DEATHSWITCHING

Identifying genes and pathways that drive molecular switches and back-up mechanisms between apoptosis and autophagy

Coordinatore	WEIZMANN INSTITUTE OF SCIENCE    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Israel [IL]
Totale costo	2˙500˙000 €
EC contributo	2˙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-2012-ADG_20120314
Funding Scheme	ERC-AG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-03-01   -   2018-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	WEIZMANN INSTITUTE OF SCIENCE  Organization address address: HERZL STREET 234 city: REHOVOT postcode: 7610001 contact info Titolo: Ms. Nome: Gabi Cognome: Bernstein Email: send email Telefono: 97289346728 Fax: 97289344165	IL (REHOVOT)	hostInstitution	2˙500˙000.00
2	WEIZMANN INSTITUTE OF SCIENCE  Organization address address: HERZL STREET 234 city: REHOVOT postcode: 7610001 contact info Titolo: Prof. Nome: Adi Cognome: Kimchi Email: send email Telefono: +972 8 934 2428 Fax: +972 8 931 5938	IL (REHOVOT)	hostInstitution	2˙500˙000.00

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 Obiettivo del progetto (Objective)

'A cell’s decision to die is governed by multiple input signals received from a complex network of programmed cell death (PCD) pathways, including apoptosis and programmed necrosis. Additionally, under some conditions, autophagy, whose function is mainly pro-survival, may act as a back-up death pathway. We propose to apply new approaches to study the molecular basis of two important questions that await resolution in the field: a) how the cell switches from a pro-survival autophagic response to an apoptotic response and b) whether and how pro-survival autophagy is converted to a death mechanism when apoptosis is blocked. To address the first issue, we will screen for direct physical interactions between autophagic and apoptotic proteins, using the protein fragment complementation assay. Validated pairs will be studied in depth to identify built-in molecular switches that activate apoptosis when autophagy fails to restore homeostasis. As a pilot case to address the concept of molecular ‘sensors’ and ‘switches’, we will focus on the previously identified Atg12/Bcl-2 interaction. In the second line of research we will categorize autophagy-dependent cell death triggers into those that directly result from autophagy-dependent degradation, either by excessive self-digestion or by selective protein degradation, and those that utilize the autophagy machinery to activate programmed necrosis. We will identify the genes regulating these scenarios by whole genome RNAi screens for increased cell survival. In parallel, we will use a cell library of annotated fluorescent-tagged proteins for measuring selective protein degradation. These will be the starting point for identification of the molecular pathways that convert survival autophagy to a death program. Finally, we will explore the physiological relevance of back-up death mechanisms and the newly identified molecular mechanisms to developmental PCD during the cavitation process in early stages of embryogenesis.'