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Details of Grant 

EPSRC Reference: EP/Y004604/1
Title: Native ambient mass spectrometry for membrane proteins
Principal Investigator: Cooper, Professor HJ
Other Investigators:
Dafforn, Professor T
Researcher Co-Investigators:
Project Partners:
AstraZeneca Stellenbosch University
Department: Sch of Biosciences
Organisation: University of Birmingham
Scheme: Standard Research
Starts: 01 December 2023 Ends: 30 November 2026 Value (£): 540,666
EPSRC Research Topic Classifications:
Analytical Science Instrumentation Eng. & Dev.
Medical science & disease
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
03 May 2023 EPSRC Physical Sciences Prioritisation Panel - May 2023 Announced
Summary on Grant Application Form
Proteins are large biomolecules that perform all the functions required for life. The myriad roles and uses of proteins are not simply down to their chemical architecture but also the shapes into which they fold. The study of proteins therefore requires a tool capable of characterization at the molecular level, which provides information on both chemical and overall three-dimensional structure. Mass spectrometry is such a tool, and has provided startling insights into the mechanisms by which proteins operate.

This proposal relates to a class of proteins known as membrane proteins. Membrane proteins are entangled with other molecules that make up the cell membrane, indeed need those molecules to maintain their shape. They present a conduit from the outside of a cell to its inner workings, and consequently represent ~ 70% of drug targets for conditions from high blood pressure and heart disease, to stroke and cancer. Membrane proteins can also be hijacked by viruses, facilitating their entry into the cell and again providing a focal point for the development of therapeutics. Despite their potential therapeutic value, structural information on membrane proteins lags behind that available for more accessible proteins because of the challenges of solubilising and maintaining the shape of the protein during analysis.

We have developed native ambient mass spectrometry (NAMS), a tool for molecular analysis of proteins and their interacting partners directly from tissue. NAMS both provides structural information and enables their spatial distribution to be visualised. To date, NAMS has been primarily applied to accessible, soluble proteins. Preliminary data, however, suggest that the approach is also suitable for the imaging and analysis of membrane proteins.

The aim of this proposal is to develop NAMS specifically for membrane proteins. We will design, build and validate a source for NAMS which enables targeted delivery of reagents to facilitate extraction of membrane proteins from tissue. Two approaches for extraction will be investigated: 1) use of solubilising detergents and 2) capture of membrane proteins together with some of the surrounding membrane molecules in a "styrene maleic acid lipid particle" or SMALP. Alternative polymers to styrene maleic acid will also be considered.
Key Findings
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Potential use in non-academic contexts
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Date Materialised
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Further Information:  
Organisation Website: http://www.bham.ac.uk