Administrative Supplement for Equipment Purchase

设备采购行政补充

• 批准号: 10797062
• 负责人: WOLFGANG G JUNGER
• 金额: $ 3.97万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797062
• 关键词: Administrative Supplement; Cell Separation; Cell physiology; Cells; Complex; Critical Care; Critical Illness; Defect; Disease; Feedback; Funding; Health; Immune; Immune System Diseases; Impairment; Infection; Microscope; Mitochondria; Patient Care; Patients; Process; Purinoceptor; Receptor Signaling; Role; Scanning; Sepsis; Signal Transduction; Speed; System; Trauma; Work; autocrine; confocal imaging; equipment acquisition; imaging system; immune function; live cell imaging; multidimensional data; parent grant; spatiotemporal; trafficking

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.

项目概要/摘要 我们的家长资助重点关注因创伤、感染和败血症而损害免疫系统造成的破坏 功能。我们发现了对于免疫细胞功能至关重要的令人兴奋的新机制，并且我们 发现这些重要的机制在危重患者中受损。我们发现函数 免疫细胞的功能依赖于 ATP 释放和通过嘌呤能受体的自分泌反馈。我们可以证明 线粒体提供驱动这些自分泌反馈机制的 ATP。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 时空高度组织化的方式。我们的工作提供了强有力的证据，证明创伤、感染和 脓毒症会损害这些微妙的信号传导过程。 为了研究与线粒体和嘌呤能相关的快速而复杂的信号传导机制 受体信号传导，我们必须使用高度复杂的显微镜系统进行活细胞成像。然而，我们的 目前的显微镜系统速度不够快，功能也不够多，无法研究贩运之间的联系。 线粒体、其激活、细胞 ATP 释放、嘌呤能受体的刺激以及 从健康受试者和重症监护患者中分离出的免疫细胞。 在此，我们请求补充资金，以便在我们现有的基础上添加某些组件 显微镜系统。这些关键部件将大大提高扫描速度和共焦采集 图像。升级后的系统将提供多维数据，有助于阐明中央 线粒体动力学在健康和疾病中免疫细胞功能中的作用。