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Molecular rules of fibroblast growth factor receptor movement, assembly and signalling
Secondary Supervisor(s): Professor Dylan Owen
University of Registration: University of Birmingham
BBSRC Research Themes:
Project Outline
Cells detect their surroundings through receptors on the cell surface. The fibroblast growth factor receptor family, FGFR1 to FGFR4, controls growth and differentiation. Its isoforms differ in extracellular structure and growth factor recognition, yet it is not known how this diversity affects receptor movement, assembly and signalling. Preliminary results show that FGFR1 isoforms move differently, supporting a family-wide study.
This project will test the hypothesis that receptor structure controls signalling by changing how FGFRs move, interact and assemble. First, the student will produce fluorescently tagged versions of the four FGFRs and their principal cell-surface isoforms in matched cell systems. Live-cell single-particle tracking will follow individual receptors at rest and after growth factor stimulation, altered availability of the cell surface sugar heparan sulphate and inhibition of receptor activity. This will reveal how each receptor moves and switches between membrane states.
Second, super-resolution microscopy will map nanoscale receptor assemblies, while biochemical assays will measure receptor activation and downstream signalling. The family-wide screen will identify the most informative differences for detailed study, keeping the project focused and achievable.
Finally, imaging and signalling measurements will be analysed together to identify shared and isoform-specific relationships between receptor structure, membrane behaviour and activation. Targeted structural changes and selected disease-associated variants will then test these relationships and probe normal receptor function.
The project will reveal fundamental principles by which molecular diversity creates specialised cellular responses. It will provide interdisciplinary training in molecular cell biology, advanced microscopy, signalling assays and reproducible quantitative analysis.
