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The Cambridge Pharmaceutical Cryo-EM Consortium Inaugurates Its Latest Krios Cryo-TEM

By 02.07.2019

It’s been an exciting time for pharmaceutical companies interested in accelerating their drug discovery research. Cryo-electron microscopy (cryo-EM), a technique that has quickly become one of the most important for studying protein structures at the molecular scale, allows drug researchers to analyze protein-based molecule assemblies that were once too large, too complex, and too resistant to crystallize.

On January 28, I attended a meeting of the Cambridge Pharmaceutical Cryo-EM Consortium where members unveiled their newest Thermo Scientific Krios Cryo Transmission Electron Microscope (cryo-TEM), designed to take cryo-EM exploration even further.

Formed in April 2016, the consortium is a partnership among the Medical Research Council Laboratory of Molecular Biology, University of Cambridge’s Nanoscience Centre, Thermo Fisher Scientific and five pharmaceutical companies: Astex Pharmaceuticals, AstraZeneca, GSK, Sosei Heptares Therapeutics, and UCB.

Through increased collaboration and shared access to cutting-edge Thermo Fisher cryo-TEMs, the consortium is helping drug makers better understand the transformative role cryo-EM can play in the drug discovery process. Since the consortium’s formation, cryo-EM has experienced steep growth. This year, for example, the number of pharmaceutical companies purchasing in-house cryo-EM instruments is expected to quadruple from 2017.

Members of the Cambridge Pharmaceutical Cryo-EM Consortium inaugurate their latest Krios Cryo-TEM at the University of Cambridge. From left to right: Dr. Harren Jhoti, Dr. Richard Henderson, Dr. Paul Midgley, and Mike Shafer.

Accelerating drug discovery research

During the conference, participants toured the new Krios, which is being housed within the University of Cambridge’s Department of Materials and Metallurgy. In addition, several members of the consortium spoke about the advances taking place using cryo-TEMs.

Dr. Richard Henderson outlining the potential and power of Cryo-EM

Dr. Richard Henderson, founder of Heptares Therapeutics and the winner of the 2017 Nobel Prize in Chemistry for his work in cryo-EM at the MRC-LMB, opened the conference by discussing this technique’s ability to solve structures that have proven difficult to tackle using other methods. Using cryo-EM, for example, researchers have been able to solve the structures of the Hepatitis B virus and Mitochondrial Complex 1 at far higher resolutions, adding significant detail to their understanding of these conditions. Researchers have also solved the cryo-EM structure of the cytoplasmic ribosome from the human malaria parasite, Plasmodium falciparum, in complex with the antibiotic emetine at 3.2 Å resolution, paving the way for new anti-malarial treatments.

Dr. Harren Jhoti, president and CEO of Astex Pharmaceuticals, spoke about the potential of cryo-EM technology in structure-based drug design, saying the consortium has sparked a high level of sharing as the pharmaceutical industry uses cryo-EM for drug discovery. Dr. Paul Midgley, Director the Department of Materials Science & Metallurgy at the University of Cambridge, talked about the potential for cryo-TEM to foster new discoveries that cut across both life sciences and materials science. Midgley also discussed the potential for microcrystal-electron diffraction (MicroED), which uses electrons to analyze crystallized protein samples that are too small and too sensitive to observe with traditional x-ray diffraction.

Doubling researcher productivity every two years

At Thermo Fisher, our goal is to continue to help pharmaceutical companies accelerate their research, and to that end, Mike Shafer, president of the Materials & Structural Analysis Division at Thermo Fisher, discussed our continued plans for product development.

Over the past three years, we’ve increased our research and development in the materials and structural analysis space considerably. Among our goals are to help researchers determine the 3D structures of even smaller proteins and to expand cryo-EM to a wider number of users by making our electron microscopes easier to use and to improve sample preparation. We also aim to double researcher productivity every two years.

With this new cryo-TEM in place, researchers can continue to develop novel cryo-EM methods that help to unravel a range of medical mysteries. With the ability to understand protein structures at the near-atomic level, pharmaceutical companies are working to accelerate drug discovery and development, which, in turn, will bring more life-saving drugs to market more quickly.

Raymond Schrijver is the Sr Director, Product Marketing, Electron Microscopy at Thermo Fisher Scientific.

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