Computational Models of Cell Division

细胞分裂的计算模型

• 批准号: 8054810
• 负责人: Pablo A. Iglesias
• 金额: $ 30.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8054810
• 关键词: Actins; Address; Affect; Binding; Biochemical; Cell Shape; Cell division; Cells; Cellular Morphology; Computer Simulation; Contractile System; Cues; Cytokinesis; Cytoskeletal Proteins; Cytoskeleton; Dictyostelium; Disease; Elasticity; Ensure; Failure; Feedback; Filament; Genes; Health; Heterogeneity; Human; Kinetics; Knowledge; Lead; Liquid substance; Malignant Neoplasms; Mammalian Cell; Measurement; Mechanics; Mediating; Methods; Mitosis; Mitotic; Modeling; Morphology; Mothers; Myosin ATPase; Myosin Type II; Process; Property; Protein Dynamics; Proteins; Regulation; Research; Sarcomeres; Signal Transduction; Simulate; Staging; Stress; Structure; Surface Tension; System; Testing; Textbooks; Traction; Variant; Viscosity; Work; base; computer framework; crosslink; daughter cell; mutant; public health relevance; simulation; tool

DESCRIPTION (provided by applicant): During the last stage of cell division, cytokinesis, cells undergo a dramatic change in morphology as they rearrange themselves so as to produce two identical daughter cells. A detailed understanding of how these processes are regulated requires a fundamental knowledge of how different cytoskeletal proteins are spatially and temporally regulated, and how the resultant heterogeneity affects the mechanical properties of the cell. The complexity of these processes makes it nearly impossible to understand without a modeling framework that allows in silico testing of ideas and conceptual models. To elucidate the mechanisms by which cells regulate cytokinesis we need to appreciate how regulation of biochemical signaling cues effect changes in cell morphology. We will develop a suitable computational framework for studying the way in which biochemical regulation of cytoskeletal proteins results in desired cellular deformations during cytokinesis. Our simulations will be used to integrate computational modeling with quantitative measurements of the temporal and spatial changes of different proteins and the associated changes in cell shape during cytokinesis. Specifically, we propose: 1. to develop a computational framework for simulating whole cell, cell shape changes during mitosis; 2. to develop an agent-based model of the actin cytoskeleton using a discrete-network representation of interacting filaments, and to use this model to investigate cell morphological changes during cytokinesis. PUBLIC HEALTH RELEVANCE: Successful cell division has long been appreciated as critical to human health. Many cancer- associated genes lead to mitotic and/or cytokinetic failure. In this research we combine computational and experimental tools to study the way that cells regulate their mechanical properties to ensure that each mother cells successfully divides into two equally-sized daughter cells.

描述（由申请人提供）：在细胞分裂的最后阶段，细胞因子，细胞在重新排列自身时会发生巨大变化，以产生两个相同的子细胞。对这些过程的调节方式的详细理解需要对不同细胞骨骼蛋白在空间和时间进行调节的基本知识，以及所得的异质性如何影响细胞的机械性能。这些过程的复杂性使得没有建模框架可以理解的建模框架，该框架允许对思想和概念模型进行计算机测试。为了阐明细胞调节细胞因子的机制，我们需要欣赏生化信号提示的调节如何影响细胞形态的变化。我们将开发一个合适的计算框架，用于研究细胞骨骼蛋白质生化调节的方式，从而导致细胞因子过程中所需的细胞变形。我们的模拟将用于将计算建模与不同蛋白质的时间和空间变化的定量测量以及细胞因子过程中细胞形状的相关变化。具体而言，我们建议：1。要开发一个计算框架，用于模拟整个细胞，有丝分裂过程中的细胞形状变化； 2。使用相互作用细丝的离散网络表示基于肌动蛋白细胞骨架的模型，并使用此模型来研究细胞因子过程中细胞的形态变化。 公共卫生相关性：成功的细胞部门长期以来对人类健康至关重要。许多癌症相关的基因导致有丝分裂和/或细胞动力学衰竭。在这项研究中，我们结合了计算和实验工具，以研究细胞调节其机械性能的方式，以确保每个母细胞成功地分为两个同等大小的子细胞。