The human genome was sequenced eighteen years ago . Since then, our understanding of the genome and how it works has advanced rapidly. However, there are still many aspects of the genome which remain poorly understood. The Tremethick lab at JCSMR is particularly focused on the open question of how genomic information is selectively utilised to direct coordinated patterns of gene expression. Our genome is assembled into chromosomes, which are intricate, multilayered three-dimensional (3D) structures in the nucleus. The 3D organisation of a chromosome changes dramatically along its length and these structural differences are thought to be fundamental to gene regulation as they can help or prevent the expression of a gene. However, the nature of these 3D structural differences and how they are assembled remains unresolved.

A landmark study on this topic by the Tremethick lab, together with the laboratory of Collas (University of Oslo) was published in Nature Genetics. This study uncovered the key internal structural elements of a chromosome and how they are modulated to control gene expression. Specifically, by employing a combination of long-range genome mapping experiments and computational 3D genome modelling, it was revealed how active and inactive genes are packaged and segregated into different 3D compartments in a chromosome during the differentiation of human stem cells into adipose or neuronal cells. This study will have important implications in understanding how disease states, such as cancer, arise by revealing the link between rapid and dynamic changes in the 3D genome and changes to cell fate