BIOSPEC

How biochemical networks encode biological specificity: Modulation of cell migration by isoform specific ERK and Akt signaling

Coordinatore	UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN    more  Organization address address: BELFIELD city: DUBLIN postcode: 4 contact info Titolo: Ms. Nome: Lauren Cognome: Montague Email: send email Telefono: +353 1 716 6832 Fax: +353 1 716 6856
Nazionalità Coordinatore	Ireland [IE]
Totale costo	181˙350 €
EC contributo	181˙350 €
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-IIF-2008
Funding Scheme	MC-IIF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-03-02   -   2011-03-01

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN  Organization address address: BELFIELD city: DUBLIN postcode: 4 contact info Titolo: Ms. Nome: Lauren Cognome: Montague Email: send email Telefono: +353 1 716 6832 Fax: +353 1 716 6856	IE (DUBLIN)	coordinator	181˙350.77
2	The Beatson Institute for Cancer Research  Organization address address: "GARSCUBE ESTATE, SWITCHBACK ROAD" city: GLASGOW postcode: G61 1BD contact info Titolo: Ms. Nome: Montague Cognome: Lauren Email: send email Telefono: 35317166832 Fax: 35317166856	UK (GLASGOW)	participant	0.00

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 Obiettivo del progetto (Objective)

'Understanding how biochemical signaling networks encode biological specificity is a fundamental challenge for biologists in the 21st century. Genome sequences by providing the “parts list” for such signaling networks, were expected to advance insight. However, it has become clear that to understand specificity analyzing only the “parts list” is not enough; it is the complex orchestration of these parts’s expression, interactions, activation, and deactivation in both space and time that encode biological specificity. Thus, understanding the biological specificity code requires investigating the spatiotemporal dynamics of biochemical signaling networks. This proposal focuses on understanding how the spatiotemporal dynamics of epidermal growth factor (EGF) gradient-induced signaling and associated feedback loops encode a cell’s decision to migrate and invade. A particular focus is on the isoform-specific roles of ERK1, ERK2, Akt1, and Akt2. Traditionally, these protein isoforms have been assumed to have very similar roles in the phenotypic response to EGF signaling. However, our preliminary data show that these isoforms have very distinct, opposing roles for control of EGF gradient-induced cell migration in an aggressively migrating mammalian cell line. To measure, interpret, and understand EGF gradient-induced signaling and the resultant cell migration, we propose using an interdisciplinary, systems biology approach combining modern biochemistry, quantitative mass spectrometry, live-cell imaging, spatially-resolved mechanistic modeling, and empirical data-driven modeling. Model-based experimental design will be the hub that connects modeling with experiments through an iterative model building cycle. As result we hope to gain a mechanistic understanding of how EGF gradient signals are spatially propagated through a cell, coupled with the ability to predict cell migration outcomes based on the spatiotemporal signaling patterns.'