权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Cell-cell interactions and the development of bacterial communities

细胞间相互作用和细菌群落的发展

基本信息

批准号：
10710043
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
项目类别：
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/10710043
关键词：
Address Adhesions Antibiotic Resistance Architecture Bacteria Behavior Biological Models Bioremediations Cell Communication Cell Density Cell Survival Cell model Cells Cellular Structures Cellularity Cholera Collaborations Color Communities Companions Consumption Data Decision Making Development Devices Diffusion Disease Endemic Diseases Environment Enzymes Extracellular Matrix Filtration Gene Expression Gene Expression Profiling Growth Habitats Human Image Imaging Techniques Imaging technology Individual Industrialization Industry Investigation Laboratories Laws 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 biophysical model cell behavior cell community cell motility cellular imaging chronic infection disease transmission empowerment experimental study individual response innovation insight microbiome mutant pathogen quorum sensing response sensory input signal processing simulation spatiotemporal success

项目摘要

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-密集的表面附着的细胞群落嵌入在一个细胞外基质生活在生物膜中的细菌具有许多优点，包括粘附于表面，对抗生素和捕食的抗性，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引起重大问题，因为它们导致慢性感染生物膜污染表面并堵塞过滤装置。生物膜如何组装和分解取决于特定的细菌物种，但存在广泛的一般原则。为了调查原则，在这里，我们问一个基本的问题：生物膜如何能够实现连贯的人口水平结果，如同步拆卸和分散，尽管大的随机变化（“噪音”），在单一的，细胞基因表达？在光片显微镜实现的突破中，我们最近追踪了模型病原体霍乱弧菌的活的、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成像相结合。单细胞基因表达的报告基因，以测量活霍乱弧菌内单个细胞水平的噪音生物膜这些新数据将使我们能够解决我们的基本问题，重点关注这些关键方面： (1)在生物膜中，单个细胞拥有多少关于其时空位置的信息？（二）生物膜细胞如何整合多种时间依赖性感觉输入，以决定是否以及何时分散，这个决定是集体做出的还是在单个细胞层面做出的？要回答这些问题，实验与生物物理建模的迭代合并。特别的建模创新将是信息- 单生物膜细胞从低细胞密度向高细胞密度转变的理论研究，群体感应和营养源信号的集成，基于代理的机械模拟扩散，一个生物膜，并为整个扩散过程的连续模型的发展。我们对宇宙出现的研究在这个易处理的模型系统中，来自嘈杂的单细胞的精确集体行为将为跨细菌物种的类似分析，以及更普遍的连贯多细胞过程。

项目成果

期刊论文数量（63）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Thermal robustness of signaling in bacterial chemotaxis.

DOI：
10.1016/j.cell.2011.03.013
发表时间：
2011-04-15
期刊：
Cell
影响因子：
64.5
作者：
Oleksiuk O;Jakovljevic V;Vladimirov N;Carvalho R;Paster E;Ryu WS;Meir Y;Wingreen NS;Kollmann M;Sourjik V
通讯作者：
Sourjik V

Cell position fates and collective fountain flow in bacterial biofilms revealed by light-sheet microscopy