About the Project
One of the main mechanisms by which bacteria sense and respond to environmental change is via 'two-component' signal transduction systems (TCSs), comprising a membrane-bound sensor kinase and a cytoplasmic response regulator. These regulators constitute excellent new targets for the design of novel inhibitors and antibacterial agents, especially as they are involved in regulating virulence factors and antibiotic resistance in many pathogenic species. Resistance to antibiotics is an increasing problem in the clinical setting. The overall aim of our research is to understand how production of virulence factors and toxins are regulated.We currently have PhD positions available to undertake fundamental studies of key two-component systems in a range of infectious bacteria.
The projects will give access to a wide experience of molecular biology techniques including recombinant DNA work, bandshifts, footprinting, protein overexpression (including membrane sensor overexpression) and purification using nickel affinity chromatography methods, SDS-PAGE, gene knockouts, DNA arrays and biochemistry. We are interested in determining the structures of the proteins involved in these signal transduction pathways, in particular the membrane sensor kinases that sense environmental triggers outside these bacterial cells. Thus, projects may also involve structural analysis, including crystal trials and, when appropriate, NMR spectroscopy.
The laboratory is well equipped and is part of the Astbury Centre for Structural Molecular Biology which has excellent facilities for all aspects of the projects.
Informal enquires: [Email Address Removed]
The application procedure is given at our internet site: http://www.fbs.leeds.ac.uk/gradschool/how_to_apply.htm
References
Ma, P., Yuille, H.M., Blessie, V., Göhring, N., Iglói, Z, Nishiguchi, K., Nakayama, J., Henderson, P.J.F. & Phillips-Jones, M.K. (2008) Expression, purification and activities of the entire family of intact membrane sensor kinases from Enterococcus faecalis. Mol. Membr. Biol. 25, 449-473.
Henderson, P., Szakonyi, G., Leng, D., Ma, P., Blessie, V., Yuille, H.M. & Phillips-Jones, M.K. (2007) Bacterial membrane drug efflux and receptor proteins. Drugs of the future 32A, 6.
Trinh, C.H., Liu, Y., Phillips, S.E.V. and Phillips-Jones, M.K. (2007) Crystal structure of the response regulator VicR DNA-binding protein. Acta Crystallog. Sect. D. D63, 266-269.
Potter, C.A., Jeong, E-L., Williamson, M.P., Henderson, P.J.F. and Phillips-Jones, M.K. (2006). Redox-responsive in vitro modulation of the signalling state of the isolated PrrB sensor kinase of Rhodobacter sphaeroides NCIB 8253. FEBS Lett. 580, 3206-3210
Laguri, C., Stenzel, R.A., Donohue, T.J., Phillips-Jones, M.K. and Williamson, M.P. (2006) Activation of the global gene regulator PrrA (RegA) from Rhodobacter sphaeroides. Biochemistry 45, 7872-7881
Day, A.M., Cove, J.H. and Phillips-Jones, M.K.(2003) Cytolysin gene expression in Enterococcus faecalis is regulated in response to aerobiosis conditions. Molecular Genetics and Genomics 269: 31-39.
Laguri, C., Phillips-Jones, M.K. & Williamson, M.P. Solution structure and DNA binding of the effector domain from the global regulator PrrA (RegA) from Rhodobacter sphaeroides: Insights into DNA binding specificity (2003). Nucleic Acids Research 31: 6778-6787.
Saidijam M., Georgios Psakis, Joanne L. Clough, Johan Meuller, Shun'ichi Suzuki, Christopher J. Hoyle, Sarah L. Palmer, Scott M. Morrison, Martin K. Pos, Richard C. Essenberg, Martin C. J. Maiden, Atif Abu-bakr, Simon G. Baumberg, Michael J. Stark, Alison Ward, John O'Reilly, Nicholas G. Rutherford, Mary K. Phillips-Jones and Peter J. F. Henderson. Collection and characterisation of bacterial membrane proteins (2003). FEBS Letters 555: 170-175.
Potter, C.A., Ward, A., Laguri, C., Williamson, M.P., Henderson, P.J.F. & Phillips-Jones, M.K.(2002) Expression, purification and characterisation of full-length heterologously expressed histidine protein kinase RegB from Rhodobacter sphaeroides. Journal of Molecular Biology 320: 201-213.
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