Horizon 2020 project at CPR - MSmed

MSmed (Mass spectrometric technology for next generation proteomics in systems medicine) is a research project funded by the European Commission under the Horizon 2020 Framework Program.

Systems medicine designates the application of global approaches to human health and disease. Genomic technologies, especially next-generation sequencing, are already pioneering this new area and there is an urgent need to advance proteomics technologies to a similar level. Advancing in this area will help revolutionize diagnosis and prognosis based on the expression levels and modifications of proteins in cells, tissues, organoids or body fluids.

The participants of the consortium are all leaders in proteomics technologies from academia and industry and have out-standing track-records in advancing both instrumentation as well as its application in biological and disease contexts. In this project we come together to develop breakthrough technology capable of more than a factor ten improvement in parameters of performance of the mass spectrometric workflow and in enabling patient-oriented proteome profiling. The proteomics workflow will be automated, multiplexed and made ‘industrial strong’ - ready for high-throughput and in-depth clinical applications. Importantly, in addition to the identification of the main protein representative of a gene, we aim to routinely identify and quantify protein modifications and isoforms by using multidimensional approaches, including new separation, enrichment and fragmentation technologies.

The breakthroughs aimed for will generate more biologically relevant data. This data will be merged with other ‘omic’ data and mined using machine learning technologies. Our results will establish the role mass spectrometry in systems medicine, making all workflows and mass spectrometry platforms available to the community. They will be used as the basis of myriad applications in biomedicine, even in the clinic. This will lead to a new eco-system around improved diagnosis, elucidations of disease mechanisms and drug action.

The University of Copenhagen (UPCH) was established in 1479 and is the largest university in Scandinavia. UCPH is ranked among the top 50 universities in the world. The university hosts about 40,000 students and 10,000 employees and consists of 6 faculties.  Novo Nordisk Foundation Center for Protein Research (CPR) was established in 2007 at the Faculty of Health and Medical Sciences to promote basic and applied discovery research on human proteins of medical relevance. CPR has rapidly established itself on the international scene as a worldwide leader in advanced protein technologies and applications hereof in health and disease. CPR comprises multidisciplinary expertise and state‐of‐the‐art equipment in key areas of protein science including proteomics, bioinformatics, structural biology, and focused protein signaling mechanism research. Details can be found at CPR’s website www.cpr.ku.dk.

Infrastructure/equipment:

The infrastructure of CPR facilitates the project experiments : world‐leading instrumental platforms with high‐resolution mass spectrometers, advanced imaging equipment, state‐of‐the‐art laboratories, including advanced microscopy‐based siRNA screening platform, genome‐editing technologies, protein production facilities and protein biophysical characterization equipment. Proteomes, Interactomes and PTMs are analyzed by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). CPR has seven of the latest generation high‐accuracy hybrid quadrupole orbitrap mass spectrometers Q Exactive HF instruments, developed by the company Thermo Fisher Scientific in Bremen with whom we have a long‐standing collaboration.

Project Coordinator and Principal Investigator (1):

Prof. Dr. Matthias Mann, Director, Novo Nordisk Foundation Center for Protein Research, Mann group - Clinical Proteomics, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark matthias.mann@cpr.ku.dk , Phone: +45 35 32 50 27

Principal Investigator (2):

Prof. Jesper V. Olsen, Vice Director, Novo Nordisk Foundation Center for Protein Research,Olsen group -  Mass Spectrometry for Quantitative Proteomics, Faculty of Health and Medical Sciences, University of Copenhagen, jesper.olsen@cpr.ku.dk, Phone: +45-3532-5022.

The Max Planck Institute of Biochemistry (MPIB) is part of  the Max Planck Society, and is  an independent nonprofit research organization dedicated to top level fundamental research. There are more than 80 Max Planck Institutes worldwide, 30 are in the biology and medical sector. The Max Planck Institute of Biochemistry in Munich‐Martinsried is a leading international research institution in the fields of biochemistry, molecular biology, and cell biology. The institute is located in the life science campus in Martinsried, where two other Max Planck Institutes (for Biochemistry and Neurobiology) as well as the Helmholtz Center, the Gene Center, the faculties of medicine, biology and chemistry of the Ludwig Maximilians University, and several biotech companies are located in close proximity.

