Computational Analysis of Spatial Dynamics of Cell Polarization

细胞极化空间动力学的计算分析

• 批准号: 1020625
• 负责人: Ching-Shan Chou
• 金额: $ 16.12万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1020625&HistoricalAwards=false
• 关键词: Computational; Analysis; Spatial; Dynamics; Cell

Cell polarity, the asymmetric organization of cellular components, is fundamental to life. Important cell functions such as differentiation and proliferation rely upon spatially and temporally accurate cell polarization and the induced cell morphologenesis. While polarization typically involves signal transduction through certain pathways, many recent experimental and theoretical studies revealed that, besides the feedback regulators, more machineries including substructure of the plasma membrane and intracellular vesicle trafficking are contributing to the architecture of cell polarity and cell morphogenesis. This project is concerned with a mathematical and computational investigation of the establishment and maintenance of cell polarity and the induced cell morphological change during yeast Saccharomyces cerevisiae mating process. The first part of this project is to study the role of microdomains on the cell membrane in cell polarization, tracking directional changes of the stimuli, and attenuating noise present in the signals. The second part will investigate potential mechanisms that maintain the polarized growth of yeast cells during mating, with models including a moving cell membrane. The roles of endocytosis and exocytosis in cell polarization will be studied with these models. A major topic in cell biology is to understand how cells sense and react to a wide variety of stimuli, which convey information essential for their growth, development and functions. Cell polarization, which relies on an asymmetric organization of intracellular components, has been widely acknowledged to be a fundamental process underlying spatial sensing of stimuli. The work seeks to address two important questions in cell biology through mathematical modeling and computation: 1) how is the cell polarity established and maintained? 2) what controls the emergence and dynamics of cell morphogenesis during signal sensing? Our models are based on the known experimental observations of polarized morphological change during yeast mating process, and they incorporate important components in the signaling network. We will investigate how the machineries such as substructure of the cell membrane and vesicle trafficking, participate in generating and retaining cell polarity, and how those machineries are incorporated in cell morphogenesis during yeast mating process. Quantitative studies of cell polarization and cell morphogenesis, based on the systems biology methodology which integrates mathematical modeling with experiments, will improve our understanding on the behavior of cell in response to the environment or its physiological setting. The developed framework and models could be applied to other systems, such as T-cell and neutrophils, which also undergo polarization and morphological changes in response to external signals. The research project is interdisciplinary and will enhance interdisciplinary training at the interface between mathematics and biology for the students associated with the project.

细胞极性，即细胞成分的不对称组织，是生命的基础。重要的细胞功能，如分化和增殖，依赖于空间和时间上准确的细胞极化和诱导的细胞形态发生。虽然极化通常涉及通过某些途径进行信号转导，但最近的许多实验和理论研究表明，除了反馈调节外，更多的机制，包括质膜亚结构和细胞内囊泡运输，对细胞极性和细胞形态发生的结构起作用。本课题对酿酒酵母交配过程中细胞极性的建立和维持以及诱导细胞形态变化进行了数学和计算研究。这个项目的第一部分是研究细胞膜上的微域在细胞极化中的作用，跟踪刺激的方向性变化，并减弱信号中存在的噪声。第二部分将通过包括移动细胞膜的模型来研究在交配过程中维持酵母细胞极化生长的潜在机制。内吞作用和胞吐作用在细胞极化中的作用将用这些模型来研究。细胞生物学的一个主要主题是了解细胞如何感知和对各种刺激做出反应，这些刺激传达了对细胞的生长、发育和功能至关重要的信息。细胞极化依赖于细胞内成分的不对称组织，已被广泛认为是刺激空间感知的基本过程。这项工作试图通过数学建模和计算来解决细胞生物学中的两个重要问题：1)细胞极性是如何建立和维持的？2)在信号感应过程中，是什么控制了细胞形态发生的出现和动态？我们的模型是基于已知的酵母交配过程中极化形态变化的实验观察，它们包含了信号网络中的重要组成部分。我们将研究细胞膜的亚结构和囊泡运输等机制如何参与细胞极性的产生和保持，以及这些机制如何参与酵母交配过程中的细胞形态发生。基于数学建模和实验相结合的系统生物学方法，对细胞极化和细胞形态发生进行定量研究，将有助于我们更好地理解细胞对环境或其生理环境的响应行为。开发的框架和模型可以应用于其他系统，如T细胞和中性粒细胞，这些系统也会因外界信号而发生极化和形态变化。该研究项目是跨学科的，将加强与该项目相关的学生在数学和生物之间的跨学科培训。