Structural biology of growth factor signalling and cell polarity

Lead Research Organisation: The Francis Crick Institute

Abstract

My main research interest is the structural biology underlying the assembly and activation of cell signalling complexes. Cell signalling deregulation is a hallmark of cancer and is frequently associated with altered catalytic functions of pathway components. My group uses structural methods, biophysical methods, enzymatic and cell-based assays. We collaborate with cell biologists and medicinal chemists both within and outside of the Crick Institute.

Technical Summary

This work was supported by the Francis Crick Institute which receives its core funding from the UK Medical Research Council (FC001000), the Wellcome Trust (FC001000),and Cancer Research UK (FC001000)

Our overall research aim is to understand the structural biology underlying the assembly and activation of growth factor signalling complexes. Growth factor pathway deregulation is a hallmark of cancer and is frequently associated with altered catalytic functions of pathway components. To tackle these large and challenging membrane-associated assemblies, we use multiple structural methods (crystallography, EM and SAXS), biophysical methods (calorimetry and fluorescence polarisation), enzymatic and cell-based assays. We also collaborate with cell biologists and medicinal chemists both within and outside of the LRI.

Our current and future research activities are directed at understanding structural aspects of three signalling areas;

1. Cell surface receptor activation and oncogenic deregulation
2. Polarity signalling assemblies at the plasma membrane
3. Rho-actin signalling from the plasma membrane into the nucleus

Publications

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