Targeting a conserved structural module in Phytophthora effectors for disease resistance

到 2050 年，人口预计将达到 97 亿。植物病害造成的农作物损失威胁着养活快速增长的人口这一迫在眉睫的挑战。疫霉属是丝状真核病原体，可引起多种破坏性植物病害，包括导致爱尔兰大饥荒期间超过 150 万人死亡的马铃薯晚疫病和导致数百万棵林木死亡的橡树突然死亡。作为一类具有历史和现实意义的病原菌，防治疫病是农业的一项重要使命和重大挑战。该项目旨在阐明疫霉菌发病机制的分子机制，并根据这些知识，在马铃薯和其他重要作物中培养持久的抗性。因此，该项目不仅将深入了解植物与病原体相互作用的基础生物学，而且将直接使美国农业受益。该项目更广泛的影响包括为博士后研究人员、研究生和本科生提供遗传学、生物化学和分子生物学尖端技术的跨学科培训。它还将接触马铃薯种植者等利益相关者，向他们通报有关提高作物抗病性的最新发现和技术。该项目由 NSF 和 NIFA/USDA 联合资助。疫霉属利用大量毒力蛋白（称为效应子）来促进感染。效应器直接操纵植物细胞过程，在与宿主的军备竞赛中发挥着重要作用。全面了解效应器功能及其多样化和适应的分子机制对于实现持久耐药性至关重要。该项目基于一个令人兴奋的发现，即大量疫霉菌效应子含有保守结构模块的串联重复，该模块可耐受高水平的序列灵活性。该项目将结合遗传、分子生物学和生化方法，检验这一假设，即该保守模块可能作为基本构件，使效应器能够进化出新的活性，从而促进毒力。此外，针对该保守模块的植物防御机制可能能够有效抵抗破坏性疫霉病。该项目的目标是：1）阐明这一保守结构模块在疫霉效应子功能和进化中的作用； 2) 鉴定识别野生马铃薯种疫霉效应子保守结构的抗性基因。该项目的成果将在对疫霉病的基本认识方面取得重大进展。该项目是转化性的，因为从野生马铃薯种质中鉴定出的抗性基因可以被纳入优良品种中，以赋予对晚疫病的抗性。这些基因还可用于赋予对多种疫霉属物种的可持续抵抗力。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The human population is projected to reach 9.7 billion by 2050. The looming challenge of feeding the rapidly growing population is threatened by crop losses from plant diseases. Phytophthora are filamentous eukaryotic pathogens that cause numerous destructive plant diseases including potato late blight that was responsible for over 1.5 million deaths during the Great Irish Famine and the sudden oak death that has killed millions of forest trees. As a group of pathogens with both historical and current importance, battling Phytophthora diseases is an important mission and a major challenge in agriculture. This project aims to elucidate the molecular mechanisms underlying Phytophthora pathogenesis and, based on this knowledge, develop durable resistance in potato and other important crops. As such, this project will not only provide insight into basic biology of plant-pathogen interactions but also directly benefit US Agriculture. Broader impacts of this project include providing interdisciplinary training to postdoctoral researchers, graduate students and undergraduate students on cutting-edge technologies of genetics, biochemistry and molecular biology. It will also reach out to stakeholders, such as potato growers, by informing them with the latest findings and technologies on developing disease resistance in crops.This project is funded jointly by NSF and by NIFA/USDA.Phytophthora employs a large arsenal of virulence proteins, called effectors, to facilitate infection. Directly manipulating plant cellular processes, effectors play an essential role in the arms race with the hosts. An overall understanding of effector functions and the molecular mechanisms underlying their diversification and adaptation is critical to implement durable resistance. This project is based on the exciting discovery that a large number of Phytophthora effectors contain tandem repeats of a conserved structural module, which tolerates a high level of sequence flexibility. Using a combination of genetic, molecular biology, and biochemical approaches, this project will test the hypothesis that this conserved module may serve as a basic building block to enable effector evolution for novel activities and thereby contributing to virulence. Furthermore, plant defense mechanism targeting this conserved module may enable effective resistance against the destructive Phytophthora diseases. The goals of this project are: 1) elucidating the role of this conserved structural module in Phytophthora effector function and evolution; and 2) identifying resistance genes that recognize this conserved structure of Phytophthora effectors from wild potato species. The outcome of this project will make major advancement in the fundamental understanding of Phytophthora diseases. This project is translational because the resistance genes identified from wild potato accessions may be incorporated into elite varieties in order to confer resistance to late blight. These genes could also be used to confer sustainable resistance to a broad variety of Phytophthora species.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.