THERE IS A CRITICAL, UNMET NEED FOR NOVEL TOOLS TO PREVENT AND TREAT DISEASE OUTBREAKS AT AQUACULTURE FACILITIES. RECENTLY, MARINE BACTERIA BELONGING TO THE GENUS PHAEOBACTER HAVE EMERGED AS HIGHLY PROMISING TARGETS FOR DEVELOPMENT OF DISEASE PREVENTION AGENTS FOR LARVICULTURE. USING IN VIVO INFECTION MODELS, CERTAIN PHAEOBACTER STRAINS DEMONSTRATE IMPRESSIVE HOST PROTECTION IN COD, TURBOT, OYSTER, AND SCALLOP LARVAE.HOWEVER, WE CURRENTLY LACK FUNDAMENTAL KNOWLEDGE OF THE MOLECULAR MECHANISMS THAN ENABLE THE FAVORABLE INTERSPECIES INTERACTIONS BETWEEN HOST, PATHOGEN, AND PHAEOBACTER.THE LONG-TERM GOAL OF OUR INVESTIGATION IS TO DEVELOP NEW TOOLS TO ENHANCE AQUACULTURE.HERE, WE WILL DEFINE MOLECULAR MECHANISMS THAT DETERMINE THE SURVIVAL OF OYSTER LARVAE WHEN EXPOSED TO A PROBIOTIC BACTERIUM, PHAEOBACTER INHIBENS S4, AND A PROBLEMATIC, WIDESPREAD SHELLFISH PATHOGEN WITH A BROAD HOST-RANGE, VIBRIO CORALLIILYTICUS RE22. WE RECENTLY DEMONSTRATED THAT S4 IS A SAFE AND EFFECTIVE DISEASE PREVENTION TOOL FOR OYSTER HATCHERIES. THIS PROJECT WILL NOW TEST THE HYPOTHESIS THAT SPECIFIC AND DIRECTED MOLECULAR MECHANISMS EMPLOYED BY THE HOST, PROBIONT, AND PATHOGEN DETERMINE THE OUTCOMES OF INTERSPECIES INTERACTIONS AND, ULTIMATELY, THE HEALTH AND SURVIVAL OF THE OYSTER. MUTAGENESIS WILL BE USED TO ELUCIDATE THE ROLE OF TARGETED PATHWAYS, ESPECIALLY THOSE INVOLVED IN TYPE VI SECRETION SYSTEMS (T6SS), THAT INFLUENCE INTERACTION OUTCOMES. GENOMIC AND (META)TRANSCRIPTOMIC ANALYSIS WILL BE USED TO FURTHER ILLUMINATE PATHWAYS INVOLVED IN PROBIONT-PATHOGEN INTERACTIONS. THIS PROJECT ADDRESSES PROGRAM OBJECTIVES TO DEFINE MOLECULAR AND WHOLE-ANIMAL ASPECTS RELATED TO DISEASE PREVENTION AND THERAPEUTIC INTERVENTION.