Fall Workshop Homepage

Top Down Proteomics 

November 2-3, 2017

Hyatt Regency Boston Harbor
Boston, MA

Organizers

Ying Ge, University of Wisconsin-Madison
Ljiljana Paša-Tolić, Pacific Northwest National Laboratory

A comprehensive analysis of all proteoforms that arise from genetic variations, alternative splicing, and post-translational modifications (PTMs), is essential to gain a transformative understanding of disease mechanisms and identify new therapeutic targets. Top-down mass spectrometry (MS)-based proteomics is arguably a disruptive technology for the comprehensive characterization of proteoforms by providing a “bird’s eye” view of all proteoforms to decipher the PTM codes together with genetic variations that regulate cellular signaling in healthy and diseased states. 

In the top-down approach, intact proteins are analyzed without proteolytic digestion. Subsequently, specific proteins of interests can be isolated and modification sites could be mapped by tandem MS (MS/MS) strategies. In contrast, the traditional bottom-up approach has intrinsic limitations for the analysis of proteoforms as a result of protein digestion which includes dramatically increased complexity in examining an already complicated proteome as each protein is digested into many peptide components; incomplete sequence coverage since only a fraction of the digested peptides are recovered, loss of information of co-occurring PTMs and mutations, as well as the inability to distinguish between splicing variants with high sequence similarity.

Over the last decade we have made significant strides to advance top-down MS and bring it to the mainstream. As a result, interest in top-down MS has grown considerably and a number of studies have already showcased the potential of top-down proteomics for the unraveling of disease mechanisms and discovery of new biomarkers. 

In this workshop, world-leading experts in top-down MS-based proteomics will present the most advanced technologies and approaches. The workshop will cover a wide range of topics, including sample preparation, intact protein separation, MS and MS/MS for intact proteins, bioinformatics and data analysis tools for top-down proteomics, as well as the biomedical applications. Each presentation will be a tutorial aimed at beginners/newcomers to the top-down proteomics field. The Workshop will conclude with a dynamic moderated discussion/quiz session.

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