The Shaping and Unshaping of DNA
Date:
Colloquia
Time: 11:00-12:15
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Erez S. Lieberman Aiden
Abstract: Stretched out from end-to-end, the human genome is a two meter long polymer chai ... Read more Stretched out from end-to-end, the human genome is a two meter long polymer chain. But this one-dimensional polymer is arranged inside a three-dimensional nucleus, so that genomic elements far apart along DNA can come into close spatial proximity. This interplay between linear genomic space, in which the heteropolymer’s complex monomer sequence is arrayed, and three-dimensional nuclear space, where the polymer actively interacts with its environment, gives rise to the genome’s 3D architecture. It has long been known that this architecture has the potential to regulate gene activity and drive cellular identity and function. Yet for decades, the principles governing the genome's shape were largely unknown. My research has focused on deciphering these principles—developing technologies to map the genome’s 3D structure and using the resulting maps to discover fundamental folding mechanisms in living cells. We and our collaborators have shown that the polymer chain adopts conformations at multiple scales: simple physical constraints at large scales, domain formation and compartmentalization at intermediate scales, and highly regulated, non-equilibrium loop extrusion events at fine scales.I will also show how we've applied these methods to accelerate genome sequencing, enabling us to study the evolution of chromosome architecture across the tree of life. This has led to the discovery of chromosome (sub)fossils in the remains of extinct creatures, and revealed how the DNA in these fossils gradually loses its shape over deep time.Close abstract
