** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** GLOBAL CLIMATE CHANGE AND ITS IMPACT ON AGRICULTURE, THROUGH DIRECT WEATHER EFFECTS, EXTREME EVENTS ON ANIMAL WELLBEING, CHANGES IN THE DISTRIBUTION OF LIVESTOCK DISEASES, AND IMPACT ON THE ENVIRONMENT, IS A DEFINING CHALLENGE OF OUR TIME. THERE IS AN URGENT NEED TO DEVELOP WAYS TO GENETICALLY IDENTIFY (SELECTION MARKERS) DISEASE TOLERANT ANIMALS THAT CAN OVERCOME THE NEGATIVE EFFECTS OF DISEASE. TRYPANOSOMIASIS IS ONE SUCH DISEASE, CONTRIBUTING TO DRAWBACKS IN CATTLE AGRICULTURE, FOOD INSECURITY, AND MAJOR ECONOMIC LOSS. ADDITIONAL RESEARCH IS NEEDED ON THE BIOLOGICAL PATHWAY(S) THAT MEDIATE IMMUNE RESPONSE TO TRYPANOSOMIASIS, THEREBY CONFERRING TOLERANCE IN CATTLE. IN THIS PROJECT, WE WILL UTILIZE GENOMIC AND MOLECULAR APPROACHES TO UNCOVER THE IMPACT OF GENETICS, INCLUDING SMALL MOLECULES LIKE NON-CODING RNAS, ON IMMUNE SYSTEM PATHWAYS TO UNDERSTAND IMPORTANT IMMUNE REGULATORS DURING TRYPANOSOMIASIS. ULTIMATELY, WE WILL CATALOGUE SIGNATURES FOR DISEASE TOLERANCE AND DEVELOP MARKERSFOR GENOMIC SELECTION TO CURTAIL DISEASE. THE ADDITIONAL BENEFIT OF MARKERS FOR IMPROVED CATTLE PRODUCTIVITY AND THE LONG-TERM SUSTAINABILITY OF ANIMAL AGRICULTURE IS URGENT. PARTNERING WITH OVERSEAS COLLABORATORS TO DECIPHER APPROACHES FOR DIAGNOSIS AND DISEASE CONTROL, CATTLE BREEDING AND GENETIC MANIPULATION, INCLUDING TRANSLATIONAL APPLICATION TO US AGRICULTURE INDUSTRY, IS SIGNIFICANT.