NanoLC System for Ultrasensitive Hydrogen/Deuterium Exchange Mass Spectrometry

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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.