Staphylococcal Biofilm and Disease

在前一个供资周期中，我们题为“葡萄球菌生物膜与疾病”的计划项目 采用深入的机械论方法来定义重要的发育和代谢过程 金黄色葡萄球菌生物被膜的形成。这个项目的协同效应的一个关键方面是， Gain被用作上下文，以提供对可用营养素获得的更详细的理解 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 使人们对金黄色葡萄球菌适应宿主环境的方式有了极大的了解， 为生物被膜的发展提供新的基本见解和临床管理的新方法 葡萄球菌性疾病。推动拟议计划项目目标的总体假设，S.aureus 生物膜的发展创造了独特的代谢生态位，促进了免疫抑制 环境，是当前供资周期的自然产物，并在四个协同作用和 包含广泛的协同和高度协作活动的互补性项目 从生物膜发育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。为支持这四项计划的工作，我们建议设立 延续我们的生物成像核心，维护生物通量微流控系统，用于生物膜生长和 分析、共聚焦显微镜和活体成像系统(IVIS)。此外，我们还提出了一种新的 代谢组学核心，将建立和维护支持这四个项目所需的方案和建模 与此PPG关联的项目。重要的是，我们的愿景是，这个核心的工作将导致 一个基于网络的代谢组学工具(通过一个单独的机制提供资金)，它不仅将作为 教育工具，以加强对金黄色葡萄球菌代谢组的全面了解，也可作为假说 支持科学研究的发电机。一旦建立并验证了此工具，我们将使其可用 作为一个基于Web的资源，与我们现有的 内布拉斯加州转座突变图书馆(NTML)网站。最后，我们提出了一个行政核心，它将 提供必要的行政支持，以最大限度地促进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.