December 17, 2004

VUMC, Oak Ridge research projects take flight

Featured Image

Staff move a young patient across the 400-foot-long connector between the old Children's Hospital and the new Monroe Carell Jr. Children’s Hospital at Vanderbilt. Faculty, staff and many volunteers helped move 112 patients and equipment to the new building in early February.
photo by Dana Johnson

VUMC, Oak Ridge research projects take flight

Vanderbilt University researchers, primarily in the physical sciences, have had a long history of collaboration with Oak Ridge National Laboratory (ORNL). Recently, Vanderbilt University Medical Center researchers have also begun working with ORNL to answer some of the most pressing questions in medicine.

Located in Oak Ridge, Tennessee, ORNL is the Department of Energy's largest science and energy laboratory. The laboratory's budget, which exceeded one billion dollars in fiscal year 2003, is managed by a partnership between the University of Tennessee and Battelle, LLC, an Ohio-based non-profit management organization.

As a national laboratory, ORNL has a staff of world-class scientists and state-of-the-art research facilities accessible to scientists from industry, government agencies and academic centers. Recently, a number of VUMC researchers have found that their research questions are well matched with the unique resources and expertise of ORNL.

“VUMC is ideally positioned to become the major biological partner of ORNL,” said Jeffrey R. Balser, M.D., Ph.D., associate vice chancellor for Research. “We view this as one of our most important strategic initiatives in the research enterprise.”

Science at the nano-scale

In September, a multi-institutional, multi-disciplinary alliance between Vanderbilt and ORNL was established by a planning grant from the National Institutes of Health. The Vanderbilt Alliance for Nanomedicine, co-directed by James E. Crowe, Jr., M.D., professor of Pediatrics and assistant professor of Microbiology and Immunology, and David W. Wright, Ph.D., assistant professor of Chemistry, will use nanotechnologies to explore the molecular and cellular basis of immunity.

The alliance researchers will use nano-tools — devices so small that they are not visible even with a traditional microscope — to study the various phases of the body's immune response to viruses like respiratory syncytial virus, the leading cause of pneumonia and wheezing in children, and HIV.

“In the short term, the Alliance will develop tools to measure immune and cell responses of single cells, and these technologies can likely be developed as miniature devices that can be used as point-of-care diagnostic devices,” Crowe said.

Molecular snapshots

To be completed in 2006, the Spallation Neutron Source (SNS) at ORNL will provide the most intense pulsed neutron beams in the world for scientific research. The SNS will be one of only a few sites to permit the work Walter J. Chazin, Ph.D and his structural biology colleagues have in mind.

Chazin, Chancellor's Professor of Biochemistry and Physics, and director of the Center for Structural Biology, will use the technique of neutron scattering to obtain dynamic pictures of the interactions between biological molecules (proteins, DNA, RNA) and how their shapes and sizes change when their surrounding conditions change.

Also, the SNS enables the use of a technique called neutron diffraction crystallography, which Chazin and colleagues will use to determine atomic-resolution three-dimensional structures of these molecules. Having such detailed molecular structures and interactions could aid in the development of new drugs.

“Vanderbilt currently has no instrumentation to obtain this kind of information on the complex systems we study using other structural techniques,” Chazin said. “The knowledge obtained is an ideal complement to the three-dimensional structures we determine by traditional X-ray crystallographic or NMR techniques.”

Big computers for big data

ORNL will soon be home to the world's fastest civilian supercomputer. When completed, the supercomputing facility will be a major aid for the complex kinds of problems that cannot be addressed by the computing resources at Vanderbilt.

“Basically, we need high performance computing to tackle problems where the calculations take too long on an everyday computer,” said William Stead, M.D., associate vice chancellor for health affairs.

Vanderbilt currently performs complex computing tasks by breaking data into sets and analyzing the separate sets in parallel by multiple small computers — a system known as parallel computing, the technique employed by the newly formed, trans-institutional Advanced Computing Center for Research and Education (ACCRE).

“Other problems have to be tackled by a machine architecture where individual components are faster than ones that are affordable to our research community. It is this latter type of problem that will be targeted to the ORNL resource,” Stead said.

“We hope ORNL will bring us computation expertise, and we hope to bring them new classes of important problems.”

One type of problem that may be amenable to the leadership class computing resources of ORNL is the complex imaging analysis called spectral deconvolution microscopy being done by David Piston, Ph.D., professor of Molecular Physiology and Biophysics and director of the W. M. Keck Free-Electron Laser Center.

Spectral deconvolution imaging allows Piston to use multiple colored labels in live cells to follow the course of the expression patterns of numerous different proteins in real time. However, the massive amounts of data can get too cumbersome for the parallel computing resources at Vanderbilt.

“It would take us weeks to process that on our computers. That may be something that we could submit (to ORNL) and we would get data back overnight,” Piston said. “That could really keep science moving.”

Collaborating for dollars

Researchers from the two institutions are also teaming up to compete for major center grants from the National Institutes of Health.

Heidi Hamm, Ph.D., chair of Pharmacology, and colleagues are submitting a proposal for a Center of Systems Biology to study the cellular signaling pathways underlying chemotaxis, the movement of cells in response to a chemical gradient. This process is key to immune system function, as well as the proper localization of cells during development.

“ORNL's expertise in bioinformatics, visualization of data and systems biology will be key to the success of the proposal,” Hamm said. “We are excited to work together, leveraging the expertise of both groups to create an exciting environment in Systems Biology.”

Another group led by Susan Wente, Ph.D., chair of Cell and Developmental Biology, and Richard Caprioli, Ph.D., Stanley Cohen Professor of Biochemistry, is drafting a proposal for a National Technology Center for Networks and Pathways to study the dynamics of RNA-protein complexes. This includes both understanding the life of RNA from the moment it is transcribed from DNA to its translation into protein, as well as the fate of viral RNA in cells.

Vanderbilt joins core universities

In addition to these traditional research collaborations, Vanderbilt University recently became part of ORNL's “core universities,” a group of seven universities that will “help shape the research agenda” at the laboratory.

Core university membership will allow for joint faculty appointments between Vanderbilt and ORNL. This enables university faculty to conduct research at the laboratory for extended periods, with the costs shared by the two institutions.

“Core university membership is not making the (ORNL resources) available to Vanderbilt faculty. There is no exclusivity about lab use conferred by (membership),” said Dennis Hall, Ph.D., associate provost for research. “(It) is really about participating in the process that determines the long-term directions at ORNL.”