Coupled Biological and Mathematical Model of Neuronal P

神经元 P 的生物学和数学耦合模型

• 批准号: 6828747
• 负责人: Marit Nilsen-Hamilton
• 金额: $ 29.26万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6828747
• 关键词: bioengineering /biomedical engineering; biological models; biological signal transduction; brain; cell biology; cell differentiation; cell migration; cell population study; computational biology; developmental neurobiology; extracellular matrix proteins; laboratory mouse; mathematical model; model design /development; nerve stem cell; neurotrophic factors; organ culture; tissue /cell culture

DESCRIPTION (provided by applicant): A fundamental question in biology is how development of the elaborately organized mammalian brain is orchestrated. Current knowledge suggests that the pattern formation during brain development is guided by a variety of signals including diffusible neurotrophic factors and preformed distributions of extracellular matrix proteins including adhesion molecules. The relative contributions of these elements and the number of permutations of each type of signal is unknown. To develop a better understanding of the movement and differentiation of neural stem cells (NSCs) in vivo, we propose to develop a mathematical model, using a cell culture system to provide quantitative data for the model. We will test the hypothesis that individual cells in a NSC population are diverse in their capability of responding to their environment by migration and differentiation. As a corollary to this hypothesis, we will test whether NSCs respond with different behaviors to unique combinations of signals from diffusible neurotrophic factors and preformed distributions of extracellular matrix (ECM) proteins. Based on this hypothesis, we propose the following specific aims: 1) Develop a biological model to test the role of extracellular matrix proteins and diffusible factors on NSC patterning. 2) Develop a mathematical model that can predict the outcome of perturbations in the biological model, and 3) Test the mathematical model using an organ culture system for NSC patterning. The current team is well prepared to carry out the proposed project and includes a developmental biologist, a molecular biologist, a polymer chemist, a mathematician, and a numerical modeler. Several individuals in this group have collaborated for many years and the group met and discussed this problem over the period of a year before submitting the application. This interdisciplinary approach will provide fundamental insights into the process of stem cell behavior during tissue integration.

描述（由申请人提供）：生物学的一个基本问题是如何精心组织哺乳动物大脑的发育。目前的知识表明，大脑发育过程中的模式形成是由多种信号引导的，包括扩散性神经营养因子和细胞外基质蛋白（包括粘附分子）的预先分布。这些元素的相对贡献以及每种类型信号的排列数量未知。为了更好地理解体内神经干细胞（NSC）的运动和分化，我们建议开发一个数学模型，使用细胞培养系统为模型提供定量数据。我们将检验这样一个假设：NSC 群体中的各个细胞通过迁移和分化来响应环境的能力是不同的。作为这一假设的推论，我们将测试 NSC 是否会对来自扩散性神经营养因子和细胞外基质 (ECM) 蛋白预先形成的分布的信号的独特组合做出不同的反应。基于这一假设，我们提出以下具体目标：1）开发生物模型来测试细胞外基质蛋白和扩散因子对 NSC 模式的作用。 2) 开发一个可以预测生物模型中扰动结果的数学模型，以及 3) 使用用于 NSC 模式的器官培养系统测试数学模型。 目前的团队已做好执行拟议项目的充分准备，包括一名发育生物学家、一名分子生物学家、一名高分子化学家、一名数学家和一名数值建模师。该小组中的几个人已经合作多年，并且在提交申请之前的一年内，该小组会面并讨论了这个问题。这种跨学科方法将为组织整合过程中干细胞行为过程提供基本见解。