**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CRYPTOSPORIDIOSIS POSES A GLOBAL PUBLIC HEALTH THREAT CHARACTERIZED BY LIFE-THREATENING DIARRHEA IN NEONATES, BUT SEVERE CLINICALDISEASE IN ADULT CATTLE AND PEOPLE IS UNCOMMON. DESPITE SUBSTANTIAL IMPACTS ON THE HEALTH AND ECONOMY OF THE CATTLE INDUSTRY AND THE PUBLIC, EFFECTIVE PREVENTATIVE AND THERAPEUTIC INTERVENTIONS ARE LACKING. THIS IS, IN PART, DUE TO GAPS IN OUR UNDERSTANDING OF HOW CRYPTOSPORIDIOSIS CAUSES DISEASE DIFFERENTLY IN NEONATES COMPARED TO ADULTS, AND A LACK OF ROBUST MODELS TO STUDY THIS DISEASE. INTERACTIONS BETWEEN INTESTINAL CELLS, IMMUNE CELLS, AND FACTORS IN THE TISSUES SERVE AS THE FIRST LINE OF DEFENSE AGAINST CRYPTOSPORIDIOSIS AND ULTIMATELY DETERMINE THE SEVERITY OF THE DISEASE. THE OBJECTIVE OF THIS WORK IS TO: 1) IDENTIFY NEW TARGETS FOR TREATING CRYPTOSPORIDIOSIS BY UNRAVELING THE IMPACT OF AGE (CALVES VS. ADULTS) ON THE DEVELOPMENT OF PROTECTIVE IMMUNITY TO CRYPTOSPORIDIOSIS AND 2) TO VALIDATE AN AGE-SPECIFIC MODEL TO STUDY CRYPTOSPORIDIOSIS. THIS PROJECT HYPOTHESIZES THAT THESE IMMUNE INTERACTIONS (CELLS AND TISSUE FACTORS) WILL DIFFER IN MAGNITUDE AND TYPE IN CALVES COMPARED TO ADULT CATTLE IN AN AGE-DEPENDENT MANNER. THIS WORK WILL ADVANCE OUR KNOWLEDGE OF HOW THE IMMUNE SYSTEM DEVELOPS IN CALVES' OVERTIME AND WILL DETERMINE HOW IMMUNE SYSTEM DEVELOPMENT CONTRIBUTES TO AGE-RELATED SUSCEPTIBILITY TO INFECTION. IN DOING SO, THIS STUDY WILL IDENTIFY PREVENTATIVE AND THERAPEUTIC TARGETS THAT WILL LATER BE EVALUATED FOR EFFICACY. FURTHER, THE ROBUST MODEL AND APPROACH USED HERE WILL SUPPORT AN INVESTIGATION INTO HOW OTHER INFECTIOUS AGENTS CAUSE DISEASE AND PROMOTE THERAPEUTIC DISCOVERY FOR COUNTLESS OTHER INFECTIONS IN CATTLE.