Covalent stereoprobes: Chemical tools for biomedical discovery

This project will integrate high throughput experimentation and chemical proteomics to discover and optimise novel classes of covalent stereoprobes for elucidating biomedical mechanisms.<br /> <br /> Bioactive small molecules continue to dominate our ability to treat disease (as drugs), and to enable understanding of biological mechanisms (as chemical probes). Chemical probes have been shown to have a transformational effect on the biomedical science that is investigated, and can help address the historically uneven exploration of protein biology. Covalent probes (i.e. that modify proteins), combined with proteomic technologies, are of particular value for discovery biomedicine, and covalent drugs have enjoyed a recent renaissance. Crucially, chemical probes can bridge discovery and translational biomedicine by: illuminating disease biology in native contexts; clarifying mechanisms of drug candidates; and unlocking new therapeutic opportunities. <br /> <br /> Covalent stereoprobes are enantiomerically pure probes that form covalent links to their target proteins; the enantiomeric probe has identical physicochemical properties and can serve as a control. Covalent stereoprobes can provide invaluable insights into biomedical mechanisms through e.g. context dependent protein modification or targeted protein degradation. However, current sets of covalent stereoprobes are very small and necessarily lack chemical diversity. This project will focus on the development of high throughput methods for the discovery or covalent stereoprobes, and will exemplify them in the elucidation of biological mechanisms.<br /> <br /> The specific objectives of the PhD project are:<br /> 1. To establish methods for the high-throughput discovery of stereoselective protein modifiers. <br /> The student will develop methods for the plate-based synthesis of arrays of candidate stereoprobes from building blocks. A direct-to-biology approach will be used to discover stereoprobes that stereoselectively modify target proteins.<br /> <br /> 2. To discover and optimise covalent stereoprobes that modify a specific protein.<br /> An iterative, high-throughput approach will be used to discover and optimise covalent stereoprobes for a specific target protein (such as Aurora A kinase). Validation will involve resynthesis of promising compounds, and confirmation of stereoselective labelling.<br /> <br /> 3. To exemplify the value of covalent stereoprobes in discovery biomedicine.<br /> Finally, we will use optimised stereoprobes to elucidate the biology of their target protein. We will focus on alkynylated stereoprobes whose cellular targets can be profiled using chemical proteomics.<br />

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<p>To apply for this project you will need to make a formal application for research degree study through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University website</a>. You will need to create a login ID with a username and PIN. </p> <p>•    For <strong>Application type</strong> please select <strong>Research Degrees, Research Postgraduate</strong>. <br /> •    The admission year for this project is <strong>2026/27</strong> Academic Year. <br /> •    You will need to select your <strong>Planned Course of Study</strong> from a drop-down menu. For this project, scroll down and select <strong>EPSRC Engineering and Physical Sciences DTP.</strong> <br /> •    The project start date for this project is <strong>1 October 2026</strong>, please use this as your <strong>Proposed Start Date of Research</strong>. <br /> •    Please state clearly in the research information section that the research degree you wish to be considered for is <strong>Covalent stereoprobes: Chemical tools for biomedical discovery </strong>as well as <a href="https://eps.leeds.ac.uk/chemistry/staff/4180/professor-adam-nelson">Professor Adam Nelson</a> as your proposed supervisor.</p> <p><strong>Please state in the Finance section that the funding source you are applying for is EPSRC Doctoral Landscape Award 2026/27: Chemistry.</strong></p> <p>More information on how to apply is available on our website <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">here</a>. You will be required to provide a personal statement which outlines your interest in the project you are applying for, why you have chosen it and how your skills map onto the requirements of the project.</p> <p>Applications will be reviewed and assessed after the closing date of Friday 15 May 2026. We welcome and strongly encourage any potential applicants to contact the supervisor(s) for an informal discussion, prior to applying, and recommend submitting your application early.</p> <p><strong>Please note that you must provide the following documents in support of your application by the closing date of Friday 15 May 2026:</strong></p> <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date including grading scheme</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> </ul> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements below.</p> <p><em>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.</em></p>

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.

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.

<p>A highly competitive EPSRC Doctoral Landscape Award Studentship, based in the School of Chemistry, providing the award of full academic fees, together with a tax-free maintenance grant of £21,805 per year for 3.5 years. Training and support will also be provided.<br /> <br /> This opportunity is open to UK applicants only. All candidates will be placed into the EPSRC Doctoral Landscape Award Studentship Competition and selection is based on academic merit.<br /> <br /> Please note that there is only 1 funded place available to UK applicants only and this project is in competition with 2 other projects to secure this funding. Please note that whilst you may be successful in securing an academic offer for any project linked to this funding opportunity, this does not mean that you have been successful in securing an offer of funding. Funding is awarded on a competitive basis.</p> <p><strong>Important:</strong> Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website or our <a href="https://www.leeds.ac.uk/undergraduate-fees/doc/fee-assessment">fee assessment page</a> for information regarding Fee Status for Non-UK Nationals.</p> <p><strong>Eligibility Criteria</strong></p> <ul> <li>Applicants must be eligible to pay fees at the Home (UK) rate.</li> </ul> <p>If you are unsure whether you are eligible for UK fees/funding, please see our <a href="https://www.leeds.ac.uk/undergraduate-fees/doc/fee-assessment">fee assessment page</a>.</p> <p><strong>Other Conditions</strong></p> <ul> <li>Candidates who have previously been awarded a PhD or are currently registered on a PhD are excluded from applying. Those who were previously studying for a PhD but did not complete may be considered. </li> <li>Awards must be taken up by 1st October 2026.</li> <li>Applicants must live within a reasonable distance of the University of Leeds whilst in receipt of this scholarship.</li> </ul>

<p>For further information about this project, please contact Professor Adam Nelson by emailing <a href="mailto:A.S.Nelson@leeds.ac.uk">A.S.Nelson@leeds.ac.uk</a>.</p> <p>For further information about your application, please contact PGR Admissions by email to <a href="mailto:phd@engineering.leeds.ac.uk">phd@engineering.leeds.ac.uk</a>.</p>