Scientific Report 2007

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. CIMBio now houses 20 research groups representing disciplines including chemistry, cell and molecular biology, electron microscopy, x-ray crystallography, advanced light microscopy, computational biology, and technology development. Floyd Romesberg, Philip Dawson, and Anette Schneemann have relocated their research groups here, occupying new laboratories on the second floor of the building and adding strengths in chemistry and structural biology.

Our faculty members have made a number of noteworthy scientific advances, a fact reflected in the number of papers published in top-ranking scientific journals. The following list highlights some of this groundbreaking science. In the journal Cell, Clare Waterman-Storer and her coworkers described fundamental dynamic molecular relationships that underlie rapid cell migration over substrates. Geoffrey Chang and members of his laboratory published an article in Science describing the high-resolution structure of a membrane protein transporter involved in multidrug resistance. Also in Science, Bridget Carragher, Clint Potter, Jack Johnson, and their colleagues reported the structure of an infectious phage, including visualization of the capsid; the tightly spooled, packaged DNA; and the tail machinery that senses when packaging is complete. In an article published in Nature, groups headed by Dr. Carragher, Dr. Potter, and William Balch described the underlying structure of the coat protein complex-II molecular cage that mediates intracellular transport. Also in Nature, Ron Milligan and colleagues described the mechanism of minus-end directed motion by a microtubule-bound kinesin. In Nature Medicine, Mari Manchester's group reported the use of a fluorescently labeled plant virus as a biosensor for vascular imaging. This novel method can be used to effectively image the complete embryonic vasculature and highlight the process of angiogenesis in developing tumors.

It was a banner year for Clare Waterman-Storer. She received a number of honors and awards, including the R.R. Bensley Award in Cell Biology from the American Association of Anatomists, the Director's Pioneer Award from the National Institutes of Health, and an Established Investigatorship from the American Heart Association.

During November 2005, 41 students from the United States, Canada, and Europe attended a 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. 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 research seminars attracted many attendees from the local scientific community. In all, 27 instructors and 18 assistants were involved in the course. Financial support for the course was provided by the National Center for Research Resources; the Agouron Institute; FEI Company; Gatan Inc.; Protochips Inc.; Tietz Video and Image Processing Systems; and Scripps Research.

The fourth in a series of training workshops on software for automated molecular microscopy was held in February 2006. Representatives from 5 institutions (Oxford; Purdue; Brandeis; University of California, San Diego; and State University of New York) attended and received intensive training on installation and use of software developed at the National Resource for Automated Molecular Microscopy.

In the coming year, Scripps Research will be the first research institution worldwide to receive a novel compact synchrotron light source. This Scripps campus synchrotron, to be housed in CIMBio, will significantly accelerate the pace of determining challenging protein structures (e.g., membrane proteins and large macromolecular complexes) and structure-based drug design by enabling real-time experimental evaluation with high-intensity, tunable x-rays. This research is part of the new technology developments of the Accelerated Technologies Center for Gene to 3D Structure (http://www.atcg3d.org) in the laboratories of Peter Kuhn and Raymond Stevens.

These activities and successes during the past year highlight the collaborative, interdisciplinary nature of the science being carried out at CIMBio. The enthusiasm of our faculty, staff, fellows, and students and their commitment to our collaborative mission are also evident at the standing-room-only biweekly forums—short seminars designed to promote interdisciplinary interactions.