February 2012

'Living Lab' tackles molecular structures involved in disease

The National Institutes of Health and the scientific instruments company FEI have created the Living Lab Structural Biology Center. This new laboratory will exploit near-atomic-resolution microscopy and other structural biology techniques to better understand the molecular basis for diseases such as cancer and HIV/AIDS.

The laboratory will be located on the NIH campus in Bethesda, Md. Experts from FEI, the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases will collaborate in the fields of cryoelectron microscopy, nuclear magnetic resonance spectroscopy, X-ray diffraction and biochemistry. A Titan Krios transmission electron microscope, one of the most powerful electron microscopes commercially available, also will be used in experiments.

Methods like NMR and X-ray diffraction techniques determine molecular structures of proteins. Although structural information about a wide variety of medically important proteins and drugs has been obtained by these methods, they have limitations. Cryoelectron microscopy is a complementary analytical technique that provides near-atomic resolution; it doesn’t require crystallization or particular molecular sizes and complexity, which limit the other techniques. Living Lab researchers will develop methods and workflows, from sample preparation to data analysis, based on integrating all of these technologies together.

Sriram Subramaniam, the senior investigator of NCI’s Laboratory of Cell Biology, is the laboratory’s director. “The prospects for applying cryoelectron microscopy to study the structures of a broad spectrum of medically relevant complexes has changed dramatically in recent years with advances in microscope hardware and powerful new methods for image analysis,” he said in a statement. “Our goal with the Living Lab is to capture the synergy between the latest methods by studying selected large molecule complexes that span the range from viral and DNA-binding proteins to integral membrane proteins and nucleic acids that are representative of key scientific challenges in modern structural biology.”

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