASK QUESTIONS. >> (INAUDIBLE) THE RESEARCH INSTITUTE. NATIONWIDE CHILDREN'S HOSPITAL. SO ONE OF THE ISSUES THAT I HAVE BEEN FACING, SO I WORK IN PROTEOMICS DATA ANALYSIS WISE, THE METHODS EXIST TO DO COMPLEX DATA ANALYSIS THAT HASN'T BEEN ACTUALLY DONE BEFORE, BUT THEY ARE IN THE HANDS OF MATHEMATICIANS, COMPUTATIONAL BIOLOGISTS, I'M FORTUNATE BECAUSE THE RESEARCH INSTITUTE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed HAS THE RESULTS INSTITUTE OF MATHEMATICAL MEDICINE. BUT WE NEED POST-DOCS POST-DOCTORAL FELLOWS THAT NEED TO BE TRAINED BETWEEN US AND THEM. IT NEEDS A MIND SET AND TIME. I DON'T HAVE TIME, THEY DON'T HAVE TIME. TO SIT DOWN AND TEACH OURSELVES NOTIONS THAT WE -- I SHOULD HAVE LEARNED IN GRADUATE SCHOOL AND THEY SHOULD HAVE LEARNED IN MEDICAL SCHOOL. SO WE NEED POST-DOCTORAL POSITIONS, A LOT OF THESE EXPERTISE IS EXISTING IN EUROPE. I HAVE SEVERAL PEOPLE I WORK WITH WHO ARE IN EUROPE AND I HAVE BEEN SEARCHING FOR FELLOWSHIPS THAT WE COULD BRING SOME PEOPLE IN THAT THEY COULD WORK FOR THREE OR FOUR YEARS. THESE ARE SOME IDEAS THAT I FELT VERY IMPORTANT. >> (INAUDIBLE) UNIVERSITY OF WISCONSIN MADISON. (INAUDIBLE) MADE COMMENT OF THIS, WE HAD A BIG DISCUSSION ABILITY THE IMAGING AND THE TRANSCRIPTOMEICS OR THE OMICS. ONE THING THAT CAME UP WAS WHEN WE SORT YOU HAVE OMICS DATA WE'RE TREATING -- MY TABLE ALONE, WE MAYBE A MINORITY, NO OFFENSE BUT EVEN IN MY OWN WORK WHEN YOU SCREEN LARGE AMOUNTS OF INFORMATION WE SEPARATE ACCORDING TO CLINICAL DIAGNOSIS SO OUR CLINICIANS ARE REALLY IMPORTANT BUT SAMPLES ARE COLLECTED AHEAD OF TIME. IF YOU LOOK AT THE IMAGING AND THE CLINICAL DIAGNOSIS AS THE IMPORTANT COMPONENT, AND EITHER HAVE DATA OR SAMPLES STORED AND ANALYZED OR DO IT WITHIN A LARGE GROUP, IT'S A CAN SOURCE YUM OF GROUPS, SAMPLES TO LANCE OR -- DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THEN WE CAN SORT OUR DATA ACCORDING TO WHAT'S ACTUALLY OCCURRING IN TERMS OF IMAGING DATA SO YOU HAVE FORM AND FUNCTION WHICH WE LEARNED A ABOUT IN GRADUATE SCHOOL OR MEDICAL SCHOOL. WE FEEL TRUE FUNCTIONALITY IF YOU CONSIDER THE REDISTRIBUTION OF BLOOD FLOW. THEN THE IMAGING POTENTIALLY OF OXYGEN OR CALCIFICATION OR THE THICKNESS OF THE -- AS YOU MENTION YESTERDAY, THE THICKNESS OF PLACENTA. SO IN TERMS OF ORGANIZING THE INFORMATION I THINK IF IMAGING COLLEAGUES CAN PUT US IN A PLACE WE CAN ACTUALLY LOOK AT THE FUNCTION OF THE PLACENTA, AND THE UTERUS AND WHAT'S GOING ON AND BEGIN TO SORT OUR DATA RELATIVE TO THESE IMPORTANT PATHWAYS WE TALKED ABOUT, IT SOUNDS LIKE THE OMICS IS TAKING A BACKSEAT BUT IT'S NOT. IT'S SAYING HOW ARE WE GOING TO LOOK AT OUR DATA SETS. SO YOU CAN DO ALL THE DATA SETS UP ON A COMPUTER, I LOVE THAT INFORMATION. I LOVE THAT. UNLESS YOU KNOW WHAT ACTUALLY HAPPENED TO THAT PARTICULAR PATIENT. IT'S GOING TO BE HARD TO GENERATE HYPOTHESIS THAT IT'S LAND SET, HYPOTHESIS GENERATING EXPERIMENTS. >> >> THIS IS A VERY IMPORTANT POINT. THE STRUGGLE HAS ALWAYS BEEN ON TWO ASPECTS, FIRST I DON'T THINK WE DEFINE WELL ENOUGH WHAT THE NORMAL RANGE OF WHAT WE SEE ON IMAGING. WHAT WE SEE IN THE POPULATION IN OUR STUDY SO THE DATA IS DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SCATTERED AND THE RANGE HAS BEEN FAIRLY WIDE. AND THAT CERTAINLY IS VERY IMPORTANT PROCESS THAT NEEDS TO BE ESTABLISHED. THE SECOND ASPECT UNTIL RECENTLY IMAGING HAS NOT BEEN VERY SPECIFIC WITH REGARD TO WHAT WE SEE WE'RE THE TIP OF THE ICEBERG WHAT WE SEE AND THE INFORMATION THAT IMAGING PROVIDES MAY NOT REFLECT SPECIFICALLY THE TOPOLOGY. NORMAL USE MORE ADVANCE IMAGING TECHNIQUES, MAYBE ABLE TO PROVIDE DATA THAT SHORE SPECIFIC TO WHAT WE DO ON THE OMI CCS SIDE. >> SO I THOUGHT THIS WAS A GREAT START TO THE MORNING. I APPRECIATE IT AND I HAVE A FEELING WITH WE'RE GOING TO HEAR A LOT OF THESE REPEATED. SO WE'RE GOING TO MOVE ON TO GENOMICS. ACTUALLY I HAVE -- OHIO DOES IT MATTER? SO I THINK WE'RE GOING TO MOVE THROUGH KIND OF QUICKLY, PICK UP A COUPLE OF THINGS THAT CAME UP IN OUR GENERAL DISCUSSION IN CROSS CUTTING SCENES, THAT UNIQUE TO THE GENOMICS AND SOME REALLY INTERESTING PERCOLATED IDEAS, WE JUST HAD A GREAT INTELLECTUAL DISCUSSION, IT WAS SUCH A TREAT. SO THAT ONE THING THAT CAME UP OUT OF OUR GROUP THAT WAS A REQUEST FOR CLARIFICATION AND ALSO A HOPE TO BETTER UNDERSTAND HUMAN PLACENTAL PROJECT AND WHERE ARE THE TRANSINSTITUTIONAL COMPONENTS AND WHERE ARE THE GLOBAL COMPONENTS TO IT? AND WOULD THAT BE SOMETHING TO ENHANCE OUT BOTH THE SCOPE AND THE TRANSDISMR. NARY CONNECTIONS ONE THING THAT CAME UP TO DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed REITERATE, SAID IN METABALOMICS BUT A DIFFERENT SCENE IS AROUND COMPUTATIONAL TOOLS SO WE CONCUR WITH THE PROTEOMICS METABALOMICS GROUP WE GOT REFERENCE REFERENCE REFERENCE NEEDS, WE HAVE ATLAS ATLAS ATLAS NEEDS, TOOLS TOOLS TOOLS NEEDS. BUT WHAT -- ONE OF THE CONCERNS IS AS YOU START TO DECONVOLUTE THE DIFFERENT TYPES, HOW MUCH RICHNESS OF THAT DATA AND CONTOUR DO YOU LOSE? THAT'S BECOMES A VERY IMPORTANT CONSIDERATION THINKING TOOL DEVELOPMENT, HOW TO NOT LOSE THE IMPORTANCE OF VERY FINE -- TO THE IMAGING DATA. METABALOMICS IT'S FUN TO SEE FOLKS COME DOWN ON EITHER SIDE OF THE ISSUE. AND BASICALLY THERE'S A PROBLEM THAT WE CAN'T SAMPLES PLACENTA IN LARGE APPRECIABLE AMOUNTS ACROSS THE LONGITUDINAL NATURE OF A GIVEN PREGNANCY. AND SO DO WE NEED ANIMAL MODELS TO ENABLE US TO DO WHAT WE CAN'T DO IN HUMANS SAFELY? AND IF WE DO ENTERTAIN ANIMAL MODELS, WHICH ONE? DO WE LIMIT CHORION PLACENTAL MAMMALS? NON-HUMAN PRIMATE? WHICH BRANCH OF NON-HUMAN PRIMATE? DO WE LOOK FOR A COMMON SET OF REGULATOR, ACROSS ALL PLACENTAL (INAUDIBLE) AND SEE WHAT ARISES FROM THAT, SO IT WAS A FUN DISCUSSION AROUND IT. DO WE LIMIT TO GENETICALLY MANIPULABLE, TECHNOLOGY TO EXPAND THE GENETIC MANIPULATION OTHER ANIMALS AND WHAT ARE THE IMPLICATIONS OF THAT. IT'S BEEN DISCUSSED AT THE APPROPRIATE SAMPLES AND I'M GOING TO TELL YOU WE'RE COMING BACK TO THIS. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WE HAD A REALLY FUN DISCUSSION WHAT IS THE MATERNAL GENOME AND WHAT IS THE PATERNAL GERM LINE THAT ACTUALLY APPEARS OUT IN THE PLACENTA. SO ONE OF THE THINGS THAT AROSE FROM OUR GROUP WAS THE CIRCULATING PERIPHERAL GENOME, IF WE DRAW BLOOD FROM THE DAD IS THAT GOING FROM THAT PLACENTA AND THE FETUS? CONSIDER YOU HAVE TO HAVE SOME LEVEL OF NORMAL PATERNAL CRINGES TO HAVE A NORMAL PLACENTA. BACKS REALLY INTERESTING QUESTION, SHOULD WE BE RUNNING AROUND DOING ANALYSIS? WE'RE GOING TO ASK A QUESTION ABOUT THE PATERNAL COMPONENT, PATERNAL GERM LINE TO ENABLE DOING THAT. AGAIN, I'M NOT GOING TO REITERATE SPECIFICITY. SO OUR GROUP DIVIDED OUT TO INDIVIDUAL QUESTIONS AND WE HAD FUN DISCUSSION AROUND THAT. SO AGAIN, I WANT TO HIGHLIGHT THE THINGS THAT ARE A LITTLE BIT DIFFERENT. FIRST IS THERE COULD BE A FRAMEWORK OF LONGITUDINAL TIMING THAT MIGHT REVEAL POTENTIAL GAPS, INSTEAD OF THINKING MUTATION OF BEING FROM IMPLANTATION DO WE THINK ABOUT IT BEING IN THIS PERICONCEPTION TO PRE-IMPLANTATION WINDOW AS WELSHING IF WE DO DO WE HAVE TO THINK ABOUT ALTERNATE WAYS WHAT GOES ON IN THAT WINDOW, LEADING TO SAMPLE AROUND IPS EMBRYOS. IF WE WITH THINK ABOUT THE SAMPLING, WHO DO WE MISS? ARE WE THEN GOING TO ONLY END UP WITH A PRIVATE INSURANCE OLDER POPULATION OUTSIDE REPUCKTIVE AGE POPULATION? ARE WE GOING TO MISS RACE, ETHNICITY GROUPS WHAT'S GOING TO HAPPEN IF WE START DEVELOPING DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THE DITCH TECHNOLOGIES AND LOOK FOR DIFFERENT WAYS TO DO IT. AND AS WE DISCUSS, THERE'S MISSING COMPONENTS AND CURRENT OPPORTUNITIES FOR PLACENTAL GENOMEE AND EPIGENOMICS TECHNOLOGY. ONE THING THAT PERCOLATED UP IS ISSUE AROUND PATERNAL GENOME AND EPIGENOME IN THE PERIPHERY, IS THAT REPRESENTATIVE OF WHAT MAKES IT TO THAT FETUS AND PLACENTA? I WANT TO BUILD THE DISCUSSION AROUND BANKING, SO OUR GROUP HAS AN INTERESTINGED AROUND SUPERBANKS. RATHER THAN REINVENT THE WHEEL, WOULD IT BE POSSIBLE FOR INVESTIGATORS TO BASICALLY APPLY TO A SUPER BANK WHERE THEY WOULD HAVE TO PROVE THE QUALITY OF THEIR SAMPLES, THE CLINICAL METADATA THAT'S TIDE TO IT, AND GET PAID BY NIH FOR SAMPLES THEY ALREADY HAVE? SO RATHER THAN SAY WHAT YOU'RE GOING TO DO WITH ALL THIS STUFF COULD WE GENERATE A CONCEPT OF THE SUPER BANK, DEVELOP THE TOOLS TO DISSEMINATE IT, DO THINGS AROUND THAT. AND OUR GROUP ALSO BROUGHT UP THE SEX DIFFERENCES AND CELLULAR HETEROGENEITY. SO WHAT DO WE NEED THAT WE DON'T HAVE WITH OUR INTERPRETATION OF QUESTION TWO. AND THE REALLY KEY THING THAT AROSE THAT WAS A LITTLE BIT DIFFERENT THAT I THOUGHT WAS REALLY CLEVER WAS INFORMATION ON PERINATAL TRAJECTORIES, NOT ONLY WHAT HAPPENS IN THE COURSE OF PREGNANT SIXER NOT ONLY WHAT CAN YOU PREDICT LATER IN LIFE RISK FOR THE OFFSPRING BUT WHAT PREDICT IF YOU USE THE PLACENTA AS A BIOMARKER FOR THE MOM'S HEALTH AND THE DAD'S HEALTH? DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SO IS THERE ANYTHING TO BE HAD BY DOING GENOMIC AND EPIGENOMIC ANALYSES THAT MIGHT TELL US WHAT HAPPENS TO THE PARENTS AND THAT COULD BE ANY NUMBER OF DIFFERENT MODEL CENTERS FOR THE REST OF THEIR LIFE. FEASIBLE AND COST EFFECTIVE SO THE MAIN COST EFFECTIVE DISCUSSION OCCURRING AROUND GENOMICS AND EPIGENOMICS WAS REALLY IS IT BETTER TO LOOK AT 100 PEOPLE 100 TIME OR A THOUSAND PEOPLE TEN TIME? HOW DO YOU MAKE THOSE DELAWARE SIGNATURES OVER POPULATION BASE VERY SMALL COHORTS. THEN THERE WAS CONCERN APT ARE WE POTENTIALLY MISSING A WINDOW OF OPPORTUNITY IF WE DON'T PRIORITIZE BANKING BACK SAMPLES. SO AS WE GO TO LARGER CLINICAL USE, IS THERE A POTENTIAL TO LOSE THIS OPPORTUNITY IN TIME TO HAVE SOME SAMPLES THAT WE COULD BE BANKING BACK FOR FUTURE DISCOVERIES AS THAT GOES AWAY. THERE WAS AN ISSUE AROUND LONGITUDINAL STUDY SPANNING GRANT CYCLES AND COMPLEX OUTCOMES. IN TERMS OF THE OVERALL VALUE OF GENOMICS AND EPIGENOMICS NHPP IT WAS OUR GROUP'S VIEW IT WAS HIGH VALUE AND HIGH SIGNIFICANCE, THERE WERE A NUMBER OF GAPS THAT WERE EVIDENT. IT WAS FELT THAT WHILE THERE ARE THINGS DIFFICULT TO OVERCOME, NOTHING WAS IMPOSSIBLE TO OVERCOME. AND THE MORE WE COLLABORATE TOGETHER AND PEOPLE WHO HAVE INHERENT SENSE OF PLACENTA BIOLOGY, HUMAN BIOLOGY REPRODUCTION AND MA TERM FETAL MEDICINE, THAT REALLY THERE'S A A LOT OF OPPORTUNITY FOR ADVANCEMENT. WE FINALLY BROUGHT UP THIS ISSUE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed OF WHAT WE CALL THE NEXT BIG THING, WE HAVE ALREADY MENTIONED SEVERAL OF THESE. ONE OR FRAMEWORK WE BROUGHT FORWARD WAS HAVING A PWAF, THAT'S SO THAT WOULD BE A PLACENTAL WIDE ASSOCIATION STUDY OR PLACENTAL EPIGENOME WIDE ASSOCIATION STUDY. I DON'T KNOW HOW MUCH OF A STRAIGHT FACE WE CAN USE WE KEEP SAYING PWAF BUT THAT WOULD BE SOMETHING. AND THEN THE PATERNAL GENOMIC MEASURES, AGAIN THAT PERCOLATED UP AS KIND OF AN INTEREST WEIGH TO THINK ABOUT A PROBLEM. >> WE HAD A DIFFERENT DISCUSSION IN YOU ARE GROUP. WE TRIED TO MERGE OUR REPORT BUT IT WENT DIFFERENT DIRECTIONS. I WANT TO POINT OUT I USED PHOTOGRAPHY AS NON-INVASIVE REAL TIME MEASURE OF WHAT HAPPENED IN YOU ARE GROUP. IN OUR GROUP. HERE IS DR. GUTTMACHER LOOKING WITH INTENSE INTEREST WHAT WAS GOING ON IN OUR GROUP. WE SPENT A LOT OF TIME WITH JUST GENERAL DISCUSSION AND CROSS CUTTING THEMES. SO THERE WAS A LOT OF DISCUSSION IN THE BEGINNING ABOUT WHAT DO WE MEAN BY GENOMICS, EPIGENOMICS, AND THEN THERE WAS A LOT OF DISCUSSION THAT INVOLVED HAVING DIRECT ACCESS TO THE PLACENTA. SO WE WERE FORTUNATE WE HAD DR. GUTTMACHER IN THE ROOM, AND ASKED SHOULD WE THINK ABOUT STUDIES THAT INVOLVE HANDLING THE PLACENTA IN SOME WAY. HE SAID NO. I BROUGHT IT UP BECAUSE EVERYBODY SHOULD KNOW THAT, THAT IS NOT THE HUMAN PLACENTA PROJECT. SO THE REAL CHALLENGE IS HOW TO DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed APPLY THESE TECHNOLOGIES, NON-INVASIVELY IN THE CLINIC IN REAL TIME IN VIVO. WE HAVE FOUR SETS OF QUESTIONS AS WELL. WHAT THE STATE OF GENOMICS TECHNOLOGY, WHAT THE GROUP FELL WERE TECHNICAL CHALLENGES, TECHNICAL REPRODUCIBILITY, BUT GENOMICS EPIGENOMICS, DIFFERENT SEQUENCING PLATFORM, DIFFERENT SOFTWARE, THE SYSTEMS DONE TALK TO EACH OTHER SO YOU CAN'T LEVERAGE A LOT OF DATA. BIOINFORMATICS, IT'S A HUGE CHALLENGE AND THERE HASN'T BEEN A SPECIFIC FUNDING ANNOUNCEMENT FOR BIOINFORMATICS RELATED TO THE HUMAN PLACENTA PROJECT BUT IT IS A HUGE NEED. THERE'S NEED FOR STANDARDS, NEED FOR REPRODUCIBILITY. THE SEQUENCING IS RELATIVELY FAST BUT ANALYSIS, STATISTICAL ANALYSIS IS NOT SO IF WE'RE GOING TO DO THIS REAL TIME WE HAVE TO HAVE RESOURCES THAT ALLOW US TO ANALYZE THE DATA QUICKLY AND REPRODUCIBLY AND WE NEED TO REDUCE THE NOISE BECAUSE THERE'S A HUGE NOISE IN THE BACKGROUND. AND ONE OF THE THINGS THAT ALSO CAME UP IN OUR GROUP WAS WOULDN'T IT BE WONFUL IF AN INDIVIDUAL POST DOC COULD ASK A QUESTION AND HAVE RESOURCES AVAILABLE WHERE THEY CAN ASK THE QUESTION AND ESSENTIALLY PLUG AND PLAY THE QUESTION AND HAVE VALIDATED REPRODUCIBLE RESOURCE TO ANALYZE THE DATA AND COME UP WITH AN ANSWERMENT AS FAR AS THE PRACTICAL CHALLENGES ARE CONCERNED, AS OTHER VERSUS SAID, WE REALLY NEED BETTER PHENOTYPING, IS A REAL CHALLENGE TO MERGE THE OMICS DATA WITH THE CLINICAL PHENOTYPING DATA, AND TO DO THAT AS OTHERS HAVE SAID DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WE NEED BETTER DEFINITIONS FOR THE VARIOUS CLINICAL CONDITIONS WE'RE GOING STUDY, AND FOR SAMPLE ELIGIBILITY AND EXCLUSION. WE NEED STANDARDIZED STUDY DESIGNS, I DON'T THINK WHAT I HEARD SO FAR IS A COMPLAINT ABOUT THE IRB BUT CERTAINLY THE IRBs RESTRICT ACCESS TO MATERIAL ESPECIALLY EARLY GESTATION AND PARTICULARLY WITH EITHER PREGNANCY LOSSES, OR GETTING AT WOMEN PRIMARY MEDICAL CARE. A HUGE CHALLENGE IS THAT THE INDIVIDUAL POST-DOC OR INDIVIDUAL PI CAN'T DO THIS MOCKERWORK ANY MORE, THIS WORK HAS TO BE DONE IN MULTI-DISCIPLINARY AND MULTI-SITE TEAMS AS WELL. SO THAT IS SOMETHING WE NEED TO CONSIDER. THE SECOND QUESTION WAS HOW HAVE OMICS BEEN APPLIED TO PLACENTA, SPECIFICALLY WHAT STUDIES HAVE BEEN DONE WITH GENOMICS. WE DISCUSS A LITTLE BIT ABOUT THE FACT THAT YOU HAVE A GENOME FOR LIFE. YOU CAN ACCESS THE FETAL GENOME IN A DIFFERENCE WAY OR NEONATAL GENOME TO CORD BLOOD DO WE NEED THE PLACENTAL GENOME. THERE IS ALREADY INFORMATION AVAILABLE IN OTHER STUDIES GWAS IN PARTICULAR, THE DATA EXIST BUS NEED FURTHER INTERPRETATION FROM THE PLACENTAL PERSPECTIVE. THERE'S ALSO SOME INFORMATION AVAILABLE ON MAJOR HISTOCOMPATIBILITY GENES AND HOW THEY AFFECT YOUR RISK OF PREECLAMPSIA SO MAYBE LOOKING AT HOW DIFFERENT COMBINATIONS OF GENES IN THE PARENTAL GENOTYPES WOULD AFFECT SPECIFIC PLACENTAL DISORDERS. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed AND WE ALSO MENTION THERE MAYBE GENOMIC DATA FROM OTHER SPECIES AVAILABLE THAT MAY INFORM OUR KNOWLEDGE OF THE HUMAN PLACENTA OR MAYBE MORE RELEVANT FOR THE PLACENTA THOSE SPECIES. THERE IS INFORMATION OUT THERE FROM OTHER SPECIES. ARE THERE BIOBANKS LEVERAGED, PLACENTAL BIOBANKS INCLUDING THE GAPS DATABASE FROM THE GATES FOUNDATION. THERE ARE REPOSITORIES WITHIN NICHD, ALAN TOLD US NICHD IS ORGANIZING THE BIOREPOSITORY, STEPHANIE ARCHER, INVALUABLE HELP IN OUR SESSION FROM NICHD MENTIONED THERE'S MATERIALS AVAILABLE IN GENOMICS AND PROTEOMICS NETWORK SPONSORED BY NICHD WITH DATA FROM THE NATIONAL CHILDREN'S STUDY PROJECT 18 ALSO MENTIONED IN OUR GROUP AND WHO DOESN'T WANT TO WORK WITH THE HAWAII PLACENTAL REPOS IR? ISLE GO THERE, I'M FROM BOSTON, NEXT JANUARY, PLEASE. THERE MAYBE INFORMATION AVAILABLE FROM OTHER COUNTRIES. I KNOW THERE ARE REPRESENTATIVES HERE FROM OTHER COUNTRIES AND I HAVE HEARD SPECIFICALLY CHINA, INDIA, I'M SURE THERE ARE OTHERS WHERE IF WE CAN LEVERAGE AN INTERNATIONAL CONSORTIUM, THAT WOULD BE EXTREMELY HELPFUL. AS FAR AS COST, WE ASK THE QUESTION IS THE SEQUENCING OF THE DNA COST HALF OF WHAT IT IS NOW, WOULD THAT CHANGE, HOW YOU USE FOR THE PLACENTA, SOME MENTIONED FOR RESEARCH PURPOSES THAT COST ISN'T IS NOT THE DRIVING FACTOR IN THEIR INSTITUTION WHEN THEY HAVE SEQUENCING DONE FOR RESEARCH PURPOSES. IT'S OBVIOUSLY EXPENSIVE TO DO SEQUENCING EPIGENOMIC SEQUENCING DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THROUGHOUT PREGNANCY, TO BE TRANSLATIONAL, TRULY TRANSLATIONAL IT HAS TO BE FASTER. SO WE NEED ADVANCES IN THAT AREA. ANOTHER ISSUE WHEN YOU GET TO OTHER OMICS IS THE NEED FOR PLACENTAL SPECIFIC ANNOTATION. MOST OF THE TRANSCRIPT OMIC GENE SEQUENCES ARE ANNOTATED NOT THE PLACENTA. SO THAT IS A MAJOR NEED. HOW IMPORTANT IS GENOMICS COMPARED TO OTHEROMICS? THE GROUP FELT MORE IS BETTER, EPIGENOMICS WAS CLEARLY IMPORTANT BECAUSE IT WAS A REFLECTION OF MINUTE TO MINUTE THINGS THAT WERE GOING ON IN THE PREGNANCY. IT'S ALSO AFFECTED BY DIET AND THE WHOLE FIELD OF NEUTRAGENOMICS. BUT ONE PERSON SAID PROTEOMICS WAS THE MOST IMPORTANT BECAUSE THAT'S THE FINAL DESTINATION. COUPLE MORE SLIDES. CAN GENOMICS BE USED RIGHT NOW? YES. WHAT ARE THE ROADBLOCKS? IRB ISSUES AGAIN, ETHICS RESEARCH ON HUMANS, EARLY STAGES POTENTIAL ROADBLOCKS. WE NEED APPROPRIATE ANIMAL MODELS BUT IT CAN BE EXPENSIVE AND EACH SPECIES HAS DIFFERENCES DIFFERENCES. AS CAME UP IN THE EARLIER PRESENTATION THE ISSUE OF SHARING DATA AND COMPUTATIONAL APPROACHES SO HOW CAN WE INCENTIVIZE PEOPLE AND COMPANIES TO TAKE A WIN WIN APPROACH? WE THOUGHT A MAJOR URGENT QUESTION TO ADDRESS IS REALLY HOW TO BEST INTEGRATE THE CLINICAL INFORMATION WITH THEOMIC INFORMATION. SO THE NEXT BIG THING IS A ORGAN DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed ON A CHIP TECHNOLOGY THAT IF YOU CAN CREATE A PLACENTA ON A CHIP YOU CAN EXAMINE CELL TYPE AND CELL INTERACTIONS. THIS COULD ALSO ALLOW YOU TO KIND OF MAKE YOUR DREAM PREGNANCY BY USING COMBINING GENOME AND WHAT THAT DOES IN TERMS OF DEVELOPMENT OF PREGNANCY. THE OTHER GROUP MENTIONED THE NANOSENSOR STAR TREK TECHNOLOGY, MAYBE THIS ISN'T SO FAR AWAY, THAT EVENTUALLY WE'LL BE ABLE TO IMPLANT OR HAVE A WOMAN SWALLOW A SENSOR AND ALLOW THE PREGNANCY BE MONITORED THAT WAY. AND WE CLEARLY NEED BIOINFORMATICS PLATFORMED THAT ARE WEB ACCESSIBLE, USER-FRIENDLY AND PROMOTE SHARING OF INFORMATION. SO I WOULD LIKE TO THANK THE VERY ACTIVE GROUP WHO WERE VERY ENGAGED AND I WOULD FACETY. FACETY. THIS IS IAN BURG FROM MADISON WISCONSIN. IT APPLIES HERE BUT REALLY TO ALL THE PROJECT. YOU MENTIONED CONCEPTS LIKE ORGONES A CHIP. ONE THING ORGANS ON A CHIP. ONE THING THAT'S BECOMING 'PARENT WHEN YOU HAVE A COMPLICATED PREGNANCY, ESPECIALLY THOSE GETTING (INAUDIBLE) THE FETUS OF THE PLACENTA IS FETAL GENOME. BUT THERE MAYBE FAILURES OF A PREGNANCY BECAUSE OF PROBLEMS PURELY IN THE MATERNAL GENOME AND WHAT I'M GETTING AT, WE HAVE ALWAYS WORKED ON A PRINCIPLE MOST YOUNG HEALTHY WOMEN WHO ARE TO BECOME PREGNANT HAVE A CAPACITY FOR VASCULAR FUNCTION THAT GOES BEYOND WHAT THEY NEED NORMALLY. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WHEN THEY BECOME PREGNANT IT BECOMES A GREATER DEMAND AND REVEAL CONDITIONS THAT DIDN'T EXIST, OLDER WOMEN CONDITIONS THAT HAVE DEVELOPED LIKE HYPERTENSION, DIABETES, OBESITY. SO SOMETIMES YOU MAY FIND A TROPE BLAST COPES FINE, IT'S HAVING TROUBLE INTERFACING WITH THE UTERUS THAT IS NOT I CAPABLE OF HANDLING THINGS JUST FINE. SO I PROPOSE WE MAY NEED TO SERIOUSLY CONSIDER OPENING THE PROJECT UP, MAY ALSO NEED THE MATERNAL GENOME, YOU MAY NEED TO KNOW THE MATERNAL CELLS AND HOW THEY BEHAVE IN THE UTERINE WALL, THE UTERINE VASCULATURE AS WELL AS PLACENTA. WE MAYBE IN DANGER OF BECOMING SO FOCUSED ON THE PLACENTA WE MISS HALF THE STORY. >> (INAUDIBLE) UNIVERSITY MEDICAL CENTER. COUPLE OF POINTS. ONE BRIEF ON THE QUESTION OF THE CHIP, THE ORGAN ON A CHIPPER HAPPENS THE A LITTLE STRETCH BUT I CERTAINLY THINK, AND I GOES ALONG WITH WHAT IAN WITH WAS SAYING, THE ABILITY TO DO MULTIPLE CELL CULTURES, SIMULTANEOUS CULTURES IN A WAY TO LOOK AT THE INTERACTION BETWEEN AND I THINK THAT'S -- THERE ARE ATTEMPTS HERE AND THERE BIT'S NOT BEEN ADDRESSED SYSTEMATICALLY. THE OTHER POINT TO TAKE UP IS ONE THAT I THINK APPLIES ACROSS, IT HAPPENS TO COME UP IN THIS SETS OF DISCUSSIONS. IT APPLIES TO THE LINKAGE BETWEEN CLINICAL AND RESEARCH DATA. THERE'S A A REAL PROBLEM THERE. I THINK SOMEONE TALKED YESTERDAY ABOUT ANNOTATION, A 40-YEAR-OLD PLACENTA WHICH WAS MEANINGS, THE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed DATAER FOR THE OMICS SET OR WHATEVER THE DATA SETS HAS TO BE GOOD CLINICAL DATA BUT THAT RAISES ANOTHER SET OF PROBLEMS, THAT RAISES PROBLEMS SUCH AS THE IRB PROBLEMS. SO I THINK THERE ARE A NUMBER OF THINGS HERE THE NIH ACT AS A FOCUS FOR AND THE HPP ACT AS A FOCUS FOR. REQUIRED DATA FORMATS THAT FORM IF THEY'RE FUNDING SOMETHING THE DATA FORMAT MUST BE FULL, IT MUST INCLUDE THIS, IT MUST GO IN THAT DATA, IT'S NOT JUST UP TO THE INVESTIGATOR WHAT THEY PUT IN OR NOT. AND I THINK HAVING THE WHIP HAND OF HANDING OUT THE MONEY IS A VERY GOOD WAY OF ENFORCING THAT SORT OF THING BUT IT ALSO REQUIRES THEN NIH BE THE FOCUS FOR GETTING THOSE REQUIREMENTS THOSE FORMATS, THOSE SORT OF THINGS TOGETHER. TO GO ALONG WITH THAT IS THE IDEA THAT I THINK THERE ARE QUITE OFTEN CONSIDERABLE PROBLEMS WITH IRBs, THEY ALL DIFFER BUT THERE ARE CLEARLY PROBLEM, I WAS TALKING TO BRIAN YESTERDAY. A NUMBER OF PEOPLE HAVING PROBLEMS WITH IRBs WHO SAY THAT HAVING LOW BIRTH WEIGHT AND COUPLE OF OTHER POOR DIFFICULT IDENTIFIERS IS SUFFICIENT NOT TO BE ALLOWED TO BE ABLE TO MOVE DATA AROUND AND SO ON. IT MAKE USE AND MOVEMENT OF DATA VERY DIFFICULT AND WE NEED TO BE ABLE TO FIRST SAY WHAT CAN BE USED AS IDENTIFYIERS IS NOT REQUIRED, WHAT IS NOT AN IDENTIFIER. AND I H THINK AGAIN, THROUGH NIH IS ONE WAY OF HAVING THAT HAPPEN. SO WE CAN SAY TO IRB, THESE SORT OF IDENTIFIERS ARE OKAY, WE CAN DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed CARRY THIS INFORMATION WITH THE DATA SET RATHER THAN RESTRICTED. THEY USUALLY GO WITH NIH GUIDELINES. THIS IS A CONTINUING PROBLEM AND WE NEED TO SORT IT OUT NOW BEFORE IT BECOMES A MUCH BIGGER AND BIGGER PROBLEM DOWN THE LINE. >> NOSE ARE ALL GOOD POINTS BUT I'M CONTINUING TO BE IMPRESSED BY THE FACT THAT HOW MUCH RESEARCH IS GETTING DONE NOW THROUGH CROWD SOURCING AND VIA THE INTERNET WITHOUT THE BURDENS OF THE IRB, GETTING CITIZEN PARTICIPANTS OF SCIENCE. SO I THINK ALMOST WE NEED TO HAVE TWO PARALLEL STREAMS OF APPROACHES, ONE THAT GOES TO TRADITIONAL INSTITUTION BASED APPROACH, BUT ONE WE MIGHT CONSIDER HAVING PREGNANT WOMEN CITIZEN PARTICIPANTS. THERE'S AN ADVANTAGE BECAUSE MOST PREGNANT WOMEN ARE MORE INTERNET SAVVY THAN MOST IN THIS ROOM, THEY'RE ON TWITTER AND SOCIAL MEDIA. THEY PROBABLY WOULD BE VERY WILLING TO PARTICIPATE IN A LOT OF THESE PROJECTS. THE VISION PROCESS TWO OR THREE YEARS AGO, BUT SO MUCH HAPPENED SENSE THEN SINCE JOKING ABOUT IT BUT IT'S SERIOUS, ESPECIALLY THE GENETICS WORLD THERE'S SO MUCH ACCOMPLISHED ALREADY IN THAT AREA OF TIME. >> SO I WANT TO BRING UP THE ISSUE, BY THE WAY, KJERSTI, THANK YOU FOR OPENING THE DOOR FOR PHILOSOPHICAL DISCUSSION. SOMETHING I WOULD EXPECT FROM YOU. SO I WANT TO TALK ANIMAL MODELS A BIT BECAUSE I HAVE HEARD SEVERAL TIMES PLACENTAS ARE DIFFERENT ACROSS SPECIES. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed ANIMAL MODELS ARE GOING TO BE CRITICAL FROM TWO STANDPOINTS. NUMBER ONE FOR METHODOLOGY DEVELOP, IN THE IMAGING SESSION THAT I WAS IN, MODALITY, MORE ALGORITHMS TO DEAL WITH MOVEMENT TO MOVE THAT NOW, ET CETERA. THESE ARE THINGS NOT WANTING TO DEVELOP USE HUMAN SUBJECTS, YOU WANT TO USE ANIMALS. FOR ME MORE IMPORTANTLY THAN THAT THERE, SNOW MODEL FOR HUMAN EXCEPT HUMAN. AND SO WE DON'T LOOK AT ANIMALS FELL SOFTICALLY BECAUSE THEY'RE IDENTICAL TO HUMANS, WE USE ANIMALS TO ESTABLISH CONCEPTS, RIGHT? AND SO I'LL GIVE YOU TWO EXAMPLES. ONE, BASED IN THE LAST FEW YEARS ON ANIMAL STUDIES, MOSTLY IN SHEEP ACTUALLY, PREGNANT SHEEP OR I SHOULD SAY PRE-PREGNANT SHEEP, PRE-PREGNANCY MATERNAL DIENARY IN-- DIETARY INTAKE HAS A PROFOUND INFLUENCE ON, OO SITE QUALITY, AND PREGNANCY OUTCOMES. NOW WE CAN TAKE THAT CONCEPT AND USE THAT IN THE GUIDANCE TO START LOOKING IF THAT'S THE CASE IN HUMANS. ANOTHER EXAMPLE IS KJERSTI'S GROUP DEMONSTRATION OF THE PLACENTAL MICROBIOME BUT NOW WE CAN TAKE THAT OBSERVATION AND USE ANIMALS TO START ASKING QUESTIONS LIKE HOW DOES THAT CHANGE THROUGHOUT A PREGNANCY, HOW DOES IT CHANGE ACROSS PREGNANCIES? HOW DOES THE PATERNAL GENOME OR PATERNAL CONTRIBUTION AFFECT THE PLACENTAL MICROBIOME. SO I WILL ARGUE STRONGLY THAT ANIMAL MODELS ARE KEY TO ESTABLISHING THESE KIND OF THINGS. >> WE HAVE SO MUCH PASSION IN DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed OUR GROUP ABOUT THIS. I HOPE OTHERS POP UP AND SHARE THAT SIMILAR PASSION. IT'S INTERESTING ANY ONE OF US COULD FORM NINE DIFFERENT OPINIONS ON THE SUBJECT. BUT IT'S AN IMPORTANT DISCUSSION TO HAVE BECAUSE THERE ARE LIMITS TO WHAT WE CAN DO. WE NEED TO UNDERSTAND WHERE IT APPLIES WHERE IT DOESN'T APPLY. SO MUCH >> (INAUDIBLE) WISCONSIN. I HAVE A COMMENT ABOUT THE ANIMAL MODELS. KJERSTI ALLUDED TO THE POSSIBILITY THAT MAYBE WE SHOULD A PRIORI SORT OUT WHICH ANIMAL MODELS ARE ARE MOST APPROPRIATE. THAT'S A VERY GOOD IDEA BUT IT WILL BE PROBABLY BETTER TO DO THAT IN ADVANCE ENOUGH TO GIVE INVESTIGATORS MUCH LEAD TIME SO THAT IF THEY DON'T HAVE THAT MODEL THEN A THEY NEED TO BE ABLE TO FIND COLLABORATIONS AND/OR DEVELOP MODELS THEY CAN ACTUALLY USE IN CONTEXT OF NOT JUST HUMAN PLACENTA PROJECT BUT IN OTHER CONTEXT. THE SECOND COMMENT I HAVE ABOUT ANIMAL MODELS, IS SIMILAR TO WHAT LARRY WAS ALLUDING TO,. ANIMAL MODELS ARE MODELS. THEY'RE NOT HUMAN DISEASES. AND IN THAT CASE THE IS FOR NOT ONLY DR. GUTTMACHER BUT ALSO EVERY MEMBER OF THE STAFF WHO IS HERE, IT WOULD BE GOOD THEY SHOULD ASK THE QUESTION DOES THE MODEL ALLOW THE INVESTIGATOR TO ASK THE QUESTION THEY'RE EXAMINE SOMETHING THAT'S OOH A CORRECT REVIEW OF AN ANIMAL MODEL OPPOSED TO MAKING RECOMMENDATIONS WHILE NOT USING THIS MODEL OR THAT MODEL. SO AS FORMER SRO I'LL SAY THAT SROs DO IN GENERAL DO WHAT YOU SAY AND I DO ALERT THE GROUP DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THAT I WANT TO CAPTURE A NUMBER OF TYPES OF THINGS, I'M A LITTLE CONCERNED THAT ANIMAL MODELS COULD BE TWO HOURS EASILY THAT WE ALL HAVE STRONG OPINION, I UNDERSTAND YOUR POINT AND I THINK IT'S A GREAT POINT,LY LET THE COMMITTEES RESPOND IF THEY WANT AND THEN WE SHOULD LET THE ANIMAL MODEL REST UNTIL LUNCHTIME. THANKS. >> IT WAS MY OPPORTUNITY TO MAKE THIS COMMENT PUBLICLY TO HIPPOAND THEREFORE (INAUDIBLE) I ACTUALLY HAVE A IMPORTANT POINT TO MAKE ABOUT IMAGING. KJERSTI MADE A GOOD POINT THAT YOU DON'T WANT TO LOSE MINOR POINTS OF THE IMAGING ANALYSIS, WHEN YOU MARRY OMICS DATA WITH IMAGING DATA. IN THAT CASE IT'S IMPORTANT FOR THE GROUPS THAT DO IMAGING STUDIES, TO DEVELOP STANDARDIZATION THAT ACCOUNTS FOR NOT ONLY THE GLOBAL CLASSIFY CASE BUT ADDRESS FINAL POINTS OF IMAGING. THAT WOULD BE A GOOD IDEA TO DO THAT AS SOON AS THE IMAGING (INAUDIBLE) >> (INAUDIBLE) VIRGINIA COMMONWEALTH UNIVERSITY. I JUST WAS WONDERING IF YOU CAN COMMENT ON THE IMPORTANCE ESPECIALLY ON THE GENOMIC STUDIES OR THE BANK WITH THE REFERENCE BECAUSE MORE WE SEE THE POPULATION DISPARITY AND MORE GENETIC BACKGROUND SEEM TO PLAY A BIG ROLE AND HOW PREGNANCY RELATED DISEASE RESULT FROM SO IF WE WANT TO CLARIFY REFERENCE I WAS WONDERING IF A POPULATION BASED GENOMIC STUDY IS IMPORTANT TO START WITH REFERENCING DIFFERENT POPULATIONS. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed >> I THINK OUR GROUP SPOKE TO THAT WAS WITH THE IDEA A THOUSAND GENOMES PROJECT. TO REITERATE THERE WAS GREAT CONCERN IN OUR GROUP THAT WHEN WE THINK ABOUT GENOMICS WE RELY UPON CONVENIENT SAMPLES FROM CBS OR IBF TO CAPTURE THOSE EARLY PREGNANCY INTERVALS. THAT IS PROBABLY NOT REPRESENTATIVE OF THE POPULATION AT LARGE IN ASSUMING A -- SIMILARLY I THINK WE HAVE SO MUCH INFORMATION ABOUT HOW TO DESCRIBE HERITABILITY AT THE GENOMIC SCALE WHETHER WE'RE LOOKING AT MITOCHONDRIAL GENOME OR LOOKING AT HERITABILITY LOCI IN THE NUCLEAR GENOME, WE KNOW A LOT ABOUT THAT. AND LEVERAGING THAT KNOWLEDGE CAREFULLY IN THE PROJECTS IS A FANTASTIC POINT. I WOULD ADD TO THAT, THERE'S ALSO AN NIH WIDE ISSUE IN THAT A LOT OF THE INFORMATION IS BEING COLLECTED IN OTHER PROJECTS AND OTHER INSTITUTES. BUT THE PROBLEM IS THEY'RE FOCUSED ON SPECIFIC ADULT CANCER AND WHILE ACT RECEIVING DIVERSE POPULATIONS FROM A GENOMIC PERSPECTIVE THEY'RE NOT THINKING ABOUT PLACENTA OR THE CHILD. AND IT'S THE SILOING THAT'S PART OF THE PROBLEM. WE ARE RECAPITULATING THE WHEEL. WHEN PEOPLE TAKE LIFE COURSE PERSPECTIVE, WE INTEGRATE THAT INFORMATION WITH OTHER DATABASES. >> P I WANTED TO CLARIFY THE ISSUE OF THE BIOINFORMATICS. SO I THINK THERE'S TWO PHASES OF BIOINFORMATICS, THE FIRST YOU TAKE THE RAW READS THAT YOU GET AND PROCESS THEM INTO SOMETHING THAT'S USEFUL FOR ASKING DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SPECIFIC QUESTIONS OR TARGETED QUESTIONS AND I THINK ONE PROBLEM WE HAVE THAT PROCESS ALL SEQUENCING IS YOU HAVE THE SHORT READ ARCHIVE AND AND INTO THAT, PROCESS THAT DATA AND PEOPLE PROCESS IT USING VERY DIFFERENT PLATFORMS AND THRESHOLDS, SO COMPARING THAT PROCESS DATA BETWEEN LABS IS REALLY DIFFICULT. SO RIGHT NOW THERE'S ONLY 300 PLACENTAL SAMPLES, HUMAN PLACENTAL SAMPLES IN THE SHORTENED ARCHIVE SO I DON'T THINK IT'S THAT CHALLENGING TO HAVE ONE PERSON MAYBE LINKED WITH THE WEBSITE PROPOSED, THAT JUST PROCESSES THOSE SAMPLES IN THE SAME WAY AND ALSO GAINS NECESSARY DATA ANNOTATION HOW SAMPLES WERE COLLECTED AND WHAT WAS BEING COLLECTED. THAT PERSON, THEN PROCESS THEM THE SAME WAY AND MAKE REPOSITORIES, THEN THE SECOND WAVE FOR OUR INTELLIGENT POST-DOCS AN GRADUATE STUDENTS, THAT GO IN AND ASK TARGETED QUESTIONS OF THAT DATA SET. SO WHEREAS BIOINFORMATICS IS A BIG LOOMING THING, THE BIOINFO MA TICKS THAT WE NEED AS A COMMUNITY -- INFORMATICS IS STRAIGHT FORWARD WHERE IT'S STANDARDIZED USING PIPELINE THAT'S DONE FOR ALL OF THE SAMPLES THAT WE AS A COMMUNITY CHECK TO GO INTO ARCHIVE AND THEN THERE'S THE SECOND BIOINFORMATICS WHICH REALLY INDIVIDUALIZED FOR INDIVIDUAL LABS AN SPECIFIC QUESTIONS THAT WOULD BE DAUNTING, TO FUND BIOINFORMATICS, THE FIRST PART PROCESS DATA EQUIVALENTLY AN ANNOTATING IT ANNOTATING CORRECTLY, THAT'S SOMETHING THAT COULD BE DONE EASILY. