MODELING

造型

• 批准号: 7664906
• 负责人: Jason M. Haugh
• 金额: $ 7.9万
• 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/7664906
• 关键词: Adhesions; Behavior; Biological; Cells; Chemicals; Computer Simulation; Computer software; Coupled; Data; Development Polarity; Funding; Goals; Human; Knowledge; Laboratories; Location; Mechanics; Modeling; Molecular; Numbers; Phase; Process; Property; Proteins; Regulation; 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.

在第一个融资阶段，建模计划构建了许多关系和生物物理模型 力学和分子现象与细胞迁移有关，并开始发展有关 虚拟单元（VC）软件中的功能。该活动可以视为最后一步 还原主义议程 - 在使用数学表示的简化机动系统的计算机重构中 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，超越人类推理的促进。这些模型 软件开发使令人兴奋的可能性在我们的定量方面迈出了巨大的至关重要的一步 从系统生物学的角度了解细胞迁移。这些模型将从 技术的观点，整合，全面和预测。我们努力的关键特征， 验证此类模型并将其用于假设预测测试工作所需的绝对必需 实验合作者没有直接输入进行建模。我们将在下面描述 该要求将始终如一地满足该要求的机制。 建模计划将以长期目标调查系统级别的迁移机制 开发细胞迁移的综合模型。该模型将具有模块化字符组合 确定性和随机成分。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， 粘附，收缩和后方 释放，然后将它们整合到 综合模型。对于每个 流程，一个“过程团队”，包括 计算生物学家和 实验生物学家（在少数情况下， 这些功能位于同一功能 实验室），将共同开发 能够捕获的“过程模型” 在分子方面的动态行为 性质（蛋白质水平，状态， 位置和活动）。是通过这个 数据将是 生产，分析和建模 迭代以发展的目标 来自模型预测的其他数据 并使用这些数据来完善模型。