2020-11-16T15:24:02-06:00 2019-12-31 910189318 MOSS ADAMS LLP 4747 EXECUTIVE DR SUITE 1300 SAN DIEGO CA 92121 990 2019-01-01 521842938 J CRAIG VENTER INSTITUTE JCRA 8582001800 4120 CAPRICORN LANE LA JOLLA CA 92037 JOHN CRAIG VENTER CHAIRMAN AND CEO 8582001800 2020-11-16 1 PATRICIA J MAYER P00188643 8586271400 76.93.182.132 2020-11-16 15:16:25 PS P DA39A3EE5E6B4B0D3255BFEF95601890AFD80709 6B76EF6C5C90AF9682C9A74185CCBCF07F3880A4 2019 2021-01-29 14:40:06Z JOHN CRAIG VENTER 4120 CAPRICORN LANE LA JOLLA CA 92037 82836259 0 X WWW.JCVI.ORG X 1993 MD JCVI IS ADVANCING THE SCIENCE OF GENOMICS THROUGH BOLD INNOVATIONS. OUR MISSION IS TO UNDERSTAND MOREABOUT THE BIOLOGICAL WORLD, AND TO DEVELOP UNIQUE INSIGHTS AND ANSWERSABOUT DISEASE, HEALTH, AND THE ENVIRONMENT FOR THE BENEFIT OF ALL. 9 6 230 6 6009 0 30012027 21442951 1188068 420120 13969741 1920374 33254 6009 45203090 23789454 2164870 2586471 0 0 22035831 21730028 0 0 663191 14610802 13109263 38811503 37425762 6391587 -13636308 117806544 108987608 35083973 35167258 82722571 73820350 X JCVI IS ADVANCING THE SCIENCE OF GENOMICS THROUGH BOLD INNOVATIONS. OUR MISSION IS TO UNDERSTAND MORE ABOUT THE BIOLOGICAL WORLD, AND TO DEVELOP UNIQUE INSIGHTS AND ANSWERS ABOUT DISEASE, HEALTH, AND THE ENVIRONMENT FOR THE BENEFIT OF ALL. 0 0 13618968 2586471 0 DEPARTMENT OF HEALTH AND HUMAN SERVICES (DHHS)DURING 2019, JCVI HAD MULTIPLE ACTIVE RESEARCH GRANTS AND CONTRACTS FROM AGENCIES WITHIN THE DHHS. AMONG THESE WAS JCVI'S LARGEST FUNDED RESEARCH PROGRAM, A 5-YEAR U54 GRANT FROM THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID/NIH) TO SERVE AS A DESIGNATED GENOME CENTER FOR INFECTIOUS DISEASES (GCID). THE GCID PROGRAM SCOPE INCLUDES ANALYSIS OF VIRAL, BACTERIAL, AND PARASITE PATHOGENS. THE BACTERIAL AND PARASITE PROGRAMS HAVE A PARTICULAR EMPHASES ON ANTIMICROBIAL RESISTANCE. THE BACTERIAL PROGRAM IS FOCUSED ON THE EVOLUTION AND TRANSMISSION OF CARBAPENEM-RESISTANT ENTEROBACTERIACEAE AND OTHER GRAM-NEGATIVE BACTERIA. ALL GENOME SEQUENCE DATA PRODUCED WITH GCID FUNDING IS RAPIDLY DEPOSITED IN PUBLIC REPOSITORIES TO PROMOTE THE WIDEST POSSIBLE USE AMONG RESEARCH SCIENTISTS. JCVI IS THE PRIMARY LEAD OF A LARGE 5-YEAR COLLABORATIVE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS/NIH) U01 GRANT WITH THE GOAL TO DEVELOP, VALIDATE AND DISSEMINATE A COMPUTATIONAL INFRASTRUCTURE FOR UNBIASED ANALYSIS OF CYTOMETRY DATA FOR BOTH DIAGNOSTIC AND DISCOVERY APPLICATIONS THAT COULD HELP OVERCOME THE CURRENT LIMITATIONS OF MANUAL ANALYSIS AND PROVIDE FOR MORE EFFICIENT, OBJECTIVE, ACCURATE, AND REPRODUCIBLE ANALYSIS OF CYTOMETRY DATA. FLOW CYTOMETRY ANALYSIS IS WIDELY USED IN TRANSLATIONAL RESEARCH LAB TO EXPLORE THE MECHANISMS OF NORMAL AND ABNORMAL BIOLOGICAL PROCESSES AND IN THE CLINICAL DIAGNOSTIC LAB FOR THE IDENTIFICATION AND CLASSIFICATION OF BLOOD-BORNE MALIGNANCIES. HOWEVER, THE CURRENT PRACTICE FOR CYTOMETRY DATA ANALYSIS RELIES ON SUBJECTIVE AND AD HOC "MANUAL GATING". THE PROJECT TEAM OF JCVI, THE UNIVERSITY OF CALIFORNIA, SAN DIEGO (UCSD), THE UNIVERSITY OF CALIFORNIA, IRVINE (UCI), AND STANFORD UNIVERSITY COLLABORATED TO CONTINUE IMPROVING THE ACCESSIBILITY, FUNCTIONALITY, AND USABILITY OF THE PROPOSED INFRASTRUCTURE. THE PROJECT TEAMS ASSEMBLED MULTIPLE FLOW CYTOMETRY DATASETS FROM IMPORTANT BIOMEDICAL PROJECTS CONDUCTED BY TRANSLATIONAL RESEARCHERS AT UC IRVINE AND FROM THE CLINICAL DIAGNOSTICS LAB AT UCSD. THE JCVI TEAM PROCESSED AND ANALYZED THE DATASETS USING THE COMPUTATIONAL INFRASTRUCTURE AND VALIDATED THE ANALYSIS RESULTS USING FOLLOW-UP STUDIES. THE COMPUTATIONAL ANALYSES OF THESE DATASETS HAVE IDENTIFIED NOVEL CELL