Meiosis is the cell division program that produces haploids from diploids. The completion of meiosis is coupled to differentiation programs that generate gametes. This project will use sporulation in the yeast Saccharomyces cerevisiae, as a model system to study signaling pathways that couple gamete formation to the completion of meiosis. Smk1 is a meiosis-specific MAPK that controls the post-meiotic program of spore formation. Smk1 is activated by phosphorylation as meiosis is being completed by the CDK activating kinase, Cak1. A meiosis-specific targeting-subunit of the anaphase promoting complex (APC) ubiquitin-ligase named Ama1 regulates the Cak1/Smk1 reaction. In addition, Ssp2, a meiosis-specific protein of unknown biochemical function is required for Smk1 activation. Collectively, these findings indicate that Ama1-dependent proteolysis of an unidentified inhibitor protein, and the association of Ssp2, control the activation of Smk1 by Cak1. One aim of this project is to establish how Cak1 and Ssp2 activate Smk1. A second aim is to identify the inhibitor of Smk1 that is targeted for destruction by Ama1 and elucidate how this inhibitor controls Smk1 activation. Most of the proteins studied in this project are evolutionarily conserved. It is therefore likely that the research will generate testable hypotheses for how meiosis and gamete formation are coupled in other organisms. As such, these studies will accelerate the pace of research on gametogenesis in a broad range of organisms including other microorganisms, plants, and animals.
Broader impact: The project provides an outstanding opportunity to train pre-doctoral students in hypothesis-driven research. To increase the impact at the undergraduate level, the principal investigator will partner with an educator at Rosemont College who is interested in studying meiotic regulation in yeast and involving talented undergraduates in the process of scientific discovery. This partnership integrates educational objectives with the research activities of this laboratory by promoting interaction between educators, researchers, predoctoral trainees, and undergraduate students.
