Structural and mechanistic studies of fibroblast growth factor receptor signalling

About the project

About the Project We have identified a previously undiscovered ‘signal switching’ mechanism used by a branch of the receptor tyrosine kinase (RTK) family – fibroblast growth factor receptors (FGFRs) – that are important in early development but also oncogenic in a range of cancers. The allosteric molecular switch that we’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. In this project you will join a vibrant and stimulating research environment within the renowned Astbury Centre for Structural Molecular Biology at the University of Leeds. You will work alongside others in the Breeze and Sobott labs, as well as our collaborator’s lab at University College London (UCL). 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 Astbury Biostructure Laboratory’s 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. Eligibility Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or international equivalent) in an appropriate discipline. Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The minimum English language entry requirement for postgraduate research study in the Faculty of Biological Sciences 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. Costs 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. Details of research degree fees can be found on the university website . For International students in the Faculty of Biological Sciences, the academic fee rate is £31,000 per year if you start in the 2025/26 session; in addition to this fee the project is likely to also require bench fees to cover the costs of the research. You would also need to fund your living costs, for which the UKRI recommend no less than £20,780 per year for 2025/26. How to apply To apply for this project applicants should complete an online application form and attach the following documentation to support their application. a full academic CV degree certificate and transcripts of marks Evidence that you meet the University's minimum English language requirements (if applicable) Evidence of funding To help us identify that you are applying for this project please ensure you provide the following information on your application form; Select PhD in Biological Sciences as your programme of study Give the full project title and name the supervisors listed in this advert For information about the application process please contact the Faculty Admissions Team: e: fbsgrad@leeds.ac.uk

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