SUBSETS FROM HUMAN LEUKOCYTES FOR INDEPENDENT ASTHMA RESEARCH PROJECTS BEING CONDUCTED AT PEDIATRICS OF UC IRVINE. THE ANALYSES HAVE ALSO IDENTIFIED A NOVEL COMBINATION OF CELL SURFACE MARKERS FOR PRECISION DIAGNOSIS OF THE CHRONIC LYMPHOCYTIC LEUKEMIA BASED ON THE CLINICAL FLOW CYTOMETRY DATA PROVIDED BY UCSD. THE RESULTS AND FINDINGS HAVE BEEN PUBLISHED ON PEER-REVIEWED JOURNALS OR REPORTED AT SCIENTIFIC CONFERENCES. THE PROJECT TEAM HAVE ALSO BEEN TRAINING THE TRANSLATIONAL RESEARCHERS OF UCI PEDIATRICS AND HEMATOPATHOLOGISTS OF UCSD PATHOLOGY FOR USING THE ADVANCED DATA ANALYTICS TOOLS ON THE COMPUTATIONAL INFRASTRUCTURE THROUGH IN-PERSON SITE VISITS AND WEBEX MEETINGS.ANTIBIOTIC RESISTANCE IS ONE OF THE BIGGEST PUBLIC HEALTH PROBLEMS OF OUR TIME. JCVI IN COLLABORATION WITH NORTHEASTERN UNIVERSITY HAVE DEVELOPED NEW METHODS TO GROW AND EXPLOIT PREVIOUSLY UNCHARACTERIZED MICROBES. JCVI HAS DEVELOPED A TRANSCRIPTION-BASED PLATFORM THAT BIOINFORMATICALLY PREDICTS WHETHER NEW POTENTIAL COMPOUNDS ARE EXPRESSING ANTIBIOTIC PROPERTIES WITH NOVEL MECHANISMS OF ACTION. PROMISING COMPOUNDS ARE VALIDATED AND BECOME LEAD ANTIMICROBIAL COMPOUNDS FOR FURTHER STUDY. JCVI, IN COLLABORATION WITH NORTHROP GRUMMAN (THROUGH SEPTEMBER 14, 2019) AND THE UNIVERSITY OF CHICAGO (SINCE SEPTEMBER 15, 2019), SERVES AS THE MAIN DEVELOPER OF THE VIRAL PATHOGEN RESOURCE (WWW.VIPRBRC.ORG) AND THE INFLUENZA RESEARCH DATABASE (WWW.FLUDB.ORG). THESE RESOURCES SERVE AS FREE PUBLIC PORTALS TO A WIDE RANGE OF INFORMATION, DATA, AND ANALYTICAL TOOLS FOR INTERPRETING VIRAL GENOMES IN THE CONTEXT OF DISEASE. OVER 3000 RESEARCHERS THROUGHOUT THE WORLD USE THESE RESOURCES EVERY WEEK. SEVERAL ADDITIONAL DHHS GRANTS AT JCVI ARE RELATED TO HUMAN MICROBIOME STUDIES. THE MICROBIOME IS THE COLLECTION OF MICROBES THAT LIVE IN AND ON THE HUMAN BODY; THESE SPECIES HAVE RECEIVED CONSIDERABLE ATTENTION IN RECENT YEARS BECAUSE A NEW APPRECIATION OF THE COMPLEX ROLES THAT THEY PLAY IN HEALTH AND DISEASE. SOME OF THESE STUDIES ARE AIMED AT BASIC CHARACTERIZATION OF THE COMPOSITION AND ACTIVITY OF THE MICROBIOME, WHILE OTHERS SEEK TO UNDERSTAND THE CONTRIBUTION OF THE MICROBIOME TO THE DEVELOPMENT OF VARIOUS DISEASES INCLUDING ALCOHOLIC HEPATITIS, TYPE 1 DIABETES, DENTAL CARIES, DIARRHEA, AND ESOPHAGEAL CANCER, AMONG OTHERS. IN COLLABORATION WITH THE SANFORD BURNHAM PREBYS INSTITUTE, THE JCVI IS DEVELOPING METHODS TO IDENTIFY NEW DRUGS THAT SPECIFICALLY TARGET AN ENZYME IN THE MALARIA PARASITE THAT WE KNOW IS ESSENTIAL FOR THE GROWTH OF THE PARASITE. MALARIA, A PARASITIC DISEASE TRANSMITTED BY MOSQUITOES, IS STILL A MAJOR THREAT TO PUBLIC HEALTH AND ECONOMIC DEVELOPMENT IN THE TROPICAL AND SUB-TROPICAL REGIONS OF THE GLOBE, AS WELL AS TO TRAVELERS TO THESE AREAS FROM THE DEVELOPED WORLD. CONTINUAL DEVELOPMENT OF NEW DRUGS AND VACCINES IS ESSENTIAL TO ENSURE THAT MALARIA CONTROL IS MAINTAINED TO PREVENT UNNECESSARY ILLNESS AND LOSS OF LIFE. THIS PROJECT HAS SHOWN THAT ONE PARTICULAR CHEMICAL THAT BLOCKS THIS ENZYME CAN KILL MALARIA PARASITES IN THE LABORATORY. THIS COLLABORATION IS NOW DEVELOPING A LABORATORY TEST THAT WE CAN USE TO SCREEN THOUSANDS OF CHEMICALS TO FIND THOSE THAT ARE MORE EFFECTIVE AT KILLING MALARIA PARASITES THAN THE FIRST CHEMICAL. THE INSTITUTE ALSO PARTICIPATES IN THE H3AFRICA PROGRAM VIA A COLLABORATION THE UNIVERSITY OF CAPE TOWN, SOUTH AFRICA, TO TRAIN COLLABORATORS IN HUMAN MICROBIOME ANALYSIS. THE PROGRAM IS SPONSORED BY THE NIH COMMON FUND TO BRING TECHNOLOGICAL RESOURCES AND TRAINING IN A CAPITAL INVESTMENT-INTENSIVE FIELD (GENOMICS) TO THE AFRICAN CONTINENT VIA COLLABORATIONS WITH US SCIENTISTS WITH EXPERTISE IN THIS FIELD. 