The Electron Microscopy Data Bank

Cryo-Electron Microscopy, a microscopy technique in which electrons play the role of light in conventional microscopes, is a central technology in attempting to understand the inner workings of the living cell. It enables researchers to obtain images of cells and molecules, instantaenously frozen and embedded in an extremely thin layer of non-crystalline ice, at an extremely high resolution, at which the inner workings of the molecular machines that drive them can be discerned. The Electron Microscopy Data Bank (EMDB) is the central data bank for storing and distributing the three-dimensional images taken using advanced electron microscopy techniques with biological samples. Initiated in 2002 by Dr Kim Henrick, the head of the Macromolecular Structure Database group of the European Bioinformatics Institute (EBI) in Cambridge, it already contains over 500 structures of macromolecular objects, and is expected to rapidly grow over the coming years, as improvements in microscope and specimen-preparation technology take effect. It provides structural biologists world-wide with a resource for the deposition, distribution, and analysis of such images to facilitate their research and further the understanding of the basic mechanisms of life, which as an ultimate goal will contribute to an improved understanding of the mechanisms of health and disease in plants, animals, and humans. The data bank is operated as an interactive web site at which researchers submit their data for deposition. To maintain the high quality of the data, every submission is curated by an experienced curator, who supports the researches in matters of quality and technical correctness, and then made publicly available through a simple, user-friendly web site. Particular care is taken to collect accurate metadata, i.e. information about the experimental background, such as the protein or cell under investigation, the conditions of its preparation, information about the imaging process and a record of the computer programs applied to the image information to reconstruct the final three-dimensional information. In cooperation with the Open Microscopy Environment developed by Prof Jason Swedlow and colleagues at the University of Dundee, the interface will be further developed to provide enhanced capabilities to its users. The Open Microscopy Environment is a set of software tools aimed at researchers in light microscopy to support the managemant of large image data sets. The collaboration between EMDB and OME for the first time links researchers in light and in electron microscopy to create improved tools for public research image databases, and leverages the technologies developed in OME to improve the general user experience. A particular goal here is to extend the user interface to accept 'rich submissions', i.e. complex three-dimensional image sets that contain a variety of information. This might include in particular details of the atomic structure of proteins derived by 'fitting' known atomic structures into the images, or annotations informing on the putative locations of molecules in larger structures. New computational techniques in electron microscopy also produce image sets showing structural variations that proteins undergo when performing in biochemical processes, and thus directly contribute to understanding the molecular machines that drive the processes of life. The technology developed in this resource will not only benefit biologists who use the resource, but also serves as a testing ground for future public biological image databases. As imaging technology in many areas develops, it is less and less often the case that a single image captures all the information a researcher needs, and more and more often large sets of images have to be used and communicated between researchers. Image databases and the new field of bioimage informatics will play a major role in this.

The Electron Microscopy Data Bank (EMDB) is the central resource for storing and distributing three-dimensional density maps of macromolecular complexes and sub-cellular structures derived from electron microscopy. It has at this time about 600 entries, a large number of which are high-resolution molecular structures derived from single-particle analysis, in which many images are combined computationally to improve resolution, and a smaller but growing number from cryo-electron tomography, in which the specimen is imaged from different directions to give a three-dimensional reconstruction of sub-cellular structures and macromolecular complexes in their native context. Improvements in specimen preparation, imaging technology, and computational processing of the images are expected to increase further the volume and quality of images derived from these technologies. In particular, cryo-electron tomography is expected to yield images of the orchestration of macromolecular complexes as they perform the molecular processes of life in the cell, thus bridging structural and cellular biology, and single-particle analysis has now reached a resolution at which the molecular structure of proteins can be solved. The goal of this project is to extend the EMDB deposition and retrieval system to deal with the increased quality and volume of image information. A novel aspect is the collaboration with the Open Microscopy Environment (OME), one of the major software tools for managing image databases in light microscopy. Combining the experience of EMDB in public scientific image databases with technologies in OME aimed at user-friendly web-based interfaces, in particular its visualization server and its metadata management, will not only maintain EMDB's technical and scientific excellence , but also serve as an example for future image databases that will arise from the rapidly developing bioimaging technology.