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Probing the mechanism of action of Shiftless, a host protein targeting programmed ribosomal frameshifting.


Department of Pathology

Sunday, January 03, 2021 Competition Funded PhD Project (UK Students Only)

About the Project

Many RNA viruses, including HIV and SARS-CoV-2, use a translational mechanism termed programmed ribosomal frameshifting (PRF) to express their replicase enzymes. In frameshifting, interaction of the ribosome with mRNA-encoded signals causes the ribosome to change reading frame and continue translation in the new frame. Recently, a host factor, Shiftless (SFL), was described to play a role in restricting virus replication through inhibition of PRF. In this project, we will determine the mechanism of action of SFL through structural, biochemical, virological and genetic approaches. These studies will be informative about antiviral strategies and further our knowledge of virus gene expression.

Funding Notes

Funding* will cover the student’s stipend at the current Research Council rate and University Fees. The studentship 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 fees

Applications from ineligible candidates will not be considered.

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References

Irigoyen N, Firth AE, Jones JD, Chung BY, Siddell SG, Brierley I. (2016). High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling. PLoS Pathog. 12:e1005473.
Napthine S, Ling R, Finch LK, Jones JD, Bell S, Brierley I, Firth AE. (2017). Protein-directed ribosomal frameshifting temporally regulates gene expression. Nat Commun. 8:15582.
Dinan, AM, Keep S, Bickerton E, Britton P, Firth AE and Brierley I. (2019). Comparative Analysis of Gene Expression in Virulent and Attenuated Strains of Infectious Bronchitis Virus at Subcodon Resolution. J. Virol. 93(18), pii: e00714-19.

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