The relatively small coding capacity of RNA viruses means that most, if not all, have evolved a variety of transcriptional and/or translational mechanisms that diversify their coding repertoire such that one gene can produce multiple different polypeptides, often from overlapping open reading frames (ORFs). Typically, each virus gene will produce a major polypeptide species, often essential for virus replication, while the variants are produced in lower abundance, are non-essential for replication but can modify viral pathogenicity and/or transmission. Furthermore, the high evolutionary rate of RNA viruses means that these accessory ORFs appear or disappear between closely related viruses, following the same evolutionary pathways for gene birth and death as proposed for DNA genomes (1,2). In turn, this suggests the hypothesis that these relatively rapid changes in viral coding strategy reflect adaptation to new environments, in particular following host jumps. This project aims to test this hypothesis using influenza A virus as a test bed, focusing on looking for signatures of positive or negative selection in overlapping ORFs suspected to encode accessory proteins because of mass spectrometric peptide “hits” . The bioinformatics methodologies used will be based on phylogenetics, Bayesian analyses (BEAST) and dN/dS measurements. In parallel, underpinned by the bioinformatics, “wet-lab” experiments will test for expression of known or suspected accessory gene proteins and, where found, will examine their function in sub-viral and viral reverse genetics systems. The successful candidate will thus gain interdisciplinary expertise in bioinformatics (including R scripting and cluster computing) and viral molecular biology. Aspects of synthetic biology will also be used to create recombinant viruses.
Application procedures:
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) http://www.eastscotbiodtp.ac.uk/how-apply-0 .
EASTBIO Application and Reference Forms can be downloaded via http://www.eastscotbiodtp.ac.uk/how-apply-0
Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [Email Address Removed]
You should also ensure that two references have been send to [Email Address Removed] by the deadline using the EASTBIO Reference Form.
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