PROTEOTOXNET

Unraveling the cellular responses to aberrantly-folded and aggregated proteins

Coordinatore	EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Switzerland [CH]
Totale costo	1˙500˙000 €
EC contributo	1˙500˙000 €
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-StG
Funding Scheme	ERC-SG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2019-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH  Organization address address: Raemistrasse 101 city: ZUERICH postcode: 8092 contact info Titolo: Prof. Nome: Paola Cognome: Picotti Email: send email Telefono: +41 44 633 25 58 Fax: +41 44 633 12 98	CH (ZUERICH)	hostInstitution	1˙500˙000.00

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 Obiettivo del progetto (Objective)

'Protein aggregation diseases are associated with the intracellular accumulation of specific misfolded protein aggregates, that are directly implicated in cellular dysfunction. A range of human disorders of previously unknown nature now falls into this category. The mechanisms of aggregation-induced cell degeneration are however unclear, resulting in poor therapeutic strategies. In this project we will characterize the network of cellular responses to a set of disease-related aggregation-prone proteins (APPs) and determine how to efficiently modulate proteotoxicity. In a discovery phase, we will use proteome-wide screens to identify functional modules that sequentially respond to APP aggregation. A novel method to probe conformational changes of proteins in their biological matrix will be applied to quantify concomitant changes in APP conformation during the toxicity cascade. Our eminently quantitative approach will allow us to characterize the kinetics of intracellular aggregate formation and the resulting cellular responses. A set of biological markers for different functional modules and toxicity stages will be measured using a selected reaction monitoring-fingerprint assay, through a set of genetic and chemical modulators of proteotoxicity. This will unravel how modulators rewire or compensate for the deregulated networks and suggest their most efficient combinations. The multi-level information will be iteratively integrated with prior data and network structure. Emerging hypotheses will be tested using a combination of genetic and biochemical tools and targeted proteomic experiments. This project features novel concepts and methods and will allow us to unravel the molecular events accompanying the onset of proteinopathies and their modulation. It will positively impact biomedical research on protein aggregation diseases, guide identification of suitable therapeutic strategies and advance our understanding of the biology of protein aggregation.'