Molecular mechanisms of motility and microtubule-remodeling by kinesins

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是由运动蛋白、肌凝蛋白和动力蛋白驱动的。我们的研究项目研究运动蛋白——这些马达中最小、最简单的一种。尽管它们的体型很小，但运动蛋白在细胞中发挥着重要作用。例如，它们将重要的突触蛋白转移到神经功能和存活所需的神经元上，并且在细胞分裂时，它们有助于在细胞之间平等地分离遗传物质。我的小组对执行后一种功能的激酶类很感兴趣。这些被称为有丝分裂动蛋白。有丝分裂运动蛋白通常形成两种相互缠绕的蛋白质复合物，其中复合物中的每个分子都与另一个分子合作以传递其货物的运动。通常情况下，许多动力蛋白复合物一起工作，共同承担一个共同的重负荷，比如微管，有时其他动力蛋白团队也试图往相反的方向拉同样的货物。这些活动对于有丝分裂过程中分离染色体的高度有序的细胞结构的正常运作是重要的-有丝分裂纺锤体。我们的研究项目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，还是作为积极移动相同货物的马达的整体。从我们的研究中获得的见解将帮助我们获得对细胞中单个马达的控制，从而可以更详细地操纵和研究它们的功能。它们还将指导纳米级机器的新生物部件的设计，这些机器可以模仿细胞中发生的运动类型。这些进步可以帮助开发基于加拿大的工程纳米系统的分子制造技术（例如硅技术和生物分子机器的杂交），或者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，新研究生参与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。

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.