The Henry Wellcome Unit for Biological EPR houses one of the best-equipped laboratories in the UK for advanced EPR studies of biological material. Several macromolecular protein complexes and associated model systems are studied using a wide range of current EPR techniques. We are looking to recruit dynamic post-graduates to work in the fast-moving area of membrane transporters. Our laboratory studies a wide range of membrane transport proteins together with a number of groups throughout the world. Examples of our current collaborations include:

- Within UEA we work together with the Medical School to study the Gram negative bacteria E. coli which is responsible for a vast array of medical ailments, from urinary tract infections and gastro-intestinal diseases to lethal conditions such as neonatal meningitis. The entry and exit of proteins and other compounds are controlled by several transport mechanisms located within membranes. One important membrane component is the TolC protein, which is involved in both the export of proteins toxic to the host and compounds toxic to the bacterium, such as antibiotics. TolC is therefore an important target for antibiotic resistance in E. coli bacteria. By altering some of the building units of TolC, we are hoping to understand how this protein works.

- Together with the MRC in Cambridge we are studying mitochondrial carrier proteins. These transport steps are important for the generation of ATP from the oxidation of sugars and fat, for the breakdown of amino acids, for the synthesis of haem and iron sulphur clusters, for heat production, and for macromolecular synthesis. Dysfunctional carriers are associated with rare but severe human diseases, such as metabolic disorders, neurodegenerative diseases and muscle dystrophy.

- Finally multidrug efflux pumps influence chemotherapy of cancer in two distinct ways by: (i) influencing the drug pharmacokinetic parameters of absorption, distribution and elimination, and (ii) conferring multi‐drug resistance. Both influences are based on the ability of these pumps to interact with a huge range of compounds by virtue of a poorly understood drug binding site. Together with colleagues at the ANC (Australia) and funded by the Wellcome Trust we aim to describe the physical properties of drug binding sites in the archetypal multidrug efflux pump P‐glycoprotein (P‐gp) and thereby define the pharmacophoric elements of substrates. There is a clear and present need to describe how drugs bind to P‐gp at a molecular level and to detail the structure of its binding sites.

All three projects have a common theme involving the use of biophysical spectroscopy (multi-frequency EPR/PELDOR) in combination with site-directed spin labelling to correlate the function of these important proteins with their structure.

This research is embedded within the EU COST Action "Molecular Machineries for Ion Translocation Across Biomembranes" which allows access to a network of experts and expertise in numerous laboratories across Europe. Funding is available to allow young scientists to visit other research labs to perform collaborative experiments and learn new techniques as well as for attendance at important conferences within the membrane protein transport field.
 

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