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Definition of a genetic network involved in congenital heart disease

Objective

This application focuses on transcriptional networks that govern the development of a heart region commonly affected by congenital heart disease (CHD). The major goal is to provide the clinical and basic science research communities with a validated list of interconnected genes required for normal heart development. To achieve this goal, we have recruited 6 European groups of scientists strongly committed to CHD research. The participants bring to the consortium significant resources and credible synergy. The entry point for the interrogation and perturbation of cardiogenic gene networks will be the transcription factor Tbx1, the major gene for 22q11.2 deletion syndrome, a common genetic cause of CHD. The project has three specific aims: 1) To define the roles and interactions of T-box transcription factors in cardiac outflow tract (OFT) development. Our hypothesis is that a critical balance of Tbx1, 2, and 3 is required to regulate homeostasis of a specific population of cardiac progenitors and their interactions with non-cardiogenic cells. 2) To define gene networks perturbed in OFT developmental defects. Innovative approaches will identify the transcriptional targets and protein interactors of Tbx1. Candidate genes will be validated in vitro and in vivo using mouse and zebrafish models. In addition, we will perform extensive transcriptome analyses using biopsy material from CHD patients in order to integrate animal and patient data. 3) To integrate gene expression, cell lineage distribution and phenotype data. Normal heart morphology is achieved through a concerted gene expression program and the integration of molecular signals and tissue interactions. Aided by 3-dimensional reconstruction of gene expression patterns and phenotypic information, we will integrate different types of data to develop models of CHD pathogenesis. Teamwork will be enhanced by shared technologies that provide homogeneity and comparability of data between the participating labs.

Field of science

  • /medical and health sciences/clinical medicine/cardiology/paediatric cardiology

Call for proposal

FP7-HEALTH-2007-B
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

FONDAZIONE TELETHON
Address
Via Varese 16/B
00185 Roma
Italy
Activity type
Research Organisations
EU contribution
€ 667 502
Administrative Contact
Irene Mearelli (Ms.)

Participants (6)

University College London
United Kingdom
EU contribution
€ 485 280
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Kent Lee (Mr.)
ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Netherlands
EU contribution
€ 473 877
Address
Meibergdreef 15
1105AZ Amsterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Andre De Graaf
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 322 415
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Stephen Conway (Mr.)
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 471 644
Address
Rue Michel Ange 3
75794 Paris
Activity type
Research Organisations
Administrative Contact
Béatrice Saint-Cricq (Ms.)
Klinik Max Planck Institut für Psychiatrie

Participation ended

Germany
EU contribution
€ 217 001,46
Address
Hofgartenstrasse 8
80539 Muenchen
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Anke Badrow (Ms.)
CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Germany
EU contribution
€ 42 280,54
Address
Chariteplatz 1
10117 Berlin
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Eveline Fräßdorf