Discovering the regulatory logic of the nucleosome

Nucleosomes are the fundamental unit of the eukaryotic genome, serving as both its structural core and an essential regulatory hub. Seemingly universally conserved, nucleosomes rarely change by more than a handful of single-residue substitutions across evolution or in disease. While vanishingly small, such innovations can transform genome function, yet despite decades of study the mechanistic basis for this remains largely unknown. Using tools from synthetic and systems biology, I’m taking advantage of nature’s experiments to discover the missing mechanisms linking the nucleosome to genomic regulation, deriving the first principles behind them, and building predictive models to improve human health.