Administrative Supplement for Equipment Purchase

项目总结/摘要 我们的母基金专注于创伤、感染和脓毒症引起的破坏， 功能我们已经发现了令人兴奋的新机制，这些机制对免疫细胞功能至关重要， 发现这些重要的机制在重症患者中受损。我们发现这些函数 免疫细胞的功能依赖于ATP的释放和通过嘌呤受体的自分泌反馈。我们可以证明 线粒体提供ATP，驱动这些自分泌反馈机制。为此， 线粒体被运输到免疫细胞内的特定区域，在那里它们以一种免疫细胞的方式递送它们的ATP。 时空高度有序的方式。我们的工作提供了强有力的证据，表明创伤，感染， 脓毒症损害这些微妙的信号传导过程。 为了研究与线粒体和嘌呤相关的快速而复杂的信号机制， 受体信号，我们必须使用活细胞成像与高度复杂的显微镜系统。但我们的 目前的显微镜系统不够快速和通用，无法研究贩运之间的联系。 线粒体，它们的活化，细胞ATP释放，嘌呤能受体的刺激， 从健康受试者和重症监护患者中分离的免疫细胞。 在此，我们要求补充资金，以便在现有的基础上增加某些组件。 显微镜系统这些关键部件将大大提高扫描速度和共聚焦成像的获取。 图像.升级后的系统将提供多方面的数据，有助于阐明 线粒体动力学在健康和疾病中免疫细胞功能中的作用。

PROJECT SUMMARY/ABSTRACT Our parent grant focuses on the disruptions caused by trauma, infection, and sepsis that compromise immune function. We have uncovered exciting new mechanisms that are essential for immune cell function and we found that these important mechanisms are impaired in critically ill patients. We discovered that the functions of immune cells depend on ATP release and autocrine feedback via purinergic receptors. We could show that mitochondria deliver the ATP that drives these autocrine feedback mechanisms. For that purpose, mitochondria are trafficked to specific regions within immune cells where they deliver their ATP in a spatiotemporally highly organized manner. Our work has provided strong evidence that trauma, infection, and sepsis impair these delicate signaling processes. In order to study the rapid and complex signaling mechanisms associated with mitochondria and purinergic receptor signaling, we must use live-cell imaging with a highly sophisticated microscope system. However, our current microscope system is not fast and versatile enough to study the connections between the trafficking of mitochondria, their activation, cellular ATP release, stimulation of purinergic receptors, and the function of immune cells isolated from healthy subjects and critical care patients. Here, we request supplemental funds that would allow addition of certain components to our existing microscope system. These key components would greatly increase scanning speed and acquisition of confocal images. The upgraded system would provide multi-dimensional data that would help to elucidate the central roles of mitochondrial dynamics in the function of immune cells in health and disease.