Friday, May 9, 2025
5/9/2025
Acquisition of a dedicated and integrated HD-MS instrument - Project Summary This funding application aims to acquire a state-of-the-art, integrated mass spectrometry-based system for hydrogen/deuterium exchange (HDX-MS) studies on complex protein systems. The system will support a large community of biomedical researchers at Case Western Reserve University and neighboring institutions, including the Cleveland Clinic Learner Research Institute, University Hospitals, the Veteran Affairs Hospital, the MetroHealth Rammelkamp Center for Education and Research, and Cleveland State University. Currently, we have eight main users and nine minor users, with six already utilizing or recently using HDX-MS for their projects. However, the existing equipment, now over 15 years old, is outdated and does not facilitate efficient, sensitive, or reliable experiments compared to the proposed instrument. Remarkably, there is no state-of-the-art HDX-MS equipment dedicated to hydrogen/deuterium exchange studies in the entire Greater Cleveland area or even in Ohio. The HDX-MS approach is vital for characterizing highly complex and challenging systems, including large protein-protein complexes, protein aggregates associated with neurodegenerative disorders, membrane channels, membrane-associated proteins, and protein-nucleic acid complexes. This technology will be an invaluable tool for structural biology research, benefiting numerous NIH-funded investigators working on fundamental biological and biomedical problems. It will expand the scope of biomedical research and foster collaborative interactions. More than 30 NIH-funded research projects will immediately benefit from this instrument. These include studies on misfolded protein aggregates, protein-protein complexes involved in cell signaling, self-assembling proteins in synaptic vesicle endocytosis, GPCRs, large multimeric membrane channels (ligand-gated channels, aquaporin channels), membrane and water-soluble receptors, and inflammasome signaling complexes. These projects contribute to a better understanding of the pathogenic processes associated with these systems. Moreover, the insights gained will aid in developing novel therapeutic strategies for various diseases, including neurodegenerative disorders, cancer, cardiovascular diseases, pain, visual impairment, bacterial and viral infections, and inflammation.
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