Spatial organization of phenotypically diverse cells during collective migration

集体迁移过程中表型多样化细胞的空间组织

基本信息

批准号：
10607159
负责人：
Lam Vo
金额：
$ 4.77万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10607159
关键词：
Address Affect Back Bacteria Behavior Biological Process Cells Chemicals Chemotaxis Consumption Disease Drug resistance Environment Escherichia coli Eukaryotic Cell Exhibits Exotoxins Frequencies Gene Expression Genes Human Immune Individual Infection Knowledge Laboratory Finding Lead Liquid substance Measurement Measures Mediating Medicine Microbial Biofilms Microbiology Microfluidic Microchips Nature Neoplasm Metastasis New Territories Pathogenesis Performance Pharmacotherapy Phenotype Physical environment Polysaccharides Population Porosity Positioning Attribute Process Production Pseudomonas aeruginosa Reporter Running Second Messenger Systems Sepharose Series Sorting Spatial Behavior Speed Structure Surface Swimming Theoretical model Time Travel Type III Secretion System Pathway Virulence Virulence Factors acute infection cancer cell cancer therapy cell motility chronic infection commensal bacteria falls host colonization human pathogen improved insight mathematical model migration new technology pathogen pathogenic bacteria pathogenic microbe physical property population migration predictive modeling resistance mutation sensor trait

项目摘要

PROJECT SUMMARY Cells within populations act collectively, allowing them to behave in ways that exceed the capability of a single cell. At the same time, even a genetically homogenous population exhibits phenotypic diversity, allowing the population to adapt in unpredictable environments. Both of these features complicate treatment of cancer, infections, and diseases. It is of critical importance to understand how phenotypic diversity modulates a population’s behaviors, yet this interaction is not fully understood. The proposed project will address this knowledge gap by studying the collective migration of commensal and pathogenic bacteria. Groups of bacteria (and eukaryotic cells) can migrate collectively by consuming attractants in the environment and chasing the moving gradient that they have created. This allows cell populations to travel over much longer distances than what can be achieved by an individual cell following external gradients. Our lab found that bacterial cells within migrating groups spatially organize themselves by their chemotaxis abilities, or the speeds at which they climb chemical gradients. This spatial organization within the migrating group allows cells with diverse motility behaviors to migrate together because it places high performers at the front, where the traveling gradient is shallower, and low performers near the back, where the traveling gradient is steeper. Here, I will examine the consequences of this spatial organization for populations that are migrating in different environments and performing pathogenesis. Aim 1 will determine how the spatial organization of motility behaviors in a bacterial population is altered when the physical properties of the environment are changed. Then, Aim 2 will explore to what extent a population of a human pathogen utilizes the spatial organization of secondary messenger levels and motility behaviors to co-sort virulence phenotypes. Our findings will be used to develop a mathematical model that describes how a migrating group of cells alters the spatial organization of its phenotypes to migrate across different environments. They will also provide insights on how the spatial organization of swimming behaviors can lead to co-organization of secondary messenger levels and virulence traits, allowing pathogens to perform multiple infection-related tasks simultaneously during migration. Because some of the basic mechanisms involved – e.g. phenotypic diversity in motility and the degradation or consumption of an external attractant to drive the collective behavior – are also present during the collective migration of immune cells and cancer cells, the findings in the project will be relevant beyond microbiology.

项目概要群体内的细胞集体行动，使它们的行为方式超出了单个细胞的能力同时，即使是遗传同质的细胞群也表现出表型多样性，从而允许人口适应不可预测的环境这两个特征都使癌症的治疗变得复杂，了解表型多样性如何调节感染和疾病至关重要。人口的行为，但这种相互作用尚未完全理解，拟议的项目将解决这个问题。通过研究共生菌和病原菌的集体迁移来弥补知识差距。（和真核细胞）可以通过消耗环境中的引诱剂并追逐他们创造的移动梯度使得细胞群能够移动比它们更长的距离。我们的实验室发现，单个细胞遵循外部梯度可以实现什么。迁徙群体通过趋化能力或攀爬速度在空间上组织自己迁移组内的这种空间组织允许细胞具有不同的运动性。行为一起迁移，因为它将高绩效者置于最前面，其中移动梯度为后面的区域较浅且表现较差，此处的行驶坡度较陡。这种空间组织对在不同环境中迁移的人口的影响目标 1 将确定运动行为的空间组织。当环境的物理特性改变时，细菌种群也会改变。 2 将探讨人类病原体种群在多大程度上利用了空间组织我们的研究结果将是共同排序毒力表型的次级信使水平和运动行为。用于开发一个数学模型，描述一组迁移的细胞如何改变空间他们还将提供有关如何组织其表型以跨不同环境迁移的见解。游泳行为的空间组织可以导致次要信使水平的共同组织毒力特征，允许病原体在迁移过程中同时执行多种感染相关的任务。因为涉及一些基本机制——例如运动性和降解的表型多样性。消耗外部引诱剂来驱动集体行为——也存在于集体行为期间免疫细胞和癌细胞的迁移，该项目的发现将超越微生物学。