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Inhibition of innate immunity by vaccinia virus: a discovery tool for host restriction factors

  • Full or part time
  • Application Deadline
    Wednesday, January 01, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

The interaction between viruses and their host reveals a fascinating conflict between host defense and virus evasion. The project concerns vaccinia virus (VACV), the live vaccine used to eradicate smallpox, and how it shuts down host innate defenses. Analysis of the cell proteome following VACV infection shows that ~265 cell proteins are downregulated and ~70% of these are degraded via the proteasome. We hypothesise that these proteins are host restriction factors that are therefore targeted by VACV. This project will test this hypothesis, evaluate the function of host proteins in innate immunity and study how VACV induces their degradation.

Funding Notes

Funding* will cover the student’s stipend at the current Research Council rate and University Fees. The studentships will be funded for three years in the first instance subject to eligibility**, with the possibility of additional funding in the fourth year depending on circumstances.

**The studentships are available to students who qualify for Home/EU fees

Applications from ineligible candidates will not be considered.

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1. Pallett, M.A., Ren, H., Zhang, R.-Y., Scutts, S.R., Gonzalez, L., Zhu, Z., Maluquer de Motes, C. & Smith, G.L. (2019). Vaccinia virus BBK E3 ligase adaptor A55 targets importin-dependent NF-κB activation and inhibits CD8+ T-cell memory. J. Virol. 93, e00051-19.
2. Gao, C., Pallett, M.A., Croll, T.I., Smith, G.L. & Graham, S.C. (2019). Molecular basis of Cul3 ubiquitin ligase subversion by vaccinia virus protein A55. J. Biol. Chem. 294, 6416-29.
3. Soday, L., Lu, Y., Albarnaz, J.D., Davies, C., Antrobus, R., Smith, G.L., & Weekes, M.P. (2019). Quantitative temporal viromics of vaccinia virus infection reveals regulation of histone deacetylases by a virus interferon antagonist. Cell Reports 27, 1920-33 e7.
4. Lu, Y., Stuart, J.H., Talbot-Cooper, C., Agrawal-Singh, SA., Huntly, B., Smid, A.I., Snowden, J.S., Dupont, L., & Smith, G.L. (2019) Histone deacetylase 4 promotes type I interferon signalling, restricts DNA viruses, and is degraded by vaccinia virus protein C6. Proc. Natl. Acad. Sci. USA 116, 11997-12006.

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