Cryo-EM Techniques to Be Exploited by UK-Based Research Consortium

A consortium has been formed to optimize the use of advanced cryo-electron microscopy techniques and to pool knowledge to promote the use of the instrument for research in structural biology and drug development.

Researchers have historically relied on NMR and X-ray diffraction techniques to determine the structures of molecular complexes and proteins that play a role in the causes of various disease states. Structural information about a variety of medically important proteins and drugs has been obtained by these methods. Cryo-EM is a complementary analytical technique that provides near-atomic resolution without requirements for crystallization or limits on molecular size and complexity imposed by the other techniques. Cryo- EM allows the observation of specimens that have not been stained or fixed in any way, showing them in their native environment while integrating multiple images to form a three-dimensional model of the sample.

To optimize the use of cryo-EM, the instrument manufacturer FEI will partner with five pharmaceutical companies: Astex Pharmaceuticals, AstraZeneca, GlaxoSmithKline, Heptares Therapeutics and UCB with the Medical Research Council Laboratory of Molecular Biology and the University of Cambridge’s Nanoscience Center to form the “Cambridge Pharmaceutical Cryo-EM Consortium”. The members of the consortium will share access to a Titan Krios cryo-transmission electron microscope and will receive expert guidance from FEI on the use of cryo-EM technology.

The Titan Krios transmission electron microscope (TEM) was tailored for use in protein and cellular imaging. Its revolutionary cryo-based technology and stability was designed to permit a full range of semi- automated applications, including: electron crystallography, single particle analysis, cryo-electron microscopy, and dual-axis cellular tomography of frozen hydrated cell organelles and cells.

“In addition to installing the Titan Krios cryo-EM system, our contribution to the consortium includes providing an application scientist that will work with the participating companies to ensure a smooth workflow throughout, from sample preparation to data collection and data processing, with a special focus on creating a standardized and robust single-particle analysis workflow,” said Peter Fruhstorfer, vice president and general manager of life sciences at FEI. “Cryo-EM three-dimensional models allow us to see and understand the workings of protein-based molecular machines that we could not analyze before because they were too large and complex or were resistant to the preparations required for other techniques. The technique was rapidly adopted by leading academic researchers and is now finding its way into early stage discovery and development in the pharmaceutical industry.”

Related Links:

FEI
Aster Pharmaceuticals
AstraZeneca
GlaxoSmithKline
Heptares Therapeutics
UCB
Medical Research Council Laboratory of Molecular Biology
University of Cambridge’s Nanoscience Centre