Molecular basis of bioelectronic medicine

摘要 在NIGMS资助的Mira奖的最后一个资助期内的研究 显著提高了对分子免疫生物学机制的理解 神经系统和免疫系统之间的接口。据报道，在一系列 高影响力的出版物，我们实验室对迷走神经控制炎症的发现， 称为“炎症反射”，是对特定神经和分子的阐明。 机制，最终在类风湿性关节炎和克罗恩病的临床试验中取得成功 疾病。这项由NIGMS Mira支持的基础免疫生物学项目的工作重点是 迷走神经回路的解剖学、电生理学和分子机制 控制先天免疫力。它被誉为建立并引领了 生物电子医学。目前的竞争性更新提出了一种合乎逻辑的、意义重大的、 这项工作的创新和有效的继续描绘了大脑是如何控制 豁免权。仍有许多重大问题悬而未决。例如，什么是 大脑中控制炎症的神经信号的起源、解剖和功能？多么 大脑是否感觉到并记录了体内炎症的存在？还有，什么是 大脑和神经系统刺激炎症的机制？其中一些 问题将直接得到回答，其他新的问题可能会在 指导额外勘探的工作进程。私家侦探和他的实验室已经组装好 带领团队完成这项工作。他们有必要的经验和轨道 记录使用光遗传学、转基因和基因敲除小鼠、免疫疾病 模型、成像技术、电和神经生理学方法以及基础 免疫学和神经生物学。他们处于成功完成的理想环境中 拟议的研究，既是为了推进NIGMS的MIRA任务，也是为了继续其 将基础科学转化为临床研究和实践的旅程。

Abstract Research during the last funding period of this NIGMS-funded MIRA award has significantly advanced understanding of the molecular immunobiology mechanisms at the interface between the nervous system and the immune system. As reported in a series of high impact publications, our lab's discoveries of vagus nerve control of inflammation, termed “the inflammatory reflex,” the elucidation of the specific neural and molecular mechanisms, culminated in successful clinical trials in rheumatoid arthritis and Crohn's disease. This NIGMS MIRA-supported work of basic immunobiology programs focuses on the anatomy, electrophysiology, and molecular mechanisms of the vagus nerve circuits controlling innate immunity. It is credited with establishing and leading the field of bioelectronic medicine. The present competing renewal proposes a logical, significant, innovative, and impactful continuation of this work delineating how the brain controls immunity. There remain many major unanswered questions. For example, what is the origin, anatomy, and function in the brain of neural signals that control inflammation? How does the brain sense and record the presence of inflammation in the body? And, what are the brain and nervous system mechanisms that stimulate inflammation? Some of these questions will be answered directly, and other new questions will likely arise during the course of work to guide additional exploration. The PI and his lab have assembled and lead teams to accomplish this work. They have the necessary experience and a track record in using optogenetics, transgenic, and knock-out mice, immunological disease models, imaging technologies, electro- and neuro-physiology methods, and basic immunology and neurobiology. They are in an ideal environment to successfully complete the proposed studies, both to advance the MIRA mission of NIGMS, and to continue their journey translating basic science into clinical investigation and practice.