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在世界范围内造成了巨大的经济损失，并威胁着粮食安全。化学杀菌剂、轮作和天然遗传抗性不能充分控制这些疾病。目前，真菌病害仍然是减少作物收获前后产量损失的一个关键战线。植物产生大量的抗真菌肽作为一套复杂的多层次防御策略的一部分。富含半胱氨酸的小分子抗真菌肽防御素具有广谱的抗真菌活性。该项目旨在深入了解两种非常不同的抗真菌防御素的抗真菌活性的机制。这些知识将促进这些肽在农业中作为有效和可持续的生物杀真菌剂的使用。重要的是，该项目提供了培训博士后研究员和代表性不足的少数民族本科生的机会。学生和博士后研究员将在蛋白质生物化学，分子生物学和真菌细胞生物学方面进行广泛的培训，以便更好地为未来的科学事业做好准备。研究经验也将提供给K-5教师从低性能的公立学校在圣刘易斯地区，使他们能够在课堂上获得的知识和在实验室进行的研究之间的连接。 本项目的目的是阐明两种来自模式豆科植物蒺藜苜蓿的植物防御素的有效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。这些肽与真菌病原体的质膜中的生物活性磷脂结合，并且每种防御素的抗真菌活性是其靶向的磷脂的功能。该项目将揭示这些肽的磷脂特异性和识别的序列基序。这些肽进入小麦真菌病原体禾谷镰刀菌细胞质的分子机制将被确定。此外，系统的生物化学和蛋白质组学的方法将进行识别这些肽在这种病原体的细胞内蛋白质的目标。该真菌基因组序列的完整和注释及其功能基因组学数据库将为研究提供必要的资源。详细了解这些肽的抗真菌作用的机理将使其在宿主植物的复杂环境中的抗真菌活性的预测更加现实，并设计出更有效的肽用于疾病控制。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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.