A one-shot Trial on the Molecules of Life

With SwissFEL scientists will be able to decipher the elusive structure of membrane proteins, which play a critical role in unraveling the mechanism of diseases like diabetes.
Arguably the most important discovery for modern biology, the determination of the structure of the DNA molecule back in 1953 is due to the use of X-ray crystallography. Today, seeing the structure of crystalline materials through X-Rays has become almost a routine. Images of non-crystalline objects like glass or single molecules, however, are a much harder nut to crack. Synchrotron radiation's power is limited in this respect. Their beam is not focused enough to make sense of the irregular structure of non-crystals. The current way out of this problem is long exposure, so as to get enough light through the sample one wants to image. But sometimes you just cannot irradiate as long as you want (see box on radiation damage below).

SwissFEL's got the power

In order to crack the structure of single molecules or non-crystalline materials a highly coherent beam is needed. Coherence means that the beam can highly be focused on a very small area. Furthermore due to coherence the individual contributions of each photon reinforce mutually leading to a sharper image of the sample. The degree of coherence of a FEL is so high that comparing SwissFEL to a Synchrotron beam, the difference is like between a laser pointer an a candle. The SwissFEL beam will be energetic enough to blow up virtually anything standing in its way. However, scientists are confident that the picture is taken before the sample falls apart. Preliminary experiments have shown that it may be possible to get a one-shot picture of, say, a virus, even though the virus itself would be destroyed by the SwissFEL flash. This would be a real breakthrough in studying the structure of biological molecules.

Especially researchers working on the design of smarter drugs will benefit from the unique brilliance of the SwissFEL beam. Membrane proteins, which are the targets of most modern drugs are almost impossible to image with existing synchrotrons. The difficulty lies in the requirement of growing large crystals of these proteins, which is necessary due to the limited brilliance and coherence of synchrotrons. At SwissFEL, however, thanks to its high beam brilliance, there will be no need of crystals to get good pictures.

Radiation Damage: Gone with the Beam

The molecules of life are the shooting stars of structural biologist's . One can think of them as lying under a microscope or seating in the experimental hutches of synchrotron facilities. Their job is all but glamorous, though. It usually requires long hours of beam exposure. And many just don’t survive the photo session.

X-Rays can cause fatal harm to biological materials. In fact, this so called radiation damage is the main limitation when trying to obtain pictures of the structures of biomolecules. On the other hand, a high radiation doses is sometimes indispensable to get the wanted atomic resolution. When imaging biomolecules, coherent illumination is an essential requirement. Coherent means that light is tightly focused on a small spot and upon deviation by the atoms of the imaged specimen, the different light ways eventually reinforce each other to make a sharp picture. Synchrotrons do not produce inherently coherent light. In order to make Synchrotron light coherent, the beam must be filtered by narrow slits which let only a tiny fraction of the original beam through. That means, that at synchrotrons coherence comes at the cost of intensity losses. SwissFEL can circumvent this dilemma due to its inherently highly coherent and extremely brilliant beam, which means that atomic resolution pictures of proteins, viruses, etc. can be obtained with one single shot, rather than after hours of irradiation. Even though the sample will be destroyed by the beam, the detectors will still be fast enough to capture the single-shot image of the biomolecule, before it is torn apart.