Regulation of meiotic chromosome segregation by post-translational modifications

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While the vast majority of cells divide through mitosis, germ cells undergo a specialised type of division called meiosis, which leads to the generation of gametes. Both meiosis and mitosis undergo a round of DNA replication, after which a clear difference is established between these divisions. While the duplicated DNA content is then divided between to daughter cells (identical to their parent cell), the meiotic division is reductional, as the DNA content in the gametes is reduced to half that of the parent cell. This is achieved by two successive rounds of chromosome segregation after DNA replication, called meiosis I and meiosis II. In meiosis one, homologous chromosomes recognise each other and undergo an 'exchange of (genetic) information', which is a great source of genetic variability. The chromosomes are then pulled apart in what is called segregation. During meiosis II, the chromatids, which are the 'halves' of each chromosome are segregated, ultimately generating four gametes from one germ cell. Once the male and female gametes undergo fertilisation, the normal DNA content is re-established. While a great deal of knowledge has accumulated related to the regulation of mitosis, far less is is known about the mechanisms germ cells utilise to guarantee faithful meiotic chromosome segregation. To better understand what mechanisms germ cells use to guarantee correct chromosome segregation into gametes, I will use the nematode C. elegans, a multicellular organism ameanable to study meiosis in great detail. A very fast and efficient way for cells to regulate protein function is to attach different 'flags' to them depending on the specific needs of the cell. These flags are called post-translational protein modifications and I am specifically interested in two of them: phosphorylation and sumoylation. Phosphorylation has been extensively studied for decades and its contribution to the mitotic division thoroughly addressed. This is not the case of sumoylation, and studies by myself and others have begun to address its role during cell division. In C. elegans, how meiotic chromosome segregation is achieved is not understood. While I have recently shown that sumoylation is important for chromosomes to 'be in the right place at the right time' prior to segregation, it has become clear that a wider view that includes both sumoylation and phosphorylation is required to understand how chromosome segregation is regulated in oocytes. This is exactly what I will address. Using several novel techniques, many of which I have developed myself, I am in a unique position to address this issue and contribute very valuable insights. I will combine in vitro and in vivo studies to better understand how sumoylation and phosphorylation regulate protein function during meiosis and thus have a better understanding of how meiotic chromosome dynamics is regulated.It is my goal that, by providing a better understanding of how chromosomes segregate in C. elegans oocytes, we will enrich our understanding of meiosis in general in a way that reproductive health will be improved for humans as well.