Staphylococcal Biofilm and Disease

葡萄球菌生物膜和疾病

基本信息

批准号：
10461790
负责人：
KENNETH W. BAYLES
金额：
$ 233.35万
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/10461790
关键词：
Abscess Acetates Amino Acids Anti-Inflammatory Agents Automobile Driving Biology Carbon Catabolism Cells Clinical Management Communities Confocal Microscopy Development Developmental Process Disease Education Ensure Environment Enzymes Funding Genetic Transcription Genome Genus staphylococcus Glucose Goals Growth Healthcare Systems Histone Deacetylase Hyaluronidase Immune Immune response Infection Inflammatory Innate Immune Response Interleukin-10 Kinetics Knowledge Libraries Life Style Ligands Medical Device Metabolic Metabolic Pathway Metabolism Microbial Biofilms Microfluidics Modeling Mus Mutation Nebraska Nitrogen Nutrient Online Systems Peptide Hydrolases Peptide Transport Peptides Phosphotransferases Polymers Production Property Protocols documentation Regulation Research Role Scientific Inquiry Source Staphylococcus aureus System Testing Tissues Virulence Factors Vision Work bioimaging extracellular fitness improved in vivo in vivo imaging system inflammatory milieu insight macrophage metabolome metabolomics mutant novel strategies nuclease online resource pathogen programs proline permease receptor synergism tool web page web site

项目摘要

During the previous funding cycle, our program project entitled “Staphylococcal biofilm and disease” has employed in-depth mechanistic approaches to define the developmental and metabolic processes important in Staphylococcus aureus biofilm development. A key aspect of the synergy of this project is that the knowledge gained was used as context to provide a more detailed understanding of the acquisition of available nutrients within specific host niches, as well as the impact of biofilm growth on the host immune response. These studies have led to a greatly enhanced understanding of the way in which S. aureus adapts to a host environment, providing new fundamental insight into biofilm development and novel approaches to the clinical management of staphylococcal disease. The overall hypothesis driving the goals of the proposed program project, S. aureus biofilm development creates unique metabolic niches that promote an immune suppressive environment, is a natural outgrowth of the current funding cycle and is tested in four synergistic and complementary projects that encompass a broad spectrum of synergistic and highly collaborative activities ranging from the basic biology of biofilm development and matrix regulation, to the host-associated metabolic processes that influence the immune response. To support the efforts of these four projects, we propose a continuation of our Bioimaging Core that maintains a BioFlux microfluidics system for biofilm growth and analysis, confocal microscopy, and an In Vivo Imaging System (IVIS). In addition, we propose a new Metabolomics Core that will establish and maintain the protocols and modeling needed to support the four projects associated with this PPG. Importantly, our vision is that the work of this core will lead to the development of a web-based metabolomics tool (funded through a separate mechanism) that will serve not only as an education tool to enhance the overall understanding of the S. aureus metabolome, but also as a hypothesis generator in support of scientific inquiry. Once this tool is established and validated, we will then make it available to the entire staphylococcal research community as a web-based resource that is integrated with our existing Nebraska Transposon Mutant Library (NTML) website. Finally, we propose an Administrative Core that will provide the administrative support needed to maximize the interactions between project leaders and to ensure that their projects maintain optimal synergy.

在上一个融资周期中，我们的计划项目名为“葡萄球菌生物膜和疾病” 采用深入的机械方法来定义重要的发展和代谢过程金黄色葡萄球菌生物膜发育。该项目协同作用的一个关键方面是知识获得的环境用作对可用营养的获取的更详细的了解在特定的宿主生态位以及生物膜生长对宿主免疫反应的影响。这些研究已经使S.金黄色葡萄球菌适应主机环境的方式有了极大的增强为生物膜开发和临床管理的新方法提供新的基本见解葡萄球菌疾病。总体假设推动了拟议计划项目的目标生物膜开发产生独特的代谢壁ni，促进免疫抑制环境，是当前资金周期的自然产物，在四个协同和完全项目涵盖了广泛的协同和高度协作活动从生物膜开发和基质调节的基本生物学到与宿主相关的代谢影响免疫反应的过程。为了支持这四个项目的努力，我们建议延续我们维护生物液体微流体系统生物生长和分析，共聚焦显微镜和体内成像系统（IVI）。此外，我们提出了一个新的代谢组学核心将建立和维护支持这四个的协议和建模与此PPG相关的项目。重要的是，我们的愿景是该核心的工作将导致发展基于Web的代谢组学工具（通过单独的机制资助），该工具不仅可以作为一个增强金黄色葡萄球菌代谢组的整体理解的教育工具，也可以作为假设支持科学探究的发电机。建立和验证此工具后，我们将其可用将整个葡萄球菌研究社区作为一个基于网络的资源，与我们现有的资源集成内布拉斯加州转座子突变库（NTML）网站。最后，我们提出了一个行政核心提供最大化项目领导者之间互动所需的行政支持并确保他们的项目保持最佳协同作用。