Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesphysical sciencesopticsmicroscopyelectron microscopy
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesmolecular biologystructural biology
Invito a presentare proposte
FP7-HEALTH-2011-two-stage
Vedi altri progetti per questo bando
Meccanismo di finanziamento
CP-IP - Large-scale integrating projectCoordinatore
08003 Barcelona
Spagna
Mostra sulla mappa
Partecipanti (12)
CB2 1TN Cambridge
Mostra sulla mappa
1165 Kobenhavn
Mostra sulla mappa
Partecipazione conclusa
3584 CX Utrecht
Mostra sulla mappa
2000 Antwerpen
Mostra sulla mappa
69117 Heidelberg
Mostra sulla mappa
80539 Munchen
Mostra sulla mappa
20121 Milano
Mostra sulla mappa
CB25 9TL Cambridge
Mostra sulla mappa
8000 Aarhus
Mostra sulla mappa
Partecipazione conclusa
413 46 Göteborg
Mostra sulla mappa
TW89GS Brentford
Mostra sulla mappa
6525 XZ Nijmegen
Mostra sulla mappa