The intersection of development and innate immune system function in Arabidopsis.

拟南芥发育与先天免疫系统功能的交叉点。

• 批准号: 8561801
• 负责人: JEFFERY L. DANGL
• 金额: $ 25.72万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8561801
• 关键词: Address; Affect; Animals; Arabidopsis; Attenuated; Biological Process; Biology; Biomedical Research; Cell Differentiation process; Cell physiology; Cells; Cellular biology; Clothing; Conflict (Psychology); Cues; Data; Development; Disease; Disease Resistance; Eating; Ecosystem; Employee Strikes; Ensure; Equilibrium; Equipoise; Eukaryota; Event; Evolution; Experimental Models; Family; Family member; Fiber; Funding; Gene Family; Genes; Genetic; Genomics; Goals; Gram-Negative Bacteria; Growth; Growth and Development function; Health; Home environment; Hormonal; Hormone Responsive; Host Defense; Human; Human Development; Immune response; Immune system; Immunity; Infection; Insecta; Investigation; Knowledge; Life; Life Style; Malignant Neoplasms; Mediating; Modeling; Molecular; Mosses; N.I.H. Research Support; National Research Council; Nature; Normal Cell; Nuclear; Oomycetes; Orthologous Gene; Output; Oxygen; Pathogenicity; Pathway interactions; Personal Satisfaction; Phenotype; Physiology; Plant Proteins; Plants; Play; Process; Productivity; Protein Family; Proteins; Pseudomonas syringae; Recording of previous events; Reporting; Research; Resource Allocation; Resources; Role; Signal Transduction; Stress; System; Tertiary Protein Structure; United States; United States National Institutes of Health; Virulence; Virulence Factors; Virulent; base; cell growth; cellular targeting; comparative; defense response; extracellular; feeding; fitness; human disease; immune function; microbial; novel; pathogen; plant growth/development; programs; public health relevance; receptor; reproductive success; research study; response; transcription factor

DESCRIPTION (provided by applicant): Plants are critical for human health and well-being. We eat plants, or animals that ate plants before we ate them; we use plant fibers for our clothes and our homes; we rely on plants to provide ecosystems conducive to environmental well-being. Plants provide us with oxygen. Without plants, human life would be impossible. Hence, research to understand plant growth, health and productivity is explicitly relevant to human health and well-being, as was stressed in the 2009 National Research Council report: 'A New Biology for the 21st Century: Ensuring the United States Leads the Coming Biology Revolution.' Plant research contributes significantly to understanding of basic processes in humans. Comparative analyses in plants led to the identification of protein families or domains involved in human disease and development. A majority of human genes suspected or known to play a role in disease have orthologs in plants -- for example, 70% of genes implicated in cancer have plant orthologs. The experimental ease of Arabidopsis genetics, genomics, and cell biology leads to discoveries about fundamental processes shared across all eukaryotes, especially those processes that cross reference normal development with a host's response to microbial pathogens, the focus of this proposal. This new project takes advantage of completed NIH supported research that revealed how the effector protein (virulence factor) repertoires from a bacterial and a eukaryotic oomycete pathogen deploy effectors that converge onto an interconnected set of intracellular host targets. This convergence is striking as these two pathogens, which are separated by ~2 billion years of evolution, have very different life styles and virulence mechanisms. These data supported the overall hypothesis that pathogens usurp normal developmental and cell biological process to counteract host immune responses. In this new proposal, our goal is to understand the functional processes of development and immunity governed by a specific subset of ancient and conserved transcription factors, called TCPs, that are repeatedly targeted by diverse pathogen effectors, and that form a tight sub-network in the current Arabidopsis interactome. TCP proteins are well-characterized regulators of development, but novel players in defense. Thus, this proposal provides a rare opportunity to dissect the molecular mechanism of transcriptional coordination across conflicting developmental and defense cues. TCP genes are an ancient gene family found in pteridophytes, lycophytes, moss and some algal species, representing an evolutionary history of about 650 million years, which enable us to study the trajectory of co-evolution of developmental and immune functions. Knowledge emerging from our experiments will benefit investigations of animal pathogens, since human pathogens also manipulate normal host cell physiology by targeting critical regulators of normal cell function.

描述（由申请人提供）：植物对人类健康和福祉至关重要。我们吃植物，或者吃植物的动物;我们用植物纤维做衣服和房子;我们依靠植物提供有利于环境福祉的生态系统。植物为我们提供氧气。没有植物，人类就不可能生存。因此，了解植物生长，健康和生产力的研究与人类健康和福祉明确相关，正如2009年国家研究理事会报告所强调的那样：“21世纪的新生物学：确保美国领导即将到来的生物学革命。“植物研究对理解人类的基本过程有重大贡献。在植物中的比较分析导致了与人类疾病和发育有关的蛋白质家族或结构域的鉴定。大多数疑似或已知在疾病中发挥作用的人类基因在植物中具有直系同源物--例如，70%与癌症有关的基因具有植物直系同源物。拟南芥遗传学、基因组学和细胞生物学的实验便利性导致了关于所有真核生物共有的基本过程的发现，特别是那些将正常发育与宿主对微生物病原体的反应交叉参考的过程，这是本提案的重点。这个新项目利用了NIH支持的研究成果，揭示了来自细菌和真核卵菌病原体的效应蛋白（毒力因子）是如何部署效应子的，这些效应子聚集在一组相互关联的细胞内宿主靶标上。这种趋同是惊人的，因为这两种病原体相隔约20亿年的进化，具有非常不同的生活方式和毒力机制。这些数据支持病原体篡夺正常发育和细胞生物学过程以抵消宿主免疫应答的总体假设。在这个新的提议中，我们的目标是了解由古老和保守的转录因子（称为TCP）的特定子集控制的发育和免疫的功能过程，这些转录因子被不同的病原体效应子反复靶向，并在当前的拟南芥相互作用组中形成紧密的子网络。TCP蛋白是发育的良好特征调节剂，但在防御中是新的参与者。因此，这一建议提供了一个难得的机会，解剖在冲突的发展和防御线索的转录协调的分子机制。TCP基因是存在于蕨类植物、石松植物、苔藓和一些藻类物种中的古老基因家族，代表了约6.5亿年的进化历史，使我们能够研究发育和免疫功能的协同进化轨迹。从我们的实验中出现的知识将有利于动物病原体的研究，因为人类病原体也通过靶向正常细胞功能的关键调节因子来操纵正常宿主细胞生理学。