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

描述(申请人提供)：植物对人类健康和福祉至关重要。我们吃植物，或先吃植物再吃植物的动物；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，人类的生命是不可能的。因此，了解植物生长、健康和生产力的研究显然与人类的健康和福祉有关，正如2009年美国国家研究委员会(National Research Council)的报告所强调的那样：《21世纪的新生物学：确保美国引领即将到来的生物学革命》。植物研究对了解人类的基本过程有很大贡献。植物中的比较分析导致确定了与人类疾病和发育有关的蛋白质家族或结构域。大多数怀疑或已知在疾病中起作用的人类基因在植物中都有同源基因--例如，70%与癌症有关的基因都有植物同源基因。拟南芥遗传学、基因组学和细胞生物学的实验简便性导致了对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引用的过程，这是本提案的重点。这个新项目利用了NIH支持的已完成的研究，该研究揭示了来自细菌和真核卵菌病原体的效应蛋白(毒力因子)是如何部署效应器的，这些效应器会聚在一组相互连接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侵占正常发育和细胞生物学过程以抵消宿主免疫反应的总体假设。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的特定子集控制的发育和免疫的功能过程，称为TCPs，这些转录因子重复地被不同的病原体效应物靶向，并且在当前的拟南芥相互作用组中形成一个紧密的子网络。Tcp蛋白是发育的典型调节者，但在防御中扮演新角色。因此，这一提议提供了一个难得的机会来剖析相互冲突的发育和防御线索之间转录协调的分子机制。TCP基因是一个古老的基因家族，存在于蕨类植物、石蕊、苔藓和一些藻类物种中，代表了大约6.5亿年的进化史，使我们能够研究发育和免疫功能共同进化的轨迹。我们从实验中获得的知识将有助于动物病原体的研究，因为人类病原体也通过瞄准正常细胞功能的关键调节因子来操纵正常的宿主细胞生理。

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.