2025-2026 Faculty Research Grants

Peter Lyons (Biology). 

Identifying neuronal substrates of carboxypeptidase O:regulation of neuronal function
through proteolytic processing of channel proteins and neuropeptides.

Information in the nervous system travels along neurons by action potentials and between neurons via synaptic transmission. All of these processes require proteins. Protein-based channels, receptors, and neuropeptides are made and activated by neurons, and often modified through proteolysis. We predict that two important molecular players in the nervous system, a component of voltage gated potassium channels named DPP6 and a neuropeptide named NAAG, are cut by a protease named carboxypeptidase O, removing their carboxy-terminal amino acids, and thus changing their ability to transmit neuronal information. We wish to use FRG funds to obtain experimental evidence of these predicted proteolytic events. We will use 2-dimensional gel electrophoresis combined with western blotting to observe changes in charge following cleavage of DPP6 acidic amino acids by CPO. We will use bioluminescence approaches to examine the cleavage of NAAG by CPO in both in vitro and cell culture systems. Finally, we will explore the possibility of expressing CPO in a simple bacterial system using recently developed expression systems. Altogether these data will advance our research program, enable continued training of undergraduate students, lead to peer-reviewed publication, and we hope result in a funded NIH grant.