Mechanisms of siRNA mediated broad-spectrum resistance to eukaryotic pathogens

siRNA介导的对真核病原体广谱抗性的机制

• 批准号: BB/W00691X/1
• 负责人: Wenbo Ma
• 金额: $ 63.37万
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW00691X%2F1
• 关键词: Mechanisms; siRNA; mediated; broad; spectrum

The sustainability of agriculture is threatened by pathogens, which cause substantial damage to crop yield and food safety. Although plants have evolved a myriad of immunity mechanisms to defend themselves, successful pathogens can overcome this surveillance system and cause disease. The dynamic interactions between virulence factors of pathogens and the innate immunity of a host determine whether disease will occur. To protect crops from pathogens, it is essential to identify new defense mechanisms and understand the molecular basis of their functions in order to design innovative approaches to elevate disease resistance.Recent research discovered a small RNA (sRNA)-based defense mechanism in plants. Small RNAs are short RNA molecules (usually 20-24 nucleotide in length) that guide the inhibition of target gene expression based on sequence complementarity. Gene silencing or RNA interference (RNAi) triggered by sRNAs is a fundamental and universal regulatory mechanism in eukaryotes that impacts a wide range of biological processes. During host-pathogen interactions, sRNAs produced from one organism have been observed to affect gene expression in the opposing organism. Although this "trans-species" RNAi is an exciting concept that represents a new perspective in host-pathogen arms race, many challenges remain. A fundamental challenge is to identify which sRNAs in plant execute target genes silencing in invading pathogens. Furthermore, direct experimental evidence demonstrating gene silencing guided by plant sRNAs in invading pathogens is lacking. These major gaps of knowledge need to be filled before sRNAs can be effectively deployed in disease control. In this project, we aim to investigate the mechanism underlying pathogen gene silencing by plant sRNAs during natural infection. This project builds on our recent discoveries suggesting that a specific family of plant sRNAs confer resistance to a filamentous eukaryotic pathogen. These sRNAs are produced from a unique biogenesis pathway that leads to the generation of a diverse sRNA pool, which has the potential to silence target genes in a broad range of eukaryotic pathogens. As such, we identified a designated family of "antimicrobial" sRNAs that may confer broad-spectrum resistance.We will use a combination of genetics, molecular biology, biochemistry, synthetic biology, and plant pathology approaches and the model Arabidopsis thaliana-Phytophthora capsici pathosystem to investigate the function of this specific family of sRNAs in plant immunity. Trans-species gene silencing will be monitored by detection of plant sRNAs in the protein complex that guides gene silencing in the invading pathogen. We will test the hypothesis that this novel defense mechanism confers broad-spectrum resistance by examining plant mutants defective in sRNA production for susceptibility to additional eukaryotic pathogens. We will further explore how sRNA-spawning sequences could be edited to produce bespoke sRNAs that can increase pathogen gene silencing and elevate resistance. The outcome of this project will be to provide novel insight into fundamental principles of plant immunity and offer new opportunities for the development of sustainable disease control strategies with far-reaching implications to a broad range of pathosystems.

农业的可持续性受到病原体的威胁，这对农作物产量和食品安全造成了重大损害。尽管植物已经发展出多种免疫机制来捍卫自己，但成功的病原体可以克服这种监视系统并引起疾病。病原体的毒力因子与宿主的先天免疫之间的动态相互作用决定了是否发生疾病。为了保护农作物免受病原体的影响，必须确定新的防御机制并了解其功能的分子基础，以设计创新的方法来提高疾病的耐药性。小RNA是短的RNA分子（通常长度为20-24个核苷酸），它们基于序列互补性指导靶基因表达的抑制。 SRNA触发的基因沉默或RNA干扰（RNAI）是真核生物中一种基本和普遍的调节机制，影响了广泛的生物学过程。在宿主 - 病原体相互作用期间，已经观察到从一种生物体产生的SRNA会影响相反生物体的基因表达。尽管这种“跨性别” RNAi是一个令人兴奋的概念，代表了宿主 - 病原体军备竞赛的新观点，但仍然存在许多挑战。一个基本的挑战是确定植物中哪些SRNA在入侵病原体中执行靶基因沉默。此外，缺乏在入侵病原体中以植物SRNA为指导的基因沉默的直接实验证据。在SRNA可以有效地部署在疾病控制中之前，需要填补这些主要知识差距。在该项目中，我们旨在研究自然感染期间植物SRNA沉默的病原体基因沉默的机制。该项目以我们最近的发现为基础，表明特定的植物SRNA家族赋予对丝状真核病病原体的抗性。这些SRNA是由独特的生物发生途径产生的，该途径会导致多种sRNA池的产生，该池有可能在广泛的真核病原体中静音靶基因。 As such, we identified a designated family of "antimicrobial" sRNAs that may confer broad-spectrum resistance.We will use a combination of genetics, molecular biology, biochemistry, synthetic biology, and plant pathology approaches and the model Arabidopsis thaliana-Phytophthora capsici pathosystem to investigate the function of this specific family of sRNAs in plant immunity.跨物种基因沉默将通过检测蛋白质复合物中的植物SRNA的检测来监测，该蛋白质复合物引导基因沉默在入侵的病原体中。我们将检验以下假设：这种新型的防御机制通过检查植物突变体在SRNA产生中有缺陷的敏感性，以使其对其他真核病原体的敏感性进行了启发。我们将进一步探讨如何可以编辑SRNA源性序列以产生定制的SRNA，从而增加病原体基因沉默并提高耐药性。该项目的结果将是为植物免疫的基本原理提供新的见解，并为开发可持续疾病控制策略的新机会，对广泛的病态系统具有深远的影响。