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| Using RNA aptamers to study cellular targets of human papilloma virus oncoproteins in a human skin model | ||||||||||||||||||
Human papilloma viruses HPV16 and 18 are the major causative agents of a range of anogenital and oropharyngeal cancers, with HPV16 associated with the majority of all cervical carcinomas. Transformation results from the expression of the E6 and E7 proteins, resulting in deregulation of the cell cycle and cellular proliferation. In studies currently funded by Yorkshire Cancer research, we are using a novel strategy using RNA aptamers as molecular probes to specifically target and block each of the E6/E7 interactions. We have generated a large number of RNA aptamers that bind to the E6 and E7 proteins. Some of these disrupt interactions with as yet undefined cellular targets. We propose to characterise a number of these interactions in vitro, and extend our studies into a human skin model. For information on the Stonehouse group see http://www.astbury.leeds.ac.uk/People/staffpage.php?StaffID=NJS Funding Notes Applications are welcome at any time, but deadlines exist for some awards. Offers are made to the most able students as soon as possible. Recent publications: Nicol C., Forrest S., Belyaeva T., Bunka D.H.J., Blair G.E. and Stonehouse N.J. Degradation of HPV16 E7 oncoprotein and induction of apoptosis by an RNA aptamer. Submitted. Foster T.L., Belyaeva T., Stonehouse N.J., Pearson A.R. and Harris M. (2010) All three domains of the hepatitis C virus nonstructural NS5A protein contribute to RNA binding. J.Virol. In press. Basnak G., Morton V.L., Rolfsson O., Stonehouse N.J., Ashcroft A.E., Stockley P.G. (2010) Viral Genomic Single-Stranded RNA Directs the Pathway Toward a T=3 Capsid. J. Mol. Biol. 395, 924–936. 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 Alison E. Ashcroft (2007) A Simple, RNA-Mediated Allosteric Switch Controls the Pathway to Formation of a T=3 Viral Capsid. J. Mol. Biol. 369, 541–552. Ellingham M., Bunka D.H.J., Rowlands D.J. and Stonehouse N.J. (2006) Selection and characterisation of RNA aptamers to the RNA-dependent RNA polymerase from foot-and-mouth disease virus. RNA 12, 1970-1979. Robinson, M.A., Wood, J.P.A, Capaldi, S.A., Baron A.J., Gell, C., Smith, D.A. and Stonehouse, N.J. (2006) Affinity of molecular interactions in the bacteriophage phi29 packaging motor. Nucleic Acids Res. 34, 2698-2709. |
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Research Assessment Exercise (RAE) 2008 Results
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