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Nanoliter-Scale NMR of Biomolecule Solutions using Dynamic Nuclear Polarization

Project description

Dynamic nuclear polarisation-enhanced NMR of nanolitre-scale biomolecule solutions

Dynamic nuclear polarisation (DNP) is a technique used to enhance the sensitivity of nuclear magnetic resonance (NMR) signals. Although compatible with both solid- and liquid-state samples, direct DNP in solutions has never been demonstrated for biomolecules. The ERC-funded LiquidStateDNP project aims to make this possible and enable DNP spectroscopy of biomacromolecules in solution volumes as small as a few hundred nanolitres, impossible even with traditional NMR techniques. LiquidStateDNP aims to enable use of the ‘solid-effect mechanism’ at room temperature and high magnetic fields. This mechanism has been used in solids for over 50 years but has rarely been used in liquids. Success will open the door to previously inaccessible biological applications at the nanolitre scale and under physiological conditions.

Objective

Dynamic nuclear polarization (DNP) is an exciting and rapidly developing field in magnetic resonance, with solid-state and dissolution DNP techniques emerging as powerful tools across various applications, ranging from materials science to medicine. However, direct DNP in solutions still suffers from a lack of general applicability to macromolecules. The LiquidStateDNP project aims to establish DNP spectroscopy in the liquid state as an innovative tool for chemistry and biology, enabling the analysis of biomacromolecules with small sample volumes as low as a few hundred nanoliters – an achievement beyond the capabilities of traditional NMR techniques. This research will focus on using the solid-effect mechanism at high magnetic fields and room temperature, which offers significant potential for investigating a wide range of molecules. Notably, the solid-effect mechanism exhibits a favorable dependence on the molecular weight of the analyte, becoming increasingly effective for larger macromolecules. To achieve the project’s goals, I will pursue the following objectives: (i) develop a DNP probehead with improved signal sensitivity and resolution; (ii) establish methodologies for various nuclei, including ¹H, ¹³C, ¹⁹F, and ³¹P; (iii) optimize the structure of polarizing agents to maximize their effectiveness in solid-effect DNP; and (iv) demonstrate the application of liquid-state DNP to biomolecules for the first time. This will involve monitoring ligand binding to nucleic acids or proteins, investigating the dynamics of native membranes, and conducting in-cell NMR studies on living cells to detect drug binding and penetration. The LiquidStateDNP project aims to develop an innovative tool for liquid-state NMR, unlocking fundamentally new opportunities for a variety of biological applications at the nanoliter scale under physiological conditions.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-STG

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Host institution

JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN
Net EU contribution
€ 1 499 950,00
Address
THEODOR W ADORNO PLATZ 1
60323 Frankfurt Am Main
Germany
Region
Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 499 950,00

Beneficiaries (1)