J Craig Venter Institute Inc

ABCD-USA CONSORTIUM: DATA ANALYSIS CENTER

THE J. CRAIG VENTER INSTITUTE GENOME CENTER FOR INFECTIOUS DISEASES

RECONSTRUCTION OF A BACTERIAL GENOME FROM DNA CASSETTES

DESIGN, SYNTHESIS, AND VALIDATION: GENOME SCALE OPTIMIZATION OF ENERGY FLUX THROUGH COMPARTMENTALIZED METABOLIC NETWORKS IN A MODEL PHOTOSYNTHETIC EUKARYOTIC MICROBE

CONSTRUCTION OF A REFERENCE SEQUENCE DATA SET FOR THE HUMAN MICROBIOME PROJECT

RECONSTRUCTION OF A BACTERIAL GENOME FROM DNA CASSETTES

CK20-004, J. CRAIG VENTER INSITUTE AND CLEVELAND VA PREVENTION AND INTERVENTION EPICENTER

GLOBAL CENTERS: CIRCLE CENTER FOR INNOVATIVE RECYCLING AND CIRCULAR ECONOMY -THIS AWARD IS FUNDED BY NSF GLOBAL CENTERS PROGRAM, AN INNOVATIVE PARTNERSHIP WITH FUNDING AGENCIES IN CANADA, FINLAND, JAPAN, REPUBLIC OF KOREA, AND THE UNITED KINGDOM, TO JOINTLY SUPPORT USE-INSPIRED RESEARCH ADDRESSING GLOBAL CHALLENGES THROUGH THE BIOECONOMY. THESE PARTNERSHIPS LEVERAGE RESOURCES TO TACKLE CHALLENGES AT A LARGER SCALE THAN WOULD BE POSSIBLE FOR ONE FUNDING AGENCY ALONE. THIS CENTER IS JOINTLY SUPPORTED BY NSF, THE NATURAL SCIENCES AND ENGINEERING RESEARCH COUNCIL AND THE SOCIAL SCIENCES AND HUMANITIES RESEARCH COUNCIL OF CANADA, THE NATIONAL RESEARCH FOUNDATION OF KOREA, AND UK RESEARCH AND INNOVATION. THE CENTER FOR INNOVATIVE RECYCLING AND CIRCULAR ECONOMY (CIRCLE) ADDRESSES THE CHALLENGES ASSOCIATED WITH RECALCITRANT WASTE STREAMS AND MANAGEMENT. AIR POLLUTION REDUCTION, AGRICULTURAL/FOOD WASTE TREATMENT, AND PLASTIC WASTE DISPOSAL ARE GLOBAL CHALLENGES THAT AFFECT HUMAN HEALTH ACROSS BORDERS. THESE ISSUES CANNOT BE ADDRESSED BY A SINGLE DISCIPLINE OR A SINGLE COUNTRY. CIRCLE SUPPORTS AN INTERNATIONAL PARTNERSHIP ACROSS SIX COUNTRIES TO TACKLE THESE GLOBAL ISSUES. IT ENGAGES MORE THAN 40 INVESTIGATORS FROM 18 ACADEMIC INSTITUTIONS AND 16 PRIVATE COMPANIES. IT LEVERAGES EXPERTISE IN CHEMISTRY, COMPUTATIONAL AND SYSTEMS BIOLOGY, MICROBIOLOGY, METABOLIC ENGINEERING, AND BIOPROCESS ENGINEERING. IT DEVELOPS INTEGRATED, NOVEL, AND SCALABLE PROCESSES FOR WASTE-STREAM VALORIZATION. IT TRAINS THE NEXT GENERATION OF SCIENTISTS AND ENGINEERS IN THE FIELD TO ENSURE THE SUSTAINABILITY OF THE APPROACH AND BROADEN ITS IMPACT. IT ALSO ENGAGES THE GLOBAL COMMUNITY THROUGH MULTIPLE OUTREACH ACTIVITIES, PROVIDING FREE GLOBAL EDUCATION. THE OVERARCHING GOAL IS TO DEVELOP DISRUPTIVE SOLUTIONS TO THE CURRENT WASTE PROBLEMS. ANOTHER AIM IS TO PROVIDE SUSTAINABLE SOLUTIONS FOR THE COMMERCIALLY VIABLE PRODUCTION OF ENERGY, CHEMICALS, AND MATERIALS. CIRCLE AIMS AT DEVELOPING THREE CORE TECHNOLOGIES: (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) TECHNO-ECONOMIC ANALYSIS (TEA), LIFE CYCLE ANALYSIS (LCA), AND RISK ASSESSMENT TO DEVELOP COMMERCIALLY VIABLE BIOPROCESSES FOR WASTE VALORIZATION. TO DEMONSTRATE THE UTILITY AND GENERALIZABILITY OF THESE CORE TECHNOLOGIES, THE CENTER FOCUSES ON THREE WASTE STREAMS: MIXED PLASTICS, C1 GASES, AND BIOGENIC WASTES (E.G., FOOD, AGRICULTURAL, AND PAPER/CARDBOARD WASTES). THESE CORE PROJECTS PROVIDE NOVEL WASTE-CONVERSION PROCESSES THAT CAN BE TRANSLATED TO COMMERCIAL-SCALE, SUSTAINABLE BIOPRODUCTION. THE CENTER ALSO PROVIDES DIVERSE GROUPS OF TRAINEES IN PARTICIPATING NATIONS WITH UNIQUE INTERDISCIPLINARY TRAINING OPPORTUNITIES, INVOLVING SYNTHETIC BIOLOGY, SYSTEMS BIOLOGY, MULTI-OMICS, BIOINFORMATICS, COMPUTATIONAL BIOLOGY, CHEMISTRY, SYSTEMS ENGINEERING, RISK ASSESSMENT, TEA/LCA, AND CHEMICAL ENGINEERING. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE PLANNED FOR THIS AWARD.

ABI DEVELOPMENT: THE ARABIDOPSIS INFORMATION PORTAL

T1D:INVESTIGATING THE GUT MICROBIOME, URINARY PROTEOME AND METABOLOME

OPTIMIZATION, MANUFACTURING AND TESTING OF A LEAD THERAPEUTIC BACTERIOPHAGE COCKTAIL FOR THE TREATMENT OF ANTIBIOTIC-RESISTANT KLEBSIELLA PNEUMONIAE INFECTIONS - PROJECT SUMMARY/ABSTRACT 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, OUR GROUP HAS DEVELOPED A 5-PHAGE LEAD CANDIDATE THERAPEUTIC COCKTAIL THAT IS CAPABLE OF INFECTING 53 OF OUR 100-STRAIN TEST PANEL. THE GOAL OF THIS PROPOSAL IS TO OPTIMIZE OUR LEAD THERAPEUTIC AND ITS PRODUCTION AS WELL AS TO CONDUCT THE REQUIRED PRE-INVESTIGATIONAL NEW DRUG (IND) TESTING AND BENCHMARKING NECESSARY FOR THE SUCCESSFUL SUBMISSION AND REVIEW OF AN IND APPLICATION FOR A PHASE 1 CLINICAL TRIAL. THE PROPOSED WORK WILL BE CONDUCTED THROUGH A PARTNERSHIP BETWEEN THE J. CRAIG VENTER INSTITUTE (JCVI), THE WALTER REED ARMY INSTITUTE OF RESEARCH (WRAIR) AND ADAPTIVE PHAGE THERAPEUTICS (APT). IT 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. THE GOAL TO PREPARE OUR LEAD CANDIDATE THERAPEUTIC FOR IND SUBMISSION TO FDA WILL MATERIALIZE THROUGH THREE MAIN OBJECTIVES: 1) TO OPTIMIZE THE LEAD THERAPEUTIC, 2) TO CONDUCT IND-REQUIRED TESTING, AND 3) TO OPTIMIZE AND SCALE-UP FOR CGMP MANUFACTURING AND TESTING. THE WORKFLOW TO ACHIEVE THESE OBJECTIVES IS INNOVATIVE, UTILIZING CUTTING-EDGE TECHNOLOGIES, AND ENCOMPASSES THE ENTIRE PROCESS FROM OPTIMIZATION AND TESTING TO GMP PRODUCTION OF THE THERAPEUTIC. MORE SIGNIFICANTLY, IT WILL BE A PLATFORM FOR DEVELOPING FUTURE PHAGE-BASED THERAPEUTICS FOR OTHER IMPORTANT BACTERIAL PATHOGENS.

OPTIMIZATION OF ENERGY FLOW THROUGH SYNTHETIC METABOLIC MODULES AND REGULATORY NETWORKS IN A MODEL PHOTOSYNTHETIC EUKARYOTIC MICROBE

CHARACTERIZATION OF BURHOLDERIA PERSISTENCE DETERMINATION AND ANTIBIOTIC RESISTANCE

BREAD: TOWARD DEVELOPMENT OF A VACCINE FOR CONTAGIOUS BOVINE PLEUROPNEUMONIA (CBPP)

TRANSFORMATIVE COMPUTATIONAL INFRASTRUCTURES FOR CELL-BASED BIOMARKER DIAGNOSTICS

AFTER THE SEQUENCING: CURATING THE MEDICAGO TRUNCATULA GENOME

MICROBIOME IN ASTHMA INDUCED BY ENVIRONMENTAL PARTICLE EXPOSURE

METAGENOMICS OF THE MICROBIOME IN ORAL HEALTH AND DISEASE

IDENTIFYING INFLUENZA VIRUS INFECTION SEVERITY AND OUTCOME SIGNATURES THROUGH ARTIFICIAL INTELLIGENCE-DRIVEN ANALYSES - ABSTRACT INFLUENZA AND ASSOCIATED DISEASES REMAIN SIGNIFICANT SOURCES OF ECONOMIC AND PUBLIC HEALTH BURDEN. EVERY YEAR, AROUND THREE TO FIVE MILLION PEOPLE COME DOWN WITH SEVERE CASES OF INFLUENZA WITH ANOTHER 300,000 TO 500,000 MORE WHO DIE WORLDWIDE. AMONGST THOSE WHO ARE DISPROPORTIONATELY AFFECTED ARE INDIVIDUALS WITH CHRONIC CONDITIONS SUCH AS DIABETES, OBESITY, CARDIOVASCULAR DISEASE, CHILDREN AND INDIVIDUALS AGED 65 YEARS AND OLDER. FOR EXAMPLE, 90% OF DEATHS FROM SEASONAL INFLUENZA AND 70% OF INFLUENZA-ASSOCIATED HOSPITALIZATION BELONG TO THIS AGE GROUP. THERE IS ALSO A SIGNIFICANT ASSOCIATION BETWEEN DEVELOPING A HEART ATTACK WITHIN A WEEK OF GETTING INFECTED WITH INFLUENZA A OR B VIRUSES. WHY SOME PEOPLE ARE MORE SUSCEPTIBLE CAN BE DUE TO A MULTITUDE OF FACTORS SUCH AS IMMUNOSENESCENCE, PRE-EXISTING IMMUNITY, GENETICS, DIET, ENVIRONMENT AND OTHER UNDERLYING DISEASES, WHICH MAY CONTRIBUTE TO THE SEVERITY OF INFLUENZA. YET, IT REMAINS DIFFICULT FOR SCIENTISTS AND CLINICIANS TO DETERMINE THE TRAJECTORY OF DISEASE SEVERITY FOR ANY GIVEN PARAMETER OR CATEGORY. THIS IS LARGELY DUE TO ASSIGNING AN OUTCOME WITH A PARTICULAR CORRELATE USING A SINGLE ASSAY OR METHOD. GIVEN THE MULTITUDE OF FACTORS THAT MAY INFLUENCE DISEASE PROGRESSION OR IMMUNITY, A METHOD BY WHICH DIFFERENT DATASETS ARE INTEGRATED TO PREDICT THE OUTCOME WOULD BE HIGHLY BENEFICIAL IN GUIDING CLINICAL PRACTICES. TOWARDS THIS GOAL, WE HYPOTHESIZE THAT A MULTIMODAL NETWORK APPROACH IN ANALYZING DIFFERENT METRICS WILL IDENTIFY FEATURES FROM COMPLEX DATASETS THAT ARE PREDICTIVE OF INFLUENZA DISEASE OUTCOME. THESE FEATURES INCLUDE HOST, COMMENSAL MICROBIAL AND VIRAL FACTORS, AND IDENTIFIABLE INTERACTIONS BETWEEN THEM ASSOCIATED WITH DISEASE AND IMMUNITY. THIS WILL POTENTIALLY REVEAL NEW INSIGHTS INTO INFLUENZA VIRUS-HOST INTERACTIONS AND TRANSFORM CLINICAL PRACTICES. WE WILL UTILIZE ESTABLISHED IMMUNOLOGICAL ASSAYS, SEQUENCING APPROACHES AND METADATA IN ORDER TO TAKE ADVANTAGE OF EXISTING METHODS AND INFRASTRUCTURES AND APPLY IT TO OUR NOVEL BIOINFORMATICS AND ARTIFICIAL INTELLIGENCE WORKFLOWS. TO DO THIS, WE WILL I) GENERATE A COMPREHENSIVE SYSTEMS LEVEL MULTIMODAL DATASET INCLUDING BOTH VIRAL AND HOST FACTORS TO ASSESS DIFFERENTIAL INFLUENZA VIRUS INFECTION SEVERITY SIGNATURES IN A HUMAN COHORT, AND II) UTILIZE MULTIMODAL NETWORK ANALYSIS AND MACHINE LEARNING TO IDENTIFY FEATURES AND INTERACTIONS PREDICTIVE OF THE TRAJECTORY OF DISEASE SEVERITY DUE TO INFLUENZA VIRUS INFECTION.

