Controlled Diversity in Bacterial Stress Response

枯草芽孢杆菌（Bacillus subtilis）是一种重要的医学和工业土壤生长菌，因其丰富的生物活性而闻名。 应力反应谱在B使用的许多巧妙的程序中。枯草杆菌科普压力 是它吸收细胞外DNA，分化成孢子，合成降解酶， 变得能动。长期以来，人们观察到B。枯草芽孢杆菌表现出表观遗传应激反应多样化： 也就是说，在相同的环境条件下，在遗传上同克隆的细胞群中，一些细胞将 开始“选择”压力反应，而其余的激活替代途径。实验室 条件被设计成不利于这种克隆多样性，这是许多人不希望的并发症。 实验和工业应用。然而，任何一种表型噪音都是虚假的，存在的原因仅仅是 对于统一的反应没有强选择;或者多样化由细胞控制， 进化的目的这一建议是基于后一种观点。我们的假设是基于一个正在成长的身体 有证据表明，微生物的压力反应多样化可能是对不可预测的环境的适应性反应。 环境，并通过我们的初步建模研究。在这里，我们提出了一个有指导的计划，以量化 在B中的多个应激反应途径上的概率决策。枯草，并阐明 网络特征引起了转换和多样化。更具体地说，我们建议系统地 测量B的分数。枯草杆菌细胞致力于孢子形成的所有可能组合， 对一系列应激反应的DNA转化、枯草杆菌蛋白酶合成和运动能力 这些条件旨在行使控制这些过程的综合网络的每一部分。因为我们的 实验设计要求一系列的压力源，而不是单一的压力源，这些数据也将开始， 量化电路中的环境记忆。我们计划在平均人口水平上收集数据， 亚群水平和单细胞水平，都与四种应激的表达模式有关 应答该数据集通过多个模态的协调测量而变得独特， 通过与数学模型的形式比较进行分析。这项研究是第一次系统地 测量，建模，并解释跨多种压力反应的协调多样化，并将形成 为今后研究微生物多样化的生理意义奠定了基础。

Bacillus subtilis, a medically and industrially important soil growing bacterium, is well known for its rich stress response spectrum. Among the many ingenious programs employed by B. subtilis to cope with stress are its ability to take up extracellular DNA, differentiateinto spores, synthesize degradative enzymes, and become motile. It has long been observed that B. subtilis exhibits epigenetic stress response diversification: that is, in a genetically isoclonal population of cells under identical environmental conditions, some cells will embark on the 'selected' stress response, while the remainder activate alternative pathways. Laboratory conditions are designed to militate against this clonal diversity, an undesirable complication in many experiments and industrial applications. However, either phenotypic noise is spurious, existing only because there is no strong selection for a uniform response; or diversification is controlled by the cell and serves an evolutionary purpose. This proposal is based on this latter view. We base this hypothesis on a growing body of evidence that stress response diversification in microbes can be an adaptive response to an unpredictable environment, and by our preliminary modeling studies. Here we propose a directed program to quantify the probabilistic decision-making across multiple stress response pathways in B. subtilis, and to elucidate the network features giving rise to switching and diversification. More specifically, we propose to systematically measure the fraction of B. subtilis cells committing to all possible combinations of spore formation, competence for DNA transformation, subtilisin synthesis, and motility, in response to a series of stress conditions designed to exercise each part of the integrated network controlling these processes. Because our experimental design calls for a series of stressors, rather than single stressors, these data will also begin to quantify environmental memory in the circuitry. We plan to collect data at an average population level, a subpopulation level, and a single cell level, all pertaining to the expression patterns of the four stress responses. This data set,made unique by the coordinated measurements across multiple modalities, will be analyzed through formal comparison to a mathematical model. This study is the first effort to systematically measure, model, and explain coordinated diversification across multiple stress responses, and will form the foundation for future studies on the physiological significance of diversification in microbes.