** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** FOOD SECURITY IS ONE OF THE MOST IMPORTANT GLOBAL CHALLENGES OF OUR AGE AND INSECT PESTS CONTINUE TO BE A PROBLEM IN AGRICULTURAL SYSTEMS, CONTRIBUTING TO BETWEEN 36%-42% LOSSES IN SOME STAPLE CROP SYSTEMS. REDUCING CROP DAMAGE BY PEST INSECTS IS ONE STRATEGY TO INCREASE FOOD PRODUCTION AND SECURITY. TOXINS FROM THE INSECT PATHOGEN BACILLUS THURINGIENSIS (BT) ARE WIDELY USED IN BIOLOGICAL CONTROL. BT TOXINS, WHICH ARE SPECIFICALLY TOXIC TO INSECTS AND NOT MAMMALS, ARE APPLIED (SPRAYED) ON CROPS AND PRODUCED BY TRANSGENIC CROPS TO CONTROL INSECT PESTS IN AGRICULTURE. HOWEVER, RESISTANCE TO THESE TOXINS IN SOME POPULATIONS OF INSECT PESTS IS A PROBLEM, MAKING BT TOXINS LESS EFFECTIVE. ONE WAY TO COMBAT RESISTANCE TO BT TOXINS IS TO USE A VARIETY OF TOXINS WITH DIFFERENT MODES OF ACTION, INCLUDING THE DEVELOPMENT OF NOVEL TOXINS. RECENTLY WE HAVE DISCOVERED THAT INSECT-PARASITIC NEMATODES, WHICH ARE CONSIDERED BENEFICIAL NEMATODES SINCE THEY KILL INSECT PESTS, PRODUCE AND RELEASE INSECTICIDAL PROTEINS INTO THEIR HOSTS. WE HAVE FOUND THAT THEY HAVE ORAL TOXICITY TO SOME INSECT PESTS AND HAVE IDENTIFIED SEVERAL PROMISING CANDIDATES AND HAVE ESTABLISHED A PIPELINE TO CHARACTERIZE OTHERS. WE PROPOSE TO DEVELOP OUR PROMISING CANDIDATES AND ASSESS THEIR EFFICACY IN TRANSGENIC PLANTS AND FOLIAR APPLICATION AS WELL AS CHARACTERIZE ADDITIONAL NEMATODE-DERIVED INSECTICIDAL PROTEINS AND TEST THE FEASIBILITY OF USING THESE TOXINS TO CONTROL INSECT PESTS IN AGRICULTURAL SYSTEMS. THE RESULTS OF THIS RESEARCH COULD LEAD TO THE DEVELOPMENT OF NEW NATURAL COMPOUNDS USEFUL FOR KILLING INSECT PESTS. THIS PROPOSAL ADDRESSES A PROGRAM AREA PRIORITY FOR PESTS AND BENEFICIAL SPECIES IN AGRICULTURAL PRODUCTION SYSTEMS BY DEVELOPING STRATEGIES TO MITIGATE RESISTANCE TO PESTICIDES AND/OR TOXINS.