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** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** RHIZOPUS MICROSPORUS IS EMERGING AS A MODEL FOR STUDYING THE BASIC BIOLOGY OF THE EARLY-DIVERGING FUNGAL SUBPHYLUM MUCOROMYCOTINA, AN UNDERSTUDIED GROUP CONTAINING SIGNIFICANT POST-HARVEST SPOILAGE AGENTS, PHYTOPATHOGENS, AND OPPORTUNISTIC HUMAN PATHOGENS. UNLIKE MOST OTHER EUKARYOTIC LINEAGES THAT RELY ON 5-METHYLCYTOSINE (5MC) DNA MODIFICATIONS, EARLY-DIVERGING FUNGI SUCH AS THE MUCOROMYCOTINA EMPLOY N6-METHYLADENINE (6MA) AS THE PREDOMINANT EPIGENETIC MODIFICATION. BACTERIA ALSO USE 6MA AS THEIR PREDOMINANT EPIGENETIC MARK AND MUCOROMYCOTINA FUNGI INCLUDING R. MICROSPORUS FREQUENTLY HARBOR HIGHLY COEVOLVED BACTERIAL ENDOSYMBIONTS. THE ABSENCE OF COGNATE ADENINE METHYLTRANSFERASES IN PLANTS AND ANIMALS AND THE SHARED EPIGENETIC PROGRAM BETWEEN THESE FUNGI AND THEIR ENDOSYMBIONTS INSPIRED MY HYPOTHESES THAT 1) ADENINE METHYLATION IS A NOVEL BIOCONTROL TARGET FOR EARLY-DIVERGING FUNGAL PATHOGENS AND 2) 6MA IS INTEGRAL TO THE SYMBIOSIS OF R. MICROSPORUS AND ITS BACTERIAL ENDOSYMBIONT, MYCETOHABITANS. TO ADDRESS MY OBJECTIVES, I WILL FIRST DEVELOP AN IN VITRO SCREENING STRATEGY OF SMALL-MOLECULE LIBRARIES FOR INHIBITION OF THE ADENINE METHYLTRANSFERASE COMPLEX IN R. MICROSPORUS TO IDENTIFY CANDIDATE BIOCONTROL AGENTS. SECOND, I WILL COMPARE THE GENOMES AND 6MA PROFILES OF ~30 R. MICROSPORUS ISOLATES THAT NATURALLY HARBOR MYCETOHABITANS AND ~30 THAT DO NOT IN ORDER TO IDENTIFY CANDIDATE SYMBIOSIS FACTORS REGULATED BY 6MA. ADENINE METHYLTRANSFERASE DELETION MUTANTS IN MYCETOHABITANS WILL FURTHER ASSESS THE ROLE OF 6MA IN SYMBIOSIS. BY DEFINING THE ROLE OF A UNIQUE EUKARYOTIC EPIGENETIC MODIFICATION IN AN AGRICULTURALLY RELEVANT FUNGAL-BACTERIAL SYMBIOSIS AND THROUGH ASSESSING ADENINE METHYLATION AS A NOVEL BIOCONTROL TARGET, I STRIVE TO INFORM MANAGEMENT STRATEGIES AND THE BASIC BIOLOGY OF THE MUCOROMYCOTINA FUNGI.

$180,000FY2024National Institute of Food and AgricultureUSDA

Cornell University, Ithaca NY

Investigators

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