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

Bringing together European excellence to uncover the mechanisms at work that determine cell fate.

Barcelona, February 13th, 2012. As life begins, embryonic stem cells start to divide and develop into tissue ("differentiate"). Each stem cell has the potential to differentiate into different types of tissue cells, such as neurons, muscle, or blood cells, and the molecular mechanisms that determine its fate are highly complex. The earliest steps of differentiation are orchestrated by sophisticated and dynamic protein machineries. Two of these are the PRC (Polycomb Repressive Complex) and NuRD (Nucleosome Remodelling and Deacetylase) complexes, which are critical for switching genes off and on at the right time and in the right cell type. Understanding how such complexes determine cell fate is a prerequisite for developing models for diseases (such as for cancer) that can be used both for further research and for developing personalized medicine therapies.

European scientists meet tomorrow in Barcelona to kick off the 4DCellFate project, funded by the European Commission under the FP7 program. 4DCellFate will tackle the question of how the PRC and NuRD complexes function across space (the genome) and time (during differentiation), by applying cutting-edge technologies, such as structural biology, light microscopy, proteomics, high-throughput sequencing, and computational modeling.

To capture all the facets of the complex molecular system, 4DCellFate will also focus on developing innovative methods. The project brings together the highest levels of European multi-interdisciplinary expertise and will profit from a close interaction between academia and industry, with the participation of eight academic labsthree research-intensive small companies, and a large pharmaceutical company. By synergizing their efforts, partners will be able to directly translate fundamental laboratory findings into new research and medical solutions, focusing on developing novel genome editing tools (Horizon Discovery), refined methods for stem cell differentiation (Cellartis), new computational models of disease (CLC bio), and, ultimately, new drugs (GlaxoSmithKline).

In addition to generating new methods and models of disease, the knowledge gained by 4DCellFate will help to develop molecules that better control stem cell differentiation ex vivo (that is, cultured in a dish outside our body). Stem cells hold great potential as a valuable source of human tissue and could be used, for example, to generate a reliable source of a tissue type (for instance, liver) to study disease progression in culture. They could also be used to screen and develop drugs, allowing the questions to be addressed of what has gone wrong in a disease and how can that be ameliorated with small molecule drugs.

The project coordinator, Luciano Di Croce, ICREA Research Professor and group leader at the CRG (Barcelona), is highly optimistic about achieving these ambitious goals, stating: "This network has brought together the optimal mix of expertise, laboratories, techniques, and resources to finally elucidate how the fate of a cell is decided and how to apply this knowledge to regenerative medicine."