Genetic Analysis of the Drosophila Immune Response

该项目的长期目标是表征果蝇在应对病原体感染时激活的信号通路，并了解信号通路如何在不同组织之间协调。在这一提议中，一组第三染色体突变，阻断免疫反应的特定方面将被表征，一个影响免疫反应的多个方面的基因，ird1，将被分子表征。1. ird1基因将被克隆，并在血细胞、脂肪体和其他幼虫细胞类型中检测其表达。基因嵌合体将被构建，以确定ird1是否影响免疫反应的多个分支，因为它协调这些反应，或者是否在每种细胞类型中都需要它。为了确定哪些信号激活ird1以及ird1如何实现免疫应答，将测试ird1与其他突变体应答的遗传相互作用。2. 控制免疫反应的特定分支和协调不同细胞类型的免疫反应的遗传途径将被定义。互补和定位实验将确定控制免疫反应的第三染色体基因的数量和位置。影响免疫反应的新基因的表型将被表征，并与先前鉴定的可能影响免疫反应的基因的表型进行比较。在所有动物中，对病原体感染的第一个快速反应是由先天免疫反应介导的。在先天免疫反应中使用的一般策略和一些分子机制似乎在无脊椎动物和脊椎动物之间是保守的。这是一个建议，以启动先天性免疫反应在果蝇的系统遗传研究。这些实验将确定识别病原体、触发对病原体的组织特异性反应和协调不同组织免疫反应所需的基因。

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.