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Vibrio fischeri as a Model for Bacterial Colonization

费氏弧菌作为细菌定植的模型

基本信息

批准号：
10338077
负责人：
MARGARET J MC FALL-NGAI
金额：
--
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-12-01 至 2022-02-02
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10338077
关键词：
Address Affect Animals Apical Automobile Driving Bacteria Bacterial Model Binding Biochemical Biological Models Biology Biophysics Birth Cell Nucleus Cells Cellular biology Characteristics Chronic Circadian Rhythms Communities Complex Confocal Microscopy Cues DNA Development Environment Epithelial Euprymna scolopes Event Exposure to Fluorescent in Situ Hybridization Fostering Gastrointestinal tract structure Gene Expression Generations Genes Genetic Genetic Transcription Genomics Goals Gram-Negative Bacteria Health Hour Human Human Microbiome Image Immune response Individual Investigation Libraries Life Light Maintenance Measures Membrane Methods Microbe Microbial Genetics Modeling Molecular Mucous Membrane Nanotechnology Nuclear Outcome Pathogenesis Pathogenicity Pattern Process RNA Reaction Research Resolution Role Scientist Series Signal Transduction Signaling Molecule Small RNA Spectrometry, Mass, Secondary Ion Squid Study models Surface Symbiosis System Time Tissues Transcript V. fischeri-squid system Variant Vesicle Vibrio Vibrio cholerae Vibrio fischeri Virulence Visualization beneficial microorganism critical period extracellular frontier gastrointestinal epithelium host colonization host microbiome host-microbe interactions human tissue infancy innovation insight microbial microbial community microbial composition microbiota nano-string nanoscale new technology normal microbiota novel imaging technique novel strategies pathogen pathogenic microbe programs response success symbiont trafficking transcriptome sequencing transcriptomics

项目摘要

Project Summary/Abstract - The long-term goals of the proposed research program are to provide insight into the complex dialogue that occurs each generation between humans and their microbiota during the critical period following birth. Recent research has indicated a strong correlation between outcomes of these early events and life-long health. However, the inaccessibility of colonized tissues and high diversity of the microbiota renders an in-depth study of early colonization of human tissues extremely challenging. When faced with such complex phenomena, biologists often turn to simpler model systems to provide insights into evolutionarily conserved features and reveal basic principles. To decipher the cellular and molecular mechanisms underlying the initiation of bacterial associations with apical surfaces of mucosal epithelia, the proposed program exploits the binary symbiosis between the bacterium Vibrio fischeri and its squid host, Euprymna scolopes. This relatively simple association has been studied for over two decades as a model for the chronic colonization of mucosa by Gram-negative bacteria. As in humans, the squid-vibrio association begins anew each generation, requiring a `winnowing' of other environmental bacteria that results in persistent association restricted to the coevolved partners. In this system, the process of symbiosis initiation occurs across ~100 microns over minutes to hours. It can be directly imaged in its entirety using confocal microscopy, which offers the rare opportunity to define, with high temporal and spatial resolution, the reciprocal molecular and biochemical dialogue that results in the establishment of a specific, life-long beneficial symbiosis. This project brings together two collaborators, each with expertise in the biology of one of the symbiotic partners, and introduces new technology to the study of host-microbe interactions, including: Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS), which allows precision tracking of symbiont molecules into host tissues; Hybridization-Chain-Reaction Fluorescent In Situ Hybridization (HCR-FISH), which enables visualization of rare transcripts in host and symbiont cells; NanoString, a new technology for simultaneous analysis of dozens to hundreds of targeted transcripts; and high-efficiency RNAseq, which produces robust transcriptional libraries from as little as 10 ng total RNA (~105 bacteria). Specific aims to be addressed are: (1) the examination of how symbiotic bacterial strain variation affects symbiosis onset and persistence; (2) the characterization of outer membrane vesicle (OMV) contents, their trafficking into host cells, and host responses to OMV cargo; and, (3) the investigation of the roles of vibrio virulence determinants in a non-pathogenic association. An understanding of the human microbiome is in its infancy, and this frontier field is currently at the stage of building paradigms. Within this context, as the squid-vibrio system has in the past, the results of the current study will shed light upon fundamental principles governing the onset of both beneficial and pathogenic associations.

项目摘要/摘要-拟议的研究计划的长期目标是提供洞察