Dissecting the innate immune response mediated by Arabidopsis Nudix hydrolase

描述（由申请人提供）：先天免疫系统提供了抵御广泛病原体的第一道防线，并且在植物和动物之间进化保守。免疫反应的精细调节对于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，以发展一个平衡的防御反应与适当的幅度和持续时间。水解核苷酸衍生物的拟南芥核酸水解酶（MPR1）最近被鉴定为基础先天免疫应答的关键介质。MPR1功能的丧失不仅导致对致病性菌株的高反应性，还导致对非致病性菌株的高反应性。有人提出，MPR1可能发挥其作用，通过传感和调节核苷酸衍生物的水平，以微调防御反应，防止过度的细胞刺激。该项目旨在确定MPR1在基础先天免疫中的确切功能，并通过采用分子，遗传，生物化学和功能基因组学工具的组合来确定植物先天免疫中的其他参与者。该研究将通过实现以下特定目标，为调节基础先天免疫信号通路的分子机制提供新的重要见解。(1)将详细描述mpr1突变体和MPR1蛋白的特征，以了解MPR1调节防御反应的确切机制。(2)mpr1突变体将被用作了解其他基因在调节先天免疫信号传导中的作用的工具。(3)将采用遗传、生物化学和分子方法来鉴定在基础免疫应答中起作用的其他组分。此外，将开发方法，以确定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，还可能增加我们对维持健康所需的人类免疫反应微妙控制机制的了解。阐明MPR1在防御中的作用也将促进其作为具有持久和广谱抗病性的作物基因工程的新工具的使用，这将减少用于疾病控制的化学品的使用，这是一个重大的环境和人类健康问题。

DESCRIPTION (provided by applicant): 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 addition, 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.