Structural and mechanistic studies of fibroblast growth factor receptor signalling

Summary

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.

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.

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.