Eukaryotic pathogens are the causative agents of some of the most devastating and intractable diseases of humans, including malaria, amebic dysentery, African sleeping sickness, Chagas disease, trichomoniasis, aspergillosis, cryptococcal fungal meningitis, toxoplasmosis and primary amebic meningoencephalitis (PAM). The global impact of these diseases is immense. It is noteworthy that many of these pathogens are the causative agents of neglected tropical diseases (NTDs), neglected diseases of poverty (NDPs) and/or are classified as bioterrorism agents. Importantly, infections caused by eukaryotic pathogens are increasing in the US due to globalization. The primary goal of this COBRE proposal is to increase the number of NIH-funded scientists in the state of South Carolina by supporting a world-class research center, the Eukaryotic Pathogens Innovation Center (EPIC), at Clemson University (CU). The scientific focus of EPIC is a multidisciplinary study of important global eukaryotic pathogens. EPIC is the first-and-only in the state with a focus on infectious diseases, and the first- and-only in the country with a focus on eukaryotic pathogens. Four projects from target junior investigators will be supported. Their projects are 1) Functional roles of ncRNA, afu-182, in azole response and pathobiology of Aspergillus fumigatus and 2)Evaluating anti-parasitic diazacyclobutenes (with additional projects coming soon). These investigators will be matched with external and internal mentors who are established NIH-funded researchers. The projects will be supported by a well-organized Administrative Core and two state-of-the-art Scientific Cores in Genomics, and Imaging/Cell Sorting. The center also has a substantial infrastructure base and significant institutional support. For example, CU will recruit two additional faculty members and two post-doctoral fellows to expand activities of this center over the course of the project period. Pledges of graduate assistantships, equipment, and space further exemplify the institutional commitment. The continuation of this COBRE-funded center will significantly expand research in South Carolina and will facilitate recruitment, training, and retention of a critical mass of investigators with cross-disciplinary skills in this important research area.