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HYPROTIN SIGNED

Hyperpolarized Nuclear Magnetic Resonance Spectroscopy for Time-Resolved Monitoring of Interactions of Intrinsically Disordered Breast-Cancer Proteins

Total Cost €

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EC-Contrib. €

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Partnership

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 HYPROTIN project word cloud

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

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Project "HYPROTIN" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT WIEN 

Organization address
address: UNIVERSITATSRING 1
city: WIEN
postcode: 1010
website: www.univie.ac.at

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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 Coordinator Country Austria [AT]
 Total cost 1˙990˙728 €
 EC max contribution 1˙990˙728 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-STG
 Funding Scheme ERC-STG
 Starting year 2019
 Duration (year-month-day) from 2019-03-01   to  2024-02-29

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT WIEN AT (WIEN) coordinator 1˙990˙728.00

Map

 Project objective

HYPROTIN proposes a pioneering research platform for hyperpolarized magnetic resonance of breast-cancer related proteins that will revolutionize our view on tumorigenesis at the atomic level, through bottom-up reconstitution of medicinal relevant interaction pathways involving the breast cancer susceptibility protein 1 (BRCA1). The risk to develop a hereditary breast or ovarian cancer (HBOC) increases to 55-65 % upon mutation of the BRCA1 gene. Yet, little is known about the biochemistry of tumorigenesis, so that drugs directed towards molecular targets are not satisfactory. To date, mastectomy remains the only preventive treatment. This dramatic lack of knowledge is a consequence of BRCA1 being an intrinsically disordered protein (IDP). Recognizing the importance of IDPs has revolutionized structural biology in the last decade, but this also represents a huge experimental challenge. To date, nuclear magnetic resonance (NMR) is the only technique available to study IDPs at high resolution. However, several limits of the technique must be overcome. Its low sensitivity impedes investigations under biologically meaningful conditions, so that new approaches are required. The HYPROTIN project aims to achieve two methodological goals: 1) Residue-resolved studies of the BRCA1 IDP under physiological conditions; and 2) real-time monitoring of BRCA1-ligand binding, thereby adding a time-resolved dimension to the NMR characterization of IDPs. This systematic approach will provide unprecedented insight into the BRCA1 interactome, provide medically relevant data and residue-resolved protein interaction kinetics. This will open a new knowledge base for rational drug design. The project will employ cutting-edge equipment that is unique worldwide, and will represent the first facility in Europe suited for these ground-breaking experiments. The PI has unique interdisciplinary experience enabling the demanding hyperpolarization approach to IDPs.

 Publications

year authors and title journal last update
List of publications.
2020 Gregory L. Olsen, Or Szekely, Borja Mateos, Pavel Kadeřávek, Fabien Ferrage, Robert Konrat, Roberta Pierattelli, Isabella C. Felli, Geoffrey Bodenhausen, Dennis Kurzbach, Lucio Frydman
Sensitivity-enhanced three-dimensional and carbon-detected two-dimensional NMR of proteins using hyperpolarized water
published pages: 161-171, ISSN: 0925-2738, DOI: 10.1007/s10858-020-00301-5
Journal of Biomolecular NMR 74/2-3 2020-04-15
2019 Sami Jannin, Jean-Nicolas Dumez, Patrick Giraudeau, Dennis Kurzbach
Application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts
published pages: 41-50, ISSN: 1090-7807, DOI: 10.1016/j.jmr.2019.06.001
Journal of Magnetic Resonance 305 2019-09-04
2019 Giuseppe Sicoli, Hervé Vezin, Karin Ledolter, Thomas Kress, Dennis Kurzbach
Conformational tuning of a DNA-bound transcription factor
published pages: 5429-5435, ISSN: 0305-1048, DOI: 10.1093/nar/gkz291
Nucleic Acids Research 47/10 2019-08-05
2019 Thomas Kress, Astrid Walrant, Geoffrey Bodenhausen, Dennis Kurzbach
Long-Lived States in Hyperpolarized Deuterated Methyl Groups Reveal Weak Binding of Small Molecules to Proteins
published pages: 1523-1529, ISSN: 1948-7185, DOI: 10.1021/acs.jpclett.9b00149
The Journal of Physical Chemistry Letters 2019-05-28

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