Understanding the 3D structure of gene promoters

In mammalian cells, gene promoters are the sites of transcriptional initiation and crucial for gene expression. Studies over many years have investigated DNA sequence components that are important for gene transcription, histone modifications and accessory proteins. This information is often presented in a “linear” or two-dimensional format, but this belies the underlying 3D architecture and dynamics of gene promoters in cells. In this project we will use techniques we have developed in the lab to investigate the 3D structure of gene promoters. This research is though on the cusp of what is experimentally feasible, we will therefore work closely with colleagues in the School of Physics to build polymer models of promoters. This virtuous cycle of modelling and experimental analysis will enable us to develop new hypotheses that we can experimentally test, but more importantly provide insight into the factors that are most likely to be important for the evolution of gene promoter structure. Finally, we will investigate clinical mutations that occur in gene regulatory regions to understand why these molecular changes provide cells with a selective advantage in diseases like cancer, and relate gene structure, to function and disease.