The Center for Integrative Molecular Biosciences (CIMBio) is a new, interdisciplinary facility organized to bring together the talents of several TSRI groups in divergent disciplines such as chemistry, biochemistry, structural biology, and cell biology. The investigators' interests converge in one area—the structures of the tiny machines that buzz with activity inside cells. These include the transcription complexes that make messages from the genes, membrane channels and pumps that import and export materials, and the tiny molecular tracks and motors that move cells and form important structures like the mitotic spindle.
Members of CIMBio seek to speedily obtain and analyze these structures through the combined use of x-ray crystallography and electron microscopy (EM). Customized support rooms and large open laboratories contribute to an overall infrastructure that makes CIMBio one of the most advanced biological microscopy centers in the world.
The centerpiece of CIMBio and the focal point for the building's design is a microscopy suite containing six state-of-the-art electron microscope rooms. When combined with the x-ray structures of the component parts, 3-D EM maps can yield a detailed description of the structure and action of an entire cellular machine. CIMBio is devoted to determining both the structure of the proteins and nucleic acids in complexes that carry out the work of the cell and the dynamics of those cellular machines—their assembly, disassembly, and control over time.
Another development at the center is the automation of the EM technique, which, done manually, can take weeks or even months.
Two investigators in CIMBio's Automated Molecular Imaging group are creating algorithms for automated data collection and analysis, which should simplify the technique of electron microscopy and enable throughput to be increased dramatically. They have succeeded in developing software for both collection and analysis, and they aim to apply their techniques to projects that would otherwise not be possible due to the labor involved. To date, they have succeeded in constructing one of the best 3-D maps of the tobacco mosaic virus in less than two days using fully automatic techniques—work that would have taken months just a few years ago and weeks using conventional methods today.