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National Center for Macromolecular Imaging

Center Overview

Protein molecules and macromolecular assemblies perform the vast majority of chemical and physical actions within the cell. These tiny molecular machines perform extremely complex actions, and yet are only 10-100 nm in size. This is too small to be seen using the best possible light microscope, as they are smaller than the wavelength of visible light. In transmission electron microscopy (TEM), imaging is performed using electrons, with wavelengths of less than 0.001 nm. While the resolution of TEM is still limited due to the radiation sensitivity of biological molecules, it has now achieved resolutions ranging from 0.3 nm to 5 nm, depending on the specific technique used. TEM is capable of visualizing objects ranging from individual protein/RNA/DNA molecules to regions of cells, providing detailed information about their physical structure and function.

The National Center for Macromolecular Imaging is focused on extending the resolution, speed, and flexibility of electron cryomicroscopy (cryo-EM) for three-dimensional structure determination of biological macromolecular assemblies. The resource tackles structural problems that are too complex or too difficult for X-ray crystallography and nuclear magnetic resonance spectroscopy. Xray crystallography, the historically dominant technique in structural biology, requires the molecules under study to be rigidly locked into a single conformation. Cryo-EM, unlike crystallography, can visualize molecules under near-native conditions, and can yield images of individual molecules in a range of different conformations as they exist in solution. While these individual molecular images are highly noisy, using sophisticated computer algorithms it is possible to take tens of thousands to millions of these individual images and characterize the dynamics of these proteins in a quantitative way. Other cryo-EM techniques such as cryo-electron tomography are being developed to capture molecular structures in-situ, that is, rather than biochemically purifying a single species of molecule and studying its behavior under "artificial" conditions, actual biological molecules can be imaged within the cell at sufficient resolution to observe their conformations.

Impact on Human Health

NCMI cryo-EM hardware, software and methodologies are particularly targeted to study structures of biologically active nanomachines, which are potential drug targets for treating or preventing diseases.

NCMI collaborative research covers structures closely tied to infectious diseases. These include viruses such as Herpesvirus, and Venezuelan Equine Encephalitis Virus, which is also a bioterrorism agent; bacteria such as Salmonella and cyanobateria; nuclear receptor superfamily protein complexes, which is a major drug target of breast cancer, and parasites such as Trypanosoma brucei, the causative agent of African Sleeping Sickness. Another focus is on neurodegenerative diseases and aging, involving the study of the misfolding of proteins found in Huntington's, Parkinson's and Alzheimer's Diseases and the potential use of molecular chaperonins to prevent their protein aggregation. In a third area, NCMI is contributing structural details to solve the puzzle of cardiovascular disease, investigating lipoprotein assemblies, ion channels, and the formidably complex structure of the human blood platelet, which plays a critical role in the initial stages of clot formation.


Animations, Cryo-EM, cryo-ET


ResourceDescriptionSupported PlatformsSupported FormatsData TypeData Size (compressed)
National Center for Macromolecular Imaging

Full featured scientific image processing suite. Mainly targeted at the transmission electron microscopy community, but also used in other areas. Includes a library of nearly 1000 algorithms with an integrated openGL GUI and full Python bindings.

Linux, Mac OSX, Windows Amira, CNS or XPLOR...(more) N/A N/A
National Center for Macromolecular Imaging

Electronic lab notebook and  Object oriented database (OODB). Flexible web-based interface requires no database experience to use, yet permits rich data mining/query capabilities. Currently supports 600+ users with >15 TB of image data, yet trivial to install for small-scale sites. Python based.

Linux, Mac OSX AJAX, Binary N/A N/A
National Center for Macromolecular Imaging

Volume segmentation tool targeted at Cryo-EM density maps. This is a plugin for Chimera.

Linux, Mac OSX, Windows Aligned FASTA, Aligned NBRF/PIR,...(more) N/A N/A