NIH partners with industry to create new ‘Living Lab’ for research into molecular structures that can affect disease
A new type of lab has been created to utilize near-atomic resolution microscopy and other structural biology technologies to help accelerate important medical discoveries relating to global health challenges, such as cancer and HIV/AIDS. The Living Lab Structural Biology Center was formed through a cooperative research and development agreement between the National Institutes of Health and FEI, Hillsboro, Ore., a scientific instruments company.
The lab, which will be located on the NIH campus, is a unique interdisciplinary collaboration among experts from FEI and scientists from the National Cancer Institute (NCI) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), both part of the NIH, in the fields of cryo-electron microscopy, nuclear magnetic resonance spectroscopy, X-ray diffraction, and biochemistry. A Titan Krios transmission electron microscope, one of the world’s most powerful commercially-available electron microscopes, will be located at NIH to enable the collaborative research.
“NIH is excited at the prospect of creating the Living Lab to harness intramural strength in the multiple disciplines in structural biology,” said Michael Gottesman, M.D., deputy director for intramural research at NIH. “This type of collaboration will help serve NIH’s mission to foster innovative research strategies in an effort to protect and improve the public’s health.”
The collaboration involves the development of methods and workflows, from sample preparation through data analysis, that combine information from all of the technologies in the Living Lab. Scientists have historically relied on nuclear magnetic resonance and X-ray diffraction techniques to determine the structures of molecular complexes and proteins that play a role in the causes of various diseases, such as AIDS, diabetes, and cancer. Although structural information about a wide variety of medically important proteins and drugs has been obtained by these methods, they have limitations that put some of the critical biological answers out of reach. Cryo-electron microscopy 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.
“Technical advances make it possible to tackle extraordinarily challenging problems, such as analyzing structures of complex assemblies like intact HIV particles,” said Robert Wiltrout, Ph.D., director of NCI’s Center for Cancer Research. “Successful integration of cryo-electron microscopy, X-ray diffraction, and nuclear magnetic resonance results could accelerate discovery of biological mechanisms and provide powerful tools to assist drug design.”
Sriram Subramaniam, Ph.D., senior investigator in NCI’s Laboratory of Cell Biology is the director of the Living Lab. Other NIH researchers participating in the Lab include leading nuclear magnetic resonance spectroscopists Adriaan Bax, Ph.D, and G. Marius Clore, M.D., Ph.D., both NIH distinguished investigators in NIDDK; X-ray crystallographers Alex Wlodawer, Ph.D., chief of the NCI Macromolecular Crystallography Laboratory; Fred Dyda, Ph.D., senior investigator in the NIDDK Laboratory of Molecular Biology; and biochemists Suresh Ambudkar, Ph.D., and Stuart Legrice, Ph.D., both senior investigators in the Center for Cancer Research, NCI .
“The prospects for applying cryo-electron 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,” said Subramaniam. “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.”
For more information, please go to http://electron.nci.nih.gov.
The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
The NIDDK, a component of the NIH, conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and kidney, urologic and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe and disabling conditions affecting Americans. For more information about the NIDDK and its programs, see www.niddk.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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