Of telescopes and lightposts: The evolution of mass spectrometry to tackle ever larger proteins in complex mixtures

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Neil L. Kelleher, kelleher@scs.uiuc.edu, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801
Though I never met Arthur Findeis, I have come to know him through third parties as a colorful and outspoken advocate for measurement science. I hope to do his legacy justice in describing our laboratory's improvements to the "Top Down" measurement approach. Gallileo did not invent the telescope, but substantially improved it, illuminating new heavenly moons in the process. One main aim for my laboratory is to bring the molecular logic used by Eukaryotic cells for intracellular signalling into better view. This line of investigation is typified by histones, with tens to hundreds of discrete protein forms resolved by high performance Q-FT mass spectrometry through the cell cycle. For Top Down Proteomics generally - our contributions have spanned across sample fractionation, instrument automation, and bioinformatics, with our software now accessed free by hundreds of laboratories over the Internet. I look forward to sharing our recent advances and hope they contribute broadly to the Human Proteome Project in coming years. I thank Professors Fred McLafferty, Alan Marshall, Donald Hunt, Jonathan Sweedler and Paul Bohn for their advocacy and advice over the last decade.