NSF Award
2309093
The goal of this research project is to understand how a group of enzymes, namely lysine deacetylases, control biological processes in cells. This project will also provide experimental approaches that can be applied to related avenues of research, with subsequent impact on understanding of fundamental biology and medicine. The activities in this project will be performed primarily by undergraduate students and recent graduates from underrepresented groups in scientific fields. Students and recent graduate technicians will gain meaningful research skills and training relevant for progression into graduate programs and the scientific workforce.<br/><br/>Lysine deacetylases (KDACs or HDACs) are a family of closely related enzymes that regulate post-translational acetylation of proteins through removal of acetyl groups from lysine residues. The overall goal of this research is to understand how four KDACs regulate cellular activity, by (1) identifying the molecular interactions of KDACs that determine substrate selectivity, and (2) identifying the specific KDAC responsible for deacetylation of particular acetylated lysine residues in non-histone proteins. A combination of in vitro activity assays, molecular dynamics simulations, and a cell-based approach involving genetically encoded but catalytically inactive KDACs will lead to identification of cellular substrates and a detailed understanding of the particular molecular interactions driving activity between a specific KDAC and the acetylated protein. Overall, the project will result in a physical map of the surface of each KDAC that determines selectivity, as well as definitive substrate identification leading to a conceptual map of the cellular processes controlled by the KDACs via their substrates.<br/><br/>This project is jointly funded by the Molecular Biophysics cluster in the Division of Molecular and Cellular Biosciences (MCB) and the Established Program to Stimulate Competitive Research (EPSCoR).<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
