“Polymer physics of cancer genomes”
While every cell in our bodies contains the same genome, different sets of genes are active in different types of cell, and the “switching on and off” of specific genes must be tightly controlled as cells develop. Gene regulation is tightly related to the spatial organisation of the chromosomes within the cell nucleus. A number of physical mechanisms through which this organisation is controlled have been identified, and polymer physics models have proved extremely useful for understanding these. I will present recent work in which polymer models were used to understand genome rearrangements in cancer. There are several methods which the cell employs to repair the genome should the DNA get broken, however these sometimes do not work correctly, and genome rearrangements can arise. For example, two different broken chromosomes could get joined together; this changes the spatial organisation, disrupts gene regulation, and can give rise to disease. Our polymer simulations were able to predict the changes in gene expression which result from genome rearrangements commonly found in B-cell cancers, shedding light on this poorly understood process. The results also allowed us to identify specific sites on the DNA which drive oncogene overexpression after the rearrangement. We are now performing genome editing experiments which target these sites with a view to reversing the over-expression; this will provide new understanding which could eventually lead to new therapies.
