4D model
The central goal of Learn4DChromosome is to develop a 4D model for the statistical folding of chromosomes and its implications for function. The development of new experimental Hi-C, chromosome, techniques has recently generated a breakthrough in measuring chromosome structure. Unlike a microscope, however, these experiments don’t yield easily interpretable images, but rather a statistical metric for average pairwise interactions between chromosomal regions. Interpreting Hi-C maps at their full quantitative potential remains a major hurdle to overcome.
Physics of living systems
Chase Broedersz is theoretical physicist at the VU Amsterdam Department of Physics. His research group studies the Physics of Living Systems, like bacteria. Bacteria play a major role in human health and disease. Bacterial chromosomes not only have to be highly condensed to fit inside the cell, but their organisation must also facilitate vital processes such as gene transcription, DNA replication, and segregation.
“Bacterial chromosomes are not folded in a completely random fashion, like a regular polymer. Nor are they folded in a regular structure, like many proteins. It’s something in between that I term statistical chromosome folding, which is highly controlled by the cell. This statistical folding characterizes the inherently variable and dynamic nature of chromosomes. Understanding the statistical organisation of chromosome organisation in living, growing, and replicating bacteria is a major outstanding challenge’’, says Chase Broedersz.
Ambitious goals
When asked about the most ambitious goals of his project, Broedersz says: “Developing a theoretical ‘lens’ that decodes the information in Hi-C maps, thereby providing not only direct ‘pictures’ but also ‘movies’ for the 4D statistical organisation of bacterial chromosomes.” The key to Broedersz’ data-driven theoretical approach is to combine information and physics-guided learning techniques. Beyond offering new insight into key biological processes like how chromosomes separate before cell division, the results and tools developed in Learn4DChromosome may help unravel how bacterial chromosomes respond to genetic perturbations and drug treatments like anti-biotics.