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Structural and mechanistic studies of fibroblast growth factor receptor signalling

PGR-P-1920

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 Alexander Breeze
Additional supervisors
Professor Frank Sobott
Schools
School of Molecular and Cellular Biology
<h2 class="heading hide-accessible">Summary</h2>

The School of Molecular and Cellular Biology invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25.<br /> <br /> We have identified a previously undiscovered &lsquo;signal switching&rsquo; mechanism used by a branch of the receptor tyrosine kinase (RTK) family &ndash; fibroblast growth factor receptors (FGFRs) &ndash; that are important in early development but also oncogenic in a range of cancers.<br /> <br /> The allosteric molecular switch that we&rsquo;ve found triggers an order-to-disorder transition within the kinase domain, revealing a cryptic binding site for PI3 kinase. Conservation of this cryptic binding motif across RTKs suggests wider physiological relevance well beyond the FGFRs themselves.

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

<p>In this project you will join a vibrant and stimulating research environment within the renowned <a href="https://astbury.leeds.ac.uk/" rel="noopener noreferrer" target="_blank">Astbury Centre for Structural Molecular Biology</a> at the University of Leeds. You will work alongside others in the <a href="https://astbury.leeds.ac.uk/people/prof-alex-breeze/" rel="noopener noreferrer" target="_blank">Breeze</a> and <a href="https://astbury.leeds.ac.uk/people/professor-frank-sobott/" rel="noopener noreferrer" target="_blank">Sobott</a> labs, as well as our <a href="https://www.research.manchester.ac.uk/portal/chiara.francavilla.html" rel="noopener noreferrer" target="_blank">collaborator&rsquo;s lab</a> at University College London (UCL).</p> <p>As a candidate, you will preferably have an interest in, and aptitude for, structural molecular biology and computational and biophysical analysis. This is primarily a structural biology project in which you will learn and use cutting-edge techniques including NMR, HDX mass spectrometry, EPR, and X-ray crystallography, plus the accompanying computational skills. You will have access to the <a href="https://astbury.leeds.ac.uk/facilities/" rel="noopener noreferrer" target="_blank">Astbury Biostructure Laboratory&rsquo;s</a> world-class infrastructure including ultra-high field NMR (cryoprobe-equipped 950 MHz Bruker Avance III HD) and structural mass spectrometry (Waters Synapt G2 with HDX plus Thermo Orbitrap UHMR). You will also become proficient in kinase assays and biophysical techniques including ITC and SPR. Via collaboration with our UCL colleague, you will also learn fluorescent cell imaging techniques.</p>

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

<p>To apply for this project opportunity applicants should complete an <a href="https://biologicalsciences.leeds.ac.uk/research-degrees/doc/how-to-apply">online application form</a> and attach the following documentation to support their application.&nbsp;</p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks</li> <li>Evidence that you meet the University&#39;s minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Biological Sciences as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul> <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>

<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>This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.&nbsp;</p> <p>&nbsp;</p>

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

<p>For information about the application process please contact the Faculty Admissions Team:</p> <p>e: <a href="mailto:fbsgrad@leeds.ac.uk">fbsgrad@leeds.ac.uk</a></p>