Meeting the challenge with a new facility

The conclusion of the Genome Sequencing Project – far from providing the solution to the problem of human disease – has created further questions that had not previously been considered. Hence, the age of genomics has initiated the need to examine the body’s real biochemical actors: proteins, to learn about their role in human health and disease.

‘Proteomics’ – the large scale study of such proteins and their functions and structures – is the next big wave in life sciences and the Max Planck Institute of Biochemistry in Germany has acknowledged its importance by opening a brand new proteomics facility this summer.

The Max Planck Institute of Biochemistry in Martinsried, Germany has established the new ‘Proteomics and Signal Transduction’ department which opened on July 1st 2005 with the aim of furthering Germany’s position as a leading light in the field proteomics. The new facility is comprised of 30 people and headed by a leading authority in the field, Prof. Dr. Matthias Mann.

Having been involved in mass spectrometry based proteomics since the beginning of its emergence, Dr Mann is well placed to lead the new facility’s activities which they anticipate will create avenues for future cooperation with the Biotech Campus Martinsried-Grosshardern near Munich.

The aims of studying proteomics are well established, yet the technology used to gain the necessary information about proteins is still evolving. Such work forms a significant part of the Proteomics department’s focus, with almost half of the team dedicated to researching this aspect of proteomics. The center works with several partners in different areas of proteomics: ThermoElectron collaborate with mass spectrometric instrumentation; Beijing Genomed Institute are involved in bioinformatics of proteomics; Proxeon Biosystems work in chromatography and Advion Biosciences collaborate with the institute in chip based nanoelectrospray. This cooperation between science and industry was funded through the European Commission’s 6th Framework Programme (FP 6) by way of the integrated project named ‘Interaction Proteome’. This project is the largest proteomics initiative in Europe and will be financed over five years – from 2004 to 2008.

Revolutionary technology

The first major achievement of Interaction Proteome has been the development of a new generation of mass spectrometers, the LTQ Orbitrap. The official inauguration of the new piece of equipment at the MPI was in August 2005. Dr Anne Katrin Werenskiold, Project Manager of Interaction Proteome spoke about the recent presentation: “On Tuesday August 30th, 2005 Matthias Mann invited 150 proteomics scientists and journalists to the MPI to show them around his new MPI department and to present, together with Thermo, the new Orbitraps – which now make the Mann department in Martinsried the best equipped proteomics lab worldwide.”

Developed by ThermoElectron, the LTQ Orbitrap mass spectrometer is based on a novel concept that enables the detection of proteins with high accuracy and sensitivity. This technological breakthrough represents a significant advancement of IP’s primary objectives. “The project (Interaction Proteome) is fully on course…one of the major goals of Interaction Proteome is already achieved, after just one and half years of a five-year project,” explains Werenskiold, “Our scientific officer was present during the meeting and was quite impressed with the developments within the IP. The next step will now be the mid-term review by the EC, which will take place in December 2005.”

Interaction Proteome

The main objective of Interaction Proteome is to establish Europe as the international leader in the analysis of protein interaction networks. Eleven institutions from six European countries are working together to develop new ways of investigating how proteins interact, in order that we can eventually develop a more thorough understanding of the biological processes involved in human diseases.

Specific research is carried out to develop the following areas:

• Mass spectroscopic methods and visualisation techniques
• A new public database to collect and compare data
• Algorithms to predict how proteins interact via computer modeling

Should the five year project achieve its goals, the field of proteomics will possess the means to significantly further its cause – a major advancement in the world of drug discovery as well as for the human race! And the new proteomics facility at MPI is an important development that will enable this to happen.

Two decades of experience

Matthias Mann, a German native, was trained in physics and mathematics and studied with John Fenn for his Ph.D. which he received from Yale University in 1989. After postdoctoral work with Peter Roepstorff in Denmark, he became group leader at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. Since 1998 he has been full professor at the University of Southern Denmark, Odense where he is now the director of the Center for Experimental BioInformatics (CEBI). As of July 2005 he is also Director at the Max-Planck Institute for Biochemistry in Martinsried, near Munich.

Dr. Mann’s work in mass spectrometry and proteomics stretches back for 20 years, starting with work on the electrospray ionization method and today encompasses a wide spectrum of cell signaling problems, which his group approaches with proteomic techniques. He has been elected member of the European Molecular Biology Laboratory (EMBO), visiting professor at Harvard Medical School as well as to the Danish Society of Arts and Sciences. He is author or co-author of more than 250 publications and is the recipient of many international prizes.

Summary of work

Matthias Mann has been involved in mass spectrometry based proteomics from the very beginning. As a graduate student with John Fenn at Yale University, he was a member of the team that developed electrospray, a key technology that won the Nobel prize for John Fenn in 2002. Later, his group at the European Molecular Biology Laboratory pioneered a set of technologies consisting of the first algorithm to identify peptides in sequence databases by their mass spectrometric fragmentation spectra (‘Peptide Sequence Tag’ algorithm) – a method to make small amounts of gel separated proteins amenable to mass spectrometry and a miniaturised, highly efficient version of electrospray working at very low flow rates (‘nanoelectrospray’). This allowed extremely sensitive protein sequencing and resulted in the cloning of important biological molecules such as the catalytic subunit of telomerase and Caspase-8. His group also performed the first, large scale identification of proteins linking ‘proteome’ to genome for the first time. His group also initiated work on protein-protein interaction detection by mass spectrometry and first used mass spectrometry to characterise multi-protein complexes. Recently, Dr. Mann’s group described a quantitative proteomics technology termed Stable Isotope Labeling with Amino acids in Cell culture or SILAC. The SILAC technology has been applied to signal dependent protein – protein interactions and to quantify relative changes in phosphorylation upon signaling. By comparing several states, SILAC has allowed the protein composition of the human nucleolus in response to perturbation to be determined and allowed mapping the time-order of activation in signaling pathways. These developments now allow proteomics to study dynamic processes.