BioWorld International Correspondent

BORNHEIM, Germany - The first projects of a DM130 million (US$57 million) German government program on "new efficient methods for functional proteome analysis" have gotten under way in the past month.

More effective tools are needed to develop the economic potential of proteome analysis in drug discovery and other areas, an official of the ministry said.

An independent panel has selected nine projects that involve 48 groups from academia and other public and private enterprises.

Protagen AG, of Bochum, is leading nine academic groups and two other companies to find new procedures of investigating the proteome of the human brain.

"These processes need to be automated. Too much work has been done by hand," said Petra Weingarten, Protagen's project manager, target discovery.

The project includes simplifying 2-dimensional gelelectrophoresis. 2-D gels are a major tool in proteome research. They separate proteins by molecular weight and electric charge. Thus, each protein makes a single spot on the gel. The researchers in the Protagen-led network want to automate sample preparation for electrophoresis and pick the protein spots from the gel for further investigation by mass spectrometry, which is needed to investigate the proteins' amino acid sequences. The project includes development of special bioinformatic tools.

"We want to set up a proteome map of the human brain," Weingarten said. The researchers plan initially to set up maps from healthy human tissue, provided by a brain tissue bank. After these initial steps they will validate whether proteome maps derived from mouse models can be used for research on human diseases like Huntington's, Alzheimer's and Parkinson's.

At the Center for Advances European Studies and Research (CAESAR) in Bonn, researchers are developing a new tool for functional proteome analysis called microbalance array mass spectroscopy (MAMS). This platform includes aptamers bound to resonant oscillating quartz sensor chips. The aptamers are highly specific to certain protein domains. Following protein binding the oscillation in the chip changes. Thus, it generates an electric signal, which can be further evaluated. The CAESAR researchers want to build up microarrays on the chips, which can check for up to 100 protein domains simultaneously, said CAESAR project leader Daniel Hoffmann. There is also need for a complex bioinformatics platform to be developed.

Once a protein's domain has bound to the chip, the researchers further characterize the whole protein by mass spectrometry. The tool may also detect the amount of a certain protein bound to the chip. Others in the network are Qiagen N.V., of Hilden; Nascacell GmbH, of Munich; Bruker Daltronic GmbH, of Bremen; the GMD National Research Center for Information Technology; and groups from the universities of Bonn and Cologne.

Other projects currently fueled by the government's proteome program are:

  • New methods of depicting the proteome of cell organelles (academic and industry groups led by the University of Gvttingen).

  • Investigation of Gram-positive bacteria's proteome (led by the University of Greifswald).

  • Methods of systematically investigating proteins bound to the cell wall (led by the University of Munich).

  • Development of fully automated technologies for proteome analysis (led by Max Planck Institute [MPI] of Biochemistry in Munich).

  • Efficient methods of proteome analysis in microbes relevant in medicine (led by MPI of Infection Biology in Berlin).

  • High-throughput fluorescence microscopy for investigation of C. elegans' proteome (led by MPI of Molecular Cell Biology and Genetics in Dresden).

  • Innovative methods for detection of protein-protein interactions in plants (led by MPI of Plant Breeding Research in Cologne).

The selection of further projects is expected to take place in June.

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