THE HISTONE DEMETHYLASE JMJD1C IN HUMAN ACUTE MYELOID LEUKEMIA

NEW; TITLE: INTEGRATED SYSTEMS BIOLOGY OF METABOLIC AND TRANSCRIPTIONAL NETWORKS IN A MODEL PHOTOSYNTHETIC MICROBE; PI: ANDREW ALLEN

A PROTEIN-PROTEIN INTERACTION MAP OF ESCHERICHIA COLI

SINGLE CELL GENOMICS OF HUMAN MICROBIAL FLORA

INTERPLAY BETWEEN THE HEAT SHOCK RESPONSE AND HISTIDINE KINASE PATHWAYS IN THE THERMALLY DIMORPHIC FUNGAL PATHOGEN HISTOPLASMA CAPSULATUM

NEW; TITLE: THE STUDY OF MICROBIAL ENVIRONMENTAL PROCESSES RELATED TO THE NATURAL ATTENUATION OF URANUIM AT THE RIFLE SITE USING SYSTEMS-LEVEL BIOLOG

DEVELOPMENT OF CELERA WHOLE GENOME SHOTGUN ASSEMBLER

ENHANCED ALGAL PRODUCTION OF CA FOR IMPROVED ATMOSPHERIC DELIVERY OF CO2 TO PONDS.

CHARACTERIZATION AND EXPRESSION OF DRUG RESISTANCE GENES IN MDROS ORIGINATING FROM COMBAT WOUND INFECTIONS

MOVING BEYOND DIVERSITY BY REVEALING BIOLOGICAL FUNCTIONS OF UNCULTURED BACTERIA

HYDROGEN FROM WATER IN A NOVEL RECOMBINANT CYANOBACTERIAL SYSTEM

EDGE FGT: ESSENTIAL NEW MOLECULAR GENETIC TOOLS FOR DEFINING PHENOTYPE IN THE GLOBAL, HARMFUL ALGAL BLOOM-PRODUCING DIATOM, PSEUDO-NITZCHIA SPP.

THE PURPOSE OF THIS AGREEMENT IS TO FUND RESEARCH IN SUPPORT OF BTO IN THE AMOUNT OF 1,291,589 ON CONTRACT HR0011-18-2-0015.

ALGORITHMICALLY-TUNED PROTEIN FAMILIES, RULE_BASE AND CHARACTERIZED PROTEINS

DIETARY MODULATION OF GUT MICROBIOME AND HOST GENE EXPRESSION ACROSS HUMAN EVOLUTION AND THE EMERGENCE OF MODERN HUMAN DISEASE

ABI DEVELOPMENT: A NOVEL PROTEIN FRAGMENT ASSEMBLER FOR METAGENOMIC DATA ANALYSIS

HTS ASSAY FOR P. FALCIPARUM APICOPLAST GLUTAMYL-TRNA SYNTHETASE

GENOMICS OF TETRAHYMENA

STUDY OF THE IMPACT OF LONG-TERM SPACE TRAVEL ON THEASTRONAUT'S MICROBIOMEOUR GOAL IS TO DETERMINE HOW THE COMPOSITION OF THE HUMAN MICROBIOME CHA

ELUCIDATING THE CENTRAL PATHWAY OF MICROBIAL ELECTRON TRANSPORT SYSTEMS IN COMPLEX CONSORTIA

MAXIMIZING MULTI-ENZYME SYNERGY DEGRADATION IN YEAST

URETHRAL CATHETER-ASSOCIATED POLYBACTERIAL BIOFILM FORMATION AND DISPERSAL

REGULATION OF CHEMR23 IN RESOLUTION OF INFLAMMATION

SYNTHETIC ENGINEERING OF BACTERIOPHAGE FOR TREATMENT OF WOUND INFECTIONS

TAS::89 0222::TAS; NEW; TITLE: MANAGING RISKS OF SYNTHETIC BIOLOGY: ASSESSING THE U.S. REGULATORY SYSTEMS; PI: MICHELE GARFINKEL

THERAPEUTIC INHIBITORS OF BACTERIAL QUORUM SENSING FROM FILAMENTOUS FUNGI

GENOME-WIDE PREDICTION AND ANALYSIS OF CODING VARIANTS

ROLE OF THE DIATOM MITOCHONDRIA IN CELLULAR NITROGEN METABOLISM

HOST-PATHOGEN INTERACTIONS IN INVASIVE ASPERGILLOSIS

HIGH-THROUGHPUT GENE KNOCKOUT PRODUCTION IN TETRAHYMENA THERMOPHILA

DEVELOPING GENOME TRANSPLANTATION FOR NON-MYCOPLASMA BACTERIA TO ENHANCE THE CREATION OF SYNTHETIC CELLS -IN 2010, RESEARCHERS CONSTRUCTED A SYNTHETIC BACTERIAL CELL WHOSE GENOME WAS SYNTHESIZED FROM LABORATORY CHEMICALS. IT WAS ANTICIPATED THAT THIS FIRST SYNTHETIC CELL WOULD BE FOLLOWED BY MANY OTHERS CONSTRUCTED BY SCIENTISTS ALL OVER THE WORLD. INDEED, RESEARCHERS ANTICIPATED THAT BACTERIA OF ALL TYPES WOULD BE DESIGNED AND CONSTRUCTED TO SOLVE HUMAN PROBLEMS IN MEDICINE, ENERGY, INDUSTRY, ENVIRONMENTAL REMEDIATION AND BASIC RESEARCH. THAT HAS YET TO HAPPEN BECAUSE IT IS DIFFICULT TO TRANSPLANT A RATIONALLY DESIGNED SYNTHETIC GENOME INTO A SUITABLE RECIPIENT BACTERIAL CELL. IN THE PROJECT PROPOSED HERE, THE ORIGINAL INVENTORS OF THE GENOME TRANSPLANTATION PROCEDURE WILL ADAPT THE TECHNIQUE SO THAT IT CAN BE APPLIED TO OTHER BACTERIA. THIS WILL ALLOW ACADEMIC AND INDUSTRIAL BACTERIOLOGISTS AND SYNTHETIC BIOLOGISTS TO BUILD NEW BACTERIA WITH REMARKABLE CAPABILITIES. IN ADDITION TO REMOVING A HUGE TECHNICAL HURDLE STALLING THE CONSTRUCTION OF SYNTHETIC CELLS, THIS PROJECT WILL FACILITATE THE TRAINING OF THE NEXT GENERATION OF SCIENTISTS IN THE FIELD OF SYNTHETIC BIOLOGY AND WILL BE USED AS A PLATFORM FOR DISCUSSIONS WITH THE SCIENTIFIC COMMUNITY, INDUSTRY AND PUBLIC. 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 HUMANS. TO DATE, GENOME TRANSPLANTATION HAS ONLY BEEN ACHIEVED USING A SMALL SUBSET OF THE ATYPICAL BACTERIA CALLED MYCOPLASMAS. THE GOALS OF THIS PROJECT ARE TO INVESTIGATE 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. A POTENTIAL OUTCOME IS TO ESTABLISH A SET OF RULES THAT SYNTHETIC CELL BUILDERS CAN USE TO TRANSPLANT ISOLATED WHOLE SYNTHETIC BACTERIAL GENOMES AND PRODUCE NEW SYNTHETIC CELLS WITH DESIRED PROPERTIES. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

COLLABORATIVE RESEARCH: CELLULAR, ECOLOGICAL, AND BIOGEOCHEMICAL IMPACTS OF A NOVEL BLUE COPPER FERRITIN -PHYTOPLANKTON REQUIRE IRON TO GROW AND TO PRODUCE THE ORGANIC MATTER THAT FUELS MARINE ECOSYSTEMS, HELPING TO DRAW DOWN CARBON FROM THE ATMOSPHERE. BUT THE ABILITY TO UNDERSTAND HOW IRON AVAILABILITY IN THE OCEAN IMPACTS PHYTOPLANKTON PRODUCTIVITY AND CARBON DRAWDOWN IS CONSTRAINED BY A LIMITED UNDERSTANDING OF THE RESERVOIRS OF IRON IN THE MARINE ENVIRONMENT. THIS RESEARCH INTO PHYTOPLANKTON IRON STORAGE MECHANISMS PROVIDES NEW INSIGHTS INTO THE PRODUCTION OF BIOGENIC MOLECULES BY PHYTOPLANKTON WHICH HELP MAINTAIN IRON IN THE WELL-LIT UPPER LAYERS OF THE OCEAN. THE STUDY CHARACTERIZES THE MECHANISM OF A NOVEL PROTEIN ? A COPPER-BASED FERRITIN ? AND EXPLORES HOW THIS ENVIRONMENTALLY ABUNDANT CLASS OF PROTEINS MAY PROVIDE AN ECOLOGICAL ADVANTAGE TO SOME MARINE PHYTOPLANKTON AND HELP EXPLAIN THE MAINTENANCE OF DISSOLVED IRON IN THE WATER COLUMN. IT ADVANCES THE UNDERSTANDING OF HOW IRON LIMITATION AFFECTS MARINE ECOSYSTEMS AND THEIR CAPACITY TO DRAW DOWN CARBON. FURTHERMORE, THE PROJECT SUPPORTS THE DEVELOPMENT OF A K-8 EDUCATIONAL MODULE USING HANDS-ON TIDEPOOL CHEMISTRY AND ECOLOGY TO TEACH CHILDREN BROADER CONCEPTS IN BIOGEOCHEMICAL CYCLING. THIS EDUCATIONAL EFFORT TARGETS 600 SEVENTH-GRADE STUDENTS FROM A MIDDLE SCHOOL SERVING UNDERSERVED POPULATIONS IN SOUTHEASTERN SAN DIEGO. THE EDUCATIONAL MODULE IS TO BE MADE BROADLY AVAILABLE VIA MARINE SCIENCE EDUCATIONAL WEBSITES. THIS PROJECT IS GUIDED BY MECHANISTIC, PHENOTYPIC, AND BIOGEOCHEMICAL HYPOTHESES. RECENT STATE-OF-THE-ART ADVANCES IN METALLOPROTEOMICS ARE LEVERAGED TO UNDERSTAND THE ELECTROCHEMICAL LOADING AND UNLOADING OF IRON IN NOVEL BLUE COPPER FERRITINS, BOTH IN-VIVO AND IN-VITRO, USING THE MODEL DIATOM PHAEODACTYLUM TRICORNUTUM. REVERSE GENETICS TECHNIQUES ARE USED TO CHARACTERIZE HOW BLUE COPPER FERRITINS CONTRIBUTE TO ECOLOGICAL ADVANTAGE IN IRON-LIMITED OCEANS. BECAUSE THESE BLUE COPPER FERRITINS, NEW TO SCIENCE, ARE SELF-ASSEMBLING, THERMOSTABLE, ELECTROCHEMICALLY-CONTROLLED CARGO DELIVERY PROTEINS, THEIR DESCRIPTION CAN BE OF INTEREST TO NANO- AND BIO-ENGINEERS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

ROL:FELS:RAISE: BUILDING AND MODELING SYNTHETIC BACTERIAL CELLS

TRANSCRIPTOMICS FROM SINGLE CIRCULATING TUMOR CELLS

CONSTRUCTION OF THE FORENSIC MICROBIOME DATABASE WITH ENHANCED GEOSOURCING

HYDROGEN FROM WATER IN A NOVEL RECOMBINANT CYANOBACTERIAL SYSTEM

DEFINING THE COMPETITIVE EDGE: CELLULAR SYSTEMS THAT ENABLE NITRATE ASSIMILATION IN MARINE DIATOMS

THE PURPOSE OF THIS COOPERATIVE AGREEMENT IS TO FUND RESEARCH IN SUPPORT OF (DARPA), (BTO) BIOLOGICAL CONTROL PROGRAM IN THE AMOUNT OF 897,316.

