IEEE/EG International Symposium on Volume Graphics

Electron tomography is uniquely suited to obtain three-dimensional images of large pleiomorphic structures, such as supramolecular assemblies, organelles or even whole cells. With the advent of automated data acquisition, facilitated by technological advances (computer-controlled electron microscopes and large area CCD cameras), it has become possible to examine frozen-hydrated samples in a close-to-life state under non-critical electron dose conditions and to attain resolutions which allow the docking of high resolution component structures. High-resolution tomograms of organelles or cells are essentially 3-D images of the cell's entire proteome and should ultimately enable us to map the spatial relationships of macromolecules in a functional cellular context. However, it is no trivial task to retrieve this information because of the poor signal-to-noise ratio of such tomograms and the crowded nature of the cytoplasm and many organelles. Denoising procedures can help to combat noise and to facilitate visualization, but advanced pattern recognition methods are needed for detecting and identifying with high fidelity specific macromolecules based on their structural signature (size and shape).

Experiments with phantom cells, i.e. lipid vesicles encapsulating a known set of proteins have shown that such a template-matching approach is feasible. Once the challenges of obtaining sufficiently good resolution and of creating efficient data-mining algorithms are met, and comprehensive libraries of template structures become available, we will be able to map the supramolecular landscape of cells systematically and thereby provide a new perspective for analyzing the molecular interaction networks underlying higher cellular functions.

References

1. Medalia, O., I. Weber, A.S. Frangakis, D. Nicastro, G. Gerisch and W. Baumeister:
Macromolecular architecture in eukaryotic cells visualized by cryoelectron tomography.
Science 298, 1209-1213 (2002).

2. Beck, M., F. Förster, M. Ecke, J. Plitzko, F. Melchior, G. Gerisch, W. Baumeister and O. Medalia:
Nuclear pore complex structure and dynamics revealed by cryoelectron tomography.
Science 306, 1387-1390 (2004).

3. Nickell, S., C. Kofler, A. Leis and W. Baumeister:
A visual approach to proteomics.
Nat. Rev. Mol. Cell Biol. 7, 225-230 (2006).

Short Biography

Wolfgang Baumeister studied biology, chemistry and physics at the Universities of Muenster and Bonn, Germany, and he obtained his Ph.D. from the University of Düsseldorf in 1973. He spent time at the Cavendish Laboratory in Cambridge, England, and in 1978 became lecturer in biophysics. In 1983 he moved to the Max-Planck Institute of Biochemistry in Martinsried, Germany, where he became director in 1988 and head of the Department of Structural Biology: He is also an Honorary Professor of Physics at the Technical University of Munich. Wolfgang Baumeister is the recipient of numerous prizes including Otto Warburg Medal, Schleiden-Medal, Louis-Jeantet Prize for Medicine, Stein and Moore Award and Harvey-Prize in Science and Technology. He is a member of several academies including the American Academy of Arts & Sciences.

Wolfgang Baumeister's research interests are in the field of cellular protein quality control. He has discovered and characterized several novel complexes which play key roles in protein folding and degradation and he made seminal contributions to our understanding of the structure and function of the proteasome. Moreover, he has pioneered the development of cryoelectron tomography, an emerging imaging technique with unique potential for molecular cell biology.