Strukturelle und funktionelle Analysen des synaptonemal Komplexes während der Meiose

减数分裂是细胞分裂的一种形式，通过染色体数量减少一半，导致单倍体配子的形成。它在两个阶段（减数分裂I和减数分裂II）中展开，染色体经历一系列精心安排的事件，最终确保它们的适当分离。特别是在减数分裂期间，同源染色体配对，突触和重组。这些步骤中的任何一个失败都会导致严重的后果，如人类不孕、流产和出生缺陷。尽管减数分裂对有性生殖的生物体是必不可少的，但我们仍然没有完全了解它。本研究旨在研究秀丽隐杆线虫突触复合体（SC）的大分子组装及其在染色体分离中的作用。我们的第一个目标是研究如何分化的生物最终形成一个结构，在电子显微镜（EM）水平上是很好的保守。我们将通过在异源系统中表达已知的秀丽隐杆线虫中心区域成分（SYP-1, SYP-2），并确定其相对于其他生物体中的对应物的功能结构来解决这个问题。此外，将通过免疫电镜在不同减数分裂阶段进行定位研究。我们的第二个目标是确定SC在染色体分离中的作用。最近的研究表明，SC的解体与交叉重组和第一次减数分裂前靶向释放内聚有关。我们将通过监测SC在改变交叉事件分布时的分解，并通过共免疫沉淀和两种杂交试验检查参与该过程的蛋白质-蛋白质相互作用，直接解决这个问题。

Meiosis is a form of cell division through which chromosome number is reduced by half, leading to the formation of haploid gametes. It unfolds in two phases (meiosis I and meiosis II) where chromosomes undergo a series of well-orchestrated events ultimately ensuring their proper segregation. In particular, during meiosis I homologous chromosomes pair, synapse and recombine. A failure in any of these steps leads to serious consequences such as infertility, miscarriages and birth defects in humans. Despite being essential for sexually reproducing organisms meiosis is still not fully understood. This proposal aims to investigate the macromolecular assembly of the synaptonemal complex (SC) and its roles in chromosome segregation in Caenorhabditis elegans. Our first aim is to investigate how diverged organisms ultimately form a structure that is well conserved at the electron microscopical (EM) level. We will address this by expressing known C. elegans central region components (SYP-1, SYP-2) in a heterologous system and determining their functional structure with respect to their counterparts in other organisms. Furthermore, localization studies will be performed throughout different meiotic stages by immuno-EM. Our second aim is to determine the role(s) of the SC in chromosome segregation. Recent studies suggest that SC disassembly is coupled to crossover recombination and the targeted release of cohesion prior to the first meiotic division. We will directly address this by monitoring SC disassembly upon altering the distribution of crossover events, and by examining protein-protein interactions involved in this process through co-immunoprecipitation and two hybrid assays.