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Development of high-field DNP-enhanced MAS NMR techniques for structure determination of viral capsids

Objective

The atomic-level characterization of large viral particles is one of the greatest challenges of modern structural biology, as well as a fundamental step for the design of effective antiviral treatments. In viruses, the viral genome (double- or single-stranded RNA or DNA) is associated to multiple copies of a capsid protein, forming predominantly icosahedral or helical architectures. These complex superstructures are often studied by X-ray crystallography and electron microscopy (EM). However, only information at low resolution is usually available from EM, and extended and flexible architectures do not provide single crystals amenable to diffraction studies. Over the last years, solid-state NMR (ssNMR) has developed into a powerful structural tool for studying structure and dynamics of solid biological samples at atomic resolution and is now uniquely positioned to complement diffraction-based techniques for the characterization of large functional assemblies.
However, proteins of large size or that are available in limited amounts are still inaccessible to site-specific NMR studies. Exploiting a unique equipment available in the host institution, the project aims to remove the current bottlenecks and develop improved dynamic nuclear polarization (DNP)-enhanced ssNMR methodology to push forward the limits of applicability of this technique to macromolecular assemblies, opening new avenues to ssNMR in structural biology. Innovative experimental approaches will be developed to overcome the resolution barriers that currently limit the application of high-field DNP, and new spectroscopic tools will be introduced to allow the structure determination of biomolecules under DNP conditions. The effectiveness and versatility of the newly developed methods will be tested on two viral nucleocapsids of different architectures, the icosahedral capsid of non-tailed bacteriophage AP205 and the filamentous, helical nucleocapsid of Measles virus.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

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.

MSCA-IF-EF-ST - Standard EF

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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) H2020-MSCA-IF-2014

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
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.

€ 185 076,00
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.

€ 185 076,00
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