COLLABORATIVE RESEARCH: IRON BIOAVAILABILITY IN HIGH-CO2 OCEANS: NEW PERSPECTIVES ON IRON ACQUISITION MECHANISMS IN DIATOMS

COLLABORATIVE RESEARCH: SYNERGISTIC EFFECTS OF IRON, CARBON DIOXIDE & TEMPERATURE ON THE FATE OF NITRATE: IMPLICATIONS FOR FUTURE CHANGES IN EXPORT P

SOFTWARE AND SERVER FOR TAXONOMIC BINNING OF METAGENOMIC SEQUENCES

PROBING MOLECULAR INTERACTIONS IN THE NITROGEN FIXING CYANOBACTERIA-FEATHER MOSS SYMBIOSIS

INVESTIGATING ORAL PATHOGEN VIRULENCE WITHIN COMPLEX ORAL BIOFILM COMMUNITIES

A DIGITAL MICROFLUIDIC SYSTEMS FOR GENE SYNTHESIS, SEQUENCING AND RECOVERY

COLLABORATIVE RESEARCH: DIRECTION AND MECHANISMS OF SEASONAL CHANGE IN ARCTIC MICROBIAL COMMUNITIES

SELECT: SELECTING ELITE-PERFORMERS WITH LONGITUDINAL EPIGENOMIC CHARACTERIZATION AND TRACKING

COMPARATIVE STUDY OF SECRETION SYSTEMS IN INTRACELLULAR PATHOGENS

ENGINEERING SKIN MICROBIOMES FOR THERMAL REGULATION

DIMENSIONS: COLLABORATIVE RESEARCH: FUNCTIONAL DIVERSITY OF MARINE EUKARYOTIC PHYTOPLANKTON AND THEIR CONTRIBUTIONS TO THE C AND N CYCLING

TAS::89 0222::TAS; NEW; TITLE: BACTERIAL NANOWIRES AND EXTRACELLULAR ELECTRON TRANSFER TO HEAVY METALS AND RADIONUCLIDES BY BACTERIAL ISOLATES FROM D

IDENTIFYING THE MOLECULAR DETERMINANTS OF THERMOADAPTATION AND PARASITIC GROWTH OF HISTOPLASMA CAPSULATUM - PROJECT SUMMARY HISTOPLASMA CAPSULATUM CAUSES PULMONARY AND SYSTEMIC INFECTIONS IN BOTH HEALTHY AND IMMUNOCOMPROMISED INDIVIDUALS AND IS THE MOST COMMON CAUSE OF FUNGAL RESPIRATORY INFECTIONS IN HEALTHY HOSTS. HISTOPLASMA IS A DIMORPHIC FUNGAL PATHOGEN THAT CAN SENSE AND RESPOND TO HUMAN BODY TEMPERATURE BY CHANGING ITS GROWTH PROGRAM FROM A HYPHAL (MOLD) FORM TO A PARASITIC YEAST FORM. INFECTION OCCURS WHEN THE SOIL IS DISRUPTED, FACILITATING DISPERSION OF HYPHAL FRAGMENTS OR SPORES THAT ARE INHALED BY HUMANS. SPORES AND HYPHAL FRAGMENTS ARE THE PRIMARY INFECTIOUS AGENTS; HOWEVER, ONCE INTRODUCED INTO THE HOST, THE PATHOGEN CONVERTS TO A BUDDING- YEAST FORM, WHICH SURVIVES AND REPLICATES WITHIN HOST MACROPHAGES. HISTOPLASMA STRAINS ARE CLASSIFIED INTO AT LEAST EIGHT GEOGRAPHICALLY ISOLATED CLADES: NORTH AMERICAN CLASSES 1 AND 2 (NAM 1 AND NAM 2), LATIN AMERICAN GROUPS A AND B (LAM A AND LAM B), EURASIAN, NETHERLANDS, AUSTRALIAN AND AFRICAN, AND AN ADDITIONAL DISTINCT LINEAGE (H81) COMPRISED OF PANAMANIAN ISOLATES. GIVEN THE DIVERSITY IN PHENOTYPIC TRAITS, DISEASE MANIFESTATION AND GEOGRAPHIC DISTRIBUTION, HISTOPLASMA SPECIES PRESENT A UNIQUE MODEL, WHERE VARIATION IN PHENOTYPIC TRAITS CAN BE STUDIED IN CONJUNCTION WITH THE PHYLOGENETIC MARKERS. OUR LONG-TERM RESEARCH GOAL IS TO DETERMINE THE GENETIC PATHWAYS THAT GOVERN THERMOADAPTATION AND VIRULENCE TRAITS, WHICH ARE BOTH REQUIRED FOR THE PARASITIC LIFESTYLE OF HISTOPLASMA SPECIES. THE GOAL OF THE PROPOSED PROJECT IS TO IDENTIFY GENES OR GENOMIC REGIONS IN HISTOPLASMA THAT CONTROL THERMOADAPTATION AND INTRACELLULAR GROWTH. PREVIOUSLY PUBLISHED STUDIES SHOWED THAT HISTOPLASMA SPECIES CAN DISPLAY DIFFERENCES IN YEAST-PHASE MORPHOLOGY AND VIRULENCE. WE RECENTLY PUBLISHED COMPARISONS OF THE CHROMOSOMAL-LEVEL ASSEMBLIES OF FIVE HISTOPLASMA GENOMES (H143, H88, G186AR, WU24, AND G217B), AND SHOWED THAT THESE GENOMES ARE RELATIVELY INVARIANT IN TERMS OF GENE CONTENT. INSTEAD, THE PRIMARY DIFFERENCES BETWEEN THE GENOMES ARE IN THE ORGANIZATION OF GENES AND THE ABUNDANCE OF REPEATS AND TRANSPOSABLE ELEMENTS. THUS, WE HYPOTHESIZE THAT THE DIFFERENCES IN GENE ORDER, REPEAT CONTENT AND SINGLE NUCLEOTIDE VARIATIONS (SNVS) CAN DRIVE SOME OF THE OBSERVED VARIATIONS IN THERMOADAPTATION AND VIRULENCE TRAITS. IN THIS PROJECT, WE WILL SEQUENCE AND FULLY ASSEMBLE ~150 NEW CLINICAL ISOLATES OF HISTOPLASMA AND MAKE ASSOCIATIONS WITH GENE ORDER, REPEAT CONTENT AND SNVS TO THERMOADAPTATION (AIM 1) AND INTRACELLULAR GROWTH (AIM 2) OF HISTOPLASMA. WE ANTICIPATE THAT THESE RESULTS WILL REVEAL NEW GENES AND GENOMIC REGIONS THAT ARE CRITICAL IN REGULATING PARASITIC LIFESTYLE OF HISTOPLASMA. A BETTER UNDERSTANDING OF HISTOPLASMA GENOME CONTENT AND IDENTIFICATION OF REGULATORS OF HISTOPLASMA PARASITIC GROWTH CAN ALSO LEAD TO DEVELOPMENT OF BETTER MOLECULAR DIAGNOSTIC SCREENS FOR HISTOPLASMA IN CLINICAL SETTINGS.

DEVELOPMENT OF NOVEL PROTEIN-BASED VACCINE FORMULATIONS TO PREVENT PNEUMOCOCCAL COLONIZATION AND DISEASE

REPRODUCIBLE ANALYTICS FOR SECONDARY ANALYSES OF IMMPORT VACCINATION-RELATED CYTOMETRY DATA

EXPLORING THE ECOLOGICAL ROLE OF ROTHIA MUCILAGINOSA AND IT'S IRON BINDING SIDEROPHORE ENTEROBACTIN - PROJECT SUMMARY THE ORAL CAVITY IS A HIGHLY DIVERSE MICROBIAL ENVIRONMENT, CONSISTING OF >2000 BACTERIAL, ARCHAEAL, AND FUNGAL SPECIES MOST OF WHICH HAVE NOT BEEN FUNCTIONALLY CHARACTERIZED. NUMEROUS STUDIES HAVE IDENTIFIED THAT ORAL ROTHIA MUCILAGINOSA, A GRAM-POSITIVE ORAL COMMENSAL ACTINOBACTERIA, IS HIGHLY ABUNDANT IN SALIVA AND DENTAL PLAQUE IN GLOBAL HUMAN POPULATIONS, HOWEVER, ITS ECOLOGICAL ROLE IS UNKNOWN. WE IDENTIFIED THAT R. MUCILAGINOSA PRODUCED THE CATECHOL SIDEROPHORE ENTEROBACTIN, THE STRONGEST IRON-CHELATING MOLECULE KNOWN. WE ALSO IDENTIFIED THE ENTEROBACTIN BIOSYNTHETIC GENE CLUSTER (ENT-BGC) IN GLOBAL ROTHIA GENOMES, WHICH SUGGESTS THAT ENTEROBACTIN IS CRUCIAL IN ROTHIA ECOLOGY. THE PURIFIED ENTEROBACTIN COMPOUND IMPACTED GROWTH DIFFERENTIALLY WHEN AMENDED TO CULTURES OF OTHER ORAL BACTERIAL SPECIES. IT BOOSTED THE GROWTH OF COMMENSAL STREPTOCOCCUS SALIVARIUS WHILE IT REDUCED THE GROWTH OF SOME STRAINS OF PATHOGENIC S. MUTANS. THE OVERARCHING GOAL OF THIS STUDY IS TO DETERMINE THE ROLE OF R. MUCILAGINOSA PRODUCED ENTEROBACTIN IN INTERACTIONS WITH BOTH THE ORAL MICROBIOTA AND HUMAN ORAL EPITHELIAL CELLS REPRESENTING THE ORAL MUCOSA. WE PROPOSE AN INTERDISCIPLINARY RESEARCH APPROACH WITH TWO SPECIFIC AIMS: AIM 1: CHARACTERIZATION OF MOLECULAR AND ECOLOGICAL RESPONSES OF ORAL BACTERIA TO R. MUCILAGINOSA PRODUCED ENTEROBACTIN. THE ACTIVITIES OF ENTEROBACTIN WILL BE CHARACTERIZED BOTH IN HIGHLY DIVERSE ORAL IN VITRO GROWN BIOFILMS, AND IN BACTERIAL MONOCULTURES. THE CAPACITY TO IMPORT ENTEROBACTIN BY DIFFERENT BACTERIAL COMMUNITY MEMBERS WILL BE REVEALED BY AMENDING GROWTH CULTURES WITH FLUORESCENTLY RHODAMINE- LABELED ENTEROBACTIN, FLUORESCENCE-ACTIVATED CELL SORTING, AND CONFOCAL MICROSCOPY. MULTI-OMICS SEQUENCING WILL BE CONDUCTED TO CHARACTERIZE FUNCTIONAL CHANGES BOTH IN BIOFILM COMMUNITIES AS WELL AS IN SINGLE AND DUAL- SPECIES CULTURES, SPECIFICALLY TARGETING GENES ENCODING TRANSPORT PROTEINS AND RELEASE MECHANISMS OF ENTEROBACTIN. AIM 2: DETERMINE THE IMPACT OF ENTEROBACTIN ON ORAL MUCOSAL SENTINEL CELLS. CO-CULTIVATION SYSTEMS INCLUDING BOTH 2D AND 3D MODELS OF HUMAN ORAL EPITHELIAL CELLS WILL BE APPLIED TO STUDY INTERACTIONS WITH THE ORAL MICROBIOTA AND ENTEROBACTIN. OUTCOMES OF THE INTERACTIONS WILL BE CHARACTERIZED BY USING A MULTIPRONGED APPROACH INCLUDING A COMPARATIVE GENE TRANSCRIPTION APPROACH AND A GENE REPORTER SYSTEM THAT REVEALS ROS ACTIVATION IN HOST CELLS. PRODUCTION OF EXTRACELLULAR PRO- AND ANTI-INFLAMMATORY CYTOKINES IN CELL MEDIUM RELATION TO ENTEROBACTIN AND ORAL BACTERIA WILL ALSO BE ADDRESSED TO ELUCIDATE INTERACTIONS OF IMPORTANCE. THE PROPOSED STUDY PROVIDES A UNIQUE OPPORTUNITY TO EXPAND OUR KNOWLEDGE ON ENTEROBACTIN FUNCTIONAL ROLE IN THE ORAL MICROBIOTA, AND IN INTERACTIONS WITH HUMAN ORAL EPITHELIAL CELLS, WHICH IS SEVERELY LACKING. A DEEPER KNOWLEDGE OF THE ROLE OF IRON SCAVENGING SIDEROPHORES IN THE ORAL CAVITY WILL LIKELY BRING ABOUT A SHIFT IN THE RESEARCH FIELD OF ORAL MICROBIAL ECOLOGY AND SHINE A NEW LIGHT ON THE IMPORTANCE OF IRON METABOLISM IN ORAL HEALTH.