2528127 0 0 JCVI IS THE RECIPIENT OF A LARGE COLLABORATIVE ASSISTANCE AWARD FROM THE US DEPARTMENT OF ENERGY. AWARDED TO THE VALUE OF $10.7M, THE JCVI AND ITS COLLABORATORS, COLORADO STATE UNIVERSITY, VANDERBILT UNIVERSITY AND THE UNIVERSITY OF CALIFORNIA, SAN DIEGO, SEEK TO LEVERAGE SIGNIFICANT RECENT ADVANCES IN DIATOM GENOME ENGINEERING AND METABOLIC MODELING; INCLUDING THE ABILITY TO INTRODUCE CHROMOSOME-LIKE EXPRESSION PLATFORMS, WHICH SUBSTANTIALLY ADVANCE POSSIBILITIES FOR HIGH-THROUGHPUT GENERATION AND SCREENING OF GENETICALLY ENGINEERED DIATOMS. RESEARCH PROPOSED HERE WILL RESULT IN DRAMATIC IMPROVEMENTS IN THE PREDICATIVE CAPACITY OF EXISTING GENOME SCALE METABOLIC MODELS OF DIATOM METABOLISM. FOR THE FIRST TIME ON A LARGE SCALE, FLUXOMICS, WHICH IS COMPOUND SPECIFIC INCORPORATION OF AN ISOTOPICALLY-LABELED FEEDSTOCK, WILL BE USED TO PROVIDE BETTER FIRST STEP CONSTRAINTS ON CO2 ASSIMILATION OF IN DIATOMS. STATE-OF-THE-ART HIGH THROUGHPUT IN VITRO EXAMINATIONS OF NEARLY ALL 200 DIATOM TRANSCRIPTION FACTORS WILL BE CONDUCTED TO BETTER UNDERSTAND REGULATORY ARCHITECTURE UNDERLYING DIATOM METABOLISM AS WELL AS SERVE AS A SOURCE FOR NEW TOOLS FOR GENOME ENGINEERING. TAKEN TOGETHER, RESEARCH PROPOSED HERE WILL ADDRESS CURRENTLY LIMITING BOTTLENECKS THROUGH FOSTERING STATE-OF-THE-ART INTEGRATION OF GENOME-SCALE MODELING WITH GENOME ENGINEERING TO OPTIMIZE ENERGY AND METABOLTE FLUX THROUGH SUBCELLULAR COMPARTMENTS TO PROMOTE EFFICIENT PRODUCTION OF HIGH VALUE AND FUEL-RELATED METABOLITES. 2953065 0 0 DURING 2019, JCVI HAD MULTIPLE ACTIVE RESEARCH AWARDS FROM THE DEPARTMENT OF DEFENSE (DOD). THESE AWARDS FOCUS ON THE UNDERSTANDING OF POLYMICROBIAL INFECTIONS IN WOUNDS, THE DEVELOPMENT OF SYNTHETIC GENOMIC TECHNOLOGIES FOR MANIPULATION OF CHROMOSOMES AND GENOMES AND FOR THE DEVELOPMENT OF SAFE METHODS FOR DNA ISOLATION AND ANALYSIS FROM BIOTHREAT AGENTS. FUNDED BY THE DEFENSE ADVANCED RESEARCH PROJECTS AGENCY (DARPA) BIOLOGICAL ROBUSTNESS IN COMPLEX SETTINGS (BRICS) PHASE II PROGRAM, THE JCVI IS USING INNOVATIVE RESEARCH APPROACHES TO DEVELOP A MICROBIOME FORENSIC MICROBIAL SYSTEM (FMS) THAT WILL DETECT WHETHER AND WHEN AN OBJECT ENCOUNTERED A PARTICULAR ENVIRONMENT. IN ADDITION, THE FMS SHOULD CONTAIN A SAFETY MECHANISM THAT WILL ENSURE ITS REMOVAL FROM THE ENVIRONMENT FOR CONTAINMENT. THIS FMS WILL ULTIMATELY ALLOW FOR BROAD RANGE FORENSIC APPLICATIONS OF SYNTHETIC MICROBIOMES THAT INCLUDE, BUT ARE NOT LIMITED TO, GEOSOURCING, TRACKING, AND CRIME SCENE INVESTIGATIONS. THE JCVI IS PROVIDING LONGITUDINAL DNA METHYLATION PROFILING, LONGITUDINAL HISTONE MODIFICATION PROFILING AND LONGITUDINAL METABOLOME PROFILING ON MULTIPLE SAMPLES IN COLLABORATION WITH DARPA FOR THE SELECTING ELITE-PERFORMERS WITH LONGITUDINAL EPIGENOMIC CHARCTERIZATION AND TRACKING (SELECT) PROJECT.WOUND MICROBIOME PROJECT - CHRONIC WOUNDS ARE WOUNDS THAT FAIL TO HEAL AFTER 3 MONTHS UNDER STANDARD OF CARE WOUND MANAGEMENT. THE GOAL OF THIS DOD STUDY IS TO GAIN A BETTER UNDERSTANDING OF THE DIFFERENT CLASSES OF MICROBES THAT COULD BE PRESENT IN HUMAN CHRONIC WOUNDS (I.E. THE WOUND MICROBIOME), AND ASK WHETHER SPECIFIC MICROBES OR MICROBIAL COMMUNITIES ARE ASSOCIATED WITH NON-HEALING WOUNDS. NEXT GENERATION SEQUENCING WILL BE USED TO IDENTIFY AND CATALOG THE MICROBIAL SPECIES OF BACTERIA, FUNGI, AND VIRUSES THAT ARE PRESENT IN CHRONIC WOUND SPECIMENS. COMPUTATIONAL AND BIOINFORMATICS ANALYSES OF THE MICROBIAL COMMUNITY DNA SEQUENCES WILL BE CARRIED OUT TO CHARACTERIZE THE PRESENCE ANY PATHOGENIC, VIRULENCE, AND ANTIMICROBIAL RESISTANCE-RELATED GENES AND PATHWAYS. THE EVENTUAL