Identification of interferon stimulated genes that restrict cross-species transmission of influenza A virus
Influenza A virus (IAV) causes major epidemic and pandemic outbreaks in humans and important livestock species such as pigs and chickens. The flow of IAV between poultry, pigs and humans underlies pandemic outbreaks by aiding exchange of genetic material between viruses adapted to these species. However, the occurrence of viral jumps from one species to another is relatively rare due to the difficulty of adapting to a new species.
IFN is an important early host defence to viral infections, with evolutionary differences in IFN response in different species representing a major barrier to zoonotic and epizootic IAV infection and adaptation. We are interested in determining how these differences contribute to the barriers in zoonotic spread and how IAV adapts to overcome these barriers, potentially leading to dangerous pandemic outbreaks.
Systematic analysis using arrayed Interferon Stimulated Gene (ISG) expression libraries have proven a powerful method for identifying key components of the IFN response in human cells [1-3]. We have recently developed genome-wide CRISPR Cas9 knockout libraries for pig and chicken and have secured funding for the generation of ISG libraries in the same species. We aim to use these tools to dissect the role of the IFN factors during zoonotic spread of IAV.
The project aims to identify and characterise species-specific novel host-virus interactions and by comparing screen data between humans, pigs and chickens, further our understanding of the molecular processes involved in zoonotic viral spread.
In addition to gaining a solid foundation in core molecular virology techniques, the project offers the opportunity to gain experience and expertise in cutting-edge, high throughput approaches such as CRISPR-Cas9 gene editing and arrayed lentiviral expression library screening, with results having potentially important implications for our understanding of pandemic IAV outbreaks in humans and animals.
Funding: This project is eligible for a University of Edinburgh 3.5 year PhD studentship.
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.
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 please state clearly the title of the studentship and the supervisor/s in your covering letter.
1 Dittmann, M. et al. A serpin shapes the extracellular environment to prevent influenza A virus maturation. Cell 160, 631-643, doi:10.1016/j.cell.2015.01.040 (2015).
2 Kane, M. et al. Identification of Interferon-Stimulated Genes with Antiretroviral Activity. Cell host & microbe 20, 392-405, doi:10.1016/j.chom.2016.08.005 (2016).
3 Schoggins, J. W. et al. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472, 481-485, doi:10.1038/nature09907 (2011).