Plant diseases are the cause for dramatic losses in crop production. Resistance of plants to pathogenic microorganisms is often mediated by disease resistance (R) genes that mediate recognition of pathogens and trigger defense reactions. Accurate regulation of R gene activity levels is critical for their function. However, mechanisms of R gene regulation are not well understood. The recently identified EDM2 protein is a novel regulator that controls transcription (mRNA synthesis) of R genes. Screens using the yeast two-hybrid system (an in vivo assay detecting protein/protein interactions) identified multiple proteins that physically interact with EDM2. Combining genetic and biochemical methods molecular roles of EDM2 and its interaction partners in regulating R gene activity and disease resistance will be examined. Physical interactions between EDM2 and its putative partners will be analyzed in untreated and defense-activated plants. Plant lines with mutations in the genes encoding EDM2 and its interaction partners will be tested for effects on the activities of R genes. In addition, binding of these proteins to regulatory DNA regions of R genes will be examined and characterized. These studies will increase our understanding of mechanistic details of R gene regulation and will provide a detailed characterization of several novel components of the plant immune system. Broader impacts: An important component of this project is strong involvement of undergraduate students, mainly from minority groups. The project will be linked to the ongoing NSF-REU Plant Cell Biology program within the Center for Plant Cell Biology at UC-Riverside. In addition, the project will provide an outstanding platform for training of postdoctoral scholars and graduate students in the fields of molecular genetics, genomics and phytopathology. Results from this study are likely to allow the design of new strategies to improve disease resistance in crops by manipulating function of EDM2 and its interactors.