Dissecting the innate immune response mediated by Arabidopsis Nudix hydrolase

先天免疫系统提供了针对广泛病原体的第一道防线， 在植物和动物之间进化保守。免疫反应的精细调节 对有机体的健康和生长至关重要。积极和消极的信号通路相互作用， 发展一种平衡的防御反应，具有适当的幅度和持续时间。拟南芥营养系 水解核苷酸衍生物的水解酶（MPR1）最近已被鉴定为 基础先天免疫反应MPR1功能的丧失不仅会导致高反应性 病原性菌株以及非病原性菌株。建议MPR1可以 通过检测和调节核苷酸衍生物的水平来微调防御反应， 防止细胞过度刺激。建议的项目旨在界定MPR1的确切功能， 基础的先天免疫，并通过采用组合来鉴定植物先天免疫中的其他参与者， 分子、遗传、生物化学和功能基因组学工具。这项研究将提供新的和 对调节基础先天免疫信号通路的分子机制的重要见解 实现以下具体目标。(1)mpr1突变体和MPR1蛋白的特征在于： 详细了解MPR1调节防御反应的确切机制。(2)的 mpr1突变体将被用作了解其他基因在调节先天免疫中的作用的工具 信号(3)将采用遗传、生物化学和分子方法来鉴定其他的 在基础免疫反应中起作用的成分。此外，还将制定方法， 鉴定MPR1的生理底物。 这项拟议中的研究不仅将促进我们对植物先天免疫反应的理解， 也增加了我们对免疫反应微妙控制机制的了解， 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 作为一种新的工具，用于具有持久和广谱疾病的作物的基因工程 耐药性，这将减少使用化学品控制疾病，一个大的环境和人类 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.