FEI has partnered with five pharmaceutical companies: Astex Pharmaceuticals, AstraZeneca, GlaxoSmithKline, Heptares Therapeutics, and UCB; the Medical Research Council Laboratory of Molecular Biology (MRC-LMB); and the University of Cambridge’s Nanoscience Centre, to form the “Cambridge Pharmaceutical Cryo-EM Consortium,” which is the first of its kind worldwide.
As part of the three-year agreement, FEI will provide sample preparation and data collection services on a Titan Krios™ cryo-transmission electron microscope (cryo-EM)to the consortium companies for early-stage drug discovery research. The five companies involved in the consortium will share access to the microscope with colleagues from the MRC-LMB and the University of Cambridge in return for expert guidance on the use of cryo-EM technology.
FEI’s Titan Krios will be installed at the Nanoscience Centre in May. Richard Henderson, pioneer in the field of cryo-EM at MRC-LMB, states, "It is delightful to know that the development of cryo-EM, which many people have worked on for many years, has now reached mainstream structural biology. It is particularly satisfying that pharmaceutical companies are keen to evaluate the approach for drug development."
Prof. Sir Mark Welland, director of the Nanoscience Centre, said, “This is a great opportunity for researchers across the University to access a microscope.” Cryo-EM has quickly become one of the most important techniques used by structural biologists to obtain molecular-scale three-dimensional(3D) information about protein structures.
When combined with traditional methods for structure determination, such as x-ray crystallography and nuclear magnetic resonance spectroscopy, the resulting models can reveal the structure of complex, dynamic molecular assemblies down to the scale of individual atoms.
The consortium’s Titan Krios will use the Relion software package, developed by Sjors Scheres at MRC-LMB, to process the image data into a visual 3D model that helps researchers see and understand the structure and function of the protein.
“Cryo-EM 3D 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,” states Peter Fruhstorfer, vice president and general manager of the Life Sciences business, FEI. “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.”
Fruhstorfer adds, “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.”