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

剖析免疫信号和防御相关自噬之间的功能联系

• 批准号: BB/T006102/1
• 负责人: Tolga Bozkurt
• 金额: $ 59.86万
• 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: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT006102%2F1
• 关键词: Dissecting; functional; link; between; immune

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.

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。丝状真菌属植物病原体包括卵菌和真菌，它们引起最具破坏性的作物病害，并对我们的粮食安全构成重大威胁。由爱尔兰饥荒病原体致病疫霉引起的晚疫病是马铃薯和番茄的致命疾病。由晚疫病引起的爆发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。对该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。新出现的菌株对杀真菌剂敏感性的降低使情况恶化。一个可持续的替代方案是通过基因提高抗性，这是一种具体而有针对性的方法，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基因工具包，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防御寄生虫。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分子都不同。这些表面受体的激活触发免疫-称为模式触发免疫，或PTI。这启动了复杂的信号级联，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中的作用是公认的。然而，导致PTI活化后抗性增强的分子机制尚未完全理解。尽管如此，成功地将表面免疫传感器从模式植物物种转移到农作物上，引发了人们对理解PTI内部机制的新兴趣。与其他丝状植物病原体一样，晚疫病病原体通过称为吸器的指状延伸侵入宿主细胞，通过吸器分泌免疫破坏因子以控制入侵细胞。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来防止进一步感染。虽然PTI涉及防御化合物的生产，部署对病原体吸器，PTI调节靶向的细胞运输途径的病原体接口的程度是未知的。所有植物和动物都经历一个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构建模块。最近，我们自己和其他人发现，自噬被激活有助于防御致病疫霉，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回收作用更复杂。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，以及它在多大程度上被PTI改变是未知的。我们已经产生了大量的初步数据，防御相关的自噬机制的调节与PTI信号组件相互作用。因此，我们将特别关注研究PTI和防御相关的自噬途径之间的分子相互作用，以阐明导致增强抗病性的分子事件。通过解密这些机制，我们将产生基础知识，这将有助于重塑植物免疫系统，提高病原体抗性。这项工作将具有深远的影响，因为防御相关的自噬机制提供了对多种重要病原体的抵抗力。

项目成果

AF2-multimer guided high accuracy prediction of typical and atypical ATG8 binding motifs

• DOI: 10.1101/2022.09.25.509395
• 发表时间: 2022-09
• 期刊: bioRxiv
• 作者: Tarhan Ibrahim;Virendrasinh Khandare;Federico G. Mirkin;Yasin Tumtas;D. Bubeck;T. Bozkurt

AlphaFold2-multimer guided high-accuracy prediction of typical and atypical ATG8-binding motifs.

• DOI: 10.1371/journal.pbio.3001962
• 发表时间: 2023-03
• 期刊: PLoS biology
• 影响因子: 9.8

Time-Resolved Chemical Phenotyping of Whole Plant Roots with Printed Electrochemical Sensors and Machine Learning

• DOI: 10.1101/2023.03.09.531921
• 发表时间: 2023-03
• 期刊: bioRxiv
• 作者: Philip Coatsworth;Y. Cotur;Atharv Naik;Tarek Asfour;A. Collins;S. Olenik;L. Gonzalez-Macia;T. Bozkurt;Dai-Yin Chao;Firat Güder

Resurrection of plant disease resistance proteins via helper NLR bioengineering.

• DOI: 10.1126/sciadv.adg3861
• 发表时间: 2023-05-03
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Contreras, Mauricio P.;Pai, Hsuan;Selvaraj, Muniyandi;Toghani, AmirAli;Lawson, David M.;Tumtas, Yasin;Duggan, Cian;Yuen, Enoch Lok Him;Stevenson, Clare E. M.;Harant, Adeline;Maqbool, Abbas;Wu, Chih-Hang;Bozkurt, Tolga O.;Kamoun, Sophien;Derevnina, Lida
• 通讯作者: Derevnina, Lida