Approaches to Top-Down Proteomics: In Honour of Prof. Patrick H. O'Farrell

Dear Colleagues,

Presaging the current discipline of Proteomics, Prof Patrick H. O’Farrell* recognized the critical need for detailed protein analyses to dissect and thereby understand molecular mechanisms. His development of two-dimensional gel electrophoresis (2DE) has proven a cornerstone of modern protein science and, together with developments in mass spectrometry and genomics, laid the groundwork for current Systems Biology approaches to understanding the molecular basis of physiological states in health and disease. Notably, as refined over the last 40 years, 2DE provides the only currently available, optimized, routine, Top-down analytical approach that resolves proteoforms (i.e., protein species including isoforms and post-translationally modified variants)—those protein entities that define biological functions. The future clearly holds even more promise in terms of the further development of both Discovery and Targeted Top-down Proteomics to understanding biological pathways and mechanisms.

Thus, we are soliciting for interest and suggestions for manuscripts for this Special Issue (SI). In addition to an already commissioned historical perspective reviewing gel electrophoresis, immunoblotting, pull-downs, and so forth, we plan for this SI to include papers on current top-down Discovery approaches (e.g., modern gel-based/gel-free techniques and MS-intensive analytical approaches as the future), as well as Targeted Proteomics approaches (e.g. antibody arrays/protein atlas approaches, QconCAT, proximity/hybridization-based methods, and others). The overarching criteria for final acceptance of any manuscript will be critical reasoning and rigor; presenting and examining the genuine pros and cons of different analytical approaches in order to yield a SI of broad interest as a teaching tool and analytical resource for students through to experienced researchers. We expect this approach to help revise much of the dogma that has arisen in the literature over the last 20+ years with regard to Top-down Proteomics and to illuminate promising directions in further dissecting and understanding molecular mechanisms and thus cellular processes. We will be seeking a balance between review articles and original scientific reports, with the latter being favored (or a combined approach reviewing the field and presenting original data concerning the analytical approach in focus).

Prof. Dr. Jens R. Coorssen
Dr. Alfred L. Yergey
Guest Editors

*Prof. O’Farrell is a leading molecular biologist who made crucial contributions to the development of 2-dimensional protein electrophoresis (2DE). He graduated from McGill University (Montreal) and did his graduate work in the University of Colorado, where he developed the technique of 2DE. In 1979 he joined the Department of Biochemistry at UCSF and became one of the pioneers of molecular analysis of embryonic pattern formation. He identified the gene encoding the homeodomain protein Engrailed and his analysis of its function in segmentation defined processes used throughout the regulatory cascade that patterns the embryo. He turned to study the control of the cell cycle during development using Drosophila genetics, molecular biology and imaging. Recent work has demonstrated the importance of regulation of the S phase duration in these events. A newer project area explores the biology and genetics of the mitochondrial genome.

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