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Transforming single-molecule mass measurement by rotating total internal reflection mass photometry

Project description

Pioneering label-free optical microscopy leveraging total internal reflection

Understanding how biomolecules behave requires the ability to watch them in motion dynamically. With the support of the Marie Skłodowska-Curie Actions programme, the NanoMassPhotometry project aims to develop a pioneering label-free optical microscopy approach to visualise biomolecules in solution with unprecedented detection ability and molecular resolution. To do so, the team will rely on ‘total internal reflection’ to boost optical contrast and suppress background signatures. This phenomenon will be employed for the first time in interferometric microscopy. The resulting technology has the potential to be superior to state-of-the-art mass photometry, opening the door to previously inaccessible studies that can be done using single-molecule mass measurement.

Objective

We aim to develop a novel label-free optical microscopy approach to transform our ability to characterize and quantify biomolecular dynamics and interactions at the single small-molecule level. The core of the technology, termed rotating total internal reflection mass photometry (RoMP), rests on delivering a step change in label-free detection and quantification of light scattering from individual biomolecules in solution. We will achieve this by leveraging the advantages of total internal reflection to boost optical contrast, and suppress background signatures. This will be enabled for the first time in the context of interferometric microscopy through the use of a specifically-designed optical attenuation optic. Compared to the state-of-the-art Mass Photometry (MP), RoMP will transform the quantitative detection limit and improve mass resolution from ~50 kDa to 10 kDa and from 20 kDa to 2 kDa, respectively. These advances will dramatically expand the range and identity of studies that can be performed by single molecule mass measurement, representing an advance comparable to the change in resolution from 15 to 1.5 Angstrom in cryo-electron microscopy over the past decade. The interdisciplinary and complementary aspects foster two-way transfer of optical nano-imaging knowledge between the applicant (illumination-modulated fluorescence microscopy) and the host (detection-modulated label-free mass microscopy), ultimately catalyzing innovative biochemical investigations and their application by a broad user base for maximum impact.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 260 347,92
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
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Total cost

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