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Computational Analysis and Modeling of Contractile Ring Assembly

收缩环组件的计算分析和建模

基本信息

批准号：
7683760
负责人：
Sharon Xiaolei Huang
金额：
$ 19.27万
依托单位：
LEHIGH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7683760
关键词：
Actins Actomyosin Age Amines Animals Automobile Driving Binding Biochemistry Bundling Cell Cycle Stage Cell division Cells Chemicals Classification Color Computer Analysis Computing Methodologies Cytokinesis Cytoplasm Cytoskeleton Data Development Diffusion Filament Fission Yeast Fluorescence Microscopy Generations Genetic Models Goals Image Image Analysis Imagery Label Length Life Light Location Measures Mechanics Mediating Membrane Methods Microfilaments Microscopy Modeling Molecular Motion Motor Activity Myosin ATPase Organism Pattern Physical condensation Process Proteins Side Simulate Site Spatial Distribution Staging Structure System Takeda brand of pioglitazone hydrochloride Testing Time Viscosity Work Yeasts base calponin computerized tools constriction design fungus mathematical model movie novel open source polymerization reconstruction research study role model tool

项目摘要

DESCRIPTION (provided by applicant): During cytokinesis, actin, myosin, formins and associated proteins, self-assemble into the equatorial acto-myosin contractile ring. The constriction of the ring separates the cytoplasm of dividing cells into two. While the list of molecular players is almost complete, the molecular and collective mechanisms driving the assembly and constriction of the ring remain unclear. We will collaborate with experimentalists to develop computational tools for the analysis of images of dividing fission yeast cells expressing fluorescent markers for actin (GFP-CHD) and myosin (Rlc1p-RFP), which reveal crucial information on the pattern of contractile ring formation. We will then use the information to develop and test mathematical and numerical models of the mechanics and dynamics of contractile ring assembly and to motivate further experiments. In fission yeast, the contractile ring assembles through the actin-dependent condensation of a broad band of membrane-bound "nodes" containing myosin Myo2p, formin Cdc12p, and other proteins. The condensation mechanism is highly dynamic involving continuous actin polymerization and disassembly and intermittent node motions. Cdc12p presumably nucleates actin filaments which establish transient connections between nodes that are pulled together and form a ring through Myo2p motor activity. We will test this hypothesis by developing novel computational methods to segment actin filaments in 3D static images and to track actin filaments and bundles in time-lapse movies. This will enable us to analyze the topology and dynamics of condensing actomyosin networks and systematically quantify the locations of vertices, filament lengths, rates of polymerization, disassembly, and bundling. By correlating these dynamics to the locations of Myo2p nodes we will rigorously establish the relationship between nodes and sites of actin remodeling. Successful tracking of actin motions will further allow us to extract biophysical parameter values such as filament diffusion coefficients, cytoplasmic viscosity, and forces. We will model the role of physical constraints on the mechanism of establishing connections between nodes and the effect of force on formin-mediated actin elongation. We will test global models of ring assembly and develop statistical analysis and visualization methods for systematic comparison of model predictions to experiment. Cytokinesis, the final step of cell division, is driven by the constriction of an equatorial contractile ring consisting of actin and associated proteins. Despite the biomedical importance of deciphering the mechanisms and controls of cell division, the precise mechanistic steps of contractile ring assembly and constriction remain unclear. We will resolve quantitative details of the assembly of the contractile ring by analyzing fluorescence microscopy images of dividing cells and by developing numerical and mathematical mechanistic models.

描述（由申请人提供）：在胞质分裂期间，肌动蛋白、肌球蛋白、形成蛋白和相关蛋白质自组装成赤道肌动蛋白-肌球蛋白收缩环。环的收缩将分裂细胞的细胞质一分为二。虽然分子参与者的名单几乎是完整的，但驱动环组装和收缩的分子和集体机制仍然不清楚。我们将与实验学家合作开发计算工具，用于分析表达肌动蛋白（GFP-CHD）和肌球蛋白（Rlc 1 p-RFP）荧光标记的分裂酵母细胞的图像，这些图像揭示了收缩环形成模式的关键信息。然后，我们将使用这些信息来开发和测试收缩环组件的力学和动力学的数学和数值模型，并激励进一步的实验。在分裂酵母中，收缩环通过肌动蛋白依赖性的包含肌球蛋白Myo 2 p、CDc 12 p和其他蛋白质的宽带膜结合“节点”的缩合而组装。凝聚机制是高度动态的，包括连续的肌动蛋白聚合和分解以及间歇性的节点运动。Cdc 12 p可能使肌动蛋白丝成核，肌动蛋白丝在节点之间建立瞬时连接，这些节点被拉在一起并通过Myo 2 p运动活动形成环。我们将通过开发新的计算方法来测试这一假设，在3D静态图像中分割肌动蛋白丝，并在延时电影中跟踪肌动蛋白丝和束。这将使我们能够分析凝聚肌动球蛋白网络的拓扑结构和动力学，并系统地量化顶点的位置，细丝的长度，聚合，分解和捆绑的速率。通过将这些动态与Myo 2 p节点的位置相关联，我们将严格地建立节点与肌动蛋白重塑位点之间的关系。肌动蛋白运动的成功跟踪将进一步使我们能够提取生物物理参数值，如细丝扩散系数，细胞质粘度和力。我们将模拟物理约束的作用，在节点之间建立连接的机制和力对formin介导的肌动蛋白伸长的影响。我们将测试环组件的全球模型，并开发统计分析和可视化方法，用于模型预测与实验的系统比较。胞质分裂是细胞分裂的最后一步，由肌动蛋白和相关蛋白组成的赤道收缩环的收缩驱动。尽管破译细胞分裂的机制和控制具有生物医学重要性，但收缩环组装和收缩的精确机械步骤仍不清楚。我们将通过分析分裂细胞的荧光显微镜图像和开发数值和数学机制模型来解决收缩环组装的定量细节。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Multi-feature based Benchmark for Cervical Dysplasia Classification Evaluation.

DOI：
10.1016/j.patcog.2016.09.027
发表时间：
2017-03
期刊：
Pattern recognition
影响因子：
8
作者：
Xu T;Zhang H;Xin C;Kim E;Long LR;Xue Z;Antani S;Huang X
通讯作者：
Huang X

Segmentation and tracking of cytoskeletal filaments using open active contours.

DOI：
10.1002/cm.20481
发表时间：
2010-11
期刊：
CYTOSKELETON
影响因子：
2.9
作者：
Smith, Matthew B.;Li, Hongsheng;Shen, Tian;Huang, Xiaolei;Yusuf, Eddy;Vavylonis, Dimitrios
通讯作者：
Vavylonis, Dimitrios

Oscillatory dynamics of Cdc42 GTPase in the control of polarized growth.