In Focus pubs.acs.org/acschemicalbiology
Building Up a Chemical Proteomics Network in Europe and Beyond Maja Köhn,*,† Michael M. Meijler,‡ and Markus Kaiser*,§ †
European Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany Department of Chemistry and National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Be’er-Sheva 84105, Israel § University of Duisburg-Essen, Chemical Biology, ZMB, Faculty of Biology, Universitätsstr. 2, 45117 Essen, Germany ‡
C
science exchange programs. Such networks are open to all interested scientists, although funding is limited to European groups. Along these lines, the chemical proteomics CM1004 COST action (www.cost.eu/domains_actions/cmst/Actions/ CM1004) aims to bring together and train chemical proteomics researchers, thereby fostering collaborations and idea exchange between scientists from the field. As long-term goals, we hope that these endeavors will help to enlarge and strengthen the chemical proteomics community in Europe and even beyond.
hemical probes have evolved into important tools to study biological pathways or to identify and validate new drug targets. In chemical proteomics, small molecule probes are used to reduce the complexity of or gain functional insight into proteomic analyses. In the most widely known chemical proteomics methodology, which is activity-based protein profiling (ABPP), chemical probes denoted as activity-based probes (ABPs) react covalently with distinct target proteins in a mechanism-dependent manner, thereby allowing functional insight into the activity states of enzymes. Alternatively, photoactivation of appropriately labeled ligands allows for identification of receptors in a process termed photoaffinity protein profiling (PPP). In other chemical proteomics techniques, small molecule probes are used to elucidate or predict potential sites for post-translational modifications such as protein lipidation or phosphorylation. Finally, the identification of protein targets of small molecule probes, for example from phenotypic screening of chemical libraries or of bioactive natural products, is a common challenge in chemical proteomics research. Independent of the exact task, chemical proteomics, as all chemical biology areas, tremendously benefits from intense collaborations between chemists who are willing to prepare useful chemical probes and (chemical) biologists or physicians that meaningfully apply these probes in their basic biomedical research. While chemical proteomics is a young and thriving field of science, the decision to work in this area is often followed by some disillusion due to unexpected challenges. For example, although the chemical proteomics research network in Europe is growing, it is nevertheless still rather fragmented, and there is no common platform for identifying potential collaborators or for the exchange of scientific ideas, chemical probes, or practical protocols. In addition, research groups that are interested to move into the chemical proteomics field, for example by developing novel probes or by applying them in basic biomedical research, are sometimes blocked right in the beginning by a limited infrastructure such as high-end mass spectrometry in their own research institutions. In order to overcome such palpable limitations and challenges and to create more synergistic and concerted efforts in the area of chemical proteomics, a European Cooperation in Science and Technology (COST) Action devoted solely to chemical proteomics was created in the end of 2012, and in the meantime, it has grown to comprise thirty-five laboratories from 14 European countries. COST does not fund primary research, but it supports the establishment of European networks via financing scientific meetings, workshops, training schools, or © 2014 American Chemical Society
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THE COST ACTION CM1004 CHEMICAL PROTEOMICS SPRING MEETING To achieve these ambitious goals, the action holds as corner point each spring an annual conjoint meeting exclusively devoted to all facets of chemical proteomics. After a kick-off meeting in Jerusalem, Israel, subsequent meetings were held in Berlin, Germany, and in Cambridge, U.K. In addition, a training school was organized in Essen, Germany (see below). The meetings have seen continuously increasing numbers of participants. This year’s spring meeting in Cambridge attracted more than 100 participants and was organized by Ed Tate and David Spring. The meeting usually takes place over 2 days, and the sessions focus on topics ranging from chemical probe design to chemical probe synthesis and protocol development to the application of chemical proteomics in different organisms. Each session is thereby started by a plenary lecture given by outstanding experts in chemical proteomics, often from outside of Europe. In Cambridge, these were Matt Bogyo from Stanford University, U.S.A., who as one of the founders of activity-based protein profiling reported how his group applied activity-based probes to uncover pathways that regulate mammalian host cell invasion by parasite pathogens, and Hening Lin from Cornell University, U.S.A., who presented his group’s achievements in identifying new functions and unexpected posttranslational modifications of histone deacetylases via specifically developed chemical probes. These talks were complemented from two plenary lecturers from Europe. Stephan Sieber from the TU Munich, Germany, presented natural product-derived probes and their application to studying bacterial virulence and resistance. Finally, Jason Chin as a local representative introduced a new technology (SORTM) that enables chemical labeling, imaging, and identifying proteins in specific tissues at precise developmental stages in model organisms such as drosophila. Published: August 15, 2014 1647
dx.doi.org/10.1021/cb5005299 | ACS Chem. Biol. 2014, 9, 1647−1648
ACS Chemical Biology
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CONCLUSION Although the COST action has already been established, it is open for further chemical proteomics researchers. Direct funding is limited to European researchers, but non-European researchers are welcome to participate at the events organized from our action. Along these lines, the next chemical proteomics meeting will be held in Oxford, U.K., in the spring of 2015. It will be organized by Renier van der Hoorn, a plant chemical biologist who is using chemical proteomics techniques for elucidating plant pathogen interactions. We welcome to this meeting and to the COST action scientists from Europe and beyond who will join us to shape and enlarge the chemical proteomics network, creating synergism and alleviating obstacles to advance the research in this challenging field.
