Strukturelle und funktionelle Analysen des synaptonemal Komplexes während der Meiose

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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.