In an effort to "glue" together large groups of scientists pursuing some of the biggest unsolved problems in biomedicine today, the National Institute of General Medical Sciences has provided $5 million for the first of five years to a consortium of basic scientists called the Alliance for Cellular Signaling (AFCS). NIGMS anticipates spending a projected total of $25 million on the project over the course of five years.
This innovative way to fund science grew out of NIGMS' consultations with leaders in the scientific community who said repeatedly that the thorniest biological problems require the expertise and input of large, multifaceted groups of scientists.
Glue grants aim to do just that. "The purpose of the glue grant is to help address problems that are beyond the reach of individual investigators," said Dr. Marvin Cassman, director of NIGMS. "The idea is to provide resources to a lot of people working together to collaboratively attack these problems."
Just what will the AFCS tackle? How cells talk.
The project will set out to study all aspects of cellular communications in two cell types: cardiomyocytes (heart muscle cells that can beat in a dish) and B-cells (immune cells that are accustomed to roving around the bloodstream carrying out duties for the body). According to Dr. Alfred G. Gilman, a pharmacologist at the University of Texas Southwestern Medical Center at Dallas and leader of the AFCS effort, a few characteristics helped him and his colleagues to narrow the search to finding an "ideal cell" to study. The team sought "interesting" cells that could also live in a plastic lab dish long enough for scientists to study their features in great detail.
After much internal debate, the AFCS team chose to study cardiomyocytes and B-cells from the mouse, a mammalian model system that Gilman says is "extremely relevant to human health problems."
A key goal of the effort is to map out in both cell varieties the vast number of signals that course through these cells, including--but not by any means limited to--those signals communicated through a class of specialized liaison molecules called G proteins. He and the late Dr. Martin Rodbell received the 1994 Nobel Prize in physiology or medicine for discovering G protein signaling.
According to Gilman, studying mouse cells makes perfect sense since many of the molecules that scientists know are central to communication inside and between cells are nearly identical between the cells of mice and people. Within the next year or so, the complete genetic sequence of the mouse will be spelled out, Gilman predicts, enabling AFCS scientists to inventory the entire collection of genes involved in making mouse cardiomyocytes and B-cells do what they do.
"We hope to create a piece of a virtual cell," said Gilman, adding that he anticipates drug developers will ultimately be able to test new compounds "in silico," meaning that they will have the ability to search for new drugs using a computer alone.
The AFCS project is a meaty effort because thousands of signaling molecules have been identified in cells, and assembling a catalog of all of the possible--and more importantly, authentic--interactions among them is a mind-boggling feat.
"Advances in genomics, proteomics, and informatics make the timing right for this bold experiment in how science is conducted," said Dr. Rochelle Long, a pharmacologist at NIGMS. "Al Gilman's vision is to transform the way cell signaling research is done, and he's dedicating his career from this point forward to making this work," she added.
The "Alliance," as the AFCS is also called, is a consortium of approximately 50 scientists working at 20 different academic institutions around the country. AFCS researchers will work in specially designed core laboratories located at several different academic centers, including the California Institute of Technology in Pasadena; the San Francisco Veterans Administration Medical Center; Stanford University; the University of California, San Diego; and of course UT Southwestern, where Gilman's group and key collaborators are located. The Alliance effort will also be partially funded with money from the pharmaceutical industry and several private donors.
In addition to the academic institutions involved, two biotechnology companies will participate directly in Alliance studies by providing custom-made materials such as antisense reagents (ISIS Pharmaceuticals of Carlsbad, Calif.) and a technology called two-hybrid analysis, a popular method scientists use to track encounters between proteins inside cells (Myriad Genetics, Inc. of Salt Lake City, Utah).
Central to maintaining close and regular contact among the AFCS scientists is keeping communication channels wide open, Gilman said. The communications "glue" for the consortium will be a sophisticated virtual conferencing system that can be operated using "Internet2," a new university-based version of the Internet. High-capacity computing power will be necessary to house and organize the AFCS database of scientific results; computers at the University of California, San Diego will be used for these purposes.
Science For All
Impressive as it is, the AFCS effort stands out in another important way. Alliance scientists working in the specially designed core laboratories have pledged to forgo two of the most coveted products of the biomedical science endeavor: intellectual property rights and first rights to publish in peer-reviewed journals, the respected anthology of scientific progress. Instead, all of the data produced in the core laboratories will be deposited immediately into the publicly accessible database.
Why would any right-minded scientist agree to such stipulations? Gilman is relying on the fact that many investigators will jump at the chance to participate in an interactive, collaborative science project they simply could not pull off in their own laboratories. And he would appear to be right, since to date, Gilman said, 250 scientists around the world have signed on as "Members," hosting topic-specific Web sites called "Molecule Pages" that will be important auxiliary components of the Alliance public database.
This database will be freely accessible to any scientist with a computer and Internet access. Effectively, according to Gilman, thousands of scientists will be either participating in, or benefiting from, the Alliance. Gilman created these strict rules to encourage the free exchange of ideas and to foster other researchers' efforts to translate research data into medically useful information. Once the data is posted publicly, any scientist whether part of the Alliance or not can pursue it via conventional strategies that may lead to publications and/or patents.
In addition to support from NIGMS, other funding for the AFCS project will be provided by several pharmaceutical companies and non-profit organizations, including Eli Lilly and Company, Johnson and Johnson, the Merck Genome Research Institute, Novartis Pharmaceuticals Corporation, Chiron Therapeutics, Aventis, and the Agouron Institute.
NIGMS has reannounced the glue grant funding opportunity and hopes to lend a helping hand to researchers trying to solve other major biological mysteries.
For comment on the glue grant program, call Alison Davis in the NIGMS Offfice of Communications and Public Liaison at (301) 496-7301 to arrange an interview with NIGMS director Dr. Marvin Cassman or Dr. Michael Rogers, director of NIGMS' Division of Pharmacology, Physiology, and Biological Chemistry.
For comment on the AFCS, call Phil Schoch in the UT Southwestern Office of News and Publications at (214) 648-3404 to arrange an interview with Dr. Alfred G. Gilman, or call Alison Davis to arrange an interview with Dr. Rochelle Long, a pharmacologist in NIGMS' Division of Pharmacology, Physiology, and Biological Chemistry.
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