GOAL IS TO IDENTIFY ANY PATHOGENIC SPECIES OR FEATURES THAT ARE ASSOCIATED WITH NON-HEALING WOUNDS, AND COULD BE USED AS DIAGNOSTIC AND TREATMENT TARGETS OF CHRONIC WOUNDS. SYNTHETIC ENGINEERING OF BACTERIOPHAGE FOR TREATMENT OF WOUND INFECTIONS ANTIMICROBIAL RESISTANCE IN BACTERIAL PATHOGENS IS STEADILY INCREASING AND RECOGNIZED AS ONE OF THE GREATEST THREATS TO GLOBAL PUBLIC HEALTH. SHORTLY AFTER THE BEGINNING OF THE WARS IN AFGHANISTAN AND IRAQ, THE MILITARY HEALTH SYSTEM EXPERIENCED A MAJOR INCREASE IN WOUND AND HEALTHCARE-ASSOCIATED INFECTIONS CAUSED BY MULTIDRUG RESISTANT ORGANISMS (MDROS) WITH EXTREMELY LIMITED TREATMENT OPTIONS. FUNDED THROUGH THE US MEDICAL RESEARCH ACQUISITION ACTIVITY, THE JCVI IN COLLABORATION WITH THE MILITARY AND THE WALTER REED ARMY INSTITITUTE OF RESEARCH, IS COLLABORATING WITH THE GOAL TO DESIGN, BUILD, TEST AND CHARACTERIZE NOVEL ENGINEERED BACTERIOPHAGE BIOLOGICS SPECIFICALLY TARGETING MDROS FOR USE AS NOVEL THERAPEUTICS FOR TREATING AND PREVENTING COMBAT WOUND INFECTIONS USING PIONEERING TECHNOLOGY DEVELOPED AT JCVI. THIS OBJECTIVE WILL BE ACCOMPLISHED THROUGH EXPERIMENTS FOCUSED ON PRODUCING SYNTHETICALLY ENGINEERED PHAGE WITH AN ENHANCED HOST RANGE SUFFICIENT TO COVER CURRENT AND FUTURE CIRCULATING MDR STRAINS OF S. AUREUS AND K. PNEUMONIAE COMMONLY FOUND IN THE MILITARY HEALTH SYSTEM, INCLUDING METHICILLIN-RESISTANT S. AUREUS AND CARBAPENEM-RESISTANT K. PNEUMONIAE STRAINS. CANDIDATE ENGINEERED THERAPEUTIC PHAGE CHASSIS WILL BE PRODUCED, CHARACTERIZED AND TESTED IN MOUSE WOUND INFECTION MODELS BY RESEARCHERS AT WRAIR AS A PRELUDE TO FUTURE HUMAN USE. IT IS ANTICIPATED THAT WE WILL DEVELOP ONE OR MORE PHAGE CHASSIS CAPABLE OF SPECIFICALLY TARGETING AND KILLING EACH PATHOGEN BOTH IN VITRO AND IN VIVO."FUNDED BY THE DEFENSE THREAT REDUCTION AGENCY (DTRA), THE JCVI IS INVESTIGATING AN ASPECT OF THE WELL-RECOGNIZED PUBLIC HEALTH THREAT OF ANTIBIOTIC DRUG RESISTANCE IN PATHOGENIC BACTERIA. IN ADDITION TO STANDARD BACTERIAL RESISTANCE TO ANTIBIOTICS, INFECTION CAUSING BACTERIA ARE ABLE TO ASSUME A METABOLIC STATE THAT MAKES THE BACTERIA HIGHLY TOLERANT OF MASSIVE DOSES OF ANTIBIOTICS. THIS STATE IS TERMED THE PERSISTER STATE AND ACCOUNTS FOR ANTIBIOTIC FAILURE IN PATIENTS BEING TREATED FOR INFECTIONS AND FOR THE REEMERGENCE OF AN INFECTION AFTER AN APPARENT CLEARING OF THE DISEASE BY ANTIBIOTIC TREATMENT. JCVI IS INVESTIGATING THE GENETIC/GENOMIC INFRASTRUCTURE OF THE PERSISTER STATE IN THE PUBLIC HEALTH AND BIOTHREAT BACTERIAL PATHOGEN BURKHOLDERIA PSEUDOMALLEI USING BOTH GENOME BASED TECHNOLOGIES AND TRADITIONAL MICROBIOLOGY APPROACHES WITH THE ULTIMATE GOAL OF FINDING WAYS TO ELIMINATE EVEN BACTERIA IN THE PERSISTER STATE FROM PATIENTS WITH BACTERIAL INFECTIONS. JCVI, FUNDED THROUGH THE DARPA BIOLOGICAL CONTROL PROGRAM IS APPLYING THE LESSONS LEARNED FROM MINIMIZING AND REORGANIZING A BACTERIAL GENOME TO REMODEL THE GENOME OF AN INDUSTRIALLY USEFUL, VASTLY MORE COMPLICATED EUKARYOTIC YEAST, CALLED KLUYVEROMYCES MARXIANUS. IN USING A SINGLE K. MARXIANUS CHROMOSOME AS A PLATFORM, JCVI IS DEVELOPING A GENERALIZED SET OF ALGORITHMS FOR MINIMIZATION AND DEFRAGMENTING THE GENES INTO FUNCTIONAL MODULES THAT COULD BE APPLIED TO ALL SMALL GENOME EUKARYOTES, SUCH AS YEASTS, EUKARYOTIC ALGAE, AND PARASITES. 