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed >> I AGREE, FANTASTIC POINT. THAT IF THE RESOURCES COULD BE PUT INTO CREATING THOSE DATABASES APPROPRIATELY ANNOTATED, THAT'S A RESOURCE FOR ALL, ALL CAN MINE THAT DATA, PEOPLE WILL HAVE DIFFERENCE HYPOTHESES. >> I THINK THAT'S PRETTY TO BELIEVE. -- DOABLE. OTHER PROJECTS DO THAT, THAT'S SOMETHING REALLY LOW HANGING FRUIT. >> THERE IS A DIFFERENCE IN WHAT TYPE OF DATA YOU'RE COLLECTING AND HOW MUCH OF IT YOU'RE COLLECTING AND RECENT EXPERIENCE WITH META GENOMICS, WE HAVE GOT FIVE DIFFERENT PIPELINES SO YOU'RE RIGHT TO A SEN EXTEN LOW HANGING FRUIT BUT IT'S EXPENSIVE FRUIT AND CPT DEMANDING FRUIT AND I'M NOT SURE WE NEED ABSOLUTE CONSENSUS HOW TO DO IT BECAUSE SOMETIMES DISCOVERY HAPPENS WHEN SOMEBODY DOES THE DATA A LITTLE BIT DIFFERENTLY. SO I AGREE IN GENERAL MOST IF SOMEBODY ASKING FOR DATA OR DEPOSIT IN NIGHTURE, WHATEVER WE PUT IN SRAs, BUT THAT'S A LITTLE -- THAT IS ONE ASPECT TO IT BUT THE COMPUTATIONAL TOOLS I THINK THERE'S A LOFT CAPACITY TO DEVELOP VERY SPECIFIC, I DON'T KNOW OF ANOTHER EXAMPLE I CAN THINK OF IN OMICS TRYING TO MERGE TOGETHER THREE DIFFERENT GENOMES INTO ONE. WE HAVE TO TRY -- WE'RE TRYING TO HOLD TOGETHER, THAT'S NOT TOTALLY EASY TO DO. >> THAT LEVEL OF ANALYSIS I DON'T THINK IS VERY DIFFICULT BUT I DON'T KNOW HOW YOU FUND THAT OR THE BIG QUESTION THERE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WAS BIOINFORMATICS AND I'M WONDERING WHAT THAT MEANS. SO I THINK CERTAINLY THE BIG DATA TO KNOWLEDGE INITIATIVE TOOK THE DISEASE CENTERED APPROACH AND BROAD APPROACHES THAT'S TRYING TO HANDLE SOME OF THOSE NEEDS. TO MY KNOWLEDGE THERE'S NO MENTAL ELEMENT OF REPRODUCTIVE ELEMENT (INAUDIBLE). >> THE SPEAKERS PEOPLE STANDING PEOPLE THAT ARE STANDING, WE'LL HAVE TO CUT IT OFF TO REMAIN ON TIME. (INAUDIBLE) (OFF MIC) (OFF MIC) (INAUDIBLE) IN ADDITION AFFECTS -- IF YOU HAVE OTHER (INAUDIBLE) MY LAB (INAUDIBLE) LUNG KAREN OR DIABETES, YOU COULD SEE HOW THE FETUS (INAUDIBLE) MOTHER'S FUNCTION DIABETIC RESPONSE IN A VERY AMPLIFIED SYSTEM, NOT TRYING TO (INAUDIBLE) COMPLEXITY, YOU'RE TRYING TO REPLICATE FEW CELLS INTERACTIONS IN A MICROENVIRONMENT WITH (INAUDIBLE) INNATE MICROENVIRONMENT YOU GO AFTER VERY DISTINGUISHED (INAUDIBLE). I WONDER IF (INAUDIBLE) (INAUDIBLE) >> THERE WERE DEFINITELY PEOPLE IN OUR GROUP WORKING ON IT SO WE CAN CONNECT YOU AT THE BREAK. GOOD MORNING, (INAUDIBLE) UNIVERSITY OFFERER OBJECT. IT OCCURS TO ME LISTEN -- UNIVERSITY OF VEER MON. WE MAY NEED A DIFFERENT SYSTEM FOR FUNDING AND GETTING PEOPLE IN TO THIS THIS PROJECT. WE NEED COMPUTER SCIENCE PEOPLE, WE NEED PEOPLE WHO ARE TRAINED IN COMPUTATIONAL MATHEMATICS. WE NEED LIKE DATA STORAGE, AND DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THOSE KINDS OF PEOPLE INVOLVED IN THIS PROJECT. AND WE NEED PEOPLE TO BE INVOLVED IN ORGANIZING THIS PROJECT. THERE MUST BE SOME DEFERENT WAY TO PAY OR FUND PEOPLE TO PARTICIPATE IN THIS PROJECT. I'M WORRIED THAT WHEN THIS IS ALL DONE THERE WILL BE SIX PEOPLE WHO GET BIG, BIG SOURCES OF MONEY TO TRY TO WORK ON THIS BUT ALL OTHER PEOPLE WITH VOICES AND IDEAS WON'T BE ABLE TO BE INVOLVED. I THINK WE NEED TO START TO DO THAT. SOME DIFFERENT WAY OF FUNDING THIS. SO THAT WAS POINT NUMBER ONE. THE SECOND WAS ABOUT WE'RE NOT HANDLING THE PLACENTA IN THIS PROJECT BUT THE PROBLEM IS THAT IF WE DECIDE THERE'S SOMETHING WRONG OR SOME OUTCOME THAT WE HAVE FOUND BASED ON WHATEVER CELLS OR TISSUES THAT WE HAVE ANALYZED AS PART OF ITS PROJECT, AT SOME POINT WE'RE FOCUSED ON THE PLACENTA, WE NEED TO GO BACK TO PLACENTA (INAUDIBLE) TO LOOK AT IT. THE SAME VEIN IF IF WE HAVE ANIMAL MODELS, IF YOUR OMECS APPROACH GENE ACCESS IS DOWN REGULATED OR SOME REASON IN FOR SOME DISEASE PROCESS, THEN A, THERE MIGHT BE AN ANIMAL MODEL WITH THAT GENE THAT'S KNOCKED OUT AND THE OMICS IS DONE ON THAT MODEL. SO YOU NEED TO BE ABLE TO TAKE A LOOK AT THAT OMICS DATA AS WELL IN YOUR STUDIES. >> JUST TO BE CLEAR, I THINK WHAT I HEARD ALAN SAY EARLIER THIS MORNING, IS THAT NICHD WELCOMING THOSE TYPES OF RESEARCH MOVE PROJECT BUS THEY DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WON'T BE FUNDD THROUGH THE HPP MECHANISM, THAT IS CORRECT? HE'S NODDING. >> CAN I SAY I STRONGLY AGREE WITH THE ARGUMENT ABOUT TRAINING PEOPLE NECESSARY TO GET PEOPLE WORKING IN IMAGING AND THE OTHER IMAGE -- SEEMS TO GET PEOPLE TO WORK -- GETTING TO PEOPLE TO HAVE THIS BIG DATA IS A REAL PROBLEM. WE NEED TO GROW PEOPLE UP WITHIN SPECIFIC FIELDS TO FEEL ENGAGED IN THE AREA, WORK IN THAT AREA. >> THE OTHER THING IS THE NEED FOR TRULY TRANSLATIONAL PEOPLE. YOU CAN GO TO THE DEPARTMENT OF COMPUTER SCIENCE BUT THEY'RE NOT NECESSARILY -- THEY THINK WHATEVER IS HAPPENING IN THE MEDICAL SCHOOL IS FOREIGN AND EXOTIC BUT YOU CAN FIND OCCASIONAL GRADUATE STUDENT INTERESTED IN MAYBE BEING PRE-MED. THOSE ARE THE IDEAL PEOPLE WHO ARE STRONG COMPUTATIONAL SCIENCES BUT WHO DO RECOGNIZE THE IMPORTANCE IN THE APPLICATION TO MEDICINE. BUT YOU GOT TO GET THEM YOUNG. >> JOSEPH (INAUDIBLE) FROM OHIO STATE. SO (INAUDIBLE) IMPERMEABLE FOR MYSELF AND JUST GOING TO THROW OUT (INAUDIBLE) FEASIBLE IDEA SO I'M THINKING IT'S ABOUT SIMULATION. MY FRIEND HAS BEEN WORKING ON SOME KIND OF SIMULATION SOFTWARE FOR HEAD INJURIES, (INAUDIBLE) CLINICAL STUDY BASIC STUDIES, AND (INAUDIBLE) PREDICT THE OUTCOME OF THE THERAPEUTIC STRATEGIES (INAUDIBLE). SO BASED ON THIS IDEA I DON'T KNOW IF THAT'S FEASIBLE BECAUSE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed I DON'T THINK ANY INDIVIDUAL CAN DO THAT. SO MANY PEOPLE ARE DOING EVEN OMICS AND ALSO MEDICAL WORK. SO IF THAT'S FEASIBLE THEN NIH WILL BE THE ONLY SPACE CAN DO IT -- PLACE CAN DO IT BECAUSE WE NEED A GROUP OF PEOPLE REALLY KIND OF CONSTANTLY (INAUDIBLE) AND IF WE CAN HAVE A PLATFORM PROVIDED TO CLINICAL -- THERE ARE SO MUCH INFORMATION. SO WE KIND OF CUREATE DIFFERENT OMICS STUDIES AN CLINICAL WORK AND PROVIDE A PLATFORM. THEN FOR SIMULATION, BECAUSE THIS IS -- YOU DON'T EVEN HAVE TO (INAUDIBLE) FOR THAT. SO THAT'S SOMETHING I'M THINKING IN MY DISORGANIZED BRAIN I CAN'T INTEGRATE THAT MUCH DATA. >> PLEASE. >> HELLO. MY NAME IS (INAUDIBLE) I'M FROM UNIVERSITY OF HAWAII CANCER CENTER. BY THE TITLE I WORK IN THE CANCER CENTER, HOWEVER, I GUESS ONE OF -- I'M ONE OF THOSE RARE PEOPLE WHO ACTUALLY CROSS DIFFERENT DISCIPLINES, I'M A BIOINFOMATITION BY TRAINING SO THERE IS SOMEBODY DOING COMPUTATIONAL BIOLOGY HERE IN THIS AUDIENCE. NICHD HAS BEEN PRETTY FOND OF ME MY PROPOSAL SUBMISSION, GAVE ME FAIRLY GOOD SCORE SO IT' HELPFUL HERE. IT'S GOING SOMEWHERE HOPEFULLY. SO I HAVE SEVERAL QUESTIONS REGARDING THE ROADMAP IF YOU CALL THAT, COMING UP AHEAD BECAUSE THE MEETING NEEDS TO THINK ABOUT WAYS TO INCORPORATE DIFFERENT OMICS TECHNOLOGIES INTO THE HUMAN PLACENTA PROJECT DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SEASONS I WITH WORK WITH CANCER DATA AND PCGA ATLAS, I HAVE QUITE SOME EXPERIENCE WORKING -- DEALING WITH CANCER DATA SETS. I HAVE TO SAY THERE IS FRUSTRATION FROM US, ONE CRITICAL INFORMATION IS VERY COMPLETE IN THE CANCER DATA SET, SOME OF THE VERY IMPORTANT INFORMATION LIKE PATIENT SURVIVAL IS (INAUDIBLE) AVAILABLE SO IT THAT MAKES IT HARD TO LINK TO THE CLINICAL -- THE GENOMIC INFORMATION WITH PATIENT OUTCOME WHICH IS THE GOAL OF DOING ANY KIND OF OMICS STUDY. SO HERE, FOR THIS HUMAN PLACENTA PROJECT, IT'S AT THE BEGINNING STAGE, I THINK SOME OF THE LESSONS WE LEARNED FROM OTHER PROJECTS CAN HELP ORGANIZERS HERE PREVENT PROBLEMS DOWN THE ROAD THAT COULD HAVE HAPPENED. BEFORE WE START GOING SO ONE THE CLINICAL INFORMATION, IT WOULD BE GOOD TO HAVE THIS KIND OF COMMITTEE TO STANDARDIZE WHAT KIND OF CLINICAL INFORMATION WILL BE RELEASED TO THE PUBLIC. THIS IS VERY IMPORTANT. SOMETIMES YOU LOOK AT GENOMIC INFORMATION YOU THINK FACT YOU'RE WORKING IS IT A DETERMINATION FACTOR TURNS OUT IT'S NOT BECAUSE THERE'S OTHER CONFOUNDING FACTORS THAT EXPLAIN THE EFFECT, A LOT BETTER THAN WHAT YOU'RE LOOKING FOR. I HAVE SEEN THIS OVER AN OVER DOWNLOADING PUBLIC DATA SETS. THE RESULTS, THE CONCLUSIONS THAT PEOPLE DRAW (INAUDIBLE) BECAUSE THEY'RE NOT LOOKING IN THE RIGHT VEIN. SO IT'S VERY IMPORTANT TO HAVE A COMPREHENSIVE STANDARDIZED CLINICAL INFORMATION UP FRONT. THE SECOND THING IS SOMEBODY TALKED ABOUT IT, FOR HAVING ONE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed CENTER TO PREPARE -- PROPEL THE SAMPLES OR HAVING MULTIPLE SITES. I CAN'T IMAGINE BECAUSE WHERE THE DATA COME FROM CAN CAN BE VERY DIFFERENT. SO IN TC GA THEY HAVE MULTIPLE SITES AND THAT CREATE A LOT OF PROBLEMS DOWNSTREAM FOR THE DATA ANALYSIS CENTER PEOPLE BECAUSE WE GET SAMPLES FROM DIFFERENT LOCATIONS AND THEY FOLLOW DIFFERENT PLACENTAS UP FRONT AND ALSO MORE THAN THAT, FOR DOWNSTREAM DATA ANALYSIS, DIFFERENT PIPELINES SO WHEN IT ASK THE TCGA PEOPLE I CAN'T FIND OUT THE SOFTWARE THAT YOU USE FOR THE BIOINFOR MA THE TICKS PROCESS BUT I CANNOT FIND THE PARAMETERS WE USE FOR THE BIOINFORMATICS PIPELINE. IF YOU DON'T PUBLISH, IF YOU DON'T MAKE THE PARAMETERS PUBLIC, IT IS IMPOSSIBLE TO REPRODUCE THE SAME RESULTS SO THIS KIND OF INFORMATION IS VERY IMPORTANT UP FRONT. PEOPLE WOULDN'T THINK ABOUT BIOINFORMATICS INTRODUCE A LOT OF BIAS BUT THAT'S NOT TRUE. THERE'S SO MANY TOOLS FOR IF YOU DO GENE EXPRESSION SO ALL THE DIFFERENT VARIABLES CAN (INAUDIBLE) CAN AFFECT RESULTING MORE OR LESS SO SOMEBODY BEFORE ME TALKED BIOINFORMATICS IS STRAIGHT FORWARD, IT'S NOT STRAIGHT FORWARD. (INAUDIBLE) WE DON'T HAVE WE HAVE A DIFFICULT TIME WHICH IS BESTTOR THE GIVEN DATA SET, FOR THE GIVEN PREPARATION SO IT TAKE AS LOT OF EVALUATION WORK TOLL FIND OUT THE BEST OPTIMAL PIPELINE TO DO CERTAIN WORK. SRA IS A GOOD WAY TO DEPOSIT DATA, IT'S PLATFORM EVERYBODY CAN USE, AND A WAY TO RETRIEVE SAMPLE SRA -- THERE'S DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed (INAUDIBLE) I THINK TCG HAS A GOOD POINT RELEASING DATA AT THE DIFFERENCE LEVEL, LEVEL 1 TO 4 SO DEPENDING WHAT THE NEED IS, YOU CAN GET RESTRICTED DATA OR PUBLIC DATA. IF YOU WANT TO CHECK PROTEINS FOR EXAMPLE HOW THE EXPRESSION CHANGE AMONG THE DIFFERENT SAMPLE YOU CAN LOOK TO LEVEL 3. THIS IS A GOOD IDEA THAT I LIKED ABOUT TCGA, SOPHISTICATION LEVEL OF THE USER YOU CAN GRAB THIS LEVEL OF DATA. AND I THINK IT'S REALLY IMPORTANT TO HAVE THE RAW DATA AVAILABLE SOMEWHERE USERS MAY HAVE DIFFERENT PURPOSES SO REALLY WANT TO USE DIFFERENT TOOLS WHAT WE GET FOR DIFFERENT ISOFORMS. SO HAVING THAT KIND OF FLEXIBILITY DESIGN FOR DATA RETRIEVING IS ALSO VERY IMPORTANT FOR US TO GO AHEAD. DATA SHARING AS WE ALL KNOW VERY IMPORTANT, (INAUDIBLE) DATA TRY THE SHARE AS MUCH AS POSSIBLE TO THE PUBLIC, FOR US HERE IN THE PLACENTA PROJECT BRAIN IMAGING DATA AND AND OTHER CORE PLATFORM LIKE METABALOMICS DATA, SO HOW ARE WE GOING TO SHARE THAT? FARCE I KNOW METABOLOMICS FIELD THERE'S NO PUBLIC DATA DEPOSIT PLATFORM, THERE'S VARIOUS ISSUES. >> ACTUALLY I THINK YOU HAVE DONE A BEAUTIFUL JOB OUTLINEING A LARGE NUMBER OF ISSUES AND I APPRECIATE THAT. AND WHAT I WONDER IS DID YOU PUT ANY OF THIS INFORMATION, BECAUSE I'M AFRAID THAT I WON'T BE ABLE TO REMEMBER IT. YOU KNOW THOSE BIG BOARDS UP FRONT? I'M SORRY. IT'S IN A GROUP -- SUPER. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed ALSO ON THE BIG BOARD, SOUNDS LIKE SOME OF THOSE ARE CROSS CUTTING. >> THANK YOU. I GUESS -- >> VERY PASSIONATE ABOUT THIS. >> YES, YES. ONE LAST POINT. (INAUDIBLE) I AGREE WITH THAT, EYE HOPEFUL THERE'S TRAINING GRANT MONEY TO DO THAT ACROSS DISCIPLINE AS WELL AS DOMAIN EXPERTISE, THAT'S VERY IMPORTANT TO HAVE FUTURE GENERATIONS. LIKE T-32. >> ONE LAST QUESTION. >> I'M WAYNE (INAUDIBLE) WAYNE -- ACROSS THE RIVER ONTARIO AT UNIVERSITY OF WINDSOR. MY LAB IS LOOKING AT A DOSE STRESS STIMULUS, MANY DIFFERENT KINDS OF THESE, THAT INDUCE STEM CELLS TO BREAK POTENCY TO DIFFERENTIATE. WE THOUGHT WE HAD GOOD INSIGHT UNTIL RECENTLY WE STARRED USING A SERIES OF PATENTED -- PATENTED ONGOING PATENTED REPORTER STEM CELLS, ES CELLS AND TS CELLS, POTENCY LOSS IT SHALL SHOE GAIN, LINEAGE SUPPRESSION AND ENZYMES THAT MEDIATE THESE AFFECTS. ALTHOUGH WE THOUGHT WE KNEW A LOT BEFORE, A LOT MORE IN THE LAST THREE MONTHS AND WE WILL BE ABLE TO LOOK AT DIFFERENT KINDS OF STRESS, PULSE STRESS THAT A PREGNANT WOMAN MIGHT SEE ONE DAY AND THEN IT GOES AWAY AN COMES BACK THE NEXT. WE ALREADY HAVE INSIGHT INTO THAT SO MY QUESTION IS, I ALWAYS GO TO MEETINGS WHERE I'M THE 5 WESTER, WE'RE WORKING IN MOUSE MODELS THESE STEM CELLS, WITH THE ONTARIO PEOPLE MOVING TO DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed HUMAN CELLS, I THINK THAT'S A A MANAGEMENT QUESTION, IS THERE A ROLE IN -- AFTER A MINUTE PREAMBLE I CAN SAY DISMISS THIS BECAUSE MISSED THE FIRST TWO SPEAKER THIS IS MORNING. IS THERE A ROLE FOR HIGH THROUGH PUT HIGHLY PREDICTIVE AND BIOLOGICALLY ACCURATE STEM CELL ASSAYS AND FRANKLY I WOULD LIKE TO TALK TO THE PEEP TALLET PODIUM RIGHT NOW BECAUSE WE HAVE QUESTIONS ON HOW TO ASSOCIATE OUR QUESTION SITLY ACTIVE BIOLOGICAL FINDINGS WITH MECHANISMS. IS THERE A ROLE FOR THAT IN THE HUMAN GENOME PROJECT? SHOULD IT GO AFTER SERIES A MONEY AND COME BACK IN FIVE YEARS? AND ASK YOU THE SAME QUESTIONS I'M ASKING YOU NOW? AND IF THIS WAS DISCUSSED EARLIER, I'LL LEAK AT SLIDE ON THE VIDEO. >> SOUNDS SUPER COOL AND WE WOULD LOVE TO HEAR MORE ABOUT IT. YEAH. SO I MEAN, THIS IS A ROOM FULL OF FOLKS, SOUNDS LIKE GREAT OPPORTUNITIES FOR COLLABORATION. >> CERTAINLY, ACTUALLY ASKING MORE ABOUT ACTUALLY ROOM FOR FUNDING. I THINK SERIES ARC FUNDING. THE JAPANESE MANAGEMENT PART IS I HAVE SUSAN FISHER'S IN WINDSOR BUT THEY'RE NOT REGISTERABLE AND I THINK THERE'S A (INAUDIBLE) THERE ARE LOTS OF THINGS GOING ON HERE BUT THE QUESTION IS WHETHER HIGH THROUGH PUT ACCURATE BIOLOGICALLY PREDICTIVE STEM CELL ASSAYS AS WELL OR SHOULD I WAIT IN THE BACK AND HEAR WHAT YOU'RE DEVELOP DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SOMETHING >> OUR DIRECTOR IS GOING TO WEIGH IN. >> I THIS THINK IT REALLY, IF QUESTION IS TOO VAGUE TO COMPLETELY ANSWER. IF WHAT YOU'RE DESCRIBING CAN HELP US TO UNDERSTAND STRUCTURE AND FUNCTION OF THE HUMAN PLACENTA IN REAL TIME, THEN IT HAS A ROLE IN THE HUMAN PLACENTA PROJECT. THAT SAID, WHAT YOU'RE DESCRIBING FROM WHAT I GRASPED OF IT, DOES AS KJERSTI SAID, SOUND INCREDIBLY COOL AND CERTAINLY SOUNDS LIKE IT WOULD BE ABLE TO ADVANCE SCIENCE, WE HAVE A RICH PORTFOLIO OF PLACENTAL WORK SEPARATE FROM THE HUMAN PLACENTA PROJECT. DON'T FEEL CONCERNED IF IT'S NOT RELEVANT TO THE HUMAN PLACENTA PROJECT. IT DOESN'T MEAN IT DOESN'T HAVE A PLACE AT NIH. >> THANK YOU VERY MUCH. I THINK ON THE JAPANESE MANAGEMENT LEVEL, NOT NEXT YEAR BUT FIVE YEARS FROM NOW WILL BECOME MORE CONVERGENT. THANK YOU. >> SO WE'VE DISCUSSED IT AND DECIDED THAT NOW ACTUALLY AN APPROPRIATE TIME THE TAKE A BREAK. SO WE'RE GOING TO BREAK FOR I'M GOING TO SAY TEN MINUTES BECAUSE I KNOW THAT IT'S 15 BY THE TIME Y'ALL GET BACK AND SIT. BUT TRY BECAUSE WE DON'T HAVEN'T TO GET TOO FAR BEHIND. I THINK WE'LL GET STARTED. I THINK THE ENERGY HAS BEEN REALLY GOOD. I REALLY APPRECIATED PEOPLE'S THEIR QUESTIONS AND PASSION. BE MINDFUL, TRY TO BE SUCCINCT IF YOU CAN IN YOUR QUESTIONS, THAT WAY THERE'S MORE TIME FOR EVERYBODY TO REALLY HEAR WHAT YOU HAVE TO SAY AND WE GET FEEDBACK FROM THE GROUP. SO I WILL TURN IT OVER NOW TO GRAHAM. >> OKAY. I WILL RUN THROUGH SOME OF THE TEMPLATE WE FILLED IN IN MY GROUP AND THEN WE'LL COVER OTHER POINTS, GENERAL INTEREST FROM HIS SESSION, YOEL WILL. SO WE WERE CHALLENGED WITH THE FOUR HIGH LEVEL QUESTIONS, AND I THINK BEFORE WE GOT INTO THE DETAIL OF THESE WE HAD ALSO A GENERAL DISCUSSION. IN PART IT WAS RELATING TO WHAT WHERE AND WHEN. AND THE QUESTION AROSE, REALLY, WHAT ARE WE TRYING TO DO AND HOW ARE WE GOING TO FOLLOW THE PLACENTA? AND DO WE NEED JUST TO FOCUS ON THE PLACENTA. SO I THOUGHT IT USEFUL TO HAVE A DEFINITION OF WHAT THE PLACENTA IS. BECAUSE IF YOU LOOK IN THE BOOKS, HERB THEIR OWN IDEA OF WHAT IT IS BUT'S DIFFICULT TO COME UP WITH A DEFINITION. ONE OF THE BEST I THINK WAS FROM DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed HOLLAND (INAUDIBLE) A GREAT COMPARATIVE ON TOLL GIST OF THE LAST CENTURY, AND HE SAID THE MAMMALIAN PLACENTA IS AN ACQUISITION OR FUSION OF THE FETAL MEMBRANE TO THE MUCOSA PHYSIOLOGICAL EXCHANGE. THAT SUMS UP WHAT THE PLACENTA IS. MANY FUNCTIONS THAT COME TO PHYSIOLOGICAL EXCHANGE, THE CRIME FUNCTION IS MODULATING MATERNAL METABOLISM, BUT ALL OF THESE REALLY FOCUS ON PHYSIOLOGICAL EXCHANGE BUT IT DOES HAVE OTHER FUNCTIONS. BUT THE KEY THING I THINK IN THAT STATEMENT IS THAT IT IS AN ACQUISITION OR FUSION OF TWO DIFFERENT TISSUES. FETAL AND BRAIN TO UTERINE MUCOSA SO WE SHOULDN'T FORGET WHAT IS HAPPENING IN THE MUCOSA PRIOR AND DURING IMPLANTATION AND PREGNANCY, THIS ECHOS THE POINT MADE IN THE QUESTION OR COMMENT FROM THE LAST SESSION. TO A CERTAIN EXTENT IF YOU'RE INTERESTED IN IS THIS HEALTHY PREGNANCY, WHAT IS YOUR INTERESTED IN IS HOW WELL IS THE ENDOMETRIUM FUNCTIONING PRIOR TO PREGNANCY, HOW IT INTERACTS DURING IMPLANTATION AND HOW THAT GOES THROUGH TO DELIVERY OF NUTRIENTS, ET CETERA, DURING PLACENTAL DEVELOPMENT. SO TO A CERTAIN EXTENT WE WEREN'T TO (INAUDIBLE) NECESSARY WHERE IT CAME FROM BUT MORE WHETHER IT WAS INFORMATIVE OF SUCCESSFUL PREGNANCY SO IN TERMS OF THE DETAILS OF THE QUESTION WE'LL HAVE REPETITION FROM WHAT HAS BEEN TALKED ABOUT PROTEOMICS AND GENOMICS AND DISCUSSION HOW DO TRANSCRIPTOMICS DIFFER FROM GENOMICS AND WE CALLED OURSELFINGS FUNCTIONAL GENOMICS IF YOU LIKE. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WHAT I HAVE DONE IS TO GO THROUGH THE TEMPLATE AND PERHAPS HIGHLIGHT IN BLUE WHERE WE -- WHERE THE NEW POINTS NOT TOUCHED ON, SO OBVIOUSLY IT COMES FROM THE SATE IT SHALL SHOE BEFORE, WE INCLUDED PLACENTAL BED WHICH IS AN IMPORTANT SIDE OF INTERACTION WHERE THE IMMUNE INTERACTIONS TAKE PLACE, BIOLOGICAL REMODELING, THAT IS IMPORTANT INFORMATION THERE. WE THOUGHT IT WAS AGAIN, THE ATLAS HAS BEEN MENTIONED WE THOUGHT IT WAS AN ESSENTIAL THING IF YOU CHANGE INFORMATION TO KNOWLEDGE, BUT NEED TO KNOW WHAT CELL TYPE IN THE PLACENTA IS THIS TRANSCRIPT COMING FROM. OTHERWISE YOU'RE JUST LOOKING POTENTIALLY A PHENOMENON. THERE IS THE ISSUE OF THE MATERNAL FETAL PLACENTAL CROSS TALK, THERE'S CLEARLY A DIALOGUE TAKING PLACE BETWEEN THE ENDOMETRIUM, PLACENTA AND FETUS. WE DON'T WANT -- ONE OF THE CHALLENGES WITH WE COME TO IS EXACTLY WHERE THESE MICRORNAs ARE ACTING WITH LOCALLY OR WHETHER THEY'RE HAVING DISTANT INTERACTIONS ON MATERNAL HEART, LIVER OR THYROID. THOSE WILL BE CHALLENGING TO DISSECT OUT. WE THOUGHT AGAIN RELATING TO THE ATLAS LOCALIZING WHERE THE TRANSCRIPTS ARE COMING FROM, WE NEEDED TO PERFORM SEVERAL SORTING OF THE PLACENTA TO OBTAIN CELL TYPES SPECIFIC TRANSCRIPTOMES, TO START DOING SINGLE CELL TRANSCRIPT OMICS ON WELL CHARACTERIZED TROPHOBLAST LINEAGES, WE DON'T KNOW HUMAN HOW MANY TIMES, SUBTYPE THERE ARE, WE HAVE A MUCH BETTER HANDLE IN THE MOUSE. WHERE IT IS CLEAR THERE ARE DIFFERENT SUBTYPE SO THESE WHAT DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WE CAN MEASURE ALL THE DIFFERENT TYPES OF RNA AND ALSO MAIN PLY COMING FROM THE PLACENTA BUT ALSO PERHAPS IT SHALL SHOE SPECIFIC FROM THE FETUS. BIG QUESTION WHETHER MONITORING PLACENTAL SPECIFIC MICRORNAs C-19 MICROCLUSTER FOR EXAMPLE, IN THE MATERNAL CIRCULATION IS THAT GOING TO PROVIDE SURROGATE MARKERS FOR PLACENTAL FUNCTION AND DEVELOPMENT. AND I THINK YOU NEED TO DO THE CORRELATIVE STUDIES, IMAGING LOOK PLACENTAL PATHOLOGY TO NAIL THAT QUESTION. WHEN SHOULD IT BE DONE? WE SAW ALL THE EVIDENCE FROM THE STUDIES PRECONCEPTIONAL PERICONCEPTUAL EVENTS PROFOUND IMPACT ON DEVELOPMENT AND FUNCTION. SO WE THOUGHT IT WOULD BE IDEAL TO START PRE-CONCEPTUALLY THROUGH GESTATION, THROUGH TO DELIVERY TO PICK UP WHETHER THE MATERNAL SIDE OF THE INTERACTION IS WHOLLY PRIOR TO PREGNANCY AND HOW DO TISSUES INTERACT. SO THOSE ARE THE FIRST SET OF QUESTIONS, THE CHALLENGES I THINK ARE SIMILAR TO WHAT WE HAVE HEARD BEFORE. HOW DO YOU IDENTIFY THE POPULATION, U HOW DO YOU PERFORM LONGITUDINAL STUDIES. SAMPLE SIZE, WE CAME TO ESPECIALLY DIFFERENT PATHOLOGIES THE LOW INCIDENCE OF THOSE PATHOLOGIES MIGHT MEAN THAT YOU HAVE GOT TO HAVE A VERY LARGE COHORT IN ORDER TO GET SUFFICIENT NUMBERS AT THE END OF YOUR STUDY. I TOUCHED ON THIS POINT ALREADY, BUT ASSESSING THE LOCAL VERSUS THE DISTANT ACTIONS OF THE MICRORNAs COMING FROM THE PLACENTA AGAIN, THIS DIALOGUE BETWEEN PLACENTA AND MOTHER DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed IDENTIFYING EXACTLY WHERE THOSE ARE ACTING IS GOING TO BE DIFFICULT, ANIMAL MODELS ARE GOING TO BE ESSENTIAL IN TRYING TO TEASE APART STAN STANDARDIZATION, TRANSCRIPTOME OR PROTEOME AND ONE OTHER CHALLENGE I THINK PARTICULARLY IN HUMAN IS THAT WE DON'T REALLY HAVE A RELIABLE MODEL SYSTEM FOR TROPHO BLAST DIFFERENTIATION AND DEVELOPMENT. IN THE MOSHINGS WE HAVE BEEN ABLE TO IDENTIFY TRANSCRIPTIONAL NETWORKS WHICH REGULAR LIGHT DIFFERENTIATION AND PLACENTAL DEVELOP THROUGH THE USE OF TS CELLS, WE DONE REALLY HAVE THAT SAME RESOURCE IN THE HUMAN. ANIMAL MODELS, I KNOW HAVE BEEN MENTIONED, THERE HAVE BEEN INCREDIBLY INFORMATIVE ON PLACENTAL PHYSIOLOGY, PARTICULARLY THE MOUSE IS INCREDIBLY INFORMATIVE IN TERMS OF KNOCK OUT STUDIES CONDITIONAL AND OTHERWISE. FUNCTION OF THE TRANSCRIPT IN TERMS OF PLACENTAL DEVELOPMENT AND FUNCTION. THESE ARE KEY TO TRANSFORM THIS INFORMATION, KNOWLEDGE ABOUT PLACENTA DEVELOPMENT. NEXT BIG THING, WE'RE NOT WORKING IN ISOLATION. WE NEED TO INTEGRATE THE OMICS TOGETHER. WHAT NEW TECHNOLOGIES NEED TO BE DEVELOPED, WELL IT'S H NOT REALLY A TECHNOLOGY BUT A PLACENTAL ATLAS WOULD BE A BIG STEP FORWARD, YOU CAN ASK IS IT HUMAN, MOUSE, WHAT SPECIES. WE THOUGHT BY SINCE IT'S ALREADY MENTIONED, ANOTHER ISSUE, UNIQUE TO THE TRANSCRIPTOME IS THAT TRANSCRIPTOME ACTUALLY BEING TRANSLATED. SO PARTICULARLY WHEN YOU START TO LOOK AT STRESS SITUATIONS, DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THERE'S MANY BETWEEN HAVING RNA TRANSCRIPT AND HAVING AN AFFECTED PROTEIN AT THE OTHER END. AND WE SEE IN CERTAIN CASES OF STRESS BUT THE RNA DOESN'T TELL YOU THE WHOLE STORY. SO WE NEED TO THINK ABOUT MOVING TOWARDS DIFFERENT SITUATIONS TO KNOW ARE THOSE RNAs ON THE (INAUDIBLE). AND ANOTHER SORT OF UNIQUE CHALLENGE PERHAPS IS CAN WE IDENTIFY THE FIRST TRIMESTER PHENOTYPE THAT REALLY IS NORMAL AND IS GOING TO TELL US ABOUT THE CENTRAL EARLY STAGE OF DEVELOPMENT, CLEAR MOST MAJOR (INAUDIBLE) SO THOSE ARE THOSE POINTS, MATURE METHODOLOGIES AVAILABLE FOR ANALYZING THE TRANSCRIPTOME AND THERE ARE PROVEN ROAD MAPS FOR THEIR APPLICATION, THE N CODE BEING A PARADIGM REALLY BY WHICH YOU CAN SAY TAKE THIS INFORMATION FORWARD. THERE ARE CERTAINLY PATHWAYS DEVELOPED THAT WOULD ALLOW US TO EXPLOIT THE TRANSCRIPTOME. I THINK THESE POINTS APPLY TO REALLY ALL TECHNOLOGIES WE CAME UP WITH NONETHELESS. ARE THERE OTHER TECHNOLOGIES SYNERGIZE? OBVIOUSLY THE OTHEROMICS AND THE. IMAGINING AND OF COURSE SAMPLE SIZE WAS IMPORTANT. WE ALSO DISCUSSED TISSUE BANKS AND HOW RELIABLE THOSE ARE FOR USE WHETHER THEY SHOULD BE CENTERS OF EXCELLENCE COLLECTING IT SHALL SHOES IN A STANDARDIZED WAY OR POINTS I THINK HAVE BEEN ADDRESSED ALREADY. SO THAT SUMMARIZES WHAT I WANT TO SAY ABOUT MY SESSION, HERE (INAUDIBLE) GOING TO OMPLIMENT WITH COMMENTS FROM HE IS. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed >> THANK YOU, GRAHAM. THREE PRINCIPLES GUIDED BY PRESENTATIONS HERE RIGHT NOW. THE FIRST ONE IS GRAHAM AND I HAVE MERGED OUR POINTS SO REPRESENTING MANY THINGS DISCUSSED IN OUR GROUP WHICH YOU CAN SIGH HERE. THE SECOND POINT IS I WAS THE 6TH SPEAKER WITH THE OMICS DISCUSSION SO REPETITIVENESS IS THE ENEMY. AND MY THIRD POINT IS AS YOU CAN HEAR THOUGH I'M FROM PITTSBURG I'M A CHALLENGED BY ACCENT SO I LIKE PICTORIAL DEPICKS IDEAS SO A FEW THINGS TO -- GRAHAM NOT CAPTURED COMPLETELY IN HIS TALK. SO AT THE END OF OUR GROUP DISCUSSION, WE HAD THE BIG SKY IDEA HERE SMIDDY PIX OF BIG SKY. THE BLUE SKI INTENT, I SHOW YOU WAY TO GET $41.5 MILLION FROM THE NIH. SOME HAVE BEEN DISCUSSED ALREADY BUT I SHOW YOU PICTORIALLY. DEFINE NORMAL AND DEFINE PHENOTYPES THAT INCLUDES THIS WORKS VERY POORLY. GOOD SITUATION HAVE PLAN B. NORMAL MEANS DEFINE FIELD TYPE MEAN NO, SIR MALL FIELD TYPE AND ALSO DISEASE PHENOTYPE, GEORGE (INAUDIBLE) TOUCHED ON IT, A FEW OTHERS SO DEFINE WHAT IS NORMAL, WHAT DEFINES DISEASES, EACH ONE OF THESE FIGURES YOU SEE HERE IS SPECIAL LIKE EVERYBODY ELSE. A SECOND POINT THAT WAS DISCUSSED IN OUR GROUP WAS SINGLE CELL TECHNOLOGY. I DON'T HAVE PICTURES BUT THIS IS A VERY IMPORTANT POINT WHEN STUDYING THE PLACENTA, AT LEAST THERE'S MAJOR FOUR CELL TYPES HERE, YOU CAN SEE TROPO BLAT CELLS, FIBROBLASTS MA CASH FLOW PHAGOS AND OTHERS, IF YOU WANT TO STUDY A FEE THE AT THIS COMPONENT OF TROPHO BLAST, DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SINGLE CELL ANALYSIS IS SEEABLE. THESE ARE EXAMPLES THAT WERE DISCUSSED IN OUR GROUP. IN A CONVINCING WAY THAT WILL BE ESSENTIAL FOR FUTURE RESEARCH. MY THIRD POINT, WE WERE SEGREGATED IN OUR -- OR AGGRAVATEDDED BY TECHNOLOGY AND DECEMBER CUSHION BUT SEVERAL TIMES BEFORE ALL OF US FELT THIS WAS THE BETTER WAY TO ACTUALLY AGGREGATE A PRODUCTIVE DISCUSSION AND OUR GROUP FELT STRONGLY NOT ONLY FOR DISCUSSION BUT ALSO GRANT APPLICATION AND OTHER PURSUITS, WE WOULD LIKE TO WORK WITH SOMEBODY WHO DOES IMAGING AND SOMEBODY WHO DOES BIOINFORMATICS AND SOMEBODY WHO DOES SOMETHING ELSE AND PERHAPS AGGREGATE BASED ON IDEAS CONCEPTS AND PHYSIOLOGY, NOT SHOULD HAVE BY TECHNOLOGY, MUCH MORE FRUITFUL. THE FOURTH IDEA TO PUT FORWARD, BRIEF WORD, WE CALL IT (INAUDIBLE) OMICS. WE WE JUST INVENTED A NEW FEEL. AS IMPLIED BY DISCUSSION YESTERDAY, AND TODAYS VESICALES COME IN DIVERSE TYPES, CONTAIN VERY IMPORTANT NOT ONLY RNA MESSAGES BUT ALSO PROTEIN SO PRO PROTEOMICS. METABOLOMICS AND FRAGMENTS OF DNA, NOT SURE WHAT THE SIGNIFICANCE OF THAT IS. THEY DEFINITELY CONTAIN RNA MOLECULES BUT OTHER THINGS NOT DISCUSSED SO FAR SUCH AS LIPIDS AND LIPID MESSAGES IN OTHER TYPES OF MESSAGES CARRIED FROM PLACENTA TO OTHER CELLS TO MATERNAL POTENTIALLY FETAL CIRCULATION MAYBE IMPORTANT NO. CXFC THREE MAJOR SUBTYPES MENTIONED YESTERDAY, MAYBE OTHERS THAT VESICALES ARE NOT BORN UNIFORMLY, THEY'RE DIFFERENCE TYPES AND FURTHER DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed CONTACTIZATION OF TYPES AND CARGO WOULD BE ESSENTIAL. THE FIFTH POINT TO TOUCH ON, I'M ALMOST DONE, IS SOMETHING THAT (INAUDIBLE) POINTED OUT IN HER TALK NOT SURPRISING BECAUSE WE SAT ON THE VISION MEETING TOGETHER, THAT IS THE PLACENTA (INAUDIBLE) MY DEPICTION INSTEAD OF WORDS THIS IS THE PLACENTA. AND HERE IS HOW IT BECOMES GRADUALLY ACHIEVED. DIDN'T HAVE ENOUGH TIME TO CREATE IT LAST NIGHT BUT IT'S SOMETHING WE USE FROM OUR VISION MEETING A FEW YEARS AGO, WHEN WE DID IT IT SOUNDED LIKE SCIENCE FICTION NOW AS MANY OF YOU KNOW, GROUP AROUND THE COUNTRY WHO WORK IN DIFFERENT FORMS SOME FUNDED BY NIH SOME BY OTHER FUNDING MECHANISMS BUT THEY'RE VERY IMPORTANT. THIS IS RIGHT NOW REALLY SCIENCE FICTION IT IS HARD TO ASSEMBLE THESE INTO AN ORGAN, IT'S REALLY BIOLOGY BUT IS A YEARS AGO THIS WAS SCIENCE FICTION. MY WIFE WOULD LIKE TO BELIEVE THIS IS SCIENCE FICTION, AND MY LAST POINT TO MAKE TO YOU IS OUR GROUP FELT STRONGLY, LIKE EVERYBODY ELSE, ABOUT THE CONCEPT OF HAVING SOME INTEGRATED DATA REPOSITORY THAT PUTS TOGETHER INFORMATION WE GET FROM OMICS FROM DATABASES AND FROM CLINICAL INFORMATION TOGETHER. WHO BETTER CAPTURES THAN THIS COMPANY AND I DOODLED THE GOOGLE AS YOU CAN SEE. I THOUGHT IT WAS APPROPRIATE WHEN GOOGLE ADJUSTS TO EARTH DAY AND SO FORTH, PLACENTA DAY WOULD BE APPROPRIATE. JUST TO GET A LITTLE BIT CLOSER FOR EXAMPLE IF DR. GUTTMACHER IS BEING ASKED BY DR. COLLINS DO YOU KNOW ABOUT ABOUT ISSUE OF DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THE IT CANROP HOCKER BLAST FACTOR BUT LET ME PULL OUT MY iPHONE AND GOOGLE IT AND GIVE YOU THE ANSWER. TO BE DATA BANKS AND ALSO I'M FEELING LUCKY, TO BE COMPLETELY OKAY. BUT ON A SERIOUS NOTE HERE, WE PUT BIG EMPHASIS ON NOT JUST DATABASE IN BIOBANK BUT PROTOCOLS. WE FELT FOR TRANSCRIPTOMEICS AND OTHER RNA ANOLYTES THAT IT'S CRITICAL TO HAVE PROPERTY T CONTROLS THAT ARE UNIFORM. ONE PERSONAL COMMENT ABOUT UNIFORMITY, IT'S VERY IMPORTANT FOR SCIENCE BUT UNIFORMITY CAN BE RESTRICTIVE FOR IMAGINATION. SO WE HAVE TO BE CAREFUL WHEN WE SAY UNIFORM THIS AN UNIFORM THAT, WE'RE VERY PASSIONATE ABOUT UNIFORMITY. SO IT'S A LITTLE RISKY FROM POINT OF VIEW OF CREATIVITY. SO I PREFER THE APPROACH WITH MINIMAL CRITERIA LIKE MIAMI, MICROARRAY EXPERIMENTS, MINIMAL INFORMATION BUT ALLOW US TO FLOURISH OUR CREATIVE MIND GOING DIFFERENT ROUTES. SO I LEAVE YOU WITH A PICTURE I USED YESTERDAY AND THANK YOU VERY MUCH. [APPLAUSE] >> SUPER. SO NOW WE ARE OPEN FOR DISCUSSION. REALLY? OH. GOOD. >> I WAS WONDERING IF YOU CAN COMMENT ON THE TRANSCRIPTOMIC ASPECT OF IT YOU CAN HAVE BASELINE OF ALL THE TRANSCRIPTION IDENTIFIED BUT DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SOME MAY GO INTO mRNA OR INHIBITION OF EXPRESSION, HOW THAT CAN BE OVERLAPPED WITH THE PROTEOMIC STUDY, YOU TALK TRANSCRIPTIONAL INITIATION BUT HOW WE CAN ALSO LOOK AT THE TRANSLATIONAL INITIATION, WHAT REALLY DOES CARRY ALL THE WAY THROUGH TO BE COST EFFECTIVE AT THE END. >> I DON'T THINK THAT'S PART OF THIS PROJECT FROM WHAT I HEAR. YOU NEED THE TISSUE TO BE ABLE TO COMBINE ISH AND IHC PROTEINS TO CERTAIN CELLS. IF I UNDERSTAND YOUR QUESTION CORRECTLY. >> I GUESS WHAT I I'M TRYING TO SAY IS HAVING THE INFORMATION OF THE TRANSCRIPTOMIC IS IMPORTANT BUT BECAUSE SOME DOES NOT GO ALL THE WAY TO TRANSLATIONAL STAGE, WHAT KIND OF INFORMATION CAN WE GATHER FROM THAT DATABASE? >> YOU NEED TO KNOW WHERE THE TRANSCRIPT IS COMING FROM FIRST OF ALL. WHETHER MATERNAL ENDOTHELIUM OR PLACENTA, WHETHER FROM THE -- >> I THINK HER QUESTION IS MORE MECHANISTIC AND THIS IS SOMETHING THAT DID COME UP IN OUR GROUP. AND THE IDEA WAS TO INTEGRATE A WHOLE BUNCH OF DIFFERENT METHODOLOGYIES, SO GLOBAL RUN ON SEQUENCING WHICH TELLS YOU THE TRANSCRIPTION OF THE GENE, RNA SEQ WHICH TELLS YOU STEADY STATE LEVELS, RIBO SEQ TO DETERMINE WHICH RNAs ARE ENGAGED WITH THE RIBOSOME AND BEING TRANSLATED. AND YOU CAN TAKE THAT TO THE PROTEOMICS SO THERE IS A PATHWAY FOR UNDERSTANDING -- Q. THE IMPORTANCE OF FILLING DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THOSE GAPS IN BETWEEN BEFORE WE GET TO TRANSLATIONAL STAGE. >> I WOULD LIKE TO MAKE A COMMENT ON THE LAST QUESTIONER, I THINK THIS IS ONE OF THOSE AREAS WHERE WE DO HAVE BIOINFORMATIC CHALLENGES WE HAVE LOTS OF RNA SEQ AND OTHER DATA FROM CYTOTROPHO BLAST OR BIG BANKS OF SHOTGUN MASS SPECTROMETRY DATA. WE'RE WORKING WITH A COMPANY TO INTEGRATE THE RESULTS AND TRY TO COME UP WITH PATHWAY ANALYSES, THOSE PLATFORMS, THOSE ANALYTICAL APPROACHES DON'T EXIST YET. SO I THINK IT COULD BE AN AREA WHERE TO PUT DATA TOGETHER IN THE WAY YOU SAY, WORKING WITH COMPANIES AND TRYING TO GET THEIR BUY-IN INTO THIS WOULD BE A GREAT CHANCE. >> THE REASON I BRING THIS UP, THE PROTEIN OF MY INTEREST WHEN WE HAVE FIGURED IT OUT WAS GENETICALLY IT'S THERE. BUT SOMEHOW WE DON'T HAVE THE PROTEIN AND WHEN WE LOOK AT THAT IN BETWEEN IN MINOR ADULTS GET PRODUCED BUT IT'S DECADE, -- DECAYED, IT'S TURNED OVER BEFORE IT'S MADE INTO THE PROTEIN TO BE USEFUL IN THE DOWN LINE PATHWAYS SO HAVING THIS KIND OF INFORMATION HOW IT'S TRANSLATED INTO THE PHYSIOLOGICAL STATE, HOW TO ENTERLINK THIS INFORMATION WE'RE GATHERING I THINK IS REALLY IMPORTANT. >> THANK YOU. LEE CROUSE, UT SOUTH WESTERN, I WANT TO TOUCH TWO POINTS THAT CAME UP FROM OUR GROUP THAT WERE ADDRESSED MAYBE A LITTLE BIT IN OTHER SESSIONS AND ALSO THIS CURRENT ONE. