The Resource for Native Mass Spectrometry Guided Structural Biology (nMS→SB) was established in 2018 with a 6.8M P41 grant from the NIH National Institute of General Medical Sciences. As a national Biomedical Technology Research Resource, our purpose is to develop and disseminate novel technologies throughout the broader biomedical research community. Our mission is to develop improved native MS as a routine tool and disseminate the technology to the biomedical research community through vendor partnerships and training. The Resource will work with investigators across the nation and globe on challenging biomedical projects ranging from viral hemorrhagic fevers and HIV to cataract formation and neurological disorders.
The Thermo Scientific Q Exactive Ultra-High Mass Range (UHMR) Hybrid Quadrupole-Orbitrap instrument which enables analysis of extra-large molecules (m/z 350-80,000) with high mass accuracy. The UHMR is equipped with a higher-energy collision-induced dissociation (HCD) cell capable of acceleration voltages up to 300 V, as well as in-source trapping capabilities for improved declustering of ions. The Wysocki lab has two of these instruments and they are both modified with custom surface-induced dissociation (SID) devices. The UHMRs are primarily used for analysis of proteins and protein complexes by both direct infusion and online non-denaturing separation techniques. One instrument was purchased with funds from P41GM128577 and the other is part of a direct collaboration with Thermo Scientific.
The Thermo Scientific Vanquish Duo Ultra-High-Performance Liquid Chromatography (UHPLC) system enables online separations coupled with mass spectrometry and is equipped with a dual pump, autosampler, variable wavelength detector, and fluorescence detector. The dual pump allows for 2D LC while the wavelength and fluorescence detectors allow for alternative and parallel methods of detection. The UHPLC system is primarily used for automated chromatography (e.g., size exclusion, ion exchange, immobilized metal affinity, reversed phase, online buffer exchange) online with MS.
The Waters Select Series Cyclic IMS instrument has high sensitivity, high m/z resolution (>100k FWHM) and a unique cyclic ion mobility (cIM) allowing increased ion mobility resolution via multiple ion mobility passes. The instrument will be modified to include surface-induced dissociation, which will be tightly integrated with the system via collaboration with the manufacturer. This instrument was purchased in part with supplement funds from P41GM128577 for method development for characterization of Alzheimer's Disease related aggregates and oligomers.