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

Objetivo

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.

Ámbito científico

Programa(s)

Tema(s)

Convocatoria de propuestas

FP7-HEALTH-2011-two-stage
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Régimen de financiación

CP-IP - Large-scale integrating project

Coordinador

FUNDACIO CENTRE DE REGULACIO GENOMICA
Aportación de la UE
€ 2 935 357,20
Dirección
CARRER DOCTOR AIGUADER 88
08003 Barcelona
España

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Región
Este Cataluña Barcelona
Tipo de actividad
Research Organisations
Contacto administrativo
Mariana Morlans (Ms.)
Enlaces
Coste total
Sin datos

Participantes (12)

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Última actualización: 25 Mayo 2022

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Permalink: https://cordis.europa.eu/project/id/277899/es

European Union, 2024