A unique state-of-the-art hybrid ion mobility mass spectrometer (IM-MS) equipped with electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) sources, and surface induced dissociation (SID) for characterization of a broad range of molecules is requested. This instrument will be a vital component to support the research aims of over 9 NIH-supported projects. The studies involve a variety of protein structure- related research, including the characterization of protein-protein and protein-ligand interactions, the identification of biomarkers for disease detection and prognosis, and also the determination of drug biodistribution in tissue. The research will impact a range of human health issues, including neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis (ALS), bacterial infectious diseases, radiation sensitivity, and cancer. Ion mobility measurements provide an additional dimension of separation and structural information, based on molecular size and shape, not available in a mass spectrum. Coupling IM with MALDI-MS can be especially powerful for MALDI-based tissue imaging for both large and small molecule distribution experiments. Direct tissue profiling and imaging mass spectrometry provide a detailed assessment of the complex molecular pattern and its spatial distribution within a tissue sample. MALDI-based tissue imaging of drug compounds is potentially a rapid method for determining the biodistribution in animal models, and can yield additional information on novel metabolites. Surface induced dissociation will be especially useful for probing the architecture and topology of large protein complexes, and coupling SID with IM will be a powerful tool for structural biology projects. The proposed ion mobility mass spectrometer system will be supported and administered by the UCLA Molecular Instrumentation Center (MIC), a campus-wide, integrated facility formed to enhance the accessibility of existing shared, sophisticated instrumentation facilities to the broader research community at the institution.
The new instrumentation will benefit a wide range of biomedical and structural biology studies. The high sensitivity and high specificity of the system will provide a new means to identify the mechanistic basis of a number of human diseases, such as neurodegenerative disorders and inflammatory bowel disease, and it may be used to identify new disease markers.
|Wongkongkathep, Piriya; Han, Jong Yoon; Choi, Tae Su et al. (2018) Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the Cobalt and Manganese Metal Binding of ?-Synuclein Protein. J Am Soc Mass Spectrom 29:1870-1880|
|Takemori, Nobuaki; Takemori, Ayako; Wongkongkathep, Piriya et al. (2017) Top-down/Bottom-up Mass Spectrometry Workflow Using Dissolvable Polyacrylamide Gels. Anal Chem 89:8244-8250|