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Temporal coordination of transcription, translation, and protein degradation for meiotic termination

$950,000FY2021BIONSF

Indiana University, Bloomington IN

Investigators

Abstract

This project is focused on the cell division pathway of meiosis, which is crucial for the production of gametes. During meiosis, the genetic material, which is contained in chromosomes, is duplicated and then segregated twice, resulting in gametes with half the genetic material as the progenitor cell. The goal of this project is to determine how cells exit meiosis and prevent additional rounds of chromosome segregation by irreversibly degrading proteins. This project will have broader impacts by training Indiana University graduate students and postdoctoral fellows to mentor undergraduate students who will come for a summer program to work in research labs. The graduate students will also be trained in communication skills and will record scientific development workshops that will be disseminated on a web platform for undergraduates interested in STEM fields. This project has the combined goals of revealing a complex cellular process, increasing the global network of STEM researchers, and training students in mentoring and communication. This project will identify the molecular pathway that controls meiotic exit. In budding yeast, selective autophagy prevents additional meiotic divisions by targeting proteins for degradation in meiosis II. The first objective of this project is to determine how autophagy shapes the meiotic transcriptome and proteome using RNAseq and mass spectrometry experiments to compare mRNA and protein levels at different stages of meiosis with and without autophagy inhibition. These experiments will define the genetic network regulated by autophagy and will identify autophagy substrates. The second objective is to determine how autophagy temporally regulates the degradation of specific proteins for irreversible meiotic exit. Finally, a combination of experiments and mathematical modeling will establish a systems-level understanding of the meiotic termination network. Overall, these experiments will likely uncover conserved mechanisms of meiotic regulation. This works is jointly funded by the Cellular Dynamics and Function and Genetic Mechanisms Clusters of MCB. 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.

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