Tsetse Fecundity Reduction for Trypanosomiasis Control

描述（由申请人提供）：本申请的重点是确定采采蝇生殖生理的分子靶点，以开发新的生物防治策略，预防疾病传播。采采蝇是撒哈拉以南非洲人类和动物中锥虫病的媒介，造成重大的卫生和经济问题。目前还没有控制哺乳动物宿主疾病的疫苗，只有一种高毒性药物可用于治疗晚期感染。媒介控制方法，如诱捕和喷洒杀虫剂，对减少苍蝇的威胁是有效的。由于采采蝇的繁殖速度较慢，蝇类数量较少，因此减少病媒的方法特别有效。采采蝇有一个不寻常的生殖生物学，因为它们一次只发育一个后代，并生下一个完全发育的幼虫。采采蝇的繁殖也是独一无二的，因为它需要专性互惠共生细菌的存在。发育中的宫内幼虫的营养完全由母体提供。营养物质通过一种叫做乳腺的特殊附属腺产生的乳汁分泌物从母体传递给后代。营养物质流入发育中的幼虫的中断，或共生细菌的消除，都会导致宿主丧失繁殖力。该应用程序有三个目标。第一个目标侧重于脂质从脂肪组织转移到乳腺及其调节。它将识别和表征负责调节昆虫脂质动员的保守肽激素/受体系统（脂肪动力学激素）以及负责脂质通过血淋巴的物理运动的系统（脂蛋白/脂蛋白受体）。第二个目标侧重于乳汁分泌的蛋白质成分。它将在计算机上识别新的乳蛋白，并表征启动子和调控区域，以了解负责乳腺/妊娠特异性表达模式的转录因子。第三个目标侧重于共生细菌在宿主繁殖过程中不可或缺的作用。研究共生体对寄主繁殖力的促进作用，分析寄主繁殖力相关基因在共生体治疗的不育蝇中的表达规律。总的来说，拟议的研究将确定采采蝇繁殖过程所需的关键因素。这些要素可以为用于预防锥虫病的采采蝇特定病媒控制战略提供目标。公共卫生相关性：本提案将确定采采蝇生殖系统中的分子靶点。这些靶点可用于开发新的采采蝇特异性化学物质和/或策略来破坏采采蝇的繁殖。破坏采采蝇的繁殖将是减少或消灭苍蝇种群的有效方法，从而防止锥虫传播给人类和牲畜。

DESCRIPTION (provided by applicant): The focus of this proposal is to identify molecular targets of tsetse fly reproductive physiology for the development of novel biological control strategies for the prevention of disease transmission. Tsetse are the vectors of trypanosomiasis in both humans and animals in sub-saharan Africa creating major health and economic problems. There are no vaccines to control disease in the mammalian host and only a single and highly toxic drug is available for treatment of late stage infections. Vector control methods, such as trapping and insecticide spraying, are effective in reducing fly challenge. Vector reduction methods are especially effective due to the low fly population numbers resulting from tsetse's slow reproductive rate. Tsetse has an unusual reproductive biology as they only develop one offspring at a time and give birth to a fully developed larva. Reproduction in tsetse is also unique in that it requires the presence of obligate mutualist symbiotic bacteria. Nutrients for the developing intrauterine larva are supplied entirely by the mother. Nutrients are transferred from the mother to offspring by milk secretions generated in a specialized accessory gland called the milk gland. Disruption of the flow of nutrients into the developing larva, or the elimination of symbiotic bacteria both result in loss of host fecundity. The application has three goals. The first goal focuses on the transfer of lipids from the fat body tissue to the milk gland and its regulation. It will identify and characterize the conserved peptide hormone/receptor system (adipokinetic hormone) responsible for regulating lipid mobilization in insects as well as the system responsible for the physical movement of lipids through the hemolymph (lipophorin/lipophorin receptor). The second goal focuses on the protein components of the milk secretion. It will identify novel milk proteins in silico and characterize the promoter and regulatory regions to understand the transcription factors responsible for milk gland/pregnancy specific expression patterns. The third goal focuses on the indispensable role of symbiotic bacteria in host reproductive processes. It will characterize the factors symbionts provide to facilitate host fecundity, analyze the expression patterns of host reproduction associated genes in symbiont-cured sterile flies. Collectively, the proposed studies will identify key elements required for tsetse reproductive processes. These elements stand to provide targets for tsetse specific vector control strategies for use in the prevention of trypanosomiasis. PUBLIC HEALTH RELEVANCE: This proposal will identify molecular targets in the tsetse fly reproductive system. These targets can be used to develop novel tsetse specific chemicals and/or strategies to disrupt tsetse reproduction. Disruption of tsetse reproduction would be an effective way to reduce or eliminate fly populations resulting in the prevention of trypanosome transmission to humans and livestock.