Dissecting structural and functional contributions of promoter interactions in gene regulation

Understanding how complex multicellular organisms, made up from trillions of cells within multiple tissues, develop from a single fertilised egg requires turning specific genes on and off at the right place and time, in a pre-determined order. The entire process is encoded within the DNA sequence of the genome in each individual cell.

In humans, there are about 20,000 genes, which encode functional units such as enzymes or haemoglobin, but these only constitute 1-2% of the DNA sequence in each cell. The DNA also contains surrounding regulatory elements that control the output of genes. There are 3 classes of such elements: promoters, enhancers and boundary elements.

It is becoming increasingly clear that the roles of these elements overlap one another. In this work, I will study the characteristics of promoter interactions and the resulting impact on gene regulation.

I will be particularly interested in how promoters control gene expression by changing the three-dimensional architecture of the genome as well as the conditions by which promoters interact with enhancers.

Ultimately understanding the process of gene expression will enable us to understand how these genes are normally switched on and off during development and how this goes awry in human disease.