Characterization of Hemolymph Melanization in Insects

了解动物和植物如何保护自己免受感染对基础生物学，农业和医学至关重要。 防御感染的核心是免疫系统。 在昆虫和其他节肢动物中，免疫系统的一个关键组成部分是称为酚氧化酶级联的途径，它由包括酚氧化酶在内的复杂蛋白质网络组成。 酚氧化酶反过来催化有毒免疫防御分子和一种称为黑色素的色素的形成。 许多研究表明，酚氧化酶级联反应在免疫防御中非常重要，但这一生化途径是如何调节的只有部分了解。 这个提议解决了这样一个问题：什么样的因素必须与酚氧化酶相互作用，以产生一种酶，这种酶可以将这种反应的起始底物转化为黑色素？ 为了解决这个问题，我们将进行一系列详细的生物化学研究，以确定与酚氧化酶相互作用的蛋白质，并进行功能研究，以确定产生功能性酶复合物所需的组分。 由酚氧化酶产生的分子对于除了免疫之外的许多生物过程是至关重要的。 这些包括植物的创伤反应，动物的色素沉着，以及帕金森病和黑色素癌等疾病的发病。 因此，这项研究的结果将提供重要的信息，而不仅仅是提高我们对免疫力的理解。 该研究也为促进科学培训和教育提供了一个理想的平台。 该项目将为免疫学和生物化学领域的博士后、研究生和本科生学员提供独立研究的机会。 这项研究的结果也将用于加强高中、本科和研究生阶段的课堂教学。

Understanding how animals and plants defend themselves from infection is critically important to basic biology, agriculture, and medicine. Central to defense against infection is the immune system. In insects and other arthropods, a key component of the immune system is a pathway called the phenoloxidase cascade, which consists of a complex network of proteins that includes the enzyme phenoloxidase. Phenoloxidase in turn catalyzes the formation of toxic immune defense molecules and a type of pigment called melanin. Many studies make clear that the phenoloxidase cascade is extremely important in immune defense but how this biochemical pathway is regulated is only partially understood. This proposal addresses the question of what factors must interact with phenoloxidase to produce an enzyme that can convert the starting substrate for this reaction into melanin? To address this question, we will conduct a series of detailed biochemical studies that will identify the proteins that interact with phenoloxidase, and functional studies that will identify the components required to produce a functional enzyme complex. The molecules produced by phenoloxidase are critical to many biological processes in addition to immunity. These include wounding responses in plants, pigmentation of animals, and the onset of diseases like Parkinson's and melanotic cancers. Results of this study will thus contribute information of importance that extends beyond enhancing our understanding of immunity. The proposed research also provides an ideal platform for promoting scientific training and education. The project will provide independent research opportunities for postdoctoral, graduate and undergraduate trainees in immunology and biochemistry. Results from the study will also be used to enhance classroom instruction at the high school, undergraduate, and graduate levels.