Epithelial Cell Migration: Model selectionn for mechanistic model development

细胞的集体迁移是多细胞生物的一个重要生物学过程。虽然大量的研究 虽然一直致力于研究，但我们仍然缺乏对是什么驱动细胞群运动的基本理解 集中在一个方向上。这个建议的目的是为了促进我们对因果关系的理解， 通过先进的数学建模和新颖的方法， 实验这一目标将在研究角质形成细胞在生长过程中的迁移的背景下进行。 伤口愈合的上皮化阶段。这项研究的一个中心前提是，在这一阶段的研究进展， 伤口愈合导致更深入地了解生物化学和机械信号，这些信号位于细胞的核心， 迁移阻碍对移徙问题进行深入研究的一个主要障碍是， 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， 系统可以在几个候选模型中进行选择，以找到最能代表迁移模式的模型， 那些最能描述潜在生物学的。 该项目建立在应用数学家（Bortz）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物化学和物理机制。拟议中的调查是一种新颖的混合 先进的数学和统计调查和实验验证，并反映了正在进行的协同努力 三个实验室。

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.