High-Throughput Structural Biology

In the past, out of frustration with the rate at which information on structural biology was emerging, we focused on developing new tools to change the field by accelerating the rate of determination of protein structures. This endeavor included pioneering microliter expression/purification for structural studies, nanovolume crystallization, automated image collection, and robotics for collecting synchrotron beamline data. These technologies were initially tested by the team at the Joint Center for Structural Genomics (http://www.jcsg.org) in collaboration with I. Wilson, Department of Molecular Biology, where the power of the new tools was demonstrated. To advance the technologies toward more challenging protein complexes and membrane proteins, in collaboration with P. Kuhn, Department of Cell Biology, we have created 2 new technology-focused centers funded by the National Institutes of Health.

The first center is the Joint Center for Innovative Membrane Protein Technologies (http://jcimpt.scripps.edu). Here, in collaboration with K. Wüthrich, Q. Zhang, and G. Chang, Department of Molecular Biology; M.G. Finn, Department of Chemistry; and P. Kuhn and M. Yeager, Department of Cell Biology, we do research exclusively on membrane proteins, including G protein–coupled receptors. The second center is the Accelerated Technologies Center for Gene to 3D Structure (http://www.atcg3d.org). Here we are doing collaborative work with Dr. Kuhn and with researchers from deCODE biostructures, Bainbridge Island, Washington; Lyncean Technologies, Palo Alto, California; and the University of Chicago, Chicago, Illinois.