Regulating Synaptonemal Complex Assembly: Mechanisms that Control Protein Aggregation During Meiosis

调节联会复合体组装：减数分裂期间控制蛋白质聚集的机制

基本信息

批准号：
1515551
负责人：
Sarit Smolikove
金额：
$ 55.5万
依托单位：
University of Iowa
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2020-02-29
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1515551&HistoricalAwards=false
关键词：
Regulating Synaptonemal Complex Assembly Mechanisms

项目摘要

This project examines the process of meiosis, which involves a unique cell division essential for the formation of cells such as egg and sperm. These cells are required for sexual reproduction, and when they are improperly formed the outcome is sterility. This project will investigate a critical protein complex in meiosis, named the Synaptonemal Complex (SC), in order to understand how it is formed and stabilized, and what are the factors that affect its structure and function. The project will also offer training opportunities in genetics, the science of heredity, to help develop the next generation of successful scientists and teachers. Students in various stages of their careers will be involved, including high school students, undergraduates, and graduate students. In particular, this project will help address the lack of diversity within STEM disciplines by involving underrepresented minorities in research performed at the University of Iowa. The Iowa Genetics Research program for high-school students in the department of Biology (iGRHB) will expose students to scientific methodologies, experimental design, and data interpretation in an investigation-based lab setting. iGRHB students will be recruited from the Iowa City area, from a local community with a majority of STEM-underrepresented minorities.SC formation is essential for generation of viable egg and sperm cells, and this function is evolutionarily conserved. In some aberrant conditions, proteins composing the SC aggregate, which leads to SC dysfunction. The project will investigate the molecular mechanisms regulating SC protein aggregation, which in turn affects the proper assembly of the SC. These studies will be performed in the multi-cellular organism Caenorhabditis elegans by using a combination of genetic, cytological, molecular, and biochemical tools available for this model system. The first aim will identify the mechanism by which protein modification regulates SC assembly by the prevention of SC aggregation. The second aim will investigate how nuclear transport controls SC assembly and reduces SC protein aggregation. Overall, these studies will provide crucial insights on the mechanisms regulating SC assembly and, therefore, the fundamental biological and genetic processes required for reproduction.

该项目研究减数分裂过程，该过程涉及对卵子和精子等细胞形成至关重要的独特细胞分裂。这些细胞是有性生殖所必需的，当它们形成不当时，就会导致不育。该项目将研究减数分裂中的一个关键蛋白质复合物，称为联会复合物（SC），以了解它是如何形成和稳定的，以及影响其结构和功能的因素有哪些。该项目还将提供遗传学（遗传科学）方面的培训机会，以帮助培养下一代成功的科学家和教师。处于职业生涯各个阶段的学生都将参与其中，包括高中生、本科生和研究生。特别是，该项目将通过让代表性不足的少数群体参与爱荷华大学进行的研究，帮助解决 STEM 学科内缺乏多样性的问题。爱荷华州生物学系高中生遗传学研究项目 (iGRHB) 将使学生在基于调查的实验室环境中接触科学方法、实验设计和数据解释。 iGRHB 学生将从爱荷华市地区招募，该社区以 STEM 少数族裔为主。SC 的形成对于产生可行的卵子和精子细胞至关重要，并且这种功能在进化上是保守的。在某些异常情况下，组成 SC 的蛋白质会聚集，从而导致 SC 功能障碍。该项目将研究调节 SC 蛋白聚集的分子机制，从而影响 SC 的正确组装。这些研究将结合该模型系统可用的遗传、细胞学、分子和生化工具，在多细胞生物体秀丽隐杆线虫中进行。第一个目标是确定蛋白质修饰通过防止 SC 聚集来调节 SC 组装的机制。第二个目标是研究核运输如何控制 SC 组装并减少 SC 蛋白聚集。总的来说，这些研究将为调节 SC 组装的机制以及繁殖所需的基本生物和遗传过程提供重要的见解。