Meiotic Pairing Center Function in C. elegans

线虫减数分裂配对中心功能

• 批准号: 6791507
• 负责人: Needhi Bhalla
• 金额: $ 4.3万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6791507
• 关键词: Caenorhabditis elegans; RNA interference; antibody; cell cycle proteins; genetic crossing over; genetic screening; helminth genetics; meiosis; postdoctoral investigator; proteomics

DESCRIPTION (provided by applicant): The pairing and synapsis of homologous chromosomes during meiosis is an early requirement for proper meiotic chromosome segregation. Defects in meiotic chromosome segregation generally cause the death of resulting progeny, but can also lead to serious developmental disorders, such as Down syndrome. How chromosomes identify, pair and ultimately synapse with their unique homolog is poorly understood. Genetic studies in C. elegans have implicated specific chromosomal regions at one end of each chromosome as potential pairing centers (PCs). I propose to investigate PC function by undertaking an RNA interference screen in a sensitized genetic background to identify genes required for PC activity. In addition to this genetic screen, I will identify meiotic chromosomal proteins proteomically by comparing the protein profiles of nuclei isolated from wildtype worms and mutant worms that lack a germline. Molecular factors identified by these complementary approaches will be further characterized to determine their roles in homolog pairing and synapsis.

描述（由申请人提供）： 减数分裂过程中同源染色体的配对和联会是适当减数分裂染色体分离的早期要求。减数分裂染色体分离的缺陷通常会导致后代死亡，但也可能导致严重的发育障碍，例如唐氏综合症。人们对染色体如何识别、配对并最终与其独特的同源物形成突触知之甚少。秀丽隐杆线虫的遗传学研究表明，每条染色体一端的特定染色体区域是潜在的配对中心（PC）。我建议通过在致敏遗传背景下进行 RNA 干扰筛选来鉴定 PC 活性所需的基因来研究 PC 功能。除了这种遗传筛选之外，我还将通过比较从野生型蠕虫和缺乏种系的突变型蠕虫中分离出的细胞核的蛋白质谱，从蛋白质组学上鉴定减数分裂染色体蛋白质。通过这些互补方法鉴定的分子因子将被进一步表征，以确定它们在同源配对和突触中的作用。