EAPSI: Determining host seeking through olfaction in the nematode Parastrongyloides trichosuri

人类、动物和植物的寄生线虫是经济损失和与健康相关的困难的主要来源。仅对人类健康的影响就是惊人的。目前的估计表明，全球有近10亿人患有寄生性线虫感染。尽管线虫很普遍，但我们对寄生线虫如何找到和感染它们合适的生物宿主的了解仍然很差。嗅觉被广泛认为是寻找寄主的一个重要方面，因为它是最有可能赋予物种特异性的感觉通道。这个项目将阐明寄生线虫在多大程度上依赖宿主散发的气味来寻找和感染宿主。这项研究将在澳大利亚墨尔本的拉特洛比大学与全球线虫遗传学领先者沃里克·格兰特博士合作进行。格兰特博士还在一种独特的寄生线虫--天花粉寄生线虫--方面拥有无与伦比的专业知识，这种线虫的原生宿主是澳大利亚负鼠。由于无法开发遗传上易驯化的模式物种，寄生线虫的研究工作一直受到阻碍。该项目的目标是开发一种寄生于澳大利亚负鼠的寄生线虫天花粉寄生线虫，作为气味驱动的寄主寻找和嗅神经回路遗传分析的模型。在寄生线虫中，天花粉原虫是唯一一种适合体外培养、遗传操作和转基因的线虫。该项目将专注于对天花粉蛋白进行定量行为分析、激光和遗传消融分析以及钙成像。该项目旨在深入了解寄生线虫定位宿主感染的细胞和分子机制。通过确定促进寄主寻找的特定寄主气味和行为的潜在神经基础，这项研究将促进开发新的策略来对抗线虫感染。该NSF EAPSI奖是与澳大利亚科学院合作资助的。

Parasitic nematodes of humans, animals, and plants are major sources of economic loss and health-related hardship. The impact on human health alone is staggering. Current estimates suggest that nearly 1 billion people globally harbor a parasitic nematode infection. Despite their prevalence, our understanding of how parasitic nematodes find and infect their appropriate biological hosts remains poorly characterized. Olfaction is widely thought to be an important aspect of host seeking, since it is the sensory modality most likely to confer species-specificity. This project will elucidate the extent to which parasitic nematodes rely on host-emitted odors to find and infect a host. This research will be conducted at La Trobe University in Melbourne, Australia in collaboration with Dr. Warwick Grant, a global leader on nematode genetics. Dr. Grant also has unparalleled expertise with a unique parasitic nematode, Parastrongyloides trichosuri, whose native hosts are Australian possums. Research efforts in parasitic nematodes have been hampered by an inability to develop genetically tractable model species. The goal of this project is to develop Parastrongyloides trichosuri, a parasitic nematode of the Australian possum, as a model for odor-driven host seeking and the genetic analysis of olfactory neural circuits. Among parasitic nematodes, P. trichosuri is uniquely amenable to in vitro culturing, genetic manipulation, and transgenesis. This project will focus on conducting quantitative behavioral analysis, laser and genetic ablation analysis, and calcium imaging of P. trichosuri. The project aims to gain insight into the cellular and molecular mechanisms by which parasitic nematodes locate hosts to infect. By determining the host-specific odors that promote host seeking, and the underlying neural basis for the behavior, this study will facilitate development of new strategies to combat nematode infection. This NSF EAPSI award is funded in collaboration with the Australian Academy of Science.