Cell Physiology Core

核心C项目总结 Pannexin 1（Panx 1）形成释放重要细胞间信号的质膜离子通道 分子，特别是ATP和UTP，在病理和生理条件下;通道也支持 摄取传统上用于标记凋亡细胞的各种荧光染料（例如，YO-PRO-1， TO-PRO-3）。在该PPG应用中，采用新的小鼠模型来确定Panx 1 - 1的贡献。 介导的ATP/UTP释放（和其他代谢物释放，当需要时）， 疾病，并了解Panx 1通道激活的相应机制。细胞生理学核心 通过吸收、优化和标准化Pannexin通道的关键功能， 对所有四个项目具有普遍意义的分析。（1）Panx 1通道功能分析 原代细胞的电生理学和染料摄取测定;（2）新的 Pannexin通道的小分子调节剂。同样，核心也在发展中占据主动 创新的工具和方法，可以提供一个明确的技术优势，整个研究计划。这 包括产生新的Panx 1变体和基因编辑的小鼠品系，通过CRISPR/Cas9 技术.在执行这些集中的目标时，通常对整个研究计划至关重要，核心 认识到数据质量和再现性的至关重要性。对于垂直和水平 在本PPG中提出的集成中，该核心位于蜂窝和系统级分析之间的接口 Panx 1函数

CORE C PROJECT SUMMARY Pannexin 1 (Panx1) forms plasma membrane ion channels that release important intercellular signalling molecules, specifically ATP and UTP, under pathological and physiological conditions; the channels also support uptake of various fluorescent dyes that have traditionally been used to mark apoptotic cells (e.g., YO-PRO-1, TO-PRO-3). In this PPG application, novel mouse models are employed to ascertain contributions of Panx1- mediated ATP/UTP release, (and other metabolite release, when needed) to various aspects of cardiometabolic diseases, and to understand corresponding mechanisms of Panx1 channel activation. Cell Physiology Core centralizes the functional analysis of Pannexin channels by absorbing, optimizing and standardizing the key assays of universal significance to all four projects. These include: (1) Analysis of Panx1 channel function in primary cells by electrophysiology and dye uptake assays and; (2) Electrophysiological characterization of novel small molecule modulators of Pannexin channels. Similarly, the core also takes the initiative in the development of innovative tools and methods that can provide a clear technical edge to the entire research program. This includes generation of novel Panx1 variants and gene-edited mouse lines, generated by CRISPR/Cas9 technology. In executing these centralized goals, often of salience to the entire research program, the core recognizes the paramount importance of data quality and reproducibility. For the vertical and horizontal integration proposed in this PPG, this core sits at the interface between cellular and systems levels of analysis of Panx1 function.