New project to explore ‘hidden world’ of proteins

A new project that will harness ground-breaking technologies to analyse individual proteins and decipher the complexity of bacterial communication has been awarded £5.5m by the BBSRC.

Due to begin this year and continue for five years, the project is being led by researchers from the University of Oxford in collaboration the University of Liverpool’s Centre for Proteome Research and the Wellcome Sanger Institute.

Professor Claire Eyers is part of the multidisciplinary team, which aims to develop and apply a novel approach for identifying proteins and their common modifications. Seemingly subtle protein modifications, such as phosphorylation, can drastically alter a protein’s function. However, these modifications are difficult to detect with existing technology – meaning they remain largely hidden. The new approach will help scientists understand how proteins function in health and disease.

The team’s approach leverages three technologies developed by members of the team: nanopore, electrometry and mass photometry. These technologies are already used individually to extract different types of valuable information about biomolecules, including their mass and electric charge.

The team will apply their approach to study the role of phosphorylation in individual bacteria – where the most common forms of phosphorylation tend to be more unstable and difficult to detect with existing methods. This work will enable improved understanding of microbial life, helping better combat infection and antimicrobial resistance.

Project lead Professor Justin Benesch, from the University of Oxford’s Department of Chemistry, said: “Proteins carry out the processes of life, yet harbour much complexity that current technologies cannot detect. Our approach should reveal much of this, and we really look forward to exploring what we will uncover.”

Professor Claire Eyers, Director of the Centre for Proteome Research, said: “This is a fantastic opportunity that will allow us to explore the multitude of differentially modified protein species that contribute to regulating functional responses, not only in pathogenic bacteria, but to all forms of life.”

The project was awarded a Strategic Longer and Larger (sLoLa) grant by the BBSRC. The sLoLa programme is designed to support frontier research that will address significant fundamental bioscience questions and improve our understanding of the fundamental ‘rules of life’. This project was one of just four chosen for funding.

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