Linked Contract Record

DETERMINING THE ROLES OF GIANT STARSHIP TRANSPOSONS IN HORIZONTAL GENE TRANSFER AND FUNGAL BIOLOGY - PROJECT SUMMARY/ABSTRACT MY OVERARCHING GOAL IS TO UNDERSTAND HOW EUKARYOTIC ORGANISMS MANAGE AND TRANSFER GENETIC INFORMATION TO FACILITATE RAPID EVOLUTION. IN PARTICULAR, I SEEK TO TEST THE HYPOTHESIS THAT A NEWLY IDENTIFIED GROUP OF GIANT TRANSPOSONS DRIVE BIOLOGICAL AND EVOLUTIONARY OUTCOMES IN FUNGAL EUKARYOTES BY GENERATING PHENOTYPIC VARIATION AND TRANSFERRING ADAPTIVE TRAITS. FUNGI ARE EUKARYOTIC MICROBES WHOSE ACTIVITIES POSE BOTH THREATS AND OPPORTUNITIES FOR HUMAN HEALTH AND SOCIETY. MY PROGRAM WILL ADDRESS THE URGENT NEED TO UNDERSTAND THE MECHANISMS OF FUNGAL EVOLUTION WITH THE LONG-TERM GOAL OF INTEGRATING THIS KNOWLEDGE INTO CONCEPTUALLY INNOVATIVE APPROACHES FOR DISEASE MITIGATION AND HEALTH MANAGEMENT. I RECENTLY DISCOVERED A PREVIOUSLY UNKNOWN MECHANISM OF FUNGAL EVOLUTION: GIANT TRANSPOSONS CALLED STARSHIPS. THESE ELEMENTS ARE UNLIKE ANY OTHER KNOWN FUNGAL TRANSPOSON BECAUSE THEY CARRY DOZENS OF GENES ENCODING DIVERSE FUNGAL TRAITS, LIKE SECONDARY METABOLITE PRODUCTION AND BIOFILM FORMATION. STARSHIPS ARE PRESENT ACROSS HUNDREDS OF FILAMENTOUS FUNGAL SPECIES, AND MY RECENT WORK DEMONSTRATES THEY ARE ONE OF THE FEW KNOWN MECHANISMS OF EUKARYOTIC HORIZONTAL GENE TRANSFER CAPABLE OF DISSEMINATING ADAPTIVE TRAITS ACROSS SPECIES. THOUGH MOUNTING EVIDENCE IMPLICATES STARSHIPS IN RAPID FUNGAL EVOLUTION, ROUTINE ANALYTICAL METHODS (E.G. GENOMICS, TRANSCRIPTOMICS, REFERENCE-BASED ANALYSES) NEGLECT TO ACCOUNT FOR THIS NEWLY REVEALED YET UNRESOLVED ASPECT OF FUNGAL BIOLOGY. FURTHERMORE, THERE IS A LACK OF FOUNDATIONAL KNOWLEDGE AND EXPERIMENTAL TOOLS FOR INVESTIGATING THE MOLECULAR MECHANISMS OF HORIZONTAL STARSHIP TRANSFER AND THEIR CONTRIBUTIONS TO IMPORTANT HUMAN-ASSOCIATED FUNGAL LIFESTYLES, LIKE PATHOGENESIS AND MUTUALISM. WITHOUT SUCH KNOWLEDGE, STARSHIPS WILL REMAIN A PERSISTENT SOURCE OF INEXPLICABLE BIOLOGICAL VARIATION AND THEIR BROADER IMPACTS ON HUMAN HEALTH AND DISEASE UNKNOWN. MY RESEARCH PROGRAM WILL ADDRESS THESE GAPS BY DEVELOPING AMBITIOUS YET FEASIBLE SYSTEMS AND TOOLS WITHIN THE MODEL GENUS OF ASPERGILLUS FUNGI TO INVESTIGATE THE ROLES OF STARSHIPS IN HORIZONTAL GENE TRANSFER AND FUNGAL BIOLOGY. MY GOALS ARE TO CHARACTERIZE THE MOLECULAR MECHANISMS OF STARSHIP MOBILITY, TO IDENTIFY THE GENETIC COMPONENTS GOVERNING HORIZONTAL STARSHIP TRANSFER AND TO DETERMINE IF AND HOW STARSHIPS IMPACT PHENOTYPES RELEVANT FOR FUNGAL SURVIVAL AND BIOLOGY. MY GROUP WILL LEVERAGE TECHNIQUES SPANNING EVOLUTIONARY GENOMICS AND MOLECULAR BIOLOGY, INCLUDING RECENTLY DEVELOPED PROTOCOLS IN MY LAB FOR INDUCING HORIZONTAL STARSHIP TRANSFER IN VITRO AND FOR GENERATING DELETION MUTANTS OF ENTIRE STARSHIPS TO ENABLE REVERSE GENETICS. WHEN TAKEN TOGETHER, MY INDEPENDENT AND SYNERGISTIC RESEARCH PLANS WILL PROVIDE MUCH NEEDED PRACTICAL AND INTEGRATED KNOWLEDGE FOR EVALUATING THE IMPORTANCE OF STARSHIPS IN HUMAN HEALTH WHILE ENABLING NEW DISCOVERIES IN MICROBIAL GENETICS FOR YEARS TO COME.