EAGER: Understanding the mechanisms of action of two diverse antifungal plant defensins

由真菌病原菌引起的农作物病害造成了巨大的经济损失，威胁着全世界的粮食安全。化学杀菌剂、轮作和自然遗传抗性不能提供对这些疾病的充分控制。目前，真菌病仍然是减少作物产量收获前和收获后损失的关键战场。植物产生大量的抗真菌多肽，作为一套复杂的多层次防御策略的一部分。被称为防御素的富含半胱氨酸的小分子抗真菌多肽具有很强的广谱抗真菌活性。该项目旨在深入了解从模式豆科植物中提取的两种截然不同的抗真菌防御素的抗真菌活性的机制。这一知识将有助于在农业中将这些多肽用作有效和可持续的生物杀菌剂。重要的是，该项目提供了培养博士后和未被充分代表的少数民族本科生的机会。学生和博士后将接受蛋白质生物化学、分子生物学和真菌细胞生物学方面的广泛培训，以更好地为未来的科学生涯做好准备。还将向圣路易斯地区表现不佳的公立学校的K-5级教师提供研究经验，使他们能够将在课堂上获得的知识与在实验室进行的研究联系起来。本项目的目标是阐明从模式豆科植物紫花苜蓿中提取的两种植物防御素具有强大的抗真菌活性的分子机制。这些防御素在低浓度下杀死经济上重要的真菌病原体。这些多肽与真菌病原体质膜中的生物活性磷脂结合，每个防御素的抗真菌活性是其目标磷脂(S)的功能。该项目将揭示控制磷脂特异性和对这些肽的识别的序列基序。这些多肽进入小麦真菌病原菌禾谷镰刀菌细胞质的分子机制将得到鉴定。此外，将采用系统的生化和蛋白质组学方法来确定这种病原体中这些多肽的细胞内蛋白质靶标。完整的该真菌基因组序列及其功能基因组数据库将为研究提供必要的资源。从机理上详细了解这些多肽的抗真菌作用，将能够更现实地预测它们在宿主植物复杂环境中的抗真菌活性，并设计出更有效的疾病控制多肽。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Crop diseases caused by fungal pathogens lead to tremendous economic losses and threaten food security worldwide. Chemical fungicides, crop rotation and natural genetic resistance don't provide adequate control of these diseases. At present, fungal diseases remain a key battlefront for reducing pre-and post-harvest losses of crop yield. Plants produce a large number of antifungal peptides as part of a complex set of multi-tiered defense strategies. Small cysteine-rich antifungal peptides called defensins exhibit potent broad-spectrum antifungal activity. This project seeks insight into the mechanisms that govern antifungal activity of two very different antifungal defensins from a model legume. This knowledge will facilitate use of these peptides as effective and sustainable biological fungicides in agriculture. Importantly, this project provides the opportunity to train the postdoctoral fellow and under-represented minority undergraduate students. Students and the postdoctoral fellow will be broadly trained in protein biochemistry, molecular biology and fungal cell biology so as to better prepare them for future careers in science. Research experiences will also be provided to K-5 teachers from low performing public schools in the St Louis area so that they can make connections between knowledge acquired in the classroom and research conducted in the laboratory. The goal of this project is to elucidate molecular mechanisms governing the potent antifungal activity of two plant defensins from a model legume Medicago truncatula. These defensins kill economically important fungal pathogens at low concentrations. These peptides bind to bioactive phospholipids in the plasma membrane of a fungal pathogen and antifungal activity of each defensin is a function of which phospholipid(s) it targets. This project will uncover sequence motifs governing phospholipid specificity and recognition for these peptides. Molecular mechanisms by which these peptides gain access to the cytoplasm of a wheat fungal pathogen Fusarium graminearum will be identified. In addition, systematic biochemical and proteomics approaches will be undertaken to identify intracellular protein targets of these peptides in this pathogen. The fully completed and annotated genome sequence of this fungus and its functional genomics database will provide essential resources for the research. Detailed mechanistic understanding of the antifungal action of these peptides will enable a more realistic prediction of their antifungal activity in a complex environment of the host plant and design of more effective peptides for disease control.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.