Modeling

造型

• 批准号: 7664916
• 负责人: ALEXANDER MOGILNER
• 金额: $ 12万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7664916
• 关键词: Adhesions; Behavior; Biological; Cells; Computer Simulation; Computer software; Data; Development Polarity; Funding; Goals; Human; Knowledge; Laboratories; Location; Modeling; Molecular; Numbers; Phase; Process; Property; Proteins; System; Systems Biology; Testing; Work; cell motility; computer generated; data modeling; migration; molecular mechanics; reconstitution; software development; virtual

In the first funding phase, the Modeling Initiative constructed a number of relational and biophysical models of mechanics and molecular phenomena related to cell migration and started to develop migration related capabilities within the Virtual Cell (VC) software. This activity can be considered as the last step in the reductionism agenda - in silico reconstitution of a simplified motile system using mathematical representation combining biological knowledge and hypotheses, with determination of the consequences of these hypotheses facilitated beyond human reasoning by means of computer-generated numerical calculations. These models and software development enabled the exciting possibility to make a large, critical step in our quantitative understanding of cell migration from the point of view of systems biology. The models will be standardized from the technical point of view, integrated, comprehensive and predictive. A crucial feature of our endeavor, absolutely required for validating such models and using them for hypothesis prediction-test efforts, is that no modeling is undertaken absent direct input from experimental collaborators. We will describe below the mechanism by which this requirement will be consistently met. The Modeling Initiative will investigate migration mechanisms at the systems-level with a long term goal of developing a comprehensive model of cell migration. This model will have a modular character combining deterministic and stochastic components. Our approach is to develop models for each of the component processes that drive cell migration, e.g., development of polarity, protrusion, adhesion, and contraction and rear release, and then integrate them into a comprehensive model. For each of these processes, a 'Process Team' that includes both computational biologists and experimental biologists (in a few cases, these capabilities reside within the same laboratory ), will work together to develop a 'Process Model' capable of capturing dynamic behavior in terms of molecular properties (protein levels, states, locations, and activities). It is through this collaborative team that data will be produced, analyzed, and modeled iteratively with a goal of developing additional data from model predictions and using these data to refine the models.

在第一个资助阶段，建模计划构建了许多关系和生物物理模型 与细胞迁移相关的力学和分子现象，并开始开发迁移相关的 Virtual Cell (VC) 软件中的功能。这项活动可以被视为最后一步 还原论议程 - 使用数学表示在计算机上重建简化的运动系统 结合生物学知识和假设，并确定这些假设的后果 通过计算机生成的数值计算，超越人类推理。这些型号 软件开发使我们在定量研究方面迈出了一大步关键的一步，这令人兴奋。 从系统生物学的角度理解细胞迁移。这些模型将被标准化 技术角度来看，综合性、综合性和预测性。我们努力的一个重要特点是 验证此类模型并将其用于假设预测检验工作绝对需要的是，不 建模是在没有实验合作者直接输入的情况下进行的。我们将在下面描述 一致满足这一要求的机制。 建模计划将研究系统级别的迁移机制，以实现长期目标 开发细胞迁移的综合模型。该模型将具有模块化特征，结合 确定性和随机性成分。我们的方法是为每个组件开发模型 驱动细胞迁移的过程，例如， 极性、突出的发展， 附着力、收缩性和后部 发布，然后将它们集成到 综合模型。对于每一个 流程，一个“流程团队”，包括 计算生物学家和 实验生物学家（在少数情况下， 这些功能位于同一个 实验室），将共同开发 能够捕获的“流程模型” 分子动态行为 特性（蛋白质水平、状态、 地点和活动）。正是通过这个 协作团队将数据 生成、分析和建模 迭代地开发目标 来自模型预测的附加数据 并使用这些数据来完善模型。