Formation of a diploid embryo requires that sperm and egg contribute exactly one copy of each chromosome. The cell division in charge of reducing ploidy of the genome is meiosis. Female meiosis is particularly error-prone, leading to chromosomally abnormal embryos that account for >10% of human pregnancies and, for women nearing menopause, the incidence may exceed 50%. Therefore, understanding the molecular events that guarantee proper chromosome segregation during female meiosis is of paramount relevance. In spite of this, and in contrast to mitosis, we still do not have a molecular understanding of the events regulating meiotic chromosome segregation. Our recent work has focused on chromosome segregation during oocyte meiosis using the nematode C. elegans as a model organism, which provides an excellent system for studying meiosis. We are interested in the signalling networks that guarantee that every single protein performing a function during meiosis is present at the right place, in the right time. In many instances these signals are in the form of post-translational protein modifications (PTMs) and we focus on two of these: phosphorylation and sumoylation. Within each modification pathway, there is a high level of coordination between the enzymes that add the modifications onto substrates and the enzymes that remove the modification from. Additionally, there is a high level of coordination between the pathways. Our evidence suggests that sumoylation and phosphorylation do not act in isolation during meiosis.
In order to understand the mechanism involved in accurate meiotic chromosome segregation, we will employ state-of-the-art mass spectrometry to identify key sumoylation and phosphorylation events in vivo during meiosis. Furthermore, we aim at developing a method to establish stage-specific (pre-anaphase and anaphase) meiosis I sumo- and phospho-proteomes. Once identified, we will study the roles that these sites play during meiosis in vivo though time-lapse microscopy, with high spatial and temporal resolution.
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