University of Dundee

Genome stability pathways that regulate the mammalian replisome by ubiquitylation

Eukaryotic cells contain important but poorly understood ubiquitylation pathways, which preserve genome integrity by regulating the replisome during the final stages of chromosome replication, or during mitosis if replication has not yet been completed.  We showed that a cullin ubiquitin ligase regulates replisome disassembly at the end of chromosome replication in yeast and in the C. elegansearly embryo (Maric et al, Science 2014; Maculins et al Curr. Biol. 2015, Sonneville et al Nat. Cell Biol, 2017), and we also identified a second replisome disassembly pathway that acts during mitosis in metazoa (Sonneville et al Nat. Cell Biol, 2017), driven by an E3 ligase that remains to be identified.  The new project will study such pathways for the first time in mammalian cells, using mouse embryonic stem cells as a model system.  We will identify the factors and study the mechanisms that regulate the mammalian replisome during DNA replication termination, and also during mitosis, using a wide range of cutting-edge approaches including genome editing by CRISPR-Cas9, advanced imaging, and biochemical reconstitution with purified proteins.  The project will study fundamental issues in eukaryotic cell biology that are of relevance to a range of human diseases. 

Talented students who are passionate about doing research are invited to apply for this PhD position.  The successful applicant will be part of the MRC PPU PhD programme, but will be funded by a 4-year PhD studentship from Cancer Research UK, with a non-taxable annual stipend of £20,000 plus payment of university tuition fees.  Students of all nationalities are eligible to apply.

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience.

More details of the work in Karim Labib’s group can be found at: http://www.lifesci.dundee.ac.uk/groups/karim-labib/

Eligibility