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed FIRST THIS IDEA OF HYPOTHESIS DRIVEN RESEARCH FROM OMICS. I WOULD LIKE TO STAND HERE AT THE MICROPHONE AND SAY I THINK THAT'S A BAD IDEA. THAT IT ACTUALLY -- AT LEAST ONE PERSON AGREES, I THINK IT'S REALLY CIRCUM INVESTMENTS THE POWER OF -- CIRCUMVENT IT IS THE POWER OF THE OMICS. A HYPOTHESIS BASICALLY ASSUMES A CERTAIN LEVEL OF KNOWLEDGE, YOU'RE INJECTING BIAS INTO THE QUESTION YOU'RE ASKING. THAT IS WHY WE DEVELOP OMICS PROCESSES OR METHODOLOGIES IN THE FIRST PLACE IS TO GO TO THOSE DARK AREAS THAT ARE OUTSIDE OF DIRECTLY UNDER THE STREET LIGHT AND PROBED THE AREAS THAT WE HAVE NO KNOWLEDGE ABOUT. I THINK AT THIS POINT WE SHOULD BE BEYOND THAT. IT IS A COMMON THING YOU SEE IN GRAND REVIEWS, THIS ISN'T HYPOTHESIS DRIVEN SO THERE IS A POLICE FOR OMICS IN TESTING HYPOTHESIS. YOU CAN DO IT IN A GLOBAL WAY. THERE NEEDS TO BE A STRONG COMPONENT IN ALL THIS WHERE WE SAY THE HYPOTHESIS IS THAT THE PROTEOME OR THE TRANSCRIPTOME REFLECTS THE BIOLOGY OF TISSUE. THAT'S THE HYPOTHESIS AND WE'LL FIGURE OUT THE DETAILS LATER. THAT IS ONE POINT. THE OTHER POINT THE MAKE, THERE'S A LOT OF DISCUSSION ABOUT WHAT'S THE BEST LEVEL TO BE STUDYING THE BIOLOGY, SHOULD WITH WE LOOK EARLY IN PREGNANCY, IS THE DELIVERED PLACENTA A GOOD MODEL? AGAIN, I WANT TO CAUTION AGAINST STANDING AND BEATING YOUR FIST AND SAYING THIS IS THE BEST WAY TO DO IT, THIS IS THE ONLY WAY TO DO IT. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THEN I THINK THE SCIENCE BECOMES VERY PAROCHIAL AND WE START FIGHTING ABOUT THINGS THAT PREVENT US FROM LOOKING BIGGER PICTURE AND UNDERSTANDING EACH VIEWPOINT HAS TO CONTRIBUTE TO THE OVERALL UNDERSTANDING. THAT'S THE POINT I'LL PUT OUT THERE. >> AGREED. >> IT'S REALLY HARD TO DO THAT, WHEN COMPANY CHANGES CONTROLS AN YOU HAVE TO REPEAT YOUR EXPERIMENTS ALL OVER AGAIN ON THE I RAY PLATFORMS. I WANTED TO SPEAK TO SOMETHING UL RAISED NICELY, WITH GREAT GOOD HUMOR AS ALWAYS AS SOON SAN MENTIONED AS WELL. WE NEED PUBLIC PRIVATE PARTNERSHIP FOR THIS THIS, WE NEED GOOGLE, I LOVE THE IDEA OF A PLUG GOOGLE AS THE ATLAS FOR THE PLACENTA AND WHO KNOW ALSO THEY WOULDN'T LIKE THE IDEA AS WELL. THE COMPUTATIONAL SKILLS AND NECESSARY COMPUTER SKILLS TO BE ABLE TO BUILD THE ATLAS THAT JOHN ELIKAS IS ASKING US ALL TO SUBMIT IDEAS FOR, WE CAN MODEL IT AFTER THE CANCER SITES. WE CAN USE MORE MATURE FIELDS AS AN EXAMPLE. BUT THE WAY TO GET THE PUBLIC INVOLVEMENT THE PRIVATE INVOLVEMENT OF INDIVIDUALS WHO ARE PREGNANT, WHO MAYBE WILLING TO CARRY THE SENSOR THAT WE WERE INTRODUCED TO YESTERDAY IS TO BE WORKING THROUGH THE CUTTING EDGE TECHNOLOGIES COMING FROM SILICON VALLEY AND ELSEWHERE. I DON'T KNOW NIBBLE IN GOOGLE BUT AT LEAST THEIR -- I DON'T KNOW ANYBODY IN GOOGLE, BUT THE CHAIR IS A WOMAN, RIGHT? OR -- HAVE I GOT THE WRONG -- DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed OKAY. RIGHT. WE HAVE A REPRESENTATIVE OF GATES HERE, THERE IS OPPORTUNITY GIVEN HOW MUCH EFFORT THE NIH PUTS INTO THIS TO SAY E WE WANT TO DO THIS DIFFERENTLY. WE DONE WANT INDIVIDUAL LABS POSTING THEIR DATA TO REPOSITORY. WE WANT TO INTEGRATE IT AND THAT MIGHT TAKE THAT PARTNERSHIP. >> THANK YOU. I HAVE BEEN PERSONALLY WISHING THERE WAS A WAY TO GET IBM WATSON INVOLVED. >> CRAIG REUBENS FROM THE GAS PROGRAM. THANKS FOR WHAT YOU HAVE DONE TODAY AND STILL DOING, IT'S A GREAT OPPORTUNITY TO SHARE IDEAS. JUST OUT OF THE BOX IDEA AND ALSO TO LET YOU KNOW GASTRO REPOSITORY WE'RE TRYING TO ADDRESS THESE VERY THINGS YOU GUYS BROUGHT OUT. IT IS DOABLE. AND THE ERB ISSUES ARE DOABLE AND WE'RE HAPPY TO SHARE THAT, WE'RE PUTTING A LOT OF OUR TOOLS THAT WE DEVELOP FOR OUR OWN REPOSITORY OUT ONLINE SO THAT ALL OF YOU CAN HAVE ACCESS TO THEM ON OUR GAP WEBSITE. VALIDATED QUESTIONNAIRES PROTOCOLS FOR QAQE PROCEDURE, THAT SORT OF THING AND WE'LL UPDATE EVERY SIX MONTHS WE ARE NOT LAYING CLAIM THEY ARE OURS. A LOT COME FROM YOU AND PUT THEM IN HOW YOU COLLECT WHAT WE'RE TRYING TO DO, WE HAVE PLACENTAL SAMPLES THAT NEED TO BE USED. MY POINT SNOT TO ADVERTISE BUT TO TELL YOU OTHERS TOO. NOT JUST US. ONE LAST THING IS WE'RE TRYING DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed TO GET A REGISTRY STARTED, COUPLE IN MCGILL AND ONE COMING OUT OF OXFORD, PEOPLE CAN GO AND PUT IN WHAT THEY'RE ACTUALLY COLLECTING. AND WHO TO CONTACT WHERE YOU GO WHO IS COLLECTING WHAT AND WHAT POPULATIONS, I THINK THE IDEA OF TRYING TO DO A SUPERBANK WILL BE A CHALLENGE, IT MAY MISS POPULATIONS THAT REALLY IMPACTED BY ALL THE DIFFERENT TYPES OF ADVERSE OUTCOMES IN PREGNANCY. WHERE YOU LIVE GEOGRAPHY, THE ENVIRONMENT YOU LIVE IN, SO IT'S VERY IMPORTANT WE UNDERSTAND WHERE PEOPLE ARE ACTUALLY DOING THE POPULATION BASED COLLECTING THE KIND OF SAMPLES AND KIND OF DATA THEY COLLECT. SO LET'S PUT THAT OUT THERE AND HAPPY TO ANSWER ANY QUESTIONS, I'M AROUND TODAY. THE OTHER IS A LITTLE OUT OF THE BOX IDEA. ONE THAT MAYBE WILL TIE INTO IMAGING COLLEAGUES HOPEFULLY THEY WILL HAVE SOME COMMENT. THERE'S WORK DONE ON ISSUE ENGINEERING AN RE-ENGINEERING. THIS BRINGS IN OUR STRUCTURAL BIOLOGY AND ENGINEER AS WELL. WHAT ABOUT PLACENTA 3-D PRINTING PROGRAM, STUDYING AS IT GROWS THROUGH THAT KIND OF TECHNOLOGY. IT SOUNDS LATE ODD AND UNUSUAL BUT WE'RE BUILDING A HEART SO WHY CAN'T WE BUILD A PLACENTA AND THEN USE IT TO ACTUALLY STUDY WHAT'S GOING ON, IT MAY HELP GET AROUND THE ISSUES OF EARLY SAMPLING AND WHAT'S GOING ON IN EARLY GESTATION. AND COUPLED WITH SOME OF THE COOL IMAGING WE SAW YESTERDAY IT OFFERS MAYBE SOME OPPORTUNITY BUT BRINGS IN ANOTHER COUPLE OF FIELDS THAT WE HAVEN'T REALLY MAYBE EMPHASIZED. THANK YOU. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed >> JUST TO COMMENT REAL QUICK BACK TO CRAIG. THE 3-D IMAGING IS 3-D PRINTING IS AN INTERESTING ONE, WE HAVE TAKEN THAT ON WITH RICE UNIVERSITY AND THE RICE 360 PROGRAM. THERE ARE SOME UNIQUE CHALLENGES IN TERMS OF DOING PLACENTAL 3-D PRINTING BUT NONE OF WHICH ARE NOT OVERCOMABLE, BUNCH OF MUCH SMARTER PEOPLE THAN MY GROUP JUMPED IN ON IT BUT THERE ARE FOLKS THAT ARE WORKING ON IT IN UNDERGRAD TYPESETTINGS BECAUSE THIS IS SUPER SUPER GREAT WORK FOR UNDERGRADS. >> IT'S LOUISE LORN FROM UC SAN DIEGO. FIRST I WANT TO SECOND WHAT LEE SAID, I DID ANY GRAD STUDIES WITH PAT BROWN STANFORD IN EARLY DAYS OF MICROARRAY, I REMEMBER CONTENTIOUS BIOCHEMISTRY DEPARTMENT RETREATS, WHEN PAT WAS BEING ATTACKED FOR NOT HAVING HYPOTHESIS, HE RESPONDED THAT WE'RE NOT SMART ENOUGH TO KNOW WHAT WE DON'T KNOW. WE LEARNED A LOT FROM HIS WORK. I WANT TO SPEAK MORE ABOUT POTENTIAL IDEAS FOR STRUCTURING COLLABORATIONS CURRENTLY IN ONE OF TWO ERCCs NIH SPONSORS WHICH HAS BEEN A WONDERFUL CONSORTIUM WHERE PEOPLE COMING TO WITH DIFFERENCE EXPERTISE. THEY COME IN WITH THEIR OWN GRANTS OWN FOCUSES THAT ARE ENCOURAGED TO WORK TOGETHER IN WORKING GROUPS. OUT OF THAT WORKING GROUP WE HAVE BUILT A NUMBER OF CONSENSUS STANDARD OPERATING PROCEDURE WHICH IS ARE NOT MEANT TO BE PROSCRIPTIVE BUT MEANT TO BE SHARED AMONGST THE COMMUNITY, THEY HAVE BEEN SHARED ON THE SRA DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed PORTAL. THEY HAVE THINGS USEFUL TO THIS GROUP BECAUSE THEY HAVE TO DO WITH SAMPLE COLLECTION PROCESSING AND STORAGE, RNA ISOLATION FROM DIFFERENT BIOFLUIDS AND SOON POSTED PROTOCOLS FOR SEQUENCING LIBRARY. INSTRUCTION. OTHERS HAVE DONE BY VIRTUAL REPOSITORY AND WE HAVE A METADATA AND DATA STANDARDS GROUP WHICH IS HEAVILY POPULATED BY DATA MANAGEMENT GROUP DMRR WHICH HAS A PIPELINE PERSONAL RNA SEQUENCING ANALYSIS. SO THERE'S DIFFERENCE ORGANISMS NOT JUST HUMAN BUS ROOTING DOWN TO DOWNSTREAM NETWORK BUILDING AND VISUALIZATION. SO THOSE ARE RESOURCES THAT EXIST ALREADY THAT I THINK WE CAN BUILD ON AND POTENTIALLY MODEL SOME OF THE CONSTRUCT HOW THE RFAs COME OUT AND HOW PEOPLE ENCOURAGED TO WORK TOGETHER. THE OTHER THING IS THERE'S THE OTHER ERCC WHICH IS THE EXOGENOUS RNA CONTROL CONSORTIUM THAT HAS SYNTHETIC LONG RNAs AVAILABLE FROM LIVE TECH ACTUALLY FOR SPIKE AN CONTROLS AND IN THE PROCESS OF BUILDING SMALL RNA STANDARDS AS WELL. SO WE HAVE THINGS THAT NIH THAT HAS INVESTED IN THAT I THINK WE CAN PROBABLY LEVERAGE. IN ADDITION WHAT'S REALLY NICE IS DMRR FOR ERC CONSORTIUM WILL HELP US UP LOAD OUR DATA TO DB GAP SO AS LONG AS WE PUT IN OUR DATA TO THE NIH SITE THROUGH METADATA THEY WILL HELP GO THROUGH LONG AND TEDIOUS PROCESS THAT KJERSTI WAS ALLUDING TO SO THAT ENCOURAGES EARLY DATA SHARING SO WHEN YOU PUBLISH THE PAPERS THE UP LOAD HAPPENS DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed RELATIVELY PAIN FREE. THANKS. >> I WANT TO ECHO LOUISE'S COMMENT, IT'S IMPORTANT TO USE RESOURCES AVAILABLE FROM NIH IS A SOFTWARE PACKAGE CALLED INNER MINE WHICH IS A WEB TOOL TO BUILD COMMUNITY PLATFORMS JUST LIKE THE GO GOOGLE. THAT SOFTWARE IS NOW USED BY ALL MODEL ORGANISMS AS WELL AS SOME OF THE CANCER DATABASES. IT'S DEVELOPED YOU CAN COMPARE LISTS OF DATA SETS, YOU CAN TAKE HUNDREDS OF SEQUENCING LIBRARIES FROM SHORT READ ARCHIVE AND COMPARE THEM SO WE CAN SAY IF I HAVE THESE HUNDRED LISTS OF LIBRARY, WHAT ARE THE TOP TEN THINGS THAT COME OUT IN ALL THE THIS. YOU CAN DO THAT WITH CHIP SEQ DATA, OUTS A REALLY COMPREHENSIVE WAY TO LOOK AT LARGE DATA SETS AND PROBE PUBMED AND OTHER THINGS AND IT'S ALREADY BEEN DEVELOPED THROUGH NIH AND IS BEING USED. I THINK IT COULD BE USED QUICKLY BY THIS COMMUNITY TO GET A LAUNCH REALLY INEXPENSIVELY BECAUSE THE PLATFORM ALREADY EXISTS. TOE TO CHANGE ZEBRAFISH TO PLACENTA AND AWAY WE GO. SO THE RESOURCES EXIST IS MY POINT. >> THANK YOU. >> I HAVE BEEN HEARING A LOT HOW WE NEED TO HAVE CELL TYPE SPECIFIC AND WE DON'T KNOW TROPHO BLASTS CELL TYPES THERE ARE AND ALSO TALKING SAMPLING PLACENTAL BED. I WANT TO EMPHASIZE GOING TO OTHER DIRECTION TOO, PEOPLE FORGET ABOUT THE CHORION AND IF DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed WE'RE TALKING PLACENTA BASIC FUNCTION IS TO HAVE THESE TWO BLOODSTREAMS MEET BUT NOT CONTACT AND SO WE REALLY NEED TO BE SAMPLING AND THINKING ABOUT AND UNDERSTANDING THAT WHOLE VASCULATURE, THE FETAL VASCULATURE, PARTICULARLY FOR WORK ABOUT WHAT'S SECRETED INTO THE FETAL BLOODSTREAM, BETTER UNDERSTANDING OF THAT FIELD VASCULATURE WOULD BE KEY. >> QUITE A FEW ARE MEMBERS OF CONSORTIA, STANDARDIZATION PROTOCOLS, WE HEARD FROM DIFFERENT MEMBERS, MEMBERS MEMBERS OF DIFFERENT CONSORTIA, WE HEARD ABOUT RESOURCES SOME WHICH WE KNOW ABOUT, I'M SURE A LOT DON'T KNOW ABOUT THESE RESOURCES COULD I REQUEST THAT MAYBE JOB ONE AS NIH TRY TO SET UP A CLEARINGHOUSE, A WEBSITE THAT LISTS ALL THESE RESOURCES, SO WE CAN GO THERE FIND OUT WHAT IS AVAILABLE THEN START TO CHOOSE, IDENTIFY WHAT WE WANT TO USE? TO MAKE IT AVAILABLE? I'M SURE LIKE ME A LOT OF US DIDN'T KNOW RESOURCES THAT LOUISE OUTLINED >> I HAVE WRITTEN IT ON MY NOTE PAD A FEW MINUTES AGO. >> ALAN SAYING THAT WILL BE JOB ONE. >> I DIDN'T SAY JOB ONE, IT'S DAVID'S JOB ONE. >> GREAT DELEGATION. >> I WANT TO FOLLOW-UP WHAT STACY SAID ABOUT STANDARDIZATION AND MARKERS AND CONTROLS AND CHIPS CHANGE, PROTOCOLS CHANGING. EXPRESSION THAT COMES TO MY MIND IS THOSE WHO DON'T LEARN FROM DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed HISTORY DESTINED TO REPEAT IT. YOU'LL SEE MY POINT. REFERRING TO HISTORY OF NASA. THE APOLLO ON FIRE AND APOLLO 13 DISASTER WERE CAUSED BY THE FACT THEY STARTED WITH A SINGLE DESIGN, ANYONE SUPPOSEDLY IMPROVING IT AND WORKING AND CHANGING SYSTEM TOMS THAT BECAME INEN COMPATIBLE LED TO THE DISASTERS. THEY LEARNED THE LESSON THAT SOME POINT IN TIME, NO MATTER WHERE TECHNOLOGY MOVING FORWARD YOU LOCK IN FOR A SPECIFIC STUDY AND DON'T CHANGE IT. WHEN THEY FORGET THAT LESSON YOU HAVE THE SPACE SHUTTLE EXPLOSION S. MY POINT HERE, THERE IS A QUESTION IS IT BETTER WE DISCUSSED AT LENGTH, IS IT BETTER THIS WORK INITIALLY DONE CENTRALIZED REFERRING HERE TO THE GENOMIC TRANSCRIPTOMIC AND METABALOMIC WORK AND PROTEOMIC WORK, IS IT ACTUALLY BEST THAT SOME OF THAT BE CENTRALIZED, A SMALL NUMBER OR ONE PLACE, INCLUDING NIH ITSELF TO ESTABLISH NORMAL PREGNANCY, WHAT HAPPENS IN NORMAL PREGNANCY SO THAT EVERYTHING IS STANDARDIZED AN INTEGRATABLE INCLUDING FILE FORMATS. SO WE CAN ENTERGRATE DEBATE THAT INFORMATION. WE DO THAT ON A LIMITED SCALE AND TAKE THAT DATA AND LOOK AT DISEASE STATES AND WHERE THINGS ARE DIFFERENT. OTHERWISE WE COULD END UP RUSHING TO DO THIS, SPENDING ENORMOUS AM OF MONEY AND NEVER GETTING THE FULL OUTCOME WE WERE HOPING FOR. >> TO REITERATE THAT POINT HMP WE DID THAT AGAINST COMMUNITY DATA, WE LEARNED THE SEQUENCING DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SITE DIDN'T MATTER. WE CAN SEQUENCE ANY NUMBER OF FOUR DIFFERENT NIH GENOME CENTERS AND THAT DIDN'T MATTER FOR META GENOMIC SEQUENCING. BUT USING THE ABSOLUTE SAME PROTOCOL TO EXTRACT THE DNA WAS INCREDIBLY IMPORTANT. THAT'S WHY ONE FIRST THING WE DID WAS PUBLISH TO THE DAC WHAT THE PROTOCOL WAS, THE BEFORE WE USE T LOT NUMBERS WE USE, ET CETERA. AND STANDARDIZE THOSE PROTOCOLS FOR A REASON. SO WE FOUND WE CAN DO IT IN DIFFERENCE SITES BUT TEST AGAINST COMMUNITY STANDARDS. SO INCREDIBLY IMPORTANT POINT IN THE TRANSCRIPTOME ARM, TALKING RIBOSOMAL SEQ AND OTHER TECHNOLOGIES THAT ARE HIGHLY DYNAMIC THAT WILL BE IMPORTANT TO SAY HOW MUCH CAN YOU MESS WITH THE PROTOCOL BEFORE YOU SEE DIFFERENCES AND HOW MUCH -- WE PLAYED WITH THAT WITH PROJECT 18 FOR NCS ABOUT HOW LONG CAN YOU LEAVE PLACENTA OUT, CAN YOU MOVE I ACROSS NORTH DA CO-DARK THIS STUFF, BUT IT'S A VERY VALID QUESTION THAT EVERYBODY IN THIS ROOM HAVE DIFFERENCE LEVELS OF EXPERIENCE ADDRESSING. >> OTHER COMMENTS? WE'LL MOVE ON. WE HAVE GOT TO MOVE ON. >> IN MEETING WITH PENNY, WE DECIDED WE HAVE COMMON THEMES BUT WE HAD ADDED VALUE AND HAVING TWO SEPARATE PRESENTATIONS. SO GIVE TEN MINUTES FOR MY PRESENTATION WITH THE GROUP, I WANT TO THANK THE GROUP FOR GREAT INTERACTIONS AND VERY GOODIES CUSHION THEN PRESENT HER SLIDES. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SO VERY SIMILAR THEMES TO WHAT YOU HAVE HEARD THIS MORNING FROM ALL THE PRESENTATIONS, THERE IS A LOT OF COMMONNALTIES BETWEEN -- SO THE FIRST QUESTION POSED TO US WHAT COULD WE DO TODAY WITH THE TECHNOLOGY BOTH ULTRASOUND AND MRI? SO WE LUMP THEM TOGETHER FOR BOTH ULTRASOUND IMAGING AND MRI, TYPICAL PLACENTAL PROBLEMS WE SEE EVERY DAY SUCH AS CRY DAS, SO FORTH THAT I SHOWED YESTERDAY. WORE GOOD WITH BIOMETRY, BOTH TECHNOLOGY ASSESSING PLACENTAL VOLUME WITH 3-D ULTRASOUND, MRI LENGTH THICKNESS, BASAL PLATE THICKNESS SO FORTH. THAT'S LIMITED USE FOR MRI BEFORE 16 WEEKS, THERE'S A GAP THERE BECAUSE OF SAFETY ISSUES, ULTRASOUND IS BETTER IN EARLY GESTATION BECAUSE YOU CAN GET THE WHOLE PLACENTA WITHIN A 3-D VOLUME SO YOU CAN GET MORE ACCURATE MEASUREMENTS AN BIOMETRIC MEASUREMENTS, YOU DON'T HAVE TO RECONSTRUCT PLACENTA FROM MULTIPLE VOLUMES. VASCULAR FLOW, BOTH TECHNOLOGIES DO VASCULAR FLOW TODAY, IT'S UNCLEAR TO WHAT EXTENT THIS IS DONE, DIFFERENT APPROACHES OF ULTRA VASCULAR INDEXING 3-D, COLOR AND SPECTRAL DOPPLER, THE CONVENTIONAL STUFF, I ADDED HERE WE NEED TO UNDERSTAND WHAT WE ARE ACTUALLY MEASURING. WE NEED TO COMPARE TECHNOLOGY TO SEE ARE WE MEASURING THE RIGHT THINGS AND WITH NEWER TECHNOLOGY, BOTH MR AND ULTRASOUND, THIS AREA WILL IMPROVE. WE BOTH CAN DO TISSUE STRUCTURE SUCH AS STIFFNESS WITH BUT WE DO NOT KNOW BECAUSE THE TECHNOLOGY PHYSIOLOGY OF WHAT WE ARE DOING ARE BASICALLY DIFFERENT BETWEEN DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed ULTRASOUND AND MR, WE'RE NOT SURE WE ARE MEASURING THE SAME THING. SO WE'RE MEASURING DENSITY OF TISSUE BUT CERTAINLY THIS WOULD BE NICE TO HAVE CONFIRMATION BETWEEN TWO THE TECHNOLOGY ON WHAT WE'RE DOING. SPECIFICALLY FOR MRI BEYOND THIS LIST IS WE DO QUANTITATIVE THE IT SHALL SHOE PARAMETER MAPPING, OXYGENATION TO A LIMITED EXTENT, NOT FULLY DEVELOPED. BOLD MRI CONCEPT, ALSO OXYGEN MAPPING OF PLACENTA BUT NOT QUANTITATIVE. IT IS THE SPECTROSCOPY AND DIFFUSION WEIGHTED IMAGING. NEXT QUESTION, WHAT ARE THE KEY TECHNICAL CHALLENGES FOR THE TECHNOLOGY FOR ULTRASOUND, CERTAINLY THEY'RE DIFFERENCE THAN ANTERIOR PLACENTA THERE'S DEGRADATION, BECAUSE OF THE DISTANCE OF PLACENTA BECAUSE OF EARLY GESTATION BUT THERE'S ANOTHER ELEMENT BECAUSE OF PROXIMITY OF PLACENTA TO MA TERM PELVIC VESSELS THE MOTION ARTIFACT IS AMPLIFIED IN THE PLACENTA SO IT'S AN AREA TO BE EVALUATED. IN GENERAL MOTION ARTICLE ART FACT, -- ARTIFACT, THOUGH IT'S LIMITED TO THIS BUT CERTAINLY FETAL MOTIONS AND SO FORTH THROUGHOUT THE -- POSTERIOR PLACENTA MAY HAVE IMPACT. MRI MACHINE CAPABILITIES RESOLUTION THAT NEEDS TO BE WORKED UP FROM THE TECHNICAL ASPECT. THERE WAS SOME DISCUSSION ABOUT A BENEFIT IN HAVING COMMERCIAL COMPANIES DEVELOP A SPECIAL COIL FOR PREGNANCY, SPECIAL FLEXIBLE COIL RATHER THAN THE COIL THAT EXISTS TODAY THAT'S A HARD COIL. AND MOTION ARTIFACT ALSO IS AN ISSUE FOR MRI. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SO BOTH BMI IS ISSUE FOR ULTRASOUND ESPECIALLY LATER IN GESTATION BECAUSE OF LACK OF ACCESS OF TRANSVAGINAL APPROACH. BUT ALSO FOR MR BMI AN ISSUE IN THE -- A THEME THAT CAME ACROSS THROUGHOUT THE STANDARDIZATION, HOW TO STANDARDIZE WHAT WE DO, THE APPROACH, TO THE EXAMINATIONS, AND ALSO HOW DO WE DEFINE WHAT IS NORMAL NORMALITY AND COMPARABILITY BETWEEN THE PATIENTS. LACK OF COMPATIBILITY AS WE DISCUSSED THROUGHOUT THE MORN AND RELATING TO PREGNANCY OUTCOME. THE OTHER QUESTION AS WELL AS KEY PRACTICAL CHALLENGES FOR ULTRASOUND, STANDARDIZATION OF EXAMPLE PES THE USER LIKE WHEN WE DO FOR INSTANCE PLACENTAL INDEXING, DO WE STANDARDIZE THE BOX, THE DEPTH HOW MUCH VELOCITY WE ARE PICKING UP WITH WITHIN THAT VOLUME, SO ALL THESE THINGS I THINK NEED TO BE STANDARDIZED. AND EQUIPMENT, USER APPROACH AND EQUIPMENT. DEFINING RATES OF NORMALITY AND VARIABILITY WITHIN THE POPULATION, AND EXPERTISE IS AVAILABLE TRY TO REFINE METHODOLOGY THAT NEEDS TO BE SOME TRAINING SOME EXPANSION OF THE EXPERTISE ASPECT OF IMAGING. MRI THE SAME, ESPECIALLY EARLY GESTATION THAT'S DURING THE DISCUSSION THERE WAS A COMMON THEME THAT MRI IS FAIRLY GOOD BUT HAS NOT TESTED BEFORE 16 WEEKS THAT'S KNOWING THE HUMAN PLACENTA PROJECTS TARGET IS IDENTIFIED, EARLY PREGNANCY EVENTS, SO A BIG LIMITATION OF MRI TODAY. COST P AND ACCESS ISSUE FOR MRI, AND IT'S NOT PRACTICALLY IN THE WAY IT IS DONE AS A SCREENING TOOL. SO THAT SOMETHING NEEDS TO BE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed ADDRESSED MAYBE WE CAN COME UP WITH A FOCUS PLACENTAL APPLICATION ON MRI THAT'S EASIER AND DOES NOT REQUIRE COST TIME AND SO FORTH. EDUCATION AN AWARENESS ALSO IS AN AREA TO BE ADDRESSED. OVERALL VALUE TO THE HUMAN PLACENTA PROJECT. STRENGTH, HEART RATE NEEDS TO BE IMPROVED. ULTRASOUND PROBES CERTAINLY HIGHER RESOLUTION, HIGHER ACCESS TO THE PLACENTA. IMPROVEMENT IN ELECT PHOTOGRAPHY, STANDARD POSTERIOR PLACENTA, BETTER ASSESSMENT OF PROFUSION OF PLACENTA. SAFE CONTRAST AGENT, THAT'S A -- NOT AN EASY TARGET, WE STRUGGLED EXTENSIVELY TO MAKE CONTRAST AGENTS AVAILABLE IN THE UNITED STATES AND WE'RE STILL HAVING TROUBLE MANY YEARS BEHIND OTHER COUNTRIES TO MAKE IT AVAILABLE FOR PREGNANCY IS A DIFFICULT TASK. WE DISCUSS THERMAL IMAGING, THAT'S AN AREA TO BE EXPLORED, OPTS MALL IMAGING ALSO THE DISCUSSED. LIMITATION IT IS SAME DAY TO DEPTH OF FIELD THAT YOU NEED TO ACCESS THE PLACENTA. WE DISCAN YOUD ASSESSMENT OF METABOLIC RATE AND OXYGENATION BY IMAGING, THIS WAS AN APPEALING CONCEPT, GO THERE BOTH WITH MR AND ULTRASOUND AND AUTOMATED AND SEGMENTED ULTRASOUND APPROACH TO COMPARE PLACENTAS AT VARIOUS STAGES. THE NEXT BIG THING WE WERE ASKING TO THINK ABOUT, WHAT COULD BE -- PROBABLY WE COULD HAVE THOUGHT BEYOND THE BOX WE WERE IN BUT FOCUSED TIME ON WHAT COULD BE COMBINED TECHNOLOGIES AND ENHANCE CREATE SYNERGY BETWEEN THE BENEFIT OF ULTRA DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SOUND CAN BE ADDED TO THE BENEFIT OF MRI. WE TALK ABOUT HAVING SENSORS THAT ARE LESS INVASIVE, MAYBE ATTACHED TO A TRANSVAGINAL ULTRASOUND PROBE CLOSE TO THE PLACENTA IN VERY EARLY GESTATION AND MEASURE OXYGENATION OR MEASURE THINGS THAT ARE FOUND TO BE OF VALUE AND THAT SHORT WINDOW EARLY ON IN PREGNANCY. COST CONSIDERATION, COST CONTRIBUTION SHOULD BE TAKEN INTO ACCOUNT, INFRASTRUCTURE THROUGH PUT FOR MI WE TALK THE COSTS ARE DROPPING AND THAT SHOULD NOT BE AN IMITATION BECAUSE I GAVE AN EXAMPLE, I BOUGHT A HIGH END ULTRASOUND MACHINE WHEN I FIRST MOVED TO EASTERN VIRGINIA MEDICAL SCHOOL AND TODAY I CAN BUY THE HIGH END MACHINE FOR LESS COST THAN I BOUGHT IN 22 YEARS AGO. SO I THINK THE COST OF THE TECHNOLOGY IS COMING DOWN. THAT WILL BE DRIVEN ALSO BY CLINICAL PRESSURES FROM THE MARKET BUT CERTAINLY THAT COST SHOULDN'T LIMIT US WHAT WE DO. DETERMINE WHAT IS SUBSTANTIAL FOR WIDESPREAD USE, HOW TO APPLY ROUTINELY TO SCREEN PREGNANCY. THE DATA HAS TO BE PUSHING BEHIND THESE DECISIONS, SUPPORT FOR FUNDING SMALLER CLINICAL SITES, LARGER SITES TO DO CUTTING EDGE SCIENCE, SIMILAR THEMES DISCUSSED FOR STANDARDIZATION AND GETTING THE DATA AND THEN EXPANDING THE SCOPE. HIGHLY SOPHISTICATED TECHNOLOGIES UNLIKELY WIDELY BUT CAN USE TO IMPROVE SCREENING AND WHAT WE HAVE TODAY. ROADBLOCKS, (INAUDIBLE) ACROSS MULTIPLE SITES, DIFFERENT TIME POINTS IN PREGNANCY, CLINICAL GUIDELINES STANDARDIZATION, DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed HAVING CONSENSUS IN THE APPROACH, BOTH ON THE USER AND THE TECHNOLOGY, LIMITATIONS IN THE FIELD OF VIEW ESPECIALLY ULTRASOUND LATER IN GESTATION. VALIDATING IMAGE FINDINGS WITH UNDERLYING ANATOMY, HISTOLOGY, THIS WAS DISCUSSED UNDERSTANDING THAT IT'S BEYOND THE SCOPE OF WHAT WE'RE TRYING TO DO. AND THEN VALIDATION HARDWARE AND ST. WARE INDUSTRY AND TRANSPARENCY WITH INDUSTRY AND INTELLECTUAL -- HOW CAN WE GET THE INDUSTRY TO TALK TOGETHER. ON THE 3-D AS SOMETHING WE DON'T HAVE A COMMON VOLUME WAY TO STORE VOLUMES FROM DIFFERENT INDUSTRY INTO ONE REPOSITORY EACH MANUFACTURER HAVE THEIR OWN WAY OF GENERATE 3-D VOLUME DATA THAT'S AN ASPECT WE NEED THE TRY TO RESOLVE. AGAIN BANKED IMAGES WE DISCUSSED. VAULT OF TECHNOLOGY OVERALL, WE FEEL -- VALUE OF THE TECHNOLOGY OVERALL, WE FEEL THE PROJECT OVERALL IS EXTREMELY VALUABLE, IT WILL HELP MATERNAL NEONATAL OUTCOME, PRENATAL CARE WORLDWIDE AND ENHANCES UNDERSTANDING OF MATERNAL AND CHILD PHYSIOLOGY. SO THIS IS MY GROUP, MAYBE DAVID WILL HOLD THE QUESTIONS UNTIL PENNY DOES HER PIECE. >> SO THE THINGS WE DISCUSSED IN YOU ARE GROUP HAVE BEEN ADDRESSED IN THE PROCEEDINGS DISCUSSIONS AND I HAVE BEEN AMAZED THAT SOMEBODY HAS BEEN INTERACTIVE IN OMICS SECTION SYNERGIES AND THE COMMONNALTIES THAT ARE ADDRESSED THE FIRST TWO SLIDES HERE ARE ABOUT NUMEROUS DATA AND STANDARDIZATION TO BE DISCUSS AD LOT BUT THIS IS A MAJOR THEME IN OUR GROUP, WE TALKED ABOUT THIS A LOT AND IT'S DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed ACTUALLY COMING BACK TO THE LAST QUESTION, QUICK WINS IN REDS THAT TAKE MORE TIME AND CERTAINLY THAT WAS ONE THING THAT CAME OUT, WE COULD GET DATA SETS REPRODUCE DATA SETS NOW FROM LIMITED NUMBERS OF SITES, I THINK THE NIH HAS THE POWER TO MANUFACTURE THROUGH BLOCKAGE SORTING THIS PROBLEM OUT. THIS IS AN AREA NEEDS TO BE RESOLVED. I WON'T GO THROUGH THE DETAILS BECAUSE THINGS HAVE BEEN DOES CUSSED. THE INFLOOR TICKS INFRASTRUCTURE AGAIN, REALLY IMPORTANT LINKING MR AND ULTRASOUND DATA IMAGING DATA WITH THE METABALOMIC AND PARTICULARLY CLINICAL MEASURES AND BARRIERS TO FINDING STORING AND COLLECTING THAT CLINICAL DATA DISCUSSED. SO MOVING ON, WHAT CAN WE DO NOW WITH IMAGING? AS WITH WE GET -- DISCUSS STRUCTURAL IMAGING VASCULARITY OF FLOW, I WANT TO SHOW THIS SLIDE AND GIVE FROM WAYNE STATE UNIVERSITY SHOWING CHRONIC VESSELS IMAGE OF CHRONIC VESSELS FROM MRA DATA. E LAST TOGRAPHY, BETTER CORRELATIONS IN THE MRI AND ULTRASOUND DATA. WHAT WOULD HAVE AN IMMEDIATE CLINICAL IMPACT? NEW THINGS HAVE IMMEDIATE CLINICAL IMPACT. RAPID DIAGNOSIS AND TIME FOR CLINICAL CARE, DIRECT MEASUREMENT OF OXYGENATION DISCUSSED. ONE THING THAT I MEAN UP IS MEASURING -- ONE THING THAT CAME UP IS THREE EDEMA AN INFLAMMATION, THAT'S SOMETHING THAT COULD BE ADDRESSED IMMEDIATELY. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed MEASURE PLACENTA RESERVE METABOLISM, AND COME BACK TO THAT. DEALING WITH LATE FORM (INAUDIBLE) AREA UNDER INVESTIGATED. REIMBURSEMENT NEEDS TO BE CONSIDERED IN THIS CASE. THE NEXT BIG THING, A LOT OF IMAGINATIVE IDEAS ABOUT THE NEXT BIG THINGS. WE TALKED ABOUT NEW CONTRAST AGENTS. EXOGENOUS CONTRAST AGENT, HOW TO DO THIS SAFELY, NORMAL CONTRAST AGENTS, GADOLINIUM CONTRAST AGENTS THAT DOER DON'T CROSS THE PLACENTA. I HAVE NOT PUT ACKNOWLEDGMENT WHERE THIS CAME FROM BUT A GROUP DOING NEW CONTRAST AGENTS, THAT DON'T CROSS PLACENTA. CONTRAST AGENTS CONSIDERED DRUGS LIMITED IN DEVELOPMENT IN THE BY THE NIH. FDA. THANK YOU. AND AGENTS THAT PROBE CIRCULATION AS OPPOSED TO JUST MATERNAL CIRCULATION. MRS, SO THERE ARE MANY DIFFERENT NUCLEI YOU CAN STUDY WITH MRI MOST OF THE WORK IS WITH PROTONS FOR IMAGING WE CAN DO 31 OTP METABOLISM, WE CAN SEE CARBON -- EDGINESS ENERGETICS. TO DO THIS, WHOLE BODY COILS TO DO MR SPECTROSCOPY IN THE FETUS. EWE NEED SYSTEMS THAT DO THIS NOT EVERY MR SCANNER CAN DO THAT. WE NEED TO QUANTIFY THIS, ABUNDANCE OR LABEL, THE NEW KID ON THE BLOCK MRI, IT'S UNIQUE AND ONLY A FEW SITES AT THE MOMENT AND PROVIDES MESSAGE OF IMPROVING SENSITIVITY OF CARBON 13 SPECTROSCOPY, CARBON 13 MASS SPECTROSCOPY, CARBON 13 ISOTOPES NON-EYE RECOGNIZING RADIATION. YOU CAN LOOK AT A VARIETY OF DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed BIOCHEMISTRY IN VIVO AND DMP MASSIVELY INCREASES SENSITIVITY OF THIS TECHNIQUE. AND THIS IS WORK FROM ONTARIO LOOKING AT LACTATE UPTAKE, PYRUVATE UPTAKE IN MICE PLACENTA. (INAUDIBLE) IS ANOTHER TECHNIQUE WITH MRI THAT CAN BE USED TO LOOK NOT ONLY AT THINGS LIKE GLUCOSE NATURALLY OCCURRING ENDOGENOUS AGENT BUT SETH CONTRAST AGENTS CONTRAST AGENTS ACCESS. (INAUDIBLE) WAS DISCUSSED, PHOTO ACOUSTIC IMAGING AND THE COMBINATION OF MRI AND ULTRASOUND. THERE WAS A LOT OF TALK ABOUT OXYGEN UPTAKE, IN PARTICULAR LOOKING AT FREE RADICAL DAMAGE DUE TO HYPEROXIA ADMINISTERED IN PREGNANCY AND PARTICULARLY GENE LABOR. PRACTICAL LIMITATIONS. DISCUSS PATIENT COMPLIANCE, WHAT WERE THE PATIENTS PUT UP WITH, HOW MANY -- HOW LONG PATIENT SATISFIES SURVEY IS REQUIRED. OBESITY AND CLAUSTROPHOBIA WILL LIMIT APPLICATION, HOW EARLY CAN WE DO MRI. 