Dissecting the innate immune response mediated by Arabidopsis Nudix hydrolase

先天免疫系统是抵御多种病原体的第一道防线。 进化上保守的介于植物和动物之间的。免疫反应的微妙调节是 对生物体的健康和生长至关重要。正向和负向信号通路都相互作用于 制定一个具有适当幅度和持续时间的平衡防御反应。拟南芥--努迪克斯 水解核苷酸衍生物的水解酶(Mpr1)最近被认为是一种关键的介导物。 基础的先天免疫反应。Mpr1功能的丧失不仅导致高反应性 丁香假单胞菌的致病菌株，也包括非致病菌株。现建议MPr1可 通过感知和调节核苷酸衍生物的水平来微调防御反应，从而发挥其作用 并防止过度的细胞刺激。拟议的项目旨在定义Mpr1在 基础先天免疫，并通过使用组合来确定植物先天免疫中的其他参与者 分子、遗传、生化和功能基因组学工具。这项研究将提供新颖和 基础先天免疫中调节信号通路的分子机制的重要见解 通过实现以下具体目标。(1)Mpr1突变体和Mpr1蛋白将在 详细了解Mpr1调节防御反应的明确机制。(2) Mpr1突变将被用作了解其他基因在调节先天免疫中的作用的工具。 发信号。(3)将使用遗传、生化和分子方法来识别其他 在基础免疫反应中起作用的组件。此外，方法将朝着以下方向发展： 鉴定Mpr1的生理底物。 这项拟议的研究不仅将促进我们对植物先天免疫反应的理解，而且可能 也增加了我们对微妙控制免疫反应的机制的了解 人类需要保持良好的健康。阐明Mpr1在防御中的作用也将促进其 作为一种新工具，用于对具有持久和广谱病害的作物进行基因工程 抗药性将减少用于疾病控制的化学品的使用，这是一个巨大的环境和人类问题 健康问题。

The innate immune system provides the first line of defense against broad ranges of pathogens and is evolutionally conserved between plants and animals. Delicate regulation of the immune response is essential for an organism's health and growth. Both positive and negative signaling pathways interplay to develop a balanced defense response with appropriate amplitude and duration. An Arabidopsis Nudix hydrolase (MPR1) which hydrolyzes nucleotide derivatives has recently been identified as a key mediator of the basal innate immune response. Loss of MPR1 function causes hyper-responsiveness to not only pathogenic strains but also non-pathogenic strains of Pseudomonas syringae. It is proposed that MPR1 may exert its role by sensing and modulating the level of a nucleotide derivative to fine-tune the defense response and prevent excessive cell stimulation. The proposed project aims to define the precise function of MPR1 in basal innate immunity and to identify additional players in plant innate immunity by employing a combination of molecular, genetic, biochemical, and functional genomics tools. The study will provide novel and important insights into molecular mechanisms that regulate the signaling pathway in basal innate immunity by achieving the following specific aims. (1) The mpr1 mutant and MPR1 protein will be characterized in detail to understand the definitive mechanism by which MPR1 modulates the defense response. (2) The mpr1 mutant will be used as a tool to understand roles of other genes in regulating innate immunity signaling. (3) Genetic, biochemical, and molecular approaches will be employed to identify additional components functioning in the basal immune response. In addtion, methods will be developed towards identifying physiological substrates of MPR1. The proposed study will not only advance our understanding of plants' innate immune responses but may also increase our knowledge of the mechanisms involved in the delicate control of immune responses in humans necessary to maintain good health. Elucidating the role of MPR1 in defense will also promote its use as a new tool for the genetic engineering of crops that have durable and broad-spectrum disease resistance which would reduce the use of chemicals for disease control, a big environmental and human health concern.