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Developing a global understanding of the PRC and NuRD complexes in stem cell differentiation, in health and disease

Objective

Embryonic stem (ES) cells have the potential to differentiate into any type of cell as well as to renew indefinitely in culture. They hold great potential for the development of personalized medicines. However, the molecular mechanisms underpinning cell fate decisions by individual cells are poorly understood. There is compelling evidence that two large multi-protein machines, the Nucleosome Remodelling and Deacetylation (NuRD) complex and the Polycomb Repressive Complexes (PRCs), modulate chromatin structure to control stem cell renewal, lineage commitment and differentiation. Moreover, they are clearly implicated in cancer.

The goal of 4DCellFate is to understand how the PRC/NuRD complexes and their plethora of interactions (protein/protein, protein/nucleosome, protein/nucleic acids) regulate cell fate. To obtain this global, quantitative and dynamic – 4D – understanding of the structure/functions of these two multi-protein machines during ES cell differentiation and in different disease states, we propose a large scale multi-disciplinary “data-gathering” approach combining European excellence in interactomics (affinity purification, quantitative mass spectrometry-based proteomics, ChIP-seq analysis, light microscopy), structural biology (X-ray crystallography, NMR, native-state mass spectrometry, Electron Microscopy, biochemistry/biophysics), cellular, tumour, and computational biology. We expect to significantly advance the technology, mainly in the fields of proteomics, structural biology, and small molecule screening, and to make our knowledge, reagents and data publicly available to the scientific community.

The ultimate outcome of 4DCellFate will be to lay the foundations for understanding the role of the PRC/NuRD complexes in ES cell differentiation and cancer, specifically in leukaemogenesis. Three SMEs and one large multi-national pharma will be actively involved ensuring that our findings can be translated into new ways to control complex diseases.

Call for proposal

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

Funding Scheme

CP-IP - Large-scale integrating project

Coordinator

FUNDACIO CENTRE DE REGULACIO GENOMICA
Address
Carrer Doctor Aiguader 88
08003 Barcelona
Spain
Activity type
Research Organisations
EU contribution
€ 2 935 357,20
Administrative Contact
Mariana Morlans (Ms.)

Participants (12)

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 3 184 984,40
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Renata Schaeffer (Ms.)
KOBENHAVNS UNIVERSITET
Denmark
EU contribution
€ 804 300
Address
Norregade 10
1165 Kobenhavn
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Ivan Kristoffersen (Mr.)
UNIVERSITAIR MEDISCH CENTRUM UTRECHT

Participation ended

Netherlands
EU contribution
€ 135 392,79
Address
Heidelberglaan 100
3584 CX Utrecht
Activity type
Higher or Secondary Education Establishments
Administrative Contact
E.Th. Erik Van Den Broek (Mr.)
UNIVERSITEIT ANTWERPEN
Belgium
EU contribution
€ 664 888
Address
Prinsstraat 13
2000 Antwerpen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Anne Adams (Ms.)
EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany
EU contribution
€ 1 274 530
Address
Meyerhofstrasse 1
69117 Heidelberg
Activity type
Research Organisations
Administrative Contact
Genevieve Reinke (Ms.)
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany
EU contribution
€ 779 703
Address
Hofgartenstrasse 8
80539 Munchen
Activity type
Research Organisations
Administrative Contact
Ulrike Jendis (Ms.)
ISTITUTO EUROPEO DI ONCOLOGIA SRL
Italy
EU contribution
€ 622 877,60
Address
Via Filodrammatici 10
20121 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ilaria Foti (Ms.)
Horizon Discovery Limited
United Kingdom
EU contribution
€ 379 100
Address
Cambridge Research Park
CB25 9TL Cambridge
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Christopher Torrance (Dr.)
QIAGEN AARHUS AS
Denmark
EU contribution
€ 572 500
Address
Silkeborgvej 2
8000 Aarhus
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Kenneth G. Johansen (Mr.)
Takara Bio Europe AB

Participation ended

Sweden
EU contribution
€ 40 586
Address
Arvid Wallgrens Backe
413 46 Göteborg
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jenny Goodwin (Ms.)
GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LTD.
United Kingdom
EU contribution
€ 9 000
Address
Great West Road 980
TW89GS Brentford
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Elaine Irving (Dr.)
STICHTING RADBOUD UNIVERSITEIT
Netherlands
EU contribution
€ 579 184,01
Address
Houtlaan 4
6525 XZ Nijmegen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Geurt Van Renselaar (Mr.)