or
Continue with FacebookLooking to list your PhD opportunities? Log in here.
This project is no longer listed on FindAPhD.com and may not be available.
Click here to search FindAPhD.com for PhD studentship opportunities
Prof N J Stonehouse
Prof E Blair
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
Aptamers are oligonucleotides, produced by the iterative process SELEX, that fold into complex structures and bind target molecules in a conformation-dependent manner. RNA aptamers can be delivered to live cells and are non-immunogenic. Furthermore, because of the high affinity of binding, these molecules have the ability to modulate the function of target molecules and therefore have therapeutic potential. We have characterised RNA aptamers to a range of protein targets. We have been able to generate aptamer molecules that are stable in cells for at least 48 hours post-transfection and label molecules with fluorophores for detection. Of particular interest are the aptamers that exert direct, inhibitory effects on the E6 and E7 oncoproteins from human papilloma virus16 (HPV16) both in vitro and when delivered to transformed cell lines by lipofection [Nicol et al, 2011 and 2013].
Objectives:
In order to evaluate the aptamer molecules as potential therapeutics, we propose to develop novel systems to deliver the molecules into skin.
We will monitor delivery of aptamers conjugated to a fluorophore (Cy5) by microscopy of tissue sections.
Objectives:
In order to evaluate the aptamer molecules as potential therapeutics, we propose to develop novel systems to deliver the molecules into skin.
We will monitor delivery of aptamers conjugated to a fluorophore (Cy5) by microscopy of tissue sections.
References
Selected references:
Forrest S., Lear Z., Herod M.R., Ryan M., Rowlands D.J. and Stonehouse N.J. (2014) Inhibition of the foot-and-mouth disease virus subgenomic replicon by RNA aptamers. Journal of General Virology. J. Gen. Virol. 95, 2649–2657
Tulloch F., Pathania U., Luke G.A., Nicholson J., Stonehouse N.J., Rowlands D.J., Jackson T., Tuthill T., Haas J., Lamond A. I, Ryan M.D. (2014) FMDV replicons encoding green fluorescent protein are replication competent. J. Virological Methods 209, 35–40
Belyaeva T.A., Nicol C., Cesur Ö., Travé G., Blair G.E. and Stonehouse N.J. (2014) An RNA Aptamer Targets the PDZ-Binding Motif of the HPV16 E6 Oncoprotein. Cancers, 6, 1553-1569
De Colibus L., Wang X., Spyrou J.A.B., Kelly J., Ren J., Grimes J., Puerstinger G., Stonehouse N., Walter T.S., Hu Z., Wang J., Li X., Peng W., David J Rowlands D.J. ,Fry E.E., Rao Z & Stuart D.I.(2014) More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules. Nature Struc. Mol. Biol doi:10.1038/nsmb.2769
Doble R., McDermott M.F., Cesur Ö., Stonehouse N.J. Wittmann M. IL-17A RNA Aptamer: Possible Therapeutic Potential in
Some Cells, More than We Bargained for in Others? Journal of Investigative Dermatology. In press. doi:10.1038/jid.2013.399
Nicol C., Cesur Ö., Forrest S., Belyaeva T.A., Bunka D.H.J., Blair G.E. and Stonehouse N.J. (2013) An RNA aptamer provides a novel approach for the induction of apoptosis by targeting the HPV16 E7 oncoprotein
Plos One 5, e64781
Nicol C., Bunka D.H., Blair G.E., Stonehouse N.J. (2011) Effects of single nucleotide changes on the binding and activity of RNA aptamers to human papillomavirus 16 E7 oncoprotein. Biochem Biophys Res Commun. 405, 417-421.
Bentham M., Holmes K., Forrest S., Rowlands D.J. and Stonehouse N.J.(2012) Formation of higher-order FMDV 3Dpol complexes is dependent on elongation activity. J. Virol. 86, 2371-2374.
Forrest S., Lear Z., Herod M.R., Ryan M., Rowlands D.J. and Stonehouse N.J. (2014) Inhibition of the foot-and-mouth disease virus subgenomic replicon by RNA aptamers. Journal of General Virology. J. Gen. Virol. 95, 2649–2657
Tulloch F., Pathania U., Luke G.A., Nicholson J., Stonehouse N.J., Rowlands D.J., Jackson T., Tuthill T., Haas J., Lamond A. I, Ryan M.D. (2014) FMDV replicons encoding green fluorescent protein are replication competent. J. Virological Methods 209, 35–40
Belyaeva T.A., Nicol C., Cesur Ö., Travé G., Blair G.E. and Stonehouse N.J. (2014) An RNA Aptamer Targets the PDZ-Binding Motif of the HPV16 E6 Oncoprotein. Cancers, 6, 1553-1569
De Colibus L., Wang X., Spyrou J.A.B., Kelly J., Ren J., Grimes J., Puerstinger G., Stonehouse N., Walter T.S., Hu Z., Wang J., Li X., Peng W., David J Rowlands D.J. ,Fry E.E., Rao Z & Stuart D.I.(2014) More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules. Nature Struc. Mol. Biol doi:10.1038/nsmb.2769
Doble R., McDermott M.F., Cesur Ö., Stonehouse N.J. Wittmann M. IL-17A RNA Aptamer: Possible Therapeutic Potential in
Some Cells, More than We Bargained for in Others? Journal of Investigative Dermatology. In press. doi:10.1038/jid.2013.399
Nicol C., Cesur Ö., Forrest S., Belyaeva T.A., Bunka D.H.J., Blair G.E. and Stonehouse N.J. (2013) An RNA aptamer provides a novel approach for the induction of apoptosis by targeting the HPV16 E7 oncoprotein
Plos One 5, e64781
Nicol C., Bunka D.H., Blair G.E., Stonehouse N.J. (2011) Effects of single nucleotide changes on the binding and activity of RNA aptamers to human papillomavirus 16 E7 oncoprotein. Biochem Biophys Res Commun. 405, 417-421.
