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PRIMES: Protein interaction machines in oncogenic EGF receptor signalling

Objetivo

PRIMES focuses on the role of protein interactions to assemble dynamic molecular machines that receive and process information to coordinate cellular responses. PRIMES investigates the following: (i) How do protein interactions contribute to the generation of biological specificity in signalling? (ii) How do pathogenetic perturbations affect protein interaction networks? (iii) How can we exploit protein interactions as therapeutic targets? We focus on the EGFR/ERBB signalling network and its role in colorectal cancer (CRC), the third most frequent cancer. The ERBB network is frequently altered in CRC either through overexpression or mutation of the receptors or downstream components. Network components have become important drug targets. Poor response rates and resistance demonstrate we lack sufficient insight to design efficacious therapies. Using proteomics, structural biology, advanced imaging and mathematical modelling we (i) map static and dynamic protein interactions in the ERBB network (ii) unravel the design principles and emergent network properties conferred by protein interactions; and (iii) validate these findings in genetic mouse models of CRC and human tissues. PRIMES aims to (i) enhance the functional pathogenetic understanding of CRC (ii) identify mechanisms of drug resistance and drug efficacy; and (iii) identify drugs that affect protein interactions to rationally manipulate network functions related to individual genetic mutations. Outcomes include (i) a dynamic, mechanistic flowchart of how protein interactions compute biochemical and biological specificity in signalling networks (ii) a functional protein interaction network of healthy and oncogenic ERBB signalling validated in mouse models of CRC and human tissues (iii) network level insights towards personalised CRC treatment based on genotype-phenotype relationships; and (iv) chemical compounds targeting protein interactions to restore normal ERBB network function or break oncogenic circuits.

Convocatoria de propuestas

FP7-HEALTH-2011-two-stage
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Coordinador

UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Dirección
Belfield
4 Dublin
Irlanda

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Donal Doolan (Mr.)
Aportación de la UE
€ 2 226 380

Participantes (13)

TEAGASC - AGRICULTURE AND FOOD DEVELOPMENT AUTHORITY
Irlanda
Aportación de la UE
€ 309 667
Dirección
Oak Park
R93 Carlow

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Dowling Anne (Ms.)
THE UNIVERSITY OF EDINBURGH
United Kingdom
Aportación de la UE
€ 810 300
Dirección
Old College, South Bridge
EH8 9YL Edinburgh

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Angela Noble (Ms.)
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Aportación de la UE
€ 753 996
Dirección
Wellington Square University Offices
OX1 2JD Oxford

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Stephen Conway (Dr.)
BEATSON INSTITUTE FOR CANCER RESEARCH LBG
United Kingdom
Aportación de la UE
€ 853 000
Dirección
Switchback Road Garscube Estate
G61 1BD Bearsden

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Tipo de actividad
Research Organisations
Contacto administrativo
Peter David Winckles (Mr.)
FUNDACIO CENTRE DE REGULACIO GENOMICA
España
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€ 833 440
Dirección
Carrer Doctor Aiguader 88
08003 Barcelona

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Tipo de actividad
Research Organisations
Contacto administrativo
Stefan Ponisch (Mr.)
EBERHARD KARLS UNIVERSITAET TUEBINGEN
Alemania
Aportación de la UE
€ 980 000
Dirección
Geschwister-scholl-platz
72074 Tuebingen

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Christine Augustin
JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN
Alemania
Aportación de la UE
€ 766 560
Dirección
Theodor W Adorno Platz 1
60323 Frankfurt Am Main

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Mareike Schmitt (Ms.)
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Alemania
Aportación de la UE
€ 885 750
Dirección
Hofgartenstrasse 8
80539 Munchen

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Research Organisations
Contacto administrativo
Barbara Dobruchowski (Ms.)
KUNGLIGA TEKNISKA HOEGSKOLAN
Suecia
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€ 893 440
Dirección
Brinellvagen 8
100 44 Stockholm

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Åke Eriksson (Mr.)
UPPSALA UNIVERSITET
Suecia
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€ 1 186 998
Dirección
Von Kraemers Alle 4
751 05 Uppsala

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Erik Ullerås (Prof.)
VICHEM CHEMIE KUTATO KORLATOLT FELELOSSEGU TARSASAG
Hungría
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€ 1 000 110
Dirección
Viola Utca 2
8200 Veszprem

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Tipo de actividad
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contacto administrativo
Zoltán Dobai (Mr.)
THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO
Canadá
Dirección
Kings College Circle 27
M5S 1A1 Toronto

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Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Igor Stagljar (Prof.)
South Australian Health and Medical Research Institute
Australia
Aportación de la UE
€ 499 999
Dirección
121 King William Street Level 9
5000 Adelaide

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Tipo de actividad
Research Organisations
Contacto administrativo
Terence Dear (Prof.)