Mass-spectrometry-based proteomic analysis of protease activity during SARS-CoV-2 infection

SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, causing tens of millions of infections and hundreds of thousands of deaths globally. While licenced vaccines are likely to appear in the near future, there remain few therapeutic options available to treat COVID-19 disease.

You will build on preliminary and prior data from the Emmott lab on host protein cleavage during SARS-CoV-2 infection. We used mass spectrometry to identify 15 new cellular targets of the viral proteases, 12 of which resulted in a 100-fold drop in viral titres following siRNA inhibition, and several have inhibitors available in clinical use. You will extend and combine this data with cutting-edge single-cell proteomic approaches to study how cleavage events vary between infected cells, and the impact this variation has on the outcome of coronavirus infection at single-cell level, and in vitro and cell-based assays to characterize and validate cleavage.

This project covers both ‘wet-lab’ and computational training. You will receive training in mass spectrometry including N-terminomics, single-cell proteomics (SCoPE2), in vitro and cell-based assays, data analysis in Matlab or R, including merging datasets, and standard cell culture and virological methods for handling SARS-CoV-2.

The project is suited to a student with at least a good B.Sc. Upper Second in Biological or Life Sciences (Especially in virology, biochemistry and systems biology/bioengineering).

If you are interested in applying, please send a CV including details of two referees, and a one-side A4 cover letter covering your experience and motivation to Dr Edward Emmott by the application closing date. Please also direct any informal queries to Dr Emmott at [Email Address Removed]