'S COMMON WE DON'T DO IT BEFORE 18, 17, 16 WEEKS. BECAUSE SAFETY STUDY VERSUS NOT BEEN DONE, WE NEED MODELING FOR HEAT POSITION. THAT'S SOMETHING WE CAN DO EASILY. IT WAS SAID EVEN IF WE CAN'T GO TEN WEEKS IF YOU GO BETWEEN TEN AN 18 WEEKS THAT HELPS WITH THE PERIOD OF PRESENTATION. EVEN IF WE CAN SCAB THEN IS THE SPATIAL RESOLUTION LIMITING, SUGGESTION THAT IF WE CAN GET IRB APPROVAL WE CAN LOOK AT TERMINATIONS TO LOOK AT SCANNING IMAGE RESOLUTION IN THIS PERIOD. EVEN IF WE HADN'T ADDRESSED DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed SAFETY ISSUES. STANDARD DESIGN NEEDS TO BE ADDRESSED PARTICULARLY FOR CLAUSTROPHOBIA OBESE PATIENTS, IT HAS TO DO WITH CLAUSE PHOBIC PATIENTS, MUCH NUCLEAR SPECTROSCOPY IS EXPENSIVE, SPECIALLY DESIGNED COILS ARE EXPENSIVE. WE NEED TO BUY IN (INAUDIBLE) TOLL RESOLVE THESE ISSUES. WE DISCUSS NOTION, WE HAVE INADEQUATE POST PROCESSING CAPABILITY. MR DATA RECONSTRUCTION (INAUDIBLE) SAME FOR ULTRASOUND VERY LOCALIZED WE NEED TO SCAN THE MANUFACTURES TO GET INVOLVED AN HELP ADDRESS THIS PROBLEM AND ROBUST TRANSFERABLE WAY. WE NEED ANIMAL MODELS AND I WAS EXCITED BY 3-D IMAGING FOR MRI IN THIS AREA. THE REGULATORY ENVIRONMENT NEEDS TO BE ADDRESSED FOR CONTRAST AGENTS, AND ALSO IRBs. FINALLY, WHAT'S GOOD ABOUT THE HPP? IT'S BOTTOM UP, IT'S SCIENCE-FOCUSED, IT'S CONSIDER LONG TERM BENEFITS TO (INAUDIBLE) ADULT DISEASE SO IT'S CONSIDERING THE LONG TERM NOT JUST SHORT TERM DISEASES. INTERDISCIPLINARY HAVE BEEN TALKED ABOUT ALREADY THAT'S AN IMPORTANT ASPECT OF THIS PROGRAM. WE NEED TO CLOSE LOOPS TO GET INFORMATION BACK TO HANDS OF CLINICIANS TO GET NEONATAL OUTCOMES BACK TO THE SCIENTISTS. THE VALUE OF IMAGING HPP IS AN EXCELLENT TOOL FOR EXPERIMENTAL MEDICINE AND CLINICAL RESEARCH, THAT CAN BE QUANTITATED AND USED TO CHARACTERIZE LONGITUDINAL PHENOTYPE, IMAGING CAN LOOK AT SPATIAL VARIATION, SINGLE ORGANS RATHER SIMPLY SYSTEMATIC EFFECTS DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed AND IN PARTICULAR IT CAN STUDY FETAL AND MATERNAL CHANGES SEPARATELY. AND IT'S NON-INVASIVE. THANK YOU. [APPLAUSE] >> WE HAVE TIME FOR QUESTIONS. >> TWO COMMENTS I WOULD LIKE THE MAKE. FIRST WITH RESPECT TO ULTRASOUND AND THIS DIDN'T COME UP ULTRASOUND TECHNOLOGY IS OPT CUSP P OF MAJOR CHANGE, MOST BASE ON PRINCIPLES IN THE '90s OF BEAM FORMING WHERE YOU REDUCE THE DATA TO ONE VIRTUAL SENSOR NOW COMPUTING REACHED THE POINT INDEPENDENT SOURCES OF INFORMATION. SO THE ELASTOGRAPHY EFFORTS ARE THE FIRST OF THAT BUT WE'LL SEE MORE INTERESTING CHANGES IN THAT DOMAIN, ONE CHALLENGE TO SEEING THAT HAPPEN IS VENDORS ARE CLOSED, TO COMPARE ULTRASOUND TO MRI THE FILTER SOUND SYSTEMS ARE HARD TORE TAKE APART AND MODIFY COMPARED TO MRI SYSTEMS. ANOTHER COMMENT WHICH IS UNRELATED IS THAT THE ONE CHALLENGE WE FACE WITH MRI IS THAT A LOT OF THE TECHNOLOGIES WE'RE THINKING ABOUT HAVE ALL BEEN IMPORTED FROM NEUROSCIENCE. AND I THINK IN MANY CASES THERE NEEDS TO BE A RETHINKING OF HOW THEY WORK. SO TO GIVE EXAMPLES OF THAT, WE TALK ABOUT PROFUSION AND ARTERIAL SPIN LABELING BUT THE IDEA OF BEING DELIVERED TO THE PLACENTA IS NOT NECESSARY, THE METRIC WE'RE MOST INTERESTED IN, THE FACT THE 02 CIRCULATION EXCHANGES EXTREMELY IMPORTANT. SIMILARLY DIFFUSION WEIGHTED DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed IMAGING AS WE HEARD NICELY YESTERDAY, THERE'S SO MUCH MOTION THAT -- THE IDEA THAT WE'RE TALKING ABOUT BROWNIAN MOTION IS NOT REALLY THE RIGHT WAY TO BE THINKING ABOUT THIS TECHNOLOGY, SIMILARLY BOLD WHICH IS THE TECHNOLOGY E KNOW AND LOVE FOR NEUROSCIENCE DOESN'T EXACTLY HAVE THE SAME INTERPRETATION OF PLACENTA BECAUSE YOU HAVE THESE TWO CIRCULATIONS, YOU WANT TO KNOW ABOUT OXYGEN TRANSPORT AS WELL AS WHAT IS BEING CONSUMED BY THE PLACENTA SO THERE'S SOME RATIONALIZATION OF TECHNOLOGIES THAT IS YESTERDAY TO HAPPEN. I THINK IF WE CAN OVERCOME THAT WE CAN MAKE A LOT OF PROGRESS. >> >> SO THE TITLE OF THIS IS PLACENTAL STRUCTURE AND FUNCTION IN REAL TIME. IN TERMS OF STRUCTURE AND FUN YESTERDAY WE SAW IMAGING FOR STRUCTURE AND BLOOD FLOW WHICH IS A MAJOR FUNCTION OF PLACENTA BUT ANOTHER FUNCTION I HAVE BEEN INVOLVED WITH IS PRODUCTION OF STEROIDS. SO I'M INVOLVED NOW MEASURING ALL STEROIDS FROM THE PLACENTA BY MASS SPEC. I WANTED TO BRING THIS UP BECAUSE IT'S SOMETHING THAT WILL REALLY HASN'T BEEN TALKED ABOUT HERE AS INDEX OF PLACENTAL FUNCTION. THAT IS STEROID PRODUCTION. WHAT WE FIND OUT WITH MASS SPEC BECAUSE WE SEE SO MANY, I DON'T KNOW ABOUT ALL BUT STEROIDS IN METABOLITES IS MANY METABOLITES ARE FUNCTIONAL WHEN WE DIDN'T THINK THEY WERE AND THE BEST EXAMPLE I HAVE IS PROGESTERONE A FIVE ALPHA REDUCED PROGESTERONE, FULLY FUNCTIONAL TO MAINTAIN DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed PREGNANCY IN HORSES IF YOU REMOVE THE SOURCE OF PROGESTERONE EARLY IN PREGNANCY, THE CORPUS LITHEUM. SO THE OTHER PART OF THAT IS REAL TIME I'M WARE OF SIX COMPANIES AS OF LAST YEAR, THAT ARE DEVELOPING MINIATURIZED MASS SPEC THAT YOU CAN TAKE INTO THE FIELD SO I WANTED TO THROW THAT OUT AS A TREMENDOUS WAY TO MONITOR PLACENTAL FUNCTION THAT WE HAVEN'T TALKED ABOUT. >> (INAUDIBLE) I WANT TO REITERATE JOHN'S POINTS, I THINK THEY'RE VERY IMPORTANT. I THINK WE NEED TO WORK ON DEVELOPING PLACENTAL-SPECIFIC IMAGING MODALITIES THAT TAKE INTO ACCOUNT THE UNIQUE STRUCTURE OF THE PLACENTA. TO OVERCOME THE ISSUES THAT HAS -- THAT ARE PRESENT WITH THE CURRENT GENERIC SEQUENCES FROM GE AND PHILLIPS AND SIEMENS. THAT IS VERY DOABLE. IN ORDER TO DO IT WE HAVE TO TEST THOSE SE SEQUENCE UNDER DIFFERENT CONDITIONS PERTURBATIONS, LOW FLOW, OXYGEN NATION, THE COMBINATION OF ANIMAL MODELS SO WE CAN TEST, WE HAVE TO BUILD QUANTITATIVE MODELS THAT WE CAN GENERATE HYPOTHESES FROM THAT WILL BEHAVE THIS WAY UNDER THESE CONDITIONS. THEN GO TO THE HUMAN, ULTIMATELY WHAT WE WANT, WE HAVEN'T TALKED ABOUT IT IN A GENERAL SENSE, THE PLACENTA HAS TREMENDOUS RESERVE, MAKES SENSE. WE HAVE TONE RICH OUR POPULATION TO LOOK FOR BAD PLACENTAS BUT WHAT WE WANT TO DO IS IDENTIFY AT RISK PLACENTA PHENOTYPE THAT CAN THEN BE CONNECTED TO THE O H MIX AND STRUCTURAL DEVELOPMENT, IN ORDER TO DO THAT, WE NEED TO DEVELOP NEW TOOLS AND THE OTHER DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed THING WE NEED TO DO FROM IMAGE STANDPOINT IS DO SOMETHING THAT IS CONSISTENT WITH THE PLACENTAL STRUCTURE, SO OUR 3-D MAPPING THE'S CONSISTENT WITH WHERE THE VESSELS ARE, SO THAT WHEN WE DELIVER AND BIOPSY AND WE GIVE IT TO UL YOU'LL KNOW WHEN TAKING THESE CELLS THIS WAS A LOW FLOW LOW OXYGEN OPPOSED TO HIGH FLOW HIGH OXYGEN. THESE ARE DOABLE. BIT'S AN IMPORTANT THING TO FOCUS ON. >> ANDREA LORNER FROM HRI IN PASADENA. I THINK THIS IS MORE A COMMENT, SOMETHING ALLUDED TO THIS EARLIER WHICH GOT ME REALLY EXCITED. THAT THESE THINGS NEED TO BE AVAILABLE NOT ONLY FOR BIG SITES AND I'M AN IMMUNOLOGIST BY TRAINING SO I UNDERSTAND HARDLY ANYTHING OF ALL THESE VERY SPECIFICS ABOUT IMAGING BUT WHAT GETS ME EXCITED IS SOMEBODY WILL SIT THERE AND SCAN THIS PLACENTA AND HAVE A GOOD IDEA WHAT'S HAPPENING IN IT OR WHAT MIGHT BE WRONG WITH IT STRUCTURALLY AND I CAN GET BLOOD SAMPLE FROM THAT PERSON AND LOOK AT THE SAME PERSON AND FIND OUT WHAT THE IMMUNE SYSTEM DID IN RESPONSE TO WHATEVER HAPPENED THERE VERSUS SOMEBODY WHERE THAT DIDN'T HAPPEN. THAT'S WHERE I H THINK INTEGRATION OF TECHNIQUES, DOESN'T MATTER THE VIEW, WHEN WE COME TO THE SAME PERSON FROM A DIFFERENT ANGLE THAT'S WHERE WE CAN LEARN AND THE NEXT TIME YOU SEE THAT PLACENTA WITH THAT CERTAIN THING, YOU ALREADY KNOW WHAT THE IMMUNE SYSTEM DOES. YOU DON'T HAVE TO LOOK ANY MORE. THAT'S HOW WE REALLY ADVANCE. DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed I DON'T THINK THAT -- MULTI-CENTER HUGE STUDIES ARE WONDERFUL BUT HONESTLY ALL I NEED IS ONE IMAGING DYE AND ONE MASS SPEC GUY. THESE SMALLER COLLABORATION WHERE IS YOU HAVE REALLY INDIVIDUAL THAT DON'T NEED INFRASTRUCTURE ARE VALUABLE BECAUSE WE CAN DO OUR PART OF THE NICHE. I PEOPLE SAYING THAT BECAUSE I GOT FRUSTRATED WHEN MY BOSS SAID NOT APPLICABLE FOR GRANTS BECAUSE WE'RE TOO SMALL. WE WANT SOME OF THAT TOO TO BE ABLE TO WORK TOGETHER. IN MY EXPERIENCE IN THE END WHAT IT BOILS DOWN TO IS INDIVIDUAL PEOPLE. THEY CAN TALK TOGETHER. I DON'T HAVE TO KNOW EVERYTHING THAT YOU KNOW, AS LONG AS WE TALK ABOUT IT WE CAN LEARN TOGETHER. THAT DOESN'T HAVE TO BE A HUGE SETTING. IT CAN HAPPEN IN SMALL INSTITUTES TOO. >> I THINK THE IDEA BY HAVING BIG DATA SETS DEFINE WHAT'S NORMAL, IN SCANNING THE THE INDIVIDUAL PERSON YOU CAN WORK OUT IS THERE AN OUTLIAR BUT YOU CAN CONTRIBUTE YOUR DATA TO DATA POOLING EXERCISE. >> GEORGE (INAUDIBLE) UTMV. TWO THINGS JUST DAWNED ON ME JUST NOW WITH THE QUESTION AND ANSWER ACTUALLY. FIRST IN THAT OF ALL THE TECHNOLOGIES WITH WE TALKED ABOUT THE PAST TWO DAY, ULTRASOUND IS THE ONLY ONE THAT WAS SPECIFICALLY DEVELOPED FOR PREGNANCY. AND IT'S THE ONLY ONE THAT'S A REAL REAL TIME THAT YOU CAN LOOK DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed AT THINGS WITH IT WHILE LOOKING YOU CAN SEE THE CHANGES. ON THE OTHERS YOU HAVE TO WAIT FOR SOMEBODY TO RUN WHATEVER YOU'RE DOING OR EVEN MRI IS NOT REAL TIME. BUT ON THE OTHER HAND THOUGH WE HAVE THESE TWO GREAT ADVANTAGES FOR ULTRASOUND, SEEMS TO ME SOMEHOW, I DON'T KNOW MAYBE I HAVE THE WRONG FEELING THAT WE'RE NOT DOING ENOUGH TO PUSH ULTRASOUND AS MUCH AS WE DO FOR THE OTHER AREAS AND THE OTHER TECHNOLOGIES. ALSO BECAUSE THE OTHER TECHNOLOGIES ARE BEING DEVELOPED OUTSIDE OBSTETRICS PROTEOMICS, GENOMICS, ALL OF THEM. SO I THINK UNLESS WE PUT A SPECIFIC EMPHASIS ULTRASOUND BY NICHD, INCLUDING OTHER RESEARCHERS, ALSO THERE WAS A QUESTION ABOUT INDUSTRY, UNLESS WE DO A SPECIFIC PUSH TO IMPROVE ULTRASOUND AND ANALYZING AND STUDYING THE PLACENTA, IT'S NOT GOING TO DEVELOP AS WELL AS THE OTHER TECHNOLOGIES. >> (INAUDIBLE) FROM BOSTON CHILDREN'S. I WANT TO GET CLARIFICATION ON THE ROLE OF THE PLACENTA AND EVEN PLACENTA PROJECT IN N SAID WE CAN DEVELOP NOVEL GENE APPROACHES TO BETTER CAPTURE THE STRUCTURE OF THE PLACENTA BUT WE NEED TO ANCHOR IT IN THE ACTUAL AGNATTY OF THE PLACENTA THE PATHOLOGY. SO IS THAT NOT INCLUDED IN THIS INITIATIVE, THAT KIND OF CORRELATION WITH THE PATH SPECIMEN? >> SO THIS PARTICULAR -- IS IT TIME TO HAVE THIS CONVERSATION? THIS PARTICULAR FUNDING ANNOUNCEMENT IS AIMED AT DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed ENABLING US TO PUSH FORWARD NOVEL TECHNOLOGY FOR ASSESSMENT. AND MANY IN THE PROCESS OF DOING THAT, OF COURSE IT WILL HAVE TO BE WAYS TO VALIDATE THAT TECHNOLOGY. SO IT IS HIGHLY LIKELY YOU HAVE TO LINK IT WITH OTHER TYPES OF DATA MEASUREMENTS. BUT WHAT WE RECOGNIZE IS THAT THE TIME HORIZON FOR DEVELOPING NOVEL TECHNOLOGY, REALLY PUSHING THE ENVELOPE BEYOND WHERE WITH WE ARE, WE NEEDED TO INCENTIVIZE THAT SPECIFICALLY. SO THAT'S WHAT THIS RFA IS AIMED AT DOING. I ALSO WANT TO SAY BECAUSE IT'S WHAT WE ALWAYS TRY TO EMPHASIZE, NICHD IS FULLY COMMITTED TO SUPPORTING ALL ASPECTS OF PLACENTAL BIOLOGICAL RESEARCH BECAUSE WE RECOGNIZE THAT THE UNDERPINNINGS OF EVERYTHING THAT WE TALKED ABOUT TODAY AND EVERYTHING HPP COMES FROM THE WORK ALL OF YOU OUT THERE HAVE DONE. SO WE HAVE SUPPORTED IT AND CONTINUE TO SUPPORT IT. DID I ANSWER YOUR QUESTION? >> I'M SORRY THEN -- >> IN OTHER WORDS I GUESS CON LEWDING PATH CORRELATION IN THE DIFFERENT METHODS WE DEVELOP WOULD BE ACCEPTABLE. THAT'S THE QUESTION I HAVE OR IS PATHOLOGY NOT HAVE PLACE AT THE TABLE HERE? >> ARE YOU TALK CURRENT UO 1? TO VALIDATE WHAT WE'RE DOING. >> I CLEARLY DROPPED THE BALL. >> CLEARLY WE'RE NOT GO TO THOUGH SOMETHING OUT BECAUSE IT HAS PAST CORRELATION IN IT. YOU DON'T NEED PAST CORRELATION, DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed IF IT'S ONLY PAST CORRELATION IT WON'T BE PARTICULARLY INTERESTING. P BUT THE -- AGAIN, TO VALIDATE NEW TOOLS WE'RE GOING TO WANT TO ROLE THOSE TO OLDER MORE ESTABLISHED ONES. >> COUCH COMMENTS WE WORKING ON COILS FOR THE PREGNANT WOMAN AND WE HAVE DONE THAT IN THE PAST FOR AGE GROUPS AND THE BIGGEST PROBLEM WE HAVE IS INDUSTRY PICKING IT UP AND DEVELOPING A COIL APPLICABLE BECAUSE OF THE PREVALENCE IN PARTICULAR AGE GROUPS GROUPS SO IF IF THERE'S -- AND IDEAS HOW TO COLLABORATE ON THAT AND GET VENDORS TO PICK THESE UP I WOULD LOVE TO HEAR FROM BECAUSE WE LOVE TO HAVE THESE COILS WE DEVELOP THEM BE PICKED UP BY INDUSTRY. THAT'S A HUGE EFFORT. THEN ON THE TIN FOR MA TICKS SIDE THERE'S A LOT OF -- INFORMATICS, THERE'S A LOT OF I 2B 2 AND COMMON PLATFORMS USED FROM ELECTRONIC MEDICAL RECORD AND THERE'S EFFORT LINKING THE COSTS THROUGH M ZONE CLOUD AND THERE ARE INITIATIVES FROM THE INFORMATICS SIDE TRYING TO PULL IN THE IMAGING AN FIGURING HOW TO DO THAT INTELLIGENTLY SO A LOT OF HOSPITAL VERSUS THOSE INFORMATICS TEAM SO IT'S A MATTER OF APPROACHING AND HELPING THEM UNDERSTAND TO PUT IMAGING TO THEIR STRUCTURE. >> >> MY NAME IS (INAUDIBLE) FROM AMERICAN MEDICAL SYSTEMS. I'M IN CHARGE OF -- MANAGING CLINICAL COLLABORATIVE RESEARCH PROGRAM. REGARDING THE 3-D PRINTING. WE HAVE A 3-D PRINTING PROGRAM AT (INAUDIBLE) RESEARCH CENTER DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed AND I WOULD BE WILLING TO ENGAGE ANYBODY WHO IS INTERESTED. >> DAVID (INAUDIBLE) WAYNE STATE. I WAS IMPRESSED BY ERICA'S TALK AND I HAVEN'T HEARD IDEAS ABOUT THIS BUT AS FAR AS I UNDERSTAND NIH EPIDEMIOLOGICAL SUPPORT FOR GRANTS, IF WE WANT TO EMPHASIZE REALLY EARLY EVENTS AND -- WE NEED MORE HIGH RESOLUTION EPIDEMIOLOGICAL SCREEN AND WITH THE BURGEONING NUMBER OF CELL PHONE APPS WE CAN IMPROVE WHAT (INAUDIBLE) IS DOING 20 YEARS, START MISDEMEANOR EUROPE. THERE ARE LOTS OF GREAT APPS OUT THERE, THERE'S A PROGRAM CALLED MONITOR ME, I RECOMMEND WATCHING. BUT IT'S ONE OF THE HIGHEST GROWTH AREAS OF SOFTWARE DRIVEN APPLICATIONS. AND I'LL GIVE AN EXAMPLE, THERE'S AN APP FOR HEARING LOUD NOISES IN THE ENVIRONMENT, YOU CAN HAVE A STUDY WHERE WOMEN HAVE THAT APP TURNED ON, YOU CAN CALL THEM AFTERWARDS AND YOU CAN GET A STRESS RESPONSE, IF YOU ADD THE IBS MEDIUM THEY PROGRESS MORE SLOWLY SO WE'RE COMING DOWN THE PIPE WHERE WE WANT TO CONNECT THE DOTS, WE CAN START TO RELEASE THE GOOD EPIDEMIOLOGY FIRST IN EARLY TRIMESTER AND ENCOURAGE HPP TO LOOK INTO THAT AS WELL. >> YOU'LL BE GLAD TO KNOW THAT NICHD IS WORKING WITH SOMETHING CALLED MY PREGNANCY WITH NUMBER OF PARTNERS FOR WHICH WE ARE THE LEAD AND THE IDEA IS TO TRY TO MAKE BETTER USE OF THIS EXPERIMENT THAT'S DONE A MILLION TIMES A YEAR IN THE U.S. ALONE, THAT IN PREGNANCY AND IT IS AN APP BASICALLY THAT WILL BE MADE DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed AVAILABLE IN THE NEXT YEAR OR SO, TO PREGNANT WOMEN ASKING LONGITUDINALLY ABOUT THEIR PREGNANCY EXPERIENCE AN DEPENDING UPON WHAT A WOMAN ANSWERS SHE'LL BE LED DOWN VARIOUS PLACES IN THE ALGORITHM SO IT'S PRIMARILY TO GET EXACTLY THAT KIND OF EPIDEMIOLOGIC DATA ABOUT THE NORMAL COURSE OF PREGNANCY. B WILL ALSO SUPPLY INFORMATION FROM TRUSTED FOLKS LIKE ACOG, MARCH OF DIMES TO PREGNANT WOMEN THAT WILL BE CALLED UP DEPENDING WHAT THEY ENTER AND C, OR THREE, I CAN REMEMBER WHICH WAS DOING THIS, ALSO BE AN OPPORTUNITY FOR THOSE OF YOU WHO ARE DOING RESEARCH OR LIKE TO ENROLL PREGNANT WOMEN TO ACTUALLY HAVE SOMETHING THAT P POPS UP AND SAYS GEE, YOU ARE IN WEEK 12 OF YOUR PREGNANCY AND YOU ARE HAVING NAUSEA. UNIVERSITY OF SUCH AND SUCH IS DOING A STUDY OF WOMEN IN THE 12th WEEK OF PREGNANCY WHO HAVE NAUSEA IF YOU'RE INTERESTED GO TO THIS URL. >> THAT'S EXCELLENT. AND WILCOX AT NIH HAS BEEN DOING STUDIES SELF-REPORTING SORTS OF STUDIES FOR YEARS BUT THE CELL PHONE APP IS AS LONG AS THE CELL PHONE IS CHARGED, WILL ALLOW A NON-BIASED APPROACH TO MONITORING IN REAL TIME NOT SELF-REPORTING LATER, EVENTS IN THAT WOMAN'S LIFE, SEEING WHETHER WE CAN HELP HER HAVE A BETTER PREGNANCY BY UNDERSTANDING THE STRESSES DAY BY DAY. >> AND I SHOULD ALSO MENTION THE M HEALTH PART OF THE -- PRECISION MEDICINE INITIATIVE WHICH IS NOW FORMING AND THERE'S AN M HEALTH COMPONENT TO THAT DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed AND YOU'LL BE GLAD TO KNOW NICHD IS A COCHAIR OF THAT. >> I'M REALLY INTERESTED IN THIS CONNECTION BETWEEN BIOMARKERS AND IMAGING BECAUSE WHEN -- SO I THINK IF WE THINK OF CANCER AS AN EXAMPLE, I THINK WHEN SOMEBODY HAS CANCER THEY'RE IMAGED BUT IN ORDER TO MAKE ACCURATE DIAGNOSIS AND THE PROGNOSIS OF SURVIVAL, THEN THE CANCER BIOLOGISTS BIOPSY OR GO AND LOOK FOR CELLS LIVING AROUND IN THE CIRCULATION. I'M WONDERING WHAT THE EXPERTS THINK ARE THE DISEASES THAT ACTUALLY COULD BE DIAGNOSED WITH GREAT IMAGING TOOLS. AND THOSE FOR EXAM P PRE-TERM LABOR OR PREECLAMPSIA MIGHT BE MUCH MORE DIFFICULT THAT WOULD THEN REQUIRE MORE BIOMARKERS OR MORE INVASIVES. >> I THINK THERE MAY COME DAY IN THE FUTURE WHERE EVERYTHING BECOMES BIOMARKERS. AND YOU WOULD KNOW WHAT I'M GOING TO ANSWER BY SAMPLING THE AIR AROUND ME BUT I THINK JUST TO ANSWER YOUR QUESTION, AT LEAST FROM MY PERSPECTIVE IT'S HARD REALLY TO KNOW HOW TO ANSWER THIS BECAUSE I DON'T THEE WE UNDERSTAND IN EARLY GESTATION THE MECHANISMS, THE UNDERLYING MECHANISMS OF THE PLACENTAL LEVEL THAT LEAD TO PREECLAMPSIA LATER ON OR WITH SOME SPECIFICITY THAT TODAY WE CAN USE THE TECHNOLOGY TO ANSWER THAT. PART OF THE HUMAN PLACENTA PROJECT IS TO GET TO A LEVEL OF KNOWLEDGE THAT WE WILL BE ABLE TO MARRY THESE TECHNOLOGIESING TO IN THE FUTURE. SO WE KNOW ENOUGH TODAY FROM ALL THE LITERATURE OUT THERE THAT DAE490.6659BC334A6B637EDB1228C83 CBFB7C4C17 06707&itag=121&ns=yt-ems-t&key=y t_qc&id=Dk 7XARReoJChTwu1WojgRQ142867901863 4279&spara ms=id%2Citag%2Cns%2Cexpire&expir e=14323918 94 http://upload.youtube.com/closed EVENTS THAT WE SEE WAY DOWNSTREAM IN PREGNANCY, HAVE SOME COMMONNALTIES IN THE FIRST TRIMESTER. AND WHETHER THE BABY'S GROWTH RESTRICTED OR THE PREGNANCY HAS PREECLAMPSIA OR OTHER THINGS OR PRE-TERM LABOR MAY HAVE A LOT OF THESE ORIGINS EARLY ON. I THINK THE CONCEPT OF MARRYING ULTRASOUND TO OTHER TECHNOLOGIES IS VERY -- OR MRE FOR THAT PURPOSE IS VERY APPEALING BECAUSE WE HAVE SEEN A SHIFT IN PREGNANCY WITH REGARDS TO RISK PROFILING OVER THE PAST FIVE TO TEN YEARS. QUESTION RELY ON ULTRASOUNDD ON OTHER BIOCHEMICAL MARKERS TO ASSESS RISK FOR ANY OTHER THINGS FOR PREECLAMPSIA, SO THERE'S A LOT OF BENEFIT IN BRINGING TECHNOLOGY THAT ARE SYNERGISTIC AND TRYING TO -- BUT THE QUESTION SYSTEM TO GET TO THAT LEVEL WE HAVE TO UNDERSTAND NORMAL VARIABILITY AND NORMAL -- AND SOME OF THE DISEASE PROFILES. >> I THINK IT'S NOT GOING TO BE A CASE OF JUST IMAGING AS IT'S NOT JUST A CASE OF CLINICAL MARKERS. IT'S GOING TO BE COMBINATION OF IMAGING OMICS AND CLINICAL MARKERS THAT WILL ALLOW YOU TO IDENTIFY PARTICULAR PATIENTS, PARTICULAR DISEASE PROGRESSION. >> I'M SORRY TO DO THIS TO YOU BUT WE'RE INTO THE LUNCH HOUR. AND SO WE'RE GOING TO CUT OFF THE QUESTIONS. HOWEVER, FIRST I WANT TO THANK THESE GROUP LEADERS FOR THEIR EFFORTS. [APPLAUSE] THANK YOU, THANK YOU ALL FOR COMING BACK. THIS AFTERNOON IS BECOME TO BE REALLY INTERESTING. WE'RE GOING TO HAVE THREE TALKS. SORT OF DIFFERENT FROM WHAT WE HAD ON DAY ONE AND I THINK THEY'RE GOING TO BE VERY INTERESTING, AND I THINK THEY'RE GOING TO BE QUITE STIMULATING AND THEN WE'RE GOING TO HAVE, WE'RE ANYTHING TO GET TO ONE OF THE THINGS THAT IS VERY IMPORTANT TO US. AND THAT'S TALKING ABOUT ROAD MAP. HOW DO WE ACTUALLY TRANSLATE THE THINGS THAT WE'VE BEEN THINKING ABOUT AND TALKING ABOUT? HOW DO WE ACTUALLY TRANSLATE THEM INTO MOVING THE HUMAN PLACENTA PROJECT FORWARD? AND WE REALLY NEED YOUR HELP IN DOING THAT. WE WANT THIS TO BE BASED ON INPUT FROM THE SCIENTIFIC COMMUNITIES THAT YOU REPRESENT SO YOU WILL NOTE, IF YOU LOOK AT YOUR AGENDA, I'LL TELL YOU THAT YOU WON'T SEE A BREAK. HOWEVER, WE UNDERSTAND. WE ALL HAVE NEEDS AND SO WE INVITE YOU TO DO, YOU KNOW, THAT SORT DIFFUSION REACTION IN AND OUT OF THE ROOM AS YOU NEED TO. OKAY OKAY. SO WITHOUT ANYMORE DELAY, I'M BEING TO ASK OUR FIST SPEAK TORE COME UP AND DAVID RELMAN FROM TAN FORD UNIVERSITY. >> DA VERY CLOSUNIVERSITY.THANKS, DAVID, IT'S AN HONOR AND A PLEASURE TO JOIN YOU HERE TODAY. DAVID ASKED, AND ALAN ASKED THAT I TALK ABOUT LESSONS LEARNED FROM THE MICRO BRBIOM AND I'VE INTERPRETED THIS QUITE LOOSELY WITH SOME LATITUDE ALLOWED AND SO I HOPE WHAT I HAVE TO OFFER IS USEFUL, AND I'M CERTAINLY MORE THAN HAPPY TO REDIRECT MY COMMENTS, IN RELATION TO QUESTIONS YOU MAY HAVE AFTERWARDS. SO I THOUGHT I WOULD TALK A% LITTLE BIT ABOUT PERSPECTIVE AND I'LL SAY BY MEANS OF SPRUNG THAT I DON'T PLAN TO TALK AS MUCH ABOUT PROGRAMMATIC BE FEEDS AND ORGANIZATION OF PROGRAMS AND LITTLE BIT MORE ON THE BIOLOGY AND HOW A PROJECT LIKE THE MICRO BIOM COMPLEXITY, AND I MEAN THIS QUITE BROADLY NOW, THE GLOBAL INVOLVEMENT IN THIS PROJECT, HOW IT HAS CHANGED THE WE WE VIEW AND THINK ABOUT BIOLOGY AND IN PARTICULAR, WITH THIS AREA OF SCIENCE, THE PERSPECTIVE THAT'S BEEN PROVIDED BY THE STUDY OF A PARTICULAR SUBSET OF ALL MICROBIAL COMMUNITIES HAS REALLY CHANGED THE WE WE THINK IT MEANS TO BE HUMAN AND IT CERTAINLY HAS BEEN AFFORDED BY INVOLVEMENT IN THIS LINE OF WORK BY MANY DIFFERENT KINDS OF PEOPLE. PEOPLE WHO HAVE FOR HUNDREDS OF YEARS, BEEN THINKING ALREADY, IN WAYS THAT ARE SHOUT DIFFERENT FROM THOSE CLINICIANS LIKE MYSELF AND OTHERS, TEND TO THINK. FOR EXAMPLE, ECOLOGIST THEY WOULD VIEW A HUMANLIKE THEY WOULD ANY OTHER SUITABLE HABITAT FOR A COMMUNITY AS AN ISLAND OR A HABITAT PATCH. WHAT HAPPENS ON THESE PATCHES IS RANDOM. IT'S ALL ABOUT EXACTLY THE OPPOSITE. SO LESSON ONE, A PROJECT LIKE THE MICRO BIOPROJECT, AND THE PLACENTA PROJECT SHOULD AND CHANGE THE WAY YOU WILL NOT JUST ABOUT THE PLACENTA AND GESTATION, BUT ABOUT HUMAN BIOLOGY IN GENERAL. WHEN WE HAVE THOUGHT ABOUT THE PARTICIPATION CONTRIBUTION OF THE MICRO BY ONLY TO HUMAN BIOLOGY, WE TEND TO COME UP WITH LISTS OF BENEFIT THAT IS WE DERIVE FROM THIS ASSOCIATION AND THERE ARE SIMILAR LISTS THAT THE MICRO BIOTA DERIVE FROM AND THIS IS SHOUT NOW A FAMILIAR LIST TO MANY OF YOU, AND PROBABLY APPLIES LARGELY TO THE GUT MICRO BIODA BUT NOT JUST THE GUT. AND INGOTS USEFUL TO THINK ABOUT IN A COUPLE OF WAYS THINK ABOUT HOW SYSTEM WIDE THESE PROPERTIES ARE THAT ARE REALIZED PIE THE PRESENCE OF A MICRO BIODA AND THE FACT THAT A LOT THIS IS HAPPENING AT A DISTANCE. IN FACT, THE SUBTITLE UP HERE I THINK IS REALLY IMPORTANT THAT ALL OF THESE PROPERTIES, ASSOCIATED WITH THE MICROBIOM WE THINK ARE PROBABLY RELEVANT TO FETAL HEALTH AND TO PREGNANCIES IN GENERAL. SO THINK FOR THE ONES JUST LOCALLY, BUT GLOBALLY ACROSS THE HUMAN BIOLOGICAL LANDSCAPE. ANOTHER EARLY LESSON AND THIS WAS ACTUALLY LEARN MANY YEARS AGO IS THE SITE SPECIFCITY, THE SPATIAL DIFFERENTIATION OF THIS THING, THE MICRO BIOME. WE KNOW THE MANY COMMUNITIES AND SUBHABITATS OF THE MOUTH, ARE STINK DISK, NOT JUST IN TAXONOMIC C, BUT IN THEIR FUNCTIONAL A CREDIBILITIES. SO MUCFUNCTION -- FUNCTIONAL ATTRIBUTES. THE COMMUNITIES ON EACH OF YOUR TONGUES ARE DIFFERENT THAN THE COMMUNITIES OF YOUR OWN GUT THAN THE FUNCTION OF THOSE NEXT TO YOU EVEN THOUGH YOU, LET'S ASSUME, DON'T KNOW THAT PERSON NEXT TO YOU. BUT YOU SEE SPATIAL LOCATION, GEO LOCATION ON THE BODY MEANS A HUGE AMOUNT IN THIS CASE AND THIS, TOO, MAY HAVE SOME IMPORTANT RELEVANCE TO THE STUDY OF A PARTICULAR BODY SITE OR AT THE BIOLOGY THAT HAPPENS WITHIN. THERE OF COURSE A NUMBER OF STUDIES FROM THE LENSES IN WHICH WE LOOK AT THIS FEATURE AND OF COURSE, THE ORIGINAL LENGTHS, THE MICROSCOPE LENS, AND SUBSEQUENTLY, THE CUT VISION LENS AND NOW, IT'S THE MOLECULAR LENS. IT'S THE, IN MANY CASES, A SEQUENCE OF A MOLECULE THAT TELLS US A LOT WHAT MIGHT BE THERE AND WHAT'S HAPPENING. THE LESSON AT LEAST WHAT I TAKE FROM A LIST LIKE THIS IS THAT EACH OF THESE TELLS US A DIFFERENT STORY. EACH OF THESE IS IMPORTANT, UNTO ITSELF, NONETHELESS. TOGETHER, THEY ACHIEVE MUCH GREATER VALUE AS KINDS OF INFORMATION FOR UNDERSTANDING SOMETHING LIKE THE MICRO BIOME AND THERE ARE SYNERGIES BETWEEN THEM. BUT THE BIT THAT I HAVE HEIGHTED IN GREEN IN LARGER FONT AT THE BOTTOM IS ANOTHER MESSAGE THAT I TAKE FROM ALL OF THIS WHICH IS THAT DESPITE MEASUREMENTINGS OF PROTEINS AND PROTEIN FUNCTIONS AND STRUCTURES AND EVEN SMALL MOLECULE. WE DON'T REALLY GET TO, THE KINDS OF FUNCTIONSES THAT ARE REFLECTED IN THE PREVIOUS SLIDES ARE BENEFITS. THOSE ARE CALLED ECOSYSTEM SERVICES, IF YOU'RE AN ECOLOGIST, ANY I AWAY. ACTUALLY, THOSE ARE VERY HARD TO MEASURE AND THEY'RE NOT IMMEDIATELY RECOGNIZED AND UNDERSTOOD FROM ALL OF THESE KINDS OF MORE SPECIFIC MEASUREMENTS. SO THAT'S A BIG CHALLENGE RIGHT NOW IN THE STUDY OF THE HUMAN MICRO BIOME. HOW DO WE GO ABOUT MEASURE ANYTHING MONITORING THE OVER ALL COMMUNITY WIDE FUNCTIONS, ESPECIALLY AT EYE SYSTEM LEVEL. REFLECT THE TO BIOLOGY. LIKE COMETABOLISM. AND I THINK THAT IS GOING TO BE, OF COURSE, EYE RELEVANT ISSUE FOR THE STUDY OF SOMETHING ANATOMIC BEALLY FOCUSED LIKE THE PLACENTA OR GESTATION. BUT THERE'S BEEN SOME UNEXPECTED BIOLOGY REVEALED FROM SOMETHING LIKE THE MICROBIOME. THIS IS VERY CONCRETE IN THIS PARTICULAR CASE, BUT WORK BY MIKE BEEL FISHBACH AND OTHERS, HAS SHOWN THAT EVEN IN STARING AT GENOMES AND NOW LOOKING AT CLUSTERS OF GENES ON GENOMES, ONE CAN BEGIN TO PREDICT WITH MUCH GREATER CLEARITY, THE SMALL MOLECULE PRODUCT THAT ARE THE RUT OF THESE SEQUENTIALS ENCODED BY THESE GENE CLUSTERS AND THESE GENE CLUSTERS TURN OUT TO PROTECT OR AT LEAST PREDICTD TO PRODUCE AND SHOWN TO PRODUCE SMALL MOLECULES WITH REAL MEASURABLE, BIOLOGICAL ACTIVITY. THIS IS A NOVEL ANTIBIOTIC LIKE COMPOUND MADE BY A SINGLE ORGANISM IN THIS CASE, THAT'S NOT UNCOMMONLY FOUND IN THE VAGINA. THIS MOLECULE WAS NOT PREVIOUSLY RECOGNIZED OR UNDERSTOOD AND MICHAEL AND HIS COLLEAGUES FOUND IT BY GAZING AT GENE CLUSTERS AND USING SOME MACHINE LEARNINGOLOGLEARNINGOLOGY RHYTHMS AND TRYING TO CENSUSES PANNED TA. ONE OF THE STORIES WITH RESPECT TO THE MICRO BIOME, THE IMMENSE SIGNALING BETWEEN CELLS OF DIFFERENT TYPES BETWEEN GROUPS OF CELLS AND OTHERS AS A STARTING POINT FOR FURTHER POSSIBLE LESSONS, AND INTERESTING QUESTIONS ONE MIGHT ASK NOW. MORE SPECIFICALLY, WITH THE RESPECT TO THE MICROBIAL WORLD. OF COURSE, THE FINDINGS IN THIS PAPER, WERE BASED LARGELY ON THE STUDY OF NUCLEIC ACIDS. OF DNA IN A PARTICULAR PLACE OF THE HUMAN BODY, AND OF COURSE, WERE RESULTS THAT WERE SHOUT SURPRISING. SO YOU MIGHT THEN STEP BACK AS MANY HAVE AND ASK WHAT DOES THAT KIND OF FINDING.? WHAT DOES IT ALLOW US TO PREDICT ABOUT THE PRESENCE OF MICROBES OR THE BIOLOGY OF MICROBES, POSSIBLY? OF COURSE, WHEN WONG FINDS NUCLEIC ACID, ONE MIGHT ASSUME THERE TO BE PRESENT, IN-TACT CELLS BUT THAT'S NOT NECESSARILY THE CASE AND WE TALKED ABOUT VESICLES BUT THEY ARE CLEARLY COMPONENTS OF CELLS THAT CAN BE FOUND AND HAVE MEANINGFUL, LOCAL BIOLOGY. NOT JUST AS BREAKDOWN PRODUCTS ON THE WAY TO FURTHER DEGRCDATION AND THESE MICHAEL BUCKLEY R MICROBIAL COMPONENTS CLEARLY HAVE IMPORTANT BIOLOGICAL ACTIVITY, MANY OF THE RECEPTORS YOU'RE FAMILIAR WITH AND OTHER RECOGNITION PATHWAYS IN CELLS. OUTSIDE OF CELLS. SO I DON'T MEAN TO SUGGEST THAT WERE THIS DNA NOT TO COME FROM CURRENTLY PRESENT IN-TACT CELLS, IT'S NOT MEANINGFUL. COULD BE. BUT WE DON'T KNOW, AND THIS ISSUE OF WHETHER THERE ARE IN-TACT CELLS AND WHETHER THEY ARE VIABLE IS AN IMPORTANT THING. ESPECIALLY IF WE'RE GOING TO TALK ABOUT COMMUNITIES, WHICH IS A POINT WE'RE GOING TO COME TO. YOU MIGHT ASK WHERE DOES IT COME FROM IN IT WAS FOUND IN PLACENTAL TISSUE. ONE WITH, OF COURSE, RESOLVE THE LOCATION BY MICRO DISSECTION, ET CETERA. IT STILL LEAVES ONE WITH A SERIES OF POSSIBILITIES, I WOULD SAY. SOME MIGHT BE MORE LIKELY THAN OTHERS. THEY ALL HAVE SAFETY CENSUS AU IMPLICATIONS. EVEN THE ENVIRONMENTAL CONTAMINATION. BEFORE THEY WERE IN PLACENTA, THEY WERE IN LOCAL TISSUES LET'S SAY AND THEREFORE N A CONSISTENT, MEANINGFUL MANNER. WELL, THAT IS AN PERSONALITY BIOLOGICAL ISSUE THAT STILL NEEDS TO BE SORTED OUT. I'M GOING TO SUGGEST THAT THESE ARE NOT FULLY ANSWERED YET AND THEY ARE PROBABLY IMPORTANT TO HAVE TO ANSWER. LIKE WISE, THE DNA OR THE CELLS MAY HAVE COME FROM A DISTANT HUMAN SITE AND IN FACT, A QUITE PLAUSIBLE, CREDIBLE POSSIBILITY AS WELL AND ONE OF THOSE SORTS OF FINDINGS IS THIS. FROM YEARS NOW, THESE, STUDIES RICHE THESE GO BACK AT LEAST 20 YEARS, MORE IF ONE IS FOCUSING ON CULTURE. AND THE QUESTION IS IS THERE OTHER EVIDENCE OF LET'S SAY, BACTERIAL DNA IN THE BIRTH SACK AND OF COURSE, AS YOU WELL KNOW PROBABLY BETTER THAN I, THE ANSWER IS YES, THAT BOTH CULT AND YOU ARE MOLECULAR METHODS HAVE REVEALED BACTERIAL DNA IN AMNIOTIC FLUID, FOR EXAMPLE, IT'S BEEN FOUND MORE OFTEN IN THE SETTING OF ROBERTO ROMERO IS HERE, IN ONE OF THE SO-CALLED FOUR GREAT [INDISCERNIBLE] SYNDROMES. THIS IS WORK WE DID IN COLLABORATION WITH HIM. BUT IT'S ALSO TRUE THAT ONE CAN FIND BACTERIAL DNA IN THE ABSENCE OF OVER DISEASE. AND I MIGHT ASK WELL, WHAT DO THE SEQUENCES ITS. AS YOU KNOW, FROM THE PAPER I HIGHLIGHTED AND FROM WORK OF PERHAPS YOURS AND OTHERS, SEQUENCES SOMETIMES SUCCESS A POSSIBLE OR POSSIBLE SITE OF ORIGIN FOR, IN THIS CASE, THE BACTERIA IS DNA. YOU CAN'T