Functional Analyses of NPR1 in Plant Defense

描述（申请人提供）：克服感染是所有真核生物在无处不在的微生物中生存和进化所必须面对的斗争。研究宿主-微生物相互作用对医学、农业和许多其他人类事务的发展至关重要，包括对抗生物恐怖主义的威胁。该项目的长期目标是了解植物防御感染的分子机制。拟南芥NPR 1蛋白是多种防御途径的主要调节因子。它是水杨酸（SA）介导的系统获得性抗性（SAR）所必需的。NPR 1突变消除SA诱导的基因表达和SAR。在诱导时，NPR 1位于核内以激活基因表达。然而，这一关键调控步骤的机制尚不清楚。除了SAR，NPR 1还参与SA介导的茉莉酸诱导的防御途径的串扰抑制。了解NPR 1在SAR和JA信号传导中的双重作用对于理解这些途径之间的控制机制和相互作用至关重要。此外，NPR 1在每个反应中的靶基因的鉴定将导致对这些防御反应的分子基础的新见解。因此，本项目的两个具体目标是：（1）确定控制NPR 1活性的调节机制。通过这一特定目标，将确定细胞SA水平的升高如何导致核转位和NPR 1蛋白的活化。不同的化学修饰，如二硫键形成和蛋白磷酸化对NPR 1蛋白活性的影响将被检查。(2)阐明NPR 1在不同防御途径中的功能。这一具体目标将集中于了解NPR 1如何响应SA，发挥双重作用，作为SAR的正调节因子和JA介导的防御途径的负调节因子，以及NPR 1在这两种防御途径中调节哪些基因。深入了解植物免疫具有重要的理论和实践意义。比较植物和动物的免疫反应可能会发现宿主-微生物相互作用的共同机制。利用植物的天然免疫力来控制作物病害可能会导致农药的替代，其中许多农药会造成环境污染并对人类健康有害。

DESCRIPTION (provided by applicant): Overcoming infection is a struggle that all eukaryotic organisms have to face to survive and evolve among the ubiquitously present microorganisms. Studying host-microbe interactions is of fundamental importance to the development of medicine, agriculture and many other human affairs, including the fight against the threat of bio-terrorism. The long-term goal of this project is to understand the molecular mechanisms by which plants defend themselves against infection. The Arabidopsis NPR1 protein is a master regulator of multiple defense pathways. It is required for the salicylic acid (SA)-mediated systemic acquired resistance (SAR). Mutations in NPR1 abolish SA-induced gene expression and SAR. Upon induction, NPR1 is nuclear localized to activate gene expression. However, the mechanism of this key regulatory step is unknown. Besides SAR, NPR1 is also involved in SA-mediated cross-talk inhibition of a defense pathway induced by jasmonic acid. Understanding the dual role of NPR1 in SAR and JA-signaling will be essential for understanding the control mechanisms and interactions between these pathways. Moreover, identification of target genes of NPR1 in each response will lead to new insights into the molecular basis for these defense responses. Therefore, the two specific aims of this project are: (1) Determine the regulatory mechanisms that control NPR1 activity. Through this specific aim, it will be determined how elevation of cellular SA levels leads to nuclear translocation and activation of the NPR1 protein. The effects of different chemical modifications such as disulfide bond formation and protein phosphorylation on NPR1 protein activity will be examined. (2) Elucidate NPR1 functions in different defense pathways. This specific aim will focus on understanding how NPR1, in response to SA, plays a dual role as a positive regulator of SAR and a negative regulator of JA-mediated defense pathway and what genes NPR1 regulates in these two defense pathways. Better understanding of plant immunity will have both theoretical and practical significance. Comparing immune responses in plants and animals may lead to discovery of common mechanisms governing host-microbe interactions. Using plants' innate immunity to control crop disease may lead to replacement of pesticides, many of which cause pollution of the environment and are harmful to human health.