A Computational Survey of Excitable Competence Circuits in Bacillus subtilis

枯草芽孢杆菌兴奋能力回路的计算调查

• 批准号: 1038319
• 负责人: Marc Turcotte
• 金额: $ 48.23万
• 依托单位: University of Texas at Arlington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-24 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1038319&HistoricalAwards=false
• 关键词: Computational; Survey; Excitable; Competence; Circuits

This project is a theoretical investigation focused on the phenomenon of competence in Bacillus subtilis. Competence is the state during which this bacterium can accept and incorporate, into its own genome, DNA from the environment. The competent state is adopted at random times and for random durations and is thought to be an evolutionary strategy to facilitate adaptation to changing environmental stress. In this project computational and simulation approaches will be used 1) to develop hypotheses for plausible theoretical gene regulation topologies that underlie competence, and 2) to compute, numerically, their observable phenotypes. The approach consists of systematically simulating the stochastic behavior of the hypothetical gene regulatory circuit topologies. The work includes deriving, analytically, the continuous limit of each model; it involves connecting the discrete and continuous models, and performing phase plane analyses. Parameter continuation will be used to map the dynamical regimes of these systems. Comparisons with the stochastic behavior will be made and differences leading to potentially interesting biological phenotypes will be identified. The project is expected to suggest new gene regulation circuits to "reengineer" in the bacterium and test in the laboratory. Key issues that are addressed in this project concern the redistribution of noise in gene regulatory networks as a function of circuit topology; whether general principles of noise conservation (or trade off) exist; and the extent to which such principles might inform our understanding of evolutionary processes. Broader Impacts: This project will provide training at the interface of mathematics, computer simulation and biology for undergraduate and graduate students, and for a postdoctoral fellow who is interested in using mathematics and computational simulations in the study of biology. The STARS program (Science Teacher Access to Resources at Southwestern) will provide opportunities for high-school teachers and their students to become engaged in this project. New educational programs at the interface of mathematics and biology will be developed, together with new portable simulation-oriented teaching material for direct use in the classroom. STARS will facilitate interactions with the Dallas Independent School District (DISD) schools and provide access to this project for traditionally underrepresented groups.

该项目是一项理论研究，侧重于枯草芽孢杆菌的能力现象。能力是该细菌可以接受并纳入其自身基因组DNA的状态。在随机的时间和随机持续时间内采用了胜任的状态，被认为是一种进化策略，以促进适应不断变化的环境压力。在此项目中，将使用1）使用构成能力的理论基因调节拓扑的合理理论基因调节的假设，以及2）以数值的方式计算其可观察到的表型。该方法包括系统地模拟假设基因调节电路拓扑的随机行为。这项工作包括在分析上得出每个模型的连续限制；它涉及连接离散和连续模型以及执行相平面分析。参数延续将用于绘制这些系统的动态态度。将与随机行为进行比较，并确定导致潜在有趣的生物学表型的差异。预计该项目将建议在细菌中“重新设计”并在实验室进行测试。该项目解决的关键问题涉及基因调节网络中噪声的重新分布，这是电路拓扑的函数；是否存在噪声保护（或权衡）的一般原则；以及此类原则可能会在多大程度上了解我们对进化过程的理解。更广泛的影响：该项目将为本科生和研究生的数学，计算机模拟和生物学界面提供培训，并为有兴趣在生物学研究中使用数学和计算模拟的博士后研究员提供培训。 明星计划（科学老师在西南地区获得资源的访问）将为高中老师及其学生提供参与该项目的机会。将开发数学和生物学界面上的新教育计划，以及新的便携式模拟教学材料，可在课堂上直接使用。明星将促进与达拉斯独立学区（DISD）学校的互动，并为传统代表性不足的群体提供该项目的访问权限。