Revealing the Physical Principles Underlying Epigenetic Regulation Using Theory, Simulation, and Experiment

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In this project, the PIs will reveal the physical principles underlying epigenetic regulation. Historically, the central dogma of genetics asserted that DNA sequence holds all of the information that orchestrates cellular function. However, histone and DNA modifications alter the physical packaging of genomic DNA, resulting in dramatic changes in the expression of the packaged genetic material. This notion of epigenetic regulation represents a paradigm change in how we think about genetic traits. In Thrust 1, the PI will develop a theoretical model to address the segregation of chromatin into transcriptionally active heterochromatin and transcriptionally silent euchromatin. In Thrust 2, the PI will perform experimental measurements and theoretical modeling of the reorganization dynamics of chromosomal DNA within Saccharomyces cerevisiae and Schizosaccharomyces pombe. In Thrust 3, the PI will establish a kinetic model that captures the function of the proteins that maintain and amplify the epigenetic code based on cooperative interactions with the proteins that control chromosomal organization. By combining theoretical and computational modeling with experimental measurements, the PI will establish an unprecedented level of physical understanding of the mechanisms of epigenetic regulation. The PI's outreach efforts include the establishment of the LABScI program, which develops and implements teaching modules for the education of high school students that are being treated for childhood cancer. Future outreach efforts aim to further expand the program nationwide as a general laboratory science curriculum for hospital-school education.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences.