Function of hemolymph plasma proteins in insect immune responses

昆虫有一个先天免疫系统，可以防止病原体的感染， 寄生虫本项目的总体目标是研究昆虫血淋巴血浆中的蛋白质 参与昆虫免疫的不同方面。这个实验室以前的工作 建立了鳞翅目昆虫，天蛾，作为一个模型系统，非常适合 血淋巴蛋白质复杂功能的生化表征。我们计划 研究由血浆蛋白介导的免疫的三个方面。(1)我们将 表征血浆蛋白与革兰氏阴性和革兰氏阴性的肽聚糖的相互作用 触发丝氨酸蛋白酶激活，从而启动蛋白酶级联反应的阳性细菌 导致酚氧化酶和Toll途径的激活。(2)我们将研究如何 血淋巴的氧化还原环境在免疫应答过程中受到调节， 假设免疫蛋白质可以通过巯基修饰来调节。(3)哺乳动物有 用于剥夺入侵微生物的铁的充分表征的机制;然而， 昆虫中与免疫相关的铁抑制仍然知之甚少。我们将使用M。sexta作为 发现昆虫中保守的铁抑制机制的模型。根本 作为这项研究的结果获得的生物化学知识预计将更好地刺激 了解昆虫血淋巴中蛋白酶级联途径和分子的调节 这有助于免疫过程中的氧化调节，并导致了解铁 通过昆虫媒介影响人类疾病传播。这笔资金将用于 来自代表性不足群体的本科生，以获得研究经验， 通过参与项目进行培训。

Insects have an innate immune system that protects against infections by pathogens and parasites. The overall goal of this project is to investigate proteins in insect hemolymph plasma that participate in different aspects of insect immunity. Previous work from this laboratory has established the lepidopteran insect, Manduca sexta, as a model system well suited for biochemical characterization of the complex functions of hemolymph proteins. We plan to investigate three aspects of immunity that are mediated by plasma proteins. (1) We will characterize interactions of plasma proteins with peptidoglycan from Gram-negative and Gram- positive bacteria that trigger activation of a serine protease, thereby initiating protease cascades that result in activation of phenoloxidase and the Toll pathway. (2) We will investigate how the redox environment of hemolymph is regulated during an immune response and test a hypothesis that immune proteins may be regulated by thiol modifications. (3) Mammals have well-characterized mechanisms for depriving invading microorganisms of iron; however, immune-related iron-withholding in insects is still poorly understood. We will use M. sexta as a model for discovering conserved iron-withholding mechanisms in insects. The fundamental biochemical knowledge gained as a result of this research is expected to stimulate better understanding of regulation of protease cascade pathways and molecules in insect hemolymph that contribute to oxidative modulation during immunity, and lead to understanding of how iron influences human disease transmission by insect vectors. This supplement will fund an undergraduate student from an underrepresented group to gain research experience and training by participating in the project.