READ THE NAMES HERE BOIL POINT OUT, OTHER STUDIES HAVEN SHOW, IF AMNIOTIC FLUID, BACTERIAL SEQUENCE IS SUGGESTS, THE ORGANISM IS TYPICALLY PHONAL IN THE MOUTH OR IN THE GUT AND OR TYPICALLY PHONAL IN THE VAGINA OR SKIN. AND IN FACT, THERE IS, I THINK AN EMERGING STORY THAT SPEAKSES TO THE TRAFFICKING OF AT LEAST DNA F NOT, MICROBE BE IAL COMPONENTS, IF NOT, IN-TACT CELLS THROUGHOUT BODY, EVEN IN STATES OF HEALTH. THESE ARE DATA FROM MID TRIMESTER. OTHERWISE HEALTHY WOMEN DURING PREGNANCY AND ALTHOUGH IT'S A SMALL FRACTION OF ALL SUCH SAMPLES TESTED, IT'S 1 AND A HALF%. THESE ARE SEQUENCES THAT WE THINK ARE LIKELY NOT TO BE CONTAMINANTS AND RAISE THE SAME QUESTION. WHAT DOES IT MEAN TO FIND THESE SEQUENCES IN AMNIOTIC FLUID. I'LL SAY, THE CANDIDACY SEQUENCES WERE FOUND IN WOMEN WITH IUD'S THAN WOMEN WITHOUT. BUT AGAIN, WHAT'S THE CONTEXTUAL MEANING AND THE CONSEQUENCE OF FINING SUCH DATA IN WE DON'T SPIRAL KNOW. I MENTIONED THAT THERE'S A GROWING NOW, BUT TILL SMALL BODY OF DATA THAT SUGGESTS THAT AT ANY POINT IN TIME, IN ANY OF US RIGHT NOW, OTHERWISE FEELING WELL, ALTHOUGH I HAVE A LITTLE COLD, I PROBABLY MOSTLY CATEGORIZE MYSELF AS RELATIVELY WELL. THERE WILL BE MICROBIAL DNA IN OUR BLOOD STREAM AND IN PARTICULAR, IN THE SELF REFRACTION OF PLASMA. THIS IS WORK SHOWN. I'M FAMILIAR WITH THE WORK OF STEVE QUAKE,WHO IS A COLLEAGUE AT STANFORD K AND HE IN FACT, AS THIS HEADLINE SHOWS, OR SUGGESTS, HAS FOUND FOR THE ONES JUST SAY, VIRAL OR BACTERIAL OR FUNGAL DN ARC IN SELF-REFRACTION OF BLOOD AND HEALTHY INDIVIDUAL, BUT ALSO RNA. RNA TRANSCRIPTS. AND THIS, OF COURSE, GETS TO AN EARLIER DISCUSSION THIS MORNING ABOUT HOW ONE MIGHT BEGIN TO THINK ABOUT RELATIVELY NONINVASIVE, AT LEAST NOT IMMEDIATELY INVASIVE TO THE PLACENTA, WITH SURVEYING VARIOUS KINDS OF BIOLOGICALLY IMPORTANT MOLECULES SUCH AS MRNA'S OR LONG RNS, ALL OF WHICH HAVE BEEN RECOVERED FROM PLASMA AND THIS FIGURE, IN CASE YOU WANT TO LOOK AT THIS PAPER, SHOWS CERT OF A TEMPORAL SHIFT OF ABUNDANCE OF TRIPS, RELEVANT TO THE PLACENTA, AT EACH OF THE VARIOUS TRIMESTERS DURING PREGNANCY. THE OTHER QUESTION ABOUT FINDING DNA SEQUENCES AS THEY COME FROM MULTIPLE ORGANISMS. DOES THIS MEAN WE HAVE A COMMUNITY IN AND I KNOW THE TERM IS FOUGHT WITH A LITTLE HISTORY AND MAYBE BAGGAGE. I THINK THIS IS A REALLY IMPORTANT QUESTION. TO AN ECOLOGIST, A MICROBE BE IAL COMMUNITY IS A VERY SPECIFIC KIND OF PHENOMENON. IT'S AN ASSEMBLAGE, BUT IT'S AN ASSEMBLAGE THAT'S NONRANDOM. AND IT'S NOT ONLY CHARACTERIZED BY, BY SHAPED BY INTERACTIONS THAT OCCUR AMONG MEMBERS. AND A LOT OF THE SCIENCE IN MICROBE BE IAL ECOLOGY HAS TO DO WITH UNDERSTAND BEING THE NATURE OF THESE BE R INTERACTIONS, AND HOW STRONG ARE THEY, WHAT IS THE SPATIAL SCALE. ONE IS DEFINING A COMMUNITY AS SUCH AND DISTINCT FROM ANOTHER. AND WHAT IS ITS RELATIONSHIP OF A LOCAL ENVIRONMENT. I THINK THYSELF ARE ALSO IMPORTANT QUESTIONS THAT DESERVE TO BE ASKED ABOUT COMMUNITIES THAT MIGHT HAVE DIRECT BEARING AND IMPACT ON GESTATION. WHICH THEN LEADS TO ANOTHER QUESTION ABOUT CLINICAL RELEVANCE. WE'RE NOW TALKING ABOUT COMMUNITIES AS A UNIT OF INTEREST AND IT MIGHT BE THE ASSOCIATION OF A COMMUNITY WITH HEALTH. MIGHT BE AN ASSOCIATION WITH A COMMUNITY WITH DISEASE. IF EITHER CASE, IT'S A LINKAGE THAT DESERVES FURTHER CHARACTERIZATION WITH RESPECT TO THE POSSIBILITY OF CAUSATION, ONE CANNOT SO EASILY ADDRESS OR SATISFY POSTULATES. THERE ARE IN FACT, A NUMBER OF ALTERNATIVES, PROPOSED THROUGH THE MANY YEARS. EPIDEMIOLOGISTS HAVE TALKED FOR SOME TIME ABOUT THE ROLE OF ENVIRONMENTAL FACTORS IF CANCER CAUSATION AND HOW ONE MIGHT GO ABOUT BUILDING A CASE, IN BUILDING CAUSATION. [INDISCERNIBLE] IS WELL KNOWN FOR HAVING PROPOSED A SERIES OF POSTULATES THAT WOULD HELP BUILD ONE OF SUCH CASES AND THESE ARE SOME OF THE FEATURES THAT HE TALKS ABOUT AND OTHERS HAVE TALKED ABOUT SINCE. SO WHAT IS THE SPECIFICITY AND SENSITIVITY THAT HAVE ASSOCIATION. WHAT IS ITS TEMPORAL RELATIONSHIP. HEALTH, SUBSEQUENT HEALTH OR SUBSEQUENT DISEASE. WHAT ABOUT THE SPATIAL AND ANATOMIC RELATIONSHIPS. WHAT DID A DOSAGE EFFECT. THAT CAN BE A VERY IMPORTANT PIECE OF A STORY FOR CAUSATION AND BY DOSAGE HERE, WE'RE TALKING ABOUT PERHAPS, THE RELATIVE B BUNKEDDANCE OF THE COMTY WIDE FEATURES OF THIS MICRO BIODA THAT WE THINK ARE RESPONSIBLE FOR HEALTH OR DISEASE. IT'S NOT JUST ONE ORGANISM WE'RE TALKING ABOUT HERE AT ALL. THERE'S THE ISSUE OF PLAUSIBLE AND OF POSSIBLE MECHANISM. AND THERE ARE MANY DIFFERENT CAUSAL RELATIONSHIPS. ONE MIGHT BE A CLASSIC WHERE THE FACTOR INITIATES A PROCESS. ANOTHER MIGHT BE AND THEY'RE NOT USUALLY EXCLUSIVE. MIGHT BE WHERE THE FACTOR HELPS TO PROMOTE OR CONTINUE, MAINTAIN EITHER HEALTH OR DISEASE IN THIS CASE. OR REINFORCE IT SOMEHOW. BUT REMEMBER THAT A FACTOR LIKE A COMMUNITY MIGHT PLAY AN IMPORTANT ROLE AND YET, BE EITHER NECESSARY NOR SUFFICIENT, BUT SIMPLY, A PART OF A MUCH LARGER STORY OF CONTRIBUTING FACTORS TOWARDS CAUSATION, ONE OF WHICH IS NECESSARY OR ONE OF WHICH IS SUFFICIENT. AND SO, YOU KNOW, YOU CAN THINK OF EXAMPLES WHERE THESE VARIOUS FEATURES, THE PIECES OF THE CASE HAVE START TO BE ABOUT THE, AND I'LL JUST POINT TO ONE BE THAT'S FROM OUR OWN WORKS BECAUSE I KNOW IT WELL. IN THE CASE OF THE EXAMINATION OF AMNIOTIC FLUID OF BACTERIAL D NETWORK ARC IN THE SETTING OF PRETERM LABOR WITH IN-TACT MEMBRANES. WE, TOGETHER WITH ROBERTO LOOKED AT THE RELATIVE ABUNDANCE OF DNA AND LOOKED AT THE DIFFERENCES BETWEEN THE SETS OF SAMPLES AND SUBJECT WHERE WE HAD MOLECULAR EVIDENCE, OF BACTERIAL DNA AND FLUID, VERSUS THOSE WE DID NOT. I'LL TURN YOUR ATTENTION TO TWO CURVE HERE. THE PLUONE ARE THE DATA WHERE WE HAD POSITIVES DNA. AND WE HAD INCOME CULTURES AND INCOME BE CULTURES. TIME BETWEEN AMNO SENSOR-BASED CEASE, AND THE TIM-- AMNIOC ERK N -- SINTE ASE IS. PRANCE IN THIS IS CA, STIMULATING AN INFLAMMATORY RESPONSE. SO HOW MIGHT THESE SORTS OF MICROBIOME ACTIONS HAPPEN, WITH RESPECT TO PREGNANCY? WE DON'T KNOW, BASICALLY. WE DO HAVE EXAMPLES WHERE THERE SEEM TO BE DISRB ANS THAT ARE SOMEWHAT DISTANT FROM THE BACTERIAL SAC, AND WE HAVE SPECK BE LAKES ABOUT POSSIBLE MECHANISMS, INCLUDING TRANSLOCATION OF ACTUAL ORGANISMS. CHANGES IN BOTH LOCAL OR SYSTEMIC IMMUNITY. ALT RIGS IN SYSTEMIC METABOLISMS, AND THESE SMALL MOLECULES CAN CIRCULATE AND HAVE AN EFFECT. IN ONE OF THE LADDER LATTER EXAMPLES. STAN HASIN SCRIBED IN HIS WORK, SHOW LINKAGES BETWEENAC TEAR IAL ACTION IN THE GUT ON ONE OF SEVERAL DIFFERENT TM AKON TRAINING DIETARY COMPOUNDS CHOLINE, ALL OF WHICH WHICH CAN BE SUBSTRATES FOR WHICH TMA IS RELEASED. THE THEN ABSORBED, AND ACTED UPON BY LIVER. TURNED INTO TMA OXIDE AND THT IS TO BE A RISK FACTOR. A NUMBER OF PEOPLE HAVE NOW PUBLISHED STUDIES LOOKING AT THIS, A NUMBER URN WAY. JACQUES RABEL HAVE LOOKED AT SAMPLES FROM THE VAJOIN A WE HAVE BEEN LOOKING AT SAMPLES FROM MULTIPLE BODY SITES. WHAT WE FIND WHERE WE'VE BEEN SAMPLING WEEKLY, AT MULTIPLE BODY SITES IS FIRST OF ALL, RELATIVE COHERENCE, BASED UPON BODY SITES, DESPITE THE PASSAGE OF PREGNANCY. SO THE COLOR HERE IS BODY SITE. THERE'S A MERGE BEING OF COLOR HERE, THESE ARE BOTH SAMPLES. THE MOUTH IS SALIVA. THE OTHER IS TOOTH-GUM SWAB. WE SEAT MAINTENANCE OF THE BODY SITE COHERENCE OVER TIME, BUT RELATIVE STABILITY. AND I'LL JUST POINT OUT THAT WE, LIKE JACQUES R ERK BEL FIND DURING PREGNANTY, THE MICRO BIONLY IS SURPRISEDLY STABLE. WE'RE STILL USING SOME RELATIVELY SUPER OFFICIAL KINDS OF MEASUREMENTS BUT HAVE PLANS AND ARE ALREADY UNDER AS ARE OTHERS, LOOK AT KINDS OF FEATURE. ALL THE FEATURES THAT MIGHT BE RELEVANT TO FETAL HEALTH ARE MAINTAINED AND ARE TRULY STABLE OVER THIS PERIOD OF TIME. AND ONE OTHER EARLY FINDINGS, AND I'LL SIMPLY CLOSE WITH SOME QUESTIONS IF WE LOOK AT THE VAGINAL BIOME OVER TIME AND COLOR CODE THE SAMPLES, BE BASED UPON WHETHER THEY CAME FROM A WOMAN WHO WOULD SUBBE CONSEQUENTLY GO ON TO DELIVER PRETERM. THAT IS THE PURPLE ONES, WE SEE A HIGHER SCORE AS MEASURED ALONG PREMATURE COORDINATE ACCESS ONE, IN THE SAMPLES OF THE PRETERM SUBJECTS THAN WE DO FROM THOSE THAT DELIVER A TERM, AND ALL OF THIS IS SIMPLY, THE SUGGESTION THAT PERHAPS THERE IS AN EARLY PREGNANCY B BE IT BEHOOVES US TO TRY RESPOND WHAT DO THESE FEATURE MEAN, HOW DO THEY OPERATE AND HOW FIGHT OTHER KINDS OF PUNISHMENTS HELP US IN UNDERSTANDING WHAT GOES ON IN THE FETUS DURING GESTATION. I'M JUST GOING TO CLOSE WITH R SOME POSSIBLE MECHANISMS, AS I MENTIONED BUT WITH THESE QUESTIONS AND LESSONS. I THINK I PROBABLY SUGGESTED SUFFICIENTLY, TO YOU, THE IMPORTANCE OF VIEWING WHAT MIGHT HAVE BEEN PREVIOUSLY VIEWED AS A SET OF INDIVIDUALS, KNEAD, AS A COHERENT COMMUNITY, AND IT CAN HAVE A LOT OF DIFFERENT BIOLOGICAL EFFECTS AT A DISTANCE OF POSSIBLE RELEVANCE TO THE FETUS AND POSSIBLY, THE PLACENTA. THERE MAY IN FACT BE COMMUNITIES AT MULTIPLE BODY SITE THAT ARE RELEVANT TO THIS TIME. I DIDN'T HAVE TIME TO EMPHASIZE SOMETHING THAT I THINK YOU ALREADY WELL APPRECIATE, WHICH IS THE IMPORTANCE OF EARLY EVENTS IN NOT ONLY THE FORMATION OF COMMUNITIES BUT THING OF ECOLOGICAL LANDSCAPE THAT HAS GREAT IMPORTANCE OF PREDICTING HELP AND THE POSSIBLE OF VALUE OF UNDERSTANDING THESE EARLY EVENTS BECAUSE OF THE OPPORTUNITY FOR INTERVENTION IN IA WAY THAT IS MUCH MORE EFFECTIVE THAN ONE MAY HAVE OTHERWISE IMAGINED. SO I THINK I WILL CLOSE HERE. LET ME JUST MENEKO A FEW PEOPLE. -- JUST MENTIONED BUT THANK YOU FOR YOUR TIME AND ATTENTION. [Applause]. >> THANKS FOR A WONDERFUL TALK. WE DO HAVE TIME FOR QUESTIONS IF ANYBODY WOULD LIKE TO ASK A QUESTION. >> HARRY MEDICAL COLLEGE. , I GUESS FOR ME, BE IT'S WHAT I DIDN'T SEE ON YOUR SLIDES. I THOUGHT IT WAS A GREAT TALK. I THINK VIRUSES NEED TO BE INCLUDED IN THE MICRO BIOMNI MOVER. AMERICA EGALO VIRUS THAT CAUSE ABNORMALITIES IN CHILDREN, AND ISSUE RESPONSIBILITY IN PROBLEMS 1% TO 2% OF LIVES BIRTH. AND PARASITIC MICRO BIOME SHOULD BE CONSIDER HERE AS WELL. >> REALLY GOOD POINT. I'M GLAD YOU MADE T. YOU'RE ABSOLUTELY RIGHT. AND IN FACT, THIS BIAS BIAS IS ONE THAT COMES AS A COST OF AGAIN, SOME OF THE LENSES THAT OF COURSE USED MOST COMMONLY, BUT SHOULD NOT CONTINUE TO BE A BIAS, GIVEN THE INCREASING COST, EFFECTIVENESS OF DOING TO EXEMPTION SEQUENCE AND USING METHODS TO PURIFY VIRUS-LIKE PARTICLES WHICH IS PROBABLY NECESSARY TO GET OUT THE TRUE DIVERSITY OF THE VIRAL COMPROCESS OF BUILDING THE METHODS BUT YOU'RE ABSOLUTELY RIGHT. >> I'D LIKE TO EXTEND HIS EXTENT, AND JUST AS WE ARE UNDER ATTACK, THE BACTERIA WHICH CAN BE PART OF THE HEALTHY MICRO BIOME COULD BE URN ATTACK. AND THAT TACK BE ONE REASON YOU'RE SEEING A SHIFT. >> EQUALLY, YOU KNOW, DEFER TO YOUR WISE COMMENT, YES, THERE ARE A NUMBER OF PEOPLE INTERESTED IN TRYING TO UNDERSTAND IN GENERAL, HOW PAGE DRIVE AND RESHAPE BACTERIAL COMMUNITIES AS THEY DO EVERYWHERE ON THE PLANET, BUT LIKE WISE IN THE HUMAN BODY, PARTICULARLY IF PREGNANCY. I KNOW SEVERAL GROUPS ARE LOOKING AT INCLUDING PAGE, FOR EXAMPLE, IN THE VAGINA, LOOKING AT WHAT SEEM TO BE, OTHERWISE, POORLY EXPLAINED BACK. >> WHY DO GERM-FREE [INDISCERNIBLE] DO SO WELL. >> DO THEY? WELL, THAT'S A WHOLE ARBITRATE DISCUSSION, ACTUALLY. WHOLE OTHER QUESTION. AND THEY PROBABLY DON'T DO SO WELL IF THE WILD, IF THERE WOULD BE SUCH A THING. TEAR CAREFULLY, CAREFULLY NURTURED AND SUPPORTED IN A LABORATORY. BUT THEY'RE MISSING A LOT OF IMPORTANT FEATURES DESPITE THE FACT THEY SEEM TO DO SOME OF THE MORE PHROSE ASPECTS OF HOST BIOLOGY. >> WHAT ABOUT THE MICROBIOME OF MOTHER'S MILK, AND THE MICRO BIOME OF THE NEWBORN'S GUT. PORTANT. SEEMS RICHE THAT WOULD BE VERY >> DAVID: FIRST CLEARLY IMPORTANT IN CHAPPING THE LATTER. YES. ABSOLUTELY. I APOLOGIZE. THERE ARE LOTS OF REALLY IMPORTANT TOPIC THAT IS REALLY SHOULD BE BE TOUCHED AND THERE'S JUST NOT ENOUGH TIME. >> MAYBE GOING INTO ONE OF THESE UPON TOICS YOU DON'T HAVE TIME TO TALK. HOW ABOUT RESPONSE TO EXISTENCE OF MICRO BIOME, WHETHER SYMPTOMATIC OR A SYMPTOMATIC AND IF THERE'S ANYTHING RELATED TO [INDISCERNIBLE] ACTIVATION IN SOME OF THE NEUROLOGICAL CONDITIONING. >> DAVID: NO. I THINK YOU'RE EXACTLY RIGHT. THERE ARE CERTAINLY DIFFERENT KINDS OF -- I DON'T WANT TO SAY SKEWED BUT DIFFERENT PATHS AND KINDS OF IMMUNE RESPONSES THAT ARE DETERMED BY DIFFERENT KINDS OF COMMUNITIES OR BY DISTURBANCES THAT TYPICALLY OCCUR AND THEY MOST CERTAINLY ARE GOING TO EFFECT THE OVER ALL MATERNAL LANDSCAPE IN WHICH A BABY IS GROWING AS WELL AS SUBSEQUENT NEWBORN. >> WE KNOW SOME VIRUSES [INDISCERNIBLE] COULD YOU COMMENT ON THAT. >> I CAUGHT MOST OF YOUR QUESTION. YOUR QUESTION IS, WHY DO SOME VIRUSES OF THE: DO WHAT? >> NO. I MEAN, LIKE, WE KNOW FOR A LONG TILE, MANY VIRUSES CAN GET INTO THE FETUS BUT SOME VIRUSES CANNOT. THEY CAN INFECT THE FETUS FROM A CAN YOU COMMENT ON THAT. >> YEAH. REALLY GOOD QUESTION. PROBABLY SOME GREAT EXPERTINGS HERE. MY WILL BE THAT YES, FACT, THERE'S A VERY, VERY TINY SUBSET OF ALL MICROBE BE IAL LIFE, INCLUDING VIRUSES THAT SEEM TO HAVE LIFESTYLE STRATEGIES THAT ARE PARTICULARLY DEDICATED TO GETTING AROUND TYPICAL HUMAN DEFENSES, BECAUSE THEY SIMPLY SEEK TERRITORY IN WHICH THEY CAN AVOID COMPETITION OR OBTAIN UNUSUAL RESOURCES AND I THINK THAT'S TRUE FOR SOME OF THESE VIRUSES. MA SEEMS TO TRAFFIC SOTERIA. EASILY. BOTH DURING GESTATION AND ALSO IN THE NEWBORN, WITHOUT CAUSING OVERT. AT LEAST, OBVIOUS, OVERT MYTHOLOGY, DESPITE GETTING INTO SOMETIME FLUID AND SO FORTH. CLEARLY, THERE'S LOCAL WHITE CELL RESPONSES TO SOME OF THESE EVENTS AND THERE MAY IN FACT BE A STORY WHERE ALL OF THESE TRANSGRESSIONS ARE ACCOMPANIED BY A CERTAIN DEGREE OF RESPONSE THAT'S ACTUALLY PART OF THE OVER ALL BENEFIT FOR BOTH PARTICIPANTS. >> I'M WONDERING, HOW REPRESENTATIVE OF TWO MICRO BIOME SAMPLES FOR THOSE MICROBIOME PRESENTED IN MUCOSA OF COLON OR MUCOSA OF THE G.I. TRACT. YOU HAVE SAMPLINGS, TOO OF THE WHAT CORRELATES TO [INDISCERNIBLE] COMMUNITY. >> VERY GOOD QUESTION. THERE ARE SHOUT DISTINCT, AS YOU MIGHT IMAGINE. THERE'S ALSO SOME OVERLAP. WHAT COMING OUT AT THE FAR END IS AN SAFETY CENSUS BUREAU MIXTURA MIXTURE OF WHAT IS FOUND INLOCATIO NS, NOT JUST LONGITUDINALLY, BUT RADIALLY IT'S THOUGHT TATHERE'S A PROTECTIVE MUCOUS LAYER WITH MULTIPLE SUBSTRATE A THAT LARGELY EXCLUDE MOST OF THE VOLUME NA BACTERIA WITH CONTACT WITH THE EPITHELIAL SURFACE OF THE GUT. THOSE OUTER LAYERS ARE CERTAINLY POPULATEPOPULATED AND IN FACT, PAGE ARE ABOUT TO PLAY A ROLE, PHAGE PLAY A ROLE TO HELP DEPOPULATE SO YOU DON'T JUST GET LARGE-SCALE VIOLATIONS OF THAT INTERSANCTUM WHERE THE STEM CELLS AND GROWTH CELLS ARE. >> MY QUESTION IS RELEVANT TO THE TRANSITIONAL. IT'S VERY FACE, THE TERMS AND [INDISCERNIBLE] FROM THE CLINICAL PROCESS OF BUILDING THE METHOD OF VIEW, YOU CANNOT REALLY IDENTIFY THAT THE BACTERIAL IN THE PATIENT AND FROM THAT POINT OF VIEW, HOW CAN YOU DETERMINE WHAT KIND OF BACTERIA INFECTED WOMAN DURING THE PROGRESS NANCY, NUMBER ONE. FOR MOST OF THE WOMEN, THEY GOT THE VIRAL INFECTION, WHICH YOU CAN REALLY NOT HAVE LAB EVIDENCE SHOWING THAT THERE IS AN INFECTION. >> THOSE ARE ALL GOOD QUESTIONS. I THINK TO A LARGE SCREEN, THE KINDS OF THINGS I WAS TALKING ABOUT ARE PROBABLY A FEW STEPS AWAY FROM DIRECT CLINICAL APPLICATION. IN PART, BE BECAUSE WE'RE NOT SURE WHAT PARTS OF THAT STORY ARE MOST PROTECTIVE OF HEALTH OR DISEASE. PARTICULAR BE BE THAT ONE DAY THERE WILL BE A MUCH MORE, YOU KNOW, PRACTICAL TEST THAT TAKES ADVANTAGE OF SOME OF THOSE FEATURE. MAYBE IT'S AN ABUNDANT BASE. PARTIALLY HOST RESPONSE BASE BECAUSE WE KNOW THAT AT LEAST IF A SIMPLE WAY OF THINKING ONE OF THE EASIER WE TO SEE IF MY QUESTION IS MATTERS IS TO ASK THE IF IT MATTERRINGS. LOOK AT THE HOST NATURE. SO I'M IMAGINING TATHERE WILL BE, AND THERE ALREADY S WHITE COUNTS. MAYBE AYE SICK LEVELS BUT THAT HOST IS RESPONSIBLY PART OF THE FOR. MARRIED TOGETHER WITH THE MICHAEL BUCKLEY CREDIBLE BE IAL FEATURES. >> NOMARRIED WITH THE MICROBE BE IALFEATUR ES. POSTMARKERS THAT HAVE GREAT SPECIFICITY. BUT BECAUSE THEY ARE RETIREDDED TO MICROBIAL SET OF FEATURES TOGETHER AS WELL. >> UNDERSTAND WHAT THE IMMUNE STANDPOINT OF YOUR PATIENTS GOING INTO THIS STUDY, WHETHER THEY HAVE BEEN INFECT, WHAT THEIR VIRAL LOAD IS, AND I KNOW THE VIRUS WE WORKED WITH CAN GET IN MOUSE MODEL, ALBEIT, THE PLACENTA CAN BE CHALKFUL OF THIS VIRUS, AND YOU CAN TAKE THE BABIES AND GRIND THEM UP, AND DO WHATEVER YOU. AND YOU WON'T FIND A SINGLE [INDISCERNIBLE] IN THE BABY. THERE ARE VIRUSES THAT WON'T GET INTO THE PLACENTA AND SOME VIRUSES GET IN AND MAKE A MESS. THE T-CELLS WORK APPARENTLY, IN THE PLACENTA, THE VIRUSES WORK. THERE'S SOME VIRUS, PLACENTA PRACTICALS THAT NEED TO BE UNDERSTAND MORE CAREFULLY AND THAT WAS COMMENT NUMBER ONE. AS YOU LOOK AT TEASE NOVAK DJOKOVICEL MECHANISMSNOVAKAT THESE NOVEL[I NDISCERNIBLE] >> THE LATTER QUESTION, I'LL TRY AND CHANNEL A RESPONSE FROM OTHERS. BUT I THINK THE WORRY IS YES. THERE IS AND SHOULD BE AN EFFORT TO INTEGRATE THOSE MUTT PELL KINDS OF DATA TO YOUR FIRST COMMENT, A VERY GOOD ONE. A LOT THIS IS NOT NECESSARILY HARMFUL, IT DOESN'T GET COMPARTMENTALIZED. BUT IT'S IMPORTANT FOR PROVOKING HOST SOMEONES THAT ARE SO I WOULD SERGEANT CAUTION MICROBE CROAKS IN A PLACE WE HADN'T SUSPECT THEM, IT'S NOT BAD. IT MAY NOT BE AT ALL. >> VIRUSES, I WORK WITH VIRUSES AND THE PLACENTA. VIRUSES HAVE SPECIFIC WAYS OF GETTING INTO THE PLACENTA. LIKE CYTOMEGLA VIRUS. CYTOTROVE PLAST, WHERE THERE ARE MULTITUDE OF CELLS THAT ARE PERMISSIVE FOR THE VIRUS INFECTION. THE OTHER POINT I WANTED TO MAKE. THERE ARE CERTAIN SITUATIONS WHERE VIRUSES CAN BE BE FOUND AND BE SUBCLINICAL. HOWEVER, THE WORK BY BARRERA SUGGESTS EVEN IN THE CASE OF IDIOPATHIC TEASE AND EVEN IN TERM PREGNANCIES, YOU WILL FIND PATH LODGE BE CAL CONSEQUENCES OF VIERAL REPLICATION REPLICATION. I JUST WANTED TO MAKE THAT COMMENT. [Applause]. >> THAT WAS GREAT. LOVE THE DISCUSSION AND NOW WE'RE BEING TO, IN THAT SAME VEIN WE'RE GOING TO ASK OUR NEXT SPEAKER. ESCALANTE OF NICHD TO COME UP AND TELL US ABOUT THE HUMAN GENOME PROJECT. >> THANK YOU. I SHOULD TELL YOU IN FULL DISCLOSURE, "ORGANIZERS WERE PUTTING THIS AFTERNOON'S SESSION, IT WOULD BE WONDERFUL TO HAVE SOME SCIENTIFIC LESSONS SO WE REACHED OUT TO THE PERSON WE SAW AS A REAL LEADER OF THAT. DAVID TO, GIVE WHAT I THOUGHT WAS A WONDERFUL TALK. AND WE THOUGHT THERE ARE ALSO SOME PHILOSOPHIC LESSON IN THE HUMAN GENOME PROJECT. SO WE ASKED FRANCIS COLLINS TO GIVE HIM TO GIVE THAT TALK. FRANCIS RESPOND HE WAS HOST BEING ABE MEETING ON THE PRECISION MEDICINE INITIATIVE AT THE SAME TIME. SO HE REALLY WASN'T AVAILABLE FOR HIS TALK. HE SAID, HOWEVER, THE GUY WHO'S MY DEPUTY DIRECTOR AT THE GENOME INSTITUTE I WOULD WORK CHEAP, SO I WAS ASKED TO GIVE THAT TALK. I SHOULD AGAIN N FULL DISCLOSURE SAY, THAT DAVID WAS INTERESTED IN THE HUMAN GENOME PROJECT, I CAME TO THE GENOME RESEARCH INSTITUTE, WAS ONLY THE DEPUTY DIRECTOR FOR THE VERY HAIL END OF THE PROJECT. SO THIS IS MORE OF A FLY ON THE WALL VIEW OF THE HUMAN GENEOME PROJECT AND WHAT WE MIGHT LEARN FROM IT. I'M GOING TO REALLY TALK PRIMARY OF THE HPP ITSELF, NOT SO MUCH THE -- THE HGP ITSELF, AND NOT SO MUCH THE HPP. THERE ARE A COUPLE PLACESSIC BEN'T HELP MYSELF AND I WILL DIVE INTO THOSE. IT. BE BOLD, ANDS THIS A QUOTE FRANCIS AND I USED TO TALK ABOUT A LOT. MAKE NO LITTLE PLAN. 35 NO MATCH TO STORE MENDS, THESE ARE VERY OLD QUOTE QUOTES FROM DANIEL BURNON. MAKE BIG PLANS, AIM HIGH IN HOPE AND WORK. REMEMBERING THAT A LOGICAL DIAGRAM ONCE RECORDED WILL NEVER DIE, BUT LONG AFTER WE ARE GONE WILL BE A LIVING, A ETERNITY SYSTEM ITSELF WITH EVER GROWING INSISTENCY, WHAT WE WOULD ALL INSPIRE TO. YOU SHOULDN'T HAVE A PROBLEMS UNLESS IT HAS SOME PRETTY BOLD GOALS THAT REQUIRES NEW APPROACHES AND TOOLS. OTHERWISE, IT'S JUST MORE SCIENCE WHICH IS IMPORTANT AND WHAT WE DOULE AT TIME BUT IF WE'RE REALLY GOING TO LAUNCH SOME SPECIFIC KIND OF THING, SHOULD REQUIRE AN APPROACH TO GOAL AND HAVE AN ULTIMATE GOAL WHICH IS AN IMPORTANT GONE. THAT WOULD CHANGE THE PARADIGM OF HOW WE DO THIN THINGS. TIME IS EVERYTHING. MY FAVORITE, FRANCIS USED TO USE THE QUOTE, AND MISATTRIBUTE IT TO WAYNE GET SKI. IT'S ACTUALLY FOR TH WAYNE GRETZKY. IT WAS HIS WALTER WHEN, SAID TO THE THEN-TEENAGE WAYNE GET SKI, GO TO WHERE THE PUC IS GOING, NOT TO WHERE THE PUCK HAS BEEN. YOU ANTICIPATED WHERE THINGS WERE GOING. AND YOU GOT THERE. SO THE IDEA OF THE HUMAN GENOME PROJECT. IS TO LAUNCH AT THE RIGHT MOMENT. NOT TOO SOON, NOT TOO LATE. IF THE APPROACH ALREADY EXIST. THAT'S WONDERFUL. JUST APPLY THEM. IF THE APPROACHES ARE SOMETIME AWAY, THEN YOU DON'T WANT TO LAUNCH A PROJECT. YOU WANT TO WAIT UNTIL THEY ARE MORE MATURE. YOU REALLY WANT TO LOOK FOR THIS TIMING SWEET SPOT. THE HUMAN GENOME PROJECT, A LOT OF SEQUENCES CENTERS. AND MAN FAILED. MANY PEOPLE WOULD LOOK AND I SARK YOU'RE FUNNELING FOLKS WHO ARE FAILING. WELL, THAT IS THE NATURE OF SCIENCE AND TECHNOLOGY DEVELOPMENT. THAT THINGS FAIL. AND WE NEED NOT TO HIDE THOSE. WE NEED TO ANTICIPATE OUR FAILURES. IT'S NOT JUST ACCEPTABLE. BUT DESIRABLE. IF YOU DON'T FAIL SOMETIMES, YOU'RE PROBABLY NOT BEING BOLD ENOUGH WITH WHAT YOU'RE TRYING TO DO. THE KEY TO THIS IS TO RECOGNIZE FILATURES EARLY AND NOT JUST TRY TO KEEP OKAYING THEM OUT, YOU KNOW, SLOWLY SO YOU CAN CONTINUE TO GET FUNNING BUT TO SAY THIS IS NOT WORKING AND THEREFORE, REDIRECT BOTH FOCUS AND FROM OUR PERSPECTIVE, FUNDING BUT BOTH OF THOSE THINGS, TO THOSE APPROACHES WHICH SEEM TO BE PROMSING I THINK ONE OF THE LESSONS IS THE TOP-DOWN COORDINATION REALLY WASN'T IMPORTANT TO MAKE THIS SUCCESSFUL. HOWEVER, IT REALLY NEEDS TO CATALYZE A DIVERSE BOTTOM-UP IDEAS. THE IDEAS NEED TO COME UP FROM THE COMMUNITIES OF RESEARCHERS AND IT'S MORE THAN ONE COMMUNITY ALL OF WHICH. AND THERE REALLY IS THIS CREATIVITY THAT I THINK IS OPTIMIZE, IF YOU HAVE BOTH OF THESE, SOME TOP DOWN, NOT HEAVY HANDED BUT TOP DOWN COORDINATION, BUT REALLY RELY ON THE TELEPHONE IDEAS OF THE RESEARCH COMMUNITY. THE MORE THE MERER. THE HUMAN GENOME PROJECT, AND YOU ALREADY HEARD THIS. YOU WANT IT TO BE, YOU NEED SCIENTISTS FROM DIVERSE BACKGROUNDS AND PERSPECTIVES. THE HUMAN GENOME PROJECT IS BOTH SCIENCE AND TECHNOLOGY 20, AND THERE WAS PRACTICAL WITHIN THE TWO, THAT EACH PROCEEDED BEST IF THE OTHER -- BECAUSE SOMETIMES THERE'S NOT DRAMATIC DIVISION BETWEEN SCIENCE ASK TECHNOLOGY. THE TWO ARE TALKING TO EACH OTHER. THE CLINICAL WORLD AND THE BASIC WORLD ARE TALKING BACK AND FORTH. THAT'S OFTEN MOST APPROPRIATE AND MOST HELPFUL. THE HUMAN GENOME PROJECT DID APHIS EXAMPLE OF TAKING GE OF THE OPPORTUNITY FOR CUT BEING EMBRAILLESSED, TRANSSESSIONENT APPROACH, IT'S AN OBVIOUS OPPORTUNITY TO REALLY TRAIN PEOPLE IN TRANSISTENTARY IT REALLY NEEDS GLOBAL RESEARCH THAT IS CUTTING EDGE. SUPPORT AT ALL LEVELS, FOR THE ONES JUST IN TERMS OF THE RESEARCHERS, BUT TRULY GLOBAL IN TERMS OF THE OTHER COMMUNITIES. WE HAVE FOLKS HERE THAT ARE INTERESTED IN HAVING THE HUMAN PLACENTA PROJECT. HAVING THE PRESENCE IN INDIA, CHINA. NOT JUST ONE OF THE REAL CARDINALS FEATURES BUT THE ADVANTAGES WAS THE FACT THAT IT WAS AN INTERNATIONAL HUMAN GENOME PROJECT, AND ARE THAT WAS PART OF THE REASON YET COORDINATION WAS NECESSARY. IT CREATES CERTAIN CHALLENGES. JEFF SCHLO FOOTWORK F WAS HERE, HOW DO YOU HAVE A WEEKLY CONFERENCE CALL, WHEN PEOPLE ARE ALL THE WAY AROUND THE GLOBE. OR YOU VARY THE TIME SO EVERYBODY WILL BE UNCOMFORTABLE ON OICATION. BESIDES HAVING MORE FUNDING IN CAPACITY, BUT YOU HAD DIFFERENT CENTERS. YOU ALSO HAVE DIFFERENT PERSPECTIVES THAT COME TO BEAR WHEN YOU HAVE DIFFERENT NATIONALITIES. DIFFERENT CULTURE, ET CETERA INVOLVED IN THIS. SO IT REALLY TAKES ADVANTAGE OF TECHNOLOGICAL, SCIENTIFIC KNOW-HOW, BUT SOME WITH DIFFERENT PERSPECTIVES AND RESORERESOURCES. CREATING NEW AND BETTER TECHNOLOGY TO ARC HOW THE SCIENCE. THIS TECHNOLOGY IS NOT UP TO THAT TASK. SO YOU NEED TO MOVE BEYOND THAT. YOU DEVELOP SOMETHING WHICH DOES THIS KIND OF ROCKET LAUNCH, AND YOU CAN EXPLORE THE UNIVERSE OF THE SO WHAT WE NEED TO DO IS DEVELOP NEW TECHNOLOGY, BUT NOT FOR THEIR OWN SAKE, BUT TO BE ABLE TO ENABLE THE SCIENTIFIC EXPIRATION. ONCE THE PROJECT ENDED, THE TECHNOLOGY CONTINUED TO DEVELOP. THE GENOME FOR A LONG TILE, PATTED ITSELF ON THE BACK AND SAID, WE'RE OBSERVING LE] LAW THAT EVERY 24 MONTHS, THE PRICE OF SEQUENCING SOME SEGMENT OF THE GENOME WENT DOWN BY 50%. WELL, THERE'S MOORE'S LAW FOR YOU AND YOU CAN SEE THAT FOR MANY YEARS, THIS WAS THE CASE. NOW, INTERESTINGINGLY THE HUMAN GENOME PROJECTENNED RIGHT THERE, AND THROUGH THAT PERIOD, IT WAS BEING FOLLOWED WHICH IS PRETTY DAMN IMPRESSIVE. HE STOPPED THE HUMAN GENOME PROJECT. YOU ALLOW TECHNOLOGY TO DEVELOP, WITH NIH HELP AS WELL. THERE'S A LOG OCCURRING. NOW, A LOT OF THAT WAS PLANTED WAY BACK HERE. BIAS YOU GET THE NEXT GEN SI KENS AND OTHER KINDS OF TECHNIQUES. THE PRICE CONTINUED TO FALL MORE AND MAR PRECIPITOUSLY. ONE OF THE TAKE-HOME LESSONS IS IT IS POSSIBLE TO E AND FEEL THAN EVEN WHEN YOU WITHDRAWL THE SAME LEVEL OF SORT OF SUPPORT FOR IT, ET CETERA, ET CETERA. YOU NEED TO CONTINUE SOME. IT CONTINUES ON ITS OWN FORETO DO AN INCREDIBLE JOB. HYPOTHESIS-FREE. THIS HAS COME UP IF SOME DISCUSSION AND I'VE DEBATED BACK AND FORTH HERE, AND I'M SURE WE'LL DISCUSS FURTHER HOW THIS INFLUENCE. BUT THERE WAS NO HYPOTHESIS FOR THE INNING. OTHER THAN-- FOR THE HUMAN GENOME PROJECT. NOW, THE DIRTY SECRET. PEOPLE TALK ABOUT THE HUMAN GENOME PROJECT. IT DID HAVE TWO HYPOTHESES, IF THE SECRET MUST BE TOLD. THE FIRST HYPOTHESIS. WE HYPOTHESIZED WE CAN SEQUENCE HUMAN GENOME, AND THERE WERE MANY AT BEGINNING WHO THOUGHT, NOT TRUE. HERE'S A PLACE I COULDN'T HELP MYSELF. FOR THE HEART ATTACK PP I THINK OUR HYPOTHESIS WOULD BE, WE CAN DEVELOP METHODS FOR MODERN HUMAN PLACENTA DEVELOPMENT OVER REAL TIME AND THE, SECRET HYPOTHESIS IS DOING SO WOULD BE A GREAT [INDISCERNIBLE] AND IN CLINICAL CARE. THE REAL DOUBTERS OF THE HPPING BEFORE IT ARE STAD ONE IS YOU CAN'T DO IT THE SECOND ONE IS, IT'S NOT WORTH DOING IT. FOR THE HPP I WOULD SAY IT'S DITTO, I THINK MANY OF US IN THIS ROOM, OTHERWISE WE WOULDN'T BE HERE, BELIEVED THAT IT WOULD HAVE GREAT VALUE AND RESEARCH, IN CLINICAL CARE. WIN FRIENDS AND FINELY PEOPLE. IN SOME WAYS, I THINK THE MOST IMPORTANT C OF THE HUMAN GENOME PROJECT IS THIS LAW. IN ALL HONESTY, HAD THERE NOT BEEN AN INTERNATIONAL HUMAN GENOME PROJECT, IT WOULD HAVE THE FACT IT WOULD HAVE TAKEN LONG TORE DO TISSUING THE DATA -- TO DO IT -- SESENSING HUMAN GENOME, AND THE REAL DIFFERENCE HERE IS WHO WILL N THIS INFERRING. AND THE HUMAN GENOME PROJECT IS NOT JUST A QUESTION WHO OWNED THE INFORMATION BUT THE FACILITATION THAT IT WAS RUPIOIDLY RELEASED. EVERY 24 HOURS IF YOU, ELECTRICITY ON THE COMPUTER, IF YOU HAD ELECTRICITY ON THE COMPUTER, YOU COULD DOWNLOAD THE INFORMATION THAT DONE BY THE HUMAN GENOME PROJECT THAT DAY. SO FREE AND OPEN ACCESS EVERY 24 HOURS ITULE AT INFORMATION WITH 43 UPON STANDARDS AND PRACTICE, TO MAKE THAT INFORMATION SERVICEABLE. IN THE AGE OF WIKIPEDIA AND EVERYTHINGES, WHERE KNOWLEDGE IS CONSTANTLY BEING IMMEDIATELY SHARE, IT'S THE SAME IDEA. THE HUMAN GENOME PROJECT WAS LARGELY PAID FOR BY YOUR FEDERAL TACK DOLLARS, AND THIS KNOWLEDGE BE IS BEING GAINED THROUGH YOUR FAX DOLLARS AND DID NOT BELONG TO THE P.I. IT BELONGS TO SOCIETY. THOSE THAT PAY TO HAVE IT DONE. THE BEST AND THE BRIGHTEST. PRETTY SIMILAR. IT DID A NICE JOB. ALL CAREER I THINK STARTED PARTICIPATINGS, SOME WILL REMEMBER THE STORY AT ONE POINT, BE I WOULDN'T QUITE SAY SAVE, BUT A CRUCIAL POINT IN THE GENOME PROJECT WAS ACTUALLY SAVE BY A GUY DOG DOOING A POST DOC, REALLY FIGURING OUT -- ... ... [PLEASE STAND BY] BE FINISH AHEAD OF SCHEDULE SURROUND BUDGET. THE HUMAN GENOME PROJECT FAMILY THIS. TILL PROBABLY TRUE. BUT WHENEVER WE WENT TO CAPITOL HILL TO TALK ABOUT THE SUCCESS, WE SOMEHOW ALWAYS MANAGED TO TALK ABOUT THE FACT THAT IT FINISHED AHEAD OF SCHEDULE UNDER BUDGET. AND I WAS WITH, I USED THAT LINE ENOUGH TIMES AND I GREW INCREDIBLY IMPRESSED WITH THE FACT NO MATTER HOW MANY TIMES WE SAID IT, PEOPLE TAUGHT THIS WAS A WONDERFUL ACCOMPLISHLET, INSTEAD OF ASKING THE OBVIOUS QUESTION. WHAT, YOU COULDN'T FIGURE OUT AHEAD OF TIME HOW MUCH IT WAS BEING TO COST YOU AND HOW LONG IT WAS GOING TO TAKE TO YOU DO THIS. IT'S IMPORTANT. I THINK TO HAVE REALISTIC GOALS AND IF YOU CAN. TO BEAT THEM. PAY TAKEN TO ECTICS ISSUES. THIS WAS AN INCREDIBLY IMPORTANT PART OF THE HUMAN GENOME PROJECT JIM WATSON BE WHEN HE WAS AHEAD OF THE PREDECESSOR NATIONAL NEWT. HE WAS ASKED AT CONGRESSIONAL HEARING ABOUT THIS AND SORT OF, JEFF MT BE ABLE TO GIVE MORE DETAILS BUT MORE OR LES OFF THE CUFF WHEN TALKIN WHEN ASKED IF THERE WERE SOME ETHICAL ISSUE HERE. HE SAID YES, THERE ARE AND WE'RE BEING TO SPEND 3% TO 5% OF OUR BUDGET RESEARCHING THOSE. I THINK IT ACTUALLY, SOME INFUSE THE WHOLE AREA OF JEN ONLYICS SO PEOPLE PAY TAKEN TO THE ETHICAL ISSUES BEFORE THINGS ARE LAUNCHED RATHER THAN FIGURING OUT ABOUT THEM AFTER THEY'RE OUT THERE IN SOCIETY. THE LARGEST AMOUNT OF MONEY SPENT ON BIOMEDICAL THINKING WAS OUT OF THE 3% TO 5%. BE READY TO BE PROVEN WRONG. YOU CAN SEE, THE AMOUNT TO WAGER WAS A MODEST DOLLARS. AS YOU GOT CLOSER AND CLOSER, YOU HAD TO PUT MORE MONEY BECAUSE BY THEN, YOU KNEW MORE. AND IN THIS SCATTERGRAM SHES. NOW, REMEMBER, THESE ARE THESE ARE THE FOLK BEES THAT ARE GOING TO GENOME CONFERENCES THAT, YOU KNOW,. I REMEMBER PUTTING THE ENVELOPE IN MY DESK, SOMETIME