MOLECULAR MECHANISMS OF DROSOPHILA IMMUNE RESPONSE

描述(改编自申请者摘要)： 拟议的研究是使用分子和基因的组合 在模型系统中确定免疫基础的方法， 黑腹果蝇。最近的研究表明，昆虫和哺乳动物 使用类似的策略来对抗细菌感染。例如, 给果蝇幼虫注射细菌或脂多糖 诱导杀菌蛋白的出现。其中之一，血林， 属于免疫球蛋白超家族。它与细菌结合在一起 细胞表面，并被认为是随后的细胞反应的中介。 大部分剩余的昆虫杀菌蛋白可分为3类： 天蚕素、防御素和粘附素。这些蛋白质组结合 细菌细胞壁和细胞膜的不同成分及其影响 协同杀灭入侵细菌。脊椎动物防御素 是从中性粒细胞和巨噬细胞中分离出来的，而天蚕素 在猪肠中被发现。 最近的研究结果表明，果蝇的产生具有杀菌作用 多肽是由调节因子细胞Dif介导的，这与 属于核因子-kappaB/Rel蛋白家族。核因子-kappaB在 哺乳动物的免疫和炎症反应。希望能有一个 DIF和信号通路的详细特征将提供 对人类免疫和急性期反应的基本认识。这个 研究计划包括四个具体目标：(一)产生和 Dif突变体的特征；(Ii)分析 调控免疫基因表达的DIF和靶向启动子； (Iii)表征调控DIF活性的信号通路 对感染或伤害的反应；以及，(4)确定获得性 免疫是由Dif自身调节调节的。

DESCRIPTION (Adapted from Applicant's Abstract): The overall goal of the proposed research is to use a combination of molecular and genetic methods to determine the basis for immunity in a model system, Drosophila melanogaster. Recent studies suggest that insects and mammals employ similar strategies to battle bacterial infections. For example, injection of Drosophila larvae with bacteria or lipopolysaccharide induces the appearance of bactericidal proteins. One of these, hemolin, belongs to the immunoglobulin superfamily. It binds to the bacterial cell surface and is thought to mediate a subsequent cellular response. Most of the remaining insect bactericidal proteins fall within 3 groups: cecropins, defensins and attacins. These groups of proteins bind different components of the bacterial cell wall and membrane, and effect synergistic destruction of invading bacteria. Vertebrate defensins have been isolated from neutrophils and macrophages, while cecropins have been found in pig intestine. Recent results suggest that the production of the Drosophila bactericidal peptides is mediated by a regulatory factor cell Dif, which is related to the NF-kappaB/Rel family of proteins. NF-kappaB plays a key role in mammalian immunity and inflammatory response. It is hoped that a detailed characterization of Dif and the signaling pathways will provide basic insights into immunity and acute phase response in human. The research plan includes four specific aims: (i) generate and characterize Dif mutants; (ii) analyze regulatory interactions between Dif and target promoters controlling the expression of immunity genes; (iii) characterize the signaling pathway that regulates Dif activity in response to infection or injury; and, (iv) determine whether acquired immunity is mediated by Dif autoregulation.