Molecular Basis of Pathogen-Induced Cell Death in Plants

这种竞争性更新的实验结合了模式植物拟南芥的强大遗传工具。 用细胞生物学和生物化学的方法来检查控制先天的主要信号通路 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。 先天免疫力。此外，PCD在植物和人类中也有类似的特征和调节。我们的龙 学期目标是了解PCD调控和执行的分子基础。这对以下各项至关重要 制定控制PCD的策略，以预防或治疗涉及PCD过多或不足的疾病 对植物和人类都有诱导作用。从研究植物免疫和PCD中学到的将是一个 理解人类中类似事件的范例。这里描述的实验建立在以前的工作基础上 在两个拟南芥基因ACD6和ACD2上。ACD6是一种新的完整的质膜蛋白，具有N- 末端锚蛋白重复结构域，控制植物中的防御和PCD。Ankyrin重复序列参与了 植物、人类和许多其他生物中的蛋白质-蛋白质相互作用。ACD6对两个地方政府都很重要 以及感染期间的系统信号。ACD2是一种新的蛋白质，它控制着ACD2的激活和程度 通过控制内源性PCD诱导分子的水平或活性来控制感染期间的PCD 或者是一种卟啉，或者是一种类似于卟啉的分子。因此，感染激活ACD6来调节防御和 PCD和ACD2调节PCD的时间和程度，以防止过度的组织损伤。建议数 研究的目的是：(I)确定ACD6激活PCD和抗病的作用机制 利用分子遗传学和生物化学方法；(2)通过以下方式确定ACD2的作用机制 结合分子遗传学、生物化学和生理学实验；(3)辨别特性和 使用细胞对因卟啉处理(感染的替代物)而死亡的细胞的信号要求 生物学方法。 卟啉在正在开发的抗肿瘤疗法中非常重要。因此，重要的是要了解 尽可能多地了解卟啉对细胞的影响。卟啉在人体内的失调(A) 一种称为卟啉症的疾病)会给人类带来严重的疾病。ACD2可以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的卟啉。一些人类疾病也是 由含有锚定蛋白的蛋白质故障引起。这项工作将产生重要的信息 关于可以用来理解和可能干扰的锚蛋白的整个类别 一些人类疾病。这些研究将揭开植物和人类的共同过程，这些过程可以 用来治疗细胞损伤过多或过少引起的疾病。因为实验进展 使用植物模型是快速的，得出的结果很快就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.