Identification of mlm receptor antagonists for treatment of cancer

PGR-P-100

Key facts

Type of research degree: PhD
Application deadline: Ongoing deadline
Project start date: Wednesday 1 October 2025
Country eligibility: International (open to all nationalities, including the UK)
Funding: Competition funded
Supervisors: Dr Richard Foster
Schools: School of Chemistry

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

Recent high impact publications have identified antagonism of the mlm receptor as a possible target for treatment of cancer. The native ligand of the receptor has been linked to cell proliferation which has been proven to be as a result of increased nitric oxide (NO) concentration. Studies have shown that NO induces components of PKC/ERK/AP-1 signalling pathways whereby PKC stimulates activity of the mitogen activated protein kinase. This triggers a phosphorylation cascade which has been linked to the activation of genes responsible for cell differentiation and proliferation. The development of antagonists for mlm thus limiting NO concentration is therefore key to the development of cancer therapeutics. No small molecule antagonists of the mlm receptor have been reported in the literature. Our strategy will be to identify antagonists by consideration of the structures of antagonists of the closely related receptors. A database of antagonists will be generated and compounds modelled at the mlm receptor. Favoured compounds will then be synthesised and screened in the panel of mlm antagonist assays. Hits will be engineered for selectivity for the mlm receptor by comparative molecular modelling using both the mlm and structurally homologous receptors.

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

This studentship will aim to achieve the following objectives: <ul> <li>to identify novel mlm antagonists as starting points for the development of novel therapeutics</li> <li>to optimise the compounds through medicinal chemistry approaches for drug-likeness and pharmaceutical and pharmacokinetic properties consistent with a bioavailable agent</li> <li>to generate selective agents (over antagonism of other receptors)</li> <li>to validate the origin of antagonism versus agonism on binding to the receptor</li> <li>to investigate high-throughput fragment screening as a tool to support the objectives of the project</li> <li>to work with our collaborators in support of the biological screening objectives of the project</li> </ul>

<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/info/130206/applying/91/applying_for_research_degrees">University's website</a>. Please state clearly in the Planned Course of Study section that you are applying for PHD Chemistry FT, in the research information section that the research degree you wish to be considered for is Identification of mlm receptor antagonists for treatment of cancer as well as <a href="https://physicalsciences.leeds.ac.uk/staff/174/dr-richard-foster">Richard Foster</a> as your proposed supervisor and in the finance section, please state clearly the funding that you are applying for, if you are self-funding or externally sponsored. 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. Applications will be considered on an ongoing basis. Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed. Please note that you must provide the following documents in support of your application by the closing date of Monday 6 January 2025 if applying for the China Scholarship Council-University of Leeds Scholarship, Monday 3 February 2025 if applying for Leeds Doctoral Scholarship or Tuesday 1 April 2025 for Leeds Opportunity Research Scholarship. If you are applying with external sponsorship or you are funding your own study, please ensure you provide your supporting documents at the point you submit your application: <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> </ul>

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

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. 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 is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

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

Self-Funded or externally sponsored students are welcome to apply. UK – The <a href="https://phd.leeds.ac.uk/funding/138-leeds-doctoral-scholarship-2025-faculty-of-engineering-and-physical-sciences#:~:text=Key%20facts&text=One%20Leeds%20Doctoral%20Scholarship%20is,rata%20for%20part%2Dtime%20study.">Leeds Doctoral Scholarship</a> (closing date: Monday 3 February 2025) and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> (closing date: Tuesday 1 April 2025). <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds. Non-UK –The <a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a> is available to nationals of China (closing date: Monday 6 January 2025). The <a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a> is available to support US citizens. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds. You will be responsible for paying the overtime fee in full in your writing up/overtime year (£320 in Session 2024/25), but the scholarship maintenance allowance will continue to be paid for up to 6 months in the final year of award. Important: Please note that that the award does not cover the costs associated with moving to the UK. All such costs (<a href="https://www.leeds.ac.uk/international-visas-immigration/doc/applying-student-visa">visa, Immigration Health Surcharge</a>, flights etc) would have to be met by yourself, or you will need to find an alternative funding source. Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.

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

For further information about your application, please contact PGR Admissions by email to <a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions</a><a href="mailto:EMAIL@leeds.ac.uk">@leeds.ac.uk</a> For further information about this project, please contact Dr Richard Foster by email to <a href="mailto:R.Foster@leeds.ac.uk">R.Foster@leeds.ac.uk</a>