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Imaging Biomolecular Self-Assembly with a Molecular Photonic Scale

Project description

Imaging of biomolecular interactions at the single-molecule level

The EU-funded PHOTOMASS project aims to shed light on biomolecular interactions and self-assembly via direct visualisation of the molecular mechanisms. The research will capitalise on the recent development of mass photometry (MP) by the project partners. MP enables the detection and imaging of single biomolecules in solution as well as the determination of their molecular mass at the single-molecule level. This technology merges the high-resolution structural and low-resolution solution-based methods for studies of biomolecular interactions and assembly. The project leads to a broad range of applications, visualising the mechanism of viral capsid assembly, cytoskeletal dynamics, the amyloid aggregation, and others beyond molecular biophysics.

Objective

We propose to transform our understanding of biomolecular interactions and self-assembly by directly visualising the associated molecular mechanisms. To achieve this, we will capitalise on our recent development of interferometric scattering mass spectrometry (iSCAMS), which enables not only the detection and imaging of single biomolecules in solution, but also the accurate determination of their molecular mass at the single molecule level. These studies, and the development of the associated technology, will bridge the gap between high-resolution structural and low-resolution solution-based methods for studies of biomolecular interactions and assembly. We will achieve these ambitious goals by pursuing five interconnected objectives chosen according to their potential to maximise scientific and societal impact by addressing fundamental questions related to biological function and health: (1) Determine the physicochemical origins of mono- and polydispersity; (2) Visualise the mechanism of viral capsid assembly; (3) Reveal the molecular basis of cytoskeletal dynamics; (4) Capture the aggregation and inhibition of amyloid aggregation. These four system-oriented objectives will be accompanied by a technological objective, (5) aimed at implementing improvements in terms of dynamic range and resolution of iSCAMS required for studying self-assembly. As a consequence of the universal applicability of our approach for characterising molecular interactions, oligomeric distributions and dynamics in a facile fashion in solution, this ambitious project opens up a broad range of exciting applications beyond molecular biophysics in fields as drug-discovery, bioanalytical and biomedical science.

Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution
€ 1 999 574,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 999 574,00

Beneficiaries (1)