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BOLD-NMR TERMINATED

Biomolecular structures elucidated by cOLD magic angle spinning NMR with dynamic nuclear polarization

Total Cost €

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EC-Contrib. €

0

Partnership

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 BOLD-NMR project word cloud

Explore the words cloud of the BOLD-NMR project. It provides you a very rough idea of what is the project "BOLD-NMR" about.

he    labelled    neurodegenerative    inter    glutamine    amyloid    aggregates    characterization    huntington    abundance    angle    global    tissue    labelling    structure    closed    polyq    fibrillar    suitable    nmr    cryostat    brain    molecular    proved    ultra    facilitated    resolution    nuclear    dynamic    environment    severe    isotopic    vitro    invaluable    native    polarization    2d    dependent    vision    contacts    probes    structures    routinely    demonstrated    implicated    expensive    structural    schemes    mas    hyperpolarization    natural    mechanisms    fibrils    notably    spinning    solution    ult    sensitivity    diffraction    parkinson    13c    methodology    situ    commercially    proteinaceous    distance    technique    uniformly    distances    diseases    dynamical    temperature    alzheimer    combined    poly    resonance    difficulty    toxicity    multiple    fibril    biomolecules    tool    levels    plaque    solid    loop    samples    disease    atomic    rely    significantly    compatible    detecting    limitations    dnp    afford    magnetic    15n    magic   

Project "BOLD-NMR" data sheet

The following table provides information about the project.

Coordinator
COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES 

Organization address
address: RUE LEBLANC 25
city: PARIS 15
postcode: 75015
website: www.cea.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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fax: n.a.

 Coordinator Country France [FR]
 Project website https://sites.google.com/site/dnpgrenoble/home
 Total cost 173˙076 €
 EC max contribution 173˙076 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-04-26   to  2020-04-25

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES FR (PARIS 15) coordinator 173˙076.00

Map

 Project objective

Magic angle spinning solid-state nuclear magnetic resonance (MAS-NMR) has proved to be an invaluable tool in the structural and dynamical characterization at atomic resolution of biomolecules that are not suitable for solution NMR or diffraction studies, notably amyloid fibrils. These proteinaceous aggregates are implicated as the cause of many neurodegenerative diseases, such as Huntington’s, Alzheimer’s, and Parkinson’s diseases. Due to severe sensitivity limitations and the difficulty in detecting long-distance contacts in uniformly 13C/15N labelled systems, the characterization of these fibrils has been carried out in-vitro using multiple expensive samples with specific isotopic labelling schemes. In addition, it has been demonstrated that fibrils can adopt various, environment-dependent structures, which result in different levels of toxicity. The global objective of this proposal is to develop a new approach for the structural characterization at atomic resolution of biomolecules, which will be compatible in a long-term vision with native in-situ samples, as for example fibrillar plaque obtained from brain tissue. This would be invaluable in understanding the mechanisms of fibril formation in neurodegenerative diseases. The concrete approach will rely on the use of samples at natural isotopic abundance studied with an emerging hyperpolarization technique ULT-MAS-DNP (Magic Angle Spinning Dynamic Nuclear Polarization at Ultra Low Temperature). The sensitivity of the commercially available MAS-DNP technique will be significantly improved by the combined use of a unique closed-loop He cryostat (allowing ULT) with high-spinning NMR probes. This will routinely afford the sensitivity required for 13C/15N 2D NMR measurements on natural isotopic abundance samples, including the facilitated measurement of inter-molecular distances. This methodology will be applied to solve the structure of challenging poly- glutamine (polyQ) fibrils implicated in Huntington’s disease.

 Publications

year authors and title journal last update
List of publications.
2019 Adam N. Smith, Katharina Märker, Sabine Hediger, Gaël De Paëpe
Natural Isotopic Abundance 13 C and 15 N Multidimensional Solid-State NMR Enabled by Dynamic Nuclear Polarization
published pages: 4652-4662, ISSN: 1948-7185, DOI: 10.1021/acs.jpclett.8b03874
The Journal of Physical Chemistry Letters 10/16 2020-04-11
2018 Adam N. Smith, Katharina Märker, Talia Piretra, Jennifer C. Boatz, Irina Matlahov, Ravindra Kodali, Sabine Hediger, Patrick C. A. van der Wel, Gaël De Paëpe
Structural Fingerprinting of Protein Aggregates by Dynamic Nuclear Polarization-Enhanced Solid-State NMR at Natural Isotopic Abundance
published pages: 14576-14580, ISSN: 0002-7863, DOI: 10.1021/jacs.8b09002
Journal of the American Chemical Society 140/44 2020-04-11

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