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: 8451418
• 负责人: Mark Alber
• 金额: $ 27.87万
• 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/8451418
• 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）：自然和临床环境中的大多数细菌随着表面附着的生物膜而生长，这些生物膜是已经自组装成包含的基质的细菌群落。在通过旋转鞭毛，通过粘液的分泌以及通过缩回IV型pili推动的细胞中观察到一种称为蜂群的表面运动模式。蜂群的研究尤其重要，因为它的调节是通过复杂和可变的多尺度事件组合来控制的。在蜂拥而至的同时，细菌群落可能会以大规模的协调模式移动，该模式超过了单个细菌的大小，具体取决于单个细胞的基因表达，保湿环境中存在的化学信号的传感以及影响附着细菌细胞的物理特征。迄今为止，细菌运动的最先进的建模工作集中在单个水平或量表上，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体病原体，可在易感人群中引起皮肤，眼睛，肺和胃肠道感染。我们建议通过开发和集成从微尺度到宏观尺度的模型来研究铜绿假单胞菌群，以与实验室实验协同分析细菌运动。量表之间的整合将导致对生物学现象的通用或通用特征以及不同量表的同时过程如何相互作用。这项提出的研究的主要假设是，细菌协调细胞密度和合作，以最大程度地提高表面运动，这需要这些细胞吸收种群，养分和物理线索。由于在实验上识别细胞相互作用非常困难，因此我们将使用多尺度模型进行预测性模拟，描述了可能控制群的复杂细菌相互作用。研究细菌模式形成机制将有助于确定细胞之间的关键相互作用，描述细菌表面定植的机制，并为工程和控制表面上的细菌生长提供知识。 这项工作的一个关键方面是将硅中获得的预测与实验观察结果进行比较，以校准模型并使用模型来生成新的生物学假设，以实验测试。要研究的特别感兴趣的是铜绿假单胞菌群所需的运动模式，表面液体特性和细胞 - 细胞物理相互作用的影响。我们提出的迭代方法将使用多尺度模型仿真和实验室实验来描述与运动和鼠李糖脂产生改变的变化，并结合实验室检查某些运动模式或rhamnolipid产生的等源性突变体的实验室检查。这项工作将使我们能够通过随着时间的流逝来确定细菌如何通过协调其运动和鼠李糖脂产生来有效地定居。