2365796 0 420120 OTHER PROGRAM SERVICES THE JCVI GRANT PORTFOLIO ALSO INCLUDED SUPPORT FROM SEVERAL OTHER FEDERAL AGENCIES AND FOUNDATIONS INCLUDING: U.S. DEPARTMENT OF JUSTICE (DOJ) JCVI IS DEVELOPING A FORENSIC MICROBIOME DATABASE (FMD) THAT WILL ALLOW FOR DEVELOPING MICROBIOME TOOLS FOR POTENTIAL IN MONITORING HUMAN TRAFFICKING. AS PART OF THIS AWARD JCVI WORKED WITH 5 INTERNATIONAL COHORTS AT DIVERSE GLOBAL LOCATIONS. THE RICHARD LOUNSBERY FOUNDATION - THE JCVI TEAM CONTINUES WORKING IN COLLABORATION WITH A GROUP IN EUROPE TO DECIPHER THE GENOME OF LEONARDO DA VINCI AND HIS RELATIVES, AND ALSO USING THE MICROBIOME AS AN APPROACH TO IMPROVE ART CONSERVATION. HUMAN VACCINES PROJECT (HVP) - JCVI, IN COLLABORATION WITH THE SAN DIEGO SUPERCOMPUTER CENTER, SERVES AS THE MAIN DEVELOPER OF THE CENTRAL DATA MANAGEMENT AND BIOINFORMATICS HUB FOR THE HVP, WITH DIRECT SUPPORT FROM THE HVP GENERAL FUND. THE MISSION OF THE HVP IS TO ACCELERATE THE DEVELOPMENT OF VACCINES AND IMMUNOTHERAPIES AGAINST MAJOR GLOBAL INFECTIOUS DISEASES AND CANCERS BY DECODING THE HUMAN IMMUNE SYSTEM. THE GOAL OF THE HVP BIOINFORMATICS HUB IS TO PROVIDE HIGH-AVAILABILITY, STANDARDIZED DATA AND ADVANCED ANALYTICAL CAPABILITIES TO THE HVP. JCVI IS ALSO CONTRIBUTING SINGLE CELL GENOMICS ASSAYS AND ANALYSIS EXAMINING CELLULAR RESPONSES TO HEPATITIS B VACCINATION. CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE (CIRM) - JCVI, IN COLLABORATION WITH THE UNIVERSITY OF CALIFORNIA, SANTA CRUZ, THE UNIVERSITY OF CALIFORNIA, SAN DIEGO, AND STANFORD UNIVERSITY, IS INVOLVED IN THE DEVELOPMENT OF THE MAIN DATA MANAGEMENT PORTAL FOR THE CIRM CENTER OF EXCELLENCE IN STEM CELL GENOMICS (CESCG). JCVI'S ROLE HAS BEEN TO DEVELOP A SERIES OF DATA STANDARDS TO SUPPORT THE INTEGRATION AND DISSEMINATION OF CESCG EXPERIMENTAL GENOMICS DATA, AND TO DEVELOP NOVEL STATISTICAL METHODS FOR SINGLE CELL GENOMICS DATA ANALYSIS.NASA - JCVI HAS RECEIVED FUNDING FROM NASA FOR UNDERSTANDING THE IMPACT OF SPACE TRAVEL ON THE HUMAN MICROBIOME.DURING 2019 JCVI PORTFOLIO INCLUDED MULTIPLE AWARDS FROM THE NATIONAL SCIENCE FOUNDATION (NSF) THAT ENCOMPASSED DIVERSE AREAS OF RESEARCH IN ENVIRONMENTAL MICROBIOLOGY, BIOREMEDIATION, COMPUTATIONAL BIOLOGY, AND EDUCATION. ONE LARGE PROGRAM IS DEVOTED TO DEVELOPMENT OF A VACCINE TO PREVENT BOVINE PLEUROPNEUMONIA, AN INFECTIOUS DISEASE OF CATTLE IN SUB-SAHARAN AFRICA. SEVERAL GRANTS PERTAIN TO ENVIRONMENTAL MICROBIOLOGY, ANALYZING THE ROLES OF MICROBES IN IMPORTANT ECOSYSTEMS THROUGHOUT THE WORLD. COLLABORATIVE RESEARCH: IRON BIOAVAILABILITY IN HIGH-CO2 OCEANS: NEW PERSPECTIVES ON IRON ACQUISITION MECHANISMS IN DIATOMS WITH THIS PROJECT THE JCVI SEEKS TO UNDERSTAND THE DIFFERENTIAL SENSITIVITY OF DIATOM IRON ACQUISITION STRATEGIES TO CHANGES IN SEAWATER PH AND CARBONATE CHEMISTRY. ULTIMATELY A MORE THOROUGH AND DETAILED MECHANISTIC UNDERSTANDING OF DIATOM IRON UPTAKE PATHWAYS WILL FACILITATE A MUCH-IMPROVED ABILITY TO FORECAST THE IMPACT OF ANTICIPATED CHANGES IN OCEAN PH AND INORGANIC CARBON CHEMISTRY ON RATES OF IRON UPTAKE BY DIATOMS. THIS CRITICAL BIOGEOCHEMICAL ISSUE IS ADDRESSED THROUGH TRACE METAL CLEAN MANIPULATION EXPERIMENTS INCORPORATING STATE-OF-THE-ART ANALYTICAL METHODOLOGY TO PROBE PHYTOPLANKTON CELLULAR PHYSIOLOGY AND BIOGEOCHEMISTRY IN LABORATORY CULTURES AND NATURAL COMMUNITIES. IN THE FIRST YEAR, LABORATORY EXPERIMENTS WITH A MODEL PENNATE DIATOM LEVERAGE A COLLECTION OF TARGETED KNOCKOUT TRANSGENIC LINES TO EVALUATE THE SUBSTRATE SPECIFICITY AND RELATIVE IMPORTANCE OF DISTINCT IRON ASSIMILATION PATHWAYS UNDER A RANGE OF PCO2 AND IRON AVAILABILITY CONDITIONS. ADDITIONALLY, QUANTITATION OF MRNA AND PROTEINS FOR KEY DIATOM IRON ASSIMILATION PATHWAYS IN NATURAL COMMUNITIES IN THE SOUTHERN CALIFORNIA CURRENT FURTHER CLARIFY THE RELATIVE IMPORTANCE AND SENSITIVITY OF DISTINCT IRON ASSIMILATION PATHWAYS IN RELATION TO PCO2 AND IRON AVAILABILITY. IN YEAR TWO A LAGRANGIAN STUDY OF IRON UPTAKE RATES AND ASSOCIATED MRNA AND PROTEIN