J CRAIG VENTER INSTITUTE

DEPARTMENT OF HEALTH AND HUMAN SERVICES: TWO MILLION PEOPLE IN THE U.S. ARE DIAGNOSED ANNUALLY WITH LIFE-THREATENING INFECTIONS CAUSED BY ANTIBIOTIC RESISTANT BACTERIA THAT ARE RESPONSIBLE FOR 35,000 DEATHS EACH YEAR WITH AN ECONOMIC IMPACT ESTIMATED TO BE AS MUCH AS $20 BILLION A YEAR IN DIRECT HEALTHCARE COSTS. DUE TO THE SPREAD OF ANTIBIOTIC RESISTANCE, VERY FEW DRUGS REMAIN THAT CAN TREAT THESE INFECTIONS. LED BY DERRICK FOUTS, PHD, (JCVI) AND FUNDED BY THE CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC), THE J. CRAIG VENTER INSTITUTE AND CLEVELAND VA PREVENTION AND INTERVENTION EPICENTER ARE DEVELOPING NOVEL INTERVENTIONS THAT WILL PREVENT THE COLONIZATION AND SPREAD OF ANTIBIOTIC RESISTANT (AR) BACTERIA THAT CAUSE HOSPITAL ACQUIRED INFECTIONS (HAI), AND TO DEVELOP DIAGNOSTICS AND INTERVENTIONS TO COMBAT THE COLONIZATION BY THE RAPIDLY EMERGING FUNGAL PATHOGEN CANDIDA AURIS. COLLABORATORS ON THIS MULTI YEAR FUNDED CENTER INCLUDE RESEARCH LABS AT DUKE UNIVERSITY, CASE WESTERN UNIVERSITY AND NORTHWESTERN UNIVERSITY. LED BY INDRESH SINGH, DIRECTOR OF INFORMATICS, THE JCVI IS A KEY COLLOBORATOR FOR THE BACTERIAL AND VIRAL BIOINFORMATICS RESOURCE CENTER (BV-BRC). USING THE ADVANCED SYSTEM ARCHITECTURE BASED ON HIGH-PERFORMANCE COMPUTING, EXTENSIBLE DATABASE MANAGEMENT APPROACH STRUCTURED ON EMERGING METADATA STANDARDS, AND SUITE OF ANALYSIS AND VISUALIZATION TOOLS AND SERVICES AVAILABLE FOR CUSTOMIZED WORKFLOW ASSEMBLY JCVI SUPPORTS ONGOING DEVELOPMENT OF THE COMPREHENSIVE INTEGRATED BV-BRC THROUGH A TEAM OF VIROLOGY, IMMUNOLOGY, BIOINFORMATICS, AND INFORMATION TECHNOLOGY PROFESSIONALS WHO FOCUS ON THE DEVELOPMENT, ENHANCEMENT, AND TRAINING OF THE BV-BRC RESOURCE FOR THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, THEIR SUPPORTED RESEARCHERS, AND THE BROADER INFECTIOUS DISEASE RESEARCH COMMUNITY. INFECTIONS CAUSED BY KLEBSIELLA PNEUMONIAE ARE INCREASINGLY PREVALENT AND DIFFICULT TO TREAT DUE TO INEFFECTIVE TREATMENT OPTIONS DUE TO INCREASED ANTIBIOTIC RESISTANCE. BACTERIOPHAGES, VIRUSES THAT INFECT AND KILL BACTERIA, ARE BEING USED TO EFFECTIVELY TREAT AND CURE INFECTIONS CAUSED BY A NUMBER OF BACTERIAL PATHOGENS. TO ADDRESS THE NEED FOR NEW TREATMENTS FOR WOUND AND PULMONARY INFECTIONS CAUSED BY K. PNEUMONIAE, DR. DERRICK FOUTS TEAM HAS DEVELOPED A 5-PHAGE LEAD CANDIDATE THERAPEUTIC COCKTAIL THAT IS CAPABLE OF INFECTING 53 OF OUR 100-STRAIN TEST PANEL. FUNDED BY THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, THE JCVI, THE WALTER REED ARMY INSTITUTE OF RESEARCH (WRAIR) AND ADAPTIVE PHAGE THERAPEUTICS (APT) WILL OPTIMIZE THE LEAD THERAPEUTIC AND ITS PRODUCTION AS WELL AS CONDUCT THE REQUIRED PREINVESTIGATIONAL NEW DRUG (IND) TESTING AND BENCHMARKING NECESSARY FOR THE SUCCESSFUL SUBMISSION AND REVIEW OF AN IND APPLICATION FOR A PHASE 1 CLINICAL TRIAL. RESEARCH WILL LEVERAGE JCVI'S HISTORY OF SYNTHETIC AND PHAGE GENOMICS, WRAIR'S EXPERIENCE DEVELOPING PHAGE THERAPEUTICS, DEVELOPMENT OF MOUSE MODELS, AND APTS CGMP PRODUCTION CAPABILITIES AND EXPERIENCE WITH PHAGE CLINICAL TRIALS.