SOMATIC MUTATION IN THE ETIOLOGY OF MULTIPLE SCLEROSIS

EXPLORING THE ECOLOGICAL ROLES OF MUTANIC ACID AND MUTANICYCLIN; TWO NOVEL SMALL MOLECULES PRODUCED BY STREPTOCOCCUS MUTANS

DEVELOPMENT OF FRESH (FAST RESCUE EMPLOYING SELF-HELPER VIRUS) - A RAPID, GENERALIZABLE METHOD TO RESCUE INFECTIOUS VIRUS FROM NONINFECTIOUS GENOMIC MATERIAL

ENGINEERING OF A TEMPERATE BURKHOLDERIA CEPACIA COMPLEX PHAGE TO IMPROVE EFFICACY AS A POTENTIAL THERAPEUTIC - PROJECT SUMMARY BACTERIA IN THE BURKHOLDERIA CEPACIA COMPLEX (BCC) CAUSE DIFFICULT TO TREAT INFECTIONS IN PATIENTS WITH COMPROMISED RESPIRATORY SYSTEMS, SUCH AS THOSE WITH CYSTIC FIBROSIS (CF). ALTERNATIVE TREATMENT OPTIONS ARE NEEDED, SINCE ANTIBIOTICS OFTEN FAIL THESE PATIENTS. BACTERIOPHAGE (PHAGE) THERAPY IS A PROMISING STRATEGY, YET THERAPEUTICALLY IDEAL PHAGES ARE DIFFICULT TO FIND AND NARROW IN THEIR RANGE OF USE DUE TO HOST SPECIFICITY. IN THE PROPOSED STUDY, WE CONTINUE DEVELOPMENT OF A POTENTIAL PHAGE THERAPEUTIC SOURCED FROM BURKHOLDERIA ITSELF. WE HAVE ISOLATED A PHAGE, CALLED BCC02, THAT WAS PRESENT WITHIN THE GENOME OF A BURKHOLDERIA BACTERIA (A PROPHAGE) AND HAVE SHOWN THAT IT CAN KILL OTHER BACTERIA WITHIN THE SAME GENUS. HOWEVER, THIS PHAGE STILL HAS THE POTENTIAL TO INTEGRATE INTO OTHER BACTERIAL GENOMES, WHICH IS AN UNDESIRABLE TRAIT FOR PHAGE THERAPY. BY ENGINEERING CHANGES TO THE BCC02 GENOME USING SYNTHETIC BIOLOGY TECHNIQUES, WE HYPOTHESIZE THAT WE CAN INCREASE ITS RANGE OF THERAPEUTIC POTENTIAL BY DISABLING ITS ABILITY TO INTEGRATE INTO THE BACTERIAL GENOME, AND THAT THIS CHANGE WILL INCREASE THE NUMBER OF BACTERIA THAT IT CAN LYSE. THE SPECIFIC AIMS OF THIS PROJECT ARE TO (1) ENGINEER THIS PHAGE TO LOSE THE ABILITY TO LYSOGENIZE (INTEGRATE INTO BACTERIAL GENOMES) THEN TEST THE EFFECTS OF THESE MODIFICATIONS ON BACTERIAL HOST RANGE AND (2) TEST ACTIVITY OF OUR ORIGINALLY ISOLATED PHAGE, BCC02 AS WELL AS OUR ENGINEERED VARIANT ON A CLINICALLY RELEVANT PANEL OF PATHO-ADAPTED ISOLATES FROM PATIENTS WITH CF. WE PROPOSE TO USE TRANSFORMATION-ASSOCIATED RECOMBINATION (TAR) CLONING METHODS TO TARGET THE LYSOGENY CONTROL REGION OF THE BCC02 GENOME FOR REMOVAL. WE HYPOTHESIZE THAT LOSS OF INTEGRATION ABILITY WILL FORCE THIS PHAGE INTO AN OBLIGATELY LYTIC LIFESTYLE, WHERE IT WILL LYSE ALL BACTERIA IT IS ABLE TO INFECT. SUCCESSFUL COMPLETION OF THIS PROJECT WILL DETERMINE THE FEASIBILITY OF ENGINEERING OBLIGATELY LYTIC BURKHOLDERIA-TARGETING PHAGES FROM BURKHOLDERIA SPP. PROPHAGES, SHED LIGHT ON THE EFFECTS OF LYTIC LIFESTYLE ON HOST RANGE, AND ESTABLISH THE UTILITY OF THESE PHAGES FOR TACKLING PARTICULARLY PROBLEMATIC CLINICAL INFECTIONS. IN ADDITION, THIS STUDY MAY PRODUCE A BCC- TARGETING PHAGE THAT IS PRIMED FOR DEVELOPMENT TO BE USED FOR PHAGE THERAPY.

COMBINATORY GENOMIC ASSEMBLY TO ASSESS HSV-1 PHENOTYPES

COLLABORATIVE RESEARCH: FUNCTIONAL GENOMIC INVESTIGATIONS OF IRON AND CARBON CYCLE COUPLING IN SELECT KEYSTONE MARINE BACTERIA HETEROTROPHS

SYNTHETIC GENOMICS TO IMPROVE A PHAGE-BASED DIAGNOSTIC FOR MULTI-DRUG RESISTANT BACTERIA

COLLABORATIVE RESEARCH: GENE CONTENT, GENE EXPRESSION, AND PHYSIOLOGY IN MESOPELAGIC AMMONIA-OXIDIZING ARCHAEA

LIFE IN AN ULTRA-BASIC AND ULTRA-REDUCING SETTING: THE CEDARS SERPENTINIZATION COMMUNITIES

GENOMICS SCHOLAR PROGRAM

REGULATORY CIRCUITS THAT LINK CELL FATE AND VIRULENCE IN HISTOPLASMA CAPSULATUM

SMALL MOLECULE INHIBITOR SCREEN AGAINST THE HISTONE DEMETHYLASE JMJD1C TO DEVELOP A TARGETED THERAPY FOR ACUTE MYELOID LEUKEMIA

HOST-PATHOGEN INTERACTIONS FOR BURKHOLDERIA SPP

A STUDY OF ANTIBIOTICS USAGE ON EARLY GUT MICROBIOME COLONIZATION AND ESTABLISHMENT IN YOUNG CHILDREN

METAGENOMICS GUIDED PATHOGEN DISCOVERY IN TRAVELERS' DIARRHEA

GENETIC MANIPULATION OF UNREAPLASMA SPP. INFECTING HUMANS USING SYNTHETIC GENOMIC

WEB-BASED BIOINFORMATICS PORTAL FOR RNA-SEQ BASED TRANSCRIPTOMICS AND GENOME-WIDE ANALYSIS OF GENE REGULATION IN AGRICULTURAL ANIMAL SPECIES

RECOVERY OF RESOURCES IS CRITICAL FOR REDUCING UP-MASS AND FACILITATING LONG-DURATION AND SELF-SUSTAINING NASA MISSIONS. THE ABILITY TO PROVIDE VITAL

CIC: (SEA): EXPLORING AZURE AS A PLATFORM FOR INTERACTIVE PROTEIN-PROTEIN DOCKING

IMPACT OF MITOCHONDRIAL GENOME VARIATION ON EXTREME PROSTATE CANCER DISPARITIES

SPACEFLIGHT HAS DEMONSTRATED CONCERNING IMPACTS TO HUMAN PHYSIOLOGY INCLUDING WELL DOCUMENTED IMMUNE SYSTEM DYSREGULATION. DIET IMMUNE FUNCTION AND THE MICROBIOME ARE INTERLINKED BUT DIET IS THE ONLY ONE OF THESE FACTORS THAT WE HAVE THE ABILITY TO EASILY AND SIGNIFICANTLY ALTER ON EARTH OR DURING FLIGHT. IT IS EXPECTED THAT AS WE UNDERSTAND DIETARY IMPACTS MORE THOROUGHLY WE MAY CONTINUE TO IMPROVE THE SPACEFLIGHT DIET IN DIRECT SUPPORT OF CREW HEALTH. WE PROPOSE HERE AN INTERDISCIPLINARY STUDY THAT WILL DETERMINE THE EFFECT OF THE CURRENT SPACEFLIGHT DIET COMPARED TO AN "ENHANCED" SPACEFLIGHT DIET (25% MORE FOODS RICH IN OMEGA-3 FATTY ACIDS LYCOPENE FLAVONOIDS FRUITS AND VEGETABLES) WITH COMPLETE DIETARY TRACKING ON IMMUNE FUNCTION GUT MICROBIOTA COMPOSITION AND NUTRITIONAL STATUS OF CREW IN GROUND-CONTROL ANALOGS AND ON ISS MISSIONS. WE HYPTHESIZE THAT BY INCREASING CONSUMPTION OF FRUITS AND VEGETABLES AND BIOACTIVE COMPOUNDS (E.G. OMEGA-3 FATTY ACIDS LYCOPENE FLAVONOIDS) AND ENHANCING OVERALL NUTRITIONAL INTAKE DURING SPACEFLIGHT (OR A GROUND-BASED ANALOG OF SPACEFLIGHT) WE WILL IMPROVE HUMAN IMMUNOLOGICAL PROFILES THE TAXONOMIC PROFILE OF THE GUT MICROBIOTA AND NUTRITIONAL STATUS BIOMARKERS. POSITIVE ASSOCIATIONS BETWEEN BENEFICIAL IMPROVEMENTS WILL PROVIDE EVIDENCE TO BETTER PREDICT THE IMPACT OF DIET ON CREW HEALTH AND ADAPTATION TO SPACEFLIGHT AND TO DESIGN TARGETED MORE-EFFICIENT DIETARY INTERVENTIONS. SPECIFICALLY WE PROPOSE TO 1) IMPLEMENT A PILOT GROUND-CONTROL STUDY WITH ANALOG CREW RANDOMIZED BETWEEN TWO SPACEFLIGHT DIETS AND DETERMINE DIET EFFECTS ON IMMUNE DYSREGULATION INCLUDING LEUKOCYTE DISTRIBUTION INFLAMMATORY CYTOKINE PROFILES T CELL FUNCTION AND OTHER RELEVANT IMMUNOLOGICAL MARKERS THE TAXONOMIC AND METATRANSCRIPTOMIC PROFILE OF THE GUT MICROBIOME AND NUTRITIONAL BIOMARKERS AND METABOLITES AT SELECTED INTERVALS AND STATISTICALLY EVALUATE TO ASSOCIATE SHIFTS ACROSS EACH MEASURE AND IN RELATION TO NUTRIENT INTAKE; AND 2) DETERMINE EFFECTS OF DIET ON IMMUNE DYSREGULATION INCLUDING LEUKOCYTE DISTRIBUTION INFLAMMATORY CYTOKINE PROFILES T CELL FUNCTION AND OTHER RELEVANT IMMUNOLOGICAL MARKERS THE TAXONOMIC AND METATRANSCRIPTOMIC PROFILE OF THE GUT MICROBIOME AND NUTRITIONAL BIOMARKERS AND METABOLITES AT SELECTED INTERVALS IN SPACEFLIGHT AND STATISTICALLY EVALUATE TO ASSOCIATE SHIFTS ACROSS EACH MEASURE AND IN RELATION TO GROUND-CONTROL DATA. THIS STUDY SPECIFICALLY ADDRESSES THE B.4 RESEARCH EMPHASIS 3 - UNDERSTANDING HOW COMPLEX ORGANISMS ADAPT TO SPACEFLIGHT BY PROVIDING DETAILED COMPREHENSIVE ANALYSIS OF THE EFFECT OF DIET ON THE HUMAN IMMUNE SYSTEM GUT MICROBIOTA AND NUTRITIONAL STATUS DURING HUMAN ADAPTATION TO SPACEFLIGHT.

