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New routes for magnetic resonance spectroscopy of biomolecules by combining EPR and NMR methods

Project description

The next era of magnetic resonance spectroscopy: insight into enzyme structure and function

Magnetic resonance spectroscopy (MRS) is an analytical technique for studying metabolic changes in the brain due to various diseases. It can complement magnetic resonance imaging (MRI) for a more complete tissue characterisation. The EU-funded BIO-enMR project aims to develop novel magnetic resonance tools that provide structural information on biomolecules not possible to acquire with existing methods. The generated approach is expected to find numerous applications such as the delineation of the molecular mechanisms of enzyme activation as well as enzyme interactions with drugs. Moreover, it will guarantee improved sensitivity and resolution in various analytical processes.

Objective

Detection of magnetic nuclei via magnetic resonance spectroscopy (NMR/EPR) or imaging (MRI) is one of the most important tools to achieve structural and functional information in natural sciences. Latest developments in this field are taking advantage of the larger (about three orders of magnitude) spin polarization of unpaired electrons in paramagnetic molecules to tremendously enhance the sensitivity of nuclear magnetic resonance. However, most protocols still suffer from several bottlenecks and lack of general applicability to bio-macromolecules. This proposal aims at expanding electron-nuclear spin polarization transfer to develop new magnetic resonance tools: 1) EPR-based nuclear spin detection for structural information in the angstrom-to-nanometer scale and 2) hyperpolarized high-field NMR in the liquid state. Research in these two directions will take advantage from concerted investigations of polarization transfer mechanisms and their representative applications to biomolecular systems. Reaching this goal will permit new studies, not feasible with current techniques, for instance understanding the molecular mechanism of enzyme activation, subunits interactions and inhibition in ribonucleotide reductases, which are important targets of cancer drugs. Our laboratory possesses suited expertise and a state-of-the art combination of EPR and NMR instrumentation, by which these questions can be tackled in synergy. The research program encompasses a variety of investigations, from new experimental and instrumental designs up to short and long-term potential applications in biomolecules, for instance in the investigations of enzyme interactions with drugs, which are currently hampered by low sensitivity and resolution. A successful establishment, combined with current progress in magnetic resonance instrumentation, i.e. the age of magnetic resonance in GHz (NMR) and THz (EPR), will offer new opportunities for analytical and biophysical investigations.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2020-ADG

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Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN 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.

€ 2 443 125,00
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
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.

€ 2 443 125,00

Beneficiaries (1)

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