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

本项目主要研究减数分裂的细胞分裂途径，减数分裂对配子的产生至关重要。在减数分裂期间，包含在染色体中的遗传物质被复制，然后分离两次，产生配子，其中一半的遗传物质作为祖细胞。该项目的目标是确定细胞如何退出减数分裂，并通过不可逆地降解蛋白质来防止额外的染色体分离。该项目将通过培训印第安纳大学的研究生和博士后来指导肯尼亚莫伊大学的本科生，从而产生更广泛的影响，这些本科生将参加一个暑期项目，在研究实验室工作。研究生们还将接受沟通技巧方面的培训，并将录制科学发展研讨会，这些研讨会将在一个网络平台上传播给对STEM领域感兴趣的本科生。该项目的综合目标是揭示复杂的细胞过程，增加未被充分代表的STEM研究人员的全球网络，并培训学生的指导和沟通。该项目将确定控制减数分裂退出的分子途径。在出芽酵母中，选择性自噬通过靶向减数分裂II中的降解蛋白来防止额外的减数分裂。该项目的第一个目标是确定自噬如何影响减数分裂转录组和蛋白质组，使用RNAseq和质谱实验来比较有和没有自噬抑制的减数分裂不同阶段的mRNA和蛋白质水平。这些实验将定义由自噬调控的遗传网络，并将确定自噬底物。第二个目标是确定自噬如何暂时调节特定蛋白质的降解，以实现不可逆的减数分裂退出。最后，实验和数学建模的结合将建立对减数分裂终止网络的系统级理解。总之，这些实验将可能揭示减数分裂调控的保守机制。本研究由MCB细胞动力学和功能及遗传机制组共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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 from Moi University in Kenya, 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 underrepresented 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.