Plenary Speaker: Measuring protein-level biology, one ion at a time

While top down mass spectrometry has become synonymous with the direct analysis of intact proteins and their complexes, the term more generally denotes an approach to measurement that recognizes the value of retaining as much information as possible about a system prior to analysis. By avoiding proteolytic digestion, proteoform-specific identifications can be made -directly. A series of vignettes will focus on both denatured and native modes of Top Down Proteomics. I will also describe a few recent advances of top down MS, like the most recent breakthroughs in individual ion mass spectrometry (i2MS) in orbitraps (joint work with the group of Mike Senko at Thermo Fisher Scientific). I will also describe a new sample introduction approach called ‘SampleStream’ that enables simultaneous buffer exchange and >20x concentration of samples in either denaturing or native modes. Providing information from intact complex mass (MS1) to subunits and their backbone fragment ions, native top-down MS even enables identification and characterization of unknown protein complexes. By more faithfully preserving post-translational modifications and non-covalent interactions throughout the measurement process, top down mass spectrometry is positioned to make basic and translational proteomics more efficient and valuable, particularly in the detection and assignment of function to proteoforms and their PTMs underlying human wellness and disease.