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Identification of mlm receptor antagonists for treatment of cancer

PGR-P-100

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
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.<br /> <br /> 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.<br /> <br />

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

<p>This studentship will aim to achieve the following objectives:</p> <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> <p>&nbsp;</p>

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

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/info/130206/applying/91/applying_for_research_degrees">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &lsquo;Identification of mlm receptor antagonists for treatment of cancer&rsquo; as well as&nbsp;<a href="https://physicalsciences.leeds.ac.uk/staff/174/dr-richard-foster">Richard Foster</a>&nbsp;as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome 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.</em></p>

<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>

<p><strong>Self-Funding Students are welcome to apply.</strong></p> <p><strong>UK&nbsp;students</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/138-leeds-doctoral-scholarships-2021-january-deadline">Leeds Doctoral Scholarship (January deadline)</a>&nbsp;and the&nbsp;<a href="https://phd.leeds.ac.uk/funding/118-lund-stephenson-clarke-scholarship-2021">Lund Stephenson Clarke Scholarship&nbsp;</a>are available to UK applicants. &nbsp;<a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>International students</strong>&nbsp;&ndash;The&nbsp;<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>&nbsp;is available to nationals of China. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a>&nbsp;is available to support US citizens. &nbsp;<a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p>

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

<p>For further information regardomg your application, please contact Doctoral College Admissions by&nbsp;email: <a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions</a><a href="mailto:EMAIL@leeds.ac.uk">@leeds.ac.uk</a>, or by telephone: +44 (0)113 343 5057.</p> <p>For further information regarding the project, please contact Dr Richard Foster by email:&nbsp;&nbsp;<a href="mailto:R.Foster@leeds.ac.uk">R.Foster@leeds.ac.uk</a></p>