Infrastructure/equipment:

The lab for Computational Systems Biochemistry at MPIB lead by Jürgen Cox has office space for 12 computational biologists and can be further extended if needed. A local air conditioned server room is shared with the department of Prof. Mann. Further servers can be hosted free of charge in the computing center of MPIB in Martinsried and at the Leibniz Supercomputing Center of the Bavarian Academy of Sciences in Garching. We hold software licenses for Microsoft Visual Studio 2012, JetBrains ReSharper, DotTrace, YouTrack and TeamCity. All open source code is hosted at GitHub. We use a Subversion code repository for internal projects. We are supported by the MPIB EU office led by Dr. AK Werenskiold who has extensive experience in the management of EU projects. The public relations office of the MPIB lead by Anja Konschak will assist in highlighting our research and communicating it to the public.

Principal Investigator:

Prof. Jürgen Cox, PhD, Independent Research Group Leader, Computational Systems Biochemistry Group, Max Planck Institute of Biochemistry, www.biochem.mpg.de/cox, cox@biochem.mpg.de, Phone: +49‐89‐85782088, Phone2: +49‐151‐64510103, Fax: +49‐89‐85782219

Founded in 1636 and located in the heart of the Netherlands, Utrecht University is one of Europe’s leading research universities. With over 30,000 enrolled students and more than 5,000 staff members it is the largest university in the Netherlands, and hosts world‐leading research centered around the themes of Life Sciences, Sustainability, Dynamics of Youth, and Institutions. The Faculty of Science is home to over 4800 students and 1100 employees with research across the fields of Mathematics, Biology, Chemistry, Physics and Astronomy, Information and Computing Sciences and Pharmaceutical Sciences.

Principal Investigator:

Prof. Albert J.R. Heck, PhD, Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands, http://www.hecklab.com, a.j.r.heck@uu.nl, Phone: +31‐30‐2536797

Thermo Fisher Scientific (Bremen) GmbH is  global market leader in mass spectrometry equipment. Product lines include high‐resolution mass spectrometers (MS) for organic analysis, isotope ratio analysis, elemental analysis, and life science. Following the development of breakthrough Hybrid Linear Trap‐ Orbitrap MS of LTQ Orbitrap family over the last decade, recent products of the company include an Orbitrap‐only MS (Exactive Plus, Exactive EMR instruments), Hybrid Quadrupole‐Orbitrap MS (Q Exactive family currently containing Q Exactive, Q Exactive Plus, Q Exactive HF, Q Exactive Focus instruments). The team in Bremen works with a team at Thermo Fisher, San Jose, CA, one of the latest results being the launch of Tribrid Quadrupole‐Linear Trap‐ Orbitrap instrument Orbitrap Fusion MS in 2013. Both sites are also collaborating with the team at Thermo Fisher, Germering, Germany on the development of nano‐ and micro‐flow LC.

Infrastructure/equipment:

The research and development team represented by Alexander Makarov has a unique track record in mass spectrometry innovation which is best represented by introduction of the ground‐breaking Orbitrap analyser, first as a part of hybrid LTQ Orbitrap and then as a basis for two further instrument families, (Q) Exactive and Orbitrap Fusion. Culture of continuous innovation enabled a number of significant technological advances such as C‐trap, HCD fragmentation cell, high‐ and ultra‐high field compact Orbitrap in instrumentation, parallel filling/detection, spectra multiplexing in instrument control, enhanced Fourier transform in signal processing, Proteome Discoverer and Compound Discoverer for HR/AM applications. These innovations enforced significant instrument improvements every 2 years over the last decade and turned the Orbitrap platform into the major workhorse for most proteomic research. The group holds the  skills and equipment for successfully complete development of commercial instruments with control and application software and has access to all generations of Orbitrap instruments as well as associated liquid separations and ion sources.

Principal Investigator:

Prof. Alexander Makarov, PhD, Director of Global Research Life Science Mass Spectrometry, Thermo Fisher Scientific, www.thermoscientific.com, www.planetorbitrap.com, Alexander.Makarov@thermofisher.com, phone: +49 421‐5493‐410, Fax: +49 421‐5493‐426.