Spatial organisation of the genome

Spatial organisation of the genome

Research in our group is focussed on understanding the relationship between the three-dimensional folding of the genome and its functional outputs such as gene transcription. Previous research from group members has shown that the genome is organised into distinctly folded modules, or “topological domains”, which closely mirror the patterns of epigenetic marks (e.g. histone modifications) on the underlying chromatin fibre. This suggests an intimate relationship between gene expression and chromosome folding, although it is unclear if chromatin structure is a cause or consequence of gene activity. Using T cell development and mouse ES cells as model systems, we study the genomic conformations throughout the large-scale epigenetic and gene expression changes accompanying cellular differentiation. We aim to assess if, and how, chromosome folding can influence transcription. Our work will show how programmes of genes can be co-ordinately regulated, but will also provide insights into pathologies such as cancers, and by engineering autonomous chromatin domains, may also provide tools for gene therapy.