Bentham M., Holmes K., Forrest S., Rowlands D.J. and Stonehouse N.J.(2012) Formation of higher-order FMDV 3Dpol complexes is dependent on elongation activity. J. Virol. 86, 2371-2374.
How good is research at University of Leeds in Biological Sciences?
Research output data provided by the Research Excellence Framework (REF)
Click here to see the results for all UK universitiesProject supervisors
Career overview
Professor Nicola Stonehouse is a virologist with a focus on the fundamental aspects of the viral lifecycle and the development of novel vaccines. She completed her BSc at the University of East Anglia and obtained her PhD in 1992 from the University of Leeds. As a post-doctoral fellow, she developed an interest in high-resolution structural studies of RNA-protein complexes, which led to a long-term collaboration with Lars Liljas’ group in Uppsala, Sweden. This collaboration ultimately resulted in the award of a Career Development Fellowship from the UK Medical Research Council. Over the years, Professor Stonehouse transitioned from working on bacteriophage to picornaviruses and was appointed as Lecturer in 2001, subsequently becoming Chair in Molecular Virology in 2014. She collaborates widely, with current funding supporting vaccine development, studies of the replication of foot-and-mouth disease virus, and understanding the fundamental aspects of viral capsid assembly. Her vaccine projects involve generating a generic vaccine ''scaffold'' and developing stabilised empty viral capsids as vaccine candidates for poliovirus and other enteroviruses. Professor Stonehouse is a Fellow of the Royal Society of Biology (FRSB), the Royal Society for the encouragement of Arts, Manufacture and Commerce (FRSA), and the UK Higher Education Academy. She teaches at all levels and has taken on various roles to support junior scientists.
Research interests
Professor Stonehouse''s research focuses on viral replication and assembly, as well as vaccine development. She is particularly interested in the fundamental aspects of the viral lifecycle and the development of novel vaccines. Her work includes studies on the replication of foot-and-mouth disease virus and understanding the fundamental aspects of viral capsid assembly. Current projects involve the development of a generic vaccine scaffold and the characterisation of stabilised empty viral capsids as vaccine candidates for poliovirus and other enteroviruses. Additionally, she has a background in high-resolution structural studies of RNA-protein complexes and has collaborated on various projects related to picornaviruses.
Molecular Virology
Virus-Like Particle Vaccines
Virus Replication
Virus Assembly
Foot-and-Mouth Disease Virus
Poliovirus
RNA Biology
Vaccine Development
Structural Biology
Picornaviruses
Viral Capsid Assembly
RNA-Protein Complexes
High-Resolution Structural Studies
Infectious Diseases
Postgraduate Research
Picornaviral Replication
RNA Aptamers
Vaccine Platforms
Live Cell Imaging
Mass Spectrometry
Enterovirus Maturation
Career overview
Professor Eric Blair studied Biochemistry at the University of Edinburgh and completed doctoral studies at the University of Warwick. He conducted postdoctoral research at the universities of Aarhus in Denmark and Uppsala in Sweden. Professor Blair was a member of the Scientific Staff at the National Institute of Medical Research in London, which is now known as the Crick Institute. He joined the University of Leeds as a Lecturer in Biochemistry in 1981, was promoted to Senior Lecturer in 1988, became a Reader in 1996, and was appointed Professor in 2008.
Research interests
Professor Blair''s research focuses on small DNA tumour viruses, including adenoviruses, papillomaviruses, SV40, and polyomaviruses, which are significant in the study of cell transformation, cell cycle control, and tumour formation. Recently, adenoviruses have been explored as potential vectors for gene therapy targeting inherited diseases such as cystic fibrosis and cancer. Professor Blair investigates the mechanisms by which adenoviruses enter human cells, aiming to design viruses that can deliver therapeutic genes to correct inherited deficiencies or specifically replicate in and kill cancer cells. Additionally, the research addresses how adenoviruses and oncogenic human papillomaviruses (HPV16 and 18) evade the immune system by subverting antigen processing and presentation mediated by major histocompatibility complex (MHC) class I molecules. The focus is on understanding the biochemical mechanisms of this immune evasion, which may reveal new targets for eradicating cancer-causing viruses.
Molecular Biology
Cellular Biology
Oncogenic Viruses
Viral Gene Therapy
Immune Response
Adenoviruses
Papillomaviruses
Tumour Formation
Gene Therapy
Cancer Biology
Molecular Virology
Gene Expression
Gene Technology
Antigen Processing
Immune Evasion
Tumour Suppressor Proteins
Cancer Research
Infectious Diseases.
Find a scholarship to fund your dream Masters
Sign in to view and filter all scholarship opportunities
or
Continue with Facebook