Dissecting the innate immune response mediated by Arabidopsis Nudix hydrolase

描述(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，在进化上在植物和动物之间是保守的。对免疫反应的精细调节对生物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，形成具有适当幅度和持续时间的平衡防御反应。拟南芥核糖核酸水解酶(Mpr1)是一种降解核苷酸衍生物的酶，最近被认为是基础先天免疫反应的关键介体。Mpr1功能的丧失不仅会导致对致病菌株的高反应性，也会导致对非致病菌株的高反应性。有人认为，Mpr1可能通过感知和调节核苷酸衍生物的水平来发挥其作用，以微调防御反应，防止细胞过度刺激。这项拟议的项目旨在通过结合分子、遗传、生化和功能基因组学工具来确定Mpr1在基础天然免疫中的确切功能，并确定其他在植物天然免疫中的角色。这项研究将通过实现以下特定目的，为调节基础先天免疫中信号通路的分子机制提供新的和重要的见解。(1)将对Mpr1突变体和Mpr1蛋白进行详细的鉴定，以了解Mpr1调控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中的作用的工具。(3)将使用遗传、生化和分子方法来确定在基础免疫反应中起作用的其他成分。此外，还将开发鉴定Mpr1生理底物的方法。这项拟议的研究不仅将促进我们对植物先天免疫反应的了解，还可能增加我们对维持良好健康所必需的人类免疫反应精细控制机制的了解。阐明Mpr1在防御中的作用也将促进它作为一种新的工具，用于对具有持久和广谱抗病能力的作物进行基因工程，这将减少用于疾病控制的化学物质的使用，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.