Molecular and Cell Biology of Lipid Sensing Nuclear Receptors in Cancer

PGR-P-1342

Key facts

Type of research degree: PhD
Application deadline: Ongoing deadline
Project start date: Sunday 1 October 2023
Country eligibility: International (open to all nationalities, including the UK)
Funding: Competition funded
Source of funding: Other
Supervisors: Dr James Thorne
Schools: School of Food Science and Nutrition

<h2 class="heading hide-accessible">Summary</h2>

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.

<h2 class="heading hide-accessible">Full description</h2>

Recent publications from our research group are listed here: <ol> <li style="margin-left:8px; text-align:justify">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</li> <li style="margin-left:8px; text-align:justify">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</li> <li style="margin-left:8px; text-align:justify">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.</li> <li style="margin-left:8px; text-align:justify">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</li> <li style="margin-left:8px; text-align:justify">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.</li> </ol>

<h2 class="heading">How to apply</h2>

Formal applications for research degree study should be made online through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University's website</a>. Please state clearly in the research information section that the research degree you wish to be considered for is “Molecular and Cell Biology of Lipid Sensing Nuclear Receptors in Cancer” as well as Dr James L 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 (below). As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.

<h2 class="heading heading--sm">Entry requirements</h2>

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.

<h2 class="heading heading--sm">English language requirements</h2>

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.

<h2 class="heading">Funding on offer</h2>

This project is currently not funded so if you are interested you will also need to apply for a Scholarship to fund your studies (to include your living costs, University fees, and experimental costs. If you think you may be eligible for one of the following Scholarships, please speak to the project lead, Dr James Thorne, for further information. <ol type="1"> <li>You intend to apply for a PhD Sholarship for UK under-represented groups (https://www.leeds.ac.uk/research-funding/doc/scholarships-under-represented-groups) (UK applicants).</li> <li>You will apply to the Leeds Doctoral Scholarship scheme (https://phd.leeds.ac.uk/search?clive=leeds-pgr-web-funding&query=Leeds+doctoral+scholarship) deadline (UK applicants).</li> <li>You are eligable and intend to apply for a Leeds Sanctuary Scholarship (https://www.leeds.ac.uk/international-students/doc/sanctuary-scholarship) (overseas student now resident in the UK).</li> <li>You have secured a Scholarship to study for a PhD from your home country and are seeking a host laboratory in the UK (overseas applicants).</li> <li>You are eligable and intend to apply for a Chinese Scholarship Council award and are seeking a host laboratory (overseas applicants).</li> <li>You are a self-funding student (UK or overseas).</li> </ol> Please note – different schemes have different application deadlines.

<h2 class="heading">Contact details</h2>

For further information please contact the Environment Admissions Team: ENV-PGR@leeds.ac.uk

<h3 class="heading heading--sm">Linked research areas</h3>