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TSRI Scientific Report 2003

Center for Integrative Molecular Biosciences

Milligan/Other Ronald A. Milligan, Ph.D.

The Center for Integrative Molecular Biosciences (CIMBio) was created in 2002 to foster collaborative research to elucidate the high-resolution structures, mechanisms of action, and in vivo dynamic behaviors of the cell's molecular machines. CIMBio's second year was notable for a number of achievements and events. First, cutting-edge technologic developments for automating structure determination via electron microscopy were put on a strong footing with the award of a 5-year grant from the National Institutes of Health to establish the National Resource for Automated Molecular Microscopy under the directorship of Bridget Carragher and Clint Potter. In addition, Mari Manchester led a successful effort with M.G. Finn and Jack Johnson to obtain funding from the biomolecular sensors program of the National Cancer Institute to support high-risk, innovative research on the development of biosensors. Collaborative, interdisciplinary activities such as those supported by these recent awards are the lifeblood of CIMBio.

The end of 2002 saw completion of phase 2 construction, and 6 additional research groups relocated to the new, custom-built laboratories at the beginning of 2003. From the nucleus of investigators interested in using electron microscopic determination of structure to understand biological mechanisms at moderate resolution, the range of expertise at CIMBio has now expanded toward both the atomic level, with the addition of Geoff Chang (membrane protein crystallography), and the cellular level, with the groups of Velia Fowler, Clare Waterman-Storer, Kevin Sullivan, and Klaus Hahn (development and applications of multimode light microscopy). An important addition was the Carbohydrate Synthesis and Protein Expression Core, directed by Ola Blixt with James Paulson as principal investigator, of the Consortium for Functional Glycomics funded by the National Institutes of Health.

Peter Kuhn joined the CIMBio faculty to develop the functional proteomics program at TSRI in collaboration with the Palo Alto Research Center Institute for Advanced Biomedical Sciences. The researchers in his laboratory are uniquely positioned to explore novel proteomics technologies and to transform them into practical production systems for use in drug discovery and translational medicine. Dr. Kuhn comes from Stanford University, where he directed the structural genomics and macromolecular crystallography programs at Stanford's synchrotron laboratory.

In March 2003, 75 participants from 8 Institutions across the United States with common interests in virus-based nanotechnology convened for 3 days at CIMBio for the 6th Annual MontDiego Meeting. More than 25 presentations highlighted research ranging from the use of plant viruses as molecular circuit boards in the molecular electronics program of the Defense Advanced Research Projects Agency to virus-based drug delivery supported by the National Cancer Institute.

In April, 35 participants from local academic institutions attended a 2-day workshop on image analysis in light microscopy. The meeting was supported by the National Eye Institute Core Grant for Vision Research. Topics covered both basic software scripting and advanced image analysis algorithms, with particular emphasis on multidimensional live-cell imaging and quantitation.

The National Resource for Automated Molecular Microscopy sponsored 2 workshops. The Electron Microscopy and X-ray Crystallography Fitting and Modeling Workshop was organized jointly with the Resource for Multiscale Modeling Tools in Structural Biology, led by Charles Brooks, and attracted more than 40 participants. In April, the 2-day Multidisciplinary Workshop on Automatic Particle Selection for Cryo-Electron Microscopy had 47 participants from Europe, Australia, Japan, and the United States.

The enthusiasm of our faculty, staff, fellows, and students and their commitment to our collaborative mission are evident at the standing-room-only weekly forums. These short seminars are designed to promote communication between researchers involved in technology development and biological applications at CIMBio. The vitality of the center will only increase in the coming year, as additional world-class research groups occupy the new laboratories.



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