News Release

Massive new research effort will map inner workings of cells - San Francisco VA Medical Center chosen to host core laboratory

Grant and Award Announcement

University of California - San Francisco

A new $50 million dollar research program launched this month will begin the daunting task of mapping out the thousands of molecular interactions that cells use in responding to their environment. The San Francisco Veterans Affairs Medical Center will host one of the five core research labs that will collaborate on this project.

The Alliance For Cellular Signaling marks the first coordinated effort to describe the hundreds of pathways used by cells to convert a message from outside the cell into an appropriate response. This knowledge is essential to more efficient discovery of new drug treatments, said Paul Simpson, MD, co-director of the San Francisco core lab, staff cardiologist at the San Francisco VA Medical Center, and UC San Francisco professor of medicine. "Usually, (in cell signaling) researchers have only one or a few receptors or signaling molecules that they're interested in. This is going to look at the whole picture," he said. "It's like the human genome project of cell signaling," he said.

Last week, the National Institute for General Medical Sciences (NIGMS) announced their decision to fund the project, and anticipates spending $25 million dollars over five years for the Alliance. An equal sum will be contributed by biotechnology and pharmaceutical companies, said Simpson. At the SF VAMC, the Alliance funds will be administered by the Northern California Institute for Research and Education (NCIRE).

The payoffs for the project should be well worth the huge commitments of money and research time, Simpson said. "It should have tremendous therapeutic implications. At the moment drug development is often a hit-or-miss proposition, but if we understand how signaling works, we can design drugs that will block harmful processes; we can turn a specific switch on or off to get a specific result," he said.

The NIGMS grant will help to establish and fund core laboratories at five institutions: University of Texas Southwestern Medical Center in Dallas (the headquarters campus); San Francisco VA Medical Center; University of California, San Diego; Stanford University; and the California Institute of Technology.

The Alliance's collaborative approach is an experiment in itself, said Bill Seaman, MD, and co-director of the San Francisco core lab. "It's an attempt to change the way we do research. By pulling together different groups with different types of expertise, we can accomplish things that would be impossible for even a very large single lab," said Seaman, chief of immunology at the San Francisco VA Medical Center and UCSF professor of medicine and microbiology. And unlike most research projects, scientists in the Alliance will publish their data on the Internet immediately after it has been analyzed, instead of waiting to publish peer-reviewed papers. Alliance researchers have also agreed to give up intellectual property rights to the data. According to Al Gilman, director of the Alliance and a pharmacologist at University of Texas Southwestern, any researcher who has a computer and Internet access will be able to access the data freely, and combine it with their own research to pursue new medical treatments more intelligently.

The Alliance has assigned two key roles to the San Francisco VAMC core lab, called the Laboratory for Development of Signaling Assays. The researchers will help to develop the experiments and methods that that other labs will use to explore the cell signaling pathways, and they will try to confirm the results of successful experiments performed in the Dallas core.

The Alliance will focus the project on two types of mouse cells: heart muscle cells, and antibody-producing cells of the immune system known as B lymphocytes, said Seaman. The interactions among signaling proteins in mice are often almost identical to those in humans.

Researchers in the Alliance first will attempt to understand signaling in normal cells, Simpson said. They will culture the cells and stimulate them with various molecules that are known to activate cells. They will then observe which among the thousands of signaling molecules are turned on or off over time, and how these molecules interact. They will compare these to more general responses of the cells, such as the beating of heart muscle cells, and migration of B lymphocytes towards a chemical signal. Researchers will then attempt to shut off, or knockout, certain key signaling genes, and observe the effect on signaling patterns, and on the cellular responses.

The first major challenge for the VAMC lab, said Simpson, will be to figure out how to make newly harvested cells grow in a culture dish. Heart muscle cells are especially problematic, he said, since it is difficult to keep them alive and healthy in culture for longer than 24 hours. "We need to learn how to make these cells happy long enough so that we can study their cell signaling properties," he said.

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According to Gilman, $25 million in funding for the Alliance will be provided by several major pharmaceutical companies, including Eli Lilly and Company, Johnson & Johnson, the Merck Genome Research Institute, Novartis Pharmaceuticals, Chiron Corporation, Aventis Pharma, and the Agouron Research Institute.

Two biotechnology companies are also participating in the Alliance as scientific partners. Isis Pharmaceuticals of Carlsbad, Calif., and Myriad Genetics, of Salt Lake City, will contribute custom-made reagents and relevant expertise.

NCIRE, which will administer Alliance funds at the SF VAMC, is one of the fastest growing medical research groups in the nation. Founded in 1988, NCIRE now manages more than $20 million in funding from organizations such as the National Institutes of Health, the National Aeronautics and Space Administration, and the National Science Foundation. Based at the San Francisco VA Medical Center, NCIRE is the largest of the congressionally authorized VA research corporations.



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