HIGH RESOLUTION HYBRID FT-ICR MASS SPECT:ALZHEIMER, PARKINSON, HUNTINGTON, ALS

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This subproject is one of many research subprojects utilizing the resources provided by a Shared Instrumentation Grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the grant, which is not necessarily the institution for the investigator. DESCRIPTION (PROVIDED BY APPLICANT): A high-resolution hybrid Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer with capabilities for top-down protein sequencing and rapid duty-cycle LC-tandem MS measurements for bottom- up proteomics is requested. This instrument will be a vital component to support the specific aims of over 11 NIH-funded projects. The projects involve a variety of protein structure/function-related research, including the determination of protein-protein and protein-ligand interactions, protein phosphorylation, and the identification of protein biomarkers for disease detection and prognosis. The research will impact a range of human health issues, including neurodegenerative diseases, such as Huntington's disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), respiratory illnesses, cardiovascular and inflammatory diseases, and cancer. The hybrid FT-ICR mass spectrometer will be capable of sub-2 parts-per-million mass measurement accuracy for both intact peptides/proteins and product ions derived from MS/MS experiments. It will include a storage trapping device for increased dynamic range and have capabilities for rapid data dependent LC-MS/MS, and a resolving power sufficient to measure the isotope distribution of large, intact proteins for improved mass accuracy. Unique to this system will be capabilities for electron capture dissociation (ECD) and infrared multiphoton dissociation (IRMPD), ion activation methods advantageous for top-down protein sequencing and identification/localization of post-translational modifications. ECD greatly improves the ability to dissociate intact proteins to derive complete sequence information, as well as holding the promise of detection of post-translational modifications. An instrument with these unique capabilities is not available currently at UCLA. The instrument will be a centerpiece and will be supported and administered by the newly-created Molecular Instrumentation Center at UCLA, and it will serve researchers from across the institution.