Chromosome duplication is one of the most complex processes in eukaryotic cell biology, and is extremely important for our understanding of human cancer. Our cells produce a single near-perfect copy of the genetic blueprint in each cell cycle, and the duplicated sister chromatids must also inherit the same epigenetic landscape as their parents, and be held together by cohesion until mitosis. For all these reasons, the chromosome replication machinery is highly complex, and is regulated extensively by post-translational modifications. These are exciting times to study the process of chromosome duplication, the mechanism and regulation of which are highly conserved in all eukaryotic species. It is now possible to envisage projects that range from in vitro reconstitution of complex cellular processes, via cutting edge genetics and cell biology in yeast and worm embryos, to genome editing in mammalian cells by CRISPR-Cas9.
Project 1: The role of ubiquitylation in replication termination
We showed that disassembly of the replication machinery is controlled in yeast by a ubiquitin ligase and an ATPase called Cdc48 (Maric et al, Science, 2014, Maculins et al, Curr. Biol., 2015). The mechanisms and regulation remain to be elucidated, and we are now also searching for factors that regulate this process in higher eukaryotes.
How to Apply:
Following informal enquiries to [email protected]
, please send a CV with contact details of three referees and a cover letter to [email protected]
There is no deadline and the projects could commence anytime between October 2014and September 2015. Further information about our PhD programme can be found at http://www.ppu.mrc.ac.uk/studentships/.
We offer a 4 year studentship in which you would join a particular lab in the Unit. However, we strongly encourage prospective students to become part of the 4-year PhD programme in which you carry out rotation projects in two labs within the Unit (http://www.ppu.mrc.ac.uk/studentships/phd_projects.php). This studentship is jointly funded by the Medical Research Council and the University of Dundee and carries a tax-free stipend of £20,000 per annum
Maric, M., Maculins, T., De Piccoli, G. and Labib, K. (2014). Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication. Science 346, pp. 1253596