IN 2001 OR 2002. I CAME UP WITH 47,000. SO YOU KNOW, I'LL DECLARE THAT. A FEW YEARS BEFORE THAT,A THE UNIVERSITY OF VERMONT, I USED TO TELL THE MEDICAL STUDENT, THERE ARE A HUNDRED THOUSAND HUMAN GENES, AND I FEEL MUCH BETTER KNOWING THAT I DOUBT THE TUNES REMEMBER ANYTHING I TOLD THEM BACK THEN BECAUSE OF COURSE, THE WORRY IS 20,000, APPROXIMATELY. I THINK TELL SERVE ALL OF US WELL, TO REMEMBER, NO MATTER HOW EXPERT YOU ARE, NOT A SINGLE PERSON, IF THIS WAS THE PRICE IS RIGHT WHERE YOU HAVE TO BE UNDERNEATH. NOT A SINGLE PERSON WOULD HAVE WON THE CAR. NOTHING. SO IT'S INTERESTING THAT EXPERTS CAN BE THAT FAR OFF ABOUT SOMETHING YOU WOULD THINK IS SIMPLE TO HAVE SOME IDEA ABOUT SO THE GREEN EYED MONSTER AWAITS I ASKED FRANCIS ANYTHING YOU THINK I SHOULD BE SURE TO MENTION, HE DIDN'T HAVE THIS ILLUSTRATION FOR ME. BUT HE DID CALL IT THE GREEN ION STORY, BUT HE DEFINITELY WANTED TO MAKE THIS POINT. THE HUMAN GENOME PROJECT, A LOT OF FOLKS DID NOT LIKE IT BECAUSE THEY FELT TELEVISION KEEPING THEIR RO1 FROM BEING FUNDED. THE SORT OF WASTE OF NIH FUNDS AND MAYBE EVEN ATTENTION. YOU CAN BE BE FUNNELING MY RO1 INSTEAD OF FUNDING THAT GENOME PROJECT. WHAT KIND OF FOOLS ARE YOU? WELL, I THINK AT THE END, I WOULD ARGUE THIS WAS A GOOD INVESTMENT THAT WHAT THE HUMAN GENOME PROJECT OF ABLE TO DO IF YOU THINK ABOUT THE RO1'S TODAY, SOME OF WHICH YOU ALL HAVE PROFITED FROM, EITHER DIRECTLY FROM BEING THAT INVESTIGATOR, BENEFITING FROM THE RESEARCH, ABOUT HOW MANY RO1'S DO THE NIH AND OTHERS HAVE FUND IF THE LAST DECADE, HAVE RESTED UPON BEING ABLE TO SEQUENCE THE HUMAN GENOME, THEY USE THAT IN A ROUTINE KIND OF FASHION. IT'S KIND OF STAGGERING, IN FACT. THESE ARE ACTUAL QUOTES JUST BEFORE IT WAS LAUNCHED IN 1990. SEQUENCING THE GENOME WILL BE BE AT USEFUL AS TRANSLATING THE COMPLETE WORK BUT NOT QUITE AS FEASIBLE OR EASY TO INTERPRET. I LOVE THE IMAGE BUT NOT QUITE UP FOR ME BEST, I SHIVER AT THE THOUGHT. YOU WONDER WHERE THOSE PEOPLE ARE TODAY. I SUSPECT THEY'RE ALL DEANS AT MEDICAL SCHOOLS. [LAUGHTER] WITH ALL RESPECT, DEANS AT MEDICAL SCHOOLS. YOU WOULD SAY THINGS LIKE THAT AND PEOPLE ELEVATE YOU. SO ANOTHER LESSON IS, YOU WANT TO DECLARE VICTORY AND I ALREADY REFERRED TO THAT A LITTLE BIT YESTERDAY. NO, AS A MATTER OF FACT, IF CAN OFTEN AS YOU CAN. NOW, AGAIN, THAT'S A SECRET TO THE HUMAN GENOME PROJECT. WE IT IT TWICE. THERE WAS THIS CEREMONY. AND FRANCIS EVEN THEN, TELLING THE PRESIDENT WHAT TO DO. [LAUGHTER] SO WHEN THE DRAFT SEQUENCE WAS DONE, THERE WAS THIS BIG CEREMONY FROM THE WHITE HOUSE. DECAYING THAT WE HAD AND CLINTON, OUR CHILDREN'S WITH STARS. A WONDERFUL VICTORY CELEBRATION. IT WAS SO WONDERFUL, WE JUST HAD TO DO IT A COUPLE YEARS LATER N.2003, WHEN THE FINAL SEQUENCE WAS DONE ACCIDENT WHICH ANOTHER, IT'S NOT REALLY THE FINAL SEQUENCE, IT WAS GOOD ENOUGH WE THOUGHT BECAUSE HAD PARTS HADN'T BEEN SEQUENCED IN APRIL 2003, BUT TWO MONTHS BEFORE THAT DATE, 50 YEARS FROM WATSON AND CRICK FIRST PUBLISHED THEIR FIRST MODEL OF DNA THERE WAS EYE WONDERFUL PARTY AFTER THAT. THE LIBRARY OF CONGRESS. IT WAS JUST STUPENDOUS AND THEN, HOWEVER, IMPORTANT LESSON AS WELL, ONCE THE PROJECT WAS OVER, THEN ALL OF THE EFFORT, SOME OF , I THINK YOU COULD FAIRLY SAY THE HUMAN PIKE ROW BIOME PROJECT IS A GOOD EXAMPLE OF THAT. WHAT OUT OF THE GENOME PROJECT, BOTH IN TERMS OF THE TECHNICAL AND SCIENTIFIC KNOWLEDGE, TO THEN MOVE ON. AND BE ABLE TO APPLY THAT TO BETTERRAPHY AND ALSO INTO BETTER CLINICAL CARE. SO MY SUMMARY OF THIS IS THE FOLLOWING. WE HAVE SOME FRENCH SPEAKERS IN THE AUDIENCE. YOU HAVE TO TELL ME WHETHER THAT'S TERRITORIED CORRECTLY OR NOT. THE TASK IS NOT TO FORESEE IT, BUT TO MAKE IT POSSIBLE. AND I REALLY DO THINK THAT'S A CARDINAL LESSON OF A HUMAN GENOME PROJECT. THE FACT GOING INTO THIS, FRANCE, MAYBE BE REALLY KNEW HOW IT WAS ANYTHING TO BE DONE. I DON'T KNOW IF WE HAVE TIME FOR QUESTIONS, BRICK BATTIERS, TOMATOES, WHATEVER PEOPLE MIGHT LIKE TO RAISE. WITH THAT, LOOKING FORWARD TO OUR NEXT SPEAKER. WE HAVE A QUESTION. OR A COMMENT. KNOWING THE COMMENTER, IT'S A BRICK BATTIER. >> I PRINTOUT TOMATOES JUST TO BE BE KIND. ALAN, I THINK FIRST OF ALL, THAT WAS A GREAT TALK AND I REALLY APPRECIATE THE PERSPECTIVE BECAUSE IT BRINGS THE SORT OF HUMAN ELEMENT OF THINKING INTO THE SCIENTIFIC REALM BUT ALSO HOW YOU PERCEIVE BIG PROJECTS. ONE OF THE COMMENTS YOU MADE, IS SORT OF THE TOLERANCE OF FAILURE TO SUCCEED AND MAYBE WHAT WOULD BE HELPFUL FOR ALL OF US IS TO UNDERSTAND, YOU KNOW, IN THE CONTEXT OF THE KNOWLEDGE CHICAGO THAT WE ALL FACE IN DIFFERENT TYPES OF SKEIN AND FROM DIFFERENT ORGANIZES, HOW DO YOU SEE PROMOTING THAT WITHIN THE REALM OF WHAT NIH IS TRYING TO DO HERE THERE SURE. THAT'S A GREAT QUESTION. CRAIG, AND OBVIOUSLY, IT APPLIES SPECIFICALLY TO THE HUMAN PLACENTA PROJECT, BUT IT APPLIES TO NIH. CLEARLY WHEN FUNDING IS TIGHT, WE ALL TEND TO GET MORE CONSERVATIVE, AND THAT'S CERTAINLY TRUE OF STUDY SECTIONS, I THINK IF YOU THINK ABOUT THAT, YOU WILL REALIZE THE TIGHTER FUNNING GET, THE MORE CONSERVATIVE STUDY SECONDS TEND TO GET. IF WE KNEW AHEAD OF TIME HOW WE WERE GOING TO DO THE KIND OF THINGS WE HAVE ALL BEEN TALKING ABOUT, YOU'D ALL BE OUT THERE DOING THEM NOW. THERE WOULD BE ONE OR TWO THINGS, MAYBE THREE. WE'D AWE BE PURSUING. WE DON'T KNOW THAT NOW AND I THINK WE HAVE TO BE HONEST ABOUT THAT THE HPP LEADERSHIP, ANYONE IN THIS ROOM IS NOT GOING TO BE ABLE TO PICK OUT AHEAD OF TIME, EXACTLY, WHICH ARE GOING TO BE THE WINNERS AND I THINK WE NEED TO APPROACH THAT PROJECT WITH THAT KIND OF AWARE KNOW. CERTAINLY, WE'RE JUST NOT GOING TO RANDOMLY CAST MONEY OUT THERE, AND CLEARLY STUDY SECTIONS ARE GOING TO LOOK AT THESE THINGS THAT COME IN. TO BE HONEST, - US WHO ARE INVOLVE IN MAKING THE FINANCIAL DECISIONS IN THIS, REALIZE THINGS THAT SAME RISKIER, WHICH HAVE HIGH PROMISE NEED TO BE FUNDED. WE DON'T WANT TO FUND THREE VERSIONS OF THE SAME EXACT APPROACH. BUT IT WOULD BE BETTER TO DIVERSIFY OUR FUNNING, TO THREE DIFFERENT APPROACHES. FOR INSTANCE, HYPOTHETICAL, EVEN IF ONE OF THEM SEEMS LESS PROMISING THAN THE FIRST ONE OR WHATEVER, THAT PROBABLY MAKES SENSE TO DO THAT BUT THEN, AFTER ANG APPROPRIATEE AND A DEMONSTRATION OF WHAT'S HAPPENING, TO RELOOK AT WHICH ONES SEEM TO BE WORKING AND AGAIN, IT'S NOT JUST A QUESTION OF THE MONEY, IT'S A QUESTION OF THE SCIENTIFIC FOLK BEUS AS WELL, TO REALLY CONTINUE TO INVEST IN THE ONCE THAT SEEM TO BE MOST PRODUCTIVE. THESE ARE GOING TO NEED FOR THE DEVELOPMENT BUT I DO THINK TOOT A LESSON FROM LARGE PROJECTS BUT OTHER AREAS OF SCIENCE AS WELL THAT YOU WANT TO SEE THE NUMBER OF APPROACHES, INCLUDE THOSE THAT LOOK RISQUE. BUT THE OTHER SIDE OF THAT COIN OR WHATEVER, THERE OUGHT TO BE INTERMEDIATE METRICS AS THERE WERE FOR THE GENOME PROJECTS, AND IF PEOPLE WERE MEETING THOSE METRICS. WHY IS THAT. IT MAY BE YOU INVESTED IN THE AREA AND THAT'S A REASON TO DOUBLE DOWN THE BET OR IT MAY BE, AS YOU LOOK AT IT, THIS IS AN AREA THAT SIMPLY HAS HIT A BRICK WALL YOU'RE NOT GOING TO BE ABLE TO GOAT RID OF. >> YOU USE THE HUMAN GENOME TO LOOK AND COMPARE. SO MY QUESTION IS, LOOKING BACK TO THE HUMAN GENOME PROJECT, THAT IS A GLOBAL EFFORT, IN ADDITION TO THE U.S., THERE IS FRANCE AND DUTCH AND DENMARK AND CHIN A. RIGHT NOW FOR THE PLACENTA PROJECT, RIGHT NOW, WHAT'S FAR FROM HERE, AS THEY POINTED OUT, INDIANAIA, CHINA. WHAT'S GOING TO BE YOUR PERSONAL EXPECT BETATION TO BEING LOOK FORWARD, WHAT YOU EXPECT FROM THE GLOBAL, INTERNATIONAL EFFORT OR THE OTHER COUNTRIES. >> THERE IS MORE THAN ENOUGH WORK TO GO AROUND. AND MORE THAN ENOUGH SCIENTIFIC IDEAS. MY HOPE IS THAT THERE WOULD BE INTERNATIONAL FUNDING BECAUSE THAT ENABLES THINGS, BUT ALSO, WE WOULD HAVE BOTH TO BE OVERLY CUT AND DRIED ABOUT IT. THERE'S SCIENTIFICS AND TECHNOLOGY DEVELOP DEVELOPERS. FOR MANY COUNTRIES INVOLVED IN THIS. WITH THE IDEA THAT DIFFERENT APPROACHES. DIFFERENT QUESTIONS THAT HAVE ALREADY COME UP TODAY. THERE ARE CERTAIN EXPOSED PREGNANCIES, INY CROSS, IMPROVED AND OTHERS ARE NOT. SO FOR THAT REASON, AMONG MANY OTHERS. HAVE A LARGE COMMUNITY OF FUNDERS BUT MORE IMPORTANTLY, SCIENTISTS WORKING ON THIS. IT'S JUST THE BENEFIT OF EVERYONE. IF WE'RE LUCKY ENOUGH, HOW DO WE COORDINATE THAT. HOW DO WE DO THAT AND THAT COORDINATING DOESN'T MEAN HAVING EVERYBODY MARCH TO THE SAME STEP. OTHERWISE, WHY HAVE A VARIETY OF PERSPECTIVE BUT HOW DO WE MAKE SURE ALL DIFFERENT PARTS ARE INFORMING EACH OTHER. I'M HOPING THAT WLL BE A CHALLENGE THAT WE'LL BE BE SOLVING IN THE NEXT FEW YEARS. >> I'M SURE IF YOU HAVE COMMUNITIES AROUND THE PUBLIC, PRIVATE PARTNERSHIP, AND THE OPEN SOURCING OF INFORMATION, WE STRIKE THIS UNIQUE BALANCE BETWEEN ENENABLING SCIENCE TO MOVE FORWARD, AND FOR THE ONES PRIVATIZING THE KNOWLEDGE AND WE HAVE CERTAINLY SEEN THAT WITH MYRIAD GENETICS AND NEAR TO MANY OF OUR HEARTS, 170HP GO OVER TO MKINN ARC. SO I'M CURIOUS, HOW WE CAN PROACTIVELY LOOK TO ENABLE THE KNOWLEDGE BE TO REMAIN WITHIN THE PUBLIC SECTOR AND FOR THE GOOD OF THE PEOPLE WE SERVE. >> WE'RE TRYING TO DEVELOP SOME FAIRLY FUNDAMENTAL KNOWLEDGE, AND APPLIED KNOWLEDGE BUT AT THE UNDERSTAND OF THE DAY, WE'RE FOR THE ONES TRYING TO DEVELOP THE KNOWLEDGE. WE'RE TRYING TO GET IT APPLY F. YOU THINK ABOUT WHICH PART OF THE PUBLICTE DICHOTOMY BUT IF YOU THINK ABOUT THAT. THE PUBLIC SPHERE TENDS TO BE BE BEST AT THE BASK RESEARCH EARLY DEVELOPMENT KIND OF THING, BUT THE PRIVATE SECTOR NOT ONLY HAS CENSUSES PEER TEASE IF TERMS OF LATER STAGES OF DEVELOPMENT BUT IT'S THEY WHO ARE GOING TO GET IT APPLY. LET'S SAY WE COME UP WITH, WE'RE GOING TO TALK ABOUT A STAR WARS TRANSDUCER, ABLE ABLE TO READ THE PLACENTA OR SOMETHING. NIH IS NOT GOING TO BE PRODUCING STAR WARS TRANCE DUCEERS, AND PUNISHING THEM FOR USE IN THE U.S. IT'S GOING TO HAVE TO BE THE PRIVATE SECTOR THAT DOES THAT. SO I THINK IT'S WONDERFUL WE HAVE HAD SOME REPRESENTATIVES FROM PRIVATE SECONDER HERE. TO BE INFORMED PIE OUR DISCUSSION, AND HELP INFORM THE DISCUSSIONS. THAT'S THE WAY FOR THE HUMAN PLACENTA PROJECTS. LOOK DIFFERENTLY FROM THE HUMAN GENOME PROJECT. THERE'S SOME PAIR LES. WE HAVE A BACK AND FORTH CONSERVINGS AND A LOT OF THIS ISN'T THE PRECOMPETITIVE SPACE. WE ALL WORK TOGETHER ON THAT. ASS IT GETS TO THE COMPETITIVE SPACE. WE HAVE APHIS WAY TO HAND IT OFF. AND THAT'S A DAY WE SHALL ARCSPIRE TO. WE GET TO THE POINT WHERES I SARKS WE WANT TO DEVELOP OUR OWN VERSION OF THIS WE SEE SOME GOOD POTENTIAL HERE. THERE'S NOTHING WRONG WITH THAT. IN FACT, IF WE DON'T HAVE THAT, THEN THIS NEVER GETS IN HANDS OF CLINICIANS AND PREGNANT WOMEN TO BE ABLE TO INFORM PREGNANCY MANAGEMENT, ET CETERA. SO I THINK THERE'S A LOT OF THINGS AT NIH THAT NEED TO BE CONTINUUM AND AS YOU MOVE DOWN, THE PRIVATE SECONDER PLAYS A LARGE ROLE. OUR LAST SPEAKER, ALSO FROM NICHD IS JENNIFER LIPPINCOTT-SCHWARTZ. SO AS DAVID SAID, I'M AN NICHDER AND MY LAB STUDIES REALLY FUNDAMENTAL ASPECTS OF SEEM LARRY BLOCK BIOLOGY, BUT THE PLACENTA PROJECT REALLY CAUGHT MY ATTENTION IN TERMS OF AN AREA THAT COULD POTENTIALLY BE IMPACTED BY SOME OF THE TECHNOLOGIES THAT WE'VE BEEN WORKING ON, WHICH INCLUDE LIVE IMAGINE BEING APPROACHES. IN MY TALK TODAY, I'M GOING TO BE GIVING IN THE FIRST PART OF THE TALK, AN OVERVIEW OF SOME OF THE ADVANCES IN IMAGING THAT ARE NOT REALLY CAPABLE OF DECIPHERING SOME SOPHISTICATED DETAIL ABOUT INTERCELLULAR PROCESSES. AND IN THE SECOND PART OF THE TALK, I'M GOING TO GIVE YOU AN EXAMPLE OF HOW SOME OF TEASE TECHNOLOGIES CAN BE USED TO STUDY TROPHIC BLAST AS A SYSTEM, AS A CELLULAR SYSTEM, BASED ON SOME WORK THAT WE'VE BEEN DOING OVER THE LAST SEVEN MONTHS SINCE WE HAVE SUPERED INTO THIS EXCITING PLACENTA PROJECT SO SO IF ONE LOOK IN THE CELL, INDIVIDUAL CELLS ARE ENORMOUSLY COMPLICATE. THEY'RE FULL OF MANY DIFFERENT TYPES OF STRUCTURES, TAINCLUDE MICRO TUBE IALS. VESVESICLES. COAT PROTEINS THAT COVER DIFFERENT MEMBRANE DOMAINS. NOW, THESE, IT'S POSSIBLE TO LOOK AT THIS SYSTEM, USING CONVENTIONAL LICMICROSCOPEY. OCCURS BELOW THE TRACK LIMIT OF LIGHT, WHICH IS ABOUT 200 NANOMETERS. ANY OBJECTS THAT ARE CLOSER THAN 200 NANOMETERS ARE NOT VISIBLE, USING DIFFRACTION-LIMITED IMAGING. IF YOU HAVE A SMALL FEENEY NANOMETER VESICLE, WHICH CHARACTERIZES THE PATHWAYS. THOSE VESICLES, WHEN CLOSER THAN 200 NANOMETERS, APPEAR AS ONE BLOB. OVER THE LAST 7 TO 8 ARROYO'S, THERE HAS BEEN A REVOLUTION THAT HAS ALLOWED BIOLOGIES TO -- BIOLOGIST TO MOVE BELOW THIS DIFFRACTION LIMIT, USING THINGS MICROSCOPY DOWN TO 10 NANOMETERS. THIS VISIBILITY IS WHAT WE CALL SUPER RESOLUTION IMAGING. NOW, WHAT THESE APPROACHES DO IS BREAK THE ABBEY LIMIT OF DIFFRACTION LIMIT, THAT CONFESSIONAL LIGHT MICROSCOPE HIT, WHICH IS ROUGHLY HALF THE WAVELENGTH OF LIGHT. WITH CONVENTIONAL MICROSCOPE, ANYTHING SMALLER THAN HALF THE WAVELENGTH OF LIGHT IS GOING TO APPEAR AS A BIG, ANY TWO OBJECTS WILL APPEAR AS ONE AND IT'S WORSE IF YOU'RE LOOK LOOKING 3D AT AN OBJECT. THERE THE DIFFRACTION LIMIT IS ABOUT 500 NANOMETERS IF YOU'RE USING A GREEN LIGHT AS AN IMAGING MODALITY. AS I MENTIONED, ALL THIS HAS BEEN BROKEN AS A RESULT OF INTRODUCTION OF SEVERAL SUPER RESOLUTION IMAGING APPROACHES, WHICH BASED ON WHAT THEY OPENED UP AS A TOOL FOR US TO DO, TO LOOK AT CELL BIOLOGY. [INDISCERNIBLE] AWARD THE NOBLE PRIZE, AND THREE OTHER PEOPLE PLAYED A KEY ROLE IN THE 20 OF THESE SUPER RESOLUTION APPROACHES. AND FALL INTO BASICALLY WORK GENERAL APPROACHES. ONE IS BASED ON SINGLE MOLECULES SUPER RESOLUTION, AND THE OTHER ONE IS ILLUMINATION-BASED WHERE ESSENTIALLY, LIGHT THAT IS SHINED ON AN OBJECT IS JUST NARROWED DOWN, USING ILLUMINATION BASED TOOLS. AND I'M GOING TO TALK TO YOU BRIEFLY ABOUT THESE DIFFERENT TYPES OF SUPER RESOLUTION APPROACHES TO GIVE YOU A FLAVOR OF THE TYPES OF QUESTIONS THAT THEY ARE CAPABLE OF ADDRESSI SO IF THE CASE OF PALM OR SINGLE MOLECULE BASED IMAGINING. WHAT THIS TECHNIQUE DOES IS USES PHOTO ACTIVATED FLUORESCENT PROTEINS TO SWITCH ON SMALL SUBSETS OF MOLECULES AND THAT ARC HOUSE ONE TO MOVE FROM SEEING A CONBE VENTIONAL IMAGE, WHERE YOU ONLY HAVE ABOUT 250 NANOMETER XY RESOLUTION, WHAT WE'RE LOOKING AT HERE IS JUST AN AGGREGATE OF 50 NANOMETER BEADS BUT WITH PALM. USING THIS SINGLE MOLECULE BASED ANALYSIS APPROACH, YOU CAN NOW SEE EACH OF THESE INDIVIDUAL BEADS WITHIN THIS TIGHT-LIKE CLUSTERED ARRAY. THIS IS ACCOMPLISHED BY USING PHOTO ACTIVATION TO SWITCH ON INDIVIDUAL SUBSETS OF MOLECULES THAT COMPRISE THIS IMAGE OVER TIME AND AS EACH OF THESE INDIVIDUAL MOLECULES SWITCH O. BECAUSE EACH MOLECULE HAS A VERY DEFINED POINT SPREAD FUNK. CAN YOU FIT THE CENTROID OF THAT MURRAY SPOT, TO SINGLE SPOT AND COLLECT ALL THOSE SPOTS TO MERGE THEM INTO A SINGLE SUPER RESOLUTION IMAGE. NOW, THIS SUPER RESOLUTION IS ESSENTIALLY, ILLUMINATION-BASED TRAITED HERE, WHERE YOU BUILD YOUR IMAGE BY ISOLATING THE INDIVIDUAL MOLECULES THAT COMPRISE THE IMAGE OF INTEREST AND AS YOU ACQUIRE MORE AND MORE OF THE SINGLE MOLECULE CENTRAL AMERICAS WITH TIME, YOU CAN CREATE THE SUPER RESOLUTION IMAGE. AND THESE ARE A LIST OF THE NUMEROUS APPROACHES THAT ARE NOW BEING USED TO ACCOMH THIS TYPE OF HIGH RESOLUTION OF STRUCTURES OF INTEREST. WHAT THESE APPROACHES HAVE DONE IS TO REALLY OPEN UP A WHOLE SLEW OF AREAS THAT REALLY WERE PREVIOUSLY OFF LIMITS TO US AS CELL BIOLOGIST. FOR ONE, YOU CAN DO CORRELATIVE LIGHT PIKE ROWSCOPEY. HERE'S A MIGH HERE'S A MITOCONDRUG AND ALCOHOL AND YOU CAN SE--MITOCHONDRA.THIS I S JUST A TRAJECTORY MAP. EACH OF THESE LITTLE LINES REPRESENT ACTON MOLECULES THAT ARE MOVING ALONG IN ACTIVE FILAMENT. YOU CAN LOOK AT PROTEIN ORGANIZATION AND RECEPTORS STOKE OLYMPIAN RICK TREE FOR THE FIRST -- STOCRHIOMETRY. -- THE CLUSTER, THE CLUSTER SIZE, AND THE RELATIONSHIP OF DIFFERENT RECEPTORS THAT COMPRISE A RECEPTOR. THIS IS AN ELECTRON PHOTOGRAPH, OF AN H.I.V. TOOT BUDDING OFF THE SURFACE OF THE CELLS. THIS IS A SCANNING E.M. YOU CAN SEE THESE H.I.V. PARTICLES BUDDING OFF THE SURFACE OF THE CELL. AND THIS IS A CORRELATIVE ELECTRON MICRO GRAPH IMAGE. GAG PROTEIN THAT FORMS A COAT ON THAT COAT THAT DRIVES VIRAL BUDDING. LOCALIZED ON THESE INDIVIDUAL. AND WE WERE INTERESTED IN TRYING TO GET SOME MECHANISMIC DETAILS IN TERMS OF HOW A PARTICULAR MACHINERY, WHICH IS THE ESCORT COMPLEX DRIVES BUDDING OF THE VIRUS AND BY DOING THIS CORRELATIVE WORK-COLOR EYE PALM ARC UNTIL SIS. WE WERE ABLE TO COMPARE THE CENTRAL AMERICA AT 10 NANOMETER RESOLUTION OF THE GAG PROTEIN, WHICH IS THE SCAFFOLD THAT INITIATES THE BUDDING OF THE VIRUS WITH ESCORT 1 OR 3, WHICH IS THE MACHINERY THAT IS ASSEMBLING THAT WILL DRIVE FUSION OF THE SIERRA ION, AND SEEING THAT THESE, THIS MACHINERY, THE ESCORT LOCALIZED IN THE HEAD DOMAIN OF THIS VARIANT, SUGGESTED THAT THEY'RE WORKING IN A HEAD TO DOWN FASHION, IN TERMS OF OF ASSEMBLE BEING THIS DECISION MACHINERY THAT NARROWS THIS BUD NECK OF THE VIRUS TO ULTIMATELY THRIVE A DECISIONS OF THAT SYSTEM. AND THAT WAS ONLY POSSIBLE BY BEING ABLE TO VISUALIZE THE DISTRIBUTION OF THE MOLECULES AT THE SITE WHERE THEY'RE ACTUALLY FUNKING WITH THE SYSTEM. I MENTIONED THERE'S A WHOLE ALTERNATIVE APPROACH FOR ACHIEVING SUPER RESOLUTION AND ONE OF THOSE IS STRUCTURE ILLUMINATION MICROSCOPY. THAT GIVE US YOU A TWO-FOLD INCREASE IN RESOLUTION, IN CONTRAST TO THE PALM AND STORM APPROACH THAT IS GIRLFRIEND YOU THAT GIRLF RIENDS GIRLFRIEND -- THAT GIVES YOU 10-FOLD INCREASE. THIS TECHNIQUE CAN BE DONE LIVE IN A VERY SIMPLE WAY. SO WHAT YOU'RE LOOKING AT HERE IS JUST A 3D RECONSTRUCTION OF THE ACTON SIDE OF SKELETON OF A CRAWL BEING CELL, EACH OF THE COLORS REPRESENT DIFFERENT ACTON FILL AX MENTAL HEALTHS THAT ARE A COLOR CODED BASED ON THEIR Z POSITION. OFF SURFACE OF THE CELL. WE WANTED TO KNOW HOW THESE DIFFERENT FILL AX MINUTES ORGANIZE IN 3D. USING MICROSCOPY. IF YOU LOOK AT THIS REGION HERE, YOU REALLY CAN'T SEE ANY KIND OF ORGANIZE. BUT WITH S.I.M. BECAUSE WE HAVE THE FULL 3D SPECTRUM AT THIS HUMAN NANOMETER RESOLUTION WE CAN VERY NICELY DEFINE WHERE ALL THESE ELEMENTS ARE LOCALIZED IN THE THREE-DIMENSIONAL CONBE TEXT OF A CELL. NOW, WE CAN ALSO ZOOM UP, USING STRUCTURE ERK ELIMINATION AND LOOK AT SPECIFIC MOLECULAR MACHINES. THIS IS AMERICA IOC IRK N2 THAT FORMS FILL -- FILAMENTS THAT ANTIPARALLEL ASSOCIATE. WHAT WE HAVE DONE HERE IS ATTACHED A GREEN FLUORESCENT PROTEIN TO THE AHEAD OF THE MIOCIN FILL A MENTAL HEALTH AND A RED TO THE TAIL. WHAT WEEK SEE WHEN WE AM ZOO UP CZECH THEY'RE ORGANIZED IN A WAY IN WHICH THESE MYOCIN FILL A MINUTES ARE OPERATING TO A FASHION WHERE WE KNOW WHAT'S OCCURRING IN THE MUSCLE CELL, WHERE THE MYO SIN IS CONTRACTING THERE ARE OTHER AREAS OF IMAGING THAT IS OPENING NEW POSSIBILITIES. LIGHT OF LIGHT SHEET MICROSCOPY, WHICH IS HIGH SPEED 3D ISOTROPIC IMAGING AND WHAT YOU SEE HERE ONE OF THE EXAMPLES FROM ALEC RIDER IN MY LAB, WHERE HE'S COCULTURING CYTOTOXIC TISSUING CELLS. THE CYTOTOXIC IS IN RED. THE TARGET CELL IT'S TRYING TO KILL IS IN BLUE A DANCE BETWEEN TEASE TWO CELLS WE HAVE NEVER SEEN PREVIOUSLY BEFORE BECAUSE WE DIDN'T HAVE THE SPEED OR THE ISOTROPIC SECONDING MY LAB HAS BEEN TRYING TO DEVELOP WAYS TO DO WHERE INSTEAD OF LOOKING AT JUST TWO OR THREE SPECIMENS, TWO OR THREE AT A PARTICULAR TIME, WE CAN LOOK AT SIX OR MORE DIFFERENT FLOOR FORMS, ATTACHED TO DINNER ORGANELLE. AND WHAT YOU'RE LOOKING AT HERE IS A CELL THAT'S EXPRESSING ALL OF THESE DIFFERENT ORGANELLE MARKERS. NORMALLY, IF WE HAD EXCELLENT PRESSED THEM WITHOUT USING MULTI SPECTRAL MIXING. ALL THE SPECTRUM WOULD OF COURSE OVERLAPPING AND YOU WOULD JUST SEE YELLOW OR PINK EVERYONE. BUT BECAUSE WEEK ABLE TO APPLY ALGORITHMS TO SEPARATE THESE, WE CAN IDENTIFY EACH ONE OF THESE ORGANELLES AND FROM THAT, GET INSIGHT INTO HOW THESE ORGANELLES ARE ACTUALLY OPERATING IN THE CONTOGETHER OF A SINGLE LIVING CELL. SO HERE, WE'RE APPLYING MODELING PROFESSIONALS FOR TRACKING DIFFERENT TYPES OF ORGANELLES, AND WHERE -- HERE, WE HAVE A LIPPED DROPLET IF PLUHERE THAT WE'RE MONITORING AND PROBING TO WHAT EXTENT IT'S INTERACTING WITH OTHER ORGANELLE, INCLUDING ER, MITOCHONDRIA, GOLGI THE MITOCHONDRIA IS ALWAYS IN CONTACT WITH THIS DROPLET. IT'S INMATELY ASSOCIATED WITH THE LIPID DROPLET AND LES SO FOR THESE OTHER ORGANELLES. THIS HAS IMPORTANT POSSIBILITIES IN TERMS OF TRYING TO KEY APART THE METABOLIC PATH I WAYS THAT ARE KNOWN TO BE INVOLVE IN THE METABOLIC SHARING OF IF YOU TRENTS AND OTHER METABOLITES WITHIN THE CELL, KNOWING HOW THESE ORGANELLES ARE COMMUNICATING WITH EACH OTHER IN THIS WAY, PROMISES TO BE BE REALLY IMPORTANT. NOW, THIS IS WHERE WE'RE COMBINING THE LATTICE LIGHT SHEET WHICH GIVES YOU FAST 3D WITH THIS MULTI SPECTRAL IMAGING APPROACH. AGAIN, WE'RE LOOKING AT THOSE SIX DIFFERENT ORGANELLES. WHAT YOU CAN GET FROM THIS IMAGE IS THE CYTOPLASM IS ENORMOUSLY PACKED, CONCENTRATED WITH THE ORGANELLES AND WE NEED WAYS TO UNDERSTAND THE LANGUAGE THAT THE CELLS USING IN TERMS OF THESE INTERORGANELLE CROSS COMMUNICATION THAT IS DRIVE CELLULAR PROCESSES. NOW, IN THE REMAINING PART OF MY TALK, WANT TO JUST GIVE YOU A FLAVOR OF HOW WE CAN POTENTIALLY USE THESE MIKE CROWSCOPEY APPROACHES AND OTHER IMAGING APPROACHES FOR GETTING NEW INSIGHTS ABOUT THE PLACENTA. THIS IS PRELIMINARY WORK THAT'S BEEN DONE OVER THE LAST 4 MONTHS SINCE WE HAVE ENTERED INTO THE PLACENTA WORLD AND WE ARE VERY MUCH FEE FEE NEOPHYTINGS NEOPHYTES. THE TROPHY BLASTS IS EYE KEY CELLULAR SYSTEM WITHIN THE PLACENTA. THE WHAT IS THE BEARER BETWEEN THE MOTHER AND THE FETUS. I., IT'S THE CONDIT THROUGH WHICH THERE'S CROSS COMMUNICATION BETWEEN THE MOTHER AND THE FETUS. SO THERE'S AMINO ACIDS TACROSS BETWEEN THESE TWO. OXYGEN, CARBON DIOXIDE, FROM YOU COS, IRKON ARE GOING BACK AND FORTH. WASTE IS TRANSFERRED FROM THE FETUS ACROSS THE TROPOPLAST. GROWTH FACTORS ARE BEING SECRETED AND FINALLY, HORMONES THAT LEAD TO THE DIFFERENTIATION OF THE PLACENTAL SYSTEM IN GENERAL. NOW, THE TROPHY PLAST IT IS LINING THE CORE IONIC VILLIS. SO THIS IS THE TROPHY BLAST, IT'S ALL OF THIS GREEN REGION RIGHT HERE, AND THIS IS A SINGLE I.LL THAT HAS THOUSANDS OF BUT IT'S PLAYING THIS REALLY CRITICAL ROLE, AND IT'S SEPARATING THE MATERNAL BLOOD WHERE THE MATERNAL VESSELS DUMP THEIR BLOOD INTO THIS INTERVILLISUS SPACE FROM WHERE THE EMBRYO, ITS CAPILLARY SYSTEMS ARE LOCALIZED. OKAY. SO HOW DOES THIS TROPOPLAST DIFFERENTIATE. WHERE DOES IT COME FROM? IT COMES FROM THESE CYTOTROPOBLASTS WHICH ARE ES, LINE BEING THE WHOLE CAVITY HERE. SINCE THESE CYTOTROPOBLASTS, MICHAEL BUCKLEY GREAT INTO THENO MITRIUM AND ARC HOW THE COMMUNICATION THE TWO BLOOD SYSTEMS BETWEEN THE MOTHER AND THE FETUS. SO IT'S THE FUSION OF THESE CELLS IS THOUGHT TO ALLOW OPTIMAL TRANSFER OF NUTRIENT WASTE ACROSS FETAL BROWNARY. SO WE WERE INTERESTED IN SEE FIGURE WE COULD USE A MOEL SYSTEM TO REALLY UNDERSTAND THE TROPOPLAST AND ITS RELATIONSHIP TO THE CYTOTROPE BLAST IN TERMS OF THIS FUSION PROCESS. THIS IS AN ELECTROPHOTOGRAPH, SHOWING YOU AN AREA WHERE THE TROPOBLAST WHERE THIS GUY GUY IS ULTIMATELY GOING TO FUSE WITH THE CYTOTROPOBLAST. THIS IS A PRECURSOR. BUT WHAT I WANT TO DRAW YOUR ATTENTION TORQUE EVEN AT THE ELECTRON MICRO GRAPH LEVEL, CAN YOU SEE TREMENDOUS MORPH LOGICAL DIFFERENCES BETWEEN BE THESE3 WORK DIFFERENT CELL TYPES. JUST STARTING WITH THE NUCLEUS, CAN YOU SEAT [INDISCERNIBLE] MUCH MORE HETEROCHROMATIN, COMPARED TO WHAT YOU SEE IN THE CYTOTROPOBLAST. GROWTH FACTORS. OTHER TYPE OFMORE MONIES AND THERE'S A WHOLE EP THELIAL SUSHERE. THERE ARE MANY OTHER CHANGES, INCLUDING AN ACCUMULATION THAT CHARACTERIZE THESE CELLS. SO THE KEY QUESTION THAT WE'RE FOCUSED ON, FROM THE PERSPECTIVE OF THE PLACENTA PROJECT IS WHAT ARE THE PROGRAM CELLULAR EVENTS THAT ARE REQUIRED FOR THIS DIFFERENTIATION. THIS IS JUST A DIAGRAM OF WHAT IS ALREADY KNOWN IF THE LITERATURE. WE KNOW THERE ARE LOTS OF CELLULAR CHARGES THAT ARE OCCURRING AT DIFFERENT STEPS OF THIS WHOLE PROCESS BY WHICH THE CYTOTROPOBLAST IS FUSING TO FORM THE TROPOPLAST BUT POST FUSION. DIFFERENTIATED TROPOBLAST. YOU GET CHANGES IN THE ACTON ORGANIZATION, THE NUCLEUSES I MENTIONED, THE DROPLETS ARE ACCUMULATING. THE R THERE'S CHANGES IN TRANSPORTERS, ET CETERA. EARLY ON, IN ORDER TO DRIVE THIS WHOLE PROCESS, YOU HAVE RECRUITMENT OF FUSAGINS, WHICH ARE THE FUNCTION PROTEINS ITSELF, I JUST WANT TO EMPHASIZE WITH THIS BECAUSE I THOUGHT THE SINSITIF, 1 AND 2, WHAT'S QUITE INTERESTING, THESE ARE FUSION PROTEINS THAT ARE RETROVIRALLY DERIVE. SO THESE ARE NOT THESE ARE DERIVED FROM THE HUMAN GENOME. THEY HAVE BEEN INTRODUCED, SOMEWHERE IN REVOLUTION BY A RETROVIRUS. WHICH I THOUGHT WAS INTERESTING FROM THE TALK WE ALREADY ABOUT, THIS SYSTEM BEING SORT OF A VIRAL BACTERIAL SORT OF MEET WILL PLACE. IN SOME RESPECTS, YOU CAN THINK ABOUT, THIS IS LED ME TO START THINKING MAYBE THE PLACENTA, THE WHOLE EVOLUTIONARY GOWN WORK FOR THE PLACENTA WAS THE INTRODUCTION OF A RETROVIRUS IN THIS SYSTEM, THAT ALLOWED THIS FUSION TO ACTUALLY DRIVE FUSION OF THE CYTOTROPOBLASTS. ANY I WAXER WE'RE INTERESTED IN USING A MODEL SYSTEM TO LOOK AT DIFFERENT CHANGES THAT ARE OCCURRING POST FUSION, TO GET INSIGHT INTO WHAT'S HAPPENING, THAT ALLOWS THIS SINSETIAL TROPOPLAST TO ACT IF THIS CRITICAL WAY, AS A BARRIER BETWEEN MOTHER AND FETUS. WE'RE USING [INDISCERNIBLE] THAT CAN BE INDUCED TO FUSE INTO A TIME, BE IT'LL PRODUCE HCG. TROPOBLASTS ARE THE ONES THAT PRODUCE HC GASHING. WE'RE LOOKING AT 48 HOURS AFTER WE HAVE ADDED [INDISCERNIBLE] TO THE B WOE CELLS AND USING 3D CONFOCAL SECTIONING. CAN YOU SEE BIG DIFFERENCES IF THE OVER ALL SHAPE AND ORGANIZATION OF THESE CELLS. I WANT TO DRAW YOUR ATTENTION HERE TO HOW REMARKABLY FLAT TEASE CELLS BECOME OVER THIS THIS IS A SUPER FLAT CELL N CONTRAST TO THE CELLS THAT HAVE NOT FUSED. THIS IS JUST A ROTATION IMAGE OF THE WHOLE SERIES. THIS IS AN INDIVIDUAL BWO CELLS BEFORE THEY INFUSE INTO A SENSOR-BASED CIRCUM. YO-- SINSITIAM. NOW, ONE OF THE THINGS WE WERE INTERESTED IN IS HOW DOES THIS MORPHOLOGY ARC RISE SO WE HAVE STARTED TO LOOK AT THE ACTON SIDE OF A SKELETON, AND THE REARRANGEMENTS WHEN YOU CREATE THIS SINGLE CELL WITH ALL THESE NUCLEI, THE ACTON URN GOES DRAMATIC CHANGES AND WE THINK MIGHT BE PLAYING AN IMPORTANT ROLE IN HOW THIS THING ORGANIZES 3 DIMENSIONALLY. INTERESTING, WE SEE A RIM OF ACTON, A VERY BRIGHT REGION HERE, IT'S ESSENTIALLY SWEEPING. WE THINK POTENTIALLY SWEEPING THESE NUCLEI INTO THIS CLUSTER REGION. WHY MIGHT YOU WANT TO DO THAT IF IF YOU'RE GOING TO BE BE PASSING NUTRIENTS ACROSS THIS CELL, YOU DON'T WANT TO HAVE NUCLEI DOTTED ALL OVER THE PLACE. YOU WANT TO BE ABLE TO CLEAR OUT THE CYTOPLASM OF ALL OF THESE ORGANELLES THEY SHOWED SO THE CYTOPLASM IS PACKED FULL OF LYSOSOMES. WE THINK THAT THE ACTIVITY OF THIS ACTON SIDE OF THE SKELETON MIGHT, BY DRIVING ALL OF THESE ORGANELLES INTO THE CENTRAL REGION HERE, NOW LEAVE AREA OF CYTOPLASM, THAT ESSENTIALLY DEVOID OF ORGANELLES THAT WOULD ALLOW FOR STITIAN TRANSFORM OF ICONS, GLUCOSE,ET THE FOR THIS RAPID COMMUNICATION. NOW, ONE OF THE THINGS WE ARE INTERESTED IN, IS WHEN ALL OF THESE NUCLEI ARE DRAWN TOGETHER IN TEASE TIGHT CLUSTERS. WHAT'S GOING ON WITH THESE NUCLEI? ARE THEY FUSING WITH EACH OTHER. AND IF SOME OF OUR, IN SOME EXAMPLES, WE CAN SEE, SOME OF TEASE NUCLEI ARE, THEY LOOK AS IF THEY HAVE BECOME CONNECTED. ITS SOMETHING WE'RE STILL TRYING TO UNDERSTAND WHETHER THEY ARE GETTING FUSED WHEN THEY GET CLOSE IN HERE OR WHAT ELSE MIGHT BE BE GOING ON IN THE SYSTEM. I WANT TO MOVE TO ANOTHER REALLYCITE BEING AREA WHICH RELATES TO CHANNEL ACTIVITY, ASSOCIATED WITH THE INCISION TROPOBLAST. WE KNOW THAT CHANNEL TROPOPLAST HAS A DRAMATIC EFFECT ON DIFFERENTIATION. POTASSIUM CHANNELS. IF THIGH BECOME STIMULATED TO BE ACTIVATED, THAT WILL ACTUALLY REDUCE THE ABILITY TO FORM THESE NUKELATED INSTITIA. THAT SUGGESTS THAT THE MEMBRANE ACTIVITY OF MANY OF THESE CHANNEL PROTEINS, MIGHT BE AN IMPORTANT READ OUT FOR PLACENTAL DIFFERENTIATION. WE STARTED THINKING HARD, ABOUT, MAYBE WE CAN POTENTIALLY, LOOK AT THE MEMBRANE AND IN PARTICULAR. WE WERE EXCITED BECAUSE MEMBRANE POTENTIAL REALLY CHARACTERIZE DIFFERENT TYPES. WE HAVE STEM CELLS DOWN HERE, WHICH HAVE THE LOWEST MEMBRANE POTENTIAL AND AS YOU MOVE UP TO GET INTO THESE DIFFERENTIATED SEES. YOU CAN SEE THE MEMBRANE POTENTIAL GOES MUCH HIGHER. SO WE HAVE STARTED EXPERIMENTING WITH A THREAT BASE TO LOCALIZE MEMBRANE POTENTIAL CHANGES IN LIVE CELLS, IN PARTICULAR, IN THESE STITIAL TROPOBLASTS. WE INTRODUCE A LIPIDAI THAT CAN SERVE AS A DONOR TO A DIFFERENT, A SMALL MOLECULE THAT'S FLORESSENT, THAT MOVES BETWEEN LEAFLETTINGS BASED ON WHERE THE POSITIVE CHARGE IS ON THAT BILE AIR. SO WHEN A CELL BECOMES DEPOLARIZED, THIS FLUORESCENTS REPORTER UPON CROSS DOWN TO THE POSITIVE CHART, POSITIVE REGION WHEN THE CELL MEMBRANES BECOME POLARIZED, IT SHIFTS UP WHERE YOU CAN SEE A THREAT SIGNAL. WE USE THIS APPROACH TO LOOK AT UPON WHATS TO THESE B WOE CELL AS THEY DEFERENTIATE. SO THESE ARE JUST TO CONTROL CELLS. IF WE IMAGE THEM OVER 24 HOUR. YOU CAN SEE, THERE'S VERY LITTLE CHANGE IN THE POLARIZATION STATE OF THESE CELLS. EVEN THOUGH THEY'RE GROWING. BY CONTRAST, IN THE B WOE CELLS THAT OF COURSE STIMULATED TO DIFFERENTIATE, AND TO FUSE INTO THE SINSITIAM. YOU CAN SEE AN INCREASE IN THE POLARIZATION STATE OF THOSE CELLS AS THEY BEGIN TO FUSE THIS IS JUST A MOVIE SHOWING YOU THAT WE CAN MONITOR THIS OVER TIME AND YOU CAN SEE AS THE CELLS START FUSING, YOU GET THIS DRAMATIC INCREASE