Abstract

The term “proteomics” encompasses the large-scale detection and analysis of proteins and their post-translational modifications. Driven by major improvements in mass spectrometric instrumentation, methodology, and data analysis, the proteomics field has burgeoned in recent years. It now provides a range of sensitive and quantitative approaches for measuring protein structures and dynamics that promise to revolutionize our understanding of cell biology and molecular mechanisms in both human cells and model organisms. The Proteomics Specification in Time and Space (PROSPECTS) Network is a unique EU-funded project that brings together leading European research groups, spanning from instrumentation to biomedicine, in a collaborative five year initiative to develop new methods and applications for the functional analysis of cellular proteins. This special issue of Molecular and Cellular Proteomics presents 16 research papers reporting major recent progress by the PROSPECTS groups, including improvements to the resolution and sensitivity of the Orbitrap family of mass spectrometers, systematic detection of proteins using highly characterized antibody collections, and new methods for absolute as well as relative quantification of protein levels. Manuscripts in this issue exemplify approaches for performing quantitative measurements of cell proteomes and for studying their dynamic responses to perturbation, both during normal cellular responses and in disease mechanisms. Here we present a perspective on how the proteomics field is moving beyond simply identifying proteins with high sensitivity toward providing a powerful and versatile set of assay systems for characterizing proteome dynamics and thereby creating a new “third generation” proteomics strategy that offers an indispensible tool for cell biology and molecular medicine.

Highlights

  • From the ‡Centre for Gene Regulation & Expression, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH United Kingdom; §Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden; ¶Thermo Fisher Scientific (Bremen) GmbH, Hanna-Kunath-Strasse 11, 28199 Bremen, Germany; ʈDepartment of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, UK; **EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), UPF, Barcelona, Spain; ‡‡ICREA, Pg

  • PROSPECTS is coordinated by Matthias Mann and brings together ten top proteomics research groups from around Europe, as well as a leading mass spectrometry in

  • The PROSPECTS project arose in part from the recognition that the proteomics field was rapidly developing toward a “second generation” state, where it was possible to identify proteins with high sensitivity, but increasingly to use proteomics technologies to assay the dynamic properties of proteins in high throughput and to characterize the structure and composition of large multiprotein complexes

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Summary

Introduction

We suggest that the large-scale study of endogenous proteins, their post-translational modifications, interactions and dynamic behavior in space and time, are the core subject area of proteomics. PROSPECTS seeks to develop and optimize new technology and methodology in the proteomics field with a strong focus on how these can be deployed to maximum effect to advance our understanding of fundamental aspects of cell regulation and disease mechanisms, including stress responses and neurodegenerative syndromes. Proxeon ( Thermo Fisher Scientific, Odense), a company collaborating with the Mann group for over ten years, are specialists in the design of hardware and software for proteome analysis, bringing expertise with new instrumentation for separation of peptides and proteins by liquid chromatography at the nano scale

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