Overview
In this project, you will be working to understand how coronaviruses replicate, and how this process is shared across multiple coronaviruses. You will learn molecular virology, cell culture assays, and LC-MS/MS proteomics and transcriptomics methods alongside bioinformatic analysis in R.
About this opportunity
Coronaviruses are the causative agents of recent human pandemics and common human and animal diseases. Despite their importance, significant details of the coronavirus life cycle remain unknown. Coronaviruses produce the proteins required for genome replication by translating two long polyproteins: pp1a and pp1ab. Two viral proteases process both polyproteins into the components of the viral replication complex. This proteolytic cleavage results in over 100 theoretical fully and partially-cleaved products. The latter are termed ‘precursors’ and play vital roles in the replication of similar RNA virus families. For the coronaviruses, it has been speculated that early in infection, long partially-cleaved precursors direct antisense RNA synthesis. Late in infection, fully-cleaved polyprotein products direct sense RNA synthesis. However, experimental data and a mechanistic understanding of specific polyprotein cleavage products’ roles is lacking. Understanding this process may pave the way for the next generation of antiviral drugs.
In your PhD, you will work alongside our Wellcome-funded team to study how this process works for human and avian coronaviruses using a range of methods including reverse genetics, molecular biology, RNA sequencing, and LC-MS/MS-based proteomics. You will be based in The Emmott Lab, part of the Centre for Proteome Research, and the Department of Biochemistry, Cell and Systems Biology at the University of Liverpool.