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EASTBIO: Evolutionary dynamics of SARS-CoV-2 accessory genes


College of Medicine and Veterinary Medicine

, Wednesday, January 06, 2021 Competition Funded PhD Project (Students Worldwide)

About the Project

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 Severe Acute Respiratory Syndrome coronaviruses (SARS-CoV) and influenza A virus as test beds, focusing on looking for signatures of positive or negative selection in overlapping ORFs suspected to encode accessory proteins. 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.

Funding information and 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

You should also ensure that two references have been send to by the deadline using the EASTBIO Reference Form.

Funding Notes

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 important that we know from the outset which fees status category applicants fall under when applying to our university.

Please refer to UKRI (View Website ing-people-and-skills/find-studentships-and-doctoral-training/get-a-studentship-to-fund-your-doctorate/) and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria (View Website).

References

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
2. 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

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