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THE PROPOSED ASPERGILLUS FUMIGATUS DATAMINING (AFDM) PROJECT IS A GROUND-BASED HYPOTHESIS-DRIVEN RESEARCH INVESTIGATION DERIVED FROM ANALYZING THE OMICS DATA DEPOSITED IN THE GENELAB DATA SYSTEM (GLDS) THAT WOULD TRANSLATE SPACEFLIGHT DERIVED DATA INTO NEW KNOWLEDGE. AS A. FUMIGATUS IS AN OPPORTUNISTIC PATHOGEN CAUSING PATHOLOGIES RANGING FROM ALLERGIC ASTHMA TO INVASIVEASPERGILLOSIS WE ASSESSED SEVERAL CHARACTERISTICS OF THE INTERNATIONAL SPACE STATION (ISS) ISOLATES IN COMPARISON TO TWO EXPERIMENTALLY ESTABLISHED CLINICAL ISOLATES AF293 AND CEA10. VIRULENCE ASSESSMENT IN A LARVAL ZEBRAFISH MODEL OF INVASIVE ASPERGILLOSIS REVEALED BOTH ISSFT-021 AND IF1SW-F4 AS SIGNIFICANTLY MORE LETHAL COMPARED TO BOTH AF293 AND CEA10. ADDITIONALLY BOTH ISSFT-021 AND IF1SWF4 EXHIBITED SIGNIFICANTLY GREATER RESISTANCE TO UV254 DOSES WHEN COMPARED TO CLINICAL ISOLATES. WE PROPOSE TO ASSESS THAT THE ENHANCED VIRULENCE OF THE TWO ISS STRAINS IS MEDIATED IN PART BY UP-REGULATION OF SPORE PIGMENTS AS A PROTECTIVE RESPONSE TO ENHANCED RADIATION IN SPACE.IN ADDITION TO THE OMICS DATA OF THE A. FUMIGATUS STRAINS DEPOSITED IN THE GLDS THE AFDM PROJECT WILL COMBINE AND COMPARE THE GROUND-BASED OMICS DATA THAT ARE EITHER PUBLICLY-AVAILABLE OR GENERATED BY THE PRINCIPAL INVESTIGATORS LAB. THE AFDM PROJECT WILL CONTRIBUTE TO THE ROSBIO NASA RESEARCH ANNOUNCEMENT NNH16ZTT001N-GL RESEARCH EMPHASIS (SYSTEMS BIOLOGY EXPERIMENTAL RESEARCH USING THE GENELAB DATA SYSTEM) BY GENERATING NEW OMICS DATA ABOUT THE FUNGAL BIOLOGY AND ADDING IT TO THE GENELAB FOR THE BENEFIT OF FUTURE OPEN SCIENCE-BASED INVESTIGATIONS IN EARTH. THIS WILL ENABLE DEVELOPMENT OF RAPID MICROBIAL MONITORING SYSTEMS COUNTERMEASURES NOVEL PHARMACEUTICAL COMPOUNDS VACCINE PRODUCTION ETC. THE TRANSLATIONAL RESEARCH ASPECTS OF THE AFDM PROJECT ARE FOCUSING THE HIGH-PRIORITY RECOMMENDATIONS OF THE NRC DECADAL SURVEY (P1. ESTABLISH A MICROBIAL OBSERVATORY PROGRAM ON THE ISS TO CONDUCT LONG-TERM MULTIGENERATIONAL STUDIES OF MICROBIAL POPULATION DYNAMICS).THE AFDM PROJECT WILL ADDRESS SPECIFIC NASA SPACE BIOLOGY-RELATED QUESTIONS BY (A) INVESTIGATING SPACEFLIGHT OMICS DATA WITH SPECIFIC AIMS TO BENEFIT HUMAN HEALTH (AIMS 1 AND 2) (B) ADDRESSING EFFECTS OF SPACEFLIGHT CONDITIONS ON DYNAMICS OF MICROBES (FUNGI) WITH RESPECT TO CELL PROCESSES SUCH AS UNDERSTANDING PHYSIOLOGICAL RESPONSES (SECONDARY METABOLITE PRODUCTION AIMS 2 AND 3) UV RESISTANCE(AIM 3) AND TO THE MULTIPLE STIMULI ENCOUNTERED IN SPACEFLIGHT ENVIRONMENTS AND (C) CHARACTERIZING THE MOLECULAR RESPONSES IN SPACE GROWN FUNGI TO PATHOGENESIS (AIM 4). THE OBJECTIVE IS TO PROVIDE NASAS SPACE BIOLOGY PROGRAM WITH OMICS INFORMATION ON HOW ALTERATIONS IN GRAVITY AFFECT GENETIC MUTATIONAL METABOLOMIC AND VIRULENCE CHARACTERISTICS IN FUNGAL SPECIES.BY DATAMINING THE OMICS OF TWO ISS A. FUMIGATUS STRAINS WE WILL ADDRESS THE NASAS SPACE BIOLOGY PROGRAM SCIENCE ELEMENT (MICROBIOLOGY) AND ITS GUIDING QUESTIONS: (A) HOW THE GENETIC MOLECULAR AND BIOCHEMICAL PROCESSES OF THE ISS A. FUMIGATUS STRAINS ARE INFLUENCED BY THE SPACE ENVIRONMENT AND (B) WHAT SYSTEMS BIOLOGY MECHANISMS AND PATHWAYS ARE RESPONSIBLE FOR THE ENHANCED VIRULENCE IN ISS ISOLATES (NASA TASK REPORT 2016; BACTERIAL ARCHAEAL &FUNGAL DIVERSITY OF THE ISS--HEPA FILTER SYSTEM; 19-12829-27 UNDER TASK ORDER NNN13D111T) WHEN COMPARED TO THE WELL CHARACTERIZED CLINICAL ISOLATES.

$165,000FY2017National Aeronautics and Space AdministrationNASA

University Of Wisconsin System, Madison WI

Investigators

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