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: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630005
• 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.

运动是生活的一个决定性特征。细胞和细胞内的大部分运动是由动力蛋白、肌球蛋白和动力蛋白驱动的。我们的研究项目研究肌动蛋白--这是一种最小、最简单的马达。尽管个子很小，但肌动蛋白在细胞中发挥着巨大的作用。例如，它们将重要的突触蛋白移下神经元，以实现神经功能和生存，并且当细胞分裂时，它们有助于在细胞之间平等地分离遗传物质。我的团队对执行这些功能中的后一种功能的运动蛋白类感兴趣。这些被称为有丝分裂动蛋白。有丝分裂动蛋白通常形成两种蛋白质的复合体，相互缠绕在一起，复合体中的每个分子相互协作，传递其货物的运动。通常的情况是，许多动蛋白复合体一起工作，以分担携带共同重载的重量，例如微管，有时其他动蛋白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过程中分离染色体的高度有序的细胞结构--有丝分裂纺锤体--的正常功能非常重要。我们的研究计划感兴趣的是了解这些运动蛋白是如何工作的，无论是在分子水平上，还是作为活跃地移动相同货物的马达的集合。我们从研究中获得的见解将帮助我们控制细胞中的单个马达，以便可以更详细地操纵和研究它们的功能。他们还将指导纳米机器的新生物部件的设计，这些部件模仿细胞中发生的运动类型。这些进展可能有助于在工程纳米系统的分子制造方面开发加拿大的技术(例如，硅技术和生物分子机器的混合)，或者有助于生物医学研究工具和分子输送系统创造的新兴领域。因此，让应届毕业生参与我们这样的项目将有助于培养一支训练有素、备受欢迎的未来创新者大军。