Epithelial Cell Migration: Model selectionn for mechanistic model development

上皮细胞迁移：机械模型开发的模型选择

• 批准号: 9460745
• 负责人: David Bortz
• 金额: $ 38.5万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-10 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9460745
• 关键词: Adherens Junction; Alpha Cell; Automobile Driving; Biochemical; Biological Process; Biology; Cell Communication; Cell Mobility; Cell model; Cells; Collaborations; Data; EGF gene; Engineering; Ensure; Epithelial Cells; Experimental Designs; Experimental Models; Goals; Individual; Investigation; Lead; Mathematics; Measurement; Measures; Mechanics; Methodology; Mitogen-Activated Protein Kinases; Modeling; Motion; Multicellular Process; Organism; Pattern; Phase; Play; Research; Role; Selection Criteria; Signal Transduction; Substrate Interaction; Techniques; Theoretical model; Tissues; Trust; Validation; Work; Wound Healing; cell behavior; cell motility; density; dynamic system; experimental analysis; experimental study; improved; keratinocyte; mathematical model; migration; model development; novel; spatiotemporal; wound

The collective migration of cells is a central biological process for multicellular organisms. While substantial research has been devoted to its study, we still lack a fundamental understanding of what drives groups of cells to move collectively in a single direction. The objective of this proposal is to advance our understanding of the causal mechanisms which induce the collective movement of cells through advanced mathematical modeling and novel experiments. This objective will be pursued in this context of studying the migration of keratinocytes during the epithelialization stage of wound healing. A central premise of this research is that advances in the study this phase of wound healing lead to a deeper understanding of the biochemical and mechanical signals that lie at the core of cellular migration. A central obstacle inhibiting deeper study of migration lies in the fact that there are large number of viable explanatory mechanisms. Toward this goal, we will use information-theoretic model selection criteria for dynamical systems to choose among several candidate models to find those which best represent the migration patterns - and thus those that best describe the underlying biology. This project builds on a close collaboration between the labs of an applied mathematician (Bortz), a cell biologist/biochemist (Liu), and a statistician (Dukie). It aims to transform scientific understanding of cellular migration by discovering previously unknown biochemical and physical mechanisms. The proposed investigation is a novel blend of advanced mathematical and statistical inquiry and experimental validation and reflects the ongoing synergistic efforts of the three labs.

细胞的集体迁移是多细胞生物的中心生物学过程。同时进行大量研究 一直专门研究其研究，我们仍然缺乏对驱动细胞群体移动的基本了解 集体朝一个方向。该提议的目的是提高我们对因果关系的理解 通过高级数学建模和新颖的机制诱导细胞的集体运动 实验。在研究角质形成细胞迁移期间的这种情况下，将实现这一目标 伤口愈合的上皮化阶段。这项研究的一个主要前提是，在研究的进步这一阶段 伤口愈合导致对位于细胞核心的生化和机械信号的更深入了解 迁移。抑制更深入研究的核心障碍在于有很多可行的事实 解释机制。为了实现这一目标，我们将使用信息理论模型选择标准进行动力学 可以在几种候选模型中选择的系统，以找到最能代表迁移模式的系统 - 因此 那些最能描述潜在生物学的人。 该项目建立在应用数学家（Bortz）的实验室之间的密切合作基础上 生物学家/生物化学家（LIU）和统计学家（Dukie）。它旨在改变对细胞迁移的科学理解 通过发现以前未知的生化和物理机制。拟议的调查是一种新颖的混合物 高级数学和统计查询和实验验证，并反映了持续的协同工作 在三个实验室中。