** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** SOYBEAN CYST NEMATODE (SCN) IS THE MOST YIELD LIMITING AND ECONOMICALLY IMPORTANT PATHOGEN OF SOYBEAN IN THE UNITED STATES WITH AVERAGE ANNUAL YIELD LOSSES ESTIMATED AT $1.5 BILLION. THE MOST EFFICIENT STRATEGY TO CONTROL SCN IS THE USE OF RESISTANT SOYBEAN CULTIVARS. HOWEVER, GIVEN THE NARROW GENETIC BASE OF SCN RESISTANCE IN COMMERCIAL SOYBEAN CULTIVARS GROWN IN THE UNITED STATES TOGETHER WITH THE HIGH GENETIC DIVERSITY OF FIELD POPULATIONS, SCN POPULATIONS HAVE EVOLVED TO OVERCOME RESISTANCE IN THESE CULTIVARS. THEREFORE, IDENTIFYING MAJOR SOYBEAN RESISTANCE GENES AGAINST THIS DEVASTATING PEST IS IMPERATIVE IN ORDER TO GENERATE DURABLE RESISTANCE AGAINST SCN AND PROTECT SOYBEAN YIELD AND INCREASE THE GROWTH AND ECONOMIC PERFORMANCE OF SOYBEAN FARMS AND THE AGROINDUSTRY SECTORS. WE RECENTLY IDENTIFIED A NOVEL RESISTANCE GENE CANDIDATE AND A HOST SUSCEPTIBLY GENE, WHICH SIGNIFICANTLY IMPACTED SOYBEAN RESPONSES TO ONE OF THE MOST WIDELY SPREAD SCN RACES. THE OVERALL GOAL OF THIS RESEARCH IS TO CONFIRM THE FUNCTION OF THESE TWO GENES IN CONFERRING A HIGH LEVEL OF RESISTANCE AGAINST SCN AND GENERATE NEW SCN-RESISTANT GERMPLASM FOR CULTIVAR DEVELOPMENT. FIRST, WE WILL USE TRANSGENIC AND GENOME EDITING APPROACHES TO INVESTIGATE THE IMPACT OF THE RESISTANCE GENE CANDIDATES ON SOYBEAN RESISTANCE TO VARIOUS RACES OF SCN AND DETERMINE ANY POTENTIAL FUNCTIONAL LINKAGE WITH THE KNOWN SCN RESISTANCE GENES. SECOND, WE WILL DETERMINE THE MECHANISM OF RESISTANCE USING AN INTEGRATIVE APPROACH OF MOLECULAR, BIOCHEMICAL, GENETIC AND GENOMIC TECHNIQUES. RESULTS FROM THIS RESEARCH PROJECT WILL BE TRANSLATED TO RESISTANT SOYBEAN GERMPLASM AND INTELLECTUAL PROPERTY THAT COULD BE POTENTIALLY USED BY THE PUBLIC AND PRIVATE SEED COMPANIES THROUGH TRADITIONAL BREEDING, OR NON GMO-GENOME EDITING APPROACHES TO GENERATE IMPROVED SOYBEAN CULTIVARS WITH BROAD-SPECTRUM AND DURABLE RESISTANCE AGAINST THE MOST DAMAGING PEST OF SOYBEAN PRODUCTION IN THE UNITED STATES.