Striking advances in cryogenic electron microscopy (cryo-EM) techniques have been made in the last decade and the accompanying resolution revolution has made it the primary method in structural biology for high resolution studies of proteins, cells and tissue.

In May 2024 a research team with complementary expertise across Hamburg, Lund, Copenhagen and Aarhus kicked off a HALRIC pilot project focusing on the ion homeostasis target ClC‐1 – essential for human health and highly attractive in the treatment of for example autoimmune and neuromuscular diseases. The project focus on solution scattering techniques, but also guide cryo‐EM experiments with the University of Copenhagen at EMBION. “This is a prime example of how HALRIC can be the platform for large-scale Research Infrastructures to be used in collaboration with other types of unique infrastructures at the universities in the HALRIC consortium,” underlines Kajsa M. Paulsson, HALRIC Project Director.

Cryo-EM can be used to identify the structure of small molecules and proteins that cannot be crystallised. Both are important in the drug discovery journey in academia, as well as in industry. Additionally, with constant advances in cryogenic electron tomography (cryo-ET), large molecular complexes and cellular ultrastructures can be imaged and analyzed under near-native conditions. This can provide crucial information for clinical and academic research, particularly in disease studies.

“Compared to protein crystallography that was the dominating method in structural biology for decades, cryo-EM does not require crystals to determine structures to atomic resolution, which removes a major bottleneck in experimental structure determination and speeds up the process tremendously,” said facility manager Thomas Boesen in connection with one of the first HALRIC pilot projects, where his lab is collaborating with the University of Oslo, who prepares the samples for the joint project to decipher protease zymogen action to enable stroke therapy.

Professor Boesen was also involved, when the cryo-EM technique came to Europe around 2010 and the first electron microscopes was installed at Aarhus University. The next generation Titan Krios microscope was installed ten years later when EMBION, a new national cryo-EM facility between Danish Universities was also launched.

When looking to Sweden and Germany in the HALRIC geography, Lund University is in the process of installing its first microscope that will be placed at MAX IV and currently offers sample preparation. In Norway the University of Oslo will open the doors to their new Life Science Building in 2026 and hope to house two Titan Krios microscopes. Universität Hamburg also offers access to a multi-user cryo-EM facility, which is located within the Centre of Structural Systems Biology (CSSB) on the Science Campus Bahrenfeld.