Metabolite signalling in the breast tumour microenvironment

Supervisor(s)

Contact Dr James Thorne (Food Science and Nutrition); Dr Thomas Hughes (Medicine); Professor Andrew Hanby (Medicine); or Dr Hanne Røberg-Larsen to discuss this project further informally.

Project description

Many cancers are now thought to be preventable through diet and lifestyle choices but the exact mechanisms for prevention remain unclear. Obesity and elevated cholesterol are risk factors for cancer initiation and progression but the exact mechanisms remain unclear. Cholesterol levels are influenced by a variety of dietary and lifestyle factors, and high LDL-cholesterol has been linked to failure of cancer therapy. The cholesterol metabolic pathway is altered in cancer leading to elevated production of cholesterol oxidation products, oxysterols. Oxysterols are anti-proliferative in many cancer cell lines, yet appear to confer a selective advantage in tumour progression. 

Non-cancer host cells such as macrophages (immune system), fibroblasts (support cells) and adipocytes (fat cells) are highly efficient at converting cholesterol into oxysterols, and the presence of these cell types in the tumour microenvironment has been linked to metastasis and chemo-resistance. This project will explore the hypothesis that oxysterols, secreted by non-cancer host cells into the microenvironment, are taken up by the adjacent cancer cells where they bind and activate members of the nuclear receptor super-family of transcription factors leading to chemotherapy resistance and metastasis.

The candidate will be expected to recruit volunteers, isolate primary cells and culture them in combination with breast cancer epithelial cells using 3D methods. A range of state-of-the-art molecular biology instruments (e.g. QS7, LiCOR, Biorupter-Pico, TECAN with CO2 chamber) are available for use in this project to visualise cell migration and drug retention, measure cell proliferation and survival, measure gene and protein expression, and assess the epigenetic status of the breast cancer cells. Although experience in techniques is desirable, full training will be provided. You will work with other PhD students and post-doctoral scientists in the Diet, Cancer and Epigenetics laboratory which is part of the Nutrition and Public Health research group in the School of Food Science of Nutrition. This PhD scholarship is supported by Breast Cancer UK. 

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Entry requirements

Applicants are expected to hold a first class or 2.1 degree or a Master’s degree in a biological science with a keen interest in molecular biology, molecular nutrition. Applicants should have excellent interpersonal skills. Applicants whose first language is not English will require an English language qualification, such as IELTS (7 with no element less than 6.5).

How to apply

Formal applications for research degree study should be made online through the university's website. Please state clearly in the research information section that the PhD you wish to be considered for is the 'Metabolite signalling in the breast tumour microenvironment’ as well as Dr James Thorne as your proposed supervisor.

If English is not your first language, you must provide evidence that you meet the University’s minimum English Language requirements.

We welcome scholarship applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates.  All scholarships will be awarded on the basis of merit.