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Prof Paul Race
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
Around two thirds of all drugs in current clinical use are derived from or based upon molecules isolated from natural sources. This constitutes a multi-billion pound global market comprising antibiotics, antifungals, antiparasitics and anticancer agents. Many of these important molecules are assembled through the action of giant multifunctional enzymes found extensively in terrestrial and marine microorganisms. During this project you will employ a range of structural and functional methods to deconvolute, at the molecular level, the catalytic mechanisms of these sophisticated biological machines. Structure/function studies will then form the basis of protein engineering approaches, seeking to manipulate selected enzymes, towards the production of novel derivative products with improved therapeutic activities. Currently, we are particularly interested in systems involved in the production of hybrid polyketide/non-ribosomal peptide antibiotics/anticancer drugs, polyketide based cholesterol lowering agents, and polyunsaturated fatty acids.
Webpage: http://www.bristol.ac.uk/biochemistry/research/pr.html
Webpage: http://www.bristol.ac.uk/biochemistry/research/pr.html
References
Solovyova, A.S., Pointon, J.A., Race, P.R., Kehoe, M.A. and Banfield, M.J. (2010) Solution structure of the major (Spy0128) and minor (Spy0125 and Spy0130) pili subunits from Streptococcus pyogenes. Euro. Biophys. J. Feb;39(3):469-80.
Crow, A., Race, P.R., Jubelin, G., Varela Chavez, C., Escoubas, J.M., Oswald, E., Banfield, M.J. (2009) Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei. PLoS One. 4(5):e5582.
Race, P.R., Bentley, M.L., Melvin, J.A., Crow, A., Hughes, R.K., Smith, Sessions, R.B., W., Kehoe, M., McCafferty D.G. and Banfield, M.J. (2009) Crystal structure of Streptococcus pyogenes sortase A: implications for sortase mechanism. J. Biol. Chem. Mar 13;284(11):6924-33.
Marles-Wright, J., Grant, T., Delmeau, O., van Duinen, G., Firbank S.J., Lewis, P.J., Murray, J.W., Newman, J.A., Quin, M.B., Race, P.R., Rohon, A., Tichelarr, W., van Heel, M. and Lewis, R.J. (2008) Molecular architecture of the 'stressosome', a signal integration and transduction hub. Science. Oct 3;322(5898):92-96.
Crow, A., Race, P.R., Jubelin, G., Varela Chavez, C., Escoubas, J.M., Oswald, E., Banfield, M.J. (2009) Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei. PLoS One. 4(5):e5582.
Race, P.R., Bentley, M.L., Melvin, J.A., Crow, A., Hughes, R.K., Smith, Sessions, R.B., W., Kehoe, M., McCafferty D.G. and Banfield, M.J. (2009) Crystal structure of Streptococcus pyogenes sortase A: implications for sortase mechanism. J. Biol. Chem. Mar 13;284(11):6924-33.
Marles-Wright, J., Grant, T., Delmeau, O., van Duinen, G., Firbank S.J., Lewis, P.J., Murray, J.W., Newman, J.A., Quin, M.B., Race, P.R., Rohon, A., Tichelarr, W., van Heel, M. and Lewis, R.J. (2008) Molecular architecture of the 'stressosome', a signal integration and transduction hub. Science. Oct 3;322(5898):92-96.
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