Thermosensation in skin-penetrating parasitic nematodes

项目总结 穿透皮肤的线虫，包括人类线虫斯特氏线虫，是寄生的 感染全球近10亿人的蛔虫。它们是肠道寄生虫，会导致慢性 儿童的胃肠道不适以及发育迟缓和长期认知障碍。感染： 对于免疫抑制的人来说，严重的肺炎链球菌可能是致命的。尽管寄生虫造成的健康负担 线虫，其基本生物学的许多方面仍然知之甚少。特别是，令人惊讶的是， 了解寄生线虫如何对寄主发出的感官信号做出反应。在这份提案中，我们将调查 寄生线虫如何对高温做出反应。热是所有哺乳动物都会发出的，对许多哺乳动物来说是一种强烈的感官信号 寄生虫，包括线虫。我们将研究高温如何触发寄生虫宿主的两个不同步骤 相互作用：寻找寄主，寄生在土壤中的感染幼虫主动寻找寄主进行感染的过程； 和激活，感染的幼虫退出发育停滞状态并恢复的过程 进入寄主后生长。首先，我们将对温度驱动的主机进行定量分析- 龟纹夜蛾的寻找行为(目标1)。第二，我们将阐明分子和细胞机制。 这些行为的基础(目标2)。第三，我们将研究分子和细胞机制 加热触发激活(目标3)。这些实验将利用我们最近开发的CRISPR-CAS9 用于定向突变的系统，使我们能够识别寻找宿主所需的基因和 激活。总之，我们的结果将为感官反应如何塑造 寄生线虫与寄主的相互作用。

PROJECT SUMMARY Skin-penetrating nematodes, including the human threadworm Strongyloides stercoralis, are parasitic roundworms that infect nearly one billion people worldwide. They are intestinal parasites that cause chronic gastrointestinal distress as well as stunted growth and long-term cognitive impairment in children. Infections with S. stercoralis can be fatal for immunosuppressed individuals. Despite the health burden caused by parasitic nematodes, many aspects of their basic biology remain poorly understood. In particular, remarkably little is known about how parasitic nematodes respond to host-emitted sensory cues. In this proposal, we will investigate how parasitic nematodes respond to heat. Heat is emitted by all mammals and is a robust sensory cue for many parasites, including nematodes. We will investigate how heat triggers two different steps of the parasite-host interaction: host seeking, the process whereby the soil-dwelling infective larvae actively search for hosts to infect; and activation, the process whereby the infective larvae exit their developmentally arrested state and resume growth after entering the host. First, we will conduct a quantitative analysis of the temperature-driven host- seeking behaviors of S. stercoralis (Aim 1). Second, we will elucidate the molecular and cellular mechanisms that underlie these behaviors (Aim 2). Third, we will investigate the molecular and cellular mechanisms by which heat triggers activation (Aim 3). These experiments will leverage our recent development of a CRISPR-Cas9 system for targeted mutagenesis in S. stercoralis, allowing us to identify genes required for host seeking and activation. Together, our results will provide fundamental insights into how sensory responses shape the interactions of parasitic nematodes with their hosts.