**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THE CATTLE TICK OR CATTLE FEVER TICK IS AN EXTERNAL PARASITE OF CATTLE AND ONE OF THE MOST IMPORTANT THREATS TO THE U.S. CATTLE INDUSTRY BECAUSE IS A VECTOR OF THE BLOOD-BORNE PATHOGENS CAUSING BABESIOSIS AND ANAPLASMOSIS, TWO ECONOMICALLY IMPORTANT AND DEADLY CATTLE DISEASES. AN INFECTED TICK THAT BLOOD FEEDS ON A CALF OR COW TRANSMITS WITH ITS SALIVA THE DISEASE-CAUSING PATHOGEN. AN EFFECTIVE VACCINE DOES NOT EXIST AGAINST THE PATHOGENS THAT CAUSE BABESIOSIS. THUS, THE CONTROL OF THE DISEASE IN THE U.S. HAS BEEN SUCCESSFUL ONLY THROUGH THE CONTROL OF TICK POPULATIONS USING PESTICIDES. ALTHOUGH ERADICATED FROM THE US, THE TICK OCCASIONALLY REAPPEARS AND REMAINS COMMON IN MEXICO WHERE IT HAS BECOME RESISTANT TO THE PESTICIDES USED FOR ITS CONTROL. THESE TICKS ALSO INFEST WHITE TAIL DEER AND OTHER WILDLIFE IN SOUTH TEXAS, COMPLICATING ERADICATION. THE LEGAL ENTRY OF LIVE CATTLE FROM MEXICO INTO THE US IS A LONG-STANDING PRACTICE, WITH ANIMALS TREATED WITH PESTICIDES UPON ENTRY. BECAUSEOF THE PROBLEM OF PESTICIDE RESISTANCE, WE HAVE ONLY ONE REMAINING EFFECTIVE CHEMICAL; THUS IT IS IMPERATIVE TO DISCOVER NEW MOLECULES TO KILL TICKS THAT ARE SAFE FOR CATTLE. IN THIS MULTIDISCIPLINARY PROJECT WE WILL EVALUATE THE ANTI-TICK ACTIVITY OF SMALL MOLECULES WE DISCOVERED THAT ACT AGAINST A PROTEIN FOUND ONLY IN TICKS AND ARE NOT TOXIC TO VERTEBRATE CELLS. WE WILL STUDY OTHER MOLECULES FOUND TO IMPACT TICK FEEDING AND REPRODUCTION, AND THE RECEPTORS FOR TICK HORMONES, AS INTERFERENCE WITH THESE COULD BE DEADLY TO TICKS.THROUGH THIS PROJECT, WE WILL EXAMINE THOUSANDS OF SYNTHETIC SMALL MOLECULES USING STATE-OF-THE-ART TECHNOLOGIES. THE PROJECT WILL PRODUCE KNOWLEDGE LEADING TO THE DEVELOPMENT OF NEW STRATEGIES FOR TICK CONTROL, APPLICABLE TO OTHER TICKS AS WELL. THE PROJECT IS LED BY FOUR SCIENTISTS AND COLLABORATORS WITH COMPLEMENTARY EXPERTISE IN TICK TOXICOLOGY, PHYSIOLOGY, GENOMICS, AND CHEMISTRY.