Profile

The department of proteomics and signal transduction was established 1st of July 2005 and is currently comprised of 40 people. It is led by Prof. Matthias Mann, who moved here from earlier stations at the European Molecular Biology Laboratory (EMBL ) and from the University of Southern Denmark (SDU), where he is director of the Center for Experimental BioInformatics (CEBI).
The department develops and applies powerful tools of ‘proteomics', which is the analysis of the protein complement in protein complexes, cells, tissues and organisms. The goal of proteomics is not only to determine the expression level of proteins but also their localization, dynamics, post-translational modifications and interaction partners. Proteomics can be done at the whole cell or tissue level but, often more interestingly, can be focused on specific and functionally relevant ‘sub-proteomes' such as all phosphorylated proteins.

While the goals of proteomics are long-standing, the technology to address them is very challenging and is still in development. The department is heavily involved in this technology development and about half of our members are mainly focused on this aspect of proteomics. Currently, we collaborate with ThermoElectron in mass spectrometric instrumentation and with the Beijing Genome Institute in bioinformatics of proteomics. We also work with Proxeon Biosystems in chromatography and Advion Biosciences in chip based nanoelectrospray.
We have applied proteomics technology to a wide range of biological and biomedical problems. One long-standing interest of ours is the determination of protein interaction partners and multi-protein complexes. This started with the determination of the U1 subunit of the yeast spliceosome in 1997 with the department of Rainer Lührmann and the mapping of the human spliceosome with the group of Angus Lamond in Dundee in 1998 and 2002, with whom we have also just published an in-depth characterization of the protein composition and dynamics of the human nucleolus. We have recently developed methods for mapping protein interactions using quantitative proteomics. In this regard, we are members of the European Union project "interaction proteome", which is being coordinated here in the institute and comprises groups involved in instrumentation, structural biology, signal transduction, and systems biology.
In 2002, the group described a quantitative proteomics method called Stable Isotope Labeling by Amino acids in Cell culture (SILAC). In this method, cells are metabolically labeled by non-radioactive amino acids, which makes their proteomes distinguishable from cells labeled with ‘wild type' amino acids. This technology has become very popular and is the basis for nearly all experiments in the group.
During the last several years, we have been particularly interested in growth factor signaling. Using proteomics technology, we have discovered and cloned several new effectors in the EGF pathway and have recently used ‘temporal proteomics' to obtain kinetics and thereby time order tyrosine phosphorylated members. With the SILAC method, we have been able to define difference in the phosphotyrosine proteome in adult stem cells between closely related growth factors. One growth factor activated PI3 Kinase whereas the other one did not and we showed that this difference is a control point for differentiation of these cells to bone forming cells. This is one of the first examples, showing how quantitative proteomics - especially quantitative phosphoproteomics - may allow us to learn how cell fate decisions are actually made.
In addition to EGF signaling, we have recently concentrated on insulin signaling and ‘adipocyte proteomics'. We are studying protein-protein interactions in the insulin pathway, secretion of adipocytes in various conditions and we are trying to correlated changes in the proteome with clinically important parameters in the ‘metabolic syndrome' which encompasses obesity, insulin resistance, diabetes and other metabolic disorders. The department is a member of the Diabetes Genome Anatomy Project (DGAB), headed by Ron Kahn at the Joslin Diabetes Institute of Harvard Medical School.
Other projects in the group apply proteomic methods to infectious disease. In collaboration with Dutch groups, especially Andy Waters, we have characterized the proteome of the Malaria parasite and, most recently, described the male and female gametocyte proteome of the parasite. Other projects deal with the invasion process of pathogenic bacteria and use our proteomic tools to decipher signaling changes brought about by these microbes.
Also in the department is the group of Prof. Alfred Messerschmidt, who joined us from the department of Prof. Huber. This group is interested in structural biology, especially kinase structure and metalloproteases.