Research Fellows Directory
Professor David Barford FRS, FMedSci.
Institute of Cancer Research
The mechanisms by which organisms orchestrate cell growth and division and respond to changing environments (such as response to hormones) are governed by diverse families of regulatory proteins. Many common diseases result from mutations in genes encoding these regulatory proteins. For example, 15% of all human cancers are caused by mutations in the protein RAS.
My research interests have been centred on understanding the molecular and structural mechanisms of the proteins that contribute to signal transduction pathways and cell cycle control. We have applied the techniques of protein X-ray crystallography, taking advantage of extremely brilliant X-ray sources such as those produced by the Diamond Light Source (termed a ‘super-microscope’), to examine the three dimensional structures of proteins. These techniques provide extremely high-resolution atomic-detail images of the protein structures, enabling us to understand how the proteins change their conformations, and hence functions (typically a conversion from an ‘off’ to ‘on’ state) in response to activation by hormones, and how oncogenic mutations in proto-oncoproteins such as RAS, mimic the effects of the normal physiological regulation. Importantly, knowledge of the atomic structure of a protein provides crucial information for designing drugs that selectively interfere with the activities of the defective protein, providing a means to treat and control disease. We also apply the technique of single particle electron cryo-microscopy to determine the structure of very large proteins, although at lower resolution. This technique generates a 3D structure from experimental 2D images of the protein molecule.
Interests and expertise (Subject groups)