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

Biomechanical Regulation of Microbial Self-Organization in Confined Environments

密闭环境中微生物自组织的生物力学调节

基本信息

批准号：
10445778
负责人：
Oskar Hallatschek
金额：
$ 32.58万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10445778
关键词：
Address Bacteria Behavior Biological Assay Biological Models Biomechanics Biophysics Bone Tissue Candida albicans Cell Cycle Progression Cell Proliferation Cell Shape Cell Wall Cell model Cells Colon Communities Complement Computer Simulation Confined Spaces Crowding Data Dental Dental Implants Disease Drug Costs Drug resistance Ecosystem Engineering Environment Environmental Impact Epithelial Cells Escherichia coli Evolution Feedback Funding Generations Genetic Genetic Variation Genetic study Goals Growth Habitats Health Homologous Gene Human Individual Invaded Joints Laboratories Laws Liquid substance Measures Mechanical Stress Mechanics Medical Microbe Microfluidic Microchips Microfluidics Modeling Modernization Monitor Motion Mutagenesis Organism Outcome Pathogenicity Physiological Physiological Adaptation Population Population Dynamics Population Genetics Population Growth Process Property Regulation Research Role Saccharomyces cerevisiae Saccharomycetales Shapes Skin Structure System Techniques Testing Theoretical model Time Tissues Tooth structure Urinary tract Urinary tract infection Virulence Work Yeasts base biological adaptation to stress cell growth colonization resistance commensal microbes experimental study fungus gene network gut microbiome improved insight intestinal crypt laboratory experiment mathematical model mechanical force microbial microbial community microbiome mutant novel novel strategies opportunistic pathogen pathogen pathogenic fungus pathogenic microbe pressure resilience resistance mutation self organization simulation soft tissue spatiotemporal theories

项目摘要

Title: Biomechanical regulation of microbial self-organization in confined environments Inside hosts, microbes grow under spatial constraints and frequently become so crowded that mechanical stresses influence their behavior. For example, within humans, microbes often form fine-structured aggregates in cavities on teeth, skin follicles, or crypt-like structures in the colon, which are increasingly recognized as an important factor influencing human health. Although new layers of mechanical regulation of collective microbial growth and motion have emerged in recent years, we know little about how such regulation influences the self- organization of microbial communities. The main challenges are to experimentally monitor and theoretically model the feedback between forces and growth at the same time and across multiple scales. The objective of the proposed research is to quantify and model the direct and indirect feedback between growth and mechanical forces in order to explain and predict the self-organization of dense cellular populations. To this end, the P.I. proposes microfluidic and lineage tracking experiments spanning cellular to community-level scales, as well as extrapolating simulations and theory. The proposed research leverages the intense dialog between theory and experiment cultivated in his laboratory to achieve a predictive understanding of self- organization in microbial populations in terms of the joint actions of individual cells. The P.I. has two specific aims. First, he will identify and characterize physiological adaptations that enable microbial populations to sustain large mechanical stresses and cell shape deformations. Understanding such direct feedback between forces and growth will illuminate the role of forces in the pathogenic invasion of hosts, which is a key step for virulence. Second, he will elucidate how dense microbial populations establish in tight micro-environments, how they fend off invaders, turn over and adapt. Answering these questions will inform strategies to promote or perturb a resilient microbial ecosystem in the gut or other crowded environments. The proposed work develops state-of-the-art microfluidic techniques that enable automated spatio-temporal tracking of cells and a novel strategy to track evolutionary processes, under defined mechanical boundary conditions. The simulations developed synthesize modern population genetic theory with feature-rich biophysical simulations and bridge the gap in spatio-temporal scales between laboratory experiments and natural populations. The planned novel microfluidic devices and computer simulations will be of broad utility to the biophysics community for the goal of dissecting collective properties of microbial populations. 1

题目：密闭环境中微生物自组织的生物力学调控