Modelling Intracellular Transport

细胞内运输建模

• 批准号: 7683154
• 负责人: Clare C Yu
• 金额: $ 27.72万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7683154
• 关键词: Actin-Binding Protein; Address; Affect; Axonal Transport; Binding; Biological Assay; Blindness; Cells; Defect; Development; Dynein ATPase; Endosomes; Family; Filament; Glass; Goals; In Vitro; Individual; Intracellular Transport; Kinesin; Kinetics; Lead; Length; Measurement; Measures; Microfilaments; Microtubule-Associated Proteins; Microtubules; Mitochondria; Modeling; Molecular Motors; Motion; Motor; Myosin ATPase; Myosin Type V; Neurodegenerative Disorders; Organ; Organelles; Parkinson Disease; Pathway interactions; Polycystic Kidney Diseases; Polystyrenes; Probability; Protein Binding; Proteins; Public Health; Relative (related person); Research; Retinitis; Role; Route; Running; S cerevisiae SWI3 protein; Side; Situs Inversus; System; Testing; Transport Process; Transportation; Tropomyosin; Vesicle; Virus; Walking; War; Work; design; dynactin; genetic regulatory protein; health organization; novel therapeutic intervention; protein transport; research study; simulation; single molecule; tau Proteins; trafficking

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.

描述（由申请人提供）：细胞的空间组织取决于沿微管和肌动蛋白丝的细胞内运输。运动蛋白的动力蛋白，动力蛋白和肌球蛋白家族转运多种囊泡和细胞器，包括线粒体，内体，甚至进入细胞的病毒。了解该运输系统的各个组件如何工作，例如电动机的单分子研究。但是，关于函数如何从传输途径的多个相互作用组件中出现的知之甚少，尤其是多个电动机如何运作沿细丝的符号以及在细丝之间切换。拟议的研究的目的是了解细胞内运输的运行方式以及如何调节。特别是我们有以下目的：7 AIM 1 ：：确定货物上的多个电动机是否移动并共享负载是合作或独立的。 7 AIM 2：确定通过电动机之间的一场战争切换在相交丝中的作用。 7 AIM 3：确定与细丝结合的蛋白是否调节细丝之间的切换。我们将使用蒙特卡洛模拟来解释定量实验的结果。 与公共卫生的相关性：通过运输系统来维护一个单元内的组织，该系统分子电动机将货物从一个地方移到另一个地方。 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.更好地了解基本的细胞内运输过程将有助于设计新的治疗方法。