Molecular Basis of Pathogen-Induced Cell Death in Plants

这种竞争性更新的实验联合收割机结合了模式植物拟南芥强大的遗传工具 用细胞生物学和生物化学方法来研究控制先天性 免疫和程序性细胞死亡（PCD）。植物防御的控制与人类有许多相似之处 先天免疫此外，PCD在植物和人类中具有相似的特征和调节。我们漫长 本学期的目标是了解PCD调节和执行的分子基础。这对于以下方面至关重要： 开发策略来操纵PCD以预防或治疗涉及PCD过量或不足的疾病 在植物和人类中的诱导。从植物免疫和PCD的研究中所学到的东西将是一个 理解人类类似事件的范例。本文描述的实验建立在先前工作的基础上 两个拟南芥基因ACD 6和ACD 2。ACD 6是一种新的整合质膜蛋白，具有N- 在植物中控制防御和PCD的末端锚蛋白重复结构域。锚蛋白重复序列参与了 在植物、人类和许多其他生物体中的蛋白质-蛋白质相互作用。ACD 6对本地和 和系统性信号传导。ACD 2是一种新的蛋白质，它控制着 通过控制内源性PCD诱导分子的水平或反应性， 卟啉或卟啉样分子。因此，感染激活ACD 6来调节防御， PCD和ACD 2调节PCD的时间和程度以防止过度的组织损伤。拟议 本研究旨在：（i）确定ACD 6在激活PCD和抗病性中的作用机制 使用分子遗传学和生物化学方法;（2）通过以下方法确定ACD 2的作用机制： 结合分子遗传学、生物化学和生理学实验;（3）鉴别性质， 由于使用细胞的卟啉处理（感染的替代物）而死亡的细胞的信号传导需求 生物学方法。 卟啉在正在开发的抗肿瘤疗法中是重要的。因此，重要的是要知道， 尽可能多地了解卟啉对细胞的影响。人类卟啉类化合物的失调（a 一种叫做卟啉症的疾病）会给人类带来严重的疾病。ACD 2可能提供一种方法来帮助人们 这种疾病，因为它可能有潜力解毒卟啉。许多人类疾病也 是由含抗肿瘤蛋白质的功能障碍引起的。这项工作将产生重要的信息 关于整类锚蛋白的研究， 一些人类疾病。这些研究将揭示植物和人类的共同过程， 用于治疗由细胞损伤过多或过少引起的疾病。因为实验的进展 使用植物模型是快速的，所获得的结果很快与人类生物学和疾病有关。

Experiments in this competing renewal combine the powerful genetic tools of the model plant Arabidopsis with cell biological and biochemical approaches to examine a major signaling pathway that controls innate immunity and programmed cell death (PCD). The control of plant defenses has many parallels with human innate immunity. Furthermore, PCD has similar features and regulation in plants and humans. Our long term goal is to understand the molecular basis of PCD regulation and execution. This is essential for developing strategies to manipulate PCD to prevent or cure diseases involving excess or insufficient PCD induction in both plants and humans. What is learned from studying plant immunity and PCDwill be a paradigm for understanding similar events in humans. Experiments described herein build on previouswork on two Arabidopsis genes, ACD6 and ACD2. ACD6 is a novel integral plasma membrane protein with an N- terminal ankyrin repeat domain that controls defense and PCD in plants. Ankyrin repeats are involved in protein-protein interactions in plants, humans and many other organisms. ACD6 is important for both local and systemic signaling during infection. ACD2 is a novel protein that controls the activation and extent of PCD during infection by controlling the levels or reactivity of an endogenous PCD-inducingmolecule that is either a porphyrin or a porphyrin-like molecule. Thus, infection activates ACD6 to regulate defenses and PCD and ACD2 modulates the timing and extent of PCD to prevent excess tissue damage. The proposed research aims to: (i) determine the mechanism of action of ACD6 in activating PCD and disease resistance using molecular genetic and biochemical approaches; (2) determine the mechanism of action of ACD2 by combining molecular genetic, biochemical and physiological experiments; and (3) discern the properties and signaling requirements of cells that die due to porphyrin treatment (a surrogate for infection) using cell biological approaches. Porphyrins are important in anti-tumor therapies being developed. Therefore, it is important to know as much as possible about the effects that porphyrins have on cells. Dis-regulation of porphyrins in human (a condition called porphyria) causes severe disease to humans. ACD2 may provide a way to help people with this disease, since it likely has the potential to detoxify porphyrins. A number of human diseases are also caused by the malfunction of ankyrin-containing proteins. This work will generate important information about the whole class of ankyrin proteins that can be applied to understanding and possibly interrupting some human diseases. These studies will unravel common processes in plants and humans that can be manipulated to treat diseases caused by too much or too little cell damage. Because experimental progress using a plant model is rapid, the results obtained and quickly be related to human biology and disease.