Bioimaging core

生物成像核心

基本信息

批准号：
10198696
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/10198696
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 Virulence Factors Work acute infection base bioimaging chronic infection cost experimental study fitness implantation in vivo in vivo imaging system insight instrument instrumentation knowledge base migration novel programs

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显着能力可能在很大程度上是归因于它产生的广泛的毒力因子，并与其利用的能力相结合主机中的各种代谢壁ni。相反，它引起更多持续感染的能力是其形成生物膜的倾向的函数，该过程通过植入而增强医疗设备。当前的资金周期揭示了出色的发展过程在生物膜形成期间发生的，包括多个发育阶段，随机基因表达，以及不同结构的形成。基于这些初步结果，是假设金黄色葡萄球菌生物膜发育的不同发育阶段是在感染过程中最佳适应性所需。该假设将在三个特定的目的包括1）定义从浮游生物到无柄生活方式的过渡涉及的步骤， 2）提供对双态开关的机械洞察力，3）证明了体内的作用双重性。这些目标结合在一起，将为涉及的发展步骤提供重要的见解在金黄色葡萄球菌生物膜形成中，并在体内定义了这些过程的相关性。常见该项目的主题将是实验的高度协同性质该计划的其他项目，尤其是探测毒力调节的实验基因表达（项目3）和该法规的体内相关性（项目4）。一次完成后，这些实验的结果将大大增强我们对金黄色葡萄球菌的理解生物膜开发并洞悉这些复杂结构的特征使它们如此顽固地进行临床干预。