DAIRY COWS SUFFER FROM INFECTIOUS AND INFLAMMATORY DISEASE IN THE EARLY POSTPARTUM PERIOD. THIS LEADS TO SIGNIFICANT ECONOMIC LOSS, INCREASED ANTIMICROBIAL USAGE, AND DIMINISHED ANIMAL WELFARE. DURING THIS TIME, COWS EXPERIENCE A PERIOD OF IMMUNE DYSFUNCTION - A WELL-KNOWN CONSEQUENCE OF POOR METABOLIC ADAPTATION IN THE TRANSITION PERIOD CHARACTERIZED BY INCREASED INFLAMMATION AND REDUCED PATHOGEN CLEARANCE. THE MAGNITUDE AND PERSISTENCE OF THE INFLAMMATION IS ASSOCIATED WITH INCREASED RISK FOR DISEASE, DECREASED REPRODUCTIVE SUCCESS, AND A LOSS IN MILK PRODUCTION. THIS DYSFUNCTION IS GREATEST IN ANIMALS WITH EXCESSIVE NEGATIVE NUTRIENT BALANCE. WE LACK UNDERSTANDING OF THE MECHANISTIC LINK BEHIND THIS ASSOCIATION AND SEEK TO TARGET THIS KNOWLEDGE GAP. THE NUTRIENT-SENSING MECHANISTIC TARGET OF RAPAMYCIN (MTOR) SIGNALING PATHWAY ORCHESTRATES IMMUNE CELL PROLIFERATION AND DIFFERENTIATION IN THE FACE OF VARYING AMINO ACID (AA) AND ENERGY AVAILABILITY. IT ALSO REGULATES THE PHENOTYPE, FUNCTION, AND ACTIVATION OF CRITICAL IMMUNE EFFECTOR CELLS SUCH AS MYELOID CELLS THAT FUNDAMENTALLY DRIVE AND REGULATE INFLAMMATORY RESPONSES.OUR PROPOSED STUDIES ARE NOVEL AS THEY EXPLORE A PATHWAY IN THE BOVINE IMMUNE SYSTEM REGULATION THAT HAS A DEMONSTRATED KEY ROLE IN INTEGRATING NUTRIENT-SENSING AND SHAPING IMMUNE RESPONSE IN OTHER SPECIES, BUT HAS NOT BEEN INVESTIGATED IN THIS AGRICULTURALLY IMPORTANT SPECIES. IN ADDITION, THE RESULTS OF THIS WORK TOGETHER WITH THE STRENGTHS AND EXPERIENCES OF OUR TEAM OF INVESTIGATORS IN TRANSITION COW MANAGEMENT AND NUTRITION PROMISE TO NOT ONLY IDENTIFY A TARGET FOR NUTRITIONAL INTERVENTION, BUT ALSO PROPOSE TO APPLY THE FINDINGS DIRECTLY TO IMPROVE ANIMAL HEALTH.THIS INNOVATIVE WORK, IN OUR OPINION, FOSTERS THE UNDERSTANDING OF FUNDAMENTAL MECHANISMS AND THE IDENTIFICATION OF POSSIBLE NUTRITIONAL MITIGATION STRATEGIES TO INTERVENE AT THE CRITICAL POINT IN TRANSITION COW HEALTH.THE IMPACT OF OUR PROPOSED WORK WILL BE MEASURED AS INCREASED ANIMAL HEALTH, SUSTAINABLE PRODUCTION, AND A DECREASE IN THE USE OF ANTIMICROBIALS DURING THE EARLY POSTPARTUM PERIOD.