These plenary talks are then complemented by roughly 20 shorter presentations either from the principal investigators of the COST action or−more often−from PhD students and postdocs from the corresponding laboratories. Again, these talks encompass all facets of chemical proteomics research. For example, the Cambridge meeting featured reports on highresolution mass spectrometry of intact proteins for profiling snake venoms (Daniel Petras from the group of Roderich Süssmuth, TU Berlin, Germany). Martijn Verdoes from Nijmegen, Netherlands, gave insights into quenched fluorescent activity-based probes (qABP) for imaging active cysteine cathepsins, while Galia Blum from Israel informed the audience about her group’s work on quenched caspase probes for imaging apoptosis. Mario van der Stelt, Leiden, Netherlands, introduced his newly developed molecular tools to detect and control endocannabinoid synthesis. Rachel Gregor and Niva Levy (from the group of Michael Meijler, Ben Gurion University, Israel) introduced chemical tools to visualize interspecies information flow between bacteria and from bacteria to higher organisms. In another bacterial chemical proteomics project, Tom Charlton (from the group of Edward Tate, Imperial College, U.K.) described how the lipoproteome of the Gram-positive pathogen Clostridium dif f icile can be profiled. Tram Ncog Hong (from the group of Renier van der Hoorn, Oxford University, U.K.) discussed the application of ABPs to study pathogen plant interactions. Patrick Trouillas from Limoges, France, spoke about computational approaches in chemical biology and Steven Verhelst, TU Munich, Germany, explained how his group has developed cleavable linkers and ABPs for studying intramembrane proteases. Of note, the meeting also features more chemistry-oriented talks such as the one from Arnaud Chevalier, Rouen, France, who reported new syntheses of fluorescent probes or Paolo Quadrelli, Pavia, Italy, who described the synthetic use of nitrile oxides and nitrosocarbonyls for generating potential reporters in bioorthogonal chemistry. Although these are just some examples from the large list of contributors, it illustrates the broad scope of the spring meeting.
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In Focus
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AUTHOR INFORMATION
Corresponding Authors
*Email: [email protected]. *Email: [email protected].
■
ACKNOWLEDGMENTS We thank COST for continuous support of our network activities.
ADDITIONAL COST CM1004 EVENTS
Besides the cornerstone spring meeting, the COST network holds training schools to transfer “lab expertise” to PhD students and postdocs that aim to start chemical proteomics research. In the last training school, which took place at the University of Duisburg−Essen, Germany, in autumn 2013, 7 trainers instructed 24 trainees in basic chemical proteomics technologies but also advanced methodologies such as quantitative MS. A training school thereby consists mainly of “wet lab” experiments but also includes lectures. In the 2013 training school, these lectures were given by renowned experts such as Herman Overkleeft, Leiden, Netherlands, and Markus Kaiser, Duisburg−Essen, Germany. In addition, COST offers the funding of research internships for COST PhD students, postdocs, and even principal investigators in other COST laboratories. These action elements, commonly referred to as short-term scientific missions (STSMs), allow a thorough training of the future generation of chemical proteomics scientists in expert laboratories and a close exchange of ideas and plans between the principal investigators. 1648
dx.doi.org/10.1021/cb5005299 | ACS Chem. Biol. 2014, 9, 1647−1648
Building Up a Chemical Proteomics Network in Europe and Beyond Maja Köhn,*,† Michael M. Meijler,‡ and Markus Kaiser*,§ †
European Molecular Biology Laboratory, Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany Department of Chemistry and National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Be’er-Sheva 84105, Israel § University of Duisburg-Essen, Chemical Biology, ZMB, Faculty of Biology, Universitätsstr. 2, 45117 Essen, Germany ‡
C
science exchange programs. Such networks are open to all interested scientists, although funding is limited to European groups. Along these lines, the chemical proteomics CM1004 COST action (www.cost.eu/domains_actions/cmst/Actions/ CM1004) aims to bring together and train chemical proteomics researchers, thereby fostering collaborations and idea exchange between scientists from the field. As long-term goals, we hope that these endeavors will help to enlarge and strengthen the chemical proteomics community in Europe and even beyond.
