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Defining picornaviral replication complexes by molecular virology and state-of-the art imaging - Novel strategies for disease control

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  • Full or part time
    Prof N J Stonehouse
    Dr M.R. Herod
    Prof D.J. Rowlands
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Picornaviruses are responsible for a number of serious diseases, including polio and foot-and–mouth disease. There is an urgent need to develop new therapeutic strategies to address the continuing issue of picornavirus infection. Foot-and–mouth disease virus (FMDV) is an extremely important animal pathogen - the 2001 UK outbreak cost several billion pounds. The project aims to study the features of the viral genome responsible for both rapid replication and persistence, using a replicon system.

Replicons are mini-genomes that allow the study of replication in a safe virus-free way which is highly convenient for the study of the mechanics of genome replication. Using reciprocal complementation (together with state-of-the art imaging and structural techniques available in-house) we can dissect the functions of both the RNA and protein components of replication complex. e.g. Identifying novel roles of the essential FMDV non-structural proteins and precursors in replication, focusing on the polymerase (3D) and primer of replication (VPg) using mutagenesis and replication inhibitors.

The long-term aim of the work is to utilise our knowledge of the molecular details of replication in the development of new strategies of disease diagnosis and control.

This interdisciplinary project includes other UK academic institutions as well as the BBSRC Pirbright Institute and will involve close collaboration with partner institutions.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2019:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference allowance
• Research Costs

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.
EU candidates require 3 years of UK residency in order to receive full studentship

Not all projects advertised will be funded; the DTP will appoint a limited number of candidates via a competitive process.

https://biologicalsciences.leeds.ac.uk/directory/research-opportunities

References

Herod M. R., Gold S., Lasesca-Dykes L., Wright C., Ward J. C., McLean T.C., Forrest S., Jackson T., Tuthill T.J., Rowlands D.J. and Stonehouse N.J. (2017) Genetic economy in picornaviruses: Foot-and-mouth disease virus replication exploits alternative precursor cleavage pathways PLoS Pathog 13 (10): e1006666. doi.org/10.1371/journal.

Herod M., Ferrer-Orta C., Loundras E., Ward J. C., Verdaguer N., Rowlands D.J. and Stonehouse N.J. (2016) Both Cis- and Trans- Activities of the Foot-and-Mouth Disease Virus 3D Polymerase are Essential for Viral RNA Replication. J. Virol. 90:6864–6883

Loundras E-A., Herod M., Harris M. and Stonehouse N.J. (2016) Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases. J. Gen. Virol. 97, 2221–2230.

Herod M., Loundras E., Ward J. C. Tulloch F., Rowlands D.J. and Stonehouse N.J. (2015) Employing Transposon Mutagenesis to Investigate Foot-and-Mouth Disease Virus Replication. J. Gen. Virol. 96, 3507-18

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

Research output data provided by the Research Excellence Framework (REF)

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