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Scientific Report 2005

Center for Integrative Molecular Biosciences

The Center for Integrative Molecular Biosciences (CIMBio) was created in 2002 to foster collaborative research dedicated to elucidating the high-resolution structures, mechanisms of action, and in vivo dynamic behaviors of the cell’s molecular machines. The past year was notable for a number of achievements and events.

Scientific highlights include an article in Science by researchers in the laboratories of Gaudenz Danuser and Clare Waterman-Storer on the discovery of 2 molecularly and functionally distinct actin populations that colocalize at the protruding edge of migrating cells. The data indicate that the mechanism of cell protrusion, which had been associated essentially with the growth of a densely branched, homogeneous actin network, is mediated by a more complex bipartite actin system. How the cell regulates and exploits the specific attributes of these 2 populations in the same location to accomplish efficient protrusion is currently under investigation.

M.G. Finn and coworkers discovered a remarkable application of click chemistry in the area of solid-phase peptide synthesis. Installation of the best reactive groups for click connections at either end of a synthetic peptide chain results in the selective formation of a cyclic peptide incorporating 2 chains instead of 1 chain. Large structures are selectively produced in this way, and these molecules may have important applications in enzyme inhibition and the disruption of protein-protein interactions.

CIMBio researchers Qinghai Zhang, M.G. Finn, Geoffrey Chang, and Peter Kuhn play a major role in the Joint Center for Innovative Membrane Protein Technologies (http://jcimpt.scripps.edu) led by Ray Stevens. The goals of the members of the newly funded center, which is part of the National Institutes of Health Roadmap Initiative, are to develop and disseminate methods and technologies for production of structure-grade membrane proteins.

Peter Kuhn and Ray Stevens are co–principal investigators in the Accelerated Technologies Center for Gene to 3D Structure (http://www.atcg3d.org) funded by the National Institute of General Medical Sciences. The focus of the center is the development of novel technologies in miniaturization, integration, and automation that can lower the cost of moving from genes to structures for all researchers. The primary target area is oncology, with particular emphasis on more challenging subjects such as DNA-bound transcription factors, membrane proteins, and containing protein kinases.

Two 4-day workshops were held by the National Resource for Automated Molecular Microscopy, our Biomedical Technology Resource Center sponsored by the National Center for Research Resources and run by Bridget Carragher and Clint Potter (http://nramm.scripps.edu). Representatives from 10 institutions received intensive training on the installation and use of software for automated microscopy developed by personnel at our center. This software has now been licensed to a total of 19 electron microscopy groups worldwide.

These activities and successes illustrate the collaborative, interdisciplinary activities that are the lifeblood of CIMBio. The enthusiasm and commitment of our faculty, staff, fellows, and students to our collaborative mission are also 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. We look forward to the coming year when 3 additional groups of scientists will occupy state-of-the art laboratories in our building.


Ronald A. Milligan, Ph.D.

CIMBio Web Site