Mechanisms regulating plant immune homeostasis

植物病害占全球每年农作物损失的15%(估计价值1000亿美元)，目前需要昂贵且不利于环境的化学处理。病原体之所以能够感染农作物并导致疾病，很大程度上是因为它们可以抑制植物的免疫反应。因此，只有当我们清楚地了解植物免疫系统时，我们才能为影响我们农作物的疾病提供安全和可持续的解决方案。因为病原菌的反应必然会将植物的能量从生长中转移出去，所以一个主要的挑战是如何在不影响产量的情况下提高植物的免疫力。*我的研究计划的长期目标是了解在模式植物拟南芥中定制植物免疫信号以维持细胞动态平衡的分子机制。我特别感兴趣的是免疫信号酶是如何通过翻译后修饰和差异结合伙伴/底物来调节的，以及如何建立和控制积极和消极的信号级联反应。这项拟议的研究从分子水平上探讨了免疫信号对植物动态平衡的影响，并将分子和细胞生物学、生物化学和蛋白质组学与正向和反向遗传学相结合。由于我们的研究计划具有多学科性质，实验室人员将接受横跨分子生物学、生物化学和植物遗传学的广泛技术培训。*拟南芥和其他植物通过位于细胞表面的受体激酶来感知病原体。激酶BIK1被几种受体磷酸化(并激活)，是植物免疫信号的组成部分。证明其重要性的是，BIK1是多种无关病原体的靶标，以抑制免疫信号。我们最近发现，植物通过蛋白酶体的持续降解过程来维持BIK1的最佳水平，该过程也受到CPK28的影响，该蛋白也与BIK1相互作用并使其磷酸化。因此，BIK1似乎既受磷酸化的正向调控，也受磷酸化的负向调控，这增加了有趣的可能性，即残基特异性或数量差异导致了这两种状态。我们将表征BIK1上的磷酸化和随后的泛素化事件，并研究这些事件如何控制其周转。此外，我们还将确定与BIK1降解有关的E3连接酶(S)。为了更多地了解CPK28是如何调控的，我们将表征我们最近通过质谱学鉴定的CPK28相关蛋白质。由于需要识别参与植物免疫信号的新蛋白质，这些蛋白质也可能是病原体的靶标，我们也将使用正向遗传学来筛选这样的蛋白质。我的项目为HQP提供了一个极好的培训环境，使其使用最先进的技术在植物分子生物学方面产生很大影响，这些技术将为加拿大和世界各地的农业实践提供信息。**

Plant diseases account for 15% of annual global crop losses (estimated worth of $100 billion) and currently require costly and environmentally unfriendly chemical treatments. Pathogens are capable of infecting crops and causing disease largely because they can suppress plant immune responses. Thus, only when we clearly understand the plant immune system will we be able to offer safe and sustainable solutions to diseases that affect our crops. Because pathogen responses necessarily re-direct plant energy away from growth, a major challenge is how to boost plant immunity without affecting yield.***The long-term goal of my research program is to understand the molecular mechanisms that tailor plant immune signaling to maintain cellular homeostasis in the model plant Arabidopsis thaliana. I am particularly interested in how immune signaling enzymes are regulated by post-translational modifications and differential binding partners/substrates, and how positive and negative signaling cascades are established and controlled. The proposed research addresses the impact of immune signaling on plant homeostasis at the molecular level and integrates molecular and cell biology, biochemistry, and proteomics with forward- and reverse-genetics. Owing to the multi-disciplinary nature of our research program, lab personnel will be trained in a broad range of techniques spanning molecular biology, biochemistry, and plant genetics.***Arabidopsis and other plants perceive pathogens via receptor kinases located at the cell surface. The kinase BIK1 is phosphorylated (and activated) by several receptors and is integral to plant immune signaling. Demonstrating its importance, BIK1 is the target of multiple unrelated pathogens to dampen immune signaling. We recently showed that plants maintain an optimal level of BIK1 through a process of continuous proteasomal degradation influenced by the kinase CPK28, which also interacts with and phosphorylates BIK1. Thus, it seems that BIK1 is both positively and negatively regulated by phosphorylation, raising the intriguing possibility that residue-specific or quantitative differences contribute to the two states. We will characterize phosphorylation and subsequent ubiquitination events on BIK1 and study how these events control its turnover. Furthermore, we will identify the E3 ligase(s) responsible for BIK1 degradation. To understand more about how CPK28 is regulated, will characterize CPK28-associated proteins that we recently identified by mass-spectrometry. Because of the need to identify novel proteins involved in plant immune signaling that may also be pathogen targets, we will also screen for such proteins using forward-genetics. My program provides an excellent training environment for HQP to make a high impact in plant molecular biology using state-of-the-art technologies that will inform agricultural practices in Canada and world-wide.**