MOLECULAR MECHANISMS OF DROSOPHILA IMMUNE RESPONSES

描述（来自申请的逐字描述）：拟议研究的目标 是利用分子遗传学方法来确定先天免疫的基础 在一个模式生物，黑腹果蝇。一旦感染，昆虫就会在 通过动员血细胞和产生一系列的免疫反应， 抗微生物肽吞噬并溶解入侵的微生物。这 昆虫的自卫过程类似于哺乳动物的先天免疫系统。 先天免疫系统首先识别传染源的共同特征， 如革兰氏阴性菌膜组分脂多糖（LPS）。 这导致了肝细胞、内皮细胞和 巨噬细胞产生保护性分子和细胞因子。这些响应 作为第一道防线，帮助刺激B和T淋巴细胞， 获得性免疫系统最近的研究表明， 哺乳动物的先天免疫具有共同的进化起源。特别是 果蝇调节因子Dif与哺乳动物NF-κ B相关。此外，委员会认为， 果蝇跨膜蛋白Toll是激活 Dif，而哺乳动物Toll样受体激活NF-κ B并介导LPS 刺激免疫反应。最近的研究结果还表明，果蝇MAP 激酶参与昆虫免疫。MAP激酶是 哺乳动物的炎症反应，进一步支持哺乳动物 和昆虫免疫利用许多同源分子。这项建议旨在 检验Toll信号传导、MAP激酶通路和 可能的新分子调节果蝇免疫的不同方面。的 成功的研究成果将提供重要的 对人类进化保守的免疫过程的深入了解。这 该方案包括三个具体目标：（1）分析Dif蛋白二聚体的形成机制 特异性调节免疫基因子集;（2）鉴定新的Dif靶点 基因和新的遗传成分在自我防御过程中;（3）研究 MAP激酶途径在昆虫免疫中的作用。

DESCRIPTION (verbatim from the application): The goal of the proposed research is to use molecular genetic methods to determine the basis for innate immunity in a model organism, Drosophila melanogaster. Upon infection, insects mount an immune response by mobilizing the blood cells and producing a spectrum of antimicrobial peptides to engulf and to lyse the invading microorganisms. This insect self-defense process is similar to the mammalian innate immune system. The innate immune system first recognizes common features of infectious agents, such as the Gram-negative bacteria membrane component lipopolysaccharide (LPS). This leads to signaling events in liver cells, endothelial cells, and macrophages to produce protective molecules and cytokines. These responses serve as the first line defense and help to stimulate B and T lymphocytes of the acquired immune system. Recent studies demonstrate that insect and mammalian innate immunity share a common evolutionary origin. In particular, a Drosophila regulatory factor, Dif, is related to mammalian NF-kappaB. Moreover, the Drosophila transmembrane protein Toll is essential for the activation of Dif, while the mammalian Toll-like receptors activate NF-kappaB and mediate LPS stimulated immune response. Recent results also suggest that Drosophila MAP kinases participate in insect immunity. MAP kinases are mediators of inflammatory response in mammals, further supporting the idea that mammalian and insect immunity employ many homologous molecules. This proposal aims at testing the hypothesis that the Toll signaling, the MAP kinase pathways, and possible novel molecules regulate different aspects of Drosophila immunity. The successful achievement of the proposed research should provide important insights into the evolutionarily conserved immune process in humans. This proposal includes three specific aims: (1) Analyze how Dif protein dimers specifically regulate a subset of immunity genes; (2) Identify novel Dif target genes and new genetic components in the self-defense process; (3) Study the roles of MAP kinase pathways in insect immunity.