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CONCERT SIGNED

Description of information transfer across macromolecules by concerted conformational changes

Total Cost €

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EC-Contrib. €

0

Partnership

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 CONCERT project word cloud

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

constructs    alignment    summary    describe    molecular    heterogeneity    castration    correlation    report    first    regulates    rate    line    treat    androgen    coupling    structural    labelled    will    dipolar    suffered    experimentally    dyes    drugs    refractory    molecule    activate    instrument    ar    fashion    fascinating    biomolecules    ouml    shape    sensitive    protein    signal    discovery    hormone    residual    disease    allosteric    contained    magnetic    fluorescent    energy    kills    men    solution    resolution    collaborative    transfer    experiments    fluorescence    allostery    exquisitely    complement    precision    resistant    carry    measured    domain    receptor    concert    transduction    phenotype    steric    inter    therapy    cancer    resonance    stage    ensembles    incurable    relies    rster    nuclear    ca    male    biology    conformational    treatment    patients    concerted    therapeutic    spectroscopy    phenomena    single    prostate    biological    descriptions   

Project "CONCERT" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) 

Organization address
address: CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA
city: BARCELONA
postcode: 8028
website: www.irbbarcelona.org

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

 Coordinator Country Spain [ES]
 Total cost 1˙950˙000 €
 EC max contribution 1˙950˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2020-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) ES (BARCELONA) coordinator 1˙950˙000.00

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 Project objective

Signal transduction in biology relies on the transfer of information across biomolecules by concerted conformational changes that cannot currently be characterized experimentally at high resolution. In CONCERT we will develop a method based on the use of nuclear magnetic resonance spectroscopy in solution that will provide very detailed descriptions of such changes by using the information about structural heterogeneity contained in a parameter that is exquisitely sensitive to molecular shape called residual dipolar coupling measured in steric alignment. To show how this new method will allow the study of information transfer we will determine conformational ensembles that will report on the intra and inter-domain concerted conformational changes that activate the androgen receptor, a large allosteric multi-domain protein that regulates the male phenotype and is a therapeutic target for castration resistant prostate cancer, the condition suffered by prostate cancer patients that have become refractory to hormone therapy, the first line of treatment for this disease. To complement the structural information obtained by nuclear magnetic resonance and, especially, measure the rate of information transfer across the androgen receptor we will carry out in a collaborative fashion high precision single molecule Förster resonance energy transfer and fluorescence correlation spectroscopy experiments on AR constructs labelled with fluorescent dyes. In summary we will develop a method that will make it possible to describe some of the most fascinating biological phenomena, such as allostery and signal transduction, and will, in the long term, be an instrument for the discovery of drugs to treat castration resistant prostate cancer, a late stage of prostate cancer that is incurable and kills ca. 70.000 European men every year.

 Publications

year authors and title journal last update
List of publications.
2016 Bahareh Eftekharzadeh, Alessandro Piai, Giulio Chiesa, Daniele Mungianu, Jesús García, Roberta Pierattelli, Isabella C. Felli, Xavier Salvatella
Sequence Context Influences the Structure and Aggregation Behavior of a PolyQ Tract
published pages: 2361-2366, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2016.04.022
Biophysical journal 2020-04-01
2018 De Mol E, Szulc E, Di Sanza C, Martínez-Cristóbal P, Bertoncini CW, Fenwick RB, Frigolé-Vivas M, Masín M, Hunter I, Buzón V, Brun-Heath I, García J, De Fabritiis G, Estébanez-Perpiñá E, McEwan IJ, Nebreda ÁR, Salvatella X.
Regulation of Androgen Receptor Activity by Transient Interactions of Its Transactivation Domain with General Transcription Regulators.
published pages: , ISSN: 0969-2126, DOI:
Structure 2020-04-01
2016 Eva De Mol, R. Bryn Fenwick, Christopher T. W. Phang, Victor Buzón, Elzbieta Szulc, Alex de la Fuente, Albert Escobedo, Jesús García, Carlos W. Bertoncini, Eva Estébanez-Perpiñá, Iain J. McEwan, Antoni Riera, and Xavier Salvatella
EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor
published pages: 2499-2505, ISSN: 1554-8929, DOI: 10.1021/acschembio.6b00182
ACS Chemical Biology 2020-04-01
2017 Laura Cato, Antje Neeb, Adam Sharp, Victor Buzón, Scott B Ficarro, Linxiao Yang, Claudia Muhle-Goll, Nane C Kuznik, Ruth Riisnaes, Daniel Nava Rodrigues, Olivier Armant, Victor Gourain, Guillaume Adelmant, Emmanuel A Ntim, Thomas Westerling, David Dolling, Pasquale Rescigno, Ines Figueiredo, Friedrich Fauser, Jennifer Wu, Jaice T Rottenberg, Liubov Shatkina, Claudia Ester, Burkhard Luy, Holger Puchta, Jakob Troppmair, Nicole Jung, Stefan Bräse, Uwe Strähle, Jarrod A Marto, Gerd Ulrich Nienhaus, Bissan Al-Lazikani, Xavier Salvatella, Johann S de Bono, Andrew CB Cato, Myles Brown
Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.27159
eLife 6 2020-04-01

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