UNIFYING SYNTHETIC SMALL REGULATORY RNAS -RNA IS GENERALLY KNOWN AS A MESSENGER TO CARRY GENETIC INSTRUCTIONS FROM DNA, HOWEVER, MANY SMALL RNAS ACT AS REGULATORS CONTROLLING GENE EXPRESSION. OVER THE PAST TWO DECADES, RESEARCHERS HAVE ENGINEERED SUCH REGULATORY RNAS AND HAVE BUILT SIMPLE RNA-BASED GENETIC CIRCUITS IN BACTERIA, NEVERTHELESS, THE CONSTRUCTION OF COMPLEX RNA-BASED GENETIC CIRCUITS REMAINS CHALLENGING. THIS PROJECT INVOLVES DEVELOPING GENERALIZABLE DESIGN PRINCIPLES BY WHICH SIMPLE RNA-BASED GENETIC CIRCUITS CAN BE COMBINED TO GENERATE COMPLEX GENETIC CIRCUITS. THE UTILITY OF THESE COMPLEX CIRCUITS IS DEMONSTRATED BY ENGINEERING BACTERIA THAT PRODUCE VALUABLE CHEMICALS THAT CONTRIBUTE TO THE BIOECONOMY. IN ADDITION, THIS PROJECT PROVIDES UNIQUE INTERDISCIPLINARY TRAINING OPPORTUNITIES FOR STUDENTS, INVOLVING BIOPHYSICS, BIOCHEMISTRY, MOLECULAR BIOLOGY AND ENGINEERING. AN OUTREACH PROGRAM PROVIDES K-12 TEACHERS WITH THE MATERIALS TO LEAD THEIR STUDENTS THROUGH LAB ACTIVITIES, BROADENING STUDENT PARTICIPATION IN SCIENCE AND ENGINEERING. THE PAST TWO DECADES HAVE WITNESSED REMARKABLE PROGRESS IN UNDERSTANDING COMPLEX GENE REGULATORY NETWORKS BY BUILDING SIMPLER GENETIC CIRCUITS FROM THE BOTTOM-UP. HOWEVER, RNA-BASED GENETIC CIRCUITS HAVE SELDOM BEEN BUILT BY INTEGRATING DIFFERENT TYPES OF RNA REGULATORS THAT CONTROL MULTIPLE STEPS OF GENE EXPRESSION (E.G., BOTH TRANSCRIPTION AND TRANSLATION). CONSEQUENTLY, RNA-BASED CIRCUIT COMPLEXITY IS LIMITED. IN THIS PROJECT, THE INVESTIGATORS FIRST BUILD RNA-BASED GENE EXPRESSION CONTROLLERS (GECS) THAT DEMONSTRATE CONSISTENTLY PREDICTABLE BEHAVIORS REGARDLESS OF CONNECTED GENETIC PARTS. MATHEMATICAL MODELING IS COMBINED WITH EXPERIMENTAL CHARACTERIZATION IN ORDER TO SYSTEMATICALLY CONNECT DIFFERENT SENSORS TO RNA REGULATORS. NEXT, INSIGHTS INTO THE CIRCUIT INTEGRATION RULE ARE OBTAINED FIRST BY QUANTITATIVELY CHARACTERIZING BOTH INTEGRATED GENETIC PROGRAMS AND INDIVIDUAL GECS THEN BY COMPARING THEIR BEHAVIORS BEFORE AND AFTER INTEGRATION. FINALLY, BASED ON THE GATHERED DESIGN RULES, DYNAMIC PATHWAY CONTROLLERS ARE CREATED TO AUTONOMOUSLY MODULATE METABOLIC PATHWAYS, DEMONSTRATING ENHANCED BIOCHEMICAL PRODUCTION. THIS INTERDISCIPLINARY PROJECT PROVIDES THE RESEARCH COMMUNITY WITH A UNIFIED, STANDARDIZED RNA REGULATOR TOOLBOX FOR FUNDAMENTAL RESEARCH AND BIOTECHNOLOGICAL APPLICATIONS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

CELL TYPE HARMONIZATION OF SINGLE CELL DATA IN HUBMAP AND GTEX - PROJECT SUMMARY/ABSTRACT THE NIH COMMON FUND HAVE SUPPORTED THE GENERATION, MANAGEMENT, AND SHARING OF SINGLE CELL GENOMIC DATA FROM MILLIONS OF CELLS THROUGH SEVERAL LARGE INTERNATIONAL CONSORTIA WITH THE GOAL OF BUILDING A COMPREHENSIVE REFERENCE OF HEALTHY CELLS ACROSS MULTIPLE ORGANS IN THE HUMAN BODY. WE WILL USE SINGLE CELL/NUCLEUS RNA- SEQUENCING (SCRNA-SEQ) DATA FROM THE COMMON FUND-SUPPORTED HUMAN BIOMOLECULAR ATLAS PROGRAM (HUBMAP) AND GENOTYPE-TISSUE EXPRESSION (GTEX) CONSORTIA TO PROTOTYPE A CELL TYPE HARMONIZATION PROTOCOL FOR CONSTRUCTING A CROSS-CONSORTIA CELL CENSUS META-ATLAS. THE HUBMAP CONSORTIUM PROVIDES ORGAN-SPECIFIC CELL ATLASES FOR MULTIPLE ORGANS, WHILE GTEX PROVIDES AN INTEGRATED CROSS-ORGAN SINGLE CELL ATLAS. OUR GROUP HAS DEVELOPED AND EXTENSIVELY VALIDATED COMPUTATIONAL ALGORITHMS, NS-FOREST AND FR-MATCH, FOR BIOMARKER IDENTIFICATION AND ROBUST CELL TYPE MATCHING USING SCRNA-SEQ DATA. OUR ALGORITHMS UTILIZE RANDOM FOREST MACHINE LEARNING AND MINIMUM SPANNING TREE GRAPHICAL MODELING, WHICH PROVIDE SUPERIOR CLASSIFICATION PERFORMANCE WHILE MAINTAINING HIGH EXPLAINABILITY AND INTERPRETABILITY FOR BIOLOGICAL APPLICATIONS. IN SPECIFIC AIM 1, RIGOROUS DATA QUALITY CONTROL APPROACHES WILL BE APPLIED FOR DATASET SELECTION AND PREPARATION. THE NS-FOREST ALGORITHM WILL THEN BE USED TO IDENTIFY OPTIMAL BIOMARKER COMBINATIONS FOR CHARACTERIZATION OF ORGAN-SPECIFIC CELL TYPES OF INDIVIDUAL ORGANS IN HUBMAP AND CROSS-ORGAN CELL TYPES IN GTEX. IN SPECIFIC AIM 2, WE WILL FOCUS ON HUMAN LUNG, AS AN EXEMPLAR ORGAN, TO PROTOTYPE THE ASSEMBLY OF A CROSS-CONSORTIA META-ATLAS BY DEVELOPING A ROBUST CELL TYPE HARMONIZATION APPROACH USING OUR VALIDATED AND BENCHMARKED FR-MATCH ALGORITHM AND HUBMAP-LUNG, GTEX LUNG SUBSET, AND OTHER PUBLICLY AVAILABLE HUMAN LUNG CELL ATLAS (HLCA) DATASETS. WE WILL COMPARE AND BENCHMARK FR-MATCH WITH TWO OTHER POPULAR METHODS, AZIMUTH AND CELLTYPIST, FOR CELL TYPE MATCHING AND VALIDATE THE MATCHING RESULTS USING ALL METHODS. WE WILL ALSO FORM A DOMAIN EXPERT PANEL TO REVIEW AND VALIDATE THE CELL TYPE HARMONIZATION RESULTS USING DOMAIN KNOWLEDGE AND LITERATURE INFORMATION FOR COMMUNITY APPROVAL. WE WILL BUILD A STRATEGY FOR CAPTURING SAMPLE METADATA, ANATOMIC STRUCTURE INFORMATION, CELL TYPE NOMENCLATURE AND BIOMARKER-BASED DEFINITIONS INTO AN ONTOLOGICAL REPRESENTATION FOR THE META-ATLAS AND POPULATE THE CONTENTS INTO THE PROVISIONAL CELL ONTOLOGY. IN SPECIFIC AIM 3, WE WILL DISSEMINATE OUR RESULTS TO KEY STAKEHOLDER COMMUNITIES, INCLUDING THE HUBMAP ANATOMICAL STRUCTURES, CELL TYPES AND BIOMARKERS (ASCT+B) WORKING GROUP AND THE GTEX MULTI-GENE SINGLE CELL QUERY PLATFORM. WE WILL PRESENT THE PROJECT AND PARTICIPATE IN THE COMMON FUND DATA ECOSYSTEM SPRING MEETING FOR ENGAGING THE COMMUNITY AND SOLICITING FEEDBACK. BEYOND THE PILOT PHASE, THE CELL TYPE HARMONIZATION FRAMEWORK ESTABLISHED IN THIS PROJECT CAN BE GENERALLY APPLICABLE TO INTEGRATE SINGLE CELL-BASED CELL TYPE DATASETS ACROSS COMMON FUND AND OTHER DATA RESOURCES.

SINCE THE BEGINNING OF SPACE EXPLORATION THERE IS A CONCERN ABOUT INTERPLANETARY CROSS-CONTAMINATION. ROBOTIC VEHICLES AND THE EXTERIORS OF MANNED SPACECRAFT REPRESENT EXTREME ENVIRONMENTS FOR EARTH ORGANISMS DUE TO THE PHYSICAL EXTREMES OF OUTER SPACE AND THE THOROUGH DECONTAMINATION PROCEDURES APPLIED TO SPACECRAFT BEFORE LAUNCH. HOWEVER RECENT STUDIES SHOW THAT MAMY MICROORGANISMS ARE ABLE TO WITHSTAND THESE HARSH ENVIRONMENTS/PROCEDURES AND EVEN SURVIVE UNDER MARS-LIKE CONDITIONS. CURRENT NASA STANDARD PROCEDURES FOR ASSESSING MICROBIAL BIOBURDEN ON SPACECRAFT INVOLVE CULTURE BASED METHODOLOGIES THAT ARE TIME CONSUMING. ALSO A SERIOUS LIMITATION OF THIS APPROACH IS THAT MOST MICROBIAL ORGANISMS ARE NON-CULTIVABLE AND HENCE IT IS LIKELY TO SEVERELY UNDERESTIMATE THE LEVEL OF MICROBIAL CONTAMINATION. HERE WE PROPOSE TO DEVELOP AN EFFICIENT AND SENSITIVE MOLECULAR METHODOLOGY FOR THE RAPID IDENTIFICATION AND QUANTIFICATION OF CONTAMINATING MICROBIOTA BASED ON LAMP AMPLIFICATION AND MINION SEQUENCING. TO ACHIEVE THIS GOAL WE PROPOSE THE FOLLOWING SPECIFIC AIMS: AIM 1: QUANTITATIVE AND QUALITATIVE ANALYSIS OF MICROBIAL SPECIES PRESENT ON THE SURFACE OF CLEANROOMS BEFORE DURING AND AFTER SPACECRAFT ASSEMBLY IN PREPARATION FOR THE INSIGHT MISSION. WE WILL PERFORM BACTERIAL 16S/FUNGAL ITS1 AMPLIFICATION BY QPCR FOLLOWED BY ILLUMINA SEQUENCING OF SAMPLES COLLECTED FROM CLEANROOM SURFACES AT KEY TIME-POINTS DURING MISSION PREPARATION. QUALITATIVE AND QUANTITATIVE COMPARISON OF MICROBIAL SPECIES PROFILES BEFORE AND AFTER PMA TREATMENT WILL ALLOW US TO CONSTRUCT A CATALOG OF ORGANISMS ABLE TO ENDURE THE DECONTAMINATION TREATMENT APPLIED TO SPACECRAFT AND CLEANROOM SURFACES. AIM 2: GENOMIC CHARACTERIZATION OF MICROBIAL COMMUNITIES THAT WITHSTAND SPACECRAFT DECONTAMINATION PROCESSES AND ASSESS THEIR CAPACITY TO ENDURE OUTER SPACE OR EXTRATERRESTRIAL ENVIRONMENTS. WE WILL IDENTIFY GENETIC SIGNATURES SPECIFIC OF MICROORGANISM RESISTANT TO DECONTAMINATION AND/OR EXTRATERRESTRIAL ENVIRONMENTS THROUGH WHOLE GENOME SEQUENCING AND ANALYSIS OF 180 BACTERIAL ISOLATES THAT HAVE BEEN SHOWN TO SURVIVE IN CONDITIONS SIMILAR TO THOSE FOUND ON THE MARTIAN SURFACE. IN ADDITION WE WILL PERFORM A METAGENOMIC SEQUENCING APPROACH TO CHARACTERIZE THE METABOLIC CAPACITY OF THE MICROBIAL COMMUNITIES PRESENT IN THE INSIGHT SAMPLES AND EVALUATE THEIR POTENTIAL OF SURVIVING ON THE MARS SURFACE BY COMPARATIVE ANALYSIS AGAINST METAGENOMIC SAMPLES FROM RELEVANT EXTREME ENVIRONMENTS AND WHOLE GENOME SEQUENCING DATA FROM THE 180 RESISTANT ISOLATES. AIM 3: TO IMPLEMENT A RAPID AND COST-EFFECTIVE LAMP 16S/ITS1 AMPLIFICATION AND MINION SEQUENCING PROTOCOL FOR THE IDENTIFICATION OF MICROBIAL CONTAMINANTS PRESENT ON THE SURFACE OF ASSEMBLY CLEANROOM. WE WILL EVALUATE THE PERFORMANCE OF MINION TECHNOLOGY DURING THE CHARACTERIZATION OF EXTANT MICROBIAL COMMUNITIES FROM INSIGT SAMPLES COMPARED TO ILLUMINA-BASED TAXONOMIC PROFILES FROM AIM 1. WE WILL ALSO DEVELOP A LAMP PROTOCOL TO AMPLIFYING 16S AND ITS1 MOLECULAR MARKERS THAT WILL THEN BE SEQUENCED WITH MINION. FINALLY WE WILL ADJUST JCVI 16S/ITS1 ILLUMINA PROCESSING PIPELINE TO WORK ON MINION READS DERIVED FROM LAMP AMPLICONS TO IMPROVE MINION-BASED TAXONOMIC PROFILING. THE PROPOSED RESEARCH IS RELEVANT TO THE PLANETARY PROTECTION RESEARCH PROGRAM IN THAT ITS MAIN GOAL IS TO DEVELOP A NOVEL SENSITIVE MOLECULAR ANALYTICAL METHODS FOR THE RAPID IDENTIFICATION AND QUANTIFICATION OF A BROAD RANGE OF MICROBIAL ORGANISMS TO ASSESS THE LIKELIHOOD OF FORWARD (AND POTENTIALLY BACKWARD) CONTAMINATION. SIGNIFICANCE: ONCE DEVELOPED THE PROPOSED METHODOLOGY WILL HELP SETTING NEW MORE SENSITIVE AND INFORMATIVE STANDARDS FOR ASSESSING BIOBURDEN DURING SPACECRAFT PREPARATION AND OPERATING PROCEDURES ON EARTH THAT CAN POTENTIALLY BE APPLIED DURING SPACE MISSIONS OR IN OTHER PLANETS.