hemical probes have evolved into important tools to study biological pathways or to identify and validate new drug targets. In chemical proteomics, small molecule probes are used to reduce the complexity of or gain functional insight into proteomic analyses. In the most widely known chemical proteomics methodology, which is activity-based protein profiling (ABPP), chemical probes denoted as activity-based probes (ABPs) react covalently with distinct target proteins in a mechanism-dependent manner, thereby allowing functional insight into the activity states of enzymes. Alternatively, photoactivation of appropriately labeled ligands allows for identification of receptors in a process termed photoaffinity protein profiling (PPP). In other chemical proteomics techniques, small molecule probes are used to elucidate or predict potential sites for post-translational modifications such as protein lipidation or phosphorylation. Finally, the identification of protein targets of small molecule probes, for example from phenotypic screening of chemical libraries or of bioactive natural products, is a common challenge in chemical proteomics research. Independent of the exact task, chemical proteomics, as all chemical biology areas, tremendously benefits from intense collaborations between chemists who are willing to prepare useful chemical probes and (chemical) biologists or physicians that meaningfully apply these probes in their basic biomedical research. While chemical proteomics is a young and thriving field of science, the decision to work in this area is often followed by some disillusion due to unexpected challenges. For example, although the chemical proteomics research network in Europe is growing, it is nevertheless still rather fragmented, and there is no common platform for identifying potential collaborators or for the exchange of scientific ideas, chemical probes, or practical protocols. In addition, research groups that are interested to move into the chemical proteomics field, for example by developing novel probes or by applying them in basic biomedical research, are sometimes blocked right in the beginning by a limited infrastructure such as high-end mass spectrometry in their own research institutions. In order to overcome such palpable limitations and challenges and to create more synergistic and concerted efforts in the area of chemical proteomics, a European Cooperation in Science and Technology (COST) Action devoted solely to chemical proteomics was created in the end of 2012, and in the meantime, it has grown to comprise thirty-five laboratories from 14 European countries. COST does not fund primary research, but it supports the establishment of European networks via financing scientific meetings, workshops, training schools, or © 2014 American Chemical Society
■
THE COST ACTION CM1004 CHEMICAL PROTEOMICS SPRING MEETING To achieve these ambitious goals, the action holds as corner point each spring an annual conjoint meeting exclusively devoted to all facets of chemical proteomics. After a kick-off meeting in Jerusalem, Israel, subsequent meetings were held in Berlin, Germany, and in Cambridge, U.K. In addition, a training school was organized in Essen, Germany (see below). The meetings have seen continuously increasing numbers of participants. This year’s spring meeting in Cambridge attracted more than 100 participants and was organized by Ed Tate and David Spring. The meeting usually takes place over 2 days, and the sessions focus on topics ranging from chemical probe design to chemical probe synthesis and protocol development to the application of chemical proteomics in different organisms. Each session is thereby started by a plenary lecture given by outstanding experts in chemical proteomics, often from outside of Europe. In Cambridge, these were Matt Bogyo from Stanford University, U.S.A., who as one of the founders of activity-based protein profiling reported how his group applied activity-based probes to uncover pathways that regulate mammalian host cell invasion by parasite pathogens, and Hening Lin from Cornell University, U.S.A., who presented his group’s achievements in identifying new functions and unexpected posttranslational modifications of histone deacetylases via specifically developed chemical probes. These talks were complemented from two plenary lecturers from Europe. Stephan Sieber from the TU Munich, Germany, presented natural product-derived probes and their application to studying bacterial virulence and resistance. Finally, Jason Chin as a local representative introduced a new technology (SORTM) that enables chemical labeling, imaging, and identifying proteins in specific tissues at precise developmental stages in model organisms such as drosophila. Published: August 15, 2014 1647
dx.doi.org/10.1021/cb5005299 | ACS Chem. Biol. 2014, 9, 1647−1648
ACS Chemical Biology
■
CONCLUSION Although the COST action has already been established, it is open for further chemical proteomics researchers. Direct funding is limited to European researchers, but non-European researchers are welcome to participate at the events organized from our action. Along these lines, the next chemical proteomics meeting will be held in Oxford, U.K., in the spring of 2015. It will be organized by Renier van der Hoorn, a plant chemical biologist who is using chemical proteomics techniques for elucidating plant pathogen interactions. We welcome to this meeting and to the COST action scientists from Europe and beyond who will join us to shape and enlarge the chemical proteomics network, creating synergism and alleviating obstacles to advance the research in this challenging field.
