Folding Forum

Homepage of XFEL (X-Ray Free-Electron Laser)
http://www.xfel.eu/

Brief description
http://www.xfel.eu/overview/in_brief/

Research Possibilities
http://www.xfel.eu/research/possibilities/

Example
http://www.xfel.eu/research/examples/st ... molecules/
Bild der Wissenschaft (German)
http://www.wissenschaft.de/bildstrecken/xfel
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Part of interest
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Blitze für die Medizin
Biologen, Mediziner und Pharmakologen setzen große Hoffnungen auf den Röntgenlaser. Er soll es ihnen ermöglichen Zeitlupenfilme zu erstellen, zum Beispiel von Reaktionen die sich in Sekundenbruchteilen abspielen. Dazu werden lebende Proben in den Fokus des Röntgenlichts geschossen. Das empfindliche Material wird dadurch zerstört, wegen der ultrakurzen Belichtungszeit von knapp vier Millionstel Sekunden allerdings erst nach der Aufnahme. Wie ein Daumenkino lassen sich mehrere solcher Schnappschüsse zu einem ganzen Film zusammensetzen.
Das könnte nicht nur die Strategien vor Viren entlarven, die sich in Wirtszellen einschleusen, sondern auch dabei helfen die PROTEINFALTUNG zu beobachten. Schwere Krankheiten wie Alzheimer hängen ursächlich mit einer falschen Proteinfaltung zusammen. Allerdings weiß man noch nicht genau, was dabei schief läuft. Im Zeitlupenfilm könnte das sichtbar werden – und helfen, Medikamente zu entwickeln, die eine Falschfaltung verhindern.

Arthur
BTW: Would someone be so friendly and translate the German "Part of interest" ? (excuse me, but I do not dare to do this)

Google Translate is good enough to get the gist before someone with better skills comes along.

Lightning for medicine
Biologists, physicians and pharmacologists place high hopes on the X-ray laser. It should allow them to create slow motion movies, for example, of reactions that occur in fractional seconds. For this purpose, live samples are shot into the focus of the X-ray light. The sensitive material is thereby destroyed, but because of the ultra short exposure time of just four millionths of a second, however, only after the recording. Like a Daumenkino (flip book movie, or for the younger crowd, like a stop motion video), several such snapshots can be made into a whole film.
This could not only expose the strategies against viruses, which are introduced into host cells, but also help to observe the protein folding. Severe diseases such as Alzheimer's disease are caused by a wrong protein folding. However, you do not know exactly what is going wrong. This could be seen in the slow motion film - and help to develop drugs that prevent false folding.

"Das könnte nicht nur die Strategien vor Viren entlarven, die sich in Wirtszellen einschleusen"

Let's first correct that German

"Das könnte nicht nur die Strategien von Viren entlarven, die sich in Wirtszellen einschleusen"

This could not only expose the strategies of viruses, the way they are infiltrating into host cells, ... find the difference between active/passiv rather important. The rest is ok for my limited English skills.


And then "Falschfaltung" ... sounds very German ... "Fehlfaltung" would be better; or in Neudeutsch "misfolding"

Lots of structural biologists are excited for this to come online, but I believe the first X-ray free-electron laser (XFEL) for use in biomolecular crystallography is actually at Stanford and went into service in 2010:

https://portal.slac.stanford.edu/sites/ ... fault.aspx
https://www6.slac.stanford.edu/news/201 ... -lcls.aspx

This is a fantastic technology, but much like any structural biology method, has severe limitations since high-intensity X-ray flux can vaporize a single-protein electrospray droplet in tens of femtoseconds.

From what I understand, the Stanford XFEL has been heavily used to collect good datasets for very small protein crystals---essentially extending the range of which systems can produce useful crystals for X-ray sturctures.

XFEL enables some great science, but it really is a complementary technique to other structural biology methods and atomistic simulations.

Another technology that has become incredibly useful over the last few years is cryo-electron microscopy (cryo-EM). New detector technology has allowed cryo-EM to achieve incredible resolution of membrane proteins and large protein complexes, and the tools to solve these structures have recently been ported to GPUs.
You might enjoy this article:

http://biomedicalcomputationreview.org/ ... microscopy

Best,

John