UROP Research Mentor Project Submission Portal: Submission #845

Overall Research Project Description Microsporidia are a family of spore-forming obligate intracellular parasites that infect most animals, including humans. Microsporidia are a pathogen of increasing health interest to humans. Although they typically only infect people with compromised immune systems, the widespread prescribing of immunosuppressants for diverse human conditions (i.e., autoimmune diseases) is resulting in a recent uptick in the number of human cases of microsporidiosis. Despite this growing threat from microsporidia, there are currently zero FDA-approved treatments for these parasites. Our group is interested in studying the highly unusual proteasome of microsporidia, as a potential drug target for treatment of microsporidiosis. The proteasome, a large, complex multi-subunit protease, is responsible for the degradation of unwanted or unneeded proteins and maintains protein homeostasis in all eukaryotic cells. The proteasome is a validated drug target and there are several FDA-approved drugs used as chemotherapies. Microsporidia have a highly divergent proteasome (m26S) and may be distinct enough that it can be targeted with a drug that would not have an appreciable effect on the human proteasome. At present, there is no high-resolution structural information of the m26S. In this project, we will begin studies into one of the three sub-complexes of the m26S, the mBase, the sub-complex that contains the ATPases that unfold the proteins as they are fed into the chamber of the proteasome for degradation. Any differences between the m26S and the human 26S can serve as potential targets for treatment of microsporidiosis.