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


Institute of Systems, Molecular and Integrative Biology

, Dr Lance Turtle Applications accepted all year round Self-Funded PhD Students Only
Liverpool United Kingdom Biochemistry Cell Biology Microbiology Molecular Biology Nanotechnology Virology

About the Project

Applications will be reviewed until a suitable candidate has been found.

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 contact Dr Edward Emmott on


Funding Notes

The project is open to both European/UK and International students. It is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project.
Assistance will be given to those who are applying to international funding schemes.
The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs.
A fee bursary may be available for well qualified and motivated applicants.
Details of costs can be found on the University website:
View Website

References

1. Meyer et al. (2020) Characterisation of protease activity during SARS-CoV-2 infection identifies novel viral cleavage sites and cellular targets for drug repurposing. bioRxiv, doi: 10.1101/665307
2. Emmott et al. (2019) Polyprotein processing and intermolecular interactions within the viral replication complex spatially and temporally control norovirus protease activity. J. Biol. Chem.294(11):4259-4271
3. Emmott et al. (2017) Norovirus-mediated modification of the translational landscape via virus and host-induced cleavage of initiation factors. Mol. Cell. Proteomics 16(4s1):S215-S229

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