September 9, 2005

Consortium’s ‘team science’ approach sets sights on diabetes

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From left, Mark Magnuson, M.D., Roland Stein, Ph.D., and Christopher Wright, D.Phil.
photo by Dana Johnson

Consortium’s ‘team science’ approach sets sights on diabetes

An international “team science” effort to accelerate progress toward a cell-based therapy for type 1 diabetes kicked off in Nashville recently.

The Beta Cell Biology Consortium (BCBC), formed in 2001, entered its second phase with an expanded roster and enhanced operations.

Vanderbilt is home to both the Coordinating Center for the BCBC and one of the cornerstone scientific program projects. Together, the two grants, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), will provide over $5 million in support for the next four years, said Mark A. Magnuson, M.D., Earl W. Sutherland Jr. Professor of Molecular Physiology & Biophysics and principal investigator of both efforts.

“The Consortium is a very successful example of a 'team science' approach,” Magnuson said. “A lot has been accomplished because of it. Investigators are now using the knowledge that's been gained to devise strategies that will speed the clinical transfer of this information.”

The BCBC includes the “crème de la crème” of investigators in the area of beta cell biology, Magnuson said. Pancreatic beta cells are the only cells in the body that secrete insulin. Destruction of these precious cells by a person's own immune system gives rise to type 1 diabetes.

Scientists in the BCBC have a wide range of expertise in areas including pancreas development, directed differentiation of stem cells, and beta cell regeneration.

Each group produced its own investigator-initiated proposal to carry out research projects for obtaining information necessary to develop novel cell-based therapies for type 1 diabetes, as a way to join the BCBC. The Consortium currently consists of 10 project-type grants, one of which supports the Coordinating Center.

The Coordinating Center for the BCBC facilitates activities of Consortium investigators spread throughout the world. “We're privileged to be able to play this role in this very important area,” said Magnuson, who has served as a leader in the BCBC since its founding. Magnuson built the Coordinating Center here with the assistance of Lisa Rouse, program manager, and Jean-Philippe Cartailler, Ph.D., science writer and Web site manager.

Fifty scientists and administrators gathered at the Vanderbilt Center for Better Health for the kickoff meeting. One goal of the meeting was to have “true information exchange” between participants and to begin the planning for novel group projects.

“I liken it to throwing fruit in a blender, turning it on, and seeing what you get,” Magnuson said. “It was a very intense meeting, and we made great progress.”

The kickoff meeting discussions explored three broad themes: pancreas development, how stem cells might be useful in generating new therapies for diabetes, and mechanisms of beta cell regeneration in adult animals. To encourage joint projects between Consortium investigators, the Coordinating Center is offering a new funding mechanism called “Collaborative Bridging Projects.”

“A really nice thing that happened at the kickoff meeting was the generation of whole new experimental strategies and whole new large-scale programs that bridge our various expertise areas, which we weren't even capable of thinking about before we met,” said Christopher V. E. Wright, D.Phil., professor of Cell & Developmental Biology and director of the Program in Developmental Biology.

“The BCBC in its first four years really generated a lot of excitement,” Wright said. “The whole endeavor is producing novel basic science insights on the way to the translational goals.”

Vanderbilt's scientific program is entering its 16th year of funding. When the BCBC got its start in 2001, the Vanderbilt group had the only existing program project grant focused on beta cells, Magnuson said.

Wright, Roland W. Stein, Ph.D., professor of Molecular Physiology & Biophysics, and Raymond J. MacDonald, Ph.D., of the University of Texas Southwestern Medical Center, join Magnuson in investigating mechanisms of pancreas development.

The investigators are all focusing on a short period during development when pancreatic islets — the structures that are home to the beta cells — begin to form and then rapidly expand.

They are exploring the roles of a variety of genes and other factors and are making use of specialized mouse models.

“Our program is famous in impact for what it's generated in terms of mouse models that are seeing worldwide use,” Magnuson said.

According to Wright, Vanderbilt's coordinating role in the BCBC offers the institution a “huge opportunity to cement our leadership with a move into stem cell biology. The new Center for Stem Cell Biology, under Mark's direction, and the Program in Developmental Biology will be natural partners as we move forward to develop this area fully.

“Directed tissue differentiation, as a way of generating new therapies for diabetes, is a tenable goal,” Wright said.

For more information about the BCBC, visit its Web site: