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Prof P G Stockley
Applications accepted all year round
Competition Funded PhD Project (European/UK Students Only)
About the Project
There is worldwide interest in exploiting our modern understanding of genomics to target gene expression therapeutically via a variety of mechanisms, such as transgene insertion and CRISPR-Cas gene editing. Such approaches require the transport of large genetic cargoes across cell membranes. Laboratory protocols for this transport are not easily transposed to the clinic. Natural viruses accomplish precisely this task by delivering their genomes with significant cell tropism to new host cells. We are repurposing such natural delivery systems to deliver nucleic acid cargoes, primarily RNAs to cells using picornaviruses and alphavirus capsid proteins and information on the multiple RNA packaging signals within their genomes. Production of non-infectious, bespoke virus-like particles (VLPs) is also being used to present stable, neutralising epitopes as the basis of a synthetic vaccine.
Techniques uesd include: gene cloning; synthetic gene construction; cell culture; viral infection assays; VLP purification; electron microscopy; ultracentrifugation; single molecule spectroscopy
Techniques uesd include: gene cloning; synthetic gene construction; cell culture; viral infection assays; VLP purification; electron microscopy; ultracentrifugation; single molecule spectroscopy
Funding Notes
EU candidates must have been resident in the UK for a minimum of 3 years.
The studentship will provide fees and stipend (~£14k p.a) for 3.5 years.
Applicants should have a 2.1 or above at undergraduate level. Please include CV and transcripts with your application (link below).
The studentship will provide fees and stipend (~£14k p.a) for 3.5 years.
Applicants should have a 2.1 or above at undergraduate level. Please include CV and transcripts with your application (link below).
References
Patel N, et al. (2017) Rewriting nature’s assembly manual for a ssRNA virus. Proc Natl Acad Sci U S A. 114(46):12255-12260.
Patel N, et al. (2015) Revealing the density of encoded functions in a viral RNA. Proc Natl Acad Sci U S A., 112, 2227-32.
Twarock, R. & Stockley, P.G. (2019) RNA-mediated Virus Assembly: Mechanisms and Consequences for Viral Evolution and Therapy Ann. Rev. Biophys, 48, 495-514
40.
Patel N, et al. (2015) Revealing the density of encoded functions in a viral RNA. Proc Natl Acad Sci U S A., 112, 2227-32.
Twarock, R. & Stockley, P.G. (2019) RNA-mediated Virus Assembly: Mechanisms and Consequences for Viral Evolution and Therapy Ann. Rev. Biophys, 48, 495-514
40.
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Career overview
Professor Peter Stockley studied Chemistry at Imperial College, London, before completing a PhD on Chromatin Structure in the laboratory of Prof. Dame Jean Thomas at Cambridge. He subsequently worked with Prof. Steve Harrison at Harvard on the mechanisms of virus assembly. Professor Stockley joined the University of Leeds in 1986, where he has held various leadership roles, including Head of the Department of Genetics from 1993 to 1997, Deputy Director of the Astbury Centre for Structural Molecular Biology from 1997 to 2001, and Director from 2001 to 2008. He also served as Director of the Interdisciplinary Institute for Bionanosciences from 2002 to 2008. His laboratory has made significant discoveries regarding the self-assembly of single-stranded, positive-sense RNA viruses, which are major pathogens affecting humans and for which there are currently no effective antiviral drugs or vaccines. Professor Stockley''s research has revealed that these viruses encode self-assembly instructions within their RNA genomes, challenging previous paradigms of virus assembly. His work employs interdisciplinary approaches, combining biochemical, structural, and biophysical methods with traditional virology, and he collaborates extensively with theoretical and mathematical modelling groups.
Research interests
Professor Stockley''s research focuses on viral assembly and structural virology, particularly the self-assembly of single-stranded, positive-sense RNA viruses, which include major human pathogens lacking current antiviral drugs or vaccines. His laboratory has made significant discoveries that challenge the traditional understanding of virus assembly, revealing that RNA genomes encode self-assembly instructions in the form of sequence-specific motifs and secondary structures that interact with coat proteins. This cooperative mechanism ensures accurate virion assembly within the cellular environment and has been observed across various virus types, including Hepatitis B Virus. Current research is directed towards understanding these mechanisms in additional human pathogens, such as emerging alphaviruses and established picornaviruses. Professor Stockley employs interdisciplinary approaches, integrating biochemical, structural, and biophysical techniques with traditional virology, and collaborates with theoretical and mathematical modelling groups to further his research.
Viral Assembly
Structural Virology
Virus-Drug Interactions
Protein-Nucleic Acid Interactions
Single Molecule Spectroscopy
SELEX
Nucleic Acid Aptamers
Transcriptional Control
Genetic Regulatory Mechanisms
ssRNA Virions
Bionanotechnology
Eukaryotic Gene Expression
Pathogenic Viruses
Hepatitis B Virus
Emerging Alphaviruses
Picornaviruses
Biochemical Assays
Structural Biology
Infectious Diseases.
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