NEW POLARITY FACTORS

Discovering New Determinants of Epithelial Cell Polarity

Coordinatore	more  Organization address address: The Old Schools, Trinity Lane city: CAMBRIDGE postcode: CB2 1TN contact info Titolo: Ms. Nome: Edna Cognome: Murphy Email: send email Telefono: +44 1223 333543 Fax: +44 1223 332988
Nazionalità Coordinatore	Non specificata
Totale costo	0 €
EC contributo	0 €
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)
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-10-01   -   2011-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE  Organization address address: The Old Schools, Trinity Lane city: CAMBRIDGE postcode: CB2 1TN contact info Titolo: Ms. Nome: Edna Cognome: Murphy Email: send email Telefono: +44 1223 333543 Fax: +44 1223 332988	UK (CAMBRIDGE)	coordinator	246˙983.34

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 Obiettivo del progetto (Objective)

'Multicellularity requires the organization of cells into specialized tissues. Cells that make up epithelial tissue are polarized; distinct outer (apical) and inner (basal) faces are central to their purpose. Previous studies in animal and cell culture model systems have revealed a number of polarity determinants that act coordinately to establish and maintain epithelial cell polarity under normal conditions. Recent work in Drosophila melanogaster has demonstrated that under starvation conditions, normal polarity signaling is not sufficient; activation of a distinct low-energy polarity pathway is required to maintain polarity. This low-energy polarity pathway is mediated by the LKB1-AMPK signaling module, which acts as a sensor of energy availability. Additional components of the pathway include dystroglycan and the growth regulator TOR, which are not required for epithelial cell polarity except under starvation conditions. Intriguingly, LKB1, AMPK1, dystroglycan, and TOR are all associated with incidence or progression of human epithelial cancers. These findings reveal important, yet unexplored connections between cell polarity, energy-dependent signaling, and cancer. A critical step in the investigation of these links is the identification of additional factors mediating both the low- and normal energy polarity pathways. Large-scale reverse genetic screening in Drosophila provides a powerful, new, and comprehensive approach to this problem. Recent advances in RNAi technology enhance and streamline the screening process, allowing for multiple targeted questions to be addressed. Accordingly, the aims are as follows: Aim 1: Identify novel factors involved in regulating epithelial cell polarity under low-energy conditions. Aim 2: Identify factors required for polarity under normal but not low-energy conditions.'