Mechanisms of carbon dioxide avoidance in parasitic nematodes

描述（由申请方提供）：寄生线虫是全球范围内的主要健康问题，目前预防或消除线虫感染的策略不足。一种可能的控制策略是干扰线虫定位其宿主的能力。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，利用自由生活的线虫C。elegans和昆虫寄生线虫Heterorhabditis bacteriophora和Steinernema carpocapsae作为人类寄生线虫的模型。CO2是许多寄生线虫寻找寄主的重要信号，但线虫对CO2的反应机制尚不清楚。该提案的总体目标是进一步了解寄生线虫对CO2的反应。我已经证明了C。线虫表现出急性CO2回避，我已经确定了这种反应所需的神经元和信号通路。我还发现类似的神经元介导H中的CO2吸引力。细菌门。我现在将进一步阐明信号通路和神经网络介导的CO2反应线虫使用分子，遗传和神经生物学的方法。我将测试的假设，介导的寄生线虫的CO2反应的神经回路是类似的神经回路，介导的CO2反应在自由生活的线虫，但包含修改，反映主机寻求要求的寄生虫。寄生线虫在世界范围内引起广泛的发病率和死亡率。更好地了解寄生线虫如何找到并感染宿主，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.