Equipped with €12 million ($14.2 million) in funding from the European Union, a consortium of European researchers and companies is working on improving technologies for studying and predicting protein-protein interactions.
“We are developing new tools and testing these tools, and at the same time generat[ing] new data on protein-protein interactions,” said Ulrich Hartl, a professor of cellular biochemistry and director at the Max Planck Institute for Biochemistry in Martinsried, Germany, and the coordinator of the project.
The five-year project, called Interaction Proteome, started earlier this year and involves eight research institutes and three companies in six European countries. According to Hartl, this is the only large-scale proteomics project so far funded by the EU’s 6th Framework Program, a mega-plan for building EU-wide projects.
On the mass spec side, Thermo Electron’s branch in Bremen, Germany, will collaborate with Matthias Mann at the University of Southern Denmark to increase the sensitivity and dynamic range of Thermo’s LTQ-FT mass spectrometer. Mann has already received an LTQ-FT instrument, and Thermo will get €700,000 of the grant funds for the first 18 months of the project. Two Thermo representatives declined to elaborate on the nature of the improvements for this article, but Ken Miller, product marketing manager for Thermo, told Proteo-Monitor in February that the company will be releasing several improvements on the LTQ-FT this year, and that “we’ll have more to tell you” at ASMS in Nashville, which is being held next month (see PM 2-27-04). In addition, electron microscope manufacturer FEI Electron Optics in Eindhoven, the Netherlands; and Wolfgang Baumeister at the MPI in Martinsried; have received funding to improve the resolution of electron tomography, a technique used to visualize protein complexes in intact cells, and to build a device to tilt the specimen automatically. FEI will receive about €800,000 in the first 18 months of this project.
Luis Serrano at EMBL in Heidelberg, and Soren Brunak at the Technical University of Denmark, will receive financial support to develop new bioinformatics tools for predicting protein interactions and modeling protein networks. “The goal would be that such a system can be developed to a state where you can really make predictions about the behavior of complex protein interactions under in vivo-like conditions,” said Hartl.
The researchers also want to apply the new technologies to generate protein interaction data. Scientists working on different experimental systems — for example chaperone-assisted protein folding — signal transduction in mammalian cells, bacteria, and archaebacteria — will participate. “We decided not to just work on one particular organism or model … but we want to highlight different biological models in which the various researchers have great experience,” Hartl said. These models also serve to monitor progress of the technology over the next few years, he said.
Consortium researchers also plan to select more than 100 protein domains and more than 3,000 peptides with relevance to signal transduction and to characterize their interaction partners. Jerini, a Berlin-based company, will provide peptide microarrays for this project, and will receive about €250,000 in funding in the first 18 months.
Mann told ProteoMonitor that his group will use protein domain and peptide screens on a large scale — and quantitatively — to find signal-dependent protein interactions.
All new interaction data will go into the MINT molecular interactions database — so another aspect of the project is to overhaul MINT, which was created by Gianni Cesareni at the University Tor Vergata in Rome. “What definitely needs to be improved is the networking with other databases,” said Hartl, and MINT already has an agreement with the Biomolecular Interaction Network Database and with the Database of Interacting Proteins to improve integration, as part of HUPO’s Proteomics Standards Initiative (see PM 10-24-03).
What might have attracted the EU to fund the Interaction Proteome, he speculated, is the diversity of participants. “The goal is to analyze protein interactions, and proteomics is of course an important aspect of that,” Hartl said, ”… but it also needs biochemistry, bioinformatics, and cell biology. It’s really a consortium of people from different areas that contribute towards that goal.”