Molecular basis of olfaction in Tsetse fly

项目摘要 采采蝇将锥虫病传播给非洲约38个国家的人类和动物。 在人类中，这种疾病被称为非洲睡眠病。没有疫苗可以预防，70 数百万人处于危险之中。在动物中，这种疾病被称为Nagana， 撒哈拉以南非洲的负担。预防这些疾病最有效的方法是控制 传播它们的采采蝇，嗅觉陷阱特别有用。采采蝇发现 它们主要通过嗅觉来吸引人类和动物宿主。更好地了解采采蝇 嗅觉系统可能会导致更好的控制手段。 这项建议的重点是采采蝇Glossina morsitans的气味受体， 优先考虑在采采蝇触角中表达特征良好的受体。的 实验计划要求分析这些GmmOr受体的反应谱，这将 通过130种气味的电生理学筛选来完成。这些气味剂中的许多是 人类或动物宿主散发物。该面板包括一组气味剂， 对果蝇黑腹果蝇或疟疾蚊子冈比亚按蚊进行了测试， 便于比较G. Morsitans受体与这些物种的受体库。的 GmmOr受体将在体内表达系统"空神经元"系统中进行测试。我们将 确定受体是否广泛或狭隘的调整，以及是否有任何反应，低 宿主气味剂的浓度。引起强烈反应的气味剂将进行行为测试， 判断它们是否是G. Morsitans。气味能引起强烈的吸引力 在低浓度下的响应可用作捕获剂。嗅觉行为也会 作为性别和喂养史的功能检查;几个关键的假设将进行测试。 该提案应提供第一个详细的功能特性的气味受体， 采采蝇该实验计划旨在产生关于嗅觉的有价值的新信息 这只苍蝇的反应。这项研究还可以确定用于控制采采蝇的新药剂， 它携带的疾病。 该提案将提供电生理学、分子生物学、遗传学和载体方面的培训。 生物学博士Shimaa Ebrahim，谁在这些主题很少或根本没有经验。该项目将有利于 从一个包含大量昆虫嗅觉专业知识的环境中。此外，耶鲁是一个 世界采采蝇研究中心之一

PROJECT SUMMARY The tsetse fly transmits trypanosomiasis to humans and animals across ~38 countries of Africa. In humans the disease is called African Sleeping Sickness. There is no vaccine to prevent it, and 70 million people are at risk. In animals the disease is called nagana, and it imposes a major economic burden on sub-Saharan Africa. The most effective means of preventing these diseases is to control the tsetse flies that transmit them, and olfactory traps have been particularly useful. Tsetse flies find their human and animal hosts largely through olfactory cues. Better understanding of the tsetse olfactory system may lead to better means of control. This proposal focuses on odorant receptors of the tsetse fly Glossina morsitans, with highest priority accorded to receptors whose expression is well characterized in the tsetse antenna. The experimental plan calls for an analysis of the response profiles of these GmmOr receptors, which will be accomplished by an electrophysiological screen of 130 odorants. Many of these odorants are human or animal host emanations. The panel includes a set of odorants that have previously been tested against the fruit fly Drosophila melanogaster or the malaria mosquito Anopheles gambiae, to facilitate comparison of the G. morsitans receptors with the receptor repertoires of these species. The GmmOr receptors will be tested in an in vivo expression system, the "empty neuron" system. We will determine whether the receptors are broadly or narrowly tuned, and whether any respond to low concentrations of host odorants. Odorants that elicit strong responses will be tested behaviorally to determine whether they are strong attractants of G. morsitans. Odorants that elicit a strong attractive response at low concentrations may be useful as trapping agents. Olfactory behavior will also be examined as a function of sex and feeding history; several key hypotheses will be tested. The proposal should provide the first detailed functional characterization of odorant receptors in tsetse. The experimental plan is designed to produce valuable new information about the olfactory responses of this fly. The study could also identify new agents useful in controlling tsetse and the diseases that it carries. The proposal will provide training in electrophysiology, molecular biology, genetics, and vector biology to Dr. Shimaa Ebrahim, who has little or no experience in these topics. The project will benefit from an environment that contains a great deal of expertise in insect olfaction. Moreover, Yale is one of the world's centers of tsetse research.