Illustration of the concept of Online crystallography

Illustration of the concept of Online crystallography.

EMBL Grenoble’s High Throughput Crystallization and Fragment Screening Facility (HTX lab), offers access to fully automated, remote controlled crystallography pipelines based on the CrystalDirect technology and the CRIMS software. This unique facility is one of the core technical platforms of the Partnership for Structural Biology (PSB) and is available to external users via iNEXT-Discovery project and INSTRUCT-ERIC.

EMBL Grenoble operates the High Throughput Crystallization Facility (HTX lab), a large scale user facility offering High Throughput (HT) crystallography services. Since the start of operations in 2003 the HTX lab has provided services to over 800 scientists and processes more than 1000 samples per year.

The HTX lab has a strong focus in the development of new methods in macromolecular crystallography, including methods for sample evaluation and quality control and the creation of the CrystalDirect technology, enabling fully automated crystal mounting and processing.

The HTX lab has also developed the Crystallization Information Management System (CRIMS), a web-based laboratory information system that provides automated communication between crystallization and synchrotron data collection facilities, enabling uninterrupted information flow over the whole sample cycle from pure protein to diffraction data. This software is currently in operation in multiple laboratories across Europe.

Through the combination of the CrystalDirect technology and the CRIMS software, the HTX lab has developed the concept of Online Crystallography: fully automated, remote controlled crystallography pipelines integrating crystallization screening, crystal optimization, crystal mounting and cryo-cooling, and automated X-ray data collection (at ESRF, PETRA III and SLS synchrotrons) into continuous workflows controlled though dedicated web interfaces. This approach minimizes the delay between crystal growth and measurement, accelerating the progression of challenging projects. The CrystalDirect technology also enables automated crystal soaking making it possible to support highly efficient automated, large-scale small molecule and Fragment Screening by crystallography.

Currently The HTX Lab offers access to the following pipelines:

  • Online Crystallography (protein-to-structure pipeline)
  • Fragment Screening (based on CrystalDirect)
  • Screening and structural characterization of ligand-target complexes (based on CrystalDirect)

X-ray diffraction data collection is typically carried out at the Macromolecular crystallography (MX) beamlines of the European Synchrotron Radiation Facility (ESRF) operated by the ESRF- EMBL Joint Structural Biology Group and at the Petra III synchrotron.

In collaboration with the Synchrotron Diffraction, Instrumentation and ESRF MX Teams, the HTX lab is working towards integrating the CrystalDirect technology into the MASSIF-1 beam line environment, which will now be operated in coordination with the HTX Lab. This will increase our throughput and capabilities to support fragment screening and online crystallography. At the same time, it will enable new experimental opportunities.

Moreover, we will continue to develop the CrystalDirect technology to support serial crystallography applications as well as new approaches for the rapid analysis of membrane proteins both at cryogenic and room temperature.

For applications please contact José Marquez, head of the Crystallisation Facility.

HTX Lab contact

José Márquez
marquez@embl.fr
Head of Crystallisation Facility
Marquez Team