A PROTEIN BASED METHOD TO DISTINQUISH SEROPREVALENCE IN HUMANS FOR MULTIPLE MOSQUITO-BOURNE FLAVIRISUES

INVESTIGATING MEMBRANE ALTERATIONS AS A MECHANISM OF ACID TOLERANCE IN CARIOGENIC BACTERIA

COLLABORATIVE RESEARCH: CHANGES IN MICROBIAL COMPOSITION AND METABOLITE PRODUCTION ASSOCIATED WITH SINKING PARTICLES IN THE CALIFORNIA CURRENT SYSTEM -THE NATURAL PROCESSES BY WHICH THE OCEAN TAKES UP CARBON DIOXIDE FROM THE ATMOSPHERE AND REMOVES IT TO THE DEEP SEA ARE COLLECTIVELY CALLED THE ?BIOLOGICAL CARBON PUMP.? THESE PROCESSES ARE REGULATED, IN PART, BY MICROSCOPIC ORGANISMS ATTACHED TO SINKING ORGANIC PARTICLES. THIS STUDY WILL USE CHEMICAL ANALYSES AND INFORMATION ABOUT THE IDENTITY AND METABOLISMS OF PARTICLE-ASSOCIATED BACTERIA TO UNDERSTAND HOW THE COMPOSITION OF SINKING PARTICLES INFLUENCES MICROBIAL FUNCTION AND SURVIVAL. BROADLY, THE PROJECT WILL EXAMINE HOW MICROBES CONTROL WHETHER CARBON IS PRESERVED IN THE DEEP OCEAN OR RECYCLED BACK TO CARBON DIOXIDE. THE PROJECT WILL STRENGTHEN SCIENTIFIC UNDERSTANDING OF CARBON CYCLE PROCESSES THAT AFFECT COASTAL ECOSYSTEM HEALTH AND FISHERIES PRODUCTIVITY ALONG THE U.S. WEST COAST. IN ADDITION, IT WILL ADVANCE NATIONAL LEADERSHIP IN OCEAN SCIENCE AND DATA INTEGRATION, SUPPORT WORKFORCE DEVELOPMENT THROUGH TRAINING OF EARLY-CAREER SCIENTISTS AND CONTRIBUTE TO OPEN-SOURCE RESEARCH TOOLS AND EDUCATION. HETEROTROPHIC BACTERIA ATTACHED TO SINKING PARTICLES PLAY A CENTRAL ROLE IN ATTENUATING PARTICULATE ORGANIC CARBON (POC) FLUX AND MODULATING OXYGEN CONCENTRATIONS IN THE OCEAN?S INTERIOR. HOWEVER, THE EXTENT TO WHICH MICROBIAL COMMUNITY COMPOSITION AND METABOLISM ARE SHAPED BY PARTICLE COMPOSITION?AND HOW MICROBIAL ACTIVITY, IN TURN, TRANSFORMS POC?REMAINS POORLY CONSTRAINED. BY CHARACTERIZING THE COMPOSITION OF ORGANIC MATTER ACROSS THE PARTICULATE?DISSOLVED CONTINUUM WITHIN THE CALIFORNIA CURRENT ECOSYSTEM LONG-TERM ECOLOGICAL RESEARCH SITE, THIS PROJECT AIMS TO USE AN INTEGRATED MULTI-OMICS APPROACH TO EXAMINE MICROBE?PARTICLE INTERACTIONS IN THIS HIGHLY PRODUCTIVE AND DYNAMIC ECOSYSTEM. THE CHANGING ORGANIC CHEMISTRY OF SINKING AND SUSPENDED PARTICLES BETWEEN 50 M AND 450 M DEPTH WILL BE ASSESSED USING A COMBINATION OF TARGETED AND UNTARGETED METABOLOMIC FINGERPRINTING TECHNIQUES, PRIMARILY BASED ON LIQUID CHROMATOGRAPHY COUPLED WITH TANDEM MASS SPECTROMETRY. SIMILARLY, METAGENOMIC AND METATRANSCRIPTOMIC DATASETS FROM THE SAME PARTICLE SAMPLES WILL BE GENERATED TO CHARACTERIZE THE COMPOSITION AND METABOLIC POTENTIAL OF MICROBIAL COMMUNITIES ASSOCIATED WITH SINKING AND SUSPENDED PARTICULATE ORGANIC MATTER. TOGETHER, THESE CHEMICAL AND GENOMIC DATASETS WILL BE USED TO INVESTIGATE SINKING PARTICLE DYNAMICS, INTERACTIONS BETWEEN SINKING AND SUSPENDED PARTICLES, AND THE SUCCESSION OF PARTICLE-ASSOCIATED MICROBIAL METABOLIC TRAITS WITH DEPTH. AN ADDITIONAL GOAL OF THE WORK IS TO REFINE AND STREAMLINE THIS INTEGRATED RESEARCH FRAMEWORK TO ENCOURAGE ITS BROADER ADOPTION AND EXPAND THE DATABASE OF COUPLED METABOLOMIC AND METAGENOMIC ANALYSES. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

COLLABORATIVE RESEARCH: PHYSIOLOGICAL AND GENETIC CHARACTERIZATION OF C02 CONCENTRATING MECHANISMS IN MARINE DIATOMS

COLLABORATIVE RESEARCH: MULTIPLE ANALYTICAL WINDOW ELECTROCHEMICAL TECHNIQUES AND META-OMICS APPLIED TO STUDIES OF IRON RECYCLING AND IRON-BINDING LI

ELUCIDATING MICROBIAL ELECTRON TRANSPORT MECHANISMS FOR OPTIMIZING BIOCATALYZED PROCESSES

AUTOMATED PROTEOGENOMIC ANNOTATION FOR PROKARYOTIC GENOMES

DIMENSIONS: COLLABORATIVE RESEARCH: THE PHYLOGENETIC AND FUNCTIONAL DIVERSITY OF EXTRACELLULAR ELECTRON TRANSFER ACROSS ALL THREE DOMAINS OF LIFE

VIRUSES ARE UBIQUITOUS IN THE WORLDS OCEANS PLAYING AN ESSENTIAL ROLE IN BIOGEOCHEMICAL PROCESSES WHILE REPRESENTING A VAST SOURCE OF GENETIC DIVERSITY. YET WE STILL KNOW LITTLE ABOUT NATURAL VIRAL COMMUNITIES. HYDROTHERMAL SYSTEMS HAVE BEEN PREVALENT ON EARTH SINCE THE PLANET WAS FORMED AND ITS HYPOTHESIZED THAT LIFE MAY HAVE ORIGINATED AND EVOLVED NEAR DEEP-SEA HYDROTHERMAL VENTS MAKING THEM THE MOST ANCIENT CONTINUOUSLY INHABITED ECOSYSTEMS ON THE PLANET. EXTANT ORGANISMS LIVING IN THESE ANALOGUES OF EARLY HABITATS MAY STILL HARBOR GENETIC AND METABOLIC CHARACTERISTICS OF EARLY LIFE. VIRUSES PLAY A CRITICAL ROLE IN THE ULTIMATE SURVIVAL OF MICROBES BY MEDIATING HOST FUNCTIONAL DIVERSIFICATION AND ENHANCING ADAPTABILITY VIA HORIZONTAL GENE TRANSFER AND LYSOGENY A REPLICATION STRATEGY ENABLING THE VIRUS TO INCORPORATE ITS GENOME INTO THEIR HOSTS (PROPHAGE). IN THIS PROJECT WE WILL EXAMINE THE LIFESTYLE AND IMPACT OF VIRUSES ON MICROBIAL COMMUNITIES IN THE SUBSEAFLOOR OF DEEP-SEA HYDROTHERMAL VENTS. WE WILL INVESTIGATE DNA AND RNA VIRUSES THE LATTER COMPRISING THE MOST ANCIENT GROUP OF VIRUSES ON OUR PLANET. OUR RESEARCH PLAN WILL DETERMINE INFECTION DYNAMICS AND INTERROGATE HOST ASSOCIATIONS BOTH OF WHICH ARE KNOWN TO LEAD TO PHYSIOLOGICAL ALTERATIONS AND WIDE-RANGING EVOLUTIONARY TRAJECTORIES. SPECIFIC GOALS WE PLAN TO ADDRESS INCLUDE I) DETERMINE PHAGE HOST RANGE AND SPECIFICITY TO DIVERSE MICROBIAL HOST ISOLATES FROM DEEP-SEA HYDROTHERMAL VENTS II) DETERMINE ROLE OF VENT VIRUSES IN MICROBIAL HOST EVOLUTION AND ECOLOGY AT DEEPSEA HYDROTHERMAL VENTS III) IDENTIFY NOVEL RNA VIRUSES FROM DEEP-SEA HYDROTHERMAL VENTS. ELUCIDATION OF THESE GOALS WILL ALLOW US TO BETTER CONSTRAIN THE IMPACT OF VIRAL COMMUNITIES IN THE SUBSEAFLOOR AND EXAMINE THE NATURE OF VIRUS-HOST INTERACTIONS AS MODELS FOR UNDERSTANDING EARLY LIFE. WE WILL USE VIRAL INFECTION STUDIES TO EXPERIMENTALLY INVESTIGATE ISOLATES FROM A PHYLOGENETICALLY DIVERSE COLLECTION OF CULTURED VENT MICROBES INCLUDING BOTH BACTERIA AND ARCHAEA. THE EXISTING CULTURE COLLECTION WILL FACILITATE TESTING HOST-RANGES OF VIRAL ISOLATES INDICATING POSSIBLE EVOLUTIONARY BREAKPOINTS OF VIRAL TRANSFER. CULTURED ISOLATES WILL BE INTERROGATED USING PROPHAGE INDUCTION ASSAYS AND CHALLENGE EXPERIMENTS FOLLOWED BY SEQUENCING AND MICROSCOPY. TO IDENTIFY THE HOST RANGE/SPECIFICITY OF PHAGE ISOLATED PHAGE WILL BE MIXED WITHIN AND BETWEEN RELATED HOST MICROBIAL GENERA. INCREASES IN PHAGE TITERS WILL BE MEASURED TO EVALUATE AMPLIFICATION DURING INFECTION. GENOMIC-BASED TECHNOLOGIES OF VIRUSES AND MICROBES WILL BE LEVERAGED TO INTERROGATE VIRUSES THEIR HOSTS AND INTERACTIONS. WE WILL COMPUTATIONALLY INTERROGATE OMICS INFORMATION FOR EVIDENCE OF VIRAL-MEDIATED CELLULAR GENE TRANSFER AND LYSOGENIC CONVERSION AND HOST IMMUNITY MARKERS RESULTING FROM PAST INFECTION. FINALLY RNA VIRUSES INCLUDING RETROVIRUSES WILL BE CHARACTERIZED VIA HOMOLOGY BINNING AND PHYLOGENETICS FROM COMMUNITY METAGENOMIC TRANSCRIPTOMIC DATA. THE STUDY OF EXTREMOPHILIC ORGANISMS AND THEIR METABOLIC PATHWAYS HABITATS AND DISTRIBUTION IS ESSENTIAL TO UNDERSTANDING THE ORIGIN AND EVOLUTION OF LIFE ON EARTH THE MAIN GOAL OF NASAS EXOBIOLOGY AND EVOLUTIONARY BIOLOGY PROGRAM. VIRUSES ARE IMPORTANT EVOLUTIONARY DRIVERS OF NATURAL MICROBIAL COMMUNITIES AND EXAMINATIONS OF VIRAL COMMUNITIES IN THE ROCK-HOSTED OCEANIC SUBSEAFLOOR ARE JUST BEGINNING THAT HOLD GREAT PROMISE FOR REVEALING NEW INFORMATION ABOUT REMOTE LIFE ON EARTH AND THE POSSIBILITIES FOR LIFE ON OTHER PLANETARY BODIES. OUTREACH ACTIVITIES INCLUDE TRAINING UNDERGRADUATE STUDENTS AT A SMALL LIBERAL ARTS COLLEGE IN CUTTING-EDGE GENOMICS AND BIOINFORMATICS TECHNIQUES AND DEVELOPING AN EXTREME VIRUS MODULE FOR ELEMENTARY SCHOOL STUDENTS

