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

• 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; Regulating; Synaptonemal; Complex; Assembly; Mechanisms

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.

该项目研究了减数分裂的过程，该过程涉及对鸡蛋和精子等细胞形成至关重要的独特细胞分裂。这些细胞是性繁殖所必需的，当它们形成不当时，结果是不育的。该项目将研究减数分裂中的关键蛋白质复合物，称为Synaptonemal复合物（SC），以了解其形成和稳定的方式，以及影响其结构和功能的因素是什么。该项目还将为遗传学，遗传科学提供培训机会，以帮助发展下一代成功的科学家和教师。从事职业生涯的各个阶段的学生将参与其中，包括高中生，本科生和研究生。特别是，该项目将通过在爱荷华大学（University of Iowa）进行的研究中涉及少数群体，以帮助解决STEM学科中缺乏多样性。爱荷华州生物学系（IGRHB）的高中生的爱荷华州遗传学研究计划将在基于调查的实验室环境中暴露于科学方法论，实验设计和数据解释。 IGRHB学生将从爱荷华城地区招募，从大多数人代表少数族裔的当地社区招募。SC形成对于生成可行的鸡蛋和精子细胞至关重要，并且该功能在进化上是保存的。在某些异常条件下，蛋白质组成SC骨料，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，进而影响SC的适当组装。这些研究将通过使用遗传，细胞学，分子和生化工具的组合在秀丽隐杆线虫的多细胞生物Caenorhabditis中进行。第一个目的将确定蛋白质修饰通过预防SC聚集来调节SC组装的机制。第二个目标将研究核转运如何控制SC组装并减少SC蛋白聚集。总体而言，这些研究将提供有关调节SC组装的机制的关键见解，因此将提供繁殖所需的基本生物学和遗传过程。