Modification of blood coagulation factor X as an approach to retargeting adenovirus for gene therapy
A 3-year fully-funded PhD studentship is offered to study the interaction of blood coagulation factor X (FX) with adenovirus and to apply this knowledge to the development of novel factor X variants to retarget virus for the purpose of gene therapy.
Start date1 October 2020
Funding sourceThe Lorna & Yuti Chernajovsky Biomedical Research Foundation
UKRI-aligned stipend of ~£15,000 pa, approved University of Surrey fees and a research budget.
Adenoviruses (Ad) are used extensively in pre-clinical research and over 25% of gene therapy clinical trials worldwide. In 2008 we defined a critical new function for the Ad5 hexon. We showed blood coagulation FX binds to the hexon surface. The complex of Ad5:FX binds to hepatocytes through the FX serine protease domain which interacts with cell surface heparan sulphate proteoglycans. This critically important new information was a paradigm shift for Ad biology. In this proposal the student will explore the rational design and characterisation of high affinity FX-fusion molecules with a number of domains that will lead to efficient re-targeting and delivery of recombinant Ad to sites of pathological interest. This could represent a paradigm shift in the way that we choose to develop Ad as gene therapy vectors, or indeed vaccines. The results of this project could have significant translational impact as the retargeting strategy is widely applicable to any Ad5 based gene therapy vector.
This is a multidisciplinary project involving molecular biology, protein design and engineering and gene therapy/targeting. The candidate will gain experience and skills in mammalian cell culture, molecular biology, protein expression, purification and characterisation. In particular, they will gain experience in studying protein-protein interactions using surface plasmon resonance.
The proposed work will be carried out in the laboratory of Professor John H. McVey in the Department of Biochemical Sciences at the University of Surrey within the School of Biosciences and Medicine, which provides an interdisciplinary research environment, facilitating access to relevant resources and centrally supported equipment.
Further background information can be found in these relevant publications:
- Cell. 132, 397-409 (2008)
- J. Virol., 85, 10914-10919 (2011)
- J. Virol. 82, 10567-10579 (2008)
- Blood 114, 965-971 (2009)
- Blood 116, 2656-2664 (2010)
- PLoS Pathog 11(2): e1004673 (2015)
Related linksSchool of Biosciences and Medicine
We are looking for a graduate who is enthusiastic and strongly motivated. A true interest in research as well as excellent communication, organizational and language skills are essential. MSc and/or research experience is not essential but would be very advantageous.
Candidates must hold a First or Upper Second Class Honours degree from the UK (or equivalent qualification from EU Institutions) in a relevant subject area.
UK or EU students are eligible.
An IELTS Academic of 6.5 or above with 6 in each individual category (or equivalent qualification from other agencies). Find more details about English Language requirements.
How to apply
Informal enquiries and applications should be sent to Professor John H. McVey (firstname.lastname@example.org).
Applications should be submitted via the Biosciences and Medicine PhD course page. In your application, please mention this studentship to be considered. Instead of a project proposal, upload a cover letter indicating why you have applied and what you hope to achieve by undertaking this PhD. Your CV should include your course modules and marks (including predicted grade if you are in your final year).
Application deadline: Friday July 12th 2020. Shortlisted candidates will be contacted to arrange an interview via Zoom (expected w/c July 20th).