SPACEFLIGHT HAS DEMONSTRATED CONCERNING IMPACTS TO HUMAN PHYSIOLOGY, INCLUDING WELL DOCUMENTED IMMUNE SYSTEM DYSREGULATION. DIET, IMMUNE FUNCTION, AN

COLLABORATIVE RESEARCH: DETERMINING FUNCTIONAL CORRELATIONS BETWEEN GEOCHEMICAL FACTORS AND MICROBIAL METABOLISMS IN ULTRABASIC SERPENTINIZING ECOSYS

FUNCTIONAL GENOMIC STUDIES OF FORMOSAN SUBTERRANEAN TERMITES (COPTOTERMES FORMOSANUS)

COLLABORATIVE RESEARCH: CONSERVATION AND DIVERSIFICATION OF REGULATORY PATHWAYS CONTROLLING STEM CELL PROLIFERATION

CHARACTERIZATION OF HISTOPLASMA TRANSCRIPTION FACTORS USING IMPROVED EPISOMAL DNA MAINTENANCE AND CONTROLLABLE GENE EXPRESSION TOOLS - PROJECT SUMMARY HISTOPLASMA CAPSULATUM CAUSES PULMONARY AND SYSTEMIC INFECTIONS IN BOTH HEALTHY AND IMMUNOCOMPROMISED INDIVIDUALS, AND IS THE MOST COMMON CAUSE OF FUNGAL RESPIRATORY INFECTIONS IN HEALTHY HOSTS. IT IS A DIMORPHIC FUNGAL PATHOGEN THAT CAN SENSE AND RESPOND TO HUMAN BODY TEMPERATURE BY CHANGING ITS GROWTH PROGRAM FROM A FILAMENTOUS (MOLD) FORM TO A PARASITIC YEAST FORM. INFECTION OCCURS WHEN THE SOIL IS DISRUPTED, FACILITATING DISPERSION OF HYPHAL FRAGMENTS OR SPORES THAT ARE INHALED BY HUMANS. ONCE INTRODUCED INTO THE HOST, THE PATHOGEN CONVERTS TO A BUDDING-YEAST FORM, WHICH SURVIVES AND REPLICATES WITHIN HOST MACROPHAGES. IN THE LABORATORY, THE SWITCH BETWEEN THE INFECTIOUS AND PARASITIC STATES IS MODELED BY CHANGING THE TEMPERATURE: CELLS GROW IN THE FILAMENTOUS FORM AT ROOM TEMPERATURE, WHEREAS GROWTH AT 37ºC IS SUFFICIENT TO TRIGGER GROWTH IN THE YEAST FORM AND EXPRESSION OF VIRULENCE FACTORS. IN PREVIOUS STUDIES, WE AND OTHERS HAVE IDENTIFIED FOUR TRANSCRIPTIONAL REGULATORS, RYP1,2,3,4, WHICH ARE REQUIRED FOR YEAST-PHASE GROWTH AND VIRULENCE GENE EXPRESSION. RYPS DIRECTLY REGULATE EXPRESSION OF A SET OF YEAST-PHASE SPECIFIC GENES THAT ENCODE PROTEINS WITH PUTATIVE SECRETION SIGNALS AND TRANSMEMBRANE HELICES; THUS, FORM THE CORE OF THE YEAST-PHASE SPECIFIC TRANSCRIPTIONAL NETWORK. IN PRELIMINARY STUDIES, WE HAVE FOUND THAT TWO MAJOR PLAYERS OF THE HEAT SHOCK RESPONSE, THE HEAT SHOCK FACTOR HSF1 AND A CHAPERONE HSP90, ALSO REGULATE THE YEAST-PHASE GROWTH UNDER IN VITRO CONDITIONS. HOWEVER, THESE GENES ARE ESSENTIAL AND THEIR FUNCTION CANNOT BE STUDIED BY CONVENTIONAL KNOCKOUT STRATEGIES IN HISTOPLASMA. THERE IS LIMITED RESEARCH DONE IN HISTOPLASMA, IN PART DUE TO THE LIMITATION OF THE GENETIC TOOLS AVAILABLE. IN PARTICULAR, THERE IS NO CONTROLLABLE GENE EXPRESSION SYSTEMS THAT CAN BE USED TO STUDY GENE FUNCTION IN VIVO. IN THIS PROJECT, WE AIM TO DEVELOP CONTROLLABLE (TET-INDUCIBLE AND TET-REPRESSIBLE) GENE EXPRESSION SYSTEMS AND OPTIMIZE EPISOMAL DNA MAINTENANCE. USING THE TET-INDUCIBLE SYSTEM, WE WILL INDUCE EXPRESSION OF KNOCKDOWN CASSETTES FOR RYP1,2,3,4, HSF1 AND HSP90 UNDER IN VIVO CONDITIONS AND ASSESS THEIR ROLE IN MAINTENANCE OF THE PARASITIC GROWTH IN VIVO. IN ADDITION, WE WILL IDENTIFY CENTROMERIC SEQUENCES AND/OR DNA ELEMENTS THAT PROMOTE AUTONOMOUS REPLICATION OR SEGREGATION; AND UTILIZE THEM IN EPISOMAL VECTORS TO ENSURE PROPER SEGREGATION OF THE EPISOMAL DNA DURING CELL DIVISION. WE WILL GENERATE KNOCKDOWN AND OVEREXPRESSION MUTANTS OF YEAST- OR HYPHAL- PHASE SPECIFIC TRANSCRIPTION FACTORS USING IMPROVED EPISOMAL VECTORS. ULTIMATELY, RESULTS OF THE EXPERIMENTS PROPOSED IN THIS PROJECT WILL FURTHER ADVANCE OUR ABILITY TO STUDY GENE FUNCTION IN HISTOPLASMA, AND WILL EXPAND OUR KNOWLEDGE OF THE TRANSCRIPTIONAL NETWORK THAT GOVERNS THE PARASITIC YEAST-PHASE GROWTH.

UNDERSTANDING S. MUTANS PATHOGENESIS IN A SOCIAL AND ECOLOGICAL SETTING

BACKGROUND: IT IS EXPECTED THAT FUTURE MANNED SPACE MISSIONS INVOLVING EXTRAVEHICULAR ACTIVITIES (EVA) WILL REQUIRE NOVEL EVA ARCHITECTURES INCLUDING A SLIGHTLY HYPOBARIC HYPOXIC CABIN ATMOSPHERE (8.2 PSIA 34% O2). HUMANS ARE WELL-ADAPTED TO LIVE AT

THE DISEASE-CAUSING ORGANISMS BURKHOLDERIA MULTIVORANS B. CEPACIA GENOMOVARS OF THE B. CEPACIA COMPLEX (BCC) AS WELL AS AN UNCLASSIFIED SPECIES OF BURKHOLDERIA AND ITS RELATIVES RALSTONIA PICKETTII AND R. INSIDIOSA ACCOUNT FOR 60% OF THE BACTERIAL ISOLATES OBTAINED FROM THE FILTRATED WATER SYSTEM ON BOARD THE INTERNATIONAL SPACE STATION (ISS). MEMBERS OF THESE GENERA CAN SURVIVE LONG PERIODS IN A PLANKTONIC STATE IN DISTILLED WATER OR AS BIOFILMS WITHIN AN INFECTED INDIVIDUAL. THEY ARE ALSO NATIVELY RESISTANT TO SEVERAL ANTIBIOTICS LEAVING TREATMENT OPTIONS COMPLEX. FOR BCC ORGANISMS THIS COMPLEXITY IS INCREASED BY THE PHENOMENON OF BACTERIAL PERSISTENCE WHERE A GENETICALLY IDENTICAL SUBPOPULATION OF THE BACTERIA SUSTAINS UNDER HIGH ANTIBIOTIC CHALLENGE BY A REDUCTION IN METABOLISM AND OTHER UNKNOWN MECHANISMS. A HEALTHY ASTRONAUT COULD EASILY CLEAR A BCC OR RALSTONIA SP. INFECTION; HOWEVER AFTER PROLONGED SPACEFLIGHT A POTENTIALLY IMMUNOCOMPROMISED ASTRONAUT WITH REPEATED EXPOSURE TO THESE ORGANISMS COULD BE AT RISK FOR DISEASE. IN OUR WORK WITH BURKHOLDERIA PSEUDOMALLEI -THE CAUSATIVE AGENT OF MELIOIDOSIS- WE HAVE OBSERVED BY MEANS OF TRANSPOSON SEQUENCING (TNSEQ) THAT A COMMON SET OF GENES HELP THE WILDTYPE BACTERIA PERSIST REGARDLESS OF THE MODE OF ACTION OF THE ANTIBIOTIC USED FOR CHALLENGE. WE HAVE FOUND A CYSTEINE SYNTHASE GENE WHOSE INHIBITION COULD ENHANCE EXISTING ANTIBIOTICS BY INTERFERING WITH THE BACTERIASPECIFIC SULFUR ASSIMILATION AND CYSTEINE SYNTHESIS PATHWAYS. IT IS LIKELY THAT METABOLIC REGULATION PLAYS A ROLE IN THE ABILITY FOR BCC AND RALSTONIA STRAINS TO PERSIST IN THE ISS POTABLE WATER IN A PLANKTONIC STATE. IT IS ALSO PROBABLE THAT THE SAME MECHANISMS WHICH INCREASE SURVIVORSHIP CAN IN TURN ENHANCE VIRULENCE AND LEND TO PERSISTENT BIOFILMS IN THE GASTROINTESTINAL OR RESPIRATORY TRACT OF THE INFECTED INDIVIDUAL. TO UNDERSTAND THE MECHANISMS THAT WOULD CONTRIBUTE TO ALTERED VIRULENCE IN ISS BCC AND RALSTONIA SPECIES THE GENOMES OF 67 ISOLATES FROM 22 MISSIONS WILL BE SEQUENCED AND COMPARED TO THEIR RESPECTIVE ATCC BCC OR RALSTONIA STRAIN. THE POTENTIAL FOR INCREASED VIRULENCE WILL BE DETERMINED BY THE PRESENCE OF GENES CLUSTERED AS PATHOGENICITY ISLANDS IN THE RESPECTIVE GENOME. TO ESTABLISH IF THE STRAINS ARE BECOMING MORE RESISTANT TO ANTIBIOTICS A MINIMUM INHIBITORY CONCENTRATION (MIC) WILL BE DETERMINED FOR EACH ISOLATE USING SIX ANTIBIOTICS CURRENTLY USED TO TREAT THE INFECTIONS AND THEN COMPARED TO THE RESPECTIVE ATCC CONTROL STRAIN. FINALLY A TRANSPOSON LIBRARY WILL BE GENERATED FOR THE MOST VIRULENT RESISTANT TOLERANT OR PERSISTENT STRAIN AND THIS LIBRARY WILL BE CULTURED IN DISTILLED WATER TO SIMULATE CONDITIONS ON THE ISS. HERE WE WILL IDENTIFY GENES WHICH AID IN THE SURVIVORSHIP OF BCC AND RALSTONIA STRAINS IN THE WATER SYSTEM OF THE ISS. THE KNOWLEDGE GAINED FROM THIS GENOMIC SEQUENCING AND TNSEQ STUDY WILL ALLOW US TO ASSESS ANY INCREASED VIRULENCE OR INFECTION POTENTIAL AS WELL AS HELP TO MAKE ANTIBIOTIC RECOMMENDATIONS PREDICT TARGET GENES WHERE INHIBITION BY ADJUVANTS WILL ENHANCE ANTIBIOTIC THERAPY OR PRESENT NOVEL WATER TREATMENT OPTIONS TO ERADICATE THE BCC/RALSTONIA STRAINS FROM THE POTABLE WATER OF THE ISS.

