The project will focus on chromosome dynamics during gametogenesis in two eukaryotic models (C. elegans, M. musculus). The main direction of research will address the proteins involved in early meiotic stages during pairing and synapsis of homologous chromosomes.
Identification of new players affecting meiosis during gametogenesis is clearly very important, timely endeavor as the chromosomal dynamics and possible complications during meiotic divisions still remain incompletely understood. Yet, inaccuracies during meiotic stages are connected to chromosomal aberrations leading to severe genetic disorders as well as to male infertility.
In our preliminary experiments, we showed that vinculin/DEB-1 clearly participates in meiotic prophase progression. A depletion of DEB-1 impacts chromosomal pairing stabilization, attachment of chromosomes to cytoskeletal forces, and formation of synaptonemal complex during prophase I, resulting in meiosis delay and increased presence of chromosome univalents. Our study thus revealed an unsuspected role of DEB-1 in the progression of meiotic prophase, including chromosome dynamics and pairing that have been shown to be an essential meiotic components.
So far, nuclear functions of vinculin/DEB-1 have not been described at all, and in this project we suggest accomplishing a systematic study using a panel of structural, molecular and genetic methods in order to reveal details about its biological functions in the cell nucleus, and in meiosis in particular. We plan to achieve two main aims: Aim 1/ Mapping of vinculin at meiosis-specific structures in cell nuclei; Aim 2/Decipherment the meiosis-specific roles of vinculin and associated proteins.
Meiosis is a key process for sexual reproduction contributing to the genetic variability of organisms. Deciphering the roles of novel components of the synaptonemal complex would therefore significantly contribute to our understanding of the molecular mechanisms and dynamics of meiotic events, and may possibly also help to explain some of the fertility deficiencies, which are a prominent medial problem affecting 10 % of humans.