Thermosensation in skin-penetrating parasitic nematodes

项目摘要 皮肤穿透线虫，包括人类线虫Strongyloides stercoralis， 感染全球近十亿人的蛔虫。它们是肠道寄生虫， 胃肠道不适以及儿童生长发育迟缓和长期认知障碍。的感染 S.粪球菌对免疫抑制的个体是致命的。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， 了解寄生线虫如何对宿主发出的感觉信号作出反应。在这份提案中，我们将调查 寄生线虫对热的反应所有的哺乳动物都会散发热量，对许多哺乳动物来说， 寄生虫，包括线虫。我们将研究热如何触发寄生-宿主的两个不同步骤 相互作用：宿主寻找，土栖感染性幼虫主动寻找宿主进行感染的过程; 和激活，即感染性幼虫退出其发育停滞状态并恢复正常的过程。 进入宿主后的生长。首先，我们将对温度驱动的主机进行定量分析- S. Stercoralis（Aim 1）。其次，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S. stercoralis，使我们能够识别宿主寻找所需的基因， activation.总之，我们的研究结果将为感官反应如何塑造大脑提供基本的见解。 寄生线虫与宿主的相互作用。

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.