Dissecting the functional link between immune signaling and defense-related autophagy

到2050年，全球粮食产量需要增加70%，才能养活迅速增长的人口。包括卵菌和真菌在内的丝状植物病原体是最具破坏性的作物病害，对我们的粮食安全构成重大威胁。晚疫病是马铃薯和番茄的一种致命病害，由爱尔兰饥荒致病菌疫霉引起。由晚疫病引起的疫情，以及为管理该疾病而采取的控制措施，导致全球每年损失超过60亿英镑。这种疾病的管理依赖于昂贵的农用化学品，其中一些由于环境和健康问题而受到严格的管制。新出现的菌株杀菌剂敏感性降低使情况恶化。一种可持续的替代方法是从基因上改善抗性，这是一种具体和有针对性的方法，需要对植物免疫有更深入的了解。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。植物通过专门的免疫传感器抵御寄生虫。表面免疫传感器，识别寄生虫释放的分子，这些分子与植物中发现的任何东西都不同。这些表面受体的激活会触发免疫，即模式触发免疫（PTI）。这启动了复杂的信号级联反应，将外部免疫刺激转化为防御反应。PTI在提供对植物病原体的抗性方面的作用是公认的。然而，导致PTI活化后耐药性增强的分子机制尚不完全清楚。然而，成功地将表面免疫传感器从模式植物物种转移到作物中引发了对理解PTI内部工作原理的新兴趣。像其他丝状植物病原体一样，晚疫病病原体通过被称为吸器的手指状延伸侵入宿主细胞，并通过吸器分泌免疫破坏因子来控制被入侵的细胞。被入侵的植物细胞通常通过将其免疫反应集中在病原体延伸处以防止进一步感染。尽管PTI与向病原体吸器部署的防御化合物的产生有关，但PTI调节靶向细胞运输途径到病原体界面的程度尚不清楚。所有的植物和动物都经历一个被称为自噬的自我循环过程，这确保了细胞成分在必要时被降解，同时保留了可以在其他细胞过程中重复使用的基本成分。最近，我们和其他人发现自噬被激活有助于防御疫霉、细菌和病毒。我们后来发现，防御相关的自噬机制被转移到病原体界面，以促进靶向免疫反应。这表明自噬的功能比众所周知的循环作用更为复杂。然而，防御相关的自噬途径是如何在分子水平上被激活和调节的，以及PTI在多大程度上改变了它是未知的。在本提案中，我们的目标是表征控制防御相关自噬的分子机制。我们已经获得了大量的初步数据，表明防御相关自噬机制的调节因子与PTI信号元件相互作用。因此，我们将重点研究PTI与防御相关的自噬途径之间的分子相互作用，以阐明导致疾病抗性增强的分子事件。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，因为与防御相关的自噬机制提供了对多种重要病原体的抗性。

By 2050, global food production needs to increase by 70% to feed the rapidly growing human population. Filamentous plant pathogens including oomycetes and fungi cause the most destructive crop diseases and pose a major threat to our food security. The late blight, caused by the Irish famine pathogen Phytophthora infestans, is a deadly disease of potato and tomato. Outbreaks caused by late blight, as well as the control measures undertaken to manage the disease, lead to more than £6 billion in annual losses globally. The management of the disease relies on costly agrochemicals some of which are under rigorous regulations due to environmental and health concerns. Reduced fungicide sensitivity in newly emerging strains worsen the situation. A sustainable alternative is to genetically improve resistance, a specific and targeted approach which requires a deeper understanding of plant immunity.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 defend against parasites through specialized immune sensors. Surface immune sensors, recognize molecules released by the parasites that are distinct from anything found in the plant. Activation of these surface receptors triggers immunity - known as pattern triggered immunity, or PTI. This kickstarts intricate signalling cascades that translate external immune stimuli into defense responses. The role of PTI in providing resistance to plant pathogens is well-established. However, the molecular mechanisms leading to enhanced resistance following PTI activation are not fully understood. Nevertheless, successful transfer of surface immune sensors from model plant species to crops has sparked renewed interest in understanding the innerworkings of PTI. Like other filamentous plant pathogens, the late blight pathogen invades host cells through finger-like extensions called haustoria, through which it secretes immunity-breaking factors to gain control of the invaded cells. Invaded plant cells often respond by concentrating their immune responses at the pathogen extensions to prevent further infection. Although PTI is implicated in the production of defense-compounds that are deployed towards the pathogen haustoria, the extent to which PTI regulates targeted cellular transport routes to the pathogen interface is not known. All plants and animals undergo a process of self-recycling called autophagy - this ensures that cellular components are degraded when necessary, while preserving the building-blocks, that can be reused in other cellular processes. Recently, ourselves and others discovered that autophagy is activated to contribute to defense against Phytophthora infestans, bacteria and viruses. We later discovered that defense-related autophagy machinery is diverted to pathogen interface to contribute to targeted immune responses. This pointed to more complex functions for autophagy than the widely known recycling roles. However, how defense-related autophagy pathways are activated and regulated at the molecular level, as well as the extent to which it is altered by PTI is unknown.In this proposal, we aim to characterize the molecular mechanisms that govern defense-related autophagy. We have generated substantial preliminary data that a regulator of defense-related autophagy machinery interacts with the PTI signaling components. Hence, we will specifically focus on investigating the molecular interplay between PTI and defense-related autophagy pathways to elucidate the molecular events leading to enhanced disease resistance. 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 defense-related autophagy machinery provides resistance to a diversity of important pathogens.