Multi-cellular organisms have evolved many different strategies to defend themselves against potential pathogens. One branch of the plant immune system is mediated through disease resistance genes. The most common type of disease resistance genes encode what are known as NB-LRR proteins. Plant genomes encode hundreds of different NB-LRR proteins which specifically recognize different pathogens. Central to elucidating how NB-LRR proteins have evolved to recognize different pathogens is the understanding of how this recognition takes place at a molecular level. The investigators have identified a protein known as RanGAP2 that interacts with two potato NB-LRR proteins known as Rx and Gpa2. The RanGAP2 protein appears to mediate recognition by Rx and Gpa2 of a virus and a nematode, respectively. The project will study how RanGAP2 interacts with both the NB-LRR proteins and the pathogens using molecular biology, biochemistry and genetics. The RanGAP2 protein is also involved in numerous other cellular functions and the investigators will investigate whether these functions are related to its role in plant defense. The latter has important implications for understanding plant defense responses as well as having broader impacts in comparative immunological studies geared toward formulating general principles regarding the evolution of pathogen detection systems. For example, animals possess proteins, known as NACHT-LRRs that show striking structural and functional similarities with plant NB-LRR proteins. This project will contribute to the training of two post-doctoral associates and one graduate student. Broader impacts also include participating in biology teacher training and curriculum development workshops and providing research experiences for up to six high school or undergraduate students.