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Understanding and controlling β-strand mediated PPIs using bespoke chemical modifications

PGR-P-1288

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Funding
Non-funded
Supervisors
Professor Andrew Wilson
Additional supervisors
Dr Theodoros Karamanos
Schools
School of Chemistry, School of Molecular and Cellular Biology
<h2 class="heading hide-accessible">Summary</h2>

Chemical probes are advantageous in studying the molecular mechanisms of health and disease; they uniquely allow temporary and titratable modulation of a target protein&rsquo;s function, permitting evaluation of its functional role. Furthermore, chemical probes represent starting points for drug-discovery. <br /> <br /> This PhD studentship will exploit peptidomimetic design to develop chemical probes that can inhibit post-translation modification of proteins by small ubiquitin-related modifier (SUMO). SUMOylation regulates multiple cellular processes including transcription, replication, and DNA repair. SUMO interacting motifs (SIMs) play an important role in reading, writing and erasing SUMO. SIMs recognize SUMO through non-covalent interaction in a &beta;-strand conformation and are typically found within intrinsically disordered regions of proteins. Here we will apply a state-of-the-art combination of peptidomimetic design and advanced Nuclear Magnetic Resonance (NMR) experiments to identify and characterize chemical probes for a series of SIMS relevant to aggregation and DNA damage. The student will join a vibrant, diverse and collaborative group of researchers to gain skills and knowledge in peptide and protein chemistry, advanced NMR methods and protein-protein interactions. Ultimately, development of SIM/SUMO chemical probes will contribute to a systematic understanding of intrinsic disorder in &beta;-strand mediated PPIs and be crucial in unravelling the &ldquo;SUMO code&rdquo;.

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

<p>More details of this PhD and other opportunities can be found on<a href="https://wilson.leeds.ac.uk/opportunities/"> The Wilson Group</a> website.</p> <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/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 to <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>Understanding and controlling &beta;-strand mediated PPIs using bespoke chemical modifications</strong></em>&nbsp;as well as <a href="https://astbury.leeds.ac.uk/people/dr-theodoros-karamanos/">Dr Theodoros Karamanos</a> or <a href="https://wilson.leeds.ac.uk/">Professor Andrew Wilson</a> 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 style="margin-bottom:11px"><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>

<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 style="margin-bottom:12px"><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK</strong>&nbsp;&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:</strong>&nbsp; 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 <strong>not</strong> covered under these studentships.</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>

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

<p>For further information about your application, please contact Doctoral College Admissions:&nbsp;<a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a></p> <p>For further information about this project, please contact Professor Andrew Wilson:&nbsp;<a href="mailto:a.j.wilson@leeds.ac.uk">a.j.wilson@leeds.ac.uk</a></p>