Expanding the biological diversity of reactive fragments

Identifying and exploring new biologically-relevant chemical space is a major challenge, central to both chemical biology and medicinal chemistry. Access to high quality chemical probes dramatically influences the scope of experimentally-investigated biomedical science and is crucial for validating novel targets. With the advent of reactive fragments, and the powerful companion technology of chemical proteomics, we now envision the prospect of mapping biological coverage systematically in a native cellular context.<br /> <br /> In this project, we will develop connective reactions that enable the one-pot, plate-based synthesis of diverse sets of distinctive reactive fragments (RFs). We will thereby prepare libraries of diverse reaction fragments in plate-based format which will be screened for chemical modification of target proteins e.g. specific protein kinases. Promising reactive fragments will be optimised via further rounds of plate-based chemistry. We will thus demonstrate that diverse RF sets can provide useful starting points for the discovery of covalent probes of specific target proteins.

<p>The specific scientific objectives are:<br /> 1. To develop connective plate-based chemistries to access diverse distinctive RF sets.&nbsp; The student will develop and apply novel connective chemistries in the synthesis of diverse sets of RFs.&nbsp;&nbsp;<br /> 2. To explore the suitability of the new connective plate-based chemistry for securing starting points for the discovery of novel covalent probes.&nbsp;&nbsp;Arrays of ligands will be screened for protein modification (e.g. of a specific protein kinase) by mass spectrometry.&nbsp; The most promising ligands will be optimised through further rounds of plate-based chemistry.<br /> 3. To characterise optimised covalent ligands.&nbsp; We will harness a range of structural biology, biophysical and enzymology techniques to enable characterisation of the most promising covalent ligands that are discovered.</p>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University&#39;s website</a>. Please state clearly in the Planned Course of Study section that you are applying for <em><strong>PHD Chemistry FT</strong></em> and in the research information section&nbsp;that the research degree you wish to be considered for is <em><strong>Expanding the biological diversity of reactive fragments</strong></em>&nbsp;as well as&nbsp;<a href="https://eps.leeds.ac.uk/chemistry/staff/4180/professor-adam-nelson">Professor Adam Nelson</a> as your proposed lead 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>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> <p class="MsoNoSpacing">Applications will be considered on an ongoing basis. &nbsp;Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. &nbsp;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.</p> <p>Please note that you must provide the following documents at the point you submit your application:</p> <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> <li>Funding information including any alternative sources of funding that you are applying for or if you are able to pay your own fees and maintenance</li> </ul>

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. For this project, a Masters' Degree is also required in an appropriate discipline. 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 style="margin-bottom:12px"><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK&nbsp;</strong>&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> are available to UK applicants (open from October 2023). <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>Non-UK </strong>&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 (open from October 2023). 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. <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>Important:&nbsp;</strong> Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are <em><strong>not</strong></em> covered under this studentship.</p> <p>Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.</p>

<p>For further information about this project, please contact Professor Adam Nelson by email to&nbsp;<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 Doctoral College Admissions by email to&nbsp;<a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a></p>