IN THE POLARIZATION OF THE SYSTEM. NOW, WE'RE VERY INTERESTED IN THE POTENTIAL OF THIS SYSTEM TO GIVE US A READ OUT NOT ONLY IN TERMS OF ION CHANNELS AND MEMBRANE POTENTIAL B BUT WE BELIEVE FROM OTHER WORK THAT'S BEEN DONE, EXAMINING MEMBRANE POTENTIALS THAT IT DIRECTLY IMPACTS TRANSPORTATION STATES AND PROTEIN FOLDING AND TURNOVER STATES WITHIN THE CELL ITSELF. BUT OUR HOPE IS THAT POTENTIALLY, THROUGH THESE TYPES OF IMAGING MODALITIES LIKE THE MEMBRANE, THAT WE MIGHT BE ABLE TO EXTEND UPWARDS AND CORRELATE THAT TO OVER ALL DIFFERENTIATION STATES OF THE PLACENTA IN PARTICULAR, THE TROPOPLAST SYSTEM ITSELF, GIVEN WE CAN CLEARLY SEE BEAUTIFUL CHANGES IN THAT POLARIZATION STATE THAT CORRELATE WITH HOW THE SYSTEM IS DIFFERENTIATING. WITH THAT, I WANT TO END AND SAY, OUR GOAL AS PART OF THIS REALLY EXCITING PROJECT THAT IS SORT OF MOVING FORWARD. RELATED TO PLACENTA BIOLOGY IS TO TRY AND SPRUCE ADVANCED IMAGING AS AN APPROACH TO LOOK AT THE MECHANISMS THAT ARE COORDINATING INTRACELLULAR CHANGES, THAT ARE CRITICAL FOR NOT ONLY TROPOBLAST BUT OTHER CELLULAR PROCESSES WITHIN THE SYSTEM, AND HOPEFULLY, FROM THAT, WE CAN DETERMINE HOW DIFFERENTIATION FAILURE CAUSES DYSFUNCTION IN THE HUMAN PLACENTA SYSTEM ITSELF. WITH THAT, I WANT TO THANK NOT ONLY MY LAB BUT THE TWO CRITICAL PEOPLE WHO HAVE BEEN INVOLVED IN THIS WORK. CAROLYN [INDISCERNIBLE] HAS BEEN ON THIS PROJECT WITH ME AND WE HAVE HAD DANIEL FOOTWORK ERK L IRK CIA NETWORK O WHO HAS AS A POST DOC WHO HAS CARRY OUT MOST OF SPERMS. THANK YOU VERY MUCH. >> IT SEEMS MOST OF THESE ARE TIME COURSE TYPE LIVE IMAGES. THE, QUESTION I HAVE ACCIDENT WHAT IS THE RATIONAL FOR USING BWO CELLS. I'M NOT SURE IF THIS IS AN EXTRA VILLIS IS TROPOPLAST LINE OR A VILLIS IS TROPOPLAST LINE BECAUSE THAT BEING BE SOME PROBLEMS WITH THAT AND THE IDEA S WHY DIDN'T YOU USE PRIMARY TROPHY BLASTS. THEY WILL INCISIONIZE 72 HOURS ON THEIR OWN WITHOUT CULT IRRITATE. >> WE WANT TO USE PRIMARY CYTOTROPOBLASTS. WHAT WE HAVE DONE HERE, BECAUSE WE REALLY WANTED TO GET OUR HANDS INTO THE SYSTEM AS FAST AS POSSIBLE. WE USE THESE BIG BIG WOE CELLS TO QUICKLY ASSESS WHAT WE CAN DO MICROSCOPY WISE. AND OUR NEXT. [GROWLING] IS TNEXT GOAL IS TO GET INTOTHE TROPOBLAST . THAT REQUIRES US, YOU KNOW, TO GET OUR HANDS ON THOSE CELLS. I MEAN, WE'RE TRYING TO DO THAT RIGHT NOW IN TERPS OF GET THEM CULTURE SYSTEM. BUT RIGHT NOW, THE B-WO CELLS ARE BEING USED TO GET OUR FEET WET IN TERMS OF WHAT ARE THE CAPABILITIES OF THIS SYSTEM. THE MICRO SCOPEY SET UP. ALL OF THIS IS DONE WITH A DISK FOCAL OR LINE FOCAL SYSTEM. WE'RE GEARING UP TO TRY AND USE SOME OF THE MORE ADVANCED LIGHT SHEET ADVANCE SYSTEM. AS WELL AS SOME STRUCTURE ELIMINATION. THAT'S STILL, AGAIN, ON THE SIDELINES BEFORE WE HAVE THE SYSTEM, WE'RE REALLY JUST AT AN EXEXPLORATORY STAGE AS TO WHAT IT IS WE WANT TO HONE IN ON, IN THE SIGNIFICANCE. >> I HAVE ONE MORE QUESTION. I THINK WHAT YOU'RE DOING IS FANTASTIC. I THINK YOU CAN START LOOKING AT THINGS. I MEAN, I SHOWED THE VIRUS BUDDING. ONE THING I NOTICE ABOUT THE VIRUS BUDDING. THE NUCLEAR UPON CAS, IT LOOKED LIKE IT WAS -- NUCLEAR CAPS LOOKED LIKE IT WAS DISTORTED. I DIDN'T SEE A WELL-DEFINED CANSID. THE IDEA OF LOOKING AT VIRUS REPLICATION IN PERMISSIVE CELL TYPES AND WILL IFING IT THROUGH USING YOUR MULTI COLOR SYSTEM. I THINK THIS WILL BE IDEAL TO LOOK AT THAT AND I WONDER IF YOU HAVE PLANS TO DO THAT IN THE FUTURE. >> YES. WE DO. ACTUALLY, WE'RE DOING THAT WITH H.I.V. RIGHT NOW. >> OKAY. L THANK YOU MUCH AND I HOPE IF YOU HAVE ANY OTHER ISSUES, IT WOULD BE WONDERFUL TO CHAT. [Applause]. ALL RIGHT. THANK YOU ALL SO MUCH FOR YOUR PATIENCE THIS AFTERNOON. AND STICKING WITH US, TO GET US TO THE FIXTURE PART WHERE WE REALLY NEED YOUR HELP AND GUIDANCE IN TRYING TO MOVE FORWARD WITH THE HUMAN PLACENTA PROJECT AND TRYING TO DEFINE A ROAD MAP OFIS IS THE TIME FOR YOU TO REALLY GIVE US INPUT AS TO WHAT IT IS WE NEEDO DO. WHAT ARE THE AREAS WE NEED TO FOCUS ON AND WHAT ARE THE NEXT STEPS WE NEED ON DO. WE DO GO AHEAD AND PULL OFF OF THE BOARD OUTSIDE A ROW CAP OF THE STICKY NOTES. WE'D LIKE ON GO OVER THOSE QUESTIONS AND GET YOUR INPUT AS TO ADDITIONAL ANSWERS. THINGS THERE AREN'T PUT UP THERE ALREADY, AS WELL AS HELPING US TO PRIORITIZE, WHAT NEEDS TO BE MOVED FORWARD NEXT. WHAT ARE THE GAPS IN KNOWLEDGE. WHAT DO WE NEED TO DO TO ACHIEVE ORIENTATION ULTIMATE GOAL OF KNOWING THE HUMAN PLACENTA STRUCTURE AND FUNCTION IN REAL-TIME. CHRISTIE, THANK YOU MUCH FOR PULLING UP THE DOCUMENT. I DID GET ONE QUESTION YESTERDAY THAT ASKED TO BE A LITTLE MORE EXPLICIT ABOUT WHAT WE MEAN BY STRUCTURE AND WHAT WE MEAN BY FUNCTION AND AND SO I TRY TO PROVIDE THAT AND I'M HAPPY TO HEAR FEEDBACK ON THAT AS WELL. STRUCTURE REFERS TO THE ANAL ME OF THE PLACENTA, AS DEVELOPS CROSS GESTATION TO INCLUDE THINGS SUCH AS SHAPE AND CELL TYPES. FUNCTION RECOVERIES TO HOW THAT PLACENTA WORK. SO EXAMPLES INCLUDE THE METABOLISM. GENE EXPRESSION AND FUNCTION. PHYSIOLOGY, AN INVASION INTO THE TROPOBLAST. SO I JUST WANTED TO OUTLINE THAT THAT. SO THE FIRST QUESTION WE WERE POSING TO YOU IS WHAT ARE THE NEXT STEPS, WHAT ARE THE FIRST THINGS WE NEED TO DO, BE GIVEN WHERE WE ARE, TO ACHIEVE THE ULTIMATE GOAL OF THE HUMAN PLACENTA PROJECT? AND I'D JUST LIKE TO RUN THROUGH SOME OF THOSE THAT WERE PUT ON THE STICKY BOARD OUTSIDE AND THEN HEAR YOUR THOUGHTS, BOTH ON THESE, AS WELL AS ANY ADDITIONAL ONES YOU'D LIKE TO ADDER. ONE IDEA PUT UP WAS A NATIONALLY BIOBANK -- WITH CLINICAL PHENO TYPES, AND THOSE DATA ARE DEPOSITED IN SHARED REPOSITORIES FOR INTEGRATION. A CALL OUT FOR PLACENTAL MEMBRANES TO BE BE STUDY. LEVERAGING -- [READING] MAKING CERTAIN THAT OMEC DATA ALREADY COLLECTED ARE AVAILABLE. KEEPING PLACENTA AFTER NORTH BIRTHFUL HARMONIZING 15O TYPE. LOOKING AT FIRST TRIMESTER PHENO TYPE. USING MR SPECKS TOCOPY. USING NEW ULTRASOUND TECHNOLOGIES TO DOCUMENT PLACENTAL STRUCTURE ACROSS DEVELOPMENT THIS A LARGE COHORT OF PREGNANCIES. PLACENTAL -- I'M GUESSING THAT'S MRI. PLACENTA ON A CHIP. WE HAVE A NICE PICTURE. SYSTEMATIC ALTHOUGH MINE BEING EXISTING DATABASES, PROSPECTIVE COLLECTION. IDENTIFYING PARAMETERS TO BE BE D FOR SAMPLES SO WE HAVE GOT SOME THEMES WITH OTHER THINGS I'VE ALREADY READ. THE ROLL OF THE PLACENTA IN DOHAD. VIRAL BANKS, STANDARDIZING PROTOCOLS AND TO TRULY ADVANCE HUMAN HEALTH IT'S IMPORTANT THAT THE HUMAN PROJECT IS A ROAD MAP INITIATIVE. SO MANY LESSONS LEARNED FROM OTHER ROAD MAP. STUDYING DIFFERENT PARAMETERS ON THE SAME PATIENTS. SO GETTING THAT CLINICAL DAT AS WELL AS CHEMICAL MARKERS. DATA SHARING IN ALL UPON AS A LOT OF TIME LANGE COHORT WOULD BE HELPFUL AND VALUE FOOTBALL FOR THE STUDIES A LIST OF THINGS THAT CAN BE MEASURED SUCH AS MARKERS OF INFLAMMATION IN NORMAL AND COMPLICATED PREGNANCIES. SOMEONE ASKED FOR THE U34 TO BE REISSUE BED. ALL RIGHT. SO THIS IS THE LIST THAT WE HAVE THUS FAR. WHAT ARE THE NEXT THINGS THAT NEED TO BE DONE IN ORDER TO ACHIEVE OUR GOALS? REFLECTING BACK ON THAT LIST, WHAT ARE WE MISSING? WHAT CAN YOU THINK OF THAT WE DON'T HAVE HERE, THAT WE NEED TO DO, IN ORDER TO ACHIEVE THIS GOAL. >> SEVERAL REFERENCES TO THE STATUS OF THE MOTHER. BEFORE THE PREGNANCY OCCUR OR. >> COME UP TO THE MICROPHONE. >> ONE OTHER THING, IT MIGHT BE IMPLIED BUT I THINK WE CALLED OUT IS HOW THE FETUS IS EITHER RESPONDING OR STIMULATE BEING OR CHANGING PLACENTAL FUNCTION. I DIDN'T SEE ANYTHING SPECIFICALLY THAT CALLED OUT FETUS INTERACTION THERE I THINK I'M MISSING SOMETHING HERE. SOMEONE POINTED THIS OUT EARLIER TODAY, THE ONLY THING THAT CAN LOOK AT PLACENTA IN REAL TIME IS, WAS IN THE IMAGING PART AND WE TALKED A LOT ABOUT OTHER THINGS. WHEN YOU SAY REAL TIME, I MEAN, WHY ARE WE DOING -- WHEN YOU WANT IT IN REAL TIME, OR MAYBE BE I'M MISSING SOMETHING. >> IS THERE THINGS CIRCULATING IN THE MOM THAT WE SHOULD BE ABLE TO CAPTURE AS WAS DISCUSSED EARLIER TODAY, THWACK TELL US HOW THE PLACENTA FUNCTIONING IN REAL TIME, WITHOUT ACTUALLY TAKING A PIECE OF PLACENTA. SO YOU COULD DO OMEX ON DIFFERENT BODILY FLUIDS. THERE WAS A CALL OUT TO DO MORE THAN JUST BLOOD AND URINE, BUT ALSO TO ADD OUT SALIVA AND OTHER SECORRECTIONS. YOU COULD USE THESE TECHNOLOGY THAT IS WE HAVE TALKED ABOUT TODAY, TO EVALUATE THE PLACENTA IN REAL-TIME, ACROSS JEST A LITTLE, NONINVASIVELY. THAT'S OUR QUESTION TO YOU IS, IS THAT AN AVENUE WE SHOULD PURSUE, AND THAT WAS PART OF THE WHOLE PURPOSE OF THIS MEETING WAS TO TRY AND CALL OUT THOSE TECHNIQUS AND SAY, IS THIS SOMETHING WE SHOULD BE DOING. >> I WANT TO ONCE MORE, HIT ON THE ISSUE OF STANDARDIZATION AND I'M GOING TO GIVE A CONCRETE EXAMPLE. THERE WERE AT LEAST 13 PUBLICATIONS IN 2013, WHERE INDIVIDUAL INVESTIGATORS LIKE ANY ONE OF US. TOOK THEIR ULTRASOUND DATA OFF LINE AND DID WHAT'S CALLED SEGMENTTATION OF THE PLACENTA, WHICH IS BASICALLY, JUST DRAWING WHERE YOU THINK IT IS. AND ESTIMATING VOLUME. YOU CAN DO IT WHERE A MACHINE-DRIVEN PROTOCOL OR TO IT YOURSELF. BUT EVERYBODY DOES IT DIFFERENTLY. AND SO EVERY SINGLE ONE OF THOSE 13 STUDIES HAS DIFFERENT SENSITIVITIES AND SPECIFICITIES THEIR FINDINGS RELEVANT FOR A GIVEN JEST A LITTLAL AGE F. WE ARE GOING TO HAVE STANDARDIZED FIRST TRIMESTER MEASUREMENTS OF PLACENTAL VOLUME OR THE NEXT TWO MOST IMPORTANT NOVEL TECHNIQUES WHICH ARE FRACTIONAL MOVING BLOOD VOLUME, AND PROSECUTION OF THEUATAL PLACENTA INTERFACE WHERE THE 20 OF THE SPINAL ARTERIES OCCUR, THOSE THREE THINGS CARRY FANTASTIC POTENTIAL FOR PREDICTIVE VALUE AND MONITORING THE HEALTH OF THE PREGNANCY IF WE CAN'T GET AGREEMENT FROM ALL PARTIES THAT VOLUME IS GOING TO BE MEASURED EXACTLY THE SAME WAY, BE WHETHER YOU'RE USING A TOSHIBA, A PHILLIPS, YOU KNOW, WHATEVER THE MAKE AND THE MODEL IS, IF THOSE DATA AREN'T RELIABLY REPRODUCIBLE FROM MACHINE TO MACHINE TO MACHINE TO MACHINE, THEN THEY'RE USELESS. SO THAT STANDARDIZATION ISSUE NEEDS TO BE ADDRESSED AT SOME VERY CRITICAL EARLY POINT. NOW, SOME OF US HAVE SUBMITTED OUR GRANTS AND WE'RE GOING TO MAKE OUR SOFTWARE PUBLIC. WE WILL GIVE IT TO NIH. THAT DOESN'T MEAN IT WILL GET ADOPTED. RAPIDLY DEVELOP SOME FIRST TRIMESTER TECHNOLOGY THAT WILL BETTER ALLOW US TO PREDICT THE 27% OF THE WOMEN WHO ARE GOING TO EXPERIENCE PROBLEMS. WE NEED TO HAVE AN AGREEMENT ABOUT THAT STANDARDIZATION. >> I ENJOY YOUR TALK AND I WAS THINKING ASS YOU WERE SPEAKING ABOUT LES OVENS THAT, AN ADDITIONAL LESSON FROM THE GENOME PROJECT BUT ALSO FROM THE MICRO PROJECT IS A BETTER KNOWING BUT STILL, AN INADEQUATE KNOWING OF HOW MUCH VARYING THERE IS ACROSS HUBE MAS ON THIS PLANET AND I THINK WE PROBABLY HAVE LEARNED HOW BETTER TO ANTICIPATE, BUT ALSO DISCOVER HOW MANY DIFFERENT EXAMPLES NEED TO BE STUDIED BEFORE WE CAPTURED SOME, YOU KNOW, MEASURABLE FRACTION OF THE VARIATION BETWEEN INDIVIDUALS. THAT BULLET WAS UP THERE, BUT THERE MIGHT BE A MORE DELIBERATE EFFORT TO TRY TO UNDERSTAND AND GET OUR HANDS AROUND, HOW MANY PLACENTA FROM HOW MANY DIFFERENT KIND OF INDIVIDUALINGS MIGHT BE DESIRED TO UNDERSTAND HEALTH FIRST. THERE TERRY MORGAN. SO THIS IDEA OF CORRELATE BEING IMAGING WITH MATERNAL SERUM IS INTRIGUING. I THINK WE ALL AGREE, MATERNAL SERUM STUDIES ARE FOR THE ONES READY FOR PRIMETIME AND ONE OF THE GAPS WE'LL HAVE TO DEVELOP, HOW WE CAN PULL OUT PLACENTAA-SPECIFIC MARKERS. I THINK WE HAVE TO THINK SERIOUSLY ABOUT SNAPSHOTS IN TIME. NOT JUST MOVE MS OF THE PREGNANCY LONGITUDINALLY. WE NEED SNAPSHOTS OF TISSUE. FIRST TRIMESTER SAMPLES. HERE'S THE FLOW OF PLACENTA, AND HERE'S WHAT'S HAPPENING IN THE TISSUE. NAP SHOT OF DELIVERY. HERE'S THE OUT COME OF THE PREGNANCY, HERE'S WHAT IS HAPPENING IN THE PLACENTA. WE REALLY UPON TO ASK QUESTIONS ABOUT STRUCTURE AND FUNCTION, WE'RE GOING TO HAVE TO HAVE THAT TISSUE IN HAND FROM A HUMAN PERSPECTIVE AND I LIKE ANTONIO'S POINTS, ABOUTVILLING OUR PHENO TYPES. WE SHOULDN'T EXCLUDE RELEVANT ANIMAL MODELS ASS WE'RE ASKING THESE LONGITUDINAL QUESTIONS IN HUMANS. I THINK THAT SHOULD BE PART OF THE PROJECT. >> WANTED TO EMPHASIZE ONE IMPORTANT FUNCTION OF THE PLACENTA IS TO ALTER MATERNAL PHYSIOLOGY. SO JUST TO ELABORATE ON ONE OF THE POINTS ALREADY INCLUDED THERE IS TO LOOK AT HOW THE PLACENTA ALTERS MATERNAL RESPONSE BUT THERE ARE OTHER RESPONSES THAT WE SHOULD CONSIDER MONTANA TORRING AS A MEASURE OF PLACENTA FUNCTION, AND EYE SECOND QUESTION I HAD IS, LOOK TO ME, SO IS THIS MORE CENTERED AROUND THE HEALTH OF PREGNANCY, I JUST WANTED A CLARIFICATION. >> BOTH. THINK THE IDEA IS WE NEED TO UNDERSTAND THE PLACENTA AND HOW IT FUNCTIONS TO UNDERSTAND PREGNANCY BY. >> IT'S EYE HIGHLY INTERACTIVE SYSTEM BUT I GET THE FEELING THAT WE ARE FOCUSED ON [INDISCERNIBLE] FUNK BUT NOT THE INTERACT IDENTIFY RELATIONSHIP BETWEEN THE MOTHER AND THE PLACENTA WHICH PLAYS OUT. >> AND THE FETUS. >> AND THE FETUS. AND THE FETUS, WHICH PLAYS OUT A LOT IN WAYS, IN THE PLASMA FEATURE. >> I THINK IT'S IMPORTANT TO REMEMBER THAT WHAT WE ARE DOING HERE IS TRYING TO UNDERSTAND HUMAN PLACENTAL STRUCTURE IN REAL TIME, WHILE PREGNANCY IS ON GOING. WE'RE NOT TAKING THE PLACENTA OUT AND LOOKING AT IT, WE'RE LOOKING AT IT AS PART OF A WHOLE. THE PLACENTA IS GOING TO INTERACT WITH THE MOM. THE PLACENTA IS GOING TO ENUMERATING ACT WITH THE BABY TO PRACTICAL WITH THE BABY, AND WE NEED TO UNDERSTAND THAT. >> IF WE'RE ANYTHING TO DO OMEX IN REAL TIME. DURING THE PREGNANCY, WE'RE ANYTHING TO NEED SOME NEW TECHNOLOGIES FOR A WEARABLE MONITORS OR MY QUESTION IS, A HOME TEST OR POINT OF CARE TYPE TECHNOLOGY THAT ACHIEVES THE SENSITIVITY REQUIRED AND THAT IS ALSO COUPLED WITH KNOWLEDGE ABOUT THAT ALTERNATIVE BIOLOGICAL FLUID. WHAT IS THE NORMAL LEVELS OF MARKERS IN THAT BIOLOGICAL NUDE. THE SA LIVIA PRODIOME AND WHAT HOW DO WE NORMALIZE THE CONCENTRATION OF OUR MARKER THAT WE'RE MEASURES OVER TIME TO SOME MORE CONSTANT PROTEIN OR TRANSCRIPT IF THAT ALTERNATE IDENTIFY FLUID. YOU CAN'T ASK A WOMAN TO GO INTO THE DOCTOR EVERY DAY AND DO NIGHT A BLOOD SAMPLE TO LOOK AT A, YOU KNOW, TO LOOK AT A DAILY CHANGE IF SOME KIND OF A MARKER. WE NEED TO HAVE SOME OTHER EASY WAY TO COLLECT IT, MONITOR IT, AND TRANSLATE IT REMOTELY TO THE CHECK SITE. >> IS THERE GOING TO BE AN INTERACTION BETWEEN BE THIS INITIATIVE AND THE NATIONAL RESEARCH COHORT OF THE PERSONALIZED MEDICINE INITIATIVE? >> POSSIBLY. THE PRECISION MEDICINE INITIATIVE COHORTS JUST BEING DESIGNED AS WE SPEAK ACROSS CAMPUS. SO I THINK WE DON'T KNOW -- CROSS THE HALL. THAT'S CROSS CAMPUS. AND NOBODY KNOWS WHAT THAT WILL LOOK LIKE AT THIS POINT. WE'RE INVOLVED, PREGNANT WOMEN OR CHILDREN. I THINK MANY OF US ASSUME THEY WILL, AND THEY'RE LOBBYING FOR THAT, ET CETERA. ONE OF THE DANGERS I KNOW, IT CANNOT BECOME A CHRISTMAS TREE WHERE EVERYONE'S DESIGN IDEA HANGS OFF OF IT, BECAUSE THEN WON'T WORK. WE CAN IMAGINE, I'M SURE, ALL OF US IN THIS ROOM, WHY DON'T WE JUST, YOU KNOW, FOLLOW THOSE PLACENTA, ET CETERA. WELL, THAT MAY OR MAY NOT BE DOABLE OF THE WE'LL HAVE TO SEE HOW WE HANG THAT IN THERE BUT YES, WE SHOULD BE THINK BEING THAT FOR SURE. THEIR FIRST WORKSHOP SUMMARY DID NOT SIGH ANYTHING ABOUT PREGNANCY. SO THEY ALREADY HAD A MEETING EARLY AND THE SUMMARY IS PUBLIC. >> YES, BUT THERE WAS, I CAN TELL YOU, THERE WAS DISCUSSION BEHIND THE SCENES ABOUT PREGNANT WOMEN. I CAN ASSURE YOU OF THAT. >> SO IF WE'RE THINKING ABOUT SER BELATION OR SALIVA, THE PLACENTAL MO WE'R MOLECULES ARE FAR FAR FEW AND BETWEEN. FIEND WAYS AND NEW TECHNOLOGY TO ACTUALLY ENRICH FOR THE PLACENTA SO TRYING TO GET RID OF THE MATERNAL. HAVING MARKERS FOR THE FETAL VERSUS THE MATERNAL. I THINK THAT'S REALLY IMPORTANT. OTHERWISE, WE'RE JUST GOING TO BE SEQUENCING OR GETTING A LOT OF NOISE SO. >> I JUST WANT TO REITERATE, WHEN I'VE SAID BEFORE, NOT ONLY DO WE NEED TO LOOK AT PRECONACCEPTING, BUT POST CONCEPTION PREGNANCY, SO AFTER DELIVERY, WE KNOW WHAT THE DIAGNOSES S IF WE CAN FOLLOW AND GET SOME OF THESE SAMPLES IN THE NEXT, YOU KNOW, 6 WEEKS TO 6 MONTHS AFTER PREGNANCY, THAT MIGHT ALSO BE INFORMATIVE. THE OTHER THING I WANT TO MAKE SURE IS, YOU KNOW, AT LEAST IN THIS COUNTRY, A LOT OF PREGNANCY, POOR PREGNANCY OUTCOMES OCCUR IN MINORITY WOMEN. SO I JUST WANT TO UNDERSTAND THAT THERE IS SOME SORT OF STRUCTURE TO MAKE SURE THAT SAMPLES ARE FROM MINORITY WOMEN THAT MINORITY HEALTH IS INVOLVED IN THIS PROJECT AND IS CONSULTING ON THIS PROJECT AND THAT WHEN THE SCIENCE IS DONE, THE KINDS OF OPPORTUNITY OPPORTUNITIES TO PARTICIPATE IN THE SCIENCE ARE EQUALLY DISTRIBUTED TO BOTH SCIENCE TO PATIENT OF DIVERSE BACKGROUNDS. >> SO I WAS INVOLVED IN ONE OF LARGEST NIH STUDIES THE THING I LEARN OVER 16 YEAR SYSTEM HETEROGENEITY OF PATIENTS AND YOU COULD NEVER HAVE ENOUGH PATIENTS SO I THINK THE THING WE NEED IS BETTER PHENO TYPE AND MORE PATIENCE. IF WE'RE ANYTHING TO DO THAT, WE GOING TO DO IT, WE DO THAT WITH MORE PATIENCE. OR WE'RE GOING TOEN UP WITH BIGGER NUMBERS AND THE SAME SORT OF ISSUES SO THERE ARE VARIOUS ORGANIZES YOU'VE HEARD FROM THEM NOW, ATTEMPTING TO DO STANDARDIZATION, HARMON SITUATION, WE NEED SOMEONE TO TAKE THE LEAD, AND THE KEY STAKEHOLDERS AND THE MONEY HOLDERS, YOU CAN PERHAPS, HELP GUIDE US DOWN THAT PATH FOR STANDARDIZAT OF PATIENTECTION TO HELP ALON G THAT WAY AND I THINK THAT'S DESPERATELY NEED BEFORE WE HEAD OFF AGAIN FOR ANOTHER 10,000 PATIENTS, WHATEVER, AND DON'T GET MUCH OUT TELEVISION. THE SECOND THING IS, WE HAVE GOT ULTRASOUND NOW IN OBSTETRICS. WE CAN MATTER IT IN HI DEFINITION. 3D, COLOR, SO IT'S JUST LIKE WATCHING MY TV AT HOME. BIWE HAVE HARDLY DENTURED [INDISCERNIBLE] HOER TOOLITY. I THINK WE NEED ON SAY WHY AND WE CAN RECOGNIZE IUGR BABIES BUT WE CAN'T DO ANYTHING ABOUT T. ET CETERA. SO WHEN WE ADOPTED ULTRAUN SO, WE THREW THE BABY OUT WITH THE BATH WATER. SO WE NO LONGER MEASURE HORMONES YET WE HAVE HEARD LARRY REYNOLDSED OUR, WE KNOW LOTS MORE ABOUT THESE THING. I SUGGEST WE GO BACK, REVISIT THAT. THINGS LIKE [INDISCERNIBLE] ET CETERA. PLACENTA HEALTH. WE HAVE MARKERS. WE TEND TO IGNORE THEM BECAUSE WE THINK THERE ARE BETTER THINGS OUT THERE. MY SUGGESTION S GO BACK THERE AND LOOK AT SOME OF THESE THINGS WE HAVE ALREADY GOT. WE PROPOSE DEVELOPMENT OF NOVEL TECHNOLOGY. WHEN WE THINK ABOUT THIS WAY AND WHEN WE DO STUDIES -- IF YOU START IN THE FIRST TRIMESTER, TRYING ONLY TO VALIDATE, YOU FEED TO KEEP IN MINE, IT'S FIGURE TO TAKE AT LEAST ANOTHER SIX, SEVEN MONTHS TO VALIDATE, AND WHEN WE DISCUSS ABOUT PHENO TYPING, IN ORDER TO VALIDATE, YOU HAVE TO HAVE ANEN THAT THEY DEVELOP IN A PROSPECTIVE FASHION. JUST SAY FOR THE SAKE OF ARGUMENT TO USE IT AS AN EXAMPLE, BUT NOW, WE DISCUSSED ABOUT [INDISCERNIBLE] MILE. REACLAMCIA. SO IF WE HAVE ONLY FIVE YEARS OF FUNDING, IT'S BEING TO BE EXTREMELY, EXTREMELY CHALLENGING, EVEN IF YOU HAVE THE BIOMARKERS AVAILABLE TO BE ABLE TO VALIDATE YOUR, LET'S SAY VISION. SO I'M THINKING BIG, BUT THE VIEWERS MIGHT THINK ABOUT IN A DIFFERENT WAY, ASK THEY MIGHT THINK SMALLER. SO IT IS CREAMILY CHALLENGING BUT I AM CURIOUS FROM YOUR PERSPECTIVE AND FROM THE PERSPECTIVE OF THE VALIDATION, HOW DO YOU FEEL ABOUT THIS. >> I THINK FOR THE PROJECT, WE NEED TO BE POLED AND AMBITIOUS. WHEN ONE WRITES ONE'S PROPOSAL, BE BOLD AND AMBENEFICIARY, BUT REALISTIC. AM-- BOWL AND AMBITIOUS. YOU CAN GET DINGED FOR WHAT'S SO INTERESTING OR DINGED IF THERE'S NO WAY IN THE WORLD THEY'RE ANYTHING TO BE ABLE TO DO THIS PICKUP TRUCK TO TRY AND HIT THAT SWEET SPOT WHERE YOU HAVE CONVINCING REASONING THAT THIS IS WORTH DOING AND DURING THE LIFETIME OF THE GRANT, YOU CAN MAKE SOME REAL PRACTICAL ON. >> FOR 5 YEARS, 4 YEARS, TO ACQUIRE THE DATA TO VALIDATE AND EVEN SO, HOW MANY PATIENTS YOU NEED IN FACT TO SCREEN FROM THE FIRST TIME SET UP UNTIL END OF PREGNANCY, IN ORDER TO OBTAIN ANENT, TO ENSURE THE SCIENTIFIC COMMUNITY THAT YOU DISCOVERED IS IMPORTANT TO THEM, IT'S TRULY, VALID, USEFUL AND VERY PROMISING. IT'S ATE HARD IN THIS DISCUSSION, IN THAT WHAT WE'RE TRYING TO DO WITH THIS DISCUSSION IS REACH THE GOALS OF THE END OF THE HUMAN PLACENTA PROJECT. >> THERE IF CAN YOU DO THAT, WE'LL HAVE THAT PARTY MUCH EARLIER THAN PLANNED. >> THE RFA IS JUST ONE STEP THE CURRENT RFA ON THE STREET, AND THE TWO RFA'S THAT HAVE ALREADY COME IN. THOSE ARE JUST THE BEGINNING STEPS ON THIS PROCESS, TO GET TO THE POINT WHERE WE CAN UNDERSTAND STRUCTURE AND FUNCTION. IF IN FACT, WITH THIS CURRENT RFA THE PROPOSALS YOU ALL SEND IN, ARE ABLE TO ACHIEVE ALL OF THE AIMS OF THE HUMAN PLACENTA PROJECT, WE WILL THROAT BIGGEST PARTY. THAT WOULD BE GREAT. I UNDERSTAND THAT MAY NOT BE POSSIBLE. THIS RFA CURRENTLY ON THE TREAT IS READY TO DEVELOP NEW TECHNOLOGIES AND YES, IT IS CHANNELING TO BE ABLE TO DO EVERYTHING YOU WANT TO DO WITH IT, BUT YOU'RE UP TO THE TASK. THE GOOD THING WILL BE THE REVIEWERS OR THE MEMBERS, THE RESPECTIVE MEMBER THE REVIEW PANEL TO UNDERSTAND THE WAY THAT, YOU KNOW, WE LOOK ABOUT AND HOW ARE WE GOING TO APPROACH THIS IN EYE WAY IF YOU WOULD LIKE TO AS EXAM EXAMPLE,. >> IT'S VERY CLEAR IN THE RFA. WHAT ARE THE REVIEW CRITERIA. THIS IS AN RFA THAT WILL HAVE A LOT SCRUTINY, A LOT OF MONITORING OF HOW IT SUCCEEDS FOR A NUMBER OF REASONS SO WE ARE BEING VERY, VERY CAREFUL AND WORKING WITH, WE'LL BE WORKING WITH THE REVIEW REVIEW PANEL AND WE HAVE NO IDEA WHO IT WILL BE AT THIS POINT, WE DO NOT KNOW WHO'S GOING TO APPLY. SOME OF YOU MAY LIKELY BE ON THE REVIEW PANEL. >> ANOTHER REASON TO APPLY. REMEMBER, YOU DON'T HAVE TO SERVE AND REVIEW. THEY WILL BE PRODUCTED AS TO WHAT IS THE RATIONAL FOR THE RFA AND NUMBER THEN WHAT ARE THE REVIEW CRITERIA. >> WE HAVE GONE THROUGH PRETTY MUCH THROUGH EVERY MODE OF ANALYSIS WE CAN THINK OF TO LOOK AT THESE THINGS, WHICH IS LIKE YOU SAID, IS EYE GOOD START. BUT IF YOU THINK ABOUT THE MULTI SCALE MODEL AND SOME OF THE TALK THAT WAS GIVEN NICHELY, SOME OF THOSE THINGS CAN BE, YOU DON'T NECESSARILY HAVE TO MEASURE ALL PARAMETERS YOU CAN PREDICT AND DEDUCE WHAT THE OUTPUT SHOULD BE. AND A GOOD EXAMPLE OF THAT IS -- THERE'S ONLY ABOUT 1500 GENES IN THE GENOME THAT PREDICT 80% OF THE GENOMES GENE EXPRESSION PATTERNS, ACROSS THOUSANDS OF TISSUES AND DIFFERENT CELL GROWTH CONTINUES. SO THERE ARE CERTAINLY BELL WEATHER MARKER. YOU DON'T NECESSARILY NEED TO ISSUE EVERYTHING ALL THE TIME. YOU CAN FIND THESE PRINCIPLE COMPONENT MARKER THAT IS ALLOW TO INFER WHAT SHOULD BE HAPPENING. THE, THING THAT NEEDS TO BE BE ADDRESSED IS SOME EXPECT LENT WORK THAT WAS DONE. GOOD ENOUGH YOU GUYS SOLUTIONS TO BIOLOGY. YOU CAN FIND HETEROGENEITY RESPONSIBILITY IN THE RESPONSE TO CARDIAC DRUGS BECAUSE DURING FETAL DEVELOPMENT, WHEN THE SINUS RHYTHM IS BEING ESTABLISHED, IT'S ACTUALLY A BIOLOGICAL SOLUTION, THE FETUS SOLVES THAT PATTERN BY A JUSTING EXCELLENT BE PREGNANCIES LEVELS OF DIFFERENT ROTEENS THAT WORK FOR TRANSMISSION OF THE CARDIAC SINUS RHYTHM. AND SO WHAT YOU WIND UP WITH IS, IT'S THE SAME GENETIC MOUSE SOLVING IT THROUGH DIFFERENT LEVELS OF SOLVENT LEVELS OF PROTEIN. EACH OF WHICH ARE DELIVERING EYE SINUS RHYTHM BUT ARE SUSCEPTIBLE AND SO WHEN YOU LOOK AT ALL KINDS OF DEVELOPMENT, AND I THINK IN PARTICULARLY, A PLACENTAA DEVELOPMENT WHERE IT'S AN ADAPT IDENTIFY RESPONSE WITH THE MCCOMB COUNTY ROAD COMMISSION. THERE'S A CERTAIN AMOUNT OF PROGRAMMING ING ON. EVEN WHEN YOU TRY TO CREATE IDENTICAL COHORTS YOU MAY FIND YOUR EXCELLENT BE PROTECTION PATTERNS ARE HETEROGENEOUS BECAUSE THEY ARE TRYING TO SOLVE THE PROBLEM TO FINAL A WORKABLE SOLUTION IN BIOLOGY. >> FROM CLINICAL PHENO TYPE DATA TO THE O MIX DATA TO IMAGING. ONE OF THE LESSONS, I'LL CHIME IN FROM THE MICRO BIOME PROJECT, BE AND THE MULTIMULTI OMEC STUDY LOOKING AT LONGITUDINAL STUDY OF PREGNANCY IS WHEN STANDARDIZATION HAPPENS REALLY MATTERS IN TERMS OF THE OUTCOME. SO INNER ITS OF THE PROGRAMMATIC GOALS ARE TO STAND AND REPEAT AFTERRIZE. THE SOONER THOSE STANDARDS CAN BE CENTERED OTHE BETTER. IN TERMS OF OF HARM CONDOMINIUMIZATION. SEE WHAT THOSE DIFFERENCE ARE. THOSE TYPES OF EXPERIMENTS CAN BE BE DESIGNED AND THE SOONER THE PROGRAM WILL BE BETTER. I'M JUST ONEERING IF ANY OF THOSE TYPES OF DISCUSSIONS HAVE BEEN HAD AT THE PROGRAM LEVEL. >> YES, AND OILED ASSUME THAT YOU THINK NOT JUST THE TIMING BUT WHO'S INVOLVE IN THE PROCESS OF COMING UP WITH THOSE STANDARDS IS RATHER IMPORTANT. >> YES. IN GENERAL, I THINK IT DOES HAVE TO BE EARLY, BUT IT CAN'T BE BE TOO EARLY, OH. YOU HAVE TO HAVE SOME IDEA. I THINK WE'RE PRETTY MUCH, I DON'T THINK WE'RE IN DANGER OF BEING TOO EARLY. BUT IT'S SOMETHING WE ACTUALLY HAVE A CONFERRING ABOUT. IT'S NOT EXAMINE ABOUT HOW WE PULL TOGETHER THE RIGHT FOLKS TO DO THAT. >> ONE CASE WITH THE DEMONSTRATION PROJECTS, AND THE MICRO BY ONLY DEMONSTRATION PROJECTS ARE FROM A DIVERSE GROUP OF DISEASES AND SO A LOT OF THE CLINICAL TYPE DATA MAYBE BE WASN'T QUITE AS CRUCIAL. BUT TRYING TO PULL IN PHENO TYPE DATA WAS NEARLY IMPOSSIBLE BECAUSE EVERYBODY HAD ALREADY BEGUN ENROLLMENT. MAY BE DIFFERENT IN TERMS OF THE OPPORTUNITY TO DO MEDICAL RECORD ABSTRACTIONS. AGAIN, BUT IF IT'S DATA THAT CAN'T BE GOTTEN AGAIN, EARLY IS ALWAYS BETTER. I THINK RECRUITMENT IS VERY IMPORTANT. HOW DO YOU GO ABOUT RECRUITING WOMEN IN THESE INSTALLATION. HOPEFULLY, YOU HAVE AN INSTITUTION WHERE YOU HAVE A TEACH BEING HOSPITAL KECKED WITH YOUR CAMPUS. IT MAKES IT EASIER. OTHERWISE, IT MAKES IT MORE DIFFICULT. INTO REITERATE THAT PROBLEMS WITH PREGNANCY OUTCOMES ARE OFTENTIMES LOCALIZED AMONG DESPAIRATE POPULATIONS AND THAT HAS TO BE ADDRESSED. WHAT I HAVEN'T HEARD IS ANY OF THE INCLUSION AND EXCLUSION CRITERIA FOR THE WOMEN THAT ARE PREGNANT THAT WILL PARTICIPATE. I THINK THAT HAS TO BE ADDRESSED AND HAS TO HAVE A STANDARD ACROSS THE BOARD FOR PEOPLE THAT WILL PARTICIPATE IN THESE STUDIES. THE OTHER ISSUE IS I DON'T THINK ALL THE CELL TYPES IN THE PLACENTA OF COURSE IDENTIFIED IT'S JUST A BASIC UNDERSTANDING. I THINK THEY HAVEN'T BEEN OVER. AND I SAY THAT BECAUSE I WORK WITH PRIMARY PLACENTAL TISSUE. AND THOSE ARE DIFFERENT THAN THE NORMAL CELL TYPES THAT WILL AUTOMATICALLY OVER GROW THAT FUTURE IN A FEW DAYS. CYTOTROPOBLASTS WILL OVER GROW ANY KIND OF PRIMARIAL CULTURE AND THE OTHER CELL TYPES BECAUSE THEY'RE MORE PASS TIEDUOUS WILL NOT SURVIVE. YOU WILL NOT SEE THEM. SO I THINK THERE'S SOME CELL DISCOVERY LEFT IN THE PLACENTA THAT IS UNKNOWN, SO WHEN I ALSO THINK ABOUT THE KINDS OF SAMPLES THAT ARE GOING TO BE TAKEN, I THINK THERE SHOULD BE AN EFFORT TO LOOK AT NEW TYPES OF SPECIMENS, OF COURSE, YOU'RE LIMITED TO DOING THIS IN REAL TIME SO THERE'S A FEW SPECIMENS THAT INCLUDE NONINVASIVE TECHNIQUES TO GET AT AND THAT KIND OF LIMBS PEOPLE. PARTICULARLY WHEN MOST OF THE STUDIES THAT HAVE BEEN DONE IN PLACENTA BIOLOGY HAVE BEEN DONE WITH DELIVERED PLACENTAS. THAT BECOMES AN ISSUE. I ALSO THINK THAT WE HAVE TO LOOK AT THE NUMBERS. WHEN I SAY LOOK AT THE NUMBERS. I'M TALKING ABOUT, WHEN WE LOOK AT PREGNANCY OUTCOMES, WHAT ARE THE CAUSES OF POOR PREGNANCY OUTCOMES. I THINK INFECTIOUS DISEASE CANNOT BE BE IGNORE HERE. WHEN WE LOOK AT GROUP B STEP. CYTOMEGALOVIRUS. YOU'RE LOOKING AT ABOUT A HALF MILLION WOMEN THAT WILL GO THROUGH THIS IN A YEAR'S TYPE. THE NUMBERS HAVE TO BE RECOGNIZED IN TERMS OF HOW THIS IS GOING TO BE APPROACHED AND SO FORK. FORTH. >> I THINK YOUR POINTS ARE EXCELLENT. WE DO NOT CURRENTLY HAVE A PLAN RECRUITMENT BECAUSE WENT HAVE THAT STUDY PLANNED YET. THAT'S PART WHATEVER WE'RE TRYING TO GET AT HERE. WHAT ARE THOSE FIRST STEPS. DO WE NEED A BIG STUDY. IF SO, WE MOVE ON. TO THOSE DETAILS Q. WE GET TO THE POINT. THE ISSUES YOU HAVE RAISED ARE EXCELLENT. THANK YOU. >> I HAD A COMMENT ON THE PROCESS. JUST A THOUGHT ABOUT HOW THINGS ARE GOING. FOR MANY OF US, WE HAVE RESEARCH PROGRAMS THAT UNFORTUNATELY, CAN'T TURN ON A DIME, AS IT WERE. AND SO TO BE ABLE TO MOUNT NEW PROJECTS, I THINK A LOT OF US ARE QUITE FLEXIBLE IN WHAT WE CAN DO. IT'S NOT JUST ONE THING, IT'S SEVERAL THINGS. WHEN YOU TRY AND ENGINEER THOSE INTO A NEW PROJECT, IT'S SOMETHING THAT TAKES SOME TIME TO DO. AND I THINK FOLLOW BEING YOUR BRING, IF YOU'D LIKE, BEING BOLD UNFORTUNATELY CAN TAKE SOME TIME TO ASSEMBLE THE GROUP OF PEOPLE TO GET THEM TO SAY YES. LET'S TRY IT. LET'S THINK ABOUT IT. LET'S SEE IF WE CAN PUT SOMETHING TOGETHER. AND I UNDERSTAND THAT THE INITIATIVES THAT YOU PUT OUT SO FAR, IF YOU'D LIKE, CLEAR THE FIELD OF THINGS THAT WERE ALREADY THERE PERHAPS TO SOME DEGREE. THINGS THAT WERE ALREADY PREPARED. THINGS THAT WERE ALREADY IN TRAIN. BUT I THINK I WOULD LIKE TO PUT IN A PLEA, IF YOU'D LIKE SOME THINKING TIME. A RELEASE OF AN RFA WHERE WE HAVE TIME TO SIT DOWN, ASSEMBLE A GROUP OF PEOPLE, PUT THINGS TOGETHER. WITHOUT HAVING TO SCRAMBLE, RUN AND NOT DO THE JOB I THINK WEEK DO. >> VERY VALID POINT. YOU HAVE REALIZE, OF COURSE, IF THIS WAS MONEY, THE VAST BULK OF THIS MONEY WAS MONEY RECEIVED. AND WE NEED TO BE PAY TOGETHER BY SEPTEMBER. EVERYONE'S TIME LINE. IT'S EYE LOGISTIC BAL ISSUE AND I'D LOVE FOR YOU TO SHIRT VISION OF HOW YOU SEE THE GROUP COMING TOGETHER. THEY WILL HAVE ALL DIFFERENT TEG NOOLOGIES, PERHAPS, AND THEREFORE, WHAT IS THE EXPECT BETATION. ARE WE EXPECTED TO SHARE AND CHECK SAMPLES AND DO THEY NED TO BE BE BUILT INTO A PROJECT NOW [PLEASE STAND BY] ALL OF US MAKE BE MONEY, PRESENTING AND SCREENING IN THE FORM OF QUAD SCREENS EACH AND EVERY DAY, WE RUN AROUND INTEGRATING MULTI OMEC DATA. AS WE'RE REALLY TRYING TO FINE TUNE THIS. DOWN TO THE LEVEL OF PLACENTAL BIOLOGY X DO IT IN REAL TIME, HOW DO WE CAPTURE THE ENTIRETY OF THE FINE TUNING OF THE RESOLUTION THAT WE'RE