A Signaling Pathway that Couples Spore Formation to the Completion of Meiosis in S. Cerevisiae.

智力优点：减数分裂是细胞分裂程序，产生单倍体从二倍体。减数分裂的完成与产生配子的分化程序相结合。本计画将以酿酒酵母的孢子形成为模式系统，研究配子形成与减数分裂完成之间的信号传递路径。Smk 1是减数分裂特异性MAPK，控制孢子形成的减数分裂后程序。Smk 1在减数分裂被CDK激活激酶Cak 1完成时被磷酸化激活。减数分裂特异性靶向亚基的后期促进复合物（APC）泛素连接酶命名为Ama 1调节Cak 1/Smk 1反应。此外，Ssp 2，一个减数分裂特异性蛋白的未知的生化功能所需的Smk 1激活。总的来说，这些研究结果表明，Ama 1依赖的蛋白水解的一个身份不明的抑制剂蛋白，和协会的Ssp 2，控制激活Smk 1的Cak 1。该项目的目的之一是确定Cak 1和Ssp 2如何激活Smk 1。第二个目的是确定Smk 1的抑制剂，这是有针对性的破坏Ama 1和阐明这种抑制剂如何控制Smk 1激活。本项目中研究的大多数蛋白质在进化上是保守的。因此，这项研究很可能会产生关于减数分裂和配子形成如何在其他生物中耦合的可验证的假设。因此，这些研究将加快对包括其他微生物、植物和动物在内的广泛生物体中配子发生的研究步伐。更广泛的影响：该项目提供了一个出色的机会，培养博士前学生在假设驱动的研究。为了增加在本科阶段的影响，主要研究者将与罗斯蒙特学院的一位教育工作者合作，他对研究酵母中的减数分裂调控感兴趣，并让有才华的本科生参与科学发现的过程。这种伙伴关系通过促进教育工作者，研究人员，博士前学员和本科生之间的互动，将教育目标与本实验室的研究活动相结合。

Intellectual Merit: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.