Caitlin Hult (UNC-CH), GMA Seminar

Title: Modeling nucleosomal DNA in living yeast

Abstract:  The genome in living yeast cells is a highly dynamic system where entropic interactions and nuclear confinement drive the formation of domains of high chromosomal interaction, known as topologically associating domains.  In this talk, we investigate the dynamic organization of all 16 chromosomes in living yeast cells during interphase using coarse-grained, entropic polymer chain models.  We start by investigating loop configuration and how it regulates cell function in the yeast genome as related to nucleolus size, segregation, and level of compaction.  We have developed a microscope simulator computational program to translate simulated data from our models into equivalent microscope images, as well as a pipeline to view and analyze experimental images obtained by the Bloom lab using live cell microscopy.  Through such visualization tools and comparison with experimental data, we aim to shed insights into nucleolus dynamics and structure that are beyond current experimental resolution.  Unlike single molecule analysis or imaging, this approach enables us to discern how the rate of chain fluctuation and on and off rates of the binding protein influence the strength of interactions within the nucleolus, and thus it will further help us to understand the biophysical principles governing fluctuating chains and chromatin binding proteins.