Signaling mechanisms in plant innate immunity

植物先天免疫的信号机制

基本信息

批准号：
8077380
负责人：
JEN SHEEN
金额：
$ 36.6万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-12 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8077380
关键词：
Agriculture Amino Acids Animals Arabidopsis Autoimmune Diseases BAK1 gene Binding Biochemical Biological Assay Biological Models Case Study Cells Communicable Diseases Complex Defect Detection Environment Evolution Flagellin Future Gene Targeting Genes Genetic Genome Genomics Goals Health Human Immune Immune response Immune system Inflammatory Internet Leucine-Rich Repeat MAP Kinase Gene MAP Kinase Kinase Kinase MAP3K1 gene Mammals Mediating Microbe Mitogen-Activated Protein Kinase Kinases Modeling Molecular Mouse-ear Cress Natural Immunity Pattern Pattern recognition receptor Peptides Phosphorylation Phosphotransferases Plants Play Prevention Production Proteins Receptor Activation Receptor Signaling Regulation Research Research Project Grants Reverse Transcriptase Polymerase Chain Reaction Role Signal Pathway Signal Transduction System Transcriptional Regulation Transgenic Plants Ubiquitination base chromatin immunoprecipitation defense response fly genome wide association study innovation loss of function microbial mutant novel pathogen pattern perception receptor research study tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): Innate Immunity is the most ancient and evolutionarily conserved central defense system that distinguishes host-self from non-self microbial pathogens in plants, animals and humans. It provides the first line of inducible defense against infectious diseases and underlies the prevention of constant and omnipresent microbial invasion. A key function of innate immunity is the detection of microbe-associated molecular patterns (MAMPs, such bacterial flagellin) by pattern recognition receptors and the launch of appropriate defense responses. Recent discoveries have revealed remarkable convergent evolution in the recognition of diverse MAMPs by leucine-rich-repeat receptors and the activation of multiple MAPK cascades in plants, animals and humans. Despite the universal and essential involvement of MAPK cascades in mediating MAMP signaling in plants, worms, flies, mammals and humans, the molecular mechanisms underlying the intertwined signaling webs remain mostly elusive due to the complexity of functional redundancy, mutant lethality and shared components in distinct signaling pathways. The goal of this research project is to establish a regulatory framework for the convergent MAMP signaling using Arabidopsis thaliana as a model system. The proposed experiments aim to integrate molecular, biochemical, cellular, genetic, and genomic approaches to dissect the multifunctional BAK1-MAPKKK complexes and MAPKK-MAPK cascades, and to analyze the downstream WRKY transcription factors in controlling diverse target genes in plant defense responses. Specifically, the project will focus on characterizing and integrating the functions of 15 Arabidopsis genes in flagellin signaling using cell- based assays, transgenic plants and loss-of-function mutants with specific defects in the flagellin receptor FLS2, receptor signaling partner BAK1, MAPKKK-MAPKK-MAPK cascades and WRKY transcription factors. Protein interaction, phosphorylation and ubiquitination assays, quantitative RT- PCR, whole-genome microarray and chromatin-immunoprecipitation will be carried out to elucidate the key and conserved signaling mechanisms in plant innate immunity. Three Specific Aims are: Aim 1. Analyze interactions and regulations of BAK1-MAPKKK signaling complexes Aim 2. Dissect the MAPKK-MAPK cascade functions in convergent MAMP signaling Aim 3. Define functions and regulations of WRKY transcription factors. PUBLIC HEALTH RELEVANCE: The powerful innate immune system underlies the prevention of constant and omnipresent microbial invasion, and provides the first line of inducible defense against infectious diseases in plants, animals and humans. A key function of innate immunity is the detection of microbe- associated molecular patterns (MAMPs) and the launch of appropriate defense responses. Recent discoveries have revealed remarkable convergent evolution in MAMP perception by leucine-rich- repeat pattern recognition receptors and the activation of multiple MAPK cascades. The proposed research from receptor kinase signaling complexes to intertwined MAPK cascades and WRKY transcriptional controls will discover novel and fundamental molecular mechanisms in innate immune signaling, and provide innovative tools for future improvement of agriculture, environment and renewable energy production, as well as human health in treating infectious, inflammatory and autoimmune diseases.

描述（由申请人提供）：先天免疫是最古老和最保守的中央防御系统，它将宿主自身与植物，动物和人类中的非自身微生物病原体区分开。它提供了针对传染病的第一线防御，并奠定了预防恒定和无所不在的微生物侵袭的基础。先天免疫的关键功能是通过模式识别受体检测与微生物相关的分子模式（MAMP，此类细菌鞭毛蛋白）和适当的防御反应的发射。最近的发现揭示了富含亮氨酸的重复受体对不同MAMP的识别以及植物，动物和人类中多个MAPK级联反应的激活。尽管MAPK Cascades在介导植物，蠕虫，苍蝇，哺乳动物和人类中介导的MAMP信号传导中存在普遍且必不可少的参与，但由于功能冗余，突变型杀伤力和共享成分在独特的信号传导途径中的复杂性，这些相互交织信号网的分子机制仍然难以捉摸。该研究项目的目的是建立一个使用拟南芥作为模型系统的收敛MAMP信号传导的监管框架。提出的实验旨在整合分子，生化，细胞，遗传和基因组方法，以剖析多功能的BAK1-MAPKKKKKKK络合物和MAPKK-MAPK级联反应，并分析在植物防御反应中控制多元化靶基因中下游WRKY转录因子的下游WRKY转录因子。 Specifically, the project will focus on characterizing and integrating the functions of 15 Arabidopsis genes in flagellin signaling using cell- based assays, transgenic plants and loss-of-function mutants with specific defects in the flagellin receptor FLS2, receptor signaling partner BAK1, MAPKKK-MAPKK-MAPK cascades and WRKY transcription factors.将进行蛋白质相互作用，磷酸化和泛素化测定，定量RT-PCR，全基因组微阵列和染色质免疫沉淀，以阐明植物先天免疫中的钥匙和保守信号机制。三个具体目的是：目标1。分析BAK1-MAPKKK信号传导络合物的相互作用和法规目标2。在收敛的MAMP信号传导目标中剖析MAPKK-MAPK CASCADE函数AIM 3。定义WRKY转录因子的功能和法规。公共卫生相关性：强大的先天免疫系统是预防恒定和无所不在的微生物入侵的基础，并提供了针对植物，动物和人类中传染病的诱导性防御的第一线。先天免疫的关键功能是检测微生物相关的分子模式（MAMP）和发射适当的防御反应。最近的发现揭示了富含亮氨酸的重复模式识别受体和多个MAPK级联反应的激活在MAMP感知中的显着收敛演化。从受体激酶信号传导复合物到交织的MAPK级联和WRKY转录控制的拟议研究将发现先天免疫信号传导中的新颖和基本分子机制，并为未来改善农业，环境和可再生能源生产以及治疗炎症性和自动化和自动化和自动症的人体健康提供创新的工具。