Leonid Mirny combines biophysical modeling with analysis of large genomics data to address fundamental problems in biology. Mirny aims to understand how long DNA molecules of chromosomes are folded in 3D, and how this 3D organization is used by living cells. The Mirny group has proposed that DNA is folded by molecular motors that perform “loop extrusion”. The loop extrusion hypothesis has been confirmed experimentally and has revolutionized our understanding of chromosomes across all organisms. Now Mirny aims to understand how cells use this and other physical mechanisms to regulate its genes, repair DNA, and maintain epigenetic memory.