**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** TO MAINTAIN HUMAN AND ANIMAL HEALTH, IT IS EXTREMELY IMPORTANT TO UNDERSTAND HOW PATHOGENS LIKE VIRUSES ARE TRANSMITTED AND EVOLVE TO HIGHER VIRULENCE. THIS KNOWLEDGE IS ESPECIALLY IMPORTANT FOR SUSTAINABLE DISEASE CONTROL, PARTICULARLY REGARDING THE EFFECTIVENESS OF BIOSECURITY, GENETIC SELECTION, AND VACCINATION. THUS, IT IS NECESSARY TO COLLECT, ASSEMBLE, AND ANALYZE HIGHLY INFORMATIVE AS WELL AS DIVERSE BUT COMPLEMENTARY DATASETS TO DETERMINE THE ROLES OF THESE CONTROL MEASURES ON VIRAL TRANSMISSION AND EVOLUTIONARY DYNAMICS. IN THIS PROJECT, AN INTERNATIONAL, INTERDISCIPLINARY TEAM INVESTIGATES THE IMPACT OF THESE APPROACHES ON THE SPREAD AND EVOLUTION OF TWO AVIAN PATHOGENIC VIRUSES - MAREK'S DISEASE VIRUS (MDV) AND INFECTIOUS BRONCHITIS VIRUS (IBV) - BOTH OF WHICH ARE PRIMARILY CONTROLLED BY IMPERFECT VACCINES. IT HAS BEEN ARGUED THAT IMPERFECT VACCINES, SUCH AS THOSE TO MDV AND IBV, OR HOST GENETIC RESISTANCE MAY ALTER THE BALANCE OF SELECTION BETWEEN PATHOGEN TRANSMISSIONAND VIRULENCE BY ALLOWING A FEW MORE DIVERGENT BUT STILL VIRULENT STRAINS TO BE TRANSMITTED AT REDUCED COST. HOWEVER, THESE HYPOTHESES HAVE NOT BEEN PROVEN, AND PREDICTIVE FRAMEWORKS ARE LACKING TO DETERMINE THE COMBINED INFLUENCE OF HOST AND VIRAL GENETICS, AS WELL AS VACCINATION ON VIRAL TRANSMISSION AND EVOLUTION TO INCREASED VIRULENCE. TO ADDRESS THESE KNOWLEDGE GAPS, A SERIES OF TRANSMISSION EXPERIMENTS HAVE BEEN DESIGNED UTILIZING UNIQUE RESOURCES AND DATA FROM BIRDS UNDER HIGHLY CONTROLLED CONDITIONS. THE GOALS OF THE PROPOSED WORK ARE TO COLLECT HIGH-RESOLUTION, EMPIRICAL DATASETS TO BUILD THE NEXT GENERATION OF SYSTEMS MODELS INCORPORATING HOST, VIRAL, AND MANAGEMENT FACTORS, AS WELL AS TO ESTABLISH THE ROLE OF VIRAL GENOME VARIABILITY ON VIRULENCE EVOLUTION. FURTHERMORE, WE WILL PREDICT THE COMBINED INFLUENCE OF GENETICS, VACCINATION, AND MANAGEMENT PRACTICES ON VIRUS TRANSMISSION, AND ASSESS THE LIKELY EVOLUTIONARY DYNAMICS IN DIFFERENT SOCIO-ECONOMIC SETTINGS.