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.

植物病原体威胁着农业生产力和食品质量，对我们的粮食系统构成了明显而现实的危险。仅丝状植物病原体就占全球作物损失的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破坏苦心培育的作物抗病能力的倾向，由植物疾病引起的爆发频率有所增加。尽管植物拥有对抗疾病的遗传工具，但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)基因编码的特殊免疫传感器及时检测入侵者。然而，一些病原体逃避了R蛋白的检测，限制了这些免疫传感器在农业中的效力。遗传改良作物抗性的主要策略是将野生近缘作物的R基因转移到优良品种中。这主要是由于这些基因在预防寄生虫感染方面的特殊效力。然而，针对新出现的病原体小种的R基因的可用性有限，以及我们对R基因功能的基本理解存在差距，阻碍了作物抗病育种的成功。我们的长期目标是破译R基因介导免疫的机制，以便为作物培育抗病植物提供指导原则。核苷酸结合域富亮氨酸重复序列（NLR）免疫受体是最丰富的一类抗病蛋白，一直被用于抗病作物的育种。最近的突破表明，活化的nlr形成寡聚结构，插入细胞膜，形成微小的孔，以触发程序性细胞死亡的形式作为一种防御机制。尽管取得了这些进展，但我们对NLR在相关病原体感染过程中的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。我们最近有了一个令人兴奋的发现，即NLRs在爱尔兰马铃薯饥荒病原体疫霉（Phytophthora infestans）感染活细胞时的行为。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，可能加速免疫反应。我们现在发现了另一种NLR类型的抗性蛋白，它的目标是叶绿体，即植物细胞内产生能量的光合作用细胞器。这些发现为nlr是移动疾病探测器的概念提供了证明，它可以将防御信号传播到远处的细胞区室，并增强免疫反应的有效性。在本文中，我们旨在了解NLR向感染位点或叶绿体的不同运输的分子机制，并研究激活的NLR最终如何执行导致疾病抵抗的免疫反应。我们已经收集了令人兴奋的初步数据，这些数据支持我们的观点，即在感染期间激活前后，NLR的多向转运在功能上与调节免疫反应的强度有关，从而消除感染因子。通过解密这些机制，我们将获得有助于改造植物免疫系统以提高病原体抗性的基础知识。这项工作将具有深远的意义，因为我们研究的NLR蛋白是抗病网络的关键成员，可以抵抗多种农艺学上重要的病原体和害虫。