Abstract

Remarkably, the human genome encodes the complexity of hundreds of cell types for more than a century from transient embryonic signals. Proper organ function then relies on millions of diverse cells responding coherently to shared stimuli. Coordinating complex behavior across many cell states requires a robust mechanism. At the nanoscale, the human genome physically assembles into several thousand mass-fractal packing domains. Unlike TADs, packing domains represent nanoscale, continuous chromatin density distributions that physically couple high-density heterochromatin cores with transcriptionally active surfaces. In this talk, Dr. Almassalha describes how transcription guides the formation of packing domains by creating geometric specificity for chromatin remodeling enzymes based on their sizes. In turn, transcriptional reactions benefit from optimized physiochemical conditions at the domain surface that can be maintained for decades by the geometric specificity of the remodeling enzymes. In effect, our genome is a self-assembling geometric computational system that physically encodes transcriptional memories as packing domains in a manner reminiscent of reinforcement learning in neural networks. Dr. Almassalha will then discuss how this system is relevant to human health by examining domain formation in muscle development and aging.

About Luay Almassalha, MD, PhD

Luay Almassalha, MD, PhD is a sixth-year fellow in the Department of Gastroenterology and Hepatology at the Northwestern Feinberg School of Medicine and a 2024 Starzl Research Scholar recipient. He is working toward his goal of becoming an independent physician-scientist running a lab at the intersection of mathematics, chromatin biology, and nanoscopic imaging to address gaps in the knowledge of disease of the gastrointestinal tract. After receiving his MD and PhD training, through the Northwestern University Medical-Scientist Training Program under the mentorship of Dr. Vadim Backman and Dr. Igal Szleifer, he completed clinical training in Internal Medicine and is currently completing his training in Gastroenterology and Hepatology. Motivated by his clinical experience with patients impacted by immune disorders and cancers throughout the gastrointestinal tract, he investigates how the physical folding of the genome intersects with human disease. His goal is to apply the understanding of physical and chemical properties of the genome to these disorders to develop new treatments as well as prognostic and diagnostic tools.

Related Info

Register Now