Cell-cell interactions and the development of bacterial communities

细胞间相互作用和细菌群落的发展

• 批准号: 10516785
• 负责人: NED S WINGREEN
• 金额: $ 31.02万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10516785
• 关键词: Address; Adhesions; Antibiotic Resistance; Architecture; Bacteria; Behavior; Biological Models; Bioremediations; Cell Communication; Cell Density; Cell Survival; Cell model; Cells; Cholera; Collaborations; Communities; Companions; Consumption; Data; Decision Making; Development; Devices; Diffusion; Disease; Endemic Diseases; Environment; Enzymes; Extracellular Matrix; Filtration; Gene Expression; Growth; Habitats; Human; Image; Imaging Techniques; Imaging technology; Individual; Industrialization; Industry; Investigation; Laboratories; Laws; Lead; Learning; Ligands; Light; Location; Measures; Mechanics; Medical; Medicine; Metabolic; Microbial Biofilms; Microscopy; Modeling; Motion; Multicellular Process; Nature; New Territories; Noise; Nutrient; Outcome; Pathway interactions; Periodicity; Phenotype; Population; Positioning Attribute; Predatory Behavior; Process; Production; Reporter; Resolution; Role; Second Messenger Systems; Signal Pathway; Signal Transduction; Source; Stimulus; Structure; Surface; System; Theoretical Studies; Time; Tissues; Variant; Vibrio cholerae; Virulence Factors; antibiotic tolerance; bacterial community; base; biophysical model; cell behavior; cell community; cell motility; cellular imaging; chronic infection; disease transmission; experimental study; individual response; innovation; insight; microbiome; mutant; pathogen; quorum sensing; response; sensory input; signal processing; simulation; spatiotemporal; success

PROJECT ABSTRACT In nature, bacteria primarily exist in biofilms – dense surface-attached communities of cells embedded in an extracellular matrix. Many advantages accrue to the bacteria living in biofilms, including adhesion to surfaces, resistance to antibiotics and predation, and collective processing of nutrient sources. From a human perspective, biofilms can be beneficial, e.g. in the context of the microbiome and bioremediation. However, biofilms can also be problematic, e.g. biofilms cause major problems in medicine as they lead to chronic infections, and in industry biofilms foul surfaces and clog filtration devices. How biofilms assemble and disassemble depends on the particular bacterial species, but there exist broadly general principles. To pursue investigations of overarching principles, here we ask the fundamental question: how are biofilms able to achieve coherent population-level outcomes, such as synchronous disassembly and dispersal, despite large stochastic variation (“noise”) in single- cell gene expression? In a breakthrough enabled by light-sheet microscopy, we have recently tracked the individual cells in living, growing biofilms of the model pathogen Vibrio cholerae, from a single founder cell up to 10,000 cells. Therefore, we are now in a position to couple light-sheet imaging with our existing fluorescent reporters of single-cell gene expression to measure noise at the individual-cell level within living V. cholerae biofilms. These new data will empower us to address our fundamental question, with a focus on these key facets: (1) How much information do individual cells possess about their spatiotemporal location within a biofilm? (2) How do biofilm cells integrate multiple time-dependent sensory inputs to decide whether and when to disperse, and is this decision made collectively or at the single-cell level? Answering these questions will require a close, iterative merger of experiments with biophysical modeling. Particular modeling innovations will be information- theoretic studies of single biofilms cells transitioning from low to high cell density, pathway-based analysis of the integration of quorum-sensing and nutrient-derived signals, agent-based mechanical simulation of dispersal from a biofilm, and development of a continuum model for the entire dispersal process. Our studies of the emergence of precise collective behaviors from noisy single cells in this tractable model system will provide a paradigm for similar analyses across bacterial species, and for coherent multicellular processes more generally.

项目摘要 在自然界中，细菌主要存在于生物膜中--致密的表面附着的细胞群落嵌入到 细胞外基质。生活在生物膜中的细菌具有许多优势，包括附着在表面上， 对抗生素和捕食的抗药性，以及对营养源的集体处理。从人类的角度来看， 生物膜可以是有益的，例如在微生物组和生物修复的背景下。然而，生物膜也可以 有问题，例如，生物膜在医学和工业中会造成重大问题，因为它们会导致慢性感染 生物膜、污物表面和堵塞过滤装置。生物膜如何组装和分解取决于 特定的细菌种类，但存在广泛的一般原则。继续调查压倒一切的 原则，在这里我们问一个基本的问题：生物膜如何能够达到一致的种群水平 结果，如同步拆卸和分散，尽管大的随机变化(“噪声”)在单一的- 细胞基因表达？在光片显微镜的突破性进展中，我们最近跟踪了 霍乱弧菌活的、正在生长的生物膜中的单个细胞，从单个创始细胞到 一万个细胞。因此，我们现在能够将光片成像与我们现有的荧光相结合 在活体霍乱弧菌中测量单个细胞水平噪音的单细胞基因表达报告 生物膜。这些新数据将使我们能够解决我们的基本问题，重点放在以下几个关键方面： (1)单个细胞拥有多少关于它们在生物膜中时空位置的信息？(2) 生物膜细胞如何整合多个依赖时间的感觉输入，以决定是否以及何时分散， 这一决定是集体做出的，还是在单个细胞层面上做出的？回答这些问题需要一个结束语， 实验与生物物理模型的迭代合并。具体的建模创新将是信息- 单个生物膜细胞从低密度向高密度转变的理论研究，基于途径的分析 群体感应和营养衍生信号的集成，基于代理的扩散的机械模拟 生物膜，以及整个扩散过程的连续统模型的开发。我们对浮现现象的研究 在这个易处理的模型系统中从嘈杂的单个细胞中获得精确的集体行为将为 细菌种类间的类似分析，以及更普遍的连贯的多细胞过程。