Tsetse Fecundity Reduction for Trypanosomiasis Control

描述（由申请人提供）：本提案的重点是确定采采蝇生殖生理学的分子靶标，以开发预防疾病传播的新型生物控制策略。采采蝇是撒哈拉以南非洲人类和动物的锥虫病媒介，造成重大的健康和经济问题。没有疫苗来控制哺乳动物宿主中的疾病，并且只有一种单一的高毒性药物可用于治疗晚期感染。病媒控制方法，如诱捕和喷洒杀虫剂，可有效减少苍蝇的挑战。由于采采蝇繁殖率低，蝇类数量少，减少病媒的方法特别有效。采采蝇有一种不寻常的生殖生物学，因为它们一次只发育一个后代，并生下一个发育完全的幼虫。采采蝇的繁殖也是独特的，因为它需要专性互利共生细菌的存在。子宫内幼虫发育所需的营养完全由母体提供。营养物质通过乳汁分泌物从母亲转移到后代，乳汁分泌物产生于一个专门的附属腺体，称为乳汁腺。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繁殖力的丧失。该应用程序有三个目标。第一个目标集中在脂质从脂肪体组织转移到乳腺及其调节。它将确定和表征保守的肽激素/受体系统（脂肪运动激素）负责调节昆虫的脂质动员以及负责脂质通过血淋巴（脂蛋白/脂蛋白受体）的物理运动的系统。第二个目标集中在牛奶分泌的蛋白质成分。它将通过计算机识别新的牛奶蛋白，并表征启动子和调控区，以了解负责乳腺/妊娠特异性表达模式的转录因子。第三个目标集中在共生细菌在宿主生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，分析共生体治愈不育蝇后寄主繁殖相关基因的表达模式。总的来说，拟议的研究将确定采采蝇生殖过程所需的关键要素。这些因素为用于预防锥虫病的采采蝇特异性病媒控制策略提供了目标。公共卫生相关性：该提案将确定采采蝇生殖系统中的分子靶点。这些靶标可用于开发新的舌蝇特异性化学物质和/或破坏舌蝇繁殖的策略。干扰采采蝇繁殖将是减少或消灭蝇类种群的有效方法，从而防止锥虫向人类和牲畜传播。

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.