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4DCELLFATE – Developing a global understanding of the PRC and NuRD complexes in stem cell differentiation, in health and disease

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.

  •  2011-12-01  2016-11-30
  • FP7-HEALTH / HEALTH.2011.2.1.1-2 / FP7-HEALTH-2011-two-stage
  • Overall Cost: 16.07 M.Eur
  •   > Cellartis
      > CLC BIO
      > GlaxoSmithKline
      > Horizon Discovery
  • Other project partners
               
  • IT BE UK NL SE DE DK UK 
  • Proteins and their interactions in health and disease 
  • Life Sciences 
  • FP7 Data provision: © European Union; Source: CORDIS, Cordis | This page is not provided by the European Commission 

 cancer   pharma   Development   CRO   protein   Proteomics   purification   Analysis   europe   Screening   cell   technology   medicine   Bio   chemistry   gene   Medicines   NGS   biology   lab   molecular   disease   reagents   stem cell   Mass spectrometry   Small molecule   global   biochemistry   cells   Gen   diseases   reagent   NMR   data   molecule   culture   Personalized Medicine   control   affinity   tumour   genes   microscopy   Screen   omic   develop   Fat   scientific   large scale   nucleic acid   proteomic   ids   Cell differentiation   gent   personalized   press   Agent   interaction   acid   affinity purification   cellular   chip   Structure   medicin   nucleic acids   European   4D   interactions   crystallography   cancer   pharma   Development   CRO   protein   Proteomics   purification   Analysis   europe   Screening   cell   cancer   pharma   Development   CRO   protein   Proteomics   purification   Analysis   europe   Screening   cell   technology   medicine   Bio   chemistry   gene   Medicines   NGS   biology   lab   molecular   disease   reagents   stem cell   Mass spectrometry   Small molecule   global   biochemistry   cells   Gen   diseases   reagent   NMR   data   molecule   culture   Personalized Medicine   control   affinity   tumour   genes   microscopy   Screen   omic   develop   Fat   scientific   large scale   nucleic acid   proteomic   ids   Cell differentiation   gent   personalized   press   Agent   interaction   acid   affinity purification   cellular   chip   Structure   medicin   nucleic acids   European   4D   interactions   crystallography 


 
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