College of Medicine

Investigating the Microsporidial Proteasome as a Therapeutic Target for Microsporidiosis

-Alana Chang

Microsporidia are a group of eukaryotic, spore-forming, obligate intracellular parasites that can infect nearly all animal phyla (including humans) via contaminated food, water, and air sources. Microsporidial infections can occur in virtually any organ system and disseminated disease is often fatal in humans, even in immunocompetent individuals. Microsporidial spores can linger in a dormant but infectious state for years under ideal conditions, and at present, no broadly effective therapies for microsporidial infections exist. Thus, there is an urgent need for new therapeutic approaches for treatment of microsporidiosis. Microsporidia have undergone extensive reductive evolution and harbor an unusually degenerate proteasome. In this seminar I will discuss our current knowledge of this degenerate microsporidial proteasome and outline my plans to validate it as a new therapeutic target for microsporidiosis.

Investigating the impact of bulky post-translational modifications on proteasomal substrate proteolysis

-Tomiwa Lawal

Post translational modifications are chemical modifications to a protein that occur after it has been translated from its corresponding mRNA. These modifications play a key role in diverse biological processes, including marking individual proteins for degradation by the 26S proteasome, a large ATP-dependent protease complex that is deregulated in numerous human diseases.  Paradoxically, many bulky post translational modifications would render proteasome substrates too large to pass through its narrow passageways en route to proteolysis. This highlights a key unanswered question: how does the proteasome manage the degradation of such bulky proteins? In this talk, I will discuss the current knowledge on substrate processing by the proteasome, and describe my plans to establish and utilize substrates modified by one such bulky posttranslational modification, the small protein SUMO, as a model for dissecting how the proteasome navigates large post-translational modifications during proteolysis.