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Bioimaging core

生物成像核心

基本信息

批准号：
10665022
负责人：
LUKE D HANDKE
金额：
$ 19.74万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10665022
关键词：
Affect Animals Applications Grants Architecture Cells Characteristics Clinical Complex Confocal Microscopy Core Facility Core Grant Development Developmental Process Disease Ensure Environment Event Funding Gene Expression Gene Expression Profile Genetic Transcription Genus staphylococcus Goals Heterogeneity Human Resources Image Imaging technology Immune Immune response In Vitro Infection Intervention Laboratories Life Style Medical Device Metabolic Metabolism Microbial Biofilms Microfluidics Microscope Microscopic Monitor Mus Mutation Nature Pattern Physiological Process Program Research Project Grants Regulation Reproducibility Research Role Staphylococcus aureus Staphylococcus aureus infection Structure System Techniques Technology Testing Time Tissues Tracer Virulence Factors Visualization Work acute infection bioimaging chronic infection cost experimental study fitness implantation in vivo in vivo imaging system insight instrument instrumentation knowledge base migration novel programs virulence gene

项目摘要

The remarkable ability of Staphylococcus aureus to cause acute infections can be largely attributed to the wide array of virulence factors it produces, combined with its ability to exploit various metabolic niches within a host. In contrast, its ability to cause more persistent infections is a function of its propensity to form biofilm, a process that is enhanced by the implantation of medical devices. The current funding cycle has revealed remarkable developmental processes that occur during biofilm formation, including multiple developmental stages, stochastic gene expression, and the formation of distinct structures. Based on these preliminary results, it is hypothesized that the distinct developmental stages of S. aureus biofilm development are required for optimal fitness during infection. This hypothesis will be tested in three specific aims including to 1) define the steps involved in the transition from a planktonic to sessile lifestyle, 2) provide mechanistic insight into the bistable switch, and 3) demonstrate the in vivo role of bistability. Combined, these aims will provide critical insight into the developmental steps involved in S. aureus biofilm formation and define the relevance of these processes in vivo. A common theme of this project will be the highly synergistic nature of the experiments in the context of the other projects of this program, particularly the experiments probing the regulation of virulence gene expression (Project 3) and the in vivo relevance of this regulation (Project 4). Once completed, the results of these experiments will greatly enhance our understanding of S. aureus biofilm development and provide insight into the characteristics of these complex structures that make them so recalcitrant to clinical intervention.

金黄色葡萄球菌引起急性感染的非凡能力在很大程度上归因于它产生的广泛的毒力因子，以及它利用宿主体内的各种新陈代谢生态位。相比之下，它能够导致更持久的感染是其形成生物膜倾向的函数，这一过程通过植入医疗器械。当前的筹资周期显示了显著的发展进程。发生在生物膜形成过程中，包括多个发育阶段，随机基因表达，并形成不同的结构。根据这些初步结果，假设金黄色葡萄球菌生物膜发育的不同阶段是在感染期间保持最佳体能所必需的。这一假设将在三个具体的方面进行检验目标包括：1)确定从浮游生活方式向固着生活方式转变所涉及的步骤； 2)提供对双稳开关的机械洞察，以及3)展示在体内的作用双稳性。综合起来，这些目标将提供对所涉及的发展步骤的关键洞察在金黄色葡萄球菌生物被膜形成中的作用，并确定这些过程在体内的相关性。一种常见的该项目的主题将是在以下背景下的实验的高度协同性质该计划的其他项目，特别是探索毒力调节的实验基因表达(项目3)和这一调节的体内相关性(项目4)。一次完成后，这些实验结果将大大加深我们对金黄色葡萄球菌的了解并提供对这些复杂结构的特征的洞察让他们如此顽固地拒绝临床干预。