MRNA-DECAY

NMR Spectroscopy of very large complexes: the atomic details of the mRNA degradation machinery

Coordinatore	MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Germany [DE]
Totale costo	1˙966˙800 €
EC contributo	1˙966˙800 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2013-CoG
Funding Scheme	ERC-CG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-05-01   -   2019-04-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.  Organization address address: Hofgartenstrasse 8 city: MUENCHEN postcode: 80539 contact info Titolo: Dr. Nome: Remco Cognome: Sprangers Email: send email Telefono: +49 7071 601 1330 Fax: +49 7071 601 1308	DE (MUENCHEN)	hostInstitution	1˙966˙800.00
2	MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.  Organization address address: Hofgartenstrasse 8 city: MUENCHEN postcode: 80539 contact info Titolo: Mrs. Nome: Antje Cognome: Lemper-Rupp Email: send email Telefono: +49 7071 601307 Fax: +49 7071 601305	DE (MUENCHEN)	hostInstitution	1˙966˙800.00

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 Obiettivo del progetto (Objective)

'The cellular environment is extremely complex and contains thousands of different bio-molecules. To determine how these bio-molecules assemble into a highly organized molecular system has remained a major challenge. Here, we aim to unravel how dozens of proteins assemble into a large molecular machinery that degrades mRNA in an efficient and regulated manner.

On an atomic level, we will determine the static structures of the enzymes involved in the mRNA degradation pathways. In parallel, we will develop and exploit novel methods in NMR spectroscopy to correlate molecular motions with catalytic activity. Especially for the 450 kDa eukaryotic exosome complex, these studies will significantly push the limits of what is currently achievable. On a molecular level, we will reconstitute the mRNA degradation machinery from purified components in a stepwise manner. In this challenging approach, we will use NMR spectroscopy to follow how the enzymes engage in a network of interactions that regulate the mRNA degradation process. These studies will also provide us with the unique possibility to reproduce complex cellular behavior in a well defined and easy to manipulate in vitro system. On a microscopic level the mRNA degradation machinery assembles into cytoplasmic processing bodies. The role of these conserved cellular foci is a matter of debate and we aim to determine both the atomic details that result in this self-organization as well as the catalytic advantages that result from this clustering.

Our study will provide a very detailed and accurate description of how essential and central molecular processes in mRNA degradation are regulated and modulated. The level of detail that we aim to achieve is currently not available for any cellular pathway of such complexity. In that regard, our projects also provide knowledge and methodology required to study additional and complex cellular functions.'