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Thermosensation in skin-penetrating parasitic nematodes

皮肤穿透寄生线虫的热感觉

基本信息

批准号：
10448256
负责人：
ELISSA ANYON HALLEM
金额：
$ 62.84万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-22 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10448256
关键词：
Ablation Adult Afferent Neurons Animals Behavior Behavioral Biological Assay Biology Body Temperature CRISPR/Cas technology Calcium Candidate Disease Gene Cells Child Clustered Regularly Interspaced Short Palindromic Repeats Cues Culicidae Development Enterobius Environment Exposure to Funding Funding Agency Future Gene Expression Profiling Genes Goals Growth Health Hookworms Human Image Impaired cognition In Vitro Individual Infection Intestinal parasite Larva Lasers Life Mammals Mediating Molecular Molecular Genetics Morbidity - disease rate Mutagenesis Necator americanus Nematoda Neurobiology Neurons Old World Hookworm Parasites Parasitic nematode Penetration Persons Process Research Resource-limited setting Sensory Shapes Signal Pathway Skin Soil Strongyloides stercoralis System Temperature Testing Work behavioral response chronic gastrointestinal distress experimental study functional adaptation gastrointestinal genetic manipulation immunosuppressed insight neuromechanism response

项目摘要

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.

项目总结