KINGDOM CELL DEATH

"Autophagic cell death across Kingdoms; using the plant genetic model system Arabidopsis to characterize cell death regulators in animals, with applications for human cancer"

Coordinatore	KOBENHAVNS UNIVERSITET    more  Organization address postcode: 1017 contact info Titolo: Prof. Nome: John Cognome: Mundy Email: send email Telefono: 4528754278 Fax: 4553322128
Nazionalità Coordinatore	Denmark [DK]
Totale costo	212˙823 €
EC contributo	212˙823 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2007-4-2-IIF
Funding Scheme	MC-IIF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-01-01   -   2011-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	KOBENHAVNS UNIVERSITET	DK	coordinator	0.00

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 Obiettivo del progetto (Objective)

'Programmed cell death (PCD) is essential for plant and animal development. PCD is also invoked in pathological physiologies, as inappropriate PCD is implicated in human disease, while PCD is required for the plants innate immune response to pathogens. One type of PCD, macroautophagy, is an intracellular degradation system for cytosolic components and organelles in eukaryotes. The molecular mechanism of autophagy, although extensively studied using yeast during the past decade, remains to be elucidated. Similarly, plants undergo authophagic cell death – the genetically tractable model plant Arabidopsis thaliana represents a superior platform for understanding this process in higher eukaryotes. The recently discovered accelerated cell death 11 (acd11) mutant, a deletion of a sphingolipid transfer protein, exhibits vegetative cell death that is blocked if depleted of the defense molecule salicylic acid. Preliminary data shows that ACD11 and its human homolog FAPP2 suppress autophagy, indicating that they function in a cell death pathway conserved across the eukaryotic kingdoms. This is of extraordinary interest, since it provides a genetic tool to rapidly identify new regulators of human autophagy in Arabidopsis. Therefore, genetic screening and cloning of PCD suppressors from acd11 and related mutants, and the identification of ACD11 interaction partners, will allow us to characterize novel positive and negative regulators of PCD across kingdoms. The identification of the candidate human PCD regulator hsPRA1 by screening for ACD11-interactors in Arabidopsis is an exciting advance and points toward the validity of this approach. Furthermore, truncated versions of FAPP2 accumulate in various cancers. Our goal is to investigate the oncogenic potential of FAPP2 and novel PCD regulators in human autophagy and cancer transformation. Autophagic cell death induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality.'