NanoLC System for Ultrasensitive Hydrogen/Deuterium Exchange Mass Spectrometry

我们需要一种能够提供非常低流速（小于1微升/分钟）的液相色谱装置。这种“纳米olc”技术是一种名为氢/氘交换质谱（HX-MS）的蛋白质结构分析创新技术的核心。HX-MS是一种可以监测蛋白质分子动力学并绘制其相互作用图的技术。这项技术被用来理解细胞的作用机制，最近，它被用来帮助构建支撑这些机制的蛋白质的精确模型。我们开发了一种小型化的HX-MS技术，使这种工作成为可能，大大扩展了该技术可寻址的应用范围。它能够表征复杂的多蛋白“机器”，这是大多数细胞机制的功能要素。不幸的是，我们现有的纳米有机碳设备失败了，立即停止了几个依赖于这项技术的研究项目。这包括一个nserc资助的项目，旨在开发确定复杂系统蛋白质结构模型的新策略，以及一系列寻求破译人类细胞如何修复DNA损伤的合作项目，这是维持我们基因组完整性的重要基本机制。我们的纳米HX-MS技术是世界上第一个，使我们能够在其开发之前不可能的细节水平上研究细胞机制。新的纳米olc设备的收购将恢复8个实验室的10多名学员团队的生产力，并使我们能够将我们的培训计划扩展到加拿大和世界各地的其他实验室。

We request a liquid chromatography device capable of delivering very low flow-rates (less that 1 microliter/minute). This “nanoLC” technology is central to the operation of an innovative technology for protein structure analysis called hydrogen/deuterium exchange mass spectrometry (HX-MS). HX-MS is a technique that can monitor the molecular dynamics of proteins and map their interactions. The technology is used to understand cellular mechanisms of action and most recently, it is being used to help construct accurate models of the proteins that underpin these mechanisms. We developed a miniaturized form of HX-MS technology that makes such work possible, greatly expanding the range of applications addressable by the technique. It enables the characterization of complex multiprotein “machines”, which are the functional elements of most cellular mechanisms. Unfortunately, our existing nanoLC device has failed, immediately halting several research programs that rely upon the technology. This includes a NSERC-funded program to develop new strategies for determining protein structural models of complex systems, and a series of collaborative projects that seek to decipher how the human cell repairs DNA damage an important fundamental mechanism that maintains the integrity of our genome. Our nano-enabled HX-MS technology is a world's first, allowing us to study cellular mechanisms at a level of detail not possible prior to its development. The acquisition of a new nanoLC device will restore productivity to a team of over 10 trainees in eight labs, and allow us to expand our training program to other labs in Canada and around the world.