DISSECTING SIGNALING PATHWAYS IN PLANT IMMUNITY

***剖析植物免疫信号通路******微生物疾病是全球作物生产的主要威胁，每年导致作物产量损失10%至16%。每年花费数十亿美元在杀虫剂上，以保护农作物免受病原体的侵害。这些化学物质往往对环境有害，也可能导致抗药性病原体的进化。因此，安全、可持续的病原菌控制方法对现代农业的成功至关重要。一种成功的方法是培育具有抗病(R)基因的作物，这些基因主要编码核苷酸结合域和富含亮氨酸重复序列（NLR）的免疫受体，这些受体可以感知特定的病原体并引发强烈的防御反应。典型植物nlr根据其对应的n末端进一步分为Toll/interleukin-1 receptor （TIR）型和coil-coil （CC）型。尽管nlr介导的耐药非常有效，但其分子机制尚不清楚。我的实验室的长期目标是在分子水平上了解nlr介导的免疫，并利用这些知识开发可持续作物保护的方法。******在过去的十年中，我们建立了几个自身免疫模型，并成功地利用它们发现了许多有助于植物免疫的新成分。我们发现核胞质运输、转录调控、NLR二聚化/寡聚化、蛋白质修饰和RNA加工都在NLR介导的免疫中发挥重要作用。我们还发现了调节NLR稳态的NLR降解途径。在当前的NSERC Discovery研究项目中，我们将在这些已建立的自身免疫模型的基础上，使用下一代测序、CRISPR/Cas9基因编辑和蛋白质组学方法来确定nlr介导的免疫的关键缺失参与者，并阐明它们如何共同发挥作用，在病原体攻击时建立适当的防御。******未来五年，我们将着力实现以下两个具体目标：******表征通过辅助NLR、ADR1s和NRG1s激活的tir型NLR （TNL）介导的免疫信号通路；和* * * * * * 2。解剖依赖或独立于防御激素水杨酸的植物免疫信号通路。*** ***提出的研究不仅将丰富我们对植物如何抵御微生物病原体的理解，培养下一代高素质的多样化科学家，而且还将为设计不依赖农药保护作物植物的新策略提供新的见解。此外，由于NLR受体也存在于哺乳动物中，我们对植物NLR的研究可能会揭示其动物对应物的功能，从而可能具有潜在的健康益处。********

***Dissecting signaling pathways in plant immunity****** Microbial diseases are a major threat to global crop production, resulting in annual crop yield losses between 10 to 16%. Billions of dollars are spent each year on pesticides to protect crops from pathogens. These chemicals are often damaging to the environment and may also lead to the evolution of pesticide-resistant pathogens. Thus, safe and sustainable pathogen control methods are critical to the success of modern agriculture. One successful approach is to breed crops with disease resistance (R) genes, which mostly encode nucleotide-binding domain and leucine-rich repeats (NLR) immune receptors that can perceive specific pathogens and trigger strong defense responses. Typical plant NLRs are further classified into Toll/interleukin-1 receptor (TIR) or coil-coiled (CC) type depending on their corresponding N-termini. Despite NLR-mediated resistance being highly effective, its molecular mechanism remains unclear. The long-term goal of my lab is to understand NLR-mediated immunity at the molecular level and use that knowledge to develop methods for sustainable crop protection.****** During the past decade, we have established several autoimmune models and successfully used them to discover many novel components that contribute to plant immunity. We showed that nucleocytoplasmic trafficking, transcriptional regulation, NLR dimerization/oligomerization, protein modifications and RNA processing all play important roles in NLR-mediated immunity. We also uncovered an NLR degradation pathway that regulates the homeostasis of NLRs. In this current NSERC Discovery program of research, we will build on these established autoimmune models and use next-generation sequencing, CRISPR/Cas9 gene editing and proteomics methods to identify key missing players of NLR-mediated immunity and elucidate how they function together to mount a proper defense upon pathogen attack. ******In the next five years, we will focus on the following two specific objectives:******1. Characterize TIR-type NLR (TNL) mediated immune signaling pathways activated through the helper NLRs, ADR1s and NRG1s; and******2. Dissect plant immune signaling pathways that are dependent or independent of the defense hormone salicylic acid.*** *** The proposed research will not only enrich our understanding of how plants defend against microbial pathogens and train the next-generation of highly qualified diverse scientists, but will also provide new insight for designing novel strategies to protect the crop plants without reliance on pesticides. In addition, as NLR receptors are also present in mammals, our proposed studies on plant NLRs may shed light on how their animal counterparts function and could thus have potential health benefits.********