Staphylococcal Biofilm and Disease

在上一个资助周期中，我们题为“葡萄球菌生物膜与疾病”的项目已 采用深入的机械方法来定义重要的发育和代谢过程 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 获得的信息被用作背景，以提供对获取可用营养物质的更详细的了解 在特定的宿主生态位内，以及生物膜生长对宿主免疫反应的影响。这些研究 极大地加深了对金黄色葡萄球菌适应宿主环境的方式的了解， 为生物膜发展提供新的基本见解和临床管理的新方法 葡萄球菌病。推动拟议计划项目目标的总体假设，金黄色葡萄球菌 生物膜的发育创造了独特的代谢生态位，促进免疫抑制 环境，是当前融资周期的自然产物，并在四个协同和 涵盖广泛协同和高度协作活动的互补项目 从生物膜发育和基质调节的基础生物学到宿主相关的代谢 影响免疫反应的过程。为了支持这四个项目的努力，我们提出了 我们的生物成像核心的延续，维持用于生物膜生长的 BioFlux 微流体系统和 分析、共焦显微镜和体内成像系统 (IVIS)。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四个所需的协议和建模 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带来发展 基于网络的代谢组学工具（通过单独的机制资助）不仅可以作为 教育工具，以增强对金黄色葡萄球菌代谢组的整体了解，同时也作为一种假设 支持科学探究的发生器。一旦建立并验证了该工具，我们将使其可用 作为与我们现有的集成的基于网络的资源，向整个葡萄球菌研究界提供 内布拉斯加州转座子突变体库 (NTML) 网站。最后，我们提出一个行政核心，它将 提供所需的行政支持，以最大限度地加强项目负责人之间的互动，并确保 他们的项目保持最佳的协同效应。

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.