Molecular and Cell Biology of Lipid Sensing Nuclear Receptors in Cancer

Summary

The nuclear receptor (NR) superfamily are ligand activated transcription factors. This means NRs can integrate signals from xenobiotics (drugs, nutrients), metabolites, and hormones to regulate gene expression and cell fate decisions. NR function is often disrupted in cancer cells. Many lipids species are NR ligands, and are abundantly found in cells as a broad group of loosely related biomolecules. Lipids are essential to cellular structure, membrane function, and are also precursors to an array of hormones, vitamins, bile acids and steroids - many of which function as NR ligands. Lipid levels are constantly monitored and regulated by the NR superfamily, but as with NRs, many lipids are become deregulated in cancer.

During this PhD you will explore the molecular pathways that allow NRs to link nutrition, metabolism, and cell fate decisions, in the cancer setting. Using modulation of NR signalling with ligands that represent diverse nutrient and metabolic classes of compounds, and a range of epigenetic and cell biology laboratory methods (ChIP, NGS, immuno-based technologies), you will investigate the molecular mechanisms that underpin the dietary and lifestyle patterns that cause cancer and prevent successful cancer therapies.

Recent publications from our research group are listed here:

1. Hutchinson SA^€, Websdale A^€, Cioccoloni G, Røberg-Larsen H, Lianto P, Kim B, Rose A, Soteriou C, Wastall LM, Williams BJ, Henn MA, Chen JJ, Ma L, Moore JB, Nelson E, Hughes TA* and Thorne JL* (2021). Liver x receptor alpha drives chemoresistance in response to side-chain hydroxycholesterols in triple negative breast cancer. Oncogene doi.org/10.1038/s41388-021-01720-w
2. Soteriou C, Connell S, Kalli A, Tyler AII, Thorne JL* (2021). Advances in understanding of how lipids in the plasma membrane initiate and alter cancer cell signalling pathways using multidisciplinary methodology. Prog in Lipid Research. doi:10.1016/j.plipres.2020.101080
3. Want MY, Takemasa T, Singh P, Thorne JL, Matsuzaki J, Karasik E, Gillard B, Koya R, Lugade A, Odunsi K, Battaglia S* (2020). WHSC1/NSD2 regulates immune infiltration in prostate cancer. Journal for ImmunoTherapy of Cancer.
4. Cioccoloni G, Soteriou C, Websdale A, Wallis L, Zulyniak MA, and Thorne JL* (2020). Phytosterols and phytostanols and the hallmarks of cancer: a systematic review and meta-analysis of whole organism models. Critical Reviews in Food Science and Nutrition. doi: 10.1080/10408398.2020.1835820
5. Thorne JL*, Moore JB, Corfe BM (2020). Nutrition and cancer: evidence gaps and opportunities for improving knowledge. Proceedings of the Nutrition Society. DOI: doi.org/10.1017/S0029665120000099.

Applicants to research degree programmes in the School of Food Science and Nutrition should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline, or a good honours degree together with a Masters degree.

The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study in the School of Food Science and Nutrition is:
- IELTS - an overall band of 6.5 with no individual skill band below 6.0 in all components
- iBT TOEFL - (Internet-based Test of English as a Foreign Language): a score of 92 overall with Listening 21; Reading 21; Speaking 23; Writing 22.
The test must be dated within two years of the start date of the course in order to be valid.