Skip to main content

PRIMES: Protein interaction machines in oncogenic EGF receptor signalling

Objective

"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."

Field of science

  • /medical and health sciences/clinical medicine/cancer/colorectal cancer
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/molecular biology/structural biology
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance
  • /natural sciences/biological sciences/genetics and heredity/mutation

Call for proposal

FP7-HEALTH-2011-two-stage
See other projects for this call

Funding Scheme

CP-IP - Large-scale integrating project

Coordinator

UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Address
Belfield
4 Dublin
Ireland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 226 380
Administrative Contact
Donal Doolan (Mr.)

Participants (13)

Agricultural Catchments Programme
Ireland
EU contribution
€ 309 667
Address
Oak Park
R93 Carlow
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Dowling Anne (Ms.)
THE UNIVERSITY OF EDINBURGH
United Kingdom
EU contribution
€ 810 300
Address
Old College, South Bridge
EH8 9YL Edinburgh
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Angela Noble (Ms.)
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 753 996
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Stephen Conway (Dr.)
BEATSON INSTITUTE FOR CANCER RESEARCH LBG
United Kingdom
EU contribution
€ 853 000
Address
Switchback Road Garscube Estate
G61 1BD Bearsden
Activity type
Research Organisations
Administrative Contact
Peter David Winckles (Mr.)
FUNDACIO CENTRE DE REGULACIO GENOMICA
Spain
EU contribution
€ 833 440
Address
Carrer Doctor Aiguader 88
08003 Barcelona
Activity type
Research Organisations
Administrative Contact
Stefan Ponisch (Mr.)
EBERHARD KARLS UNIVERSITAET TUEBINGEN
Germany
EU contribution
€ 980 000
Address
Geschwister-scholl-platz
72074 Tuebingen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Christine Augustin
JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN
Germany
EU contribution
€ 766 560
Address
Theodor W Adorno Platz 1
60323 Frankfurt Am Main
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Mareike Schmitt (Ms.)
Klinik Max Planck Institut für Psychiatrie
Germany
EU contribution
€ 885 750
Address
Hofgartenstrasse 8
80539 Muenchen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Barbara Dobruchowski (Ms.)
KUNGLIGA TEKNISKA HOEGSKOLAN
Sweden
EU contribution
€ 893 440
Address
Brinellvagen 8
100 44 Stockholm
Activity type
Higher or Secondary Education Establishments
Administrative Contact
åke Eriksson (Mr.)
UPPSALA UNIVERSITET
Sweden
EU contribution
€ 1 186 998
Address
Von Kraemers Alle 4
751 05 Uppsala
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Erik Ullerås (Prof.)
VICHEM CHEMIE KUTATO KFT
Hungary
EU contribution
€ 1 000 110
Address
Hermann Otto Utca 15
1022 Budapest
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Zoltán Dobai (Mr.)
THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO
Canada
Address
Kings College Circle 27
M5S 1A1 Toronto
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Igor Stagljar (Prof.)
South Australian Health and Medical Research Institute
Australia
EU contribution
€ 499 999
Address
121 King William Street Level 9
5000 Adelaide
Activity type
Research Organisations
Administrative Contact
Terence Dear (Prof.)