Molecular mechanisms of motility and microtubule-remodeling by kinesins

驱动蛋白运动和微管重塑的分子机制

• 批准号: 356025-2013
• 负责人: Allingham, John
• 金额: $ 3.64万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572719
• 关键词: Molecular; mechanisms; motility; microtubule; remodeling

Movement is a defining characteristic of life. The bulk of movement by cells and inside of cells is driven by kinesin, myosin, and dynein motor proteins. Our research program studies kinesins - the smallest and simplest of these motors. Despite their tiny stature, kinesins perform big jobs in cells. For example, they move important synaptic proteins down neurons for nerve function and survival, and they help segregate genetic material equally between cells when they divide. My group is interested in the classes of kinesins that perform the latter of these functions. These are known as mitotic kinesins. Mitotic kinesins typically form complexes of two proteins that wind around one another, where each molecule in the complex cooperates with the other to convey movement of their cargo. It is often the case that many kinesin complexes work together to share the weight of carrying a common heavy load, such as a microtubule, and sometimes teams of other kinesins are attempting to pull the same cargo in the opposite direction. These activities are important for the proper functioning of the highly ordered cellular structure that segregates chromosomes during mitosis - the mitotic spindle. Our research program is interested in understanding how these kinesins work, both at a molecular level, and as ensembles of motors actively moving the same cargo. Insights from our studies will help us gain control of individual motors in cells so that their functions can be manipulated and studied in greater detail. They will also guide design of new biological parts for nano-sized machines that mimic the types of movement that occurs in cells. These advances could help develop Canadian-based technologies in molecular manufacturing of engineered nanosystems (e.g. hybrids of silicon technology and biological molecular machines) or contribute to emergent areas in biomedical research tool and molecular delivery system creation. Involvement of new graduate students in a program such as ours will therefore will help create a workforce of well-trained and highly sought-after future innovators.

运动是生命的一个决定性特征。细胞和细胞内部的大部分运动由驱动蛋白、肌球蛋白和动力蛋白马达蛋白驱动。我们的研究计划研究驱动蛋白-这些马达中最小和最简单的。尽管它们的体积很小，但驱动蛋白在细胞中却发挥着重要作用。例如，它们将重要的突触蛋白沿着神经元向下移动以实现神经功能和存活，并且它们有助于在细胞分裂时在细胞之间平等地分离遗传物质。我的小组对执行后一种功能的驱动蛋白类感兴趣。这些被称为有丝分裂驱动蛋白。有丝分裂驱动蛋白通常形成两种蛋白质的复合物，它们彼此缠绕，其中复合物中的每个分子与另一个分子合作以传递其货物的运动。通常情况下，许多驱动蛋白复合物一起工作以分担携带共同的重物的重量，例如微管，有时其他驱动蛋白的团队试图将相同的货物拉向相反的方向。这些活动对于在有丝分裂期间分离染色体的高度有序的细胞结构-有丝分裂纺锤体的正常功能是重要的。我们的研究计划有兴趣了解这些驱动蛋白是如何工作的，无论是在分子水平上，还是作为积极移动相同货物的马达的集合。从我们的研究中获得的见解将帮助我们控制细胞中的单个马达，以便更详细地操纵和研究它们的功能。他们还将指导纳米尺寸机器的新生物部件的设计，这些机器模仿细胞中发生的运动类型。这些进展可能有助于开发工程纳米系统（例如硅技术和生物分子机器的混合体）的分子制造中的基于葡聚糖的技术，或有助于生物医学研究工具和分子传递系统创建的新兴领域。因此，新的研究生参与像我们这样的项目将有助于培养一支训练有素、备受追捧的未来创新者队伍。