Mechanisms regulating plant immune homeostasis

植物病害占全球每年作物损失的15%（估计价值1000亿美元），目前需要昂贵且对环境不友好的化学治疗。病原体之所以能够感染作物并引起疾病，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了植物的免疫系统，我们才能为影响我们作物的疾病提供安全和可持续的解决方案。由于病原体的反应必然会将植物的能量从生长中转移出去，因此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。我的长期研究目标是了解模式植物拟南芥中调节植物免疫信号以维持细胞稳态的分子机制。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/底物调节的，以及积极和消极信号级联是如何建立和控制的。本研究在分子水平上探讨了免疫信号对植物体内平衡的影响，并将分子和细胞生物学、生物化学、蛋白质组学与正向和反向遗传学相结合。由于我们研究计划的多学科性质，实验室人员将接受广泛的技术培训，包括分子生物学，生物化学和植物遗传学。拟南芥和其他植物通过位于细胞表面的受体激酶感知病原体。激酶BIK1被几种受体磷酸化（和激活），是植物免疫信号传导的组成部分。证明其重要性，BIK1是多种不相关病原体抑制免疫信号的目标。我们最近发现，植物通过受激酶CPK28影响的持续蛋白酶体降解过程维持最佳水平的BIK1，该激酶也与BIK1相互作用并磷酸化。因此，BIK1似乎同时受到磷酸化的正调控和负调控，这就提出了残基特异性或数量差异导致这两种状态的有趣可能性。我们将描述BIK1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，我们将确定负责BIK1降解的E3连接酶。为了更好地了解CPK28是如何调控的，我们将描述我们最近通过质谱鉴定的CPK28相关蛋白。由于需要鉴定与植物免疫信号有关的新蛋白质，这些蛋白质也可能是病原体的靶点，我们也将使用正向遗传学筛选这些蛋白质。我的项目为HQP提供了一个良好的培训环境，使他们能够利用最先进的技术在植物分子生物学方面产生重大影响，这些技术将为加拿大和全世界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.