J CRAIG VENTER INSTITUTE
Programs
Program 1 [2020]
THROUGHOUT THE FISCAL YEAR 2020, THE JCVI RECEIVED FUNDING FROM VARIOUS FEDERAL AND NON-FEDERAL SPONSORING AGENCIES AND FOUNDATIONS SUPPORTING IN EXCESS OF 85 ACTIVE RESEARCH PROJECTS COVERING A RANGE OF RESEARCH AREAS INCLUDING HUMAN HEALTH, ENVIRONMENTAL SUSTAINABILITY, SYNTHETIC BIOLOGY, TECHNOLOGY AND TOOLS, EDUCATION AND POLICY. DEPARTMENT OF HEALTH AND HUMAN SERVICES (DHHS) -FUNDED BY THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID/NIH) AND IN COLLABORATION WITH THE UNIVERSITY OF CHICAGO, THE JCVI 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. JCVI CONTINUED TO LEAD A 5-YEAR COLLABORATIVE NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS/NIH) 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. FUNDED THROUGH THE NATIONAL INSTITUTE OF ALLERGY AND IMMUNOLOGY (NIAID/NIH) AND IN COLLABORATION WITH NORTHEASTERN UNIVERSITY. ANTIBIOTIC RESISTANCE CONTINUES TO BE 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 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. AS PART OF AN NIH GRANT IN COLLABORATION WITH COLLEAGUES AT UC IRVINE, THE RESEARCH TEAM HAVE BEEN APPLYING ADVANCE LABORATORY, COMPUTATIONAL, AND ARTIFICIAL INTELLIGENCE METHODS TO EXPLORE WHY SOME PEOPLE INFECTED WITH SARS-COV-2 DEVELOP SEVERE DISEASE WHILE OTHERS ARE ASYMPTOMATIC OR ONLY DEVELOP MILD SYMPTOMS. WE HAVE ALSO EXPLORED THE IMPACT THAT CORTICOSTEROID TREATMENT HAS ON COVID PATIENTS. WE FOUND THAT WHILE SEVERE COVID PATIENTS MOUNT AN EFFECTIVE ANTIBODY RESPONSE, THEY ALSO DEVELOP A MORE SEVERE GENERAL INFLAMMATORY REACTION, AND THAT THIS INFLAMMATORY RESPONSE WAS DAMPENED WITH STEROID TREATMENT. THESE FINDINGS SUGGEST THAT STEROID-BASED INTERVENTIONS COULD POTENTIAL LIMIT SEVERE COVID DISEASE AND WERE REPORTED IN A RECENT PUBLICATION IN THE JOURNAL OF LEUKOCYTE BIOLOGY (HTTPS://JLB.ONLINELIBRARY.WILEY.COM/DOI/EPDF/10.1002/JLB.4COVA0121-084RR). FUNDED BY NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES (NIEHS/NIH) MICROBIOME IN ASTHMA INDUCED BY ENVIRONMENTAL PARTICLE EXPOSURE. IN COLLABORATION WITH BROWN UNIVERSITY. MICROBIAL DYSBIOSIS IN THE GUT AND THE LUNG IS INCREASINGLY BEING ASSOCIATED WITH THE INCIDENCE AND SEVERITY OF ASTHMA, HOWEVER CAUSALITY STUDIES ARE LACKING. JCVI AND ITS COLLABORATOR, BROWN UNIVERSITY HAVE ADAPTED A MOUSE MODEL THAT FOCUSES ON THE ONSET OF ALLERGIC ASTHMA EARLY IN LIFE AFTER AN IN-UTERO EXPOSURE TO ENVIRONMENTAL PARTICLES TO STUDY HOW MICROBIOME MAY LEAD TO THE ASTHMA ONSET. IN THIS MODEL, THE RESEARCH TEAM HAS SHOWN THAT MATERNAL EXPOSURES TO ALLERGEN OR PARTICULATE MATTER, E.G. CONCENTRATED URBAN AIR PARTICLES (CAP), DIESEL EXHAUST PARTICLES (DEP) AND TITANIUM DIOXIDE PARTICLES (TIO2), TRIGGER INCREASED ASTHMA RISK IN SEVERAL GENERATIONS OF THE OFFSPRING. HUMANS ARE WIDELY EXPOSED TO THESE PARTICULATES, ESPECIALLY IN URBAN AND INDUSTRIAL SETTINGS, WHERE THE INCIDENCE OF ASTHMA IS ALSO HIGHER. RESEARCHERS FOUND THAT THE INCREASED 'PREPAREDNESS' FOR ASTHMA IN THESE NEONATES IS ASSOCIATED WITH DNA METHYLATION CHANGES IN KEY IMMUNE CELLS DENDRITIC CELLS THAT ARE ESSENTIAL IN ASTHMA ORIGIN. IMPORTANT UNANSWERED QUESTIONS ARE WHY THESE EPIGENETIC CHANGES