About the Project
Subgenomic replicons are viral mini-genomes that facilitate the study of fundamental mechanisms of viral genome replication in the absence of infectious virus and have been established for many RNA viruses. Using random mutagenesis with HEV subgenomic replicons we will dissect regions of the viral genome that are essential for replication as well as locations that are malleable for introduction of genetic tags (eg FLAG, GFP). This approach will pave the way for studies on viral molecular interaction and identify novel roles of the essential non-structural proteins and their precursors (together with biochemistry, labelling techniques and state-of-the-art imaging facilities).
The long-term aim of the work is to use a greater knowledge of the molecular details of viral replication to develop new approaches for disease control and diagnosis.
Please apply online https://studentservices.leeds.ac.uk/pls/banprod/bwskalog_uol.P_DispLoginNon and include a CV and transcripts with your application.
Candidates should have a 2.1 or above (or equivalent) in a relevant area. If English is not your first language, you will need a recognised English Language qualification https://www.leeds.ac.uk/info/123100/admissions/143/entry_requirements
Herod MR, Adeyemi OO, Ward J, Bentley K, Harris M, Stonehouse NJ, Polyak SJ. The broad-spectrum antiviral drug arbidol inhibits foot-and-mouth disease virus genome replication. J. Gen. Virol. doi: 10.1099/jgv.0.001283.
Shawli GT, Adeyemi OO, Stonehouse NJ, Herod MR. The Oxysterol 25-Hydroxycholesterol Inhibits Replication of Murine Norovirus. Viruses. 11(2)ːE97. doi: 10.3390/v11020097.
Herod MR, Gold S, Lasecka-Dykes L, Wright C, Ward JC, McLean TC, Forrest S, Jackson T, Tuthill TJ, Rowlands DJ, Stonehouse NJ. Genetic economy in picornaviruses: Foot-and-mouth disease virus replication exploits alternative precursor cleavage pathways. PLoS Pathog. 3(10):e1006666. doi: 10.1371/journal.ppat.1006666.
Herod MR, Loundras EA, Ward JC, Tulloch F, Rowlands DJ and Stonehouse NJ. (2015) Employing Transposon Mutagenesis to Investigate Foot-and-Mouth Disease Virus Replication. J. Gen. Virol. 96:3507-3518. doi: 10.1099/jgv.0.000306
Herod MR, Jones DM, McLauchlan J, and McCormick CJ. Increasing the rate of Cleavage at the Boundary Between Non-Structural Protein 4B and 5A Inhibits Replication of Hepatitis C Virus. J. Biol. Chem. 287:568-580. doi: 10.1074/jbc.M111.311407.
Goonawardane N, Gebhardt A, Bartlett C, Pichlmair A and Harris M. Phosphorylation of serine 225 in hepatitis C virus NS5A regulates protein-protein interactions. J. Virol 91:e00805-17 2017 doi:10.1128/JVI.00805-17.
Ross-Thriepland D, Harris M. Insights into the complexity and functionality of hepatitis C virus NS5A phosphorylation. J. Virol. 88 1421-1432 2014 doi:10.1128/JVI.03017-13.
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