PhD Studentship: Optimised Emerging And Zoonotic Virus Envelope Proteins As Vaccine Antigens.

University of Sussex

A Ph.D. studentship (42 months) is available from September 2018 under the supervision of Edward Wright and Pascale Schellenberger (University of Sussex) and Ashley Banyard (Animal and Plant Health Agency).

Deadline: 23rd February 2018

Emerging and zoonotic viruses pose an increasingly serious threat to both human and animal health. Many of the most highly pathogenic viral zoonoses are caused by RNA viruses. With antivirals against RNA viruses scarce, the impact of these viruses is most often mitigated through the development of vaccines that confer protection against infection. However, vaccines are only as good as the antigen(s) incorporated in the preparation. While it is known that upon infection with such viruses a strong humoral immune response is normally stimulated against the viral envelope protein(s; VEP), these a antigens are often poorly characterised. Further, virus vaccines routinely comprise serially passaged strains that may have mutated and antigens are frequently chosen based on availability of isolates rather than by informed design. Together these factors can dramatically reduce the vaccines’ public health relevance.

One example of this is the existing rabies virus (RABV) vaccines that are based on classical rabies isolates. Rabies is caused by a number of antigenically divergent viruses within the lyssavirus genus. Whilst the existing vaccines protect against the prototypic lyssavirus, rabies virus, these vaccines are unable to confer robust protection against other lyssavirus species. Therefore, a better understanding of the antigenicity of these VEP will aid the development of more broadly neutralising and potent vaccines.

This PhD will address this requirement by undertaking serological and structural studies of VEP using pseudotyped viruses (PV), which are replication defective recombinant virus-like particles. The first part will extend the our existing work on filoviruses and arenaviruses, by bringing together cutting edge in silico and in vitro technologies to achieve dramatic improvements in vaccine efficacy against all lyssavirus species. Digitally designed VEP sequences for ancestral viral isolates will be synthesised and characterised using our PV system. Promising antigens will be taken forward for in vivo analysis. Secondly, we will study the composition of the PV produced bearing the ancestral VEP. Cryo-electron tomography will be used to assess the density of VEP on the virus surface and the high resolution structure of the VEP.

Interested candidates should submit a formal application using our online application system at http://www.sussex.ac.uk/study/phd/apply, including a CV, degree transcripts and certificates, statement of interest and names of two academic referees. On the application system use Programme of Study – PhD Biochemistry.

Please make sure you include the project title and supervisor’s name with your statement of interest.

This School funded position, which covers fees and a stipend at standard RCUK rates, is open to Home / EU applicants. Ideal candidates will have a strong background in molecular biology, additional experience of virology is desirable. Eligible applicants will have recently received an MSc or a First or high 2:1 BSc in a relevant subject. Candidates for whom English is not their first language will require an IELTS score of 6.5 overall, with not less than 6.0 in any section.

Contact Anna Izykowska for application enquiries (a.izykowska@sussex.ac.uk)

Contact Edward Wright (ew323@sussex.ac.uk) for enquiries about the project.

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Type / Role:

PhD

Location(s):

South East England