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: 9127272
• 负责人: JEFFERY L. DANGL
• 金额: $ 25.7万
• 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/9127272
• 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; 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。我们吃植物或在食用植物之前吃的动物；我们将植物纤维用于我们的衣服和房屋；我们依靠植物提供有利于环境健康的生态系统。植物为我们提供氧气。没有植物，人类的生命将是不可能的。因此，了解植物生长，健康和生产力的研究明确与人类健康和福祉有关，正如2009年国家研究委员会报告所强调的那样：“ 21世纪的新生物学：确保美国领导即将来临的生物学革命。”植物研究有助于理解人类的基本过程。植物中的比较分析导致鉴定涉及人类疾病和发育的蛋白质家族或域。大多数涉嫌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，与癌症有关的基因中有70％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易度性导致了有关在所有真核生物中共享的基本过程的发现，尤其是那些交叉引用正常发育的过程以及宿主对微生物病原体的反应，这是该建议的重点。这个新项目利用了已完成的NIH支持的研究，该研究揭示了效应蛋白（毒力因子）如何从细菌和真核生物卵菌病原体部署效应子中汇总，从而收敛到一组相互联系的细胞内宿主靶标。这种融合令人惊讶，因为这两种病原体被大约20亿年的进化，具有非常不同的生活方式和毒力机制。这些数据支持了总体假设，即病原体篡夺正常发育和细胞生物学过程以抵消宿主免疫反应。在这项新提案中，我们的目标是了解由古代和保守的转录因子（称为TCP）的特定子集控制的发育和免疫力的功能过程，这些因素被称为多样化的病原体效应子，并在当前的拟南芥相互作用中形成了紧密的子网络。 TCP蛋白是发育良好的调节器，但在防御方面具有新颖的参与者。因此，该提案提供了一个难得的机会，可以剖析跨冲突的发展和防御线索的转录协调的分子机制。 TCP基因是一种在孢子菌，乳木菌，苔藓和某些藻类物种中发现的古老基因家族，代表大约6.5亿年的进化史，这使我们能够研究发育和免疫功能共同发展的轨迹。从我们的实验中出现的知识将受益于对动物病原体的研究，因为人类病原体还通过靶向正常细胞功能的关键调节剂来操纵正常的宿主细胞生理。