The regulation of gene expression is fundamental to all stages of life. In appropriate or failure of in this regulation is a major cause of disease including cancers and metabolic diseases. We are interested in understanding the molecular mechanisms of how genes are regulated, particularly by a family of transcription factors called nuclear receptors which are themselves major targets for the treatment of diseases as diverse as diabetes and cancer.
Our research primarily involves using structural and functional techniques that allow us detailed insights into the molecular functioning of transcriptional complexes and insights into the molecular pathologies when things go wrong.
There are two main areas covered in the research group. These are the structure and function of large transcriptional complexes involved in the repression of transcription, which regulates normal development and homeostasis, and the molecular mechanisms of signalling by nuclear receptors.
Students will gain experience in many diverse techniques. These include protein expression and purification, a wide range of biochemical and molecular biological techniques used to characterise proteins and protein complexes, and finally biophysical techniques (X-ray Crystallography and/or NMR Spectroscopy) required for the determination of protein structure and dynamics.
Past students in the group have been very successful with good publications and gone on to pursue scientific careers.
To apply please complete an on-line application form at: http://www.le.ac.uk/biochem/main_pages/postappformnew.html
We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.
Itoh, T., Fairall, L., Amin, K., Inaba, Y., Szanto, A., Balint, B., Nagy, L., Yamamoto, K. and Schwabe. J. W. R. (2008). Structural basis for the activation of PPARgamma by oxidized fatty acids. Nat Struct Mol Biol 15, 924-931.
Codina, A., Love, J. D., Li, Y., Lazar, M. A., Neuhaus, D., and Schwabe, J. W. R. (2005). Structural insights into the interaction and activation of HDAC3 by nuclear receptor co-repressors. Proc Natl Acad Sci U S A 102, 6009-6014.
Codina, A., Benoit, G., Gooch, J. T., Neuhaus, D., Perlmann, T., and Schwabe, J. W. (2004). Identification of a novel co-regulator interaction surface on the ligand binding domain of Nurr1 using NMR footprinting. J Biol Chem 279, 53338-53345.
Nagy, L., and Schwabe, J. W. (2004). Mechanism of the nuclear receptor molecular switch. Trends Biochem Sci 29, 317-324.
Ariyoshi, M., and Schwabe, J. W. (2003). A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. Genes Dev 17, 1909-1920.
Kallenberger, B. C., Love, J. D., Chatterjee, V. K., and Schwabe, J. W. (2003). A dynamic mechanism of nuclear receptor activation and its perturbation in a human disease. Nat Struct Biol 10, 136-140.
Clayton, G. M., Peak-Chew, S. Y., Evans, R. M., and Schwabe, J. W. (2001). The structure of the ultraspiracle ligand-binding domain reveals a nuclear receptor locked in an inactive conformation. Proc Natl Acad Sci U S A 98, 1549-1554.
Nagy, L., Kao, H. Y., Love, J. D., Li, C., Banayo, E., Gooch, J. T., Krishna, V., Chatterjee, K., Evans, R. M., and Schwabe, J. W. (1999). Mechanism of corepressor binding and release from nuclear hormone receptors. Genes Dev 13, 3209-3216