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

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.

这个项目研究了减数分裂的过程，这涉及到一个独特的细胞分裂，对形成细胞（如卵子和精子）至关重要。这些细胞是有性生殖所必需的，当它们形成不当时，结果就是不育。该项目将研究减数分裂中一个关键的蛋白质复合物，名为突触复合体（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是什么。该项目还将提供遗传学（遗传科学）方面的培训机会，帮助培养下一代成功的科学家和教师。学生在他们的职业生涯的各个阶段将参与其中，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民族参与爱荷华大学的研究，帮助解决STEM学科内缺乏多样性的问题。爱荷华州遗传学研究计划的高中学生在生物系（iGRHB）将暴露学生的科学方法，实验设计，并在基于调查的实验室设置数据解释。iGRHB学生将从爱荷华市地区招募，来自当地社区，大多数是stem代表性不足的少数民族。SC的形成对于产生有活力的卵细胞和精子细胞至关重要，而且这种功能在进化上是保守的。在一些异常情况下，构成SC的蛋白质聚集，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，这反过来又影响SC的正确组装。这些研究将在多细胞生物秀丽隐杆线虫中进行，使用可用于该模型系统的遗传、细胞学、分子和生化工具的组合。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。第二个目标将研究核转运如何控制SC组装和减少SC蛋白聚集。总的来说，这些研究将对调节SC组装的机制以及繁殖所需的基本生物学和遗传过程提供重要的见解。