Computational Analysis of Spatial Dynamics of Cell Polarization

细胞极性，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的信号转导，但最近的许多实验和理论研究表明，除了反馈调节剂之外，更多的机制包括质膜的亚结构和胞内囊泡运输都有助于细胞极性和细胞形态发生的结构。本研究以数学和计算的方法研究了酵母交配过程中细胞极性的建立和维持以及诱导的细胞形态变化。本项目的第一部分是研究细胞膜上的微区在细胞极化、跟踪刺激的方向变化和衰减信号中存在的噪声中的作用。第二部分将研究在交配过程中维持酵母细胞极化生长的潜在机制，模型包括移动的细胞膜。内吞和胞吐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课题是了解细胞如何感知和反应各种各样的刺激，这些刺激传达了对其生长，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非对称组织，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)是什么控制着信号感知过程中细胞形态发生的出现和动力学？我们的模型是基于已知的实验观察的极化形态变化在酵母交配过程中，他们纳入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，以及这些机制如何在酵母交配过程中参与细胞形态发生。基于数学建模与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生理环境的响应行为。所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，它们也会响应外部信号而发生极化和形态学变化。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学之间的接口跨学科培训。

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.