EASTBIO: Discovery and evolutionary dynamics of influenza A virus accessory genes at the University of Edinburgh

Supervisors: 

Paul Digard, Samantha Lycett

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.

1. Carvunis, A.-R., Rolland, T., Wapinski, I., Calderwood, M. A., Yildirim, M. A., Simonis, N., et al. (2012). Proto-genes and de novo gene birth. Nature, 487(7407), 370–374. http://doi.org/10.1038/nature11184

1. Pinto, R. M., Lycett, S., Gaunt, E., & Digard, P. (2020). Accessory Gene Products of Influenza A Virus. Cold Spring Harbor Perspectives in Medicine, a038380. http://doi.org/10.1101/cshperspect.a038380

• 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 protected]

• You should also ensure that two references have been send to [email protected]  by the deadline using the EASTBIO Reference Form

This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees.  The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees.

There is a cap on the number of international students the DTP recruits.  It is therefore important for us to know from the outset which fees status category applicants will fall under when applying to our university.

Please refer to UKRI websiteand Annex B of the UKRI Training Grant Terms and Conditionsfor full eligibility criteria.

Closing Date: 16th December 2021