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Chemosensation in skin-penetrating parasitic nematodes

皮肤穿透性寄生线虫的化学感应

基本信息

批准号：
10623264
负责人：
ELISSA ANYON HALLEM
金额：
$ 51.26万
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：
2019-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10623264
关键词：
Ablation Adult Afferent Neurons Ancylostoma (genus)Animals Behavior CRISPR/Cas technology Caenorhabditis elegans Calcium Candidate Disease Gene Carbon Dioxide Cells Cessation of life Chemotaxis Child Complex Cues Culicidae Detection Development Enterobius Esthesia Gene Expression Profiling Generations Genes Genetic Grant Growth Helminths Hookworms Human Image Impaired cognition Infection Interneurons Knowledge Larva Lasers Life Life Cycle Stages Maps Mediating Molecular Morbidity - disease rate Mutagenesis Necator Nematoda Neurobiology Neurons Odors Parasites Parasitic nematode Penetration Persons Process Publishing Resource-limited setting Sensory Shapes Signal Pathway Skin Soil Source Strongyloides stercoralis Testing Work behavioral response chronic gastrointestinal distress experimental study gastrointestinal genetic manipulation insight interest neural neuromechanism novel novel strategies preference response sensory mechanism

项目摘要

PROJECT SUMMARY Skin-penetrating nematodes, including the human-parasitic threadworm Strongyloides stercoralis, infect nearly one billion people worldwide and are a major source of morbidity in low-resource settings. Infections can cause chronic gastrointestinal distress, stunted growth and cognitive impairment in children, and even death in the case of S. stercoralis infection. S. stercoralis has a complex life cycle that includes a parasitic generation inside the host and a free-living generation outside the host. In previous work, we showed that the detection of carbon dioxide (CO2) and host-emitted odorants is important for multiple stages of the S. stercoralis life cycle. Moreover, we showed that CO2 and many host-emitted odorants elicit life-stage-specific behavioral responses, such that the chemosensory preferences of the infective larvae are distinct from those of the non-infective life stages. However, the neural mechanisms that mediate these chemosensory responses have not yet been investigated. Here, we propose to elucidate the molecular, cellular, and circuit mechanisms of chemosensation in S. stercoralis. In Aim 1, we will elucidate the neural mechanisms that mediate CO2 response in S. stercoralis. We will also investigate how CO2 microcircuit function is modulated across life stages to generate life-stage- specific responses to CO2. In Aim 2, we will elucidate the neural mechanisms that mediate responses to host- emitted odorants in S. stercoralis. We will also investigate how olfactory microcircuit function is modulated across life stages. In Aim 3, we will address the molecular mechanisms of chemosensation. We will identify genes and signaling pathways that mediate responses to CO2 and host-emitted odorants in S. stercoralis. We will also identify molecular mechanisms that contribute to parasite-specific and life-stage-specific chemosensory responses. Taken together, our results will provide key insights into the chemosensory mechanisms that underlie the complex interactions of parasitic nematodes with their human hosts.

项目总结