Studying the structure of macromolecules the easier and more accessible way
Research supported by the EU-funded ARISE project has led to a new method for using in situ serial crystallography to study the structure of macromolecules. Described in a paper published in ‘IUCrJ’, the method is now being used at ID23-2, a microfocus beamline for macromolecular crystallography jointly operated by ARISE coordinator European Molecular Biology Laboratory (EMBL), Germany, and the European Synchrotron Radiation Facility, France. EMBL Grenoble Fellow Nicolas Foos, the study’s first author, was part of the first generation of scientists to be trained under the ARISE project. Participating fellows receive training in research infrastructure management, career support and the opportunity to work on any technology development project of interest. In an interview posted on the EMBL website, Foos describes the new method. “The main feature of the method is that it works directly from the crystallisation plate,” he explains. “A crystallisation plate can have an average of 96 wells (very small holes), each containing three tiny drops of crystallised protein. Harvesting these crystals to find just a few good ones – which is the regular approach – is tedious and time-consuming. Instead of harvesting only the ‘best-looking’ crystals, in situ experiments consist of screening them directly in the crystallisation plate and getting the data from there. However, this type of experiment was not seen as an accessible method for everyday use.” Relying on instruments that offer excellent movement and data collection accuracy, the new technique is simple and efficient. “Once you have the right tools, you need the appropriate interface to use them in the best possible way,” notes Foos. “To ensure a reliable, precise, and well-controlled method, we developed a user interface adapted to the user’s needs.”
The method’s advantages
The new method creates a shortcut in the usual structure determination workflow, making in situ experiments straightforward and efficient. This makes the process of structure determination less costly and time-consuming. Furthermore, the method’s application in drug discovery projects would allow experiments to be conducted at room temperature since compounds are able to be screened directly on the plate. According to the researcher, making it possible to study targets in their natural state will lead to better quality and reliability in the final output. Foos adds: “Taking this a step further, we are also opening up new opportunities for even more automated experimental workflows. We may soon see the development of a ‘From the plate to the 3D model’ pipeline, without human intervention – which I believe should be the ultimate goal.” The ARISE (Career Accelerator for Research Infrastructure Scientists) project ends in April 2027. For more information, please see: ARISE project web page
Keywords
ARISE, crystallography, macromolecule, crystallisation plate, structure determination
