** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** APHIDS ARE ECONOMICALLY IMPORTANT PLANT-SUCKING PESTS WITHIN AGRICULTURAL SYSTEMS AND THEIR POPULATIONS ARE EXPECTED TO INCREASE DUE TO SHIFTING GLOBAL WEATHER PATTERNS.TWO BARRIERS THAT HAVE HINDERED THE DEVELOPMENT OF RESISTANCE BREAKING APHICIDES IS THE LACK OF KNOWLEDGE REGARDING 'DRUGGABLE' TARGETS FOR INSECTICIDE DEVELOPMENT AND THE DEVELOPMENT OF CHEMICAL SCAFFOLDS THAT ARE ACUTELY TOXIC, YET SELECTIVE FOR PEST INSECTS.OUR PUBLISHED AND PRELIMINARY DATA SUGGEST THAT BRIDGING BOTH OF THESE BARRIERS IS POSSIBLE.THE POTASSIUM-CHLORIDE COTRANSPORTER (KCC) IS A SENSITIVE NEURAL TARGET FOR INSECTICIDES AND WE HAVE SHOWN THAT N-ARYLAMIDES INHIBIT KCC TO INDUCE APHID TOXICITY.IMPORTANTLY, APPROPRIATELY SUBSTITUTED ARYL AMIDES ARE EQUITOXIC TO COMMERCIALIZED APHICIDES AND ARE HIGHLY TOXIC TO PYRETHROID-RESISTANT MYZUS PERSICAE.THEREFORE, WE AIM TO TEST THE HYPOTHESIS THAT INHIBITION OF M. PERSICAE KCC BY N-ARYLAMIDES WILL INDUCE ACUTE LETHALITY AND ALTER APHID FEEDING BEHAVIOR TO PREVENT HORIZONTAL TRANSMISSION OF PLANT VIRUSES.TO TEST THIS HYPOTHESIS, WE WILL SYNTHESIZE NOVEL N-ARYLAMIDE SCAFFOLDS (OBJECTIVE 1), TEST THE ACUTE AND CHRONIC TOXICITY AND REPELLENCY OF DEVELOPED MOLECULES (OBJECTIVE 2), DEFINE CHANGES TO HORIZONTAL TRANSMISSION AND APHID ACQUISITION OF PLANT VIRUSES AFTER EXPOSURE TO N-ARYLAMIDES (OBKJECTIVE 3), AND CATALYZE SYSTEMIC MOVEMENT OF N-ARYLAMIDES THROUGHOUT THE PLANT BY INCORPORATION OF NEW SOLUBILIZER TECHNOLOGY (OBJECTIVE 4).THE DATA GENERATED IN THIS STUDY WILL BRIDGE FUNDAMENTAL KNOWLEDGE GAPS THAT HAVE LIMITED ADVANCEMENT IN THE FIELDS OF VECTOR/DISEASE MANAGEMENT AND WILL HELP INCREASE THE SUSTAINABILITY OF THE AGRICULTURAL INDUSTRY THROUGH MANAGEMENT OF APHID POPULATIONS.?