Disrupted SUMO signalling in epithelial cancers, implications for genome stability and response to therapy.

Summary

The School of Molecular and Cellular Biology invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25.

Conjugating SUMOs1-3 (Small Ubiquitin-like Modifiers) to proteins has important roles in protein localisation, stability, and activity. SUMO signalling is implicated in a wide range of cellular processes. A small family of SUMO proteases (SENPs) remove SUMOs from proteins. When the balance between SUMOylation and deSUMOylation is disrupted, many cellular pathways can be affected. We have evidence that this occurs in several types of disease, including cancer.

Some cancers of the lung, head/neck, endometrium, and ovaries have a chromosomal amplification that includes SENP genes. This amplified region also includes important DNA repair enzymes. This project will look at the effects of the chromosomal amplification 3q, on the ability of cells to repair DNA damage caused by chemotherapy. The project will assess the contribution that 3q disrupted SUMO signalling has to chemotherapy response, and whether this can be exploited to treat cancer.

This project will use cutting edge molecular and cell biology techniques to interrogate DNA damage and SUMO signalling in cancers with and without chromosome 3q amplification. The lab is based in a newly renovated space co-located with ~12 molecular and cell biology research groups. The student will benefit from an excellent work environment supported by state-of-the-art research infrastructure within the faculty.

References:

• The deSUMOylase SENP2 coordinates homologous recombination and nonhomologous end joining by independent mechanisms. Alexander J Garvin, Alexandra K Walker, Ruth M Densham, Anoop Singh Chauhan, Helen R Stone, Hannah L Mackay, Mohammed Jamshad, Katarzyna Starowicz, Manuel Daza-Martin, George E Ronson, Alexander J Lanz, James F Beesley, Joanna R Morris. Genes Dev. 2019 Mar 1;33(5-6):333-347. doi: 10.1101/gad.321125.118.
• The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination DNA repair. Alexander J Garvin, Ruth M Densham, Sarah A Blair-Reid, Kenny M Pratt, Helen R Stone, Daniel Weekes, Kirsty J Lawrence, Joanna R Morris. EMBO Rep. 2013 Nov;14(11):975-83. doi: 10.1038/embor.2013.141.
• SUMO, a small, but powerful, regulator of double-strand break repair. Alexander J Garvin, Joanna R Morris. Philos Trans R Soc Lond B Biol Sci. 2017 Oct 5;372(1731):20160281.

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