PISILENCE

Small RNA-guided complex machinery for epigenetic silencing

Coordinatore	EUROPEAN MOLECULAR BIOLOGY LABORATORY    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Germany [DE]
Totale costo	902˙849 €
EC contributo	902˙849 €
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-2010-StG_20091118
Funding Scheme	ERC-SG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-01-01   -   2016-05-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	EUROPEAN MOLECULAR BIOLOGY LABORATORY  Organization address address: Meyerhofstrasse 1 city: HEIDELBERG postcode: 69117 contact info Titolo: Dr. Nome: Ramesh Shanmughom Cognome: Pillai Email: send email Telefono: +33 4 76207446 Fax: +33 4 76207199	DE (HEIDELBERG)	hostInstitution	902˙849.00
2	EUROPEAN MOLECULAR BIOLOGY LABORATORY  Organization address address: Meyerhofstrasse 1 city: HEIDELBERG postcode: 69117 contact info Titolo: Mrs. Nome: Sonja Cognome: Noss Email: send email Telefono: +49 6221 387 8771 Fax: +49 6221 3878575	DE (HEIDELBERG)	hostInstitution	902˙849.00

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 Obiettivo del progetto (Objective)

'Transposons are parasitic DNA elements that when activated can insert into new genomic locations, leading to genome instability. Animal germlines express a special class of small RNAs called piwi-interacting RNAs (piRNAs) which are implicated in transposon silencing. In mammals, they are believed to promote DNA methylation of transposon-rich genomic regions. Mechanisms of piRNA biogenesis and function are only beginning to be understood. Sequence analysis of piRNAs from a variety of organisms has given rise to working models for piRNA biogenesis and how piRNAs might act as guides for nuclear silencing complexes. However, key components of the pathway, especially those for biogenesis and function, remain to be discovered. Our aim is to identify and characterize new components using a combination of biochemistry, mouse genetics and small RNA bioinformatics. The regulatory potential of posttranslational modification of piwi proteins and their recognition by tudor proteins will be examined. Mouse mutants will be used to study the in vivo role of catalytic activity of piwi proteins in piRNA biogenesis and identify putative targets by transcriptomics approaches. Integrated biochemical and deep-sequencing methods will be applied to understand how small RNAs might guide nulcear silencing machinery to target locations. Finally, in a field that is dependent on model organisms, we propose to develop a cell culture system to study the piRNA pathway and carry out a high-throughput functional RNAi screen for component discovery. This proposal aims to use interdisciplinary approaches in uncovering the biochemical framework in which germline small RNAs function to protect eukaryotic genomes.'