Mechanisms Regulating Synaptonemal Complex Disassembly in C. elegans Meiosis

线虫减数分裂中联会复合体分解的调节机制

• 批准号: 1121150
• 负责人: Sarit Smolikove
• 金额: $ 45万
• 依托单位: University of Iowa
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1121150&HistoricalAwards=false
• 关键词: Mechanisms; Regulating; Synaptonemal; Complex; Disassembly

Smolikove ABSTRACT MCB-1121150 Intellectual merit:Meiosis is a fundamental biological process required for sexual reproduction, and is a major contributor to genetic variability. A crucial step in meiosis is the segregation of maternal and paternal (homologous) chromosomes during the first meiotic division. The accurate execution of this step requires the exchange of genetic information between homologous chromosomes leading to crossover formation. The synaptonemal complex (SC) is a key structure, placed in the center of events unfolding in meiosis. The SC is assembled between each pair of homologous chromosomes to ensure the formation of all obligatory crossover events, after which the SC is disassembled in a regulated fashion. In the absence of the SC, chromosomes missegregate in the first meiotic division, often leading to embryonic lethality. The understanding of SC assembly has greatly advanced in the past years, but little progress has been made in understanding the mechanisms of SC disassembly. Dr.Smolikove's research is aimed at elucidating the mechanisms of SC disassembly. To do so, she takes advantage of the numerous genetic, cytological, and molecular tools available in the model organism Caenorhabditis elegans. She has identified a gene which is specifically required for SC disassembly but which does not participate in early meiotic events such as crossover formation or SC assembly. Through molecular and cytological characterization of two alleles of the mutated gene, along with depletion of its mRNA via RNAi, she dissects the molecular pathways required for SC disassembly. Furthermore, performing genetic screens using her mutants, she is helping to reveal the pathway regulating SC disassembly. Over all, this research will lead to a better understanding of SC disassembly and its role in proper meiotic chromosome segregation. Broader Impacts:This project will provide research opportunities for undergraduates and graduate students from the University of Iowa and from local colleges, along with Ph.D. thesis projects for graduate students. The project will contribute to graduate course material and curriculum development, including a genetics lab course that features experiments using C. elegans and focusing on meiosis, It will serve as an opportunity to introduce basic genetic concepts in an appropriate model organism with a powerful genetic system. Students will be trained in cutting-edge research techniques.

智力价值：减数分裂是有性生殖所需的基本生物学过程，是遗传变异的主要因素。减数分裂的一个关键步骤是在第一次减数分裂中母系和父系（同源）染色体的分离。这一步骤的准确执行需要同源染色体之间的遗传信息交换导致交叉形成。突触复合体（synaptonemal complex， SC）是一个关键结构，在减数分裂过程中处于中心位置。SC在每对同源染色体之间组装，以确保所有必要的交叉事件的形成，之后SC以一种规范的方式拆卸。在SC缺失的情况下，染色体在第一次减数分裂时发生错离，常常导致胚胎死亡。在过去的几年里，对SC装配的理解有了很大的进步，但在理解SC拆卸的机制方面进展甚微。smolikove博士的研究旨在阐明SC分解的机制。为了做到这一点，她利用了模式生物秀丽隐杆线虫中可用的众多遗传、细胞学和分子工具。她已经确定了一个基因，该基因是SC分解所必需的，但不参与早期减数分裂事件，如交叉形成或SC组装。通过对突变基因的两个等位基因的分子和细胞学表征，以及通过RNAi耗尽其mRNA，她剖析了SC拆卸所需的分子途径。此外，使用她的突变体进行基因筛选，她正在帮助揭示调节SC分解的途径。总之，这项研究将有助于更好地理解SC的拆卸及其在减数分裂染色体分离中的作用。更广泛的影响：该项目将为爱荷华大学和当地学院的本科生和研究生提供研究机会，并为研究生提供博士论文项目。该项目将有助于研究生课程材料和课程开发，包括遗传学实验室课程，以秀丽隐杆线虫为实验对象，重点关注减数分裂，这将是一个机会，介绍具有强大遗传系统的适当模式生物的基本遗传概念。学生将接受尖端研究技术的培训。