OCCUR, AND WHETHER THERE IS A CAUSATIVE LINK TO THE ABERRANT MICROBIOME SEEN IN ASTHMA. THE JCVI HYPOTHESIZE THAT IN UTERO EXPOSURES TO PARTICLES ALTER THE MICROBIOME OF THE PREGNANT MICE AND THEIR OFFSPRING, WHICH THEN SIGNALS TO THE IMMUNE CELLS IN A WAY THAT PREDISPOSES THE OFFSPRING TO ALLERGY. WE POSTULATE TWO, POTENTIALLY INTERCONNECTED, MECHANISMS IN ASTHMA ONSET: EPIGENETICS AND THE MICROBIOME. BOTH THE EPIGENETIC ALTERATIONS IN IMMUNE CELLS AND THE DYSBIOSIS IN THE GUT AND LUNG HAVE BEEN LINKED TO ASTHMA IN HUMANS AND MOUSE MODELS BUT CAUSALITY STUDIES ARE LACKING. THE PROPOSED RESEARCH ADDRESSES THIS GAP IN KNOWLEDGE IN A STUDY DESIGNED TO TEST BASIC MECHANISMS OF RELATIVELY COMMON ENVIRONMENTAL EXPOSURES. PROJECT FUNDED THROUGH THE NATIONAL INSTITUTE OF ALLERGY AND IMMUNOLOGY (NIAID/NIH) A DEVELOPMENT OF NOVEL PROTEIN-BASED VACCINE FORMULATIONS TO PREVENT PNEUMOCOCCAL COLONIZATION AND DISEASE WITH COLLABORATOR FROM THE UNIVERSITY OF MARYLAND. ONE OF THE MAJOR PROBLEMS OF THE GREAT BURDEN OF COMMUNITY-ACQUIRED PNEUMONIAS CAUSED BY STREPTOCOCCUS PNEUMONIAE (SPN) INFECTION, IS THE ACQUISITION OF ANTIMICROBIAL RESISTANCE AND THE GLOBAL SPREAD OF RESISTANT VARIANTS. THESE PROBLEMS GET ENHANCED BY THE MAJOR DISADVANTAGES OF THE CURRENT CAPSULAR POLYSACCHARIDE-BASED VACCINES, SUCH AS COST, SEROTYPE SPECIFICITY, AND THE RESULTING INCOMPLETE COVERAGE. THIS OCCURS MAINLY BECAUSE OF DISEASE BEING CAUSED BY SEROTYPES NOT PRESENT IN THE VACCINE (MAXIMUM OF 23 OF THE >97 CAPSULE TYPES, ONLY 13 IN THE CONJUGATE VACCINE) AND REPLACEMENT CARRIAGE. THE RATIONALE FOR THIS PROJECT IS THAT DEVELOPMENT OF A SUBUNIT-BASED VACCINE UTILIZING NOVEL CONSERVED ANTIGENIC PROTEINS IN CONJUNCTION WITH NOVEL POLYPHOSPHAZENE (PPZ) ADJUVANTS, PROVEN TO INDUCE ADAPTIVE IMMUNITY WILL DEEPEN THE CURRENT TOOLKIT TO PREVENT PNEUMOCOCCAL DISEASE WITHOUT SEROTYPE LIMITATIONS. THUS, JCVI HYPOTHESIZE THAT ADDITION OF CONSERVED IMMUNOGENIC PROTEINS TO A POTENT ADJUVANT NANO-MOLECULE WILL PROVIDE THE GROUNDWORK FOR THE DEVELOPMENT OF A BROADLY PROTECTIVE PNEUMOCOCCAL SUBUNIT-BASED VACCINE. (SEE FORM 990, PART III, LINE 4A, PROGRAM SERVICE ACCOMPLISHMENTS CONTINUED).GeographiesNot indicatedDatesJan 1, 2020 – Dec 31, 2020Source990No causes providedNo populations provided–$7.9MProgram 2 [2020]
JCVI IS THE RECIPIENT OF A LARGE COLLABORATIVE ASSISTANCE AWARD FROM THE US DEPARTMENT OF ENERGY. AWARDED TO THE VALUE OF $10.7M. NOW IN ITS 4TH YEAR OF 5,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 METABOLITE FLUX THROUGH SUBCELLULAR COMPARTMENTS TO PROMOTE EFFICIENT PRODUCTION OF HIGH VALUE AND FUEL-RELATED METABOLITES.GeographiesNot indicatedDatesJan 1, 2020 – Dec 31, 2020Source990No causes providedNo populations provided–$2.6MProgram 3 [2020]
DURING 2020, 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) 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 CHARACTERIZATION 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 INSTITUTE 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."GeographiesNot indicatedDatesJan 1, 2020 – Dec 31, 2020Source990No causes providedNo populations provided–$2.7M
Copyright 2026. All rights reserved to Chario Inc. (d.b.a. Impala)