These plenary talks are then complemented by roughly 20 shorter presentations either from the principal investigators of the COST action or−more often−from PhD students and postdocs from the corresponding laboratories. Again, these talks encompass all facets of chemical proteomics research. For example, the Cambridge meeting featured reports on highresolution mass spectrometry of intact proteins for profiling snake venoms (Daniel Petras from the group of Roderich Süssmuth, TU Berlin, Germany). Martijn Verdoes from Nijmegen, Netherlands, gave insights into quenched fluorescent activity-based probes (qABP) for imaging active cysteine cathepsins, while Galia Blum from Israel informed the audience about her group’s work on quenched caspase probes for imaging apoptosis. Mario van der Stelt, Leiden, Netherlands, introduced his newly developed molecular tools to detect and control endocannabinoid synthesis. Rachel Gregor and Niva Levy (from the group of Michael Meijler, Ben Gurion University, Israel) introduced chemical tools to visualize interspecies information flow between bacteria and from bacteria to higher organisms. In another bacterial chemical proteomics project, Tom Charlton (from the group of Edward Tate, Imperial College, U.K.) described how the lipoproteome of the Gram-positive pathogen Clostridium dif f icile can be profiled. Tram Ncog Hong (from the group of Renier van der Hoorn, Oxford University, U.K.) discussed the application of ABPs to study pathogen plant interactions. Patrick Trouillas from Limoges, France, spoke about computational approaches in chemical biology and Steven Verhelst, TU Munich, Germany, explained how his group has developed cleavable linkers and ABPs for studying intramembrane proteases. Of note, the meeting also features more chemistry-oriented talks such as the one from Arnaud Chevalier, Rouen, France, who reported new syntheses of fluorescent probes or Paolo Quadrelli, Pavia, Italy, who described the synthetic use of nitrile oxides and nitrosocarbonyls for generating potential reporters in bioorthogonal chemistry. Although these are just some examples from the large list of contributors, it illustrates the broad scope of the spring meeting.
■
In Focus
■
AUTHOR INFORMATION
Corresponding Authors
*Email: [email protected]. *Email: [email protected].
■
ACKNOWLEDGMENTS We thank COST for continuous support of our network activities.
ADDITIONAL COST CM1004 EVENTS
Besides the cornerstone spring meeting, the COST network holds training schools to transfer “lab expertise” to PhD students and postdocs that aim to start chemical proteomics research. In the last training school, which took place at the University of Duisburg−Essen, Germany, in autumn 2013, 7 trainers instructed 24 trainees in basic chemical proteomics technologies but also advanced methodologies such as quantitative MS. A training school thereby consists mainly of “wet lab” experiments but also includes lectures. In the 2013 training school, these lectures were given by renowned experts such as Herman Overkleeft, Leiden, Netherlands, and Markus Kaiser, Duisburg−Essen, Germany. In addition, COST offers the funding of research internships for COST PhD students, postdocs, and even principal investigators in other COST laboratories. These action elements, commonly referred to as short-term scientific missions (STSMs), allow a thorough training of the future generation of chemical proteomics scientists in expert laboratories and a close exchange of ideas and plans between the principal investigators. 1648
dx.doi.org/10.1021/cb5005299 | ACS Chem. Biol. 2014, 9, 1647−1648
