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THE MICRO-5 SPACEFLIGHT EXPERIMENT WAS PROPOSED IN 2009 TO PROVIDE A CUTTINGEDGE INVESTIGATION OF HOST-PATHOGEN INTERACTIONS WHEN BOTH HOST AND PATHOGEN WERE SIMULTANEOUSLY EXPOSED TO THE SPACEFLIGHT ENVIRONMENT. A KEY ASPECT OF MICRO-5 WAS THE TARGETED ANALYSIS OF SPECIFIC GENE EXPRESSION (USING QRT-PCR) DURING THE INFECTION PROCESS. RECENT ADVANCES IN NEXT GENERATION GLOBAL TRANSCRIPTOMIC TECHNOLOGY HAVE ENABLED ANALYSIS OF ALL RNA TRANSCRIPTS DURING INFECTION INCLUDING BOTH HOST AND PATHOGEN AT A FRACTION OF THE COST THAT WOULD HAVE BEEN INCURRED IN 2009. THIS PROPOSAL RECOMMENDS THAT ANALYSIS OF GENE EXPRESSION PROFILING FOR MICRO-5 BE UPDATED TO THE NEW RNA-SEQ METHODOLOGY AT A NET ADDITIONAL COST OF $95 680. INCLUDED IN THIS PROPOSED WORK WILL BE RNA-SEQ ANALYSIS OF LB AND LB-M9 SAMPLES DURING SPACEFLIGHT AND SYNCHRONOUS GROUND CONTROLS (STATIC AND ROTATING). THESE SAMPLES WERE SELECTED AS OUR VIDEO OBSERVATIONS OF NEMATODE SURVIVAL FOLLOWING INFECTION HAVE DEMONSTRATED SIGNIFICANTLY ENHANCED VIRULENCE IN SPACEFLIGHT CONDITIONS COMPARED TO GROUND CONTROLS. ALSO INCLUDED IN THIS PROPOSED SUPPLEMENTAL WORK ARE SMALL CONFIRMATORY TESTS THAT MAY BE NEEDED TO VALIDATE OBSERVED PHENOTYPES. ADDITION OF THIS DATA WOULD SIGNIFICANTLY INCREASE OUR DEPTH AND BREADTH OF UNDERSTANDING OF THE DYNAMIC MOLECULAR GENETIC MECHANISMS THAT REGULATE ALTERED VIRULENCE AND INFECTION PROFILES DURING SPACEFLIGHT AND PROVIDE A FIRST-OF-ITS-KIND FOUNDATION FROM WHICH GENELAB INVESTIGATORS WOULD HAVE A RICH AND UNIQUE SOURCE FOR FUTURE DATA MINING. ACCORDINGLY THIS DATA WOULD 1) DIRECTLY BENEFIT CREW HEALTH RISK ASSESSMENTS 2) SERVE AS AN IMPORTANT FOUNDATION TO FOSTER A TRUE SYSTEMS BIOLOGY INTEGRATED APPROACH TO MEASURE HOSTPATHOGEN PARAMETERS AT A GLOBAL LEVEL AND 3) REVEAL UNEXPECTED PATHOGENESIS MECHANISMS AND THERAPEUTIC TARGETS THAT HAVE BEEN PREVIOUSLY UNOBSERVED OR UNAPPRECIATED USING TRADITIONAL EXPERIMENTAL APPROACHES.

$95,680FY2017National Aeronautics and Space AdministrationNASA

Arizona State University, Scottsdale AZ

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