How genome composition of a virus impacts virus-host interaction
The genome compositions of RNA viruses have, through evolution, been fine tuned to mimic genome signatures of the hosts they infect. This mimickry allows viruses to usurp host cell machinery, such as translational and splicing scaffolds, for their own replication.
As a specific example of how viral genetic information mimics the genome composition of the host, RNA viruses suppress CpG dinucleotide presentation. We can exploit these patterns; modifying the dinucleotide composition of a virus is now being explored as a vaccine development strategy.
This project will use large scale screening approaches to identify cellular factors important during the replication of wildtype and dinucleotide modified viruses, including influenza A virus and rotavirus. Identification and characterisation of cellular factors important in restricting the replication of dinucleotide modified viruses will inform new vaccine development and drug targeting strategies.
Through this project you will learn basic virology techniques such as reverse genetics to artifically synthesise mutant viruses, plaque assays to calculate how much infectious virus is present and how to characterise the replication fitness of a virus. You will learn basic molecular biology techniques such as western blotting for protein detection and RT-qPCR for quantification of the amounts of viral RNAs produced during infection. You will generate and analyse complex datasets from large scale screening and undertake detailed analysis and critical thinking to deconvolute mechanisms and pathways which are important for virus replication.
This project is ideally situated as a collaborative effort between the Gaunt lab, who are very experienced working with RNA viruses and in dinucleotide modification, and the Grey lab, who have extensive experience in virological large scale screening approaches.
For further information about the project please contact Elly Gaunt: [Email Address Removed].
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 2020 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships
3.5 year PhD
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.
All applicants should also apply through the University's on-line application system for September 2020 entry via
Gaunt ER, Wise H, Atkinson N, Zhang R, Beard P, Quigg-Nicol M, Dutia B, Digard P, Simmonds P. Elevation of CpG frequencies in influenza A genome attenuates pathogenicity but enhances host response to infection. eLife 2016 Feb 16 e12735.
Lee CH, Griffiths S, Digard P, Pham N, Auer M, Haas J, Grey F. Asparigine deprivation causes a reversible inhibition of human cytomegalovirus acute virus replication. mBio 2019 01651-19.