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Introducing deuterium for next generation chemical biology probes and direct imaging

Objective

"The ideal microscopy experiment would take place in native cells without genetic engineering, with 3-dimensional resolution on the single molecule scale (<10 nm) by observing the endogenous molecule itself. I propose the introduction and use of deuterium (“deuterON”) as a general method for a multimodal approach, to i) synthesize a first-in-class deuterated cyanine (Cy) fluorophore for super-resolution imaging, ii) to design and test deuterated, next-level photoswitches to restore vision, and iii) use these probes and deuterated drugs for direct and bioorthogonal, spectroscopic imaging. In particular, deuterated Cys will allow stochastic reconstruction microscopy (STORM) by using near infra-red light to break new ground in protein localization in live tissue, opening the gates for thick sample imaging (~100 m axial) with retained super-resolution (~20 nm). In addition, deuterated azobenzene photoswitches will be designed to finally reach the indispensable, and to-date unobtained light sensitivity to remote control neural signalling in vivo. Lastly, the use of ""label-free"" labelling and imaging will be explored with deuterated drugs to observe drug uptake and metabolism by utilizing the unique properties of the carbon-deuterium bond in Raman spectroscopy. Coupled to a confocal microscope, deuterated drugs will be tracked in native and live cells, without any genetic engineering strategies, and on the molecule of interest itself, reducing perturbations and artefacts to a minimum. This ground-breaking approach holds promise to be generalizable to Chemical Biology disciplines, and as an unconventional, yet attractive and powerful method to design and synthesize next generation small molecule probes. Developing a pipeline for these aims will be a game changer, with ramifications for the life sciences, cell biology, drug development and with prospective translational impact."

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Call for proposal

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(opens in new window) ERC-2021-STG

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Host institution

FORSCHUNGSVERBUND BERLIN EV
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.

€ 1 499 469,00
Address
RUDOWER CHAUSSEE 17
12489 Berlin
Germany

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Region
Berlin Berlin Berlin
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 499 469,00

Beneficiaries (1)

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