Mesh and collect: a new method to collect data from hundreds of crystals in one go

16-06-2017

Small and, until now, unexploitable crystals can now lead to solving atomic structures of proteins when grouped together in the “mesh and collect” method at the ESRF.

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“Mesh & Collect” is a development carried out by the ESRF with the Synchrotron Serial Crystallography BAG (beamline allocation group), inspired by recent developments made at X-ray Free Electron Lasers. The method consists of scientists harvesting many small crystals directly from crystallisation drops using a standard sample holder. This sample holder is then scanned in two dimensions at cryogenic temperatures using a low intensity X-ray mesh scan to automatically determine the positions of individual crystals by X-ray diffraction. From those crystals, scientists record partial diffraction data sets over a small rotation range. After integration, the individual partial data sets are sorted in clusters of isomorphous similarity, these are merged to give a complete diffraction data set that can be used for structure solution.

The ESRF has integrated this method in the last years and it is popular among users. "This method allows us to do experiments which would not have been possible a couple of years ago. It is available as an automatic workflow, ready for users to exploit it and it can play a big role in research ", explains ESRF scientist Christoph Mueller-Dieckman.

Industrial clients such as Sanofi have already started using the method. Magali Mathieu, researcher at Sanofi, is very positive about the experience: “We tested the method to check whether we could exploit it, and it is very promising in the sense that it could scan crystals that were in principle not usable. Only hiccup is that we hadn’t brought enough crystals, but we will bring more next time”.

Last week, a team from the Inserm à l’Institut de Génomique Fonctionnelle, Humboldt Universität in Berlin (Germany), University of Oxford (UK) and the Suez Canal University (Egypt) unveiled the functioning of the hormone adiponectin in Nature magazine. They could solve the structure of two receptors of the hormone thanks to the mesh and collect method.