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Bristol-Myers Squibb Company announced today that it has awarded an unrestricted $500,000 infectious-disease research grant to the Whitehead Institute for Biomedical Research to expand studies of yeast genetics. Dr. Gerald R. Fink, director of the Whitehead Institute and American Cancer Society Professor of Genetics at MIT, is principal investigator on the five-year grant.
The grant will support research on yeasts, such as Candida, that cause human illness. Candida is responsible for common vaginal infections in women, as well as severe disease in persons with AIDS, chemotherapy patients, and others with suppressed immune systems.
The new work is based on the discovery that common bakers' yeast can change into a form similar to that found in important yeast pathogens. Dr. Fink and his colleagues were studying growth-control genes in yeast when they noticed a peculiar change in certain yeast cultures. The normally round, single-celled bakers' yeast strains began growing in long chains, or filaments, when they were starved for nitrogen. This ability to change shape, previously associated with pathogenic fungi, is called "dimorphism."
"It is the classic example of how basic research targeted at something unrelated to clinical applications ends up having practical implications in the study of human disease," Dr. Fink says.
The discovery that bakers' yeast is able to switch from the round to the invasive, filamentous form opens new avenues of research. For example, although scientists understand how many bacteria cause illness, the ability of fungi to cause disease remains a mystery. "No one knows what makes a pathogen out of these organisms. If we could figure out how they cause disease in humans, we could devise a way to prevent it from happening," Dr. Fink reasons.
He adds, "Current thinking is that changing cell shape may make fungi more invasive, invisible to the immune system, or both. Using genetics, we should be able to identify the genes responsible for the shape change in bakers' yeast and then apply the information to the pathogenic fungi. If we block the form change in the pathogenic organisms and they no longer cause disease, then we have a clear strategy for drug development."
Dr. Fink's search for the gene or genes that cause yeasts to change form extends to the plant world as well. The corn smut fungus behaves exactly the same way as the fungi that infect humans, shifting from the innocuous round yeast to invade corn with filaments that damage and then kill the plant. "These genes may offer interesting targets for herbicides," Dr. Fink said. With the new grant, Dr. Fink also plans to investigate whether some of the genes that provide fungi with their dimorphic growth habits are present in plants.
As one of this year's grant recipients, the Whitehead Institute joins eight other infectious-disease research institutions that are current recipients of no-strings-attached funding from Bristol-Myers Squibb Company. In addition to the Whitehead Institute, the institutions include: The University of Chicago; Dana-Farber Cancer Institute; Fox Chase Cancer Center; University of Lund, Sweden; Mount Sinai School of Medicine; Stanford University School of Medicine; University of Washington; and Washington University in St. Louis.
Bristol-Myers Squibb initiated its program of unrestricted grants for infectious-disease research in 1991. Since then, nine grants totalling $4.5 million have been awarded to leading infectious-disease research institutions. The principal investigator at each recipient institution participates in an independent committee that selects the winner of the annual $50,000 Bristol-Myers Squibb Award for Distinguished Achievement in Infectious-Disease Research.
The infectious-disease research grants program is part of a nearly $40-million program of unrestricted medical research grants Bristol-Myers Squibb has sponsored since 1977 in infectious disease, the neurosciences, cancer, nutrition, orthopedics, pain, and cardiovascular disease.
Bristol-Myers Squibb is a research-based, diversified health care company whose principal businesses are pharmaceuticals, consumer products, nutritionals, and medical devices.
A version of this article appeared in the April 7, 1993 issue of MIT Tech Talk (Volume 37, Number 28).