Time-resolved crystallography for the masses

by Dorota Badowska

EMBL Hamburg scientists have contributed to the development of the Spitrobot, a ground-breaking experimental setup that will greatly simplify time-resolved crystallography experiments

Scientists from four research institutes in the Science City Hamburg Bahrenfeld have joined forces to develop a ground-breaking experimental setup. Their new Spitrobot greatly simplifies observing changes in proteins as they carry out their functions. This makes time-resolved crystallography accessible for non-specialist research groups, as samples can now be prepared in standard labs and processed by automated established high-throughput methods elsewhere. The device will accelerate fundamental research in health and disease. The team has now presented the concept behind the Spitrobot in Nature Communications.

To develop future drugs and design new biotechnological applications, it is fundamental that scientists understand the changes in proteins while these are taking place. Currently, the beginning and the end of the reaction can be addressed but the many intermediate steps are usually missing from the picture. The simplest way to visualise these different steps is to take ‘snapshots’ of the protein throughout the reaction. Many such snapshots put together then produce a 3D ‘stop-motion-movie’, showing the changes in the protein structure over time from all angles.

So far, such experiments have required direct access to particle accelerators (synchrotrons and XFELs) and complex experimental setups, which are out of reach for many scientists. Therefore, researchers from Hamburg University (UHH), the Max Planck Institute for the Structure and Dynamics of Matter (MPSD), EMBL Hamburg and the University Medical Center Hamburg Eppendorf (UKE) (all in Hamburg) have devised a different and far more accessible alternative – the Spitrobot.

The Spitrobot dramatically simplifies the entire sample preparation process, from the initial fixing of the protein crystals and kick-starting the reaction through to the precise cryo-trapping of the proteins at various stages of their transformation. Reactions are initiated simply by ‘spitting’ the substrate solution onto the target – a technology previously developed by the team. By vitrification of the samples (i.e. cooling them to a glass-like state) the Spitrobot uncouples sample preparation from data collection. Using industry standards ensures the convenient dispatch of the samples and their compatibility with high-throughput routines commonly available at synchrotrons and other facilities. Thus the experiment can be carried out in standard laboratories without immediate access to light sources – a major advantage to most researchers in structural biology.

EMBL Hamburg scientists from the Wilmanns Group and Schneider Group tested the robot on biological samples. They proved that it greatly simplifies monitoring each step of a biological reaction with X-rays.

“The Spitrobot is a gamechanger that will make time-resolved crystallography more accessible to the scientific community,” said Sihyun Sung, EMBL Hamburg’s Postdoctoral Fellow who participated in this work. “This breakthrough technology will undoubtedly pave the way for new discoveries in various fields of research.”

Adapted from the press release by the Max Planck Institute for the Structure and Dynamics of Matter.

This article was first published on EMBL News