About the Project
relatively small coding capacity of RNA viruses means they have evolved a variety of transcriptional and/or translational mechanisms that diversify their coding repertoire so that one gene can produce multiple different polypeptides, often from overlapping open reading frames (ORFs). As one of the largest RNA viruses, coronaviruses (CoVs) follow this principle. Whilst major genes, often essential for virus replication, are expressed from the different subgenomic RNAs, variants are produced in lower abundance, are non-essential for replication but can modify viral pathogenicity and/or transmission. Whilst CoVs have proofreading ability, their relatively high evolutionary rate 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). These relatively rapid changes in viral coding strategy may reflect adaptation to new environments, in particular related to host jumping events. This project aims to test this hypothesis using the two zoonotic-origin Severe Acute Respiratory Syndrome coronaviruses (SARS-CoV-1 and SARS-CoV-2, as well as related animal viruses) as test beds, focussing on the ORF3, 7 and 9 transcription units where gene structure has changed between bat, putative intermediate animal and human hosts. Sub-viral systems based on synthetic DNA will be used to define the suites of polypeptides made, the expression mechanisms that produce them, and their ability to interfere with normal cellular processes in bat and human cells. Viral reverse genetics will then be used to build key mutations that affect expression of potentially functionally important accessory proteins into SARS-CoV-2 to assess the resulting phenotypes in the context of a medically important virus, in vitro and potentially in animal models.
3.5 year PhD
This opportunity is open to UK and international students and provides funding to cover stipend, tuition fees and consumable/travel costs. Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.
Other projects available:
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 10th January 2021 at https://www.ed.ac.uk/roslin/work-study/postgraduate/studentships
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