**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 SOYBEAN CYST NEMATODE (SCN), A MICROSCOPIC SOIL-BORNE ROUNDWORM, IS A WIDESPREAD PATHOGEN OF SOYBEAN AND A BILLION DOLLAR PROBLEM IN US AGRICULTURE. DECADES OF PLANTING A SINGLE TYPE OF GENETIC RESISTANCE HAS LED TO WIDESPREAD VIRULENCE OF THIS PATHOGEN ON COMMERCIALLY AVAILABLE SCN-RESISTANT SOYBEAN CULTIVARS REDUCING THEIR OVERALL EFFECTIVENESS. THE GOAL OF THIS PROPOSAL IS TO BETTER UNDERSTAND THE RESISTANCE MECHANISMS OF THE SOYBEAN PLANT TO GAIN INSIGHT INTO HOW SCN ARE ABLE TO ADAPT TO OVERCOME IT AND ENABLE THE DESIGN OF MORE DURABLE RESISTANCE IN SOYBEAN. THE INVESTIGATORS WILL STUDY THE GENETIC DIFFERENCES FOUND IN A TYPE OF SOYBEAN LINKED WITH INCREASED RESISTANCE TO SCN, BUT CURRENTLY NOT BROADLY AVAILABLE TO SOYBEAN PRODUCERS. THESE GENETIC CHANGES AFFECT A SOYBEAN ENZYME INVOLVED IN FOLATE METABOLISM KNOWN AS SERINE HYDROXYMETHYLTRANSFERASE 8 (SHMT8). USING A COMBINATION OF SCIENTIFIC APPROACHES, INCLUDING STRUCTURAL BIOLOGY AND PLANT-BASED STUDIES, THE IMPACTS OF THEGENETIC DIFFERENCES IN SHMT8 ON THE SOYBEAN PLANT WILL BE CHARACTERIZED AND USED TO DEVELOP NEW WAYS TO FIGHT SCN INFESTATIONS IN SOYBEAN FIELDS. THIS IS A COLLABORATIVE EFFORT BETWEEN TWO INVESTIGATORS WITH COMPLEMENTARY EXPERTISE: THE STRUCTURAL BIOLOGY AND BIOCHEMICAL STUDIES WILL BE PERFORMED AT THE UNIVERSITY OF MISSOURI AND THE PLANT-BASED STUDIES WILL BE CONDUCTED AT THE UNIVERSITY OF GEORGIA.