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Structural Biology (ER-C-3)

The Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons – Structural Biology (ER-C-3) studies the structural biology of essential cellular processes using cryo-electron microscopy (cryo-EM) as the central method. Cryo-EM permits the investigation of biochemically purified, macromolecular structures and multi-protein complexes. The technique is important, for example, in understanding the development of neurodegenerative diseases such as Alzheimer’s.

For 3D cryo-EM, the samples are first flash-frozen and then investigated using an electron microscope. The macromolecules can be examined in vitro in their near-native environment or inside cells without the need for crystallization. The electron micrographs are then combined using computer-aided image processing techniques in order to compute their 3D structures (Figure).

Cryo-EM will become standard method in structural biology

New developments both in microscopic devices and in data analysis have made it possible to show a multitude of biological structures at an atomic resolution. Thanks to the associated increase in knowledge, cryo-EM promises to become the routine method for solving the structures of large macromolecules at a high resolution.

Further development of the method has enormous potential

In order to fully realize the potential of the technique, further hardware-based improvements and data-analysis enhancements will be required in future. Therefore, ER-C-3 has set itself the objective of developing new and improved approaches to sample preparation, macromolecule imaging, and data processing. These can be applied more generally in the challenging research on macromolecular structure determination.

Scientist in laboratory, electron cryo-microscope, computer-aided 3D-construction ER-C-3: Structure determination using the cryo-EM technique
Copyright: Forschungszentrum Jülich

Cryo-EM in the context of other biological methods

In order to gain mechanistic insights into these basic cellular processes, proteins must be purified and prepared for structural analysis. At ER-C-3, the cryo-EM structures are supplemented by high-resolution X-ray structure analyses or by biochemical or cell-biological experiments where possible. Finally, these long-term projects aim at structurally understanding the molecular and chemical principles that characterize the architecture of the cell.

Head of Institute:

Dr. Carsten Sachse