Modelling Intracellular Transport

描述（由申请人提供）：细胞的空间组织取决于货物沿沿着微管和肌动蛋白丝的细胞内运输。运动蛋白中的驱动蛋白、动力蛋白和肌球蛋白家族转运不同的囊泡和细胞器，包括线粒体、内体，甚至已经进入细胞的病毒。大量的努力已经投入到理解这个运输系统的各个组成部分是如何工作的，例如，马达的单分子研究然而，人们对运输途径中多个相互作用的组件如何发挥作用知之甚少，特别是多个马达如何发挥作用，既能沿着沿着细丝运送货物，又能在细丝之间切换。拟议研究的目标是了解细胞内转运如何运作以及如何调节。具体来说，我们有以下目标：7目标1：：确定是否多个电机的货物移动和共享负载合作或独立。7目标2：通过交叉灯丝上电机之间的拔河来确定开关的作用。7目的3：确定与纤维结合的蛋白质是否调节纤维之间的转换。我们将使用Monte Carlo模拟来解释定量实验的结果。 与公共卫生的相关性：细胞内的组织是通过一个运输系统来维持的，在这个系统中，分子马达将货物从一个地方运送到另一个地方。这种运输系统的破坏与神经退行性疾病如帕金森病和阿尔茨海默病有关，而鞭毛内运输的破坏可导致多囊肾病，失明（色素性视网膜炎）和发育缺陷，如器官错位在身体的错误一侧的位置。更好地了解基本的细胞内转运过程将有助于设计新的治疗方法。

DESCRIPTION (provided by applicant): The spatial organization of the cell depends upon intracellular trafficking of cargos along microtubules and actin filaments. The kinesin, dynein, and myosin families of motor proteins transport diverse vesicles and organelles including mitochondria, endosomes, and even viruses that have entered the cell. A great deal of effort has gone into understanding how individual components of this transportation system work, e.g., single molecule studies of motors. However, little is known about how function emerges from multiple interacting components of the transport pathway, especially how multiple motors function both to haul cargos along filaments, and to switch between filaments. The goal of the proposed research is to understand how intracellular transport operates and how it is regulated. In particular we have the following aims: 7 Aim 1: : Determine whether multiple motors on a cargo move and share load cooperatively or independently. 7 Aim 2: Determine the role of switching via a tug of war between the motors on intersecting filaments. 7 Aim 3: Determine whether proteins that bind to filaments regulate switching between filaments. We will interpret the results of quantitative experiments using Monte Carlo simulations. Relevance to public health: The organization inside a cell is maintained through a transportation system in which molecular motors haul cargo from one place to another. The breakdown of this transportation system has been associated with neurodegenerative diseases such as Parkinson's disease and Alzheimers, while disruption of intraflagellar transport can lead to polycystic kidney disease, blindness (retinitis pigmentosum), and developmental defects such as Situs Inversus where organs are misplaced on the wrong side of the body. A better understanding of fundamental intracellular transport processes will aid in the design of new therapeutic approaches.