Spatiotemporal models of intra and extra cellular processes

细胞内和细胞外过程的时空模型

• 批准号: RGPIN-2016-04314
• 负责人: Iron, David
• 金额: $ 1.09万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=709095
• 关键词: Spatiotemporal; models; intra; extra; cellular

Mathematical models are playing an increasingly important role in the understanding of biological processes. My research focuses on models related to cellular processes. Specifically I use methods from asymptotic analysis and perturbation theory to study systems which form localized structures. Such systems play important roles in many areas of biology. The new models being considered include a model of plaque formation in atherosclerosis, a model of the formation of polarity in the early C. elegans development and a model of cell surface receptor aggregation. As well we will continue to work on models of cell signal transduction and general pattern formation. Some details of each project follow. Atherosclerosis is a leading cause of death in the world today. Briefly the disease consists of the formation of a fatty plaque on the arterial wall resulting in a blockage and reduction in blood flow. We will model the system with a reaction-diffusion system consisting of the interaction between immune cells, foam cells, and low-density lipoproteins (distinguishing between the oxidized and unoxidized forms) and chemo-attractants. Previous studies have shown that such systems can form localized solutions representing a plaque. We will use the methods for studying nonlinear patterns to determine the condition under which a plaque may form and find the size of the plaque. A great deal is known about the developmental process of the nematode C. elgans. One of the first steps to occur is the formation of anterior and posterior regions the egg after fertilization. This is accomplished by the segregation of proteins to opposite ends of the cell, creating two biochemically distinct regions. We model the system with a reaction-diffusion equation which incorporates the geometry of the egg. We intend to show that the egg geometry is crucial for the formation of a robustly placed barrier. In previous work, I have considered a three dimensional model of cell signal transduction. A key element of this model was the localization of enzymes which activate messenger molecules in the signal transduction process. This work focused on the events occurring inside the cell. We now propose a model of the formation of surface receptor aggregation. We will use density dependent diffusion to model the effect of reduced motility of large groups of cell surface molecules.

数学模型在理解生物过程中起着越来越重要的作用。 我的研究重点是与细胞过程相关的模型。具体来说，我使用的方法从渐近分析和微扰理论研究系统，形成本地化的结构。 这些系统在生物学的许多领域发挥着重要作用。 正在考虑的新模型包括动脉粥样硬化斑块形成模型，早期C. elegans发育和细胞表面受体聚集的模型。 我们也将继续研究细胞信号转导和一般模式形成的模型。 每个项目的一些细节如下。 动脉粥样硬化是当今世界的主要死亡原因。 简单地说，这种疾病包括在动脉壁上形成脂肪斑块，导致血流阻塞和减少。 我们将用一个反应扩散系统来模拟这个系统，这个系统由免疫细胞、泡沫细胞和低密度脂蛋白（区分氧化和未氧化的形式）与化学引诱物之间的相互作用组成。以前的研究表明，这种系统可以形成代表斑块的局部溶液。 我们将使用研究非线性模式的方法来确定斑块可能形成的条件并找到斑块的大小。 关于线虫C. elgans。 发生的第一个步骤之一是在受精后形成卵子的前部和后部区域。 这是通过将蛋白质分离到细胞的相对两端来实现的，从而产生两个生物化学上不同的区域。 我们的反应扩散方程，其中包括鸡蛋的几何形状的系统模型。 我们打算表明，鸡蛋的几何形状是一个强大的放置障碍的形成至关重要。 在以前的工作中，我考虑了细胞信号转导的三维模型。 该模型的一个关键要素是在信号转导过程中激活信使分子的酶的定位。 这项工作的重点是细胞内发生的事件。 我们现在提出一个模型的表面受体聚集的形成。 我们将使用密度依赖性扩散来模拟大量细胞表面分子运动性降低的影响。