NATIONAL SCIENCE FOUNDATION CONTINUES TO FUND THE J. CRAIG VENTER INSTITUTE (JCVI) IN THE AREAS OF SYNTHETIC BIOLOGY, INTEGRATIVE ORGANISMAL SYSTEMS CORE PROGRAMS. FUNDED BY THE OFFICE OF INTERNATIONAL SCIENCE AND ENGINEERING, DR. TAE SEOK MOON, JCVI PROFESSOR LEADS AN INTERNATIONAL CONSORTIUM THROUGH A GLOBAL CENTER TO ADDRESS THE CHALLENGES OF RECALCITRANT WASTE STREAMS BY DEVELOPING INTEGRATED, NOVEL, AND SCALABLE PROCESSES FOR THEIR VALORIZATION, INTEGRATING RESEARCHERS ALL OVER THE WORLD AND FROM ACADEMIA AND INDUSTRY, AND PROVIDING GLOBAL EDUCATION, OUTREACH ACTIVITIES, AND WORKFORCE. GLOBAL CENTERS: CIRCLE: CENTER FOR INNOVATIVE RECYCLING AND CIRCULAR ECONOMY IS SUPORTED BY RESEARCH TEAMS IN THE UNITED STATES, CANADA, UNITED KINGDOM, KOREA, JAPAN, SINGAPORE & AUSTRALIA. THIS CENTER WILL DEVELOP THREE CORE TECHNOLOGIES, INCLUDING (1) MULTI-OMICS-BASED BIOPROSPECTING TO DISCOVER NEW ENZYMES, GENE REGULATORS, AND ORGANISMS FOR WASTE VALORIZATION, (2) PREDICTIVE COMPUTATIONAL APPROACHES TO ENABLE FORWARD ENGINEERING OF PROTEINS AND STRAINS FOR BIOMANUFACTURING, AND (3) TEA, LCA, AND RISK ASSESSMENT TO DEVELOP COMMERCIALLY VIABLE BIOPROCESSES FOR WASTE VALORIZATION. TO DEMONSTRATE THE UTILITY AND GENERALIZABILITY OF THE DEVELOPED CORE TECHNOLOGIES, WE WILL DEVELOP COMMERCIALLY VIABLE VALORIZATION PROCESSES FOR THREE WASTE STREAMS, INCLUDING MIXED PLASTICS, C1 GASES, AND BIOGENIC WASTES (E.G., FOOD, AGRICULTURAL, AND PAPER/CARDBOARD WASTES). IF SUCCESSFUL, THESE HIGH-RISK, HIGH-RETURN CENTER PROJECTS WILL PROVIDE NOVEL WASTE CONVERSION PROCESSES THAT CAN BE CONSIDERED FOR COMMERCIAL-SCALE, SUSTAINABLE BIOPRODUCTION. THIS IS MULTI-YEAR INTERNATIONAL STUDY. THE US CONSORTIUM HAS BEEN FUNDED UPTO $4.9M. NON-US COLLABORATORS HAVE BEEN FUNDED THROUGH RESEARCH AGENCIES WITHIN THEIR OWN COUNTRIES. UNDER THE DIVISION OF MOLECULAR AND CELLULAR BIOSCIENCE AND IN COLLABORATION WITH THE UNIVERSITY OF ILLINOIS MINIMAL BACTERIAL CELL COMPUTATIONAL MODELEING TEAM LED BY ZAIDA LUTHEY-SCHULTEN, JCVI RESEARCHERS LED BY DR. JOHN GLASS, ARE CARRYING OUT TRANSCRIPTOME AND METABLOMIC ANALYSES, BIOCHEMICAL AND GENETIC EXPERIEMENTS TO DISCOVER UNKNOWN GENE FUNCTIONS, OPTIMIZATION OF A MINIMAL CELL DEFINED GROWTH MEDIUM, AND CONSTRCUTION OF MINIMAL CELL MUTATNS TO FACILITATE THE WORK OF JCVI AND OTHER GROUP[S INVESTIGATING MINIMAL CELL BIOLOGY. THIS IS A MULTI-YEAR STUDY WITH COLLABORATIVE FUNDING OF $2.0M (~$0.7M JCVI).LED BY DR. JOHN GLASS, THE JCVI IS INVESTIGATING THE MECHANISM OF GENOME TRANSPLANTATION, DEVELOP GENOME TRANSPLANTATION FOR AT LEAST TWO SPECIES OF NON-MYCOPLASMA BACTERIA, AND USE MICROFLUIDICS TECHNOLOGY TO AUTOMATE AND IMPROVE THE EFFICIENCY OF GENOME TRANSPLANTATION. GENOME TRANSPLANTATION, THE INSERTION OF A COMPLETE BACTERIAL GENOME INTO A SUITABLE RECIPIENT CELL SO THAT THE DONATED GENOME COMMANDEERS THE RECIPIENT CELL TO PRODUCE A NEW CELL WITH THE GENOTYPE AND PHENOTYPE OF THE DONATED GENOME, WAS THE FUNDAMENTAL TECHNICAL DEVELOPMENT THAT ENABLED THE CONSTRUCTION OF THE FIRST BACTERIUM WITH A SYNTHETIC GENOME. AT THE ANNOUNCEMENT OF THE CREATION OF THE WORLD'S FIRST SYNTHETIC CELL, JCVI-SYN1.0, THE WORK WAS HERALDED AS A MAJOR ACCOMPLISHMENT FOR HUMANKIND. TO DATE, GENOME TRANSPLANTATION HAS ONLY BEEN ACHIEVED USING A SMALL SUBSET IF THE ATYPICAL BACTERIA CALLED MYCOPLASMAS. THIS IS A MULTI-YEAR STUDY WITH COLLABORATIVE FUNDING OF $1.0M.