Biomechanical Genome Dynamics: A Single-Molecule Look at How the Forces Acting on DNA Affect Cellular Function

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The interior of a cell is an extremely crowded world that is bustling with activity. Molecules such as DNA, RNA, proteins, polysaccharides, etc., repeatedly interact and collide with one another. DNA, for instance, is constantly being twisted, bent and displaced by these random collisions, so much so, that the cell has evolved to rely upon the noisy or 'stochastic' dynamical motion of DNA for a variety of functions. For instance, twist and tension along the DNA molecule can affect the expression of distant genes while loops that intermittently form along the molecule can actually switch genes on and off. The cell has also evolved mechanisms to counteract the effects of random collisions to the DNA. For instance, in bacteria, some segments of DNA are physically transported by the growth of tiny filaments that push pairs of DNA through the intracellular soup to opposite ends of the cell before the cell divides. We seek to develop a fundamental understanding of how the mechanics of DNA, which govern its dynamical behavior, affects the also somewhat noisy or stochastic process of gene expression and to uncover how the forces and dynamics at play within cells allow the cell to accurately distribute its DNA from one generation to the next. We will use biophysical techniques that allow us to observe and interact with individual DNA molecules, which is the most quantitative and direct way to study the mechanics and dynamics of DNA. These genome dynamics are vital to the operation and division of cells. Results within the bacterial systems we study will lead to insight into the more complicated world of plant and animal cells where functional errors in genome regulation and replication can have grave implications for agriculture and the bioeconomy of Canada. This research will also provide an exemplary, interdisciplinary training experience for both students and postdocs and lead to collaborative work across both Canada and internationally.