Understanding mammalian interphase genome structure in mouse embryonic stem cells

The nucleosome remodeling and deacetylation (NuRD) protein complex is thought to play a key role in controlling the way our genomes are packaged inside the cell, and whether particular genes are expressed. The NuRD complex controls gene expression as embryonic stem (ES) cells first start to differentiate into the different types of cells in the body.

We will conduct an inter-disciplinary research programme to study the structures of intact genomes in single cells, how genome structure is controlled by the NuRD complex, and how this changes during the early stages of differentiation. We will also attempt to develop small molecule inhibitors of NuRD complexes to control chromatin structure.

Our long-term goal is to use our findings to control the differentiation of stem cells. This could be applied to either ES cells, or adult cells that have been induced to become stem cells – induced pluripotent stem cells (iPS). It has enormous potential for providing a source of human tissue to study disease progression or to develop drugs for personalised molecular therapies. Our research may help our ability to directly influence gene expression profiles, stem cell differentiation and disease.