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Scientific Report 2004

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 events and achievements.

A total of 40 students from the United States, Europe, and Asia attended the 9-day Practical Course in Molecular Microscopy run by the National Resource for Automated Molecular Microscopy, our Biomedical Technology Resource Center sponsored by the National Center for Research Resources. Many of the leading scientists in the field participated in lectures, research seminars, and practical sessions that covered the theory and practice of electron microscopy and image analysis. The formal lectures and the research seminars attracted many attendees from the local scientific community. In all, 29 instructors and 20 assistants were involved during the course. The event was a resounding success and will be offered again in November 2005. Financial support for the course was provided by the National Center for Research Resources, Bethesda, Maryland; the Agouron Institute, Pasadena, California; FEI Company, Hillsboro, Oregon; Gatan Inc., Pleasanton, California; Tietz Video and Image Processing Systems, Gauting, Germany; and Scripps Research.

Gaudenz Danuser joined the CIMBio faculty to establish the Laboratory for Computational Cell Biology. Dr. Danuser’s interests are in analyzing the behavior of the cell’s complex molecular machinery. Members of his group develop computational tools for predictive modeling of dynamic cell processes at multiple scales, and they have already established an exciting collaboration with Clare Waterman-Storer and her group to develop software for automatic quantitative analysis of protein dynamics in time-lapse, epifluorescence light microscopy images.

Under the direction of Peter Kuhn, researchers participating in the collaboration between Scripps Research and the Institute for Advanced Biomedical Sciences at the Palo Alto Research Center made excellent scientific and technical progress during the past year. They developed new algorithms for glycan mass spectrometry analysis together with members of the Consortium for Functional Glycomics and for crystal identification together with members of the Joint Center for Structural Genomics. Proof-of-concept experiments were successfully completed on 2 emerging technologies: an enthalpy array with nanocalorimeters that will allow direct, in-parallel measurement of hundreds of molecular interactions in the proteome and a fiber array scanning technology cytometer for reliable, high-speed detection of rare cancer cells in blood (in collaboration with the Scripps Cancer Center).

Dr. Kuhn was also awarded a 5-year Biodefense Proteomics Research Program contract from the National Institute of Allergy and Infectious Diseases to carry out proteomics research on the coronavirus that causes severe acute respiratory syndrome. This award will support a comprehensive cataloging and molecular characterization of all viral related proteins and associated functions at the viral and host levels. This project involves colleagues at Scripps Research, Scripps Palo Alto Research Center; and the Burnham Institute, La Jolla, California.

This year CIMBio researchers, led by Marianne Manchester, were awarded a $10 million program project grant to study the interactions between anthrax toxin and its receptors and to develop novel multivalent nanoparticles to act as antitoxins. This program combines many disciplines, including structural biology, chemistry, molecular biology, in vivo analysis, and nanotechnology. The program partners laboratories at Scripps Research, including those of Dr. Manchester, J.E. Johnson, T. Lin, and M.G. Finn in CIMBio, those of A. Schneemann and V. Reddy in the Department of Molecular Biology, and those of John Young at the Salk Institute, La Jolla, California, and John Collier at Harvard Medical School, Boston, Massachusetts. Already this program has resulted in biochemical and structural characterization of the toxin-receptor interaction and in the development of monomeric and multivalent antitoxins that are effective in animal models.

These 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 with enthusiasm as additional world-class research groups occupy the new laboratories awaiting them.


Ronald A. Milligan, Ph.D.

CIMBio Web Site