Cell Signaling Alliance Gets Under Way

Alfred Gilman Completion of a draft of the human genome and advances in gene expression manipulation imply the potential capacity to predict altered behavior from factors such as pharmacological inputs. In an age where collaborations and joint ventures are typical, a Nobel laureate in biomedicine will lead a research alliance that ultimately should promote faster disease treatment via targeted drug remedies. Alfred Gilman, chairman of pharmacology at the University of Texas Southwestern at Dallas, will act as steering committee chair for a newly formed Alliance for Cellular Signaling (AFCS). The focus of the AFCS is to study the way cells communicate with each other to determine their functions and actions. Gilman received the 1994 Nobel Prize in physiology or medicine for his work with G proteins, which are a critical part of the "cellular switchboard." Multicellular organisms, such as mammals, have many different types of cells whose activities have to be coordinated so the organism can function efficiently. AFCS researchers will focus on two kinds of mouse cells: the cardiac myocyte, the primary contractile cell in the heart; and the B-lymphocyte, a major cell that synthesizes antibodies in the immune system. "Hypothesis-driven research is not the only way in science anymore," says Gilman, "Sequencing the genome is enabling us to think about bigger big questions in unbiased, non-hypothetically driven ways." The larger scale will be manifested in this project whereby 52 investigators at 21 institutions will collectively utilize their knowledge and expertise to determine how cells interpret signals in a context-dependent manner. According to program goals, proteins will be identified that constitute signaling systems, assessment of system information flow in normal and pathological states, and the derivation of theoretical models that describe a "virtual cell." This cell will be used to test new drugs, thus enabling optimization of drug placement for a specific patient and disease. The AFCS will study how sets of signaling inputs are interpreted and processed to alter cell function and how individual signaling modules function as part of the entire signaling function. Previous studies have looked at individual pathways in cells, but the interaction among the pathways and among the cells has not been researched as intensely. "The bigger problem is how all of these modules interact together," Gilman says. The collaboration effort is the result of a May 1999 National Institutes of General Medicine (NIGMS) Request for Applications (RFA) aimed at enabling solution of major biomedical issues and facilitating the next stage of integrative biomedicine. The purpose of the RFA was to make resources available for scientists to form research teams and to share information by posting new discoveries on the Internet. NIGMS has called the AFCS funding "glue grants." "Investigators' brains will be glued together via the Internet," says Gilman. "We need to harness the entire research community and to be catalysts. We can get a whole bunch of hits in experiments that screen for protein-protein interactions but someone needs to validate and determine the physiological significance. So one strategy is that we'll do the dirty work and do the screening for protein-protein interactions." Another novel feature is the fact that researchers will forgo any potential intellectual property rights. Contrary to being a potential deterrent to maximum project fruition, Gilman says, "Let's face it, most people don't ever profit from the basic discoveries. We'll put protocols, sequences, bioinformatics, reactions, and reagents in the public domain with no obligation to us. People will love us because the playing field will be level given that no one has a jump on the data. Information will be out immediately. This effort is functioning in the spirit of the Bayh-Dole Act [of 1980 that give grantees title to their federally funded inventions]," Gilman observes. "This will be like the [Human Genome Project]; their data were quickly available to all." Study results will be available on the Web at afcs.swmed.edu. Except for "bridging projects," small projects contributing highly specialized information, all research will be conducted in alliance-built labs. Three of the labs will be located at UT Southwestern; other institutions hosting the main laboratories for AFCS are the California Institute of Technology, San Francisco Veterans Affairs Medical Center, Stanford University, and the University of California, San Diego. In addition, more than 250 scientists worldwide have joined the alliance as members, hosting Web sites called "molecule pages" that will be important components of the alliance's public database. Gilman is looking for more experts to expand current membership. Members are selected based on expertise and specific molecules and pathways. With funding in place as of Sept. 1, the project is slated to run for 10 years at a cost of $10 million per year. "We thought we would be able to do what we needed with $10 million, but NIGMS was capped at $5 million. So we had to come up with other sources of funding and an experimental plan that would leverage the entire signaling research community." Private donors include Eli Lily and Co., Johnson & Johnson, Merck & Co., Genome Research Institute, Novartis, Chiron Corp., and, Aventis. Other funds are from the Agouron Institute and an anonymous Dallas philanthropist. "NIAID has given a supplemental award," he adds. Gilman said the remaining five years of the plan would be funded by further grants. Kate Devine can be contacted at kdevine@the-scientist.com.

Cell Signaling Alliance Gets Under Way

Interested in reading more?

Become a Member of