Highlighting the significance of structural analysis of biomolecules

In cryo-electron microscopy, for which the Nobel Prize for Chemistry 2017 was awarded, a great many images of identical biological molecules are first produced with an electron microscope. Most often the objects examined are large proteins or protein complexes – complex molecules that are responsible for countless cellular processes, which are essential for life – or larger viruses. These individual images are then compared with each other through an elaborate mathematical procedure. In the end this produces an image that shows considerably finer structures than a single image from an electron microscope could. The resolution is improved to such an extent that even the arrangement of individual atoms in the molecule becomes visible. It is crucial that the measurements are carried out at very low temperatures, below minus 150 degrees Celsius. In addition, the molecules must be flash-frozen in an aqueous solution, preventing the formation of ice crystals, using a method developed by Swiss researcher Jacques Dubochet.

The awarding of the prize underscores the fundamental significance of structural analysis of biomolecules for modern biology. The Paul Scherrer Institute PSI has a leading position in structural biology in Switzerland. For nearly 20 years, PSI has operated the Swiss Light Source SLS, which represents a gold standard in the field of structural analysis of protein crystals by means of X-rays. The X-ray free-electron laser SwissFEL went into operation in 2016 and is setting new standards in time-resolved structural analysis compared with all established methods. At the SwissFEL, researchers will be able to examine in detail not only the structure but also the movement of protein molecules.

There have also been important activities at PSI in structural analysis using electrons since Gebhard Schertler, a former long-time co-worker of this year's Nobel Prize winner Richard Henderson, became head of the Division of Biology and Chemistry at PSI in 2010. Schertler remarks: The importance of structural analysis using electrons has been clear to me for many years, and I have therefore further developed the modern electron microscopy platform at PSI, which is complementary to the Swiss Light Source SLS. We were also able to attract two renowned experts to PSI, Takashi Ishikawa for electron microscopy and Jan-Pieter Abrahams for structural analysis using electrons. Abrahams worked with Richard Henderson on the development of new detectors in the 1990s. Today, at PSI, Abrahams is developing together with the University of Basel a novel device for structural analysis of biomolecules using electrons. This will not produce images of individual molecules, as today's devices do, but rather diffraction patterns that show how electrons were diverted on their way through the molecule. This method has the potential to further advance the quality of single-molecule analysis in the biosciences by yet another major step, and to enable a new dimension in structural analysis with electrons, Abrahams explains. We are excited to see how the field develops in the coming years. Who knows? Maybe the structural biologists' long-standing dream, of making the structure of individual biomolecules visible directly within a living cell or in the tissue, will yet be realised someday.

Text: Paul Scherrer Institute/Gregor Cicchetti