Signalling DNA replication faults.

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.