Mechanisms of carbon dioxide avoidance in parasitic nematodes

描述(申请人提供)：寄生线虫是世界范围内一个主要的健康问题，目前预防或消除线虫感染的战略是不够的。一种可能的控制策略是干扰线虫定位宿主的能力。我研究的长期目标是更好地了解寄生线虫如何定位它们的宿主，使用自由生活的线虫秀丽线虫和昆虫寄生线虫Heterorhabditis bliophora和Steinenema carpocapsae作为人类寄生线虫的模型。二氧化碳是许多寄生线虫寻找寄主的重要线索，但对线虫对二氧化碳的反应机制知之甚少。这项提议的总体目标是加深我们对寄生线虫如何应对二氧化碳的理解。我已经证明线虫表现出急性的二氧化碳回避，我已经确定了这种反应所需的神经元和信号通路。我还发现，在细菌藻中，类似的神经元介导了二氧化碳的吸引。我现在将使用分子、遗传和神经生物学方法进一步阐明介导线虫二氧化碳反应的信号通路和神经网络。我将测试一个假设，即在寄生线虫中调节二氧化碳反应的神经回路与在自由生活的线虫中调节二氧化碳反应的神经回路相似，但包含反映寄生虫寻找宿主要求的修饰。寄生线虫在世界范围内造成广泛的发病率和死亡率。更好地了解寄生线虫是如何找到和感染宿主的，将有助于开发预防线虫感染的新策略。

DESCRIPTION (provided by applicant): Parasitic nematodes are a major health concern worldwide, and current strategies for preventing or eliminating nematode infections are insufficient. One possible control strategy is to interfere with the ability of nematodes to locate their hosts. The long-term goal of my research is to better understand how parasitic nematodes locate their hosts, using the free-living nematode C. elegans and the insect-parasitic nematodes Heterorhabditis bacteriophora and Steinernema carpocapsae as models for human-parasitic nematodes. Carbon dioxide is an important host-seeking cue for many parasitic nematodes, yet little is known about the mechanism of CO2 response in nematodes. The overall goal of this proposal is to further our understanding of how parasitic nematodes respond to CO2. I have shown that C. elegans displays acute CO2 avoidance, and I have identified neurons and signaling pathways that are required for this response. I have also found that analogous neurons mediate CO2 attraction in H. bacteriophora. I will now further elucidate the signaling pathways and neural networks that mediate CO2 response in nematodes using molecular, genetic, and neurobiological approaches. I will test the hypothesis that the neural circuits that mediate CO2 response in parasitic nematodes are similar to the neural circuits that mediate CO2 response in free-living nematodes, but contain modifications that reflect the host-seeking requirements of parasites. Parasitic nematodes cause extensive morbidity and mortality worldwide. A better understanding of how parasitic nematodes find and infect their hosts will enable the development of new strategies for preventing nematode infections.