Full project title: Physical Regulation of Macromolecular Condensate Dynamics Through G3BP1-Mediated Nucleation and Staufen1-Mediated Dissolution
Supervisors
Laura Spagnolo, MVLS, School of Molecular Biosciences
Massimo Vassalli, James Watt School of Engineering
David Marenduzzo, College of Science and Engineering, School of Physics and Astronomy, University of Edinburgh
ICASE INDUSTRY PARTNER - ConnectomX Ltd, OXFORD
For this project the student will be mainly based at the large national facilities campus in Harwell, in Oxfordshire, England.
PhD Project Summary:
Stress granules are dynamic, non-membrane-bound RNA–protein assemblies that form when translation is perturbed and dissolve upon recovery. Rather than being static cellular structures, stress granules are now understood as condensed soft-matter systems, formed through liquid–liquid phase separation driven by weak, multivalent interactions between RNA and proteins. As such, their behaviour is governed by the physics of complex fluids, polymer networks, and active soft matter, where collective interactions give rise to emergent material states.
The project will focus on the role of two RNA-binding proteins, G3BP1 and Staufen1, in the assembly, organisation and disassembly osmotic and mechanical stress-induced granules. G3BP1 promotes network formation and phase separation through multivalent interactions, and Staufen1 is proposed to suppress network connectivity and favour granule dissolution. Using volume electron microscopy (cryo-FIB-SEM) and Brillouin microscopy, the project will directly link the nanoscale molecular organisation of stress granules to mechanical and material properties in situ.
Using methods from physics, engineering biology, and applied mathematics, this project will seek to understand stress granule formation and dissolution as material phase transitions in living cells. These quantitative, multiscale measurements will be integrated with mathematical modelling to develop predictive frameworks describing stress granule assembly and disassembly under controlled physico-chemical perturbations.
