Divergent recruitment of disease resistance proteins to chloroplasts or pathogen interface

抗病蛋白向叶绿体或病原体界面的不同募集

• 批准号: BB/X016382/1
• 负责人: Tolga Bozkurt
• 金额: $ 64.72万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX016382%2F1
• 关键词: Divergent; recruitment; disease; resistance; proteins

Plant pathogens threaten agricultural productivity and food quality, posing a clear and present danger to our food systems. Filamentous plant pathogens alone account for 10-80% of global crop losses, enough to feed several billion people. Outbreaks caused by plant diseases have increased in frequency due to global trade, climate change, and the propensity of plant pathogens to break down the disease resistance that had been painstakingly bred into crop plants.Although plants have the genetic toolkit to fight diseases, the capacity of pathogens to adapt and evade plant immunity has constrained traditional resistance breeding. Plants prevent parasitism through a sophisticated immune system that relies on timely detection of invaders through specialized immune sensors encoded by plant disease resistance (R) genes. Yet, some pathogens evade detection by the R proteins, limiting the potency of these immune sensors in agriculture. The leading strategy to genetically improve crop resistance is by transferring R genes from wild crop relatives into elite cultivars. This is primarily due to the exceptional potency of these genes in preventing parasitic infestation. However, limited availability of R genes that operate against newly emerging pathogen races and gaps in our fundamental understanding of R gene function, hinder the success of disease resistance breeding in crop plants. Our long-term goal is to decipher the mechanisms underpinning R gene mediated immunity in order to develop guiding principles for breeding plant disease resistance into crop plants. Nucleotide-binding domain leucine-rich repeat (NLR) immune receptors are the most abundant class of disease resistance proteins that have been persistently employed in breeding disease resistant crops. Recent breakthroughs revealed that activated NLRs form oligomeric structures which insert into cellular membranes, making microscopic pores to trigger form of programmed cell death as a defense mechanism. Despite these advances, our knowledge in NLR mode of action during infection by relevant pathogens is still limited, which constrains their potential use in agriculture. We recently made an exciting discovery of how NLRs behave during live cell infection by the Irish potato famine pathogen Phytophthora infestans. Our work revealed that an NLR navigates to pathogen invasion sites (plant-pathogen interface) and upon activation further spreads to other cellular membranes, possibly to accelerate the immune response. We now discovered another NLR type of resistance protein that targets the chloroplasts, the Photosynthetic organelles that generates energy within the plant cells.These finding provide a proof of concept that NLRs are mobile disease detectors that can propagate defense signals to distant cellular compartments and enhance the effectiveness of the immune response.In this proposal, we aim to understand the molecular mechanisms of divergent trafficking of NLRs towards infection sites or the chloroplasts and investigate how the activated NLR ultimately execute the immune response leading disease resistance. We have collected exciting preliminary data that supports our view that multidirectional NLR trafficking pre-and post-activation during infection is functionally relevant to modulate the strength of the immune response to eliminate infectious agents. By decrypting these mechanisms, we will generate fundamental knowledge that will be helpful to remodel plant immune system towards improved pathogen resistance. This work will have far-reaching implications, as the NLR proteins that we work are key members of disease resistance networks, providing resistance to a diversity of agronomically important pathogens and pests.

植物病原体威胁农业生产力和食品质量，对我们的粮食系统构成明显而现实的威胁。仅丝状植物病原体就造成全球农作物损失的 10-80%，足以养活数十亿人。由于全球贸易、气候变化以及植物病原体容易破坏农作物精心培育的抗病能力，植物病害爆发的频率有所增加。尽管植物拥有抵抗疾病的遗传工具包，但其能力病原体适应和逃避植物免疫的能力限制了传统的抗性育种。植物通过复杂的免疫系统来防止寄生，该系统依赖于通过植物抗病（R）基因编码的专门免疫传感器及时检测入侵者。然而，一些病原体逃避 R 蛋白的检测，限制了这些免疫传感器在农业中的效力。从遗传角度提高作物抗性的主要策略是将 R 基因从野生作物近缘种转移到优良品种中。这主要是由于这些基因在预防寄生虫感染方面具有非凡的功效。然而，针对新出现的病原体种群的 R 基因的可用性有限，以及我们对 R 基因功能的基本了解存在差距，阻碍了作物抗病育种的成功。我们的长期目标是破译 R 基因介导的免疫的基础机制，以便制定培育作物抗病性的指导原则。核苷酸结合域富含亮氨酸重复序列（NLR）免疫受体是最丰富的一类抗病蛋白，一直被用于培育抗病作物。最近的突破表明，激活的 NLR 形成寡聚结构，插入细胞膜中，形成微小的孔，触发程序性细胞死亡作为一种防御机制。尽管取得了这些进展，我们对相关病原体感染过程中 NLR 作用模式的了解仍然有限，这限制了它们在农业中的潜在应用。我们最近对 NLR 在爱尔兰马铃薯饥荒病原体致病疫霉活细胞感染期间的行为有了令人兴奋的发现。我们的工作表明，NLR 导航到病原体入侵位点（植物-病原体界面），并在激活后进一步扩散到其他细胞膜，可能会加速免疫反应。我们现在发现了另一种 NLR 类型的抗性蛋白，其靶向叶绿体，即在植物细胞内产生能量的光合细胞器。这些发现提供了一个概念证明，即 NLR 是移动疾病探测器，可以将防御信号传播到远处的细胞区室并增强防御信号。在本提案中，我们的目标是了解 NLR 向感染部位或叶绿体不同运输的分子机制，并研究激活的 NLR 如何最终执行导致抗病性的免疫反应。我们收集了令人兴奋的初步数据，支持我们的观点，即感染期间激活前和激活后的多向 NLR 运输在功能上与调节免疫反应强度以消除感染因子相关。通过解密这些机制，我们将产生有助于重塑植物免疫系统以提高病原体抵抗力的基础知识。这项工作将产生深远的影响，因为我们研究的 NLR 蛋白是抗病网络的关键成员，可以抵抗多种农艺上重要的病原体和害虫。