University of Leeds Featured PhD Programmes
Peter MacCallum Cancer Centre Featured PhD Programmes

Signalling DNA replication faults.

Institute of Cancer and Genomic Sciences

Applications accepted all year round Self-Funded PhD Students Only

About the Project

Errors in DNA replication are key to the development of cancer. Problems in DNA replication are signalled to the cell through a cascade of post-translational modifications, best understood of which is phosphorylation. However it is now clear that many other modifications are important, including modifications with small proteins, such as ubiquitin and SUMO, and more subtle alterations such as proline isomerisation (Morris, Boutell et al. 2009, Densham, Garvin et al. 2016, Daza-Martin, Starowicz et al. 2019).

Remarkably post translational alterations perform both the role of a signalling molecule and also a structural component, and there is an emerging consensus that these act to accurately regulate proper DNA repair.

In our recent preliminary work we have identified several new modifications and shown that they are critical to proper DNA replication and repair. We now intend to map the cellular context of these changes and, critically to map out their impact on therapeutic strategies and DNA repair mechanisms.

A PhD project in this area is offered to an able, enthusiastic student. The project will entail training in molecular biology techniques, including cloning and cell biology including immunofluorescence, DNA fibre approaches and specialist DNA repair assays. Mentoring and training in scientific design, writing and presentations will also be given and the student will be part of a vibrant research laboratory, and more widely an integrated and fast-moving Institute with an interest in cancer research. A student with biochemistry and cell biology experience is preferred.

Funding Notes

: Self funded only. For Fees please see PhD, Biomedical Sciences, FT.
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Daza-Martin, M., K. Starowicz, M. Jamshad, S. Tye, G. E. Ronson, H. L. MacKay, A. S. Chauhan, A. K. Walker, H. R. Stone, J. F. J. Beesley, J. L. Coles, A. J. Garvin, G. S. Stewart, T. J. McCorvie, X. Zhang, R. M. Densham and J. R. Morris (2019). "Isomerization of BRCA1-BARD1 promotes replication fork protection." Nature 571(7766): 521-527.

Densham, R. M., A. J. Garvin, H. R. Stone, J. Strachan, R. A. Baldock, M. Daza-Martin, A. Fletcher, S. Blair-Reid, J. Beesley, B. Johal, L. H. Pearl, R. Neely, N. H. Keep, F. Z. Watts and J. R. Morris (2016). "Human BRCA1-BARD1 ubiquitin ligase activity counteracts chromatin barriers to DNA resection." Nat Struct Mol Biol 23(7): 647-655.

Morris, J. R., C. Boutell, M. Keppler, R. Densham, D. Weekes, A. Alamshah, L. Butler, Y. Galanty, L. Pangon, T. Kiuchi, T. Ng and E. Solomon (2009). "The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress." Nature 462(7275): 886-890.

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