Spontaneous Organization of Phenotypes during Collective Migration

集体迁徙过程中表型的自发组织

• 批准号: 10033186
• 负责人: Thierry Emonet
• 金额: $ 33.5万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10033186
• 关键词: Address; Affect; Agar; Automobile Driving; Back; Bacteria; Behavior; Cell division; Cells; Cellular biology; Chemotaxis; Communities; Complex; Consumption; Data; Environment; Equilibrium; Escherichia coli; Extravasation; Genotype; Growth; Heritability; Heterogeneity; Individual; Infection; Lead; Liquid substance; Measurement; Measures; Microbial Biofilms; Modeling; Monitor; Motor; Mutation; Pathway interactions; Performance; Phenotype; Physical environment; Population; Population Heterogeneity; Porosity; Positioning Attribute; Process; Pseudomonas aeruginosa; Regulation; Relaxation; Seeds; Signal Transduction; Site; Sorting - Cell Movement; Structure; Swimming; System; Testing; Time; Travel; Virulence Factors; Viscosity; cell growth; cell motility; fall risk; falls; high risk; host colonization; human migration; human pathogen; mathematical model; migration; pathogen; recruit; resilience; trait

Project Summary Bacteria live in structured communities where coordinated interactions between individuals often result in collective behaviors beneficial to the population. At the same time, even isogenic bacteria display phenotypic heterogeneity, which diversifies individual behavior and enhances the resilience of the population in unexpected situations. Understanding how the interplay of diversity and collective behavior contributes to spatial organization and function in cell populations is a fundamental problem in cell biology that has been difficult to tackle experimentally and theoretically because of difficulties in measuring and modeling processes at multiple scales. Here we focus on how phenotypic diversity in motility and chemotactic ability contributes to the spatial organization and phenotypic composition of a population of bacteria as it migrates through diverse environments. Our starting point is the recent discovery by us and others that when chasing traveling fronts of attractant generated by their own consumptions, bacteria spontaneously sort themselves along the traveling gradient: high- performing phenotypes localize at the front where the signal (gradient steepness) is weaker and low-performing phenotypes at the back where the signal is stronger but the risk of falling behind is higher. Thus, a leader-follower organization of the phenotypes emerges, even in isogenic populations, with leaders driving the migration and followers falling off and colonizing space behind the moving front. These observations raise the following basic questions: 1) How do phenotypes reorganize themselves when the population encounters a different environment where the most performant phenotype is now different? What does that tell us about the capacity of a single genotype to navigate as a group through multiple environment? 2) To what extent can cell growth partially compensate for the leakage of cells and how does this affect the phenotypic composition and organization of the migrating population? 3) To what extent does the spatial sorting of motility and chemotaxis phenotypes seed spatial organization of virulence factors that tend to be coregulated? To address these questions, we will develop new mathematical models of collective bacterial migration that include three key ingredients: a continuum of phenotypes, cell growth, and diverse environments. To constrain models, we will use E. coli chemotaxis because it is well-characterized, positioning us to discover general principles, and P. aeruginosa, an opportunistic pathogen that shares some features of the E. coli chemotaxis pathway but expresses two different stator systems necessary for migration through different environments.

项目摘要 细菌生活在结构化的群落中，个体之间协调的相互作用通常会导致 有利于群众的集体行为。与此同时，即使是同基因细菌也表现出表型 异质性，它使个体行为多样化，并增强了人口在意外情况下的弹性。 situations.了解多样性和集体行为的相互作用如何有助于空间组织 在细胞群体中的功能是细胞生物学中的一个基本问题， 实验和理论上，因为在多尺度测量和建模过程的困难。 在这里，我们集中在如何表型多样性的运动和趋化能力有助于空间 细菌种群在不同环境中迁移时的组织和表型组成。 我们的出发点是我们和其他人最近的发现，当追逐引诱剂的移动前沿时， 细菌会自发地沿着移动梯度进行自我分类：高- 表现型位于信号（梯度陡度）较弱和表现较低的前端 在后面的表型，信号更强，但落后的风险更高。因此，一个领导者-追随者 表型的组织出现了，即使在同基因群体中，领导者推动了迁移， 追随者们纷纷离开，在移动的前沿后面殖民太空。 这些观察结果提出了以下基本问题：1）表型如何重组自己时， 种群遇到不同的环境，最具表现力的表型现在不同了吗？什么 这是否告诉我们单个基因型作为一个群体在多个环境中导航的能力？ 2)细胞生长在多大程度上可以部分补偿细胞的泄漏，以及这如何影响细胞的生长。 移民人口的表型组成和组织？3)空间排序在多大程度上 运动性和趋化性表型种子空间组织的毒力因子，往往是共同调节？ 为了解决这些问题，我们将开发新的集体细菌迁移的数学模型， 包括三个关键因素：连续的表型、细胞生长和不同的环境。来约束 模型，我们将使用E.大肠杆菌趋化性，因为它是很好的特点，定位我们发现一般 原则，和铜绿假单胞菌，一种机会致病菌，共享E.大肠杆菌趋化性 途径，但表达了两个不同的定子系统所需的迁移通过不同的环境。