ABUNDANCE IS PERFORMED ON UPWELLED HIGH PCO2 WATER OVER THE COURSE OF OFFSHORE ADVECTION. ADDITIONALLY, WE CONDUCT MESOCOSM EXPERIMENTS USING NATURALLY ELEVATED HIGH PCO2 SEAWATER AS WELL AS LABORATORY EXPERIMENTS ON MULTIPLEX KNOCKOUT LINES. YEAR THREE IS DEDICATED TO DATA ANALYSES AND OVERALL PROJECT SYNTHESIS. OVERALL AIMS OF THE RESEARCH ACTIVITIES INCLUDE, 1) DEVELOPMENT AND VALIDATION OF A REFINED CONCEPTUAL MODEL OF IRON UPTAKE IN KEY MARINE PHYTOPLANKTON AND SUBSEQUENT UTILIZATION OF THE MODEL TO CHARACTERIZE THE SENSITIVITY OF DISTINCT IRON UPTAKE PATHWAYS TO THE EFFECTS OF OCEAN ACIDIFICATION, AND 2) DETERMINATION OF THE EFFECTS OF ACIDIFICATION ON IRON UPTAKE, AND QUANTIFICATION OF THE RELATIVE CONTRIBUTION OF DISTINCT IRON ACQUISITION PATHWAYS IN HIGH PCO2 PHYTOPLANKTON COMMUNITIES. 2365796 0 420120 21465956 1 1 0 0 0 0 0 1 0 0 1 0 0 0 1 1 1 0 0 0 1 1 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 0 0 0 1 35 0 1 230 1 1 1 0 0 0 0 0 0 0 0 0 1 0 X 9 6 1 0 1 0 0 0 0 1 1 0 0 1 1 1 1 1 1 1 1 0 CA MD X DR JOHN CRAIG VENTER AND MEGAN WU 8582001800 4120 CAPRICORN LANE LA JOLLA CA 92037 VENTER JOHN CRAIG CHAIRMAN & CEO 40.00 X X 1190455 0 41673 NELSON KAREN PRESIDENT 40.00 X X 709470 0 59879 KOWALSKI HEATHER CHIEF OPERATING OFFICER 40.00 X X 449646 0 7720 BRAR PAMILA CHIEF MEDICAL OFFICER 40.00 X 367668 0 59585 MULLEN JILL SR. VP OF PHILANTHROPY AND STRATEGIC ALLIANCE 40.00 X 348126 0 57586 SCHEUERMANN RICHARD H DIRECTOR, LA JOLLA CAMPUS 40.00 X 347709 0 40772 SMITH HAMILTON O DISTINGUISHED PROFESSOR 40.00 X 332483 0 17938 PEAKE ANTONY G VP FOR RESEARCH ADMINISTRATION 40.00 X 292599 0 30310 STOUT MARTIN CHIEF TECHNOLOGY OFFICER 40.00 X 276273 0 33420 YUMUL MARY VP OF HUMAN RESOURCES 40.00 X 252985 0 56460 MICHAEL TODD DIRECTOR OF INFORMATICS 40.00 X 255915 0 50869 ADELSON JULIE VP, LEG. AFFRS/GENERAL COUNSEL 40.00 X 257475 0 34100 FRIEDMAN ROBERT M VP FOR POLICY & UNIV. RELATIONS 40.00 X 190319 0 51715 NGUYEN TAI THRU 519 CHIEF FINANCIAL OFFICER 40.00 X 154633 0 14844 BADR-EL-DIN AMIN PHD TRUSTEE 4.00 X 0 0 0 HOROWITZREENA TRUSTEE 4.00 X 0 0 0 KNIGHT JESSIE TRUSTEE 4.00 X 0 0 0 MCGRORY JACK TRUSTEE 4.00 X 0 0 0 NORRBY ERLING TRUSTEE 4.00 X 0 0 0 RUGGLES RUDY TRUSTEE 4.00 X 0 0 0 5425756 0 556871 60 0 1 0 MOSS ADAMS LLP 4747 EXECUTIVE DRIVE SUITE 1300 SAN DIEGO CA 92121 ACCOUNTING AND AUDIT SERVICES 174912 MEKETA FIDUCIARY 100 LOWDER BOOK DRIVE SUITE 1100 WESTWOOD MA 02090 INVESTMENT ADVISOR 111212 CLIMATEC LLC PO BOX 51689 LOS ANGELES CA 90051 FACILITIES COMPUTER SERVICE CONSULTANT 111187 PE FACILITY SOLUTION 7976 ENGINEER ROAD SUITE 200 SAN DIEGO CA 92111 FACILITIES MAINTENANCE SERVICES 110294 TB CONSULTING 8328 E HARTFORD DRIVE SUITE 102 SCOTTSDALE AZ 85255 COMPUTER SERVICE CONSULTANT 108450 5 18024150 3418801 21442951 SEQUENCING SERVICES REVENUE 900099 419173 419173 CLONE REVENUE 900099 947 947 420120 1158537 1158537 57915758 1892884 56649877 2396928 1265881 -504044 761837 761837 K-1 PASSTHROUGH 900099 6009 6009 6009 23789454 420120 6009 1920374 2503436 2503436 83035 83035 4353907 932718 3419877 1312 14843236 9262642 5124227 456367 495886 263359 220705 11822 1145087 608141 509646 27300 891912 473683 396965 21264 286806 286806 202099 202099 182562 182562 401034 177693 207441 15900 83926 83926 500475 191307 287345 21823 1176488 34084 1138515 3889 2730935 1956941 725618 48376 433125 182738 231374 19013 91251 43653 45109 2489 69949 69949 2824701 1631384 1174518 18799 541888 180094 360087 1707 LAB EQUIPMENT/SUPPLIES 3249016 2903138 345834 44 BOOKS AND SUBSCRIPTIONS 107438 394 105303 1741 227570 37516 178709 11345 37425762 21465956 15296615 663191 4253735 4765643 