This award will provide supplementary support to enable Dr. Marc Lamphier of Harvard University to conduct collaborative research for 21 months with Dr. Tadatsugu Taniguchi of the Institute of Molecular and Cellular Biology, Osaka University, Japan. They will study the genetic regulations of the beta-interferon response. Interferons are cytokines which induce the expression of a number of genes involved in the defense against viral and bacterial infections, inhibitions of tumor growth, modulation of the immune response, and possibly in the regulation of normal growth and development. The human beta-interferon gene was cloned by Dr. Taniguchi in 1979, and initially overexpressed in E. coli in a collaboration between Taniguchi and the lab at Harvard with which Lamphier is now affiliated. Two mammalian DNA-binding proteins (IRF-1 and IRF-2) which recognize a common regulatory element in the human beta-interferon promotor have recently been identified and cloned. The present effort will investigate the mechanism by which these two factors coordinate gene regulation, and use the factors to try to identify part of the network of genes which moderate the cellular response to beta-interferon.
