New PROSPECTS for Proteomics Research
2 March 2012
Austria
‘Proteomics’ is the large-scale study of proteins, particularly their structures and functions. Proteomics holds the potential to answer questions that genomics left unsolved. The large EU project PROSPECTS is a collaborative research effort of leading European scientists in the proteomics field. PROSPECTS now presents a number of breakthroughs in a series of articles comprising a "Special Issue" of the top journal of the field: Molecular & Cellular Proteomics. Coordinated by Matthias Mann, director at the Max Planck Institute of Biochemistry (MPIB) in Martinsried, the scientists lay out their contribution to the future of proteomics with a powerful and versatile set of assay systems for characterizing proteome dynamics, a new ‘third generation’ proteomics strategy that offers an indispensible tool for cell biology and molecular medicine.
“Proteomics specification in time and space” (PROSPECTS, web: www.prospects-fp7.eu) is a five year collaborative project that commenced early in 2008 and is funded by the Research Directorate of the European Commission under the 7th Research Framework Program. PROSPECTS brings together ten leading research groups from around Europe, as well as Thermo Fisher Scientific, a mass spectrometry instrument manufacturer and chromatography company. The different groups seek new insights into the cellular function of proteins and their aberration during diseases. “We here present a perspective on how the proteomics field is moving beyond simply identifying proteins,” says Matthias Mann. “It now provides powerful tools for characterizing proteome dynamics and thereby creates a new level of proteomics research.” The "Special Issue" contains a series of 16 original research papers documenting the recent progress in all aspects of proteomic research achieved within PROSPECTS. All papers are freely accessible.
New Instruments for Mass Spectrometry
The reports describe new instruments for mass spectrometry with extraordinary sensitivity. Combined with novel software for real-time analysis of the data, proteomic studies will therefore become faster, cheaper and easier to use for a broad range of applications.
New quantitative approaches now allow the "counting" of the number of individual proteins in cells and their comparison between samples. This showed that the proteome of different types of cells is much more similar than anticipated earlier.
Many biological functions require proteins to interact in larger complexes within cells. These assemblies of proteins are notoriously difficult to analyse because of their size and the fact that they are often unstable. The development of novel cross-linking reagents that glue the components of such complexes together thus is an essential tool. A novel combination of mass spectrometry and electron microscopy now paves the way to investigate these large assemblies – zooming in from the whole complex to their individual building blocks.
New Goals for Proteomic Research
One major goal of PROSPECTS was the reorientation of proteomics from describing the protein inventory of cells at a certain point of time into a dynamic view. Like a movie, this would allow the researcher to follow proteins and their fate over time. Of special interest are changes such as in the numbers of proteins, their locations in cells and interactions with other proteins. For such a dynamic "movie" cells can be separated into organelles and subcellular structures before the analysis with the above methods. A study of autophagosomes for example identified proteins required for protein degradation mediated by the organelle. In another study, the PROSPECTS scientists investigated protein stability at a global scale and demonstrate that the components of a large protein complex are unstable and short-lived at their site of assembly, but more stable at their site of function. Further analysis showed that the differential localisation and stability may be due to subtle differences in subsets of the protein, as confirmed by a complementary analysis of protein localisation using antibodies.
It has become increasingly evident that while gathering very large amounts of data is an important part of proteomics research, their subsequent intelligent use is even more essential. The construction of computer models integrating the available data and simulating and predicting the behaviour of biological systems, for instance, is a way to improve our understanding of biological networks.
Further articles in the Special Issue demonstrate how the combined application of the new tools already bears fruit in biomedical research. Thus the analysis of heat and stress-responsive pathways in cancer cells provides insight into the action of anti-cancer drugs and may inform drug regimens in the future.
This array of improvements reaches out beyond the expert community. The ease of use of PROSPECTS' novel technologies and the steadily decreasing amounts of material required for analysis now enable a more general use of proteomics in the biological and biomedical communities. This confirms a prediction on the impact of PROSPECTS' outcome by Prof. Catherine Fenselau in her project review: "[…] that methods and demonstrative applications are emerging that will have major impact on biology and biotechnology".
Original publications
www.mcponline.org/site/home/special_issues/
“Proteomics specification in time and space” (PROSPECTS, web: www.prospects-fp7.eu) is a five year collaborative project that commenced early in 2008 and is funded by the Research Directorate of the European Commission under the 7th Research Framework Program. PROSPECTS brings together ten leading research groups from around Europe, as well as Thermo Fisher Scientific, a mass spectrometry instrument manufacturer and chromatography company. The different groups seek new insights into the cellular function of proteins and their aberration during diseases. “We here present a perspective on how the proteomics field is moving beyond simply identifying proteins,” says Matthias Mann. “It now provides powerful tools for characterizing proteome dynamics and thereby creates a new level of proteomics research.” The "Special Issue" contains a series of 16 original research papers documenting the recent progress in all aspects of proteomic research achieved within PROSPECTS. All papers are freely accessible.
New Instruments for Mass Spectrometry
The reports describe new instruments for mass spectrometry with extraordinary sensitivity. Combined with novel software for real-time analysis of the data, proteomic studies will therefore become faster, cheaper and easier to use for a broad range of applications.
New quantitative approaches now allow the "counting" of the number of individual proteins in cells and their comparison between samples. This showed that the proteome of different types of cells is much more similar than anticipated earlier.
Many biological functions require proteins to interact in larger complexes within cells. These assemblies of proteins are notoriously difficult to analyse because of their size and the fact that they are often unstable. The development of novel cross-linking reagents that glue the components of such complexes together thus is an essential tool. A novel combination of mass spectrometry and electron microscopy now paves the way to investigate these large assemblies – zooming in from the whole complex to their individual building blocks.
New Goals for Proteomic Research
One major goal of PROSPECTS was the reorientation of proteomics from describing the protein inventory of cells at a certain point of time into a dynamic view. Like a movie, this would allow the researcher to follow proteins and their fate over time. Of special interest are changes such as in the numbers of proteins, their locations in cells and interactions with other proteins. For such a dynamic "movie" cells can be separated into organelles and subcellular structures before the analysis with the above methods. A study of autophagosomes for example identified proteins required for protein degradation mediated by the organelle. In another study, the PROSPECTS scientists investigated protein stability at a global scale and demonstrate that the components of a large protein complex are unstable and short-lived at their site of assembly, but more stable at their site of function. Further analysis showed that the differential localisation and stability may be due to subtle differences in subsets of the protein, as confirmed by a complementary analysis of protein localisation using antibodies.
It has become increasingly evident that while gathering very large amounts of data is an important part of proteomics research, their subsequent intelligent use is even more essential. The construction of computer models integrating the available data and simulating and predicting the behaviour of biological systems, for instance, is a way to improve our understanding of biological networks.
Further articles in the Special Issue demonstrate how the combined application of the new tools already bears fruit in biomedical research. Thus the analysis of heat and stress-responsive pathways in cancer cells provides insight into the action of anti-cancer drugs and may inform drug regimens in the future.
This array of improvements reaches out beyond the expert community. The ease of use of PROSPECTS' novel technologies and the steadily decreasing amounts of material required for analysis now enable a more general use of proteomics in the biological and biomedical communities. This confirms a prediction on the impact of PROSPECTS' outcome by Prof. Catherine Fenselau in her project review: "[…] that methods and demonstrative applications are emerging that will have major impact on biology and biotechnology".
Original publications
www.mcponline.org/site/home/special_issues/