CONCERT SIGNED
Description of information transfer across macromolecules by concerted conformational changes
Total Cost €
0EC-Contrib. €
0Partnership
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0CONCERT 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.
Project "CONCERT" data sheet
The following table provides information about the project.
| Coordinator |
FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 2016 |
Bahareh Eftekharzadeh, Alessandro Piai, Giulio Chiesa, Daniele Mungianu, Jesús GarcÃa, 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, MartÃnez-Cristóbal P, Bertoncini CW, Fenwick RB, Frigolé-Vivas M, MasÃn M, Hunter I, Buzón V, Brun-Heath I, GarcÃa J, De Fabritiis G, Estébanez-Perpiñá E, McEwan IJ, Nebreda ÃR, 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 GarcÃa, 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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