Despite their huge differences, all the cells in our body (e.g. liver, skin, brain cells) have exactly the same DNA sequence. Unlike the DNA sequence, the pattern of epigenetic chemical marks (epigenome) – an extra layer of information that lies on top of the genome – is unique to each cell type. Epigenomes allow DNA sequences to be interpreted differently and generate diversity of cells. Although it is recognized that epigenetic factors play a crucial role in regulating normal and aberrant gene function, the detailed molecular mechanisms that explain these roles and their effects on genomic structure are not clear.
Increasing evidence suggest that epigenomes regulate gene function by directly transforming the structure of our genome at the nanoscale level. In this project, the student will develop the first multi-scale computational model capable of investigating the connection between epigenomes and regulation of genomic nanostructure. The model will be based on all-atom molecular dynamics simulations, coarse-graining techniques, theory, and experiments from collaborators. Deciphering how epigenetic marks govern the nanostructure of the genome is key for unravelling some of the most basic questions in the physics of life field, such as the physical mechanisms that control gene function. Indeed, this information is needed to improve our ability to predict and manipulate gene behaviour during disease, and ultimately provide the groundwork to develop approaches for diagnosis and treatment.