Investigations into Proton Beam Therapy in Fanconi Anaemia

Fanconi anaemia (FA) is a chromosomal Instability syndrome with extreme cancer predisposition. Squamous cell carcinoma (SCC) is a common, serious and often life limiting complication of FA. Due to the inherited DNA damage response defect of FA, treatment of SCC is challenging and often associated with extreme toxicity. Proton beam therapy (PBT) is a promising treatment modality for cancer in FA, as PBT causes less collateral damage, while inflicting more complex DNA damage in the target tissue compared to conventional radiotherapy, even more so in the presence of homologous recombination defects. For a more detailed understanding of the effects of PBT in comparison to conventional radiotherapy on FA-tissue and to optimise therapeutic efficacy of PBT in FA-related malignancies, in this project we will study the effect of PBT on FA-disrupted normal and malignant tissue using patient derived cells. We will employ cell- and molecular biology methodology and multi-omic analysis to define the cellular response to PBT in normal and FA-tissue in comparison to conventional radiation in normal and hypoxic conditions. The proposed experimental work will be carried out in purpose build new state of the art PBT research facilities in Manchester and a strong clinical focus on FA and radiation oncology, and has real potential of clinical translation.

Applicants are expected to hold (or about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in molecular and cellular biology or related subject. A Master’s degree in a relevant subject and/or practical experience this area/discipline is desirable.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. You MUST also submit an online application form - choose PhD Cancer/Oncology