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Single-cell proteomic analysis of host-factor cleavage during norovirus infection


Project Description

Human norovirus is a major human pathogen, and the causative agent behind ‘winter vomiting disease’. Typically, infection is self-limited, causing diarrhoea and vomiting lasting from 24-72 hours. However there are over 600 million cases of norovirus occurring per year, and 200,000 deaths worldwide. As yet, there are no antivirals or vaccines available to treat or prevent norovirus infection.

Norovirus generates the proteins necessary for its replication through the cleavage of a single long ‘polyprotein’. Cleavage sites within this polyprotein are recognised by both viral and cellular proteases to generate nearly 30 fully- or partially-cleaved products or proteoforms. Partially-cleaved proteoforms can have their own functions in viral replication. One example is how individual proteoforms of the protease can target different host proteins for cleavage. Understanding this process may pave the way for new antiviral strategies to treat norovirus infection.

You will build on preliminary and prior data on different forms of the norovirus protease and how these proteins each target the host cell. This will be combined with the application of 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 norovirus infection at single-cell level.

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

You will primarily be working with Dr Ed Emmott (Twitter: @edemmott, emmottlab.org) at the Centre for Proteome Research, University of Liverpool. (https://www.liverpool.ac.uk/pfg/), in collaboration with Prof. Miren Iturriza-Gomara in the Institute for Global Health. The project is suited to a student with at least a good B.Sc. Upper Second in Biological or Life Sciences (particularly Biochemistry, Virology, or Bioengineering).

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 of £3000 per year.

A fee bursary may be available for well qualified and motivated applicants.

Details of costs can be found on the University website:
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References

1. Specht, Emmott, Perlman, Koller & Slavov (2019) High-throughput single-cell proteomics quantifies the emergence of macrophage heterogeneity. bioRxiv. doi: 10.1101/665307

2. Emmott, de Rougemont, Hosmillo et al. (2019) Polyprotein processing and intermolecular interactions within the viral replication complex spatially and temporally control norovirus protease activity. J. Biol. Chem. 294:4259-4271

3. Emmott, Sorgeloos, Caddy et al. (2017) Norovirus-mediated modification of the translational landscape via virus ad host-induced cleavage of translation initiation factors. Mol. Cell. Proteomics. 16(4 suppl 1): S215-S229

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