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

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，或者在我们吃植物之前吃植物的动物；我们用植物纤维制作衣服和房屋；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密切相关，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：确保美国领导即将到来的生物学革命。”植物研究对理解人类的基本过程有重要贡献。对植物的比较分析鉴定出了与人类疾病和发育有关的蛋白质家族或结构域。大多数被怀疑或已知在疾病中起作用的人类基因在植物中有同源物——例如，70%与癌症有关的基因在植物中有同源物。拟南芥遗传学，基因组学和细胞生物学的实验容易导致发现所有真核生物共有的基本过程，特别是那些交叉参考正常发育与宿主对微生物病原体的反应的过程，这是本提案的重点。这个新项目利用了已完成的NIH支持的研究，该研究揭示了来自细菌和真核卵菌病原体的效应蛋白（毒力因子）如何部署效应蛋白，这些效应蛋白聚集到一组相互关联的细胞内宿主靶标上。这种趋同是惊人的，因为这两种相距约20亿年的病原体有着非常不同的生活方式和毒力机制。这些数据支持了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的总体假设。在这个新的建议中，我们的目标是了解发育和免疫的功能过程，这些功能过程由一组特定的古老和保守的转录因子（称为tcp）控制，这些转录因子被不同的病原体效应物反复靶向，并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因子，但也是防御的新参与者。因此，这一建议提供了一个难得的机会来剖析在相互冲突的发育和防御线索中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、石松植物、苔藓和一些藻类中，代表了大约6.5亿年的进化史，这使我们能够研究发育和免疫功能的共同进化轨迹。从我们的实验中获得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。

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.