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

牢房内部是一个极其拥挤的世界，活动熙熙攘攘。DNA、RNA、蛋白质、多糖等分子之间反复相互作用和碰撞。例如，DNA不断地被这些随机碰撞扭曲、弯曲和移位，以至于细胞进化成依赖于DNA的嘈杂或随机的动态运动来实现各种功能。例如，DNA分子上的扭曲和张力会影响远距离基因的表达，而沿着分子间歇性形成的环实际上可以打开和关闭基因。该细胞还进化出了抵消随机碰撞对DNA的影响的机制。例如，在细菌中，一些DNA片段是通过微小细丝的生长进行物理运输的，这些细丝在细胞分裂之前将成对的DNA通过细胞内浆推向细胞的两端。我们试图对控制DNA动态行为的DNA机制如何影响基因表达的噪声或随机过程有一个基本的了解，并揭示细胞内的作用力和动态如何允许细胞将其DNA准确地从一代分配到下一代。*我们将使用生物物理技术来观察并与单个DNA分子相互作用，这是研究DNA的机制和动力学的最定量和最直接的方法。这些基因组动态对细胞的运作和分裂至关重要。结果在我们研究的细菌系统中，我们将深入了解更复杂的动植物细胞世界，在这些世界中，基因组调节和复制中的功能错误可能会对加拿大的农业和生物经济产生严重影响。这项研究还将为学生和博士后提供模范的跨学科培训体验，并导致加拿大和国际上的合作。

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.********************