Dr J Seago, Dr Michael Eschbaumer, Dr T Tuthill, Prof J Haas
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
Foot-and-mouth disease virus (FMDV) is a highly infectious viral pathogen that causes foot-and-mouth disease (FMD) in cloven-hoofed animals. FMD has a major economic impact globally and is a considerable threat to food security.
FMDV is a non-enveloped, single-stranded positive-sense RNA virus in the genus Aphthovirus of the family Picornaviridae. FMDV has a small genome and therefore relies on multifunctional viral proteins and cellular factors to replicate. In vitro studies have shown that a range of mammalian cell lines from different species are permissible to FMDV infection and replication. However, many of the interactions between host and viral proteins that facilitate this replication remain unidentified. Similarly, the antiviral responses triggered following infection of these cell lines, and their effects on viral replication, is yet to be determined.
This project will help to fill these knowledge gaps by 1) determining the ability of FMDV to replicate in different mammalian cell lines, 2) characterising the innate IFN response to infection and 3) identifying the host proteins required for viral replication. The project will provide fundamental knowledge of FMDV replication that will be of major benefit to the picornavirus research community and strengthen collaborative links. The work could also inform the rational development of novel control strategies and enhance vaccine production.
Aside from the presence of a suitable receptor for infection, a number of factors influence the ability and efficiency of FMDV replication in mammalian cells. These include the effectiveness of the host’s innate immune responses and the ability of the virus to evade these, as well as the capacity of the virus to efficiently orchestrate the re-arrangement of cellular membranes to carry out viral replication and utilisation of the host’s translation machinery.
The aims of this project are to identify host factors which regulate FMDV replication in mammalian cell lines:
• Are there differences in the efficiency of FMDV replication between mammalian cell types?
• Does the host IFN response differ between these cell types and does this significantly affect viral replication in vitro?
• Which host proteins are critical for viral replication in vitro and are these conserved across host cell types?
• Do differences exist (for the above questions) between FMDV serotypes and subtypes?
Funding Notes
Open to science graduates (with or who anticipate at least 2.1 or equivalent in relevant biological subject in undergraduate degree, or a Masters degree). Other first degrees, e.g. veterinary science, considered. A fully-funded studentship open to UK and EU students. Students without English as first language must provide evidence of English language - IELTS score 7.0, no less than 6.5 in subsections.
The student will be based at The Pirbright Institute and registered with the University of Edinburgh. Student will spend 6-12 months at FLI, Germany. Eligible students will receive a minimum annual stipend of £14,553; university registration fees paid.
References
1. Grubman and Baxt. Foot-and-mouth disease. BClin Microbiol Rev. 2004 Apr;17(2):465-93.
2. Rodríguez and Sáiz. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response. Front Cell Infect Microbiol. 2017 Jun 13;7:252.
3. Zhang et al. A replication-competent foot-and-mouth disease virus expressing a luciferase reporter. J Virol Methods. 2017 Sep;247:38-44.
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