Scheme: Wolfson Research Merit Awards
Organisation: University of East Anglia
Dates: Apr 2007-Sep 2012
Summary: My work aims to understand the function of proteins which play a pivotal role in
the fundamental processes of life; energy conversion and transport of metabolites though the cell. Their biological function requires knowledge of the structure and dynamics of the participating macromolecules. Two important challenges exist when studying such systems; the determination of their 3D structure and understanding how they work. I use information from the former to correlate with information I determine from the later using magnetic resonance methods.
Electron Paramagnetic Resonance (EPR) spectroscopy, like the related technique NMR, studies the interaction of small charged particles (unpaired electrons) with an external magnetic field. They are often involved in protein function and allow us to probe how these systems work. Endogenous probes are not always present, but here we are now able to specifically label proteins with exogenous probes. EPR allows us to determine exactly which molecules in large proteins contain such elec-trons, how long they are localised on a molecule as well as probing which other molecules are nearby; exactly the information that aids the correlation of structure and function. I develop new methods to attain such information. Quinones are ubiquitous in energy-transducing systems acting as mobile electron carriers, connecting many different membrane-bound complexes. We study quinone-binding enzymes to understand their mechanism of action, which plays a central role in metabolism. A clear comprehension of such processes has a direct influence on today’s society, eg, understanding photosynthetic energy conversion helps develop efficient utilisation of solar energy. Free radicals, which are ultimately responsible for apoptosis and cell death are in-volved in many respiration processes in mitochondria without causing damage to cell, thus a detailed understanding of how proteins efficiently function also has important medical consequences.