2624266 12285562 4241716 3868838 375164 260317 866516 1022612 69499985 22969804 50740449 46530181 50308884 36161170 1553980 1253071 2841834 2840214 117806544 108987608 5772850 6031343 2556527 2528751 25089970 0 1608716 26524485 55910 82679 35083973 35167258 X 82229932 73084655 492639 735695 82722571 73820350 117806544 108987608 X -13636308 4740096 -6009 X 0 1 X 1 1 1 X 31545719 26768604 20421917 30012027 21442951 130191218 31545719 26768604 20421917 30012027 21442951 130191218 2833724 127357494 31325751 1482196 1373809 1387304 1158537 36727597 166918815 3370452 0.76300 0.76670 X RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED 2545000 X X X 0 53875009 8558062 45316947 15624976 14411742 1213234 46530181 LEASES PAYABLE 82679 82679 X 28700979 4740096 360000 5100096 23600883 182562 6009 188571 23789454 37603200 360000 360000 37243200 182562 182562 37425762 PART III, LINE 4: COLLECTION OF SCIENTIFIC WRITINGS RELEVANT TO GENOMIC RESEARCH. PART X, LINE 2: THE INSTITUTE IS A NOT-FOR-PROFIT ORGANIZATION EXEMPT FROM FEDERAL INCOME TAXES UNDER SECTION 501(C)(3) OF THE INTERNAL REVENUE CODE. THE INSTITUTE DOES NOT BELIEVE THERE ARE ANY MATERIAL UNCERTAIN TAX POSITIONS AND ACCORDINGLY, NO PROVISION FOR INCOME TAXES HAS BEEN MADE IN THE ACCOMPANYING FINANCIAL STATEMENTS. THE INSTITUTE IS SUBJECT TO ROUTINE AUDITS BY TAXING JURISDICTIONS; HOWEVER, THERE ARE CURRENTLY NO AUDITS FOR ANY TAX PERIOD IN PROGRESS. PART XI, LINE 4B - OTHER ADJUSTMENTS: K-1 PASSTHROUGH 6,009. 1 EAST ASIA AND THE PACIFIC 0 0 PROGRAM SERVICES RESEARCH SUBGRANTS 47754 SOUTH AMERICA 0 0 PROGRAM SERVICES RESEARCH SUBGRANTS 35281 CAYMAN ISLANDS INVESTMENTS 142725 0 0 0 0 0 0 225760 0 225760 EAST ASIA AND THE PACIFIC PROGRAM SERVICES 47754 WIRE SOUTH AMERICA PROGRAM SERVICES 35281 WIRE 2 1 0 0 1 1 0 PART I, LINE 2: EACH SUBGRANT IS A PASS THROUGH GRANT FROM A FEDERAL OR NON-FEDERAL GRANT OR CONTRACT AWARDED TO J. CRAIG VENTER INSTITUTE. ALL EXPENSES ARE MONITORED AS INVOICED AT LEAST QUARTERLY, BUT IN MOST CASES MONTHLY. THE INVOICES ARE REVIEWED AND APPROVED BASED ON RECEIPT OF GOODS OR SERVICES AND AGAINST AN APPROVED BUDGET. PART I, LINE 3: ACCRUAL BASIS PART III ACCOUNTING METHOD: PART II, LINE 1: ACCRUAL BASIS 1 SANFORD BURNHAM PRESBYS 10901 NORTH TORREY PINES ROAD LA JOLLA CA 92037 510197108 501(C)(3) 150028 RESEARCH SUBGRANT UNIVERSITY OF CALIFORNIA IRVINE 120 THEORY SUITE 200 IRVINE CA 92697 952226406 501(C)(3) 388744 RESEARCH SUBGRANT VANDERBILT UNIVERSITY 2201 WEST END AVE NASHVILLE TN 37235 620476822 501(C)(3) 241993 RESEARCH SUBGRANT LELAND STANFORD JR UNIVERSITY 3145 PORTER DRIVE PALO ALTO CA 94304 941156365 501(C)(3) 136925 RESEARCH SUBGRANT WOODS HOLE OCEANOGRAPHIC INSTITUTE 569 WOODS HOLE ROAD WOODS HOLE MA 02543 042105850 501(C)(3) 20999 RESEARCH SUBGRANT COLORADO STATE UNIVERSITY 6015 CAMPUS DELIVERY FORT COLLINS CO 80523 846000545 501(C)(3) 403448 RESEARCH SUBGRANT UNIVERSITY OF CALIFORNIA SAN DIEGO 9500 GILMAN DR LA JOLLA CA 92037 566001393 501(C)(3) 768275 RESEARCH SUBHRANT HARVARD MEDICAL SCHOOL P O BOX 415649 BOSTON MA 02241 042103580 501(C)(3) 15334 RESEARCH SUBGRANT UNIVERSITY OF TEXAS PO BOX 660120 DALLAS TX 75266 740000949 501(C)(3) 20835 RESEARCH SUBGRANT REGENTS UNIVERSITY OF MINNESOTA 700 ROSEDALE AVE ST LOUIS MO 63112 430653611 501(C)(3) 44378 RESEARCH SUBGRANT MRI GLOBAL 425 VOLKER BLVD KANSAS CITY MO 641102241 440545878 501(C)(3) 26024 RESEARCH SUBGRANT RHODE ISLAND HOSPITAL 1 HOPPIN STREET BOX 42 SUITE 1300 PROVIDENCE RI 029034923 050258954 501(C)(3) 200745 RESEARCH SUBGRANT SALK INSTITUTE 10010 N TORREY PINES ROAD LA JOLLA CA 92037 952160097 501(C)(3) 66229 RESEARCH