TRYING TO PEAK AT, AND AND HOW MUCH OF THAT DO WE NEED TO HAVE VERY, VERY CLEAR BENCH MARKING THAT WE CAN AVOID PUTTING OUR HANDS ON THE PLACENTA TO GET IN SOME FORMS OF DEPUTY SUPERVISORTH. SO I THINK THAT'S GOING TO BE ONE OF THE REALLY IMPORTANT CHALLENGES IS HOW DO WE DO THAT AND NOT AT END OF THE DAY, COME BACK AND I SARKS WELL, IT TURNS OUT 88TC IS A PRETTY GOOD MARKER PREGNANCY, SO REALLY HAVE AN INCREDIBLE DIFFERENT RESOLUTION THAN WHAT WE'RE ALREADY DOING. >> I THINK IT IS ABSOLUTELY ESSENTIAL THAT WE BUILD UPON THE IN THIS ROOM HAVE BUILDING THE METHOD OF PLACENTAL BIOLOGY AND TAKE THAT FORWARD IN TRYING TO UNDERSTAND AND CHARACTERIZE FUNK AND STRUCTURE ACROSS JESTATION. I THINK OUR GOAL IS REALLY TO BE ABLE TO SAY CAN YOU CHARACTERIZE THE CUTTING EDGE STRUCTURE AT 20 WEEK, 30 WEEKS, FOURTH WEEKS. WITHOUT INTERVENING AND THAT REQUIRES AN INTIMATE KNOWLEDGE. WE HAVE TALK A LOT ABOUT DIG NOSE. BUT I WOULD THINK THAT AT SPECIAL POINT, WE WOULD LIKE TO GET INTO THERAPEUTICS AND AT SOME POINT -- >> AND EVEN PREVENTION. >> YES. PARENS, OF COURSE, BUT OF COURSE, THERAPEUTICS AS WELL. BECAUSE WHAT ARE YOU GOING TO DO AT SOME POINT, YOU CAN'T JUST SAY, THERE'S SOMETHING WRONG, BE WE WILL JUST WE'LL JUST DELIVER THE BABY. MAYBE BE WE'LL MAKE A PLACENTA FROM IN VITRO AND HOOK UP THE BABY. I WANT THE TO PUT A PITCH IN, OF I WOULD SAY HUMAN PLACENTA CELLS AND CULTURE. FOR HIGH GROUP OF SCREENING OF DRUGS, I THINK THAT BECOMES IMPORTANT. AND I THINK FOR AT LEAST PART OF THAT, MAYBE WE CAN LOOK TO THE STEM CELL FIELD AND LOOK AT SOME OF THE MODELS THAT THEY HAVE DEVELOPED THAT ARE VERY USEFUL. >> I WANTED TO POINT THAT THERE IS AN ERROR IN THE SLIDE. I SAID POSTIE OR POST BIRTH. IF YOU GO UP, YOU GO UP AND YOU'VE WRITTEN POST CONCEPTION AGAIN, I WANT TO MAKE SURE THAT YOU INCLUDE POST DELIVERY OR POST BIRTH SAMPLES. AND ONE OTHER COMMUNITY, TO INCREASE A DIVERSITY QUESTION. A DIVERSITY OF FUNNING MECHANISM, AS YOU PLAN THE NEXT GRANT CYCLES THAT MAY BE GOING ON WITH THIS PROJECT, WHICH I ASSUME THEY WILL BE. BECAUSE THE COMMENTS THAT ARE MADE. TO CONSIDER PLANNING GRANTS AND CONSIDER PUTTING OUT RFA'S QUICKLY SO THAT PEOPLE HAVE TIME. PROBABLY THREE MONTHS OR SIX WEEKS IS NOT ENOUGH TO PUT TOGETHER SOMETHING THAT'S GOING TO BE BE GOOD FOR THE PROJECT. SO I'D JUST LIKE TO YOU CONSIDER THAT. >> ABSOLUTELY. THANK YOU. I'M GOING TO MOVE TO THE NEXT QUESTION THAT WE WERE ASKED TO ADDRESS AND I THINK THERE'S AND I WANT TO MAKE SURE WE AREN'T MISSING ANY GAPS. THINGS THAT WERE INCLUDE ON THE STICKY BOARD, INCLUDED THE ISSUE OF INCLUSION OF ETHICAL STUDIES OF CONNECTING RESEARCH ON PREGNANT WOMEN. MEETING STANDARDIZED, HIGHLY ACCESSIBLE COHORTS OF PREGNANT WOMEN. WHAT ABOUT CELL FATE. RE DO LIPID OMECS FIT IN. PLACENTA FUNCTION NEED TO BE CONSIDERED RELATIVE TO THE UTERINE ENVIRONMENT. DON'T FORGET TO ADD GROCIC. MAYBE IT'S RUN-O. I LIKE RUM ON. [LAUGHTER] I'M NOT GOING TO CHANGE IT. FUNKAL ASSESST, OX JANUARY NUTRIENT AND DRUG TRANSPORT. WHAT IS NORMAL PREGNANCY, IF NOT PRETERM OR PREACLAMCIA. PREGNANCY WITH AUTISTIC OFFSPRING WITH THE PLACENTA NORMAL. RING NONINVASIVE METHODS OF TRACKING FOR FREE LIVING CONDITIONS. RESPONDING PARAMETER CHANGES IN REAL TIME. HIDES TEMPORARY RESOLUTION. I'M GOING TO HAVE TO LOOK AT THAT ONE AGAIN. STANDARDIZATION OF VOLUME MEASURES ACROSS PLATFORMS. MONITOR BEING PLACENTAL HEALTH. METABOLOMICS. OXYGEN STATIC. CAREER DEVELOPMENT OPPORTUNITIES. TRAINING TUNES FOR YOUNG INVESTIGATORS A GROUP TO DEVELOP STANDARDS. PRECONCEPTION HEALTH OF BOTH PARENTS, MALARIA IN PREGNANT WOMEN. INFECTIOUS DISEASES. SUPPORT FOR ESTABLISHING AND MAINTAINING STANDARD ANIMAL MODELS. LOOK AT MATERNAL DIETARY INTAKE AND MICRO BIOME. WHAT OTHER GAPS ARE WE PISSING? IF ANY, AND I REALIZE, SOME OF THE GABS WERE LISTED. >> IN TERMS OF DEFINING THE COHORTS OF WOMEN, PARTICULARLY, THE ONES THAT ARE USED TO DEVELOP, YOU KNOW, STANDARDIZED NORMALS FOR WHATEVER OLMEC WE HAPPEN TO BE LOOKING ALT, AND I WAS JUST THINKING ABOUT A LOT OF THE EPIDEMIOLOGICAL DATA THAT IS COMING OUT, PARTICULARLY BY JIMMY COLLINS UP AT NORTH WESTERN IN CHICAGO, WHO LOOKS AT HEALTH DISPARITIES AND NEONATAL OUTCOMES AND PREGNANCY OUTCOMES, AND YOU KNOW, YOU HAVE THE STRIKING RACIAL DISPARITIES BUT WITHIN EACH RACIAL GROUP OR ETHNIC GROUP, THERE ARE CRENATIONAL EFFECTS. AND SO IF YOU HAVE, FOR INSTANCE, RECENT M GRANTS FROM THIS COUNTRY FROM THE CARIB BEAN, AFRICA OR MEXICO, FOR INSTANCE, THE OUTCOMES OF WOMEN, THE PREGNANCY OUTCOMES OF WOMEN, RIGHT AFTER THEY COME HERE ARE PRETTY SIMILAR TO THE OUTCOMES OF QUITE WOMEN. BUT AS THEY ARE HERE FOR TWO AND THREE AND FOUR GENERATIONS, THE OUTCOMES TEND TO FALL FALL OFF, WHICH SUGGEST TO ME THAT THERE ARE PERHAPS, SOME EPIGENOMIC TYPE MECHANISMS THAT PLAY THAT ARE STARTING TO IMPACT THAT POPULATION. AND EVEN IF YOU CORRECT FOR SOCIOECONOMIC STATS, THEN SAY FOR INSTANCE, WHEN YOU COMPARE THE CLERC HUCKS FASTBALLS OF THE WORLD TITLE OR THE PUBLISH BEEL OBAMAS WITH THE NANCY REAGANS OF THE WORLD TITLE, YOU KNOW, BLACK WOMEN STILL DO WORSE. EVEN IF YOU'VE CORRECTED NEAR FOR ALL THE OTHER THINGS THAT ATTEND TO AFFECT OUTCOMES SO THERE'S SOMETHING THERE THAT TENDS TO BE UNIQUELY BUILT INTO THAT PARTICULAR POPULATION AND EXACTLY WHAT THE MECHANISM IS, YOU KNOW, I'M NOT SURE BUT WITH THE GENERATIONALLESQUES THAT WE SEE, YOU KNOW, IT REALLY SEEMS TO HAVE A PROFOUND IMPLICATION FOR AN EPIGENETIC TYPE INVOLVEMENT. AS NORMAL COHORTS OF WOMEN ARE DEFINED, SAY IF YOU'RE DEFINING A NORMAL COHORT OF HISPANIC WOMEN OR AFRICAN-AMERICAN WOMEN, I THINK WE MAY HAVE TO BE A LITTLE MORE PRECISE THAN THAT, TO TRY TO REDUCE A LOT OF THE VARIABILITY WHICH WE MAY SEE IF THOSE WOMEN CROSS MULL PELL GENERATIONS AND OTHER STRATA SUCH AS SOCIOECONOMIC, ET CETERA. ET CETERA. TO ELABORATE ON IA POINT I MADE EARLIER. I THINK THERE'S A REAL GAP WITH RESPECT TO THE IMAGING TECHNOLOGY IN TERMS OF THE BIOPHYSICAL INTERPRETATION OF WHAT THESE IMAGES MEAN AND I THINK TELL BE BE A MISTAKE AT THIS POINT, BE FOR US TO STANDARDIZE ON A PARTICULAR SET OF ACBE SESSON METHODS AND THEN NEW FROM THERE, TO IDENTIFYING BIOMARKERS BECAUSE I THINK THERE WOULD BE A REAL MISSED OPPORTUNITY THAT IF WE COULD GO FURTHER WITH THESE TECHNOLOGIES, WEEK IDENTIFY THE PARAMETERS THAT WE KNOW FROM OUR PHYSIOLOGY TEXT BOOKS, WHICH HAVE THE GREAT ADVANTAGE THAT YOU COULD THEN REASON ABOUT THEM IN A WAY THAT YOU CAN IF YOU WERE TO LOCATE A BIOMARKER WHICH YOU THROW INTO A STATISTICAL LATER ON. >> I JUST WANT TO THANK DR. FOR THE HUMAN GENOME PROJECT PRESENTATION BECAUSE IN THE THINKING BOWL ABOUT THE HUMAN PLACENTA PROJECT, WE HAVE TO REMEMBER, WE DON'T KNOW HOW THE HUMAN PLACENTA FUNCTIONS DURING PREGNANCY. WE HAVE SOME MARKERS OF THINGS -- WE HAVE SOME MARKERS OF THINGS BUT IF WE DO WHAT THE HUMAN GENOME WAS OBSERVE WE SEQUENCED IT, WOULDN'T THE HAVE TO SEQUENCE IT. I THINK IT'S IMPORTANT TO COLLECT GOOD PHENOTYPIC INFORMATION FROM STUDY PARTICIPANTS BUT NOT TO DESIGN COHORTS THAT ARE TEAL BEING WITH OUR PRECONSCENARIOS LIKE WE'RE GOING TO HAVE A PRECLAMPSIA GROUP. WE DO NOT KNOW IF THOSE ARE GROUPS. THOSE ARE OUTCOMES WHICH MAY BE ARRIVED AT BY DIFFERENT PATHWAYS. LET'S COLLECT A LOT OF DATA AND NOT TRY TO PIGEONHOLE THAT BEFORE WE COLLECT IT. >> AND I WOULD ARGUE IF WE WERE TO DO THAT, IT WOULD BE IMPORTANT TO COLLECT THE DATA SO THE DIFFERENT PEOPLE BEING DEFINE THOSE OUTCOMES DIFFERENTLY. FACT, ONE COULD ARGUE, IT IS AUTO A PROBLEM BE WITH MAKING STANDARDIZED OUTCOMES. WE LUMP THINGS TOGETHER THAT MAY NOT BE BE LIVEABLE. WE NEED TO HAVE REALLY RICH ROBUST, PHENOTYPIC DATA AND LET VARIOUS RESEARCHERS COME UP WITH THEIR OWN GROUP ACCIDENT. >> A COLLEAGUE OF MINE DID [INDISCERNIBLE] AND FOUND THAT PREA CC LAMPCIA IS RELATIVE, TO ACTUAL COMMONALITY IN THE POPULATION. IF HAS PATHOLOGICAL PREGNANCIES, IT MAKES UP A CERTAIN PERCENTAGE. BUT IN TERMS OF EXPRESSION STUDIES, IT'S A MUCH LARGER PERCENTAGE. IF YOU FOLLOW MORE OF A PHENO TYPE FIRST, RATHER THAN CLUMP FIRST, BE YOU'LL KIND OF DELIVER, PHENO TYPES IN PROPORTION OF HOW THEY'RE ACTUAL NEPOPULATIONS. I THINK THAT WOULD BE BENEFICIAL. >> YEE, I'M BEING TO FOLLOW UP ON THAT. WE'RE DOING A LOT OF TALKING ABOUT PHENO TYPING AND UNFORTUNATELY, WE RELY ON SELF-DESCRIBED ETHNICITY, WHICH IS WEAK AT BEST AND CULTURALLY LOADED SO I CAN'T EVEN GET MY HOSPITAL TO RELIABLY RECORD ETHNICITY. I'M USUALLY MUCH BETTER OFF FINALLING OUT WHERE SOMEONE WAS BORN AND WHAT IS THEIR PRIMARY DESIRED LANGUAGE, IN ORDER TO BE ABLE TO CODE THESE THINGS CORRECTLY. NOW, THERE IS A VERY SIMPLE, CHEAP WAY TO GET AROUND THIS AND THAT'S CALLED BIOSCREE GRAPHIC ANCESTRY, WHICH I HAVE USED IN MY STUDIES. ANCESTRY INFORMATIVE MARKERS. THEY ARE RANDOM SNIPS, LOCATED IN NON-CODING REGIONS, THAT VARY BY GEOGRAPHIC BE ORIGIN. FOR EVERY PATIENT IF MY STUDY, I CAN SAY, THIS PERSON IS 53% NATIVE-AMERICAN. 4% EUROPEAN. 3% SOUTHEAST ASIAN AND 1% SOUTH SAHARAN AFRICAN. THESE ARE CHEAP AND WHY WE ARE NOT USING THEM IN EVERY CLINICAL TRIAL WE FUND IS BEYOND ME. >> I WOULD NOTE THAT [INDISCERNIBLE] IS INCREDIBLY IMPORTANT. ONE'S EXPERIENCE IN LIFE, IS DETERMINED BOTH BY YOUR BIOLOGICAL MAKE UP AND YOURSELF VIEW. >> BUT HOW MANY PAPERS DO YOU SEE PUBLISHED THAT GIVE YOU ANYMORE FINE GRAIN INFORMATION THAN AFRICAN-AMERICAN, BLACK, WHITE, HISPANIC, ASIAN VERY FEW. I CAN IDENTIFY EVERYBODY'S ETHNICITY IN MY TODAYS I BENEOVER BACKWARDS TO GET THAT INFORMATION. BUT IT IS NOT RECORDED ARE YOU 10LY EVERYWHERE ELSE. NOT WITH THAT RIGOR. >> I'M ACTUALLY RESPONDING TO YOUR QUESTION OF WHAT ELSE IS MISSING. ONE PERSON THING I DIDN'T SEE THERE IS AWARENESS IN OUR COMMUNITY, IN INFORMING THE JEAN-JACQUES DOE OR JANE DOE THAT THEY ARE THE STAKEHOLDER SO I HAVE NOT HAD AS MANY STUDENTS SINCE DOWNTOWN ABBEY HAD SEIZURES. SOMEBODY IN THIS MOVIE HAD A SEIZURE AND THEN APPARENTLY, PEOPLE GOOGLE ME AND THEY FOUND OUT I WORK IN PREACLAMCIA AND I THAT WANT TO COME TO MY LAB. I'M NOT WORKING IN MOVING TREATMENT PROGRAMS BUT IF WE CAN MAKE SOME MOVIE ABOUT THE PLACENTA OR SOMETHING OR ENGAGE MARKING OR WHATEVER, TO RAISE AWARENESS, THAT STUDYING THE PLACENTA ANDED IS ITING PREGNANCY IS NOT SOMETHING THAT SOME WEIRD PEOPLE LIKE US DO. I THINK IT'S VERY IMPORTANT. I HAVE SEEN HOW THIS CHANGE IN AWARENESS IMPROVES FUNDING BY MOVING FROM AN ACADEMIC INSTITUTION, THAT WASN'T AFFILIATED WITH A CHILDREN'S HOSPITAL, WITH ONE THAT IS AFFILIATED WITH A CHILDREN'S HOSPITAL AND THE IMPORTANCE OF ALL OF A SUDDEN, THE WORK YOU DO IS EXPONENTIAL. AND I THINK IT CAN REALLY, REALLY DRIVE SUCCESS OF A PROJECT. >> ISSUE OF TRAINING PROGRAMS IS ISSUED IN ONE OF THE BULLETS HERE AND I APPRECIATE THAT WE'RE GETTING THIS OFF TO A ROBUST START. BUT IF THE PROGRAM ITSELF IS GOING TO SUNSET, I HOPE THERE WILL BE A PROVISION AT SOME POINT ALONG THE LINE FOR SPECIFIC TRAINING PROGRAMS FOR THE NEXT GENERATION. >> THE LAST ONE ON THIS QUESTION, BEFORE WE GO TO THE NEXT ONE BE. >> I JUST WANT TO FOLLOW UP ON THE CONVERSATION ABOUT THE QUESTION OF SELF-IDENTIFICATION OF RACE ETHNICITY, VERSUS GENETIC MARKERS. AND I DON'T THINK IT'S REALLY AN EITHER OR. THERE'S A UTILITY TO KNOW IN BOTH. AND IT'S BEST TO TRY AND MAKE AN EFFORT TO INCLUDE BOTH FROM THE OUT SET BECAUSE YOU REALLY DON'T KNOW BE WHICH ONE'S GOING TO BE RELEVANT IN WHICH SITUATION, BUT CLEARLY, HISTORY HAS SHOWN US THAT HOW SOMEONE, YOU KNOW, AT LEAST IN THIS COUNTRY, BY FAR, THE SOCIAL CONTEXT IN RACE HAS A PROFOUND EFFECT ON OUTCOMES, THAT HAS TO BE CONSIDERED IN. I DON'T THINK IT'S AN EITHER OR, BUT I THINK TO SUBSTITUTE THE RACIAL AND ETHNIC IDENTIFYING IN THE CONTEXT OF SOCIAL DEFINITIONS, AND CLASSIFICATIONSES I THINK THAT WOULD BE MISSING AN OPPORTUNITY FOR KNOWING HOW THINGS EFFECT THE OUTCOMES WE'RE LOOKING TO PRESENT. >> THANK YOU WE'RE ANYTHING TO MOVE TO THE LAST QUESTION. AND THEN WE HAVE GOT A COUPLE OF EXTRA QUESTIONS WE WANT TO THROW IN. PLACING HPP IN CLINICAL PRACTICE. EXPLORING THE CURRENT BARRIERS FOR INCORPORATING THE HPP. IDEAS PUT UP INCLUDE A DIVERSE GROUP OF WOMEN. EXPENSE AND LACK OF SAFETY IN EARLY PREGNANCY, IMPLANTABLE PLACENTAL MONITOR. NEED NONINVASIVE TESTING. WOMEN MAY BE BE HESITANT TO SUBMIT TO AN MRI. STIMULATION PLATFORM INTEGRATE OMEX AND OTHER DATA. YEAH. ANIMAL I'M SURE. SORRY. DON'T THROW WATCHING TV PLACENTA AND NEED TO VALIDATE IMAGING FINDINGS WITH PATHOLOGY OR WHAT IS THE POINT. >> I WANT TO THANK ALAN AND KATHY AND DAVID FOR HAVING THIS CONFERENCE. FOR ME IT'S LIKE A HIGH SCHOOL REUNION. BECAUSE USUALLY, WE WORK ALONE, SO TO BE IN A ROOM WITH A COUPLE HUNDRED PEOPLE IS FANTASTIC. I OF THE JUST WANTED TO BRING A LITTLE BIT OF REALITY TO THIS FROM MY POINT OF VIEW, NOW. AND I THINK THIS QUESTION ADDRESS THIS IS. WHEN WE GO HOME WE'RE GOING TO BE GOING BACK TO OUR PLACES WHERE IN THE WORLD THAT WE LIVE IN, CHIPOLTE JUST BANNED ALL GENETICALLY MODIFY ORGANISMS, FOODS. WE HAVE RICKY LAKE, WHO HAS A DOCUMENTARY ABOUT HOME DELIVERY. THE UNITED KINGDOM HAS BASICALLY SAID THAT HOME DELIVERY IS EQUAL OR AS SAFE, IS SAFER THAN HOSPITAL DELIVERY AFTER FIRST BIRTH. ONE OF MY CONCERNS IS SORT OF THE SIMPLE VERSUS THE VERY COMPLEX. THE GATES FOUNDATION. I DON'T KNOW IF THE PERSON IS STILL HERE WHO IS HERE, AFTER HUNDREDS OF MILLIONS OF DOLLARS INVESTING IN AFRICA TO IMPROVE HEALTH. WHAT THEY REALIZE THE MOST IMPORTANT THING THEY CAN DO IS JUST HAVE CLEAN WATER. THE MOST IMPORTANT THING THEY CAN DO FOR GIRLS IS TO SUPPLY, YOU KNOW, MENTAL PADS FOR THOSE GIRLS. ONCE THEY START HAVING THEIR PERIODS, THEY DO NOT GO TO COOL ANYMORE, AND THEY'RE OUT OF COMMISSION IN TERMS OF THEIR CAREER DEVELOPMENT OR LIFE DEVELOPMENT. SO THE QUESTION IS ARE WE REALLY TRYING TO ACCOMPLISH IN TERMS OF THIS PROJECT, AND I WOULD PROPOSE THAT WE NEED TO THINK OF THIS AS LIKE "APOLLO 13." WE HAVE ONE HOUR TO PUT ROUND FILTERS INTO A SQUARE HOLE OR WE'RE GOING TO DIE OF CARBON DIOXIDE, YOU KNOW, EXCESS AND I THINK THE COMPEL BEING THING IS HOW CAN WE MAKE A TECHNOLOGY THAT IS ADOPTABLE, USABLE, THAT WILL BE USE THE PIE CLINICIANS AND ACCEPTABLE BY PATIENTS, GIVEN THE GM O ISSUE THEY MENTIONED, I THINK THERE'S A LOT CONCERN ABOUT PUTTING INNOVATIONIVE THINGS IN THEM, I THINK BLOOD IS SOMETHING THAT'S REASONABLE BUT A LOT OF THE PROPOSALS ARE NOT ANYTHING TO BE ACCEPTED BY THE CLINICIANS OR THE PATIENTS. AND ECONOMICALLY IT'S REALLY HARD TO GET PEOPLE TO DO A SIMPLE ADDITIONAL LITTLE TEST IF THE FLOW OF THINGS, GIVEN THE PRESSURES OF THE HEALTHCARE DELIVERY SYSTEMS WE SHOULD THINK IN TERMS OF SIMPLE SOLUTIONS THAT WILL BE ADOPTABLE. THAT WILL BE THE MOST IMPACT OVER THINGS THAT ARE VERY COMPLEX THAT WON'T HELP A LOT OF PEOPLE. >> I HAVE IAY REQUEST, MORE RELEVANT TO THIS LAST ONE. I THINK SOMETHING THAT CAME UP MORE AND MORE IN THE BIOMARKER DISCOVER. IT IS VERY IMPORTANT TO DEFINE THE USE OF THE MARKER FROM THE BEGINNING. SO IF YOU WANT TO FOND A MARKER FOR PRECLAMCIA OR OTHER TYPE OF -- I THINK YOU NEED TO HAVE A COHORT AND THE QUESTION BEGINNING WAS STATED. THIS DOES NOT TAKE AWAYULE THE IMPORTANT KNOWLEDGE IT'S NOTE GOING TO ANSWER THE QUESTION, DO WE HAVE A MARKER FOR A PRETERM BIRTH. YOU NEED TO DEFINE THAT VERY L. YOU HAVE THESE QUESTIONS THAT YOU CAN LOOK AT 5,000 DIFFERENT -- AND IT LETTINGS YOU DEFINE THAT. YOU JUST HAVE A LOT OF NOISE. PERHAPS YOU CAN ADDRESS A FEW QUESTIONS. >> INTHEED TO FOLLOW UP ON THE PRIOR COMMENT ON THIS SIDE OF THE ROOM. I'LL A PHYSICIAN SCIENTIST SO I REALLY DO APPRECIATE THE NEED TO HAVE SOMETHING, WANTING TO TRANSLATE THAT THE ONES INTO CLINICAL MEDICINE, AND I WANT TO POINT OUT, THERE'S A LOT WE STILL DON'T KNOW ABOUT HUMAN PLACENTA DEVELOPMENT BECAUSE WE HAVEN'T BEEN ABLE TO STUDY THE HUMAN PLACENTA THROUGH ANIMAL MODELS AND SO SOME OF THESE TOOLS MAY NOT NECESSARILY NEED TO GET TO THE POINT OF CLINICAL ADOPTION TO STILL BE OF EXTREME VALUE IN UNDERSTANDING PLACENTAA DEVELOPMENT, FUNK AND UNDERSTANDING THE IMPORTANCE OF THE PLACENTA SO THAT WE CAN DEVELOP OTHER CLINIC BEALLY ADAPTIVE TOOLS WE NEED SOME FUNDAMENTAL BIOLOGIES STILL AND THESE TOOLS ARE CRITICAL TO BEGINNING TO KNOW THE FUNDAMENTAL BIOLOGY. SO I THINK WE NEED BOTH KINDS OF APPROACHES IN THINKING ABOUT THE TOOLS. >> AND I THINK THAT'S AN IMPORTANT POINT TO BE BE SPEAKING ABOUT. SHOULD BE DOING A BETTER JOB OF MAKING CLEAR. THE ULTIMATE GOAL IS TO THINK ABOUT BEING ABLE TO MONITOR HUMAN PREGNANCY IN REAL TIME BUT . IT'S ABSOLUTELY FUNNELAMENTALLY - THIS IS SIMPLY TO DEVELOP SIMPLY, TO UNDERSTAND PLACENTAL FUNCTION. ONCE WE UNDERSTAND IT, WE CAN BEGIN TO DO THESE OTHER THINGS THAT WOULD BE OF CLINICAL VALUE. YOU'RE RIGHT. WE NEED TO TALK ABOUT THAT BETTER. >> THIS IS THE GUY THAT WAS THE EXPERT IN THE HUMAN GENOME PROJECT. >> IT WAS OVER PROMSING. IF YOU'RE GOING TO DO A LARGE DISCOVERY PROJECT LIKE THIS AND COVER A LOT OF SPACE, YOU HAVE TO UNDERSTAND THAT AND HAVE TO SET YOUR SIGHTS CORRECTLY. NOT ALL OF THE DAT ARGOING TO BE PERFECT. YOU'RE DOING SURVEYS. YOU WILL BE ABLE TO GENERATE LOTS OF HYPOTHESIS FROM THAT AND WHAT YOU WILL FIND THEN, SOME OF THE DETAILS OF THE DATA, WERE ACTUALLY WRONG. NEVERTHELESS, YOU WERE ABLE TO GENERATE THOSE HYPOTHESIS AND BRING THE FIELD FORWARD. IF YOU TRY TO BRING THIS TO THE CLINIC TOO QUICKLY. YOU'RE PROBABLY GOING TO BE DISAPPOINTED. WE CERTAINLY COVERED A LOT OF GROUND, AND GOTTEN INFORMATION FROM YOU TO TRY AND UNDERSTAND WHAT OUR NEXT STEP SHOULD BE AND I'D LIKE TO MOVE ON. TO IA COUPLE ADDITIONAL QUESTIONS. ONE OF WHICH FOCUSES ON. YEAH, I WAS GOING TO START WITH ULD THE FOCUS BE FOR FUTURE WORKSHOP. SO THIS WORKSHOP IS FOCUSED ON OMEX TECHNOLOGY AND IMAGING AND WE HEARD A LOT DIFFERENT AREAS WHERE THERE NEEDS MORE CLARITY. SOME OF THE THINGS THAT CAME UP WAS A BETTER NEED FOR USE OF NEED -- [INDISCERNIBLE] >> HOW ABOUT BLA FEEL TYPE. AND MARKERS OF THE FIELD TYPES. MARKER. GETTINGS BETTER AND BETTER AND I THINK FOR THE TROPOBLAST RESEARCH FIELD I THINK THAT NEEDS TO BE DONE. >> PLACENTAL PLASTICITY. IT'S A HIGHLY ADAPTABLE ORGAN WE DON'T UNDERSTAND. NEXT MEETING WE TALK ABOUT IT THE PATHWAY. THE PATHWAY. IN THIS MEETING WE HEARD A LOT OF THE GENOMEIC. I CAN TELL EVERYBODY IN THIS ROOM, OUR GROUP HAS BEEN WORKING OUT THE -- TURN OUT, PIE LOOKING FOR SINGLE OMIX IS A VERY DIFFICULT TO DETERMINE, WHICH IS WHY IT'S REALLY ON THE LINE THE CONDITION. AND WHEN WE STARTED, I CAN SHARE ALREADY PUBLISHED, WHEN WE STARTED WE WORKED AND WE COMPARE WHERE THE NORMAL 4 TURNS FOR THE FORETURN AND WE HAVE GOT A WHOLE A LOT OF SEQUENCING. IT'S VERY DIFFICULT TO DETERMINE WHO IS THE REAL MAGNITUDE UNDERLINE. AND WE DID TRY ORIENTATION FIRST EFFORT, TRYING TO MERGE DIFFERENT OMEX TOGETHER TOGETHER. WE COME UP PATHWAYS, FROM DIFFERENT APPROACH. DIFFERENT THAT I REALLY SUGGEST, AND I THINK IS A GOOD APPROACH. NOT FOR THIS IS PROBABLY GOING TO BE LEADING TO THE COMPLEX DISEASE, THE WAY WE SHOULD HAVE MAYBE WE SHOULD TRIAL OR SOMETHING. >> IN-VITRO IMAGING THAT WE SAW TODAY. SORT OF. YOU HAVE INTEREST IN DEVELOPING. DOING DRUG DISCOVERY OR PHARMACEUTICAL ANIMAL MODELS AND TECHNOLOGY. ANIMAL MODELS AND TECHNOLOGY LIKE STEM CELLS. FOLLOW THE PLACENTA GROWING. THERE TO REOFFER THE INTERNETRATE TOXICOLOGY AND PLACENTAL RESPONSE TO ENVIRONMENTAL. SO I HAVE ABOUT 10 OR 12 WORKSHOPS IN MIND. WHAT I'D LIKE TO REALLY SUPPORT WHAT VIRGINIA SAID, WE HAVE STUDIED HUMA HUMAN -- [INDISCERNIBLE]. THE KEY TO UNDERSTANDING THE PATHOLOGY IS THE UNDERSTANDING THE DEVELOPMENT BECAUSE UNLESS WE UNDERSTAND THE ROAD, THE PLACENTA GOES DOWN, WE'RE NOT GOING TO UNDERSTAND HOW IT GETS DERAILED. THE OTHER THING I WOULD LIKE TO PUT A PLUG IN FOR IS ENVIRONMENTAL WORK. WE HAVE DONE SOME WORK IN OUR GROUP AND I'VE WATCHED THE WORK OF OTHERS. AND IT'S CLEAR, ENVIRONMENTAL CHEMICALS AND EXPOSURES HAVE LOTS OF ACTIVITY, WITH REGARDS TO PLACENTAL CELLS AND I THINK THIS IS REALLY AN IMPORTANT AREA OF WORK THAT WE SHOULD ALL BE BE INVOLVE IN BECAUSE WE'RE BATHED IN THESE CHEMICALS, AND WE DO NOT KNOW WHAT THEY'RE TO GO, ESPECIALLY DURING DEVELOPMENT. AND FINALLY, BE I KNOW EVERY TIME I TALK TO PATHOLOGISTS, I LEARN SO MUCH AND I THINK HAVING A WORKSHOP ON PLACENTA PATHOLOGY AND CHEMICAL QUALIFYINGS, WE TALK ABOUT PRETERM LABOR BUT THERE'S SO MANY INCREASING PATHOLOGIES, SUCH AS THE PROCRETAS AND OTHER PATHOLOGIES, THAT DON'T AS MUCH EFFECT PEOPLE IF THE U.S. BUT I THINK CAN BE INCREDIBLY INFORMATIVE SUCH ASTHMA LAYERIA AND OTHER DISEASES OF THE PLACENTA THAT IMPACT PEOPLE IN OTHER COUNTRIES. >> SINCE ENVIRONMENT IS COMING UP SEVERAL TIMES. REMEMBER TO PAY TAKEN TO THE ENVIRONMENTAL ASPECT THAT'S CURRENTLY OUT THERE. AN OPPORTUNITY TO GET FUNDED, NOT JUST DISCUSSED. >> THIS IS A PIGGY BAG SUGGESTION. I WOULD SAY, IT SHOULD BE BIOMATTICS AND WE BRING IN COMPUTATIONAL BIOLOGIST AND STATISTICIANSES. >> THE MAIN DECISIONS OF THE PLACENTA THAT OF COURSE RECURRING IN THIS MEETING HAS BEEN PRECONCIA AND [INDISCERNIBLE] I ONEER, I HAVE REALLY VERY LITTLE DOUBT ABOUT HOW CAN WE DETECT PRECLAMCIA BY THE DIFFERENT WAYS WE HAVE BEEN TALKING ABOUT. NOW, I THINK THAT ALSO WE CAN DETECTABLE RIGS THAT CAN BE RELATED TO IUGR. HOWEVER, WHAT IS RELEVANT TO THE MOTHER IS NOT TO HAVE A LOW BIRTH WEIGHT BABY. IT IS WHETHER THAT BABY BE LATER ON EVERY ON THE YEARS IS GOING TO BE NORMAL OR ABNORMAL IN TERMS OF WHAT WE KNOW IS FIELD PROGRAMMING, AFFECTING THE BRAIN, AND THE CARDIOVASCULAR SYSTEM. WHAT I'M JUST SAYING IS ALTHOUGH THE PLACENTA IS REALLY RELEVANT ORGAN, I THINK IT SHOULD BE REINFORCED AS WELL. OTHER TECHNOLOGIES TO STUDY THE FETUS. FEELAL PAIN IMAGING, WHICH I THINK IS VERY RELEVANT. MAYBE THE PLACENTA BEING SHOW ALTERATIONS BUT WHAT IS RELEVANT FOR THE LIFE OF THAT BABY IS WHETHER THE DEVELOPMENT IS GOING TO BE NORMAL OR NOT. AND I CAN HARDLY SEE THAT COMING FROM THE PLACENTA, WITH THE TECHNOLOGY THAT WE'VE BEEN BEEN DISCUSSING. THANK YOU. >> TEASE TOPIC BEES ARE GREAT AND ALL OF THESE WORK UPON SHOWS WESTBOUND BE WONDERFUL TO HAVE. WE'RE REALLY TRYING TO LOOKER AT WORKSHOPS TO ACHIEVE THE GOAL OF UNDERSTANDING THE HUMAN PLACENTA STRUCTURE AND FUNCTION IN REAL TIME. SOME OF THESE ARE GOING TO BE MORE RELEVANT TO OTHER ASPECTS AT NICHD AND WE WILL PASS THOSE ON. BUT I'M RECORDING. >> MAYBE PIGGYBACKING ON SOMETHING SOMEONE ELSE SAID. BUT KNOWING THE LIFE CYCLE AND THE LIFE SPAN OF THE PLACENTA IS REALLY IMPORTANT. SO ONE OF MY COLLEAGUES IS I SAG UNLIKE OTHER ORGANS, THE PLACENTA'S ENTIRE LIFE IS SPENT IN 40 WEEKS BUT WHAT THE FUNCTION IS OVER THOSE 40 WEEKS, CHANGES OVER TIME, AND I THINK THAT'S MAYBE BEEN UNDER EMPHASIZED, GIVEN THAT WE'RE TALKING ABOUT NAP SHOTS IN TIME. DIFFERENT CELL TYPES IN THE PLACENTA. I WOULD SUGGEST TO INCLUDE A CELL TYPE THAT'S CURRENTLY DEEMED AN IMMUNE CELL TYPE AND NOT SAFETY CENSUS BUREAU TO A LOT OF PEOPLE I WOULD REALLY SUGGEST THEY CAN BE CALLED SOMETHING ELSE THAT DOESN'T BECAUSE WE HARDLY RECOGNIZE THEM. WITHOUT THEM, THERE'S NO PLACENTA THAT'S PRETTY CLEAR. SO MOST IMPORTANT AND VERY URN STUDIED, ESPECIALLY IN HUMANS. VERY UNDER STUDIED CELL TYPE THAT IS IMPORTANT DURING THE DEVELOPMENT OF THE PLACENTA. SO EVEN THOUGH THEY FALL UNDER IMMUNE, I'M NOT SURE THAT'S ACTUALLY ADEQUATE IN THAT SETTING. THEY'RE JUST IMPORTANT TO INCLUDE. IN. >> IN THIS WHOLE PROCESS, WHAT WE HAVE OVER LOOKED, IS BECAUSE WE'RE ANTICIPATING THE BABY TO BE DELIVERED AND WE'RE FOLLOW BEING UP WITH PERHAPS PARTIALLY COMPROMISED PREGNANCY BUT I BELIEVE PREGNANCY LOSS, ESPECIALLY VERY EARLY IS A HUGE FACTOR RELATED TO PLACENTA FUNCTION, WHETHER FROM AUTOIMMUNE DISEASE OR OTHERS. AND WE REALLY DIDN'T FOCUS ON THAT EARLY PREGNANCY LOSS THAT MAY IN FACT BE AN IMPORTANT CONTRIBUTION IS MAKING. >> I THINK THAT WE SHOULD SPEND SOME TIME, THINK BEING HOW ARE WE GOING TO COMPRESS OR STORE ALL OF THIS IMAGING INFERRING. WE'RE GOING TO BE SUCCESSFUL IN BEING ABLE TO LONGITUDINALLY, LOOK AT THE PLACENTA, AS A FUNKAL CHARACTERISTIC IN OUR DEVELOPMENT. WHAT WE NEED TO DO IS FIND WAYS TO STORE THAT INFORMATION SO THAT IT'S USABLE. WHAT MADE ME THINK ABOUT THAT IS THE BEAUTIFUL LIVE CELL IMAGING, CAN YOU ROTATE AND LOOK AT. SOMETHING THAT KEYS THE PLACENTA INSTRUCT IN YOUR MIND, HOPEFULLY, WITH SOME REGIONAL, FUNCTIONAL CHARACTERS THAT MIGHT BE INFORMATIVE TO LOOK AT QUESTIONS LIKE THE GREAT GRAND BURTON'S [INDISCERNIBLE] AND WHAT THE AFFECT IS LATER ON THE SECOND THING IS SPIRAL [INDISCERNIBLE] DEVELOP AND HOW TO WE UNDERSTAND THAT BETTER, WHAT EFFECTS US FROM SUSAN FISHER'S WORK AND OTHERS IN THIS FIELD. I THINK WE NEED TO SPEND IN TIME LOOKING AT THAT AS WELL. >> ALL RIGHT. WONDERFUL. SO WE WANTED TO GIVE A COUPLE OF MEETING TAKE AWAYS. FORTUNATELY, I'LL REALLY SHORT SO IT DOESN'T MATTER WHERE I STAND. WE WANTED TO GIVE A COUPLE MEETING TAKE AWAYINGS AND TALK THINK ONE OF THE MODEL VALIDATION TEST REMARKABLE THINGS OVER THE LAST TWO DAYS HAS BEEN THE INCREDIBLE ENTHUSIASM, DEDICATION AND COMMITMENT THAT WE HAVE HAD HAD IN THE ROOM. I'D LIKE A SHOW OF HANDS, DID YOU LIKE THE SYSTEM? WERE YOU ABLE TO TALK AMONG SMALL GROUPS SHOW OF HANDS YES, SHOW OF HANDS, NO. WE'LL KEEP THAT IN MIND FOR NEXT YEAR. WE APPRECIATE THE EMPHASIZE THAT MANY PEOPLE HAVE HAD ON THE FEED TO HAVE MULTIPLE DISCIPLINES INVOLVED, AND MULTIPLE STAKEHOLDERS AND WE ABSOLUTELY AGREE WITH YOU. WE WANT TO REMIND YOU THAT YOU CAN E MILE US ANY TIME WITH ADDITIONAL MENS OR QUESTIONS. NICHDHPP@MAIL.NIH.GOV. >> PEOPLE USE THAT SAME ADDRESS TO LET DAVE WEINBERG AND OTHER RESOURCES THAT OUT TO BE ACCUMULATED TOGETHER. >> YOU CAN USE DAVID'S E-MAIL WHICH IS IN THE RFA'S. IT WAS WONDERFUL THAT DAVID PUT DOWN AS HAD NUMBER BE ONE THING TO DO TO GATHER THOSE RESOURCES. I WOULD ASK YOU TO PLEASE HELP HIM WITH THAT. SOME OF YOU DID IDENTIFY THAT, SOME RESOURCES AND BROUGHT THOSE UP. SOME OF WHICH I CAN GUESS THAT DAVID WASN'T AWARE OF. SO IF YOU CAN PLEASE SHOOT HIM AN E-MAIL WITH THOSE RESOURCES, YOU ALREADY KNOW SO THAT HE CAN INCLUDE THEM, THAT WOULD BE INCREDIBLY HELPFUL. WE HAVE THE APPLICATIONS IN HOUSE. AND LOOK FORWARD TO THE WONDERFUL SCORES THAT WILL COME AND WE WILL BE ABLE TO ISSUE THOSE AWARDS. WE LOOK FORWARD TO THE APPLICATIONS YOU WILL BE SUDDENNING IN. HOPEFULLY, MANY OF YOU AND IF NOT, REMEMBER, YOU MIGHT BE TAPPED TO BE BE A REVIEWER. THAT MIGHT ENCOURAGING YOU TO WE ARE HOPEFUL, BASED ON SOME OF THE DISCUSSIONS WE HAVE HAD TODAY, AS WELL AS DISCUSSIONS WE HAVE HAD INTERNALLY, WE HAVE FUTURE RFA'S TO UNDERSTAND THE FUNCTION IN REAL TIME AND I WANT TO REMIND YOU, ONE AGAIN, WE WILL CONTINUE TO SUPPORT NON-HPP PLACENTAL BIOLOGY RESEARCH AT WE ARE CLEARLY VERY, VERY INTERESTED IN HUMAN PLACENTAL BIOLOGY AND THOSE GRANTS AND APPLICATIONS, SEND THEM IN, WE ENCOURAGING YOU TO DO SO. WE ALSO DO ANTICIPATE THAT WE WILL HAVE HPP 3. MEANING A WORKSHOP NEXT YEAR, PROBABLY AROUND THE SAME TIME AND NOT CERTAIN WHAT THAT TOPIC WILL BE AT THIS POINT, OR TOPICS. I APPRECIATE ALL OF THE IDEA THAT IS YOU HAVE GIVEN US. CERTAINLY, WE WILL WANT THAT TOPIC TO BE ONE THAT IS CENTRAL OF GETTING TO OUR GOAL OF THE HUMAN PLACENTA PROJECT AND I LOOK FORWARD TO DISCUSING THAT INTERNALLY, AND LOOKING AT ANY ADDITIONAL MENS OR RECOMMENDATIONS THAT YOU HAVE TO SEND TO US. >> I THINK THE ONE BE THING THAT I WOULD ADD BESIDES JUST THINKING YOU IS THERE'S CLEARLY BEEN A LOT OF CALLS HERE. WE HAVE HAD PREDISCUSSION ABOUT SOME OF THE STANDARDIZATION ET CETERA. WE'RE GOING WE'RE GOING TO BE TALKING MORE AND IT'S HARD TO IMAGINE, RA NOT WANTING STARCHIZATION AS PART OF THIS AND IT'S HARD TO IMAGINE DOING THAT, WITHOUT A HECK OF A LOT OF INPUT, IF NOT, LEADERSHIP FROM FOLKS IN THIS ROOM AND SOME OTHER PEOPLE AS WELL. IF YOU THINK ABOUT THE FUTURE OF THE PROJECT, REALIZE WE MAY BE CALL BEING YOU ON YOUR EXPE, ET CETERA, ET CETERA. BEYOND, IT'S NOT ALL SIMPLY ABOUT FUNNING AVAILABILITY OF THE CLEARLY, THAT'S PART OF IT. BUT IT'S BOTH TO INFORM THE PROCESS AND AGREE ABOUT SOME OF THE STASHEDDIZATION THINGS I THINK PEOPLE HAVE WISELY BEEN CALLING FOR. THEY'RE REALLY GOING TO RELY ON YOUR EXPERTISE AND THOSE OF YOUR COLLEAGUES SO WHEN YOU GET E-MAILS FROM US ABOUT THAT, PLEASE THINK POSITIVELY ABOUT THE REQUEST AND WE'LL HAVE TO FIGURE OUT HOW THAT IS STRUCTURE, ET CETERA. ET CETERA. BUT I THINK THAT IS SOMETHING FOR THE MANY REASONS PEOPLE HAVE CITED, IT'S HARD TO DO THAT KIND OF WORK TOO EARLY AND IT'S EASY TO DO IT AFTER, YOU KNOW, THE HORSES LEFT THE BARN. WE DON'T WANT TO MAKE THAT MISTAKE. NOT IN THE TOO DISTANT FUTURE, WE'LL BE REACHING OUT TO FOLKS ABOUT THAT. PLEASE GIVE THAT SOME THOUGHT WHEN YOU GET INVITATION AND I WANT TO THANK YOU. IT'S BEEN WONDERFUL TO SEAT DEGREE OF ENTHUSIASM INVESTMENT, WILLINGNESS OF PEOPLE TO LOOK AT THINGS, THROUGH MAYBE DIFFERENT LENS THAN THE ONCE THEY HAVE USUALLY APPLIED TO THIS SUBJECT. TO THINK BE BROKEDLY IN A VERY INTEGRATED FASHION. I'M REALLY EXCITED TO SEE THE APPLICATION THAT COME IN, NOT JUST TO SEE WHAT WE CAN AWARD, BUT THE KIND OF THINKING THAT'S BEEN GOING ON THE HALLWAYS OVER THE LAST COUPLE OF DAYS. IT'S GOING TO BE WONDERFUL TO SEE THAT COMMITTED TO PAPER. PLEASE GO HOME AND BE SAFE, AND KEEP DOING THE KIND OF WORK. THAT IS THE REASON ALL OF US ARE GATHERED HERE TOGETHER. THE TECHNOLOGY CAN BE USED FOR OTHER KINDS OF INTERVENTIONS CAN REALLY KNOCK A DIFFERENCE IN TERMS OF HEALTH AND WELFARE. THANK YOU VERY MUCH FOR BEING HERE.