THE CATTLE FEVER TICK OR SOUTHERN CATTLE TICK IS THE MOST ECONOMICALLY DAMAGING TICK FOR CATTLE WORLDWIDE. ALL DEVELOPMENTAL STAGES OF THE TICK FROM LARVAE TO ADULT FEED ON A SINGLE HOST ANIMAL, PREFERENTIALLY CATTLE. THE TICK CREATES A WOUND TO BLOOD FEED AND DAMAGES THE ANIMAL HIDES, DECREASING THEIR VALUE. MOST IMPORTANTLY, DURING BLOOD-FEEDING THE TICK CAN ACQUIRE OR TRANSMIT MICROORGANISMS THAT CAUSE THE CATTLE DISEASES BABESIOSIS AND ANAPLASMOSIS THAT ARE HIGHLY LETHAL TO CATTLE. THESE DISEASE-CAUSING MICROORGANISMS CAN BE TRANSFERRED TO TICK EGGS INSIDE THE FEMALE TICK, THEREFORE, TICK LARVAE BORN FROM THE INFECTED EGGS CAN TRANSMIT THE MICROORGANISM TO NEW CATTLE HOSTS, CONTINUING THE CYCLE OF DISEASE TRANSMISSION. THERE ARE NO VACCINES AVAILABLE IN THE US AGAINST THESE DISEASES. CATTLE PRODUCERS USE CHEMICAL PESTICIDES CALLED ACARICIDES TO CONTROL TICK POPULATIONS, BUT MANY OF THESE POPULATIONS HAVE DEVELOPED ACARICIDE RESISTANCE, SURVIVING PESTICIDE APPLICATIONS. ACARICIDE RESISTANCE IS WIDESPREAD IN MEXICO, AND DESPITE STRICT INSPECTION AND TREATMENT OF CATTLE AT THE US-MEXICO BORDER, INCOMING TICK POPULATIONS ARE A CONSTANT THREAT TO THE US CATTLE INDUSTRY. LIVE CATTLE AND WILD ANIMALS, SUCH AS WHITE TAIL DEER, CAN CARRY LIVE TICKS ACROSS OUR SOUTHERN US BORDER. THERE IS AN URGENT NEED TO DEVELOP NEW ACARICIDES FOR TICK CONTROL AND THIS PROJECT ADDRESSES THIS NEED TO IMPROVE ANIMAL PRODUCTION AND HEALTH.THIS RESEARCH AIMS TO FIND NEW CHEMICALS (NATURAL OR SYNTHETIC) TO KILL THESE TICKS IN NOVEL, SELECTIVE MANNERS. TO DO THIS, WE WILL IDENTIFY TICK PROTEINS BELONGING TO A PROTEIN SUPERFAMILY KNOWN AS G PROTEIN-COUPLED RECEPTORS. IDENTIFICATION OF THESE PROTEINS IS VALUABLE FOR TWO MAIN REASONS: 1) THEY ARE THOUGHT TO BE CRITICAL FOR TICK SURVIVAL AND, 2) THEIR FUNCTION CAN BE DISRUPTED BY APPLICATION OF A FOREIGN NATURAL OR SYNTHETIC MOLECULE. WE WILL USE A MOLECULAR GENETICS TECHNIQUE CALLED GENE SILENCING TO KNOCK OUT OR ELIMINATE THE ABILITY OF THESE RECEPTORS TO PERFORM THEIR NORMAL FUNCTION IN THE TICK. IT IS EXPECTED THAT THE LOST FUNCTION OF THESE RECEPTOR PROTEINS WILL INTERFERE WITH THE SURVIVAL OR REPRODUCTION OF THE TICKS PROVIDING NEW KNOWLEDGE ON TICK PHYSIOLOGY. WE WILL SELECT THE RECEPTORS THAT ARE MOST CRITICAL FOR TICK SURVIVAL AND THUS ARE GOOD CANDIDATES FOR DISRUPTION. WE WILL ALSO SCREEN CHEMICALS TO IDENTIFY THOSE THAT DISRUPT THE FUNCTION OF THE SELECTED RECEPTORS TO REDUCE SURVIVAL AND/OR REPRODUCTION OF THE TICKS. CHEMICALS THAT SUCCEED IN DISRUPTING TICK RECEPTOR PROTEIN FUNCTION WILL FORM THE BASIS FOR DEVELOPMENT OF NEW ACARICIDES URGENTLY NEEDED FOR TICK CONTROL.