SUBGRANT SANTA FE INSTITUTE 1399 HYDE PARK ROAD SANTA FE NM 875018943 850325494 501(C)(3) 19478 RESEARCH SUBGRANT 14 0 PART I, LINE 2: EACH SUBGRANT IS A PASS THROUGH GRANT FROM A FEDERAL OR NON-FEDERAL GRANT OR CONTRACT AWARDED TO J. CRAIG VENTER INSTITUTE. ALL EXPENSES ARE MONITORED AS INVOICED AT LEAST QUARTERLY, BUT IN MOST CASES MONTHLY. THE INVOICES ARE REVIEWED AND APPROVED BASED ON RECEIPT OF GOODS OR SERVICES AND AGAINST AN APPROVED BUDGET. X X X 1 1 X X X X 0 0 0 0 0 0 0 1 0 VENTER JOHN CRAIG CHAIRMAN & CEO 1174714 0 0 0 15741 0 9833 0 31840 0 1232128 0 0 0 NELSON KAREN PRESIDENT 705939 0 0 0 3531 0 13849 0 46030 0 769349 0 0 0 KOWALSKI HEATHER CHIEF OPERATING OFFICER 446752 0 0 0 2894 0 0 0 7720 0 457366 0 0 0 BRAR PAMILA CHIEF MEDICAL OFFICER 365347 0 0 0 2321 0 12750 0 46835 0 427253 0 0 0 MULLEN JILL SR. 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RELATIONS 175350 0 0 0 14969 0 7294 0 44421 0 242034 0 0 0 NGUYEN TAI THRU 519 CHIEF FINANCIAL OFFICER 153558 0 0 0 1075 0 6149 0 8695 0 169477 0 0 0 PART I, LINE 1A SCHEDULE J, PART I, LINE 1A: TAX INDEMIFICATION AND GROSS-UP PAYMENTS - CERTAIN AWARDS ARE GROSSED UP FOR INCOME TAX AND INCLUDED AS TAXABLE COMPENSATION. SCHEDULE J, PART I, LINE 1A; FIRST-CLASS OR CHARTER TRAVEL - THE ORGANIZATION PROVIDES THE CEO FIRST CLASS AND CHARTER TRAVEL FOR BUSINESS PURPOSES. NO PART OF THIS BENEFIT IS TREATED AS TAXABLE COMPENSATION. SCHEDULE J, PART I, LINE 1A; PERSONAL SERVICES - THE ORGANIZATION PROVIDES THE CEO SERVICES OF BODYGUARDS WHEN HE TRAVELS. NO PART OF THIS BENEFIT IS TREATED AS TAXABLE COMPENSATION. PART I, LINE 7 THE INSTITUTE PROVIDES SERVICE AWARDS FOR ITS EMPLOYEES FOR FIVE, TEN, FIFTEEN AND TWENTY YEARS OF SERVICE. FORM 990, PART VI, SECTION A, LINE 2 BOARD MEMBERS HEATHER KOWALSKI AND J. CRAIG VENTER HAVE A FAMILY RELATIONSHIP. FORM 990, PART VI, SECTION A, LINE 4 THE INSTITUTE AMENDED AND RESTATED ITS BYLAWS ARTICLE IV, SECTION 3, PARAGRAPH A, ON DECEMBER 15, 2019 TO REPORT THAT REGULAR MEETINGS OF THE BOARD OF TRUSTEES, WHICH ARE HELD AT LEAST THREE (3) TIMES IN EACH CALENDAR YEAR, ARE TO BE HELD IN PERSON AT LEAST ON ONE (1) OCCASION (PREVIOUSLY REPORTED AS ON TWO (2) OCCASIONS), WHILE THE OTHER MEETINGS MAY BE HELD BY CONFERENCE CALL. FORM 990, PART VI, SECTION B, LINE 11B THE FORM 990 IS REVIEWED BY MANAGEMENT. A COMPLETE COPY OF THE FORM 990 AND SUPPORTING SCHEDULES WAS PROVIDED TO THE FULL BOARD FOR REVIEW PRIOR TO BEING FILED. FORM 990, PART VI, SECTION B, LINE 12C JCVI MONITORS COMPLIANCE OF ITS CONFLICT OF INTEREST POLICY THROUGH AN ANNUAL SOLICITATION OF CONFLICT OF INTEREST STATEMENTS FROM TRUSTEES, OFFICERS, AND EMPLOYEES. IF A PERSON HAS A CONFLICT WITH RESPECT TO A TRANSACTION, SUCH PERSON IS NOT ALLOWED TO VOTE. FORM 990, PART VI, SECTION B, LINE 15 JCVI USES AN OUTSIDE COMPENSATION CONSULTANT, TO PROVIDE A LIST OF COMPARABLE SALARIES FOR THE CEO AND OFFICERS THESE ARE REVIEWED BY THE JCVI COMPENSATION COMMITTEE AND CEO BEFORE A FINAL DETERMINATION IS MADE. THIS PROCESS WAS DOCUMENTED AND LAST DONE IN OCTOBER 2018. FORM 990, PART VI, SECTION C, LINE 19 THE ORGANIZATION'S FINANCIAL STATEMENTS, GOVERNING DOCUMENTS, AND CONFLICT OF INTEREST POLICY ARE MADE AVAILABLE TO THE PUBLIC UPON REQUEST. FORM 990, PART XI, LINE 9: K-1 PASSTHROUGH -6,009. OCEAN SOLUTION LLC 4120 CAPRICORN LANE LA JOLLA CA 92037 260145075 DEVELOPMENT DE 0 0 JCVI SORCERER II LLC 4120 CAPRICORN LANE LA JOLLA CA 92037 562370157 RESEARCH RI 0 0 JCVI J CRAIG VENTER INSTITUTE MEDICAL GROUP 4120 CAPRICORN LANE LA JOLLA CA 92037 833574850 MEDICAL OFFICE CA N/A C 1.00000 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0