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Regulation of RNA virus gene expression through modulation of ribosome function

Supervisor: Dr Ian Brierley
Division: Virology
Based at Division of Virology, Addenbrooke’s Hospital
Project title: Regulation of RNA virus gene expression through modulation of ribosome function

Regulation of gene expression at the level of protein synthesis is widespread in viruses and their hosts. We study ribosomal frameshifting, a translational mechanism exploited in the expression of the replicases of many RNA viruses and retroviruses. In this process, mRNA-encoded signals instruct the ribosome to frameshift into an alternative reading frame, generating additional proteins essential to virus replication. Recently, we identified the first examples of frameshifting signals that function only with the participation of regulatory trans-acting proteins, both cellular and viral. This PhD will determine the mechanism of protein-stimulated frameshifting through molecular, cellular, virological and structural biology approaches.

Regulation of RNA virus gene expression through modulation of ribosome function

Recent publications:

Finch LK, Ling R, Napthine S, Olspert A, Michiels T, Lardinois C, Bell S, Loughran G, Brierley I, Firth AE. (2015). Characterization of ribosomal frameshifting in Theiler's murine encephalomyelitis virus. J.
Virol. 89:8580-8589.

Chung, B., Hardcastle, T., Jones, J., Irigoyen, N., Firth, A., Baulcombe D. Brierley, I. (2015). The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-Seq data analysis.
RNA, 21, 1731-1745.

Strnadova, P., Ren, H., Valentine, R., Mazzon, M., Sweeney, T., Brierley, I. and Smith G. (2015). Inhibition of Translation Initiation by Protein 169: a Vaccinia Virus Strategy to Suppress Innate and Adaptive Immunity and Alter Virus 
Virulence. PLoS Pathogens 11, e1005151.

Irigoyen, N., Firth, A.E., Jones, J.D., Chung, B.Y., Siddell, S.G. and Brierley I. (2016). High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling.
PLoS Pathogens 12:e1005473

Napthine, S., Treffers, E.E., Bell, S., Goodfellow, I., Fang, Y., Firth, A.E., Snijder, E.J., Brierley, I. (2016). A novel role for poly(C) binding proteins in programmed ribosomal frameshifting.
Nucleic Acids Res. 44:5491-5503 (NAR Breakthrough article).