Final ProgramCPSA 2012
Transforming Drug Discovery & Development Through Innovation:
Past, Present and Future
October 1 - 4, 2012
Sheraton Bucks County Hotel
Langhorne, PA
Wednesday Evening
Keynote Synopsis
Neil L. Kelleher, Ph.D.
Professor in Molecular Biosciences, Chemistry,
and the Feinberg School of Medicine
Northwestern University
Weigh Every Protein
Although the more widely used proteomics strategy has been peptide-based, unambiguous characterization of entire protein sequences and their post-translational modifications (PTMs) is often best achieved through the analysis of intact proteins. To date, the field of Top Down Proteomics has lagged behind Bottom Up in terms of high-throughput and comprehensive analysis. This has been attributed to underdevelopment of separations, MS instrumentation and bioinformatics dedicated to whole protein analysis. Recently, our lab has developed a platform for the large scale use of multiplexed 2D separations coupled to capillary LC-FTMS to achieve unprecedented proteome coverage for proteomics based on whole proteins. Given the complexity of the human proteome, the new separation platform integrates protein fractionation by charge, mass and hydrophobicity. Within a week, over 500 proteins in >1500 "proteoforms" (i.e., various modifications and splice variants) can now be identified. Such improving technical capacities now provide the basis to frame the general scope of a human proteome project based in part on Top Down technology. One key driver for development of this technology on this scale could become protein biomarkers: if "proteoform-resolved" mass spectrometry could provide stronger statistical power than Bottom Up for biomarker discovery and validation, then it presents a major opportunity to improve the early detection of human diseases. Dr. Yates has unusual perspective on the matter, adding to a special evening in recognition of his accomplishments to date.
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