Genetic Analysis of the Drosophila Immune Response

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9604323 Anderson Technical The long-term goal of the project is to characterize the signaling pathways that are activated in Drosophila in response to infection by pathogens and to learn how the signaling pathways are coordinated between different tissues. In this proposal, a set of third chromosomal mutants that block specific aspects of the immune response will be characterized and one gene that affects multiple aspects of the immune response, ird1, will be characterized molecularly. 1. The ird1 gene will be cloned and its expression in hemocytes, fat body and other larval cell types assayed. Genetic mosaics will be constructed to determine whether ird1 affects multiple branches of the immune response because it coordinates these responses or whether it is required in each of the cell types. To determine what signals activate ird1 and how ird1 implements the immune response, genetic interactions of ird1 with other mutants response will be tested. 2. The genetic pathways that control specific branches of the immune response and coordinate the immune responses of different cell types will be defined. Complementation and mapping experiments will define the number and location of third chromosomal genes that control the immune response. The phenotypes of the novel genes affecting immune response will be characterized and compared with the phenotypes of previously-identified genes that may affect the immune response. Non-technical In all animals, the first rapid response to infection by pathogens is mediated by the innate immune response. Both the general strategies used in the innate immune response and a number of molecular mechanisms appear to be conserved between invertebrates and vertebrates. This is a proposal to initiate a systematic genetic study of the innate immune response in Drosophila. These experiments will identify genes required for the recognition of pathogen, for triggering the tissue-specific responses to pathogen and for coordinating the immune responses of diff erent tissues.