**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 SOIL BACTERIUM BACILLUS THURINGIENSIS (BT) IS THE MOST SUCCESSFUL MICROBIAL INSECTICIDE USED IN AGRICULTURE, AND BT GENES CODING FOR THE PROTEINACEOUS INSECTICIDAL TOXINS ARE THE PRIMARY TRANSGENES USED IN COMMERCIALIZED INSECT-RESISTANT TRANSGENIC CROPS (BT-CROPS). BT-CROPS HAVE NOW BEEN WIDELY ADOPTED AND HAVE PROVIDED SIGNIFICANT ENVIRONMENTAL AND ECONOMIC BENEFITS. HOWEVER, THE WIDESPREAD APPLICATION OF BT TOXINS IN AGRICULTURE HAS IMPOSED INTENSE SELECTION PRESSURE ON TARGET INSECTS TO EVOLVE RESISTANCE TO THE BT TOXINS, AND RESISTANCE TO BT TOXINS IN INSECTS HAS BEEN INCREASINGLY REPORTED. TO DATE, AT LEAST 22 CASES OF PRACTICAL RESISTANCE TO BT-CROPS HAVE OCCURRED IN INSECT POPULATIONS IN AGRICULTURE. CONTINUING SUCCESS OF THE USE OF BT TOXINS FOR PEST CONTROL REQUIRES CONTINUING DEVELOPMENT OF BT BIOTECHNOLOGIES AND DEVELOPMENT OF INSECT RESISTANCE MANAGEMENT STRATEGIES, BOTH OF WHICH CRITICALLY RELY ON OUR UNDERSTANDING OF THE MECHANISMS OF INSECT RESISTANCE TO BT TOXINS. THE BT TOXIN CRY1F IS WIDELY USED IN CURRENT BT-COTTON, BT-MAIZE AND IN BT-SOYBEAN VARIETIES FOR CONTROL OF LEPIDOPTERAN PESTS. PRACTICAL RESISTANCE TO CRY1F-CROPS HAS OCCURRED IN THREE MAJOR LEPIDOPTERAN PESTS WITHIN 10 YEARS AFTER CRY1F-CROPS WERE PLANTED, AND RESISTANCE TO CRY1F HAS BEEN RECENTLY REPORTED IN MORE INSECT SPECIES AND TO BE MORE WIDELY SPREAD IN THE FIELD. IT IS AN URGENT NEED TO UNDERSTAND THE MOLECULAR GENETIC MECHANISMS OF CRY1F RESISTANCE IN INSECTS, TO PROVIDE FUNDAMENTAL KNOWLEDGE NECESSARY FOR MANAGEMENT OF INSECT RESISTANCE TO BT-CROPS IN AGRICULTURE. OUR RECENT STUDIES HAVE REVEALED A NOVEL BUT YET TO BE IDENTIFIED MECHANISM FOR CRY1F RESISTANCE IN THE CABBAGE LOOPER, TRICHOPLUSIA NI, AND WE HAVE DEVELOPED THE INSECT SYSTEM TO DISSECT THE NOVEL MECHANISM OF CRY1F-SPECIFIC RESISTANCE. IN THIS PROJECT, WE USE GENETIC, MOLECULAR AND GENE EDITING TECHNIQUES TO IDENTIFY THE NOVEL CRY1F RESISTANCE-CONFERRING GENE MUTATION AND FUNCTIONALLY REVEAL THE RESISTANCE MECHANISM. THEREFORE, THIS PROJECT AIMS TO DISCOVER A NOVEL MOLECULAR GENETIC MECHANISM OF CRY1F-SPECIFIC RESISTANCE IN INSECTS. THE FINDINGS AND INFORMATION OBTAINED FROM THIS PROJECT WILL CONTRIBUTE IMPORTANT FUNDAMENTAL KNOWLEDGE TO THE FIELD OF BT RESEARCH AND APPLICATION FOR SUSTAINABLE INSECT PEST MANAGEMENT.