Combined multiscale modeling and experimental study of bacterial swarming

细菌群落的多尺度建模与实验研究相结合

• 批准号: 8604162
• 负责人: Mark Alber
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8604162
• 关键词: Acute; Algorithms; Assimilations; Bacteria; Behavior; Biological; Biological Phenomena; Burn injury; Cell Communication; Cell Density; Cells; Characteristics; Chemicals; Clinical; Communities; Complex; Computer Simulation; Cooperative Behavior; Couples; Cues; Cystic Fibrosis; Data; Engineering; Environment; Event; Eye; Film; Flagella; Gene Expression; Generic Drugs; Genetic; Genomics; Goals; Growth; Heterogeneity; Human; Image; Individual; Infection; Knowledge; Laboratories; Laboratory Study; Lead; Liquid substance; Lung; Measures; Microbial Biofilms; Microspheres; Modeling; Motion; Movement; Nutrient; Pattern; Pattern Formation; Physical environment; Pilum; Population; Prevention; Process; Production; Property; Proteomics; Pseudomonas aeruginosa; Regulation; Reporter; Research; Rotation; Signal Transduction; Skin; Stimulus; Stress; Structure; Surface; Surface Tension; Testing; Therapeutic; Time; Variant; Work; appendage; base; cell behavior; cell motility; density; design; fluid flow; gastrointestinal infection; homoserine lactone; imaging Segmentation; improved; interest; models and simulation; multi-scale modeling; mutant; pathogen; quorum sensing; research study; rhamnolipid; simulation; surfactant; trend

DESCRIPTION (provided by applicant): Most bacteria in natural and clinical settings grow as surface-attached biofilms, which are bacterial communities that have self-assembled into an encased matrix. One mode of surface motility, called swarming, is observed in cells that are propelled by rotating flagella, by the secretion of slime, and by retracting type IV pili. Study of swarming is particularly important because its regulation is controlled by combination of complex and variable multi-scale events. While swarming, a bacterial community may move in a large-scale coordinated pattern exceeding the size of individual bacterium by orders of magnitude depending upon the gene expression of individual cells, the sensing of chemical signals present in a hydrating environment, and the physical characteristics influencing the attached bacterial cells. To date, the most advanced modeling efforts of bacterial motility have focused on single levels or scales, e.g., genomic/proteomic, cellular and population. The bacterium Pseudomonas aeruginosa is an opportunistic human pathogen that causes skin, eye, lung, and gastrointestinal infections in susceptible individuals. We propose to study P. aeruginosa swarming by developing and integrating models from micro-scales to macro-scales to analyze bacterial motility in concert with laboratory experiments. Integration between scales will lead to a much deeper understanding of the universal or generic features of biological phenomena and how simultaneous processes at different scales interact. The main hypothesis of this proposed research is that bacteria coordinate cell density and cooperation to maximize surface motility which requires assimilation of population, nutrient, and physical cues by these cells. Because identification of cell interactions is extremely difficult experimentally, we will use multi-scale models to perform predictive simulations describing complex bacterial interactions that potentially control swarming. Study of the mechanisms of bacterial pattern formation will help identify the key interactions between cells, describe a mechanism of bacterial surface colonization, and provide knowledge for engineering and controlling bacterial growth on surfaces. A key aspect of this work will be to compare the predictions obtained in silico with experimental observations to calibrate the model and use the model to generate new biological hypotheses to be tested experimentally. Of particular interests to be examined are the influence of motility patterns, surface liquid properties, and cell-cell physical interactions required for Pseudomonas aeruginosa swarming. Our proposed iterative approach will use multiscale model simulations and laboratory experiments to describe variations to swarming with alterations to motility and rhamnolipid production in combination with laboratory examination of isogenic mutants deficient in certain motility modes or rhamnolipid production. This work will allow us to determine how bacteria efficiently colonize surfaces by coordinating their motion and rhamnolipid production over time.

描述（由申请人提供）：大多数细菌在自然和临床环境中生长为表面附着的生物膜，这是一种自组装成封闭基质的细菌群落。在细胞中观察到一种称为蜂群的表面运动模式，这种模式通过旋转鞭毛、分泌粘液和收缩IV型毛来推进。蜂群的调控是由复杂多变的多尺度事件组合控制的，因此对蜂群的研究显得尤为重要。在群集的过程中，细菌群落可能以大规模协调的模式移动，其大小超过单个细菌的数量级，这取决于单个细胞的基因表达、对水化环境中存在的化学信号的感知以及影响附着细菌细胞的物理特性。迄今为止，最先进的细菌运动建模工作集中在单个水平或尺度上，例如基因组/蛋白质组学，细胞和种群。铜绿假单胞菌是一种机会性人类病原体，可引起易感个体的皮肤、眼睛、肺部和胃肠道感染。我们建议通过建立从微观尺度到宏观尺度的综合模型来研究铜绿假单胞菌的群集，并结合实验室实验来分析细菌的运动。尺度之间的整合将导致对生物现象的普遍或一般特征以及不同尺度上的同时过程如何相互作用的更深层次的理解。本研究的主要假设是，细菌协调细胞密度和合作，以最大限度地提高表面运动性，这需要这些细胞同化人口，营养和物理线索。由于细胞相互作用的鉴定在实验上是极其困难的，我们将使用多尺度模型来进行预测模拟，描述可能控制蜂群的复杂细菌相互作用。细菌模式形成机制的研究将有助于确定细胞间的关键相互作用，描述细菌表面定植的机制，并为工程和控制细菌在表面上的生长提供知识。这项工作的一个关键方面是将在计算机中获得的预测与实验观察结果进行比较，以校准模型，并使用该模型生成新的生物学假设，以进行实验验证。特别感兴趣的是运动模式的影响，表面液体性质，以及铜绿假单胞菌群集所需的细胞-细胞物理相互作用。我们提出的迭代方法将使用多尺度模型模拟和实验室实验，结合实验室检查缺乏某些运动模式或鼠李糖脂产生的等基因突变体，来描述蜂群随运动模式和鼠李糖脂产生变化的变化。这项工作将使我们能够确定细菌如何通过协调它们的运动和鼠李糖脂的生产来有效地在表面定植。