With the support from the Chemical Measurement and Imaging Program, Professor Bush at the University Washington develops a Modular Ion Mobility Mass Spectrometry (MIMMS) system that enables new experiments to probe the solution and gas-phase structures of proteins and protein complexes. The self-assembly of proteins into 'molecular machines' enables cells to perform sophisticated functions that are otherwise inaccessible. There is a growing need for complementary structural tools to determine the quaternary structures of the proteome and mass spectrometry (MS) plays an increasingly important role in fulfilling these unmet needs. The research plan makes large impacts in the field of native MS by providing new, sensitive instrumentation for multistage characterization of proteins and protein complexes, and by providing fundamental insights into the conformational landscapes of proteins and protein complexes in the gas phase, which may lead to new opportunities in the fields of analytical instrumentation, structural biology, and characterization of biopharmaceuticals. Professor Bush also provides support to a graduate student researcher with interdisciplinary training opportunities on instrument development and state-of-the-art analytical method development in the rapidly growing fields of native mass spectrometry and ion mobility spectrometry.
The research objectives are to demonstrate the use of modules to shape separate, trap, and shape select ions of proteins and protein complexes and networks of modules to perform higher-order ion mobility mass spectrometry experiments. These modules are combined to form networks that may enable new experiments that are not possible using existing mass spectrometry instruments. Key advantages of this approach are that the modules will share dimensions, design elements, and drive electronics; be individually refined independently from a complex instrument; and then be added to networks of modules, without compromising the capabilities of the other modules.