Award details

Absolute quantification of SARS-CoV-2 proteins and their human targets for informing drug strategies and accelerating vaccine development

Reference	BB/V013866/1
Principal Investigator / Supervisor	Professor Martin Buck
Co-Investigators / Co-Supervisors	Dr Jorg Schumacher
Institution	Imperial College London
Department	Life Sciences
Funding type	Research
Value (£)	320,378
Status	Completed
Type	Research Grant
Start date	09/11/2020
End date	08/11/2021
Duration	12 months

Abstract

unavailable

Summary

Understanding how the SARS-CoV-2 virus is infectious and causes disease requires a deep understanding of how the infectious particle-the virus- assembles from its component parts, and can make copies of itself and then invade cells and humans. We plan to work out how its building blocks-its proteins in particular-are produced, in what form and how much of each is made. To do so, we will use a method that weighs a protein, and counts how many proteins are in a sample from cells infected with the virus. These numbers will inform strategies for vaccine development as well as offer a deeper understanding of how the virus forms. We will use a method called Multiple-Reaction-Monitoring Mass Spectrometry (MRM-MS) with protein standards which we will manufacture in our laboratory. This methodology allows to directly measure absolute protein concentrations in complex biological samples. Our approach has great scope for upscaling, because any drug and vaccine development could adopt and benefit from our methodology. We propose to produce bespoke labelled synthetic protein standards and measure the absolute SARS-CoV-2 proteome, including some post-translational modifications, of (i) the virion (likely 9 proteins); (ii) within infected human cell lines (about viral 29 proteins), (iii) including yet undetected proteins; (iv) alongside key human proteins (19 proteins) the virus interacts with and or are considered drug targets; (v) determine the antigen-antibody ratios following vaccination trials in mice and humans and (vi) provide said standards to other laboratories to enable them to conduct similar analytics.

Committee	Not funded via Committee
Research Topics	Immunology, Microbiology, Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	Covid19 Rapid Response [2020]
Funding Scheme	X – not Funded via a specific Funding Scheme

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