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| Using RNA aptamers to study the activity of viral proteins. | ||||||||||||||||||
RNA aptamers are useful diagnostic, therapeutic and laboratory tools and we have selected and characterised RNA aptamers to several viral proteins and are using these to probe interactions between viral and host proteins. Current projects include the replicase enzyme of foot-and-mouth disease virus (FMDV) and the E6 and E7 oncogenic proteins from human paplilloma virus, associated with the development of cervical cancer. Some of the FMDV aptamers have been found to effectively inhibit the function of the replicase enzyme in vitro. This work has resulted in a patent for the future development of the aptamers for diagnostic purposes. Preliminary studies with the E7 aptamers have shown that some trigger cell cycle changes and apoptosis when transfected into cells derived from a cervical carcinoma. Projects are based at The Astbury Centre for Structural Molecular Biology in Leeds, which has state-of-the art equipment and facilities. Funding Notes Applications are welcome at any time, but deadlines exist for some awards (see http://www.astbury.leeds.ac.uk). Offers are made to the most able students as soon as possible. Recent publications: Tolley A.C. and Stonehouse N.J. (2008) Conformational changes in the connector protein complex of the bacteriophage phi29 DNA packaging motor. Computational and mathematical methods in medicine. 9, 327-337. Rolfsson O., Toropova K., Morton V., Francese S., Basnak G., Thompson G., Homans S.W., Ashcroft A.E., Stonehouse N.J., Ranson N.A. and Stockley P.G. (2008) RNA packing specificity and folding during assembly of the bacteriophage MS2. Computational and mathematical methods in medicine. 9, 339-349. Morton V.L., Stockley P.G., Stonehouse N.J. and Ashcroft A.E. (2008) Insights into Virus Capsid Assembly from Non-covalent Mass Spectrometry. Mass spectrometry reviews. 27, 575-595. Stockley P.G., Rolfsson O., Thompson G.S., Basnak G., Francese S., Stonehouse N.J., Homans S.W. and Ashcroft A,.E. (2007) A Simple, RNA-Mediated Allosteric Switch Controls the Pathway to Formation of a T= 3 Capsid. J. Mol. Biol. 369, 541-552. Ellingham M., Bunka D.H.J., Rowlands D.J.and Stonehouse N.J. (2006) RNA 12, 1970-1979. Selection and characterisation of RNA aptamers to the RNA-dependent RNA polymerase from foot and mouth disease virus. Robinson, M.A., Wood, J.P.A, Capaldi, S.A., Baron A.J., Gell, C., Smith, D.A. and Stonehouse, N.J. (2006) Nucleic Acids Res. 34, 2698-2709. Affinity of molecular interactions in the bacteriophage phi29 packaging motor. Horn W.T., Tars K., Grahn E., Helgstrand C., Baron A.J., Lago H., Adams C., Peabody D.S., Phillips S.E.V., Stonehouse N.J., Liljas L. and Stockley P.G. (2006) Structure 14, 487-496. Structural basis of RNA binding discrimination between bacteriophages QB and MS2. Wood J.P.A., Capaldi S.A., Robinson M.A., Baron A.J. and Stonehouse N.J. (2005) Journal of Theoretical Medicine 6, 127-134. RNA multimerisation in the DNA packaging motor of bacteriophage phi29. Stockley P.G., Ashcroft A.E., Francese S., Thompson G.S., Ransom, N.E. Smith, A., Homans S.W. and Stonehouse N.J. (2005) Journal of Theoretical Medicine 6, 119-125. Dissecting the fine details of assembly of a T=3 phage capsid. Ashcroft A.E., Lago H., Macedo J.M.B., Horn W.T., Stonehouse N.J. and Stockley P.G. (2005) Journal of Nanoscience and Nanotechnology 5, 1-8. Engineering thermal stability in RNA phage capsids via disulphide bonds. Horn W. T., Convery M.A., Stonehouse N.J., Adams C.J., Liljas L., Phillips S.E.V. and Stockley P.G. (2004) RNA 10, 1776-1782. The crystal structure of a high affinity RNA stem-loop complexed with the bacteriophage MS2 capsid. |
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Research Assessment Exercise (RAE) 2008 Results
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