Ultra-High Resolution Mass Spectrometer for Biomedical Research

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DESCRIPTION (provided by applicant): A high-magnetic field, ultra-high resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer with capabilities for enhanced top-down protein sequencing and metabolite detection is requested. This instrument will be a vital component to support the research aims of over 11 NIH-funded projects. The studies involve a variety of protein structure-related research, including the determination of protein-protein and protein-ligand interactions, protein phosphorylation, membrane protein structure, and the identification of protein biomarkers for disease detection and prognosis. The research will impact a range of human health issues, including aging, neurodegenerative diseases, such as Huntington's disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), and cancer. The ultra-high resolution FT-ICR mass spectrometer will be capable of sub-parts-per-million to parts-per-billion mass measurement accuracy for intact peptides/proteins and product ions derived from tandem mass spectrometry (MS/MS) experiments, and small molecule metabolite identification. It will have capabilities for multistage MS-n experiments (n greater than 2) to be conducted in the ICR trapping/detection device, thus permitting advanced top-down analysis using infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) for efficient ion activation and dissociation in the ICR cell. Electron transfer dissociation (ETD) will be available as an alternative dissociation method. Both ETD and ECD greatly improve the ability to dissociate intact proteins to derive complete sequence information, as well as holding the promise of direct detection of post-translational modifications. The instrument will be a centerpiece and will be supported and administered by the Molecular Instrumentation Center at UCLA, and it will serve researchers from across the institution and nearby institutions. PUBLIC HEALTH RELEVANCE: The new instrumentation will benefit a wide range of biomedical studies. The high sensitivity and high resolution capabilities of the system will provide a new means to identify the mechanistic basis of a number of human diseases, such as neurodegenerative disorders, and it may be used to identify new protein markers of cancer. The availability of this new, state-of-the-art mass spectrometer will require highly trained scientists to be hired and maintained for its operational use.