RECOVERY OF RESOURCES IS CRITICAL FOR REDUCING UP-MASS AND FACILITATING LONG-DURATION AND SELF-SUSTAINING NASA MISSIONS. THE ABILITY TO PROVIDE VITAL

INTERGOVERNMENTAL MOBILITY ASSIGNMENT

FUNCTIONAL GENOMIC STUDIES OF FORMOSAN SUBTERRANEAN TERMITES (COPTOTERMES FORMOSANUS)

TRANSLATIONAL GENOMICS OF ONION FOR PRIORITIZED PEST RESISTANCES (J. CRAIG VENTER INSTITUTE, INC.)

GENOME SEQUENCING, ANALYSIS, AND FUNCTIONAL GENOMIC STUDIES OF ASPERGILLUS FLAVUS

GENOME SEQUENCING ANALYSIS AND FUNCTIONAL GENOMIC STUDIES OF ASPERGILLUS FLAVUS

GENOMIC SEQUENCING AND ANNOTATION OF BABESIA BOVIS

CONFERENCE: THE 1ST INTERNATIONAL SYNBYSS CONFERENCE -THE INAUGURAL INTERNATIONAL SYNTHETIC BIOLOGY YOUNG SPEAKER SERIES CONFERENCE PROVIDES THE GLOBAL SYNTHETIC BIOLOGY COMMUNITY WITH AN OPPORTUNITY TO BRAINSTORM, ADVANCE SCIENCE AND BIOTECHNOLOGY, AND SOLVE MANY GLOBAL PROBLEMS. THE PROGRAMING INCLUDES NOT ONLY TECHNICAL PRESENTATIONS BUT ALSO PANEL DISCUSSIONS AND WORKSHOPS TO MAXIMIZE THE FEELING OF PARTICIPATION FROM ATTENDEES WHO ARE NOT SPEAKERS AND NURTURE DIVERSE OPINION SHARING. SPECIFICALLY, THE SESSIONS INCLUDE TECHNICAL PRESENTATIONS, PANEL AND ROUNDTABLE DISCUSSIONS AND ROAD-MAPPING DISCUSSIONS AMONG BROADER GLOBAL COMMUNITY MEMBERS. THE PROGRAM ALSO INCLUDES POSTER PRESENTATIONS, NETWORKING SESSIONS AND A ?MEET THE LEGEND SESSION,? WHICH IS A FORUM IN WHICH THERE IS OPPORTUNITY FOR AN INFORMAL CHAT BETWEEN TRAINEES AND PROMINENT ESTABLISHED INVESTIGATORS. WITH THESE UNIQUE FEATURES, THIS CONFERENCE PROVIDES THE GLOBAL RESEARCH COMMUNITY, THE BIOTECHNOLOGY INDUSTRY, AND POLICYMAKERS WITH THE VISION OF AND PERSPECTIVES ON ENGINEERING BIOLOGY. THE INAUGURAL INTERNATIONAL SYNTHETIC BIOLOGY YOUNG SPEAKER SERIES CONFERENCE ADDRESSES COMPELLING QUESTIONS IN MOLECULAR AND CELLULAR BIOLOGY AND CONCOMITANTLY GATHERS SYNBYSS WEBINAR SPEAKERS AND AUDIENCES TO BUILD A MORE INTERACTIVE, INCLUSIVE, SUSTAINABLE, AND COLLABORATIVE SYNTHETIC BIOLOGY COMMUNITY. IT IS A CONFERENCE ORGANIZED BY AND BASED ON COMMUNITY INPUT TO PROVIDE THE GLOBAL SYNTHETIC BIOLOGY COMMUNITY WITH AN OPPORTUNITY TO BRAINSTORM AND SOLVE MANY GLOBAL PROBLEMS THAT COULD BE SOLVED BY THE APPLICATION OF SYNTHETIC BIOLOGY. THE WIDE SPECTRUM OF SCIENTIFIC THEMES WITHIN THE CONFERENCE ADDRESSES COMPELLING QUESTIONS IN MOLECULAR AND CELLULAR BIOLOGY AS WELL AS THE ADVANCEMENT OF SYSTEMS AND SYNTHETIC BIOLOGY AS ROBUST DISCIPLINES WITHIN THE SCIENTIFIC LANDSCAPE. THROUGH ITS UNIQUE FEATURES, THE CONFERENCE PROVIDES THE GLOBAL RESEARCH COMMUNITY, THE BIOTECHNOLOGY INDUSTRY, AND POLICYMAKERS WITH THE VISION OF AND PERSPECTIVES ON ENGINEERING BIOLOGY THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

GENOME SEQUENCING, ANALYSIS, AND FUNCTIONAL GENOMIC STUDIES OF ASPERGILLUS FLAVUS

GENOME SEQUENCING, ANALYSIS, AND FUNCTIONAL GENOMIC STUDIES OF ASPERGILLUS FLAVUS

EU-US WORKING GROUP ON ENVIRONMENTAL BIOTECHNOLOGY SHORT-COURSE

GENOMICS BASED DISCOVERY OF NOVEL TRAITS IN BENEFICIAL PLANT-ASSOCIATED PSEUDOMONAS SPECIES

GENOME SEQUENCING, ANALYSIS, AND FUNCTIONAL GENOMIC STUDIES OF ASPERGILLUS FLAVUS

GENOME SEQUENCING, ANALYSIS, AND FUNCTIONAL GENOMIC STUDIES OF ASPERGILLUS FLAVUS

THE 1ST INTERNATIONAL SYNBYSS CONFERENCE - SYNBYSS_PROJECT SUMMARY THE SYNBIO YOUNG SPEAKER SERIES (SYNBYSS) IS A VIRTUAL WEEKLY SEMINAR STARTED IN 2021, THAT WILL BEGIN HAVING IN-PERSON MEETINGS. SYNTHETIC BIOLOGY IS AN INTERDISCIPLINARY FIELD WITH APPLICATIONS IN BIOMEDICINE, BIOSAFETY, BIOTECHNOLOGY, AND PHARMA. YET, THERE ARE NOW FEWER SYNTHETIC BIOLOGY CONFERENCES THAN IN THE PAST, AND NONE OF THE CONFERENCES FOCUSES ON EARLY- CAREER RESEARCHERS. MOREOVER, THE YOUNGEST MEMBERS ARE A DIVERSE AND INTERNATIONAL GROUP WITHOUT OBVIOUS REPRESENTATION. AT MOST CONFERENCES FEW OF THEM HAVE OPPORTUNITIES TO EXPRESS THEIR IDEAS, NETWORK, OR COLLABORATE. WITH THIS IN MIND, THE CONFERENCE WILL FOCUS ON WHAT THE FUTURE HOLDS FOR SYNTHETIC BIOLOGY. A CENTRAL OBJECTIVE OF THE CONFERENCE IS TO BRING THE COMMUNITY TOGETHER FOR MORE INTERACTIVE, INCLUSIVE, AND COLLABORATIVE DISCUSSIONS. TALKS WILL FOCUS ON YOUNG RESEARCHERS PAIRED WITH KEYNOTE SPEAKERS, SIMILAR TO THE ONLINE SERIES. THERE WILL BE DISCUSSION PANELS AND NETWORKING EVENTS TO ACTIVELY PROMOTE COLLABORATIONS BETWEEN RESEARCHERS AT DIFFERENT CAREER STAGES, THUS FACILITATING THE GENERATION OF AN EFFECTIVE COMBINATION OF NEW IDEAS AND EXPERTISE. FUNDING FROM NIH WILL BE USED TO OFFSET REGISTRATION FEES AND TRAVEL COSTS FOR A COHORT OF DIVERSE EARLY-CAREER NIBIB SYNBYSS FELLOWS. THIS R13 ALIGNS WITH NIBIBS ONGOING NOSI FOR SYNTHETIC BIOLOGY FOR BIOMEDICAL APPLICATIONS.

GENOME SEQUENCING, ANALYSIS, AND FUNCTIONAL GENOMIC STUDIES OF ASPERGILLUS FLAVUS

20TH INTERNATIONAL BIOINFORMATICS WORKSHOP ON VIRUS EVOLUTION AND MOLECULAR EPIDEMIOLOGY (VEME)

CONFERENCE: THE 2ND INTERNATIONAL SYNBYSS CONFERENCE -THE SECOND INTERNATIONAL SYNTHETIC BIOLOGY YOUNG SPEAKER SERIES CONFERENCE PROVIDES THE GLOBAL SYNTHETIC BIOLOGY COMMUNITY WITH AN OPPORTUNITY TO BRAINSTORM, ADVANCE SCIENCE AND BIOTECHNOLOGY, AND SOLVE MANY GLOBAL PROBLEMS. THE PROGRAMING INCLUDES NOT ONLY TECHNICAL PRESENTATIONS BUT ALSO PANEL DISCUSSIONS AND WORKSHOPS TO MAXIMIZE THE FEELING OF PARTICIPATION FROM ATTENDEES WHO ARE NOT SPEAKERS AND NURTURE DIVERSE OPINION SHARING. SPECIFICALLY, THE SESSIONS INCLUDE TECHNICAL PRESENTATIONS, PANEL AND ROUNDTABLE DISCUSSIONS AND ROAD-MAPPING DISCUSSIONS AMONG BROADER GLOBAL COMMUNITY MEMBERS. THE PROGRAM ALSO INCLUDES POSTER PRESENTATIONS, NETWORKING AND MENTORING SESSIONS AND A ?MEET THE LEGEND SESSION,? WHICH IS A FORUM IN WHICH THERE IS OPPORTUNITY FOR AN INFORMAL CHAT BETWEEN TRAINEES AND PROMINENT ESTABLISHED INVESTIGATORS. WITH THESE UNIQUE FEATURES, THIS CONFERENCE PROVIDES THE GLOBAL RESEARCH COMMUNITY, THE BIOTECHNOLOGY INDUSTRY, AND POLICYMAKERS WITH THE VISION OF AND PERSPECTIVES ON ENGINEERING BIOLOGY. THE SECOND INTERNATIONAL SYNTHETIC BIOLOGY YOUNG SPEAKER SERIES CONFERENCE ADDRESSES COMPELLING QUESTIONS IN MOLECULAR AND CELLULAR BIOLOGY AND CONCOMITANTLY GATHERS SYNBYSS WEBINAR SPEAKERS AND AUDIENCES TO BUILD A MORE INTERACTIVE, INCLUSIVE, SUSTAINABLE, AND COLLABORATIVE SYNTHETIC BIOLOGY COMMUNITY. THE CONFERENCE IS ORGANIZED BY AND BASED ON COMMUNITY INPUT TO PROVIDE THE GLOBAL SYNTHETIC BIOLOGY COMMUNITY WITH AN OPPORTUNITY TO BRAINSTORM AND PROPOSE SOLUTIONS FOR MANY GLOBAL PROBLEMS BY THE APPLICATION OF SYNTHETIC BIOLOGY. THE WIDE SPECTRUM OF SCIENTIFIC THEMES WITHIN THE CONFERENCE ADDRESSES COMPELLING QUESTIONS IN MOLECULAR AND CELLULAR BIOLOGY AS WELL AS THE ADVANCEMENT OF SYSTEMS AND SYNTHETIC BIOLOGY AS ROBUST DISCIPLINES WITHIN THE SCIENTIFIC LANDSCAPE. THROUGH ITS UNIQUE FEATURES, THE CONFERENCE PROVIDES THE GLOBAL RESEARCH COMMUNITY, THE BIOTECHNOLOGY INDUSTRY, AND POLICYMAKERS WITH THE VISION OF AND MOST RECENT PERSPECTIVES ON ENGINEERING BIOLOGY THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.