Eukaryotic cells make a single copy of their chromosomes in every cell cycle, using a large molecular machine known as the replisome. To preserve genome integrity, chromosome replication must normally be completed before sister chromatids are segregated during mitosis. However, in eukaryotic species with large genomes, it is hard to ensure that replication is always finished before mitosis has begun. For this reason, animal cells have evolved survival pathways that rapidly process sites of incomplete DNA replication during mitosis, in order facilitate subsequent chromosome segregation. One such pathway is controlled by the TRAIP ubiquitin ligase, which is an important regulator of genome integrity and is mutated in a rare form of human disease. TRAIP induces replisome disassembly during mitosis, thereby activating a recombination process that is associated with ‘mitotic DNA synthesis’. In this way, the TRAIP pathway prepares partially replicated chromosomes for segregation. We are studying the regulation and mechanisms of such pathways, both in the early embryo of the nematode Caenorhabditis elegans (Sonneville et al, 2017 & 2019) and also in mouse embryonic stem cells (Villa et al, 2021). Using a combination of cutting edge genetic and biochemical approaches, this project will explore how animal cells manage to survive the essential but dangerous business of replicating and segregating their chromosomes in each cell cycle.
At the MRC PPU, as well as the possibility of a PhD in one particular lab, we offer the possibility of two 4.5-month rotations in labs of their choice. A range of other projects from MRC PPU scientists are advertised on this website. Rotations provide valuable experience and help with deciding on the choice of PhD project and research group.
Please send a CV with contact details of three referees to and a cover letter, explaining why you have chosen to apply to MRC PPU, to [Email Address Removed]. The closing date for applications is 30th April 2022. We will chat with long-listed applicants by Zoom to select candidates to take forward. Applications from overseas students are welcome.
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