BBSRC PhD Studentship in “Cryogenic electron microscopy-based understanding of viral vector heterogeneity to aide process development"

   Department of Biochemical Engineering

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  Prof Dan Bracewell, Dr Sarah Rouse  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

About the Project

Viral vectors can be used as oncolytic viruses, gene-based vaccines, and gene therapy vectors. However, as highlighted by the adverse reactions observed with the recent ChAdOx1 nCoV-19 vaccine and gene therapy trials, gaps remain in our understanding of these products. This currently limits our ability to engineer the virus’s tropism, immunogenicity and manufacturability. We seek to address the quality of virus particle synthesis and improve the proportion of mature virus particles in the product. This will be achieved by harnessing the power of computation at multiscale resolution to capture new insights into the biological assembly and disassembly pathways of the viral capsid, centering on the role of the portal protein, towards ‘computational microscopy’ of viral infectivity.

Using adenovirus (Ad5) as our model system we have demonstrated that cryo-EM analysis can identify particle surface morphologies, e.g. fiber molecules and is a technique that could be applied to identify key quality markers on a range of viral vector-like biotherapeutics. Gathering larger cryo-electron microscopy datasets via this project will allow us to probe key structural features critical to viral infectivity, including the portal structure in the capsid and the spike proteins. Key to this is our ability to implement atomic level simulations in collaboration with the Rouse lab (the secondary supervisor) and create samples where changes to the processing conditions can be used to create samples with known changes to viral heterogeneity. Once optimised, these novel methods will be expanded to analyse lentiviral (LV) and adeno-associated virus (AAV) vector systems to fully complement the predominant platforms being applied to gene delivery.

About the BBSRC Collaborative Training Partnership in Advanced Bioscience of Viral Products (ABViP)

This PhD studentship is part of the Biotechnology and Biological Sciences Research Council (BBSRC) Collaborative Training Partnership (CTP) in Advanced Bioscience of Viral Products (ABViP). The ABViP CTP is a comprehensive, multidisciplinary training programme designed to deliver the next generation of bioscience leaders who will advance research on the underpinning bioscience of viral products for future gene therapies and vaccines. Led by Oxford Biomedica (OXB) and involving both UCL and the University of Oxford, CTP students will have access to a wide-ranging portfolio of training opportunities at the Partner sites including taught courses and case studies designed to complement the doctoral research. Students trained through the ABViP CTP will gain a holistic insight into the research and development activities required to develop the medicines of the future, with the ability to see the world of medicines development through both an academic and industrial lens. For more information about the ABViP CTP, please click on the following link.

About the Department

Department of Biochemical Engineering, University College London

The department is a founding laboratory of the discipline and boasts a long tradition of innovation. Our reputation as a world-leading teaching and research centre attracts staff and students worldwide. In the latest Research Assessment Exercise Framework (REF) 75% of academic staff were rated as 'world-leading' or 'internationally excellent'. Our interdisciplinary Advanced Centre for Biochemical Engineering (ACBE) coordinates bioprocess research and training collaborations with more than a dozen UCL departments, a similar number of external university partners and over 40 international companies.

Department of Life Sciences, Imperial College London

Imperial College London is the UK’s only university focussed entirely on science, engineering, medicine and business and we are consistently rated in the top 10 universities in the world. The Department of Life Sciences embraces the full breadth of modern life science activity and comprises one of the largest life science groups in Europe, with approximately 100+ academic staff, 180 research fellows and post-doctoral researchers, 200+ PhD students and 180+ Masters students. The vast majority (94%) of the Department of Life Science’s research activity was judged to be ‘World Leading’ (53%) or ‘Internationally Excellent’ (41%).

About Oxford Biomedica

Oxford Biomedica (OXB) is a pioneer of gene and cell therapy with a leading position in viral vector research and bioprocessing. Our mission is to deliver life-changing gene therapies to patients. OXB is an innovation and science focussed company which has developed a leading platform of novel technologies and capabilities. The OXB team provide design, development, bioprocessing and analytical development for gene-based medicines based on viral vectors, both for in-house products and for those developed with partner organisations. OXB has contract development and manufacturing organisation (CDMO) capabilities that support the development of novel gene-based medicines through all phases of clinical development to commercial manufacture. At Oxford Biomedica, we drive credible science to realise incredible results.

Entry requirements

A UK Master’s degree, or a minimum of an upper second-class UK Bachelor’s degree, in a relevant discipline, or an overseas qualification of an equivalent standard. We particularly welcome applicants from disadvantaged backgrounds, or via an unconventional career path. If you’re unclear as to whether you are eligible, we would encourage you to apply regardless. You can also contact the project supervisor (see details below). To learn more about the policies in relation to diversity and inclusion at UCL, please click here for further information.

Informal enquiries should be addressed to Prof Daniel Bracewell and Dr Sarah Rouse (E-mail [Email Address Removed], [Email Address Removed]).

English language requirements

If your education has not been conducted in the English language, you will be expected to demonstrate evidence of an adequate level of English proficiency. The English language level for this programme is: Level 1

Deadline and Application Process

The deadline for submission is 12:00 midday on Friday 16th December 2022

To apply for this PhD studentship, you must submit a formal application to the Research Degree: Biochemical Engineering RRDBENSING01 course through UCL’s application portal by the above deadline. More information about the course and application process is available here:

Biological Sciences (4) Engineering (12)

Funding Notes

This BBSRC CTP ABViP Studentship is available to UK and Overseas (including EU) students. Full maintenance (stipend & fees) is available to the UK and Overseas students for the duration of the four-year PhD. Note that up to a maximum of one fully funded studentship allocation is available for Overseas students across the Department. The annual tax-free stipend for the PhD studentship is £20,198 (estimated value, confirmed annually, using in spring by UKRI and UCL).