Molecular basis of olfaction in Tsetse fly

采采蝇嗅觉的分子基础

• 批准号: 10066218
• 负责人: Shimaa abdelsalam mohamed Ebrahim
• 金额: $ 6.93万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10066218
• 关键词: Africa; Africa South of the Sahara; African; African Trypanosomiasis; Animal Diseases; Animals; Anopheles gambiae; Behavior; Biology; Blood; CRISPR/Cas technology; Canis familiaris; Cattle; Code; Complex; Country; Cues; Culicidae; Development; Disease; Distant; Drosophila genus; Drosophila melanogaster; Economic Burden; Electrophysiology (science); Environment; Feeds; Female; Fruit; Genes; Genetic Vectors; Human; Impairment; In Situ Hybridization; Incidence; Insecta; Larva; Lead; Mammals; Measures; Molecular; Molecular Biology; Neurons; New Agents; Odorant Receptors; Odors; Olfactory Pathways; Operating System; Operative Surgical Procedures; Panthera leo; Partner in relationship; Pheromone; Pheromone Receptors; Phylogenetic Analysis; Physiological; Plants; Receptor Gene; Recording of previous events; Research; Risk; Smell Perception; System; Testing; Training; Transgenic Organisms; Trypanosomiasis; Tsetse Flies; Vaccines; Zebra; base; behavior test; behavioral response; design; egg; experience; feeding; fly; genome editing; human disease; in vivo; insight; interest; malaria mosquito; male; mutant; nagana; offspring; pregnant; prevent; receptor; response; sex

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.

项目摘要 采采蝇向约38个非洲国家 /地区的人类和动物进行锥虫病传播。 在人类中，这种疾病被称为非洲熟睡。没有疫苗可以防止它，还有70个 百万人处于危险之中。在动物中，该疾病被称为长纳（Nagana），它施加了主要的经济 撒哈拉以南非洲的负担。防止这些疾病的最有效方法是控制 发射它们的采采蝇和嗅觉陷阱特别有用。采摘苍蝇发现 他们的人类和动物主要通过嗅觉提示主持。更好地理解采摘 嗅觉系统可能会导致更好的控制手段。 该提案重点是采用TSETSE Fly Glossina Morsitans的气味受体 优先级是受体表达在采收天线中表现良好的受体。这 实验计划要求分析这些GMMOR受体的响应曲线，这将 可以通过130种气味剂的电生理筛选来完成。这些气味中有许多是 人类或动物宿主的散发。该面板包括一组以前曾经的气味 针对果蝇果蝇或疟疾蚊子的果蝇测试， 促进G. Morsitans受体与这些物种的受体曲目进行比较。这 GMMOR受体将在体内表达系统（“空神经元”系统中测试。我们将 确定受体是广泛还是狭窄的调谐，以及是否对低反应 宿主气味的浓度。引起强烈反应的气味将在行为上测试 确定它们是否是G. Morsitans的强大吸引者。引起强大吸引力的气味 低浓度下的反应可能是捕获剂。嗅觉行为也将是 被检查是性别和喂养史的函数；将测试几个关键假设。 该提案应提供第一个详细的气味受体功能表征 采取。该实验计划旨在生成有关嗅觉的有价值的新信息 这苍蝇的反应。该研究还可以确定有助于控制采集和的新药物 它带来的疾病。 该提案将提供电生理学，分子生物学，遗传学和载体的培训 对Shimaa Ebrahim博士的生物学，他在这些主题上几乎没有经验。该项目将受益 从包含昆虫嗅觉的专业知识的环境中。而且，耶鲁是一个 世界采集研究中心。