CBE Seminar: Multiscale Modeling of Chromosomal DNA and the Physical Processes Underlying Epigenetic Regulation
Abstract: Historically, the central dogma of genetics asserted that DNA sequence holds all of the information that orchestrates cellular function. However, protein and DNA modifications play a pivotal role in regulating the expression of the genome and in establishing cell identity. In other words, two organisms with identical genetic information may have vastly different behavior due to chemical modifications in their genome packaging. This notion of epigenetic regulation represents a paradigm change in how we think about genetic traits. Aberrations in epigenetic markers lead directly to a range of diseases, including various cancers, developmental disorders, obesity and diabetes. Research in our lab focuses on biological processes involving DNA to establish a predictive theoretical model that offers new and critical insight into the role of physical mechanisms involved in epigenetic regulation. In this talk, we present a multiscale approach to modeling the segregation of chromosomal DNA into condensed regions called heterochromatin. This effort leverages our field-theoretic model for predicting copolymer morphology, resulting in a framework that can translate epigenetic modifications at a single nucleosome to genome-scale segregation. We will demonstrate the impact of epigenetic modifications on chromosomal organization, and we will discuss how chromosomal organization serves as a template for re-establishing the epigenetic code over multiple cell cycles.
Bio: The Spakowitz lab is engaged in projects that address fundamental chemical and physical phenomena underlying a range of biological processes and soft-material applications. Current research in our lab focuses on four main research themes: chromosomal organization and dynamics, protein self-assembly, polymer membranes, and charge transport in conducting polymers. These broad research areas offer complementary perspectives on chemical and physical processes, and we leverage this complementarity throughout our research. Our approach draws from a diverse range of theoretical and computational methods, including analytical theory of semiflexible polymers, polymer field theory, continuum elastic mechanics, Brownian dynamics simulation, equilibrium and dynamic Monte Carlo simulations, and analytical theory and numerical simulations of reaction-diffusion phenomena. A common thread in our work is the need to capture phenomena over many length and time scales, and our flexibility in research methodologies provides us with the critical tools to address these complex multidisciplinary problems.
Host: Associate Professor Elizabeth Read