US National Institute of General Medical Sciences awards "glue grant" to create virtual cells

Bethesda 05 September 2000In an effort to "glue" together large groups of scientists pursuing some of the greatest unsolved problems in biomedicine today, the National Institute of General Medical Sciences (NIGMS) has provided a $5 million grant for the first of five years to a consortium of approximately fifty basic scientists at more than twenty academic institutions around the world, called the Alliance for Cellular Signalling (AFCS). Over the course of 5 years, NIGMS anticipates spending a projected total of $25 million on this project that will investigate major topics like the communication between the heart muscle cells and immune system cells.


The project will set out to study all aspects of cellular communications in two cell types: cardiomyocytes or heart muscle cells which can beat in a dish and B-cells or immune cells which are accustomed to roving around the bloodstream carrying out duties for the body. According to Alfred G. Gilman, a pharmacologist at the University of Texas Southwestern Medical Center in 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 has searched for "interesting" cells which could live in a plastic lab dish long enough for scientists to study their features in great detail.

The San Diego Supercomputer Centre (SDSC) will deliver the bio-informatics infrastructure and information co-ordination environment for the novel scientific AFCS endeavour. The communications "glue" for the AFCS consortium will be a sophisticated virtual conferencing system that can be operated with Internet2, a newly established university-based version of the Internet. High-capacity computing power will be necessary to house and organise the database, which will host the scientific results.

"The amount of data generated by the Alliance will be tremendous and require immense computational resources", stated AFCS participant Shankar Subramaniam, SDSC fellow and professor in the Department of Bio-engineering and the Department of Chemistry and Biochemistry at the University of California San Diego. "The SDSC facilities will serve as a gateway for worldwide researchers to access and analyse AFCS data, as we conduct data mining and other bio-informatics tasks, including database organisation and maintenance."

Shankar Subramaniam is serving as director for two AFCS core laboratories: the Bio-informatics Laboratory and the Information Dissemination and Data Co-ordination Laboratory. "The major purpose of these two laboratories will be acquisition, management, storage, analysis, and distribution of all the information relevant to the Alliance activities", Dr. Subramaniam said. "We will use a high-speed network of UNIX workstations at SDSC as database servers, and the backup will be completed with our mass-storage system. Each of the Alliance laboratories will house local computer facilities linked to the central repository at SDSC."

After much internal debate, the AFCS team chose to study cardiomyocytes and B-cells from the mouse, a mammalian model system that Dr. Gilman believes is "extremely relevant to human health problems". A key goal of the effort is to map out in both cell varieties the enormous number of signals which course through these cells, including but not limited to those signals communicated through a class of specialised liaison molecules called G proteins. Dr. Gilman and the late Martin Rodbell received the 1994 Nobel Prize in physiology or medicine for discovering G protein signalling.

According to Dr. Gilman, studying mouse cells makes perfect sense because many of the molecules, known by scientists to be central to communication inside and between cells, are nearly identical between the cells of mice and people. Within the next year, the complete genetic sequence of the mouse will be spelled out, as Dr. Gilman predicts, which will enable AFCS scientists to inventory the entire collection of genes involved in the typical activities of mouse cardiomyocytes and B-cells. "It is our hope to create a piece of a virtual cell", explained Dr. Gilman, who anticipates drug developers will ultimately be able to test new compounds "in silico", which means that they will have the opportunity to search for new drugs with the single use of a computer.

The AFCS project is a giant effort because thousands of signalling molecules have been identified in cells, and assembling a catalogue of all of the possible and authentic interactions among them constitutes a really exceptional feat. Rochelle Long, a pharmacologist at NIGMS, said that advances in genomics, proteomics, and informatics make the timing right for this bold experiment in how science is conducted. Additional academic institutions participating in the Alliance include the University of Texas Southwestern Medical Center in Dallas serving as the AFCS lead site; the California Institute of Technology in Pasadena; the San Francisco Veterans Administration Medical Center; and Stanford University.

Two biotechnology companies will participate directly in Alliance studies by providing custom-made materials. Antisense reagents will be delivered by ISIS Pharmaceuticals of Carlsbad, California. Myriad Genetics Inc. of Salt Lake City, Utah, in turn will provide a technology called two-hybrid analysis, a popular method used by scientists to track encounters between proteins inside cells. In addition to support from NIGMS, the Alliance effort will also be partially funded with money from several private donors, not-for-profit organisations, as well as the pharmaceutical industry, including Eli Lilly and Company, Johnson and Johnson, the Merck Genome Research Institute, Novartis Pharmaceuticals Corporation, Chiron Therapeutics, Aventis, and the Agouron Institute.

This innovative way to fund science grew out of NIGMS's consultations with leaders in the scientific community who stated repeatedly that the thorniest biological problems require the expertise and input of large, multi-faceted groups of scientists. Glue grants respond exactly to this aim. The AFCS effort also 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 endeavour: intellectual property rights and first rights to publish in peer-reviewed journals, as the respected anthology of scientific progress. Instead, all of the data produced in the core laboratories will be deposited immediately into the AFCS database for public access.

Dr. Gilman is convinced 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. At present, 250 scientists around the world have signed on as "Members", hosting topic-specific Web sites called "Molecule Pages" which 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 Dr. Gilman, thousands of scientists will be either participating in, or benefiting from, the Alliance.

Dr. Gilman created these strict rules to encourage the free exchange of ideas and to foster the 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 or patents. Additional information about the project can be found at the AFCS home page. If you want more details on the glue grant programme, please visit the pages of the National Institute of General Medical Sciences.

Leslie Versweyveld

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