Functional Characterization of Tsetse Odorant Receptors

采采蝇气味受体的功能表征

• 批准号: 9467917
• 负责人: Juan Sebastian Chahda
• 金额: $ 5.71万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9467917
• 关键词: Africa South of the Sahara; African; African Trypanosomiasis; Agriculture; Anatomy; Animals; Behavior; Bioinformatics; Cessation of life; Cues; Disease; Drosophila genus; Electron Microscopy; Electrophysiology (science); Family; Gene Family; Genes; Genetic; Genome; Goals; Hair; Human; In Situ Hybridization; Individual; Livestock; Mediating; Molecular; Neurons; Odorant Receptors; Odors; Olfactory Pathways; Olfactory Receptor Neurons; Organ; Pattern; Population; Poverty; Process; Sensory; Smell Perception; Surface; System; Transgenic Organisms; Trypanosomiasis; Tsetse Flies; Work; World Health Organization; avoidance behavior; base; disorder prevention; extracellular; in vivo; killings; member; mutant; nagana; novel; olfactory receptor; receptor; response; tool; transmission process; vector

Project Summary Transmission of trypanosomiasis by the tsetse fly remains a driver of poverty and disease in sub- Saharan Africa. There is no cure for trypanosomiasis and the most effective means of controlling trypanosomiasis has been to control the tsetse flies that transmit it, which has largely been done by exploitation of the tsetse olfactory system. Specialized tsetse traps and targets have been successful in reducing tsetse populations, and their efficacy is greatly enhanced by the use of attractive odorants. Synthetic tsetse repellents have also been very useful in the control of tsetse-borne disease, particularly in protecting livestock. Despite the reliance on tsetse olfactory cues to control the spread of trypanosomiasis, there is little understanding of the tsetse olfactory system. Here I aim to anatomically and functionally characterize the olfactory system of the savannah tsetse fly Glossina morsitans morsitans. This work will expand our understanding of the G. m. morsitans olfactory system on a genetic and molecular level. In the end, stable control over human and animal trypanosomiasis cannot be achieved without a detailed understanding of the tsetse olfactory system. The main olfactory organ of the tsetse fly is the antenna, which is covered with chemosensory hairs called sensilla. I characterized by electron microscopy the different types of sensilla that cover the surface and line the specialized cavities of the antenna. In order to better understand the molecular basis of olfaction in tsetse we sought to identify members of the G. m. morsitans Olfactory receptor (GmmOr) gene family. I performed bioinformatic analyses on the genome of G. m. morsitans and identified a family of 31 GmmOrs. In situ hybridization against several of the GmmOrs demonstrated expression of GmmOrs in specific subpopulations of olfactory receptor neurons in the antenna. For example, GmmOr42a and GmmOr7a are expressed in sensilla that line the sensory pit – a specialized cavity of the antenna that I hypothesize mediates host tracking. I aim to determine by In situ hybridization the expression pattern of the remaining 17 GmmOrs that have not been characterized. GmmOrs with validated expression in the antenna will be functionally analyzed using the Drosophila “empty neuron” system. The empty neuron system is based on a mutant antennal neuron, the empty neuron, that lacks endogenous odorant receptors and that does not respond to odors. GmmOrs can be systematically expressed in the empty neuron, and the odorant response profile that each individual receptor confers can be deduced by electrophysiological analysis. The functional response profiles of GmmOrs may uncover novel attractants and repellants to be used in ongoing trypanosomiasis control strategies.

项目摘要 采取锥虫病锥虫病的传播仍然是贫困和疾病的驱动力 撒哈拉非洲。无法治愈锥虫病，是控制的最有效手段 锥虫病一直是控制传输它的采采蝇，这在很大程度上是由 采取采摘嗅觉系统的开发。专业的采摘陷阱和目标已经成功 通过使用有吸引力的气味，可以大大提高采摘种群，并大大提高其效率。合成的 采取驱虫剂在控制采收疾病方面也非常有用，尤其是在保护方面 家畜。尽管采取采摘嗅觉提示可以控制锥虫病的传播，但几乎没有 了解采摘嗅觉系统。在这里，我旨在在解剖和功能上表征 Savannah Tsetse Fly Glossina Morsitans Morsitans的嗅觉系统。这项工作将扩大我们的 对G. M的理解。摩尔人嗅觉系统在遗传和分子水平上。最后，稳定 没有对人类和动物锥虫病的控制 采摘嗅觉系统。 采取蝇的主要嗅觉器官是天线，该天线被称为化学感应的头发覆盖 Sensilla。我以电子显微镜为特征 天线的专门城市。为了更好地了解采集中嗅觉的分子基础 我们试图确定G. M的成员。 Morritans嗅觉受体（GMMOR）基因家族。我表演了 对G. m的基因组的生物信息学分析。莫里特人并确定了一个31个gmmors的家庭。 与几个gmmors的原位杂交表明了gmmors在特定中的表达 天线中嗅觉受体神经元的亚群。例如，gmmor42a和gmmor7a是 在感觉坑中表达的感觉坑 - 我假设培养基的天线的专门驾驶室 主机跟踪。我的目标是通过原位杂交确定其余17 gmmors的表达模式 尚未表征的。在天线中具有验证表达的gmmors在功能上将是 使用果蝇“空神经元”系统分析。 空神经元系统基于缺乏内源性的突变触角神经元，空神经元 气味接收器，这对气味没有反应。 gmmors可以系统地在空的 神经元，以及每个接收器供认可以推论的气味响应概况 电生理分析。 Gmmors的功能响应曲线可能会发现新颖的吸引者，并且 驱虫剂用于正在进行的锥虫病控制策略。