Biophysical models of genome folding and function

About This Grant

Project Summary Our research goal for the next five years is to understand how chromosome architecture, and the mechanisms that shape it—motor-driven loop extrusion and affinity-driven compartmentalization—allow cells to read and store genetic and epigenetic information. Using polymer models, alongside existing and emerging experimental data, we aim to learn the rules by which loop extrusion operates on busy DNA, and how such operations can enable long-range communication between genomic elements. We will develop a mechanistic understanding of how enhancers are targeted to the genes they regulate, and how they execute their transcription activation roles. We will also explore how epigenetic memory of cellular identity is stored but can deteriorate with aging or disease. Our vision is that loop extrusion transforms the genome into a communication system with transmitters and receivers of regulatory information. Compartmentalization in turn allows cells to write, store, and potentially process epigenetic information. The interplay between these two global genome-folding processes may be at the heart of key developmental programs, aging, and disease.