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

生物力学基因组动力学：单分子研究作用于 DNA 的力如何影响细胞功能

• 批准号: 418251-2013
• 负责人: Milstein, Joshua
• 金额: $ 1.68万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=551310
• 关键词: Biomechanical; Genome; Dynamics; Single; Molecule

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.

细胞内部是一个极其拥挤的世界，充满了各种活动。分子，如DNA、RNA、蛋白质、多糖等，反复相互作用，相互碰撞。例如，DNA在这些随机碰撞中不断被扭曲、弯曲和移位，以至于细胞已经进化到依靠DNA的嘈杂或“随机”动态运动来实现各种功能。例如，DNA分子上的扭曲和张力可以影响远端基因的表达，而分子上断断续续形成的环实际上可以开关基因。细胞还进化出一种机制来抵消随机碰撞对DNA的影响。例如，在细菌中，在细胞分裂之前，一些DNA片段通过微小细丝的生长进行物理运输，这些细丝推动DNA对通过细胞内汤到达细胞的两端。我们试图对控制其动态行为的DNA力学如何影响基因表达的一些嘈杂或随机过程有一个基本的理解，并揭示细胞内发挥作用的力量和动力学如何使细胞准确地将其DNA从一代分配到下一代。