Each of the five known RecQ helicases play essential roles in maintaining the stability of the human genome. WRN is a large multifunctional enzyme that is thought to resolve DNA structures that can arise as products of homologous recombination, replication fork stalling or other DNA repair processes. In human, mutations within the WRN gene are associated with disease, either Werner syndrome where affected individuals rapidly age (progeria) or an increased prevalence of colorectal cancer. However, despite its relevance to human health, there is a paucity of structural data for the WRN protein. This is particularly important, as there is considerable interest in generating small molecular inhibitors of RecQ-family helices (including WRN) both as tool compounds - to enhance functional studies of WRN at the cellular level - and as potential therapies for the treatment of cancer. The principal aim of this project will be to determine the structure of human WRN and its complexes with DNA and other DNA repair proteins, by X-ray crystallography and cryoEM techniques. A range of biochemical and biophysical assays will also be developed in order to facilitate the prosecution of WRN as a therapeutic target.

The successful applicant will join the Genome Damage and Stability Centre, an internationally renowned Institute carrying out research on the response of cells to DNA damage and to genome instability. We provide a stimulating and supportive research and training environment. Our expertise covers a wide range of experimental systems. Further information about our research can be obtained from our website at: http://www.sussex.ac.uk/gdsc