Eukaryotic pathogens are the causative agents of some of the most devastating and intractable diseases of humans, including malaria, amebic dysentery, sleeping sickness, Chagas disease, and meningitis. 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) and/or are also 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 establishing a world-class research center, the Eukaryotic Pathogens Innovation Center (EPIC), at Clemson University (CU). The scientific focus of EPIC will be a multidisciplinary study of important global eukaryotic pathogens. Five projects from target junior investigators will be supported. Their projects are 1) The role of acetate fermentation in Entamoeba histolytica virulence; 2) Glycosome biogenesis in African trypanosomes; 3) Glucose Sensing and Hexokinases in the African Trypanosome; 4) Fatty acid synthesis in Trypanosoma brucei, and 5) Exploring the mechanisms of fluconazole-induced aneuploidy in Cryptococcus neoformans. These investigators will be matched with 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, Imaging and Cell Sorting, and Mass Spectroscopy. The Scientific Cores will also benefit at least two other COBRE-funded centers in the state of South Carolina and other faculty at CU. The center also has a substantial infrastructure base and significant institutional support. For example, CU will recruit three additional investigators 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. 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.