Molecular Aspects of Tsetse and Trypanosome Transmission

项目概要 此应用程序旨在预防非洲人类锥虫病 (HAT)，该病每年导致数千人死亡 年在撒哈拉以南非洲地区。该疾病是由采采蝇传播的非洲锥虫引起的。否 哺乳动物疫苗或有效且负担得起的治疗药物是存在的。相反，采采蝇的减少 尽管传统策略难以实现，但人群对于疾病控制可能非常有效 维持，因为它们需要贫困、偏远和饱受战争蹂躏地区的广泛社区参与 通常患有这种疾病。重组技术现在有望开发新的 方法，包括修改苍蝇的媒介能力。本申请建议调查 采采蝇免疫生物学的基本方面，因为它与其传播的致病性锥虫有关， 以及它赖以繁殖的专性共生共生体。该应用程序有两个目标：(1) 调查 采采蝇对锥虫传播抵抗力的分子基础，重点关注病原体的作用 识别分子，以及（2）了解采采蝇免疫反应和进化动态 调节共生稳态和载体能力的反应。宿主免疫蛋白的鉴定 导致寄生虫抗药性的药物可以加强努力，通过遗传降低采采蝇的媒介能力 修改。了解共生动物的耐受机制可能会带来新的病媒控制方法 旨在降低采采蝇繁殖力的策略。

Project Summary This application is on preventing Human African trypanosomiasis (HAT), which kills thousands of people each year in sub-Saharan Africa. The disease is caused by African trypanosomes transmitted by the tsetse fly. No mammalian vaccines, or effective and affordable therapeutic drugs exist. In contrast, reduction of tsetse populations can be highly efficacious for disease control although traditional strategies have been difficult to sustain because they require extensive community participation in deprived, remote and war-torn regions typically afflicted by this disease. Recombinant technologies now promise the development of novel approaches, including modification of the vector competence of the fly. This application proposes to investigate the fundamental aspects of tsetse immune biology as it relates to the pathogenic trypanosomes it transmits, and the obligate mutualist symbionts it relies on for fecundity. The application has two goals: (1) to investigate the molecular basis of tsetse's refractoriness to trypanosome transmission with a focus on the role of pathogen recognition molecules, and (2) to understand the responses and the evolutionary dynamics of tsetse's immune reactions that regulate symbiotic homeostasis and vector competence. Identification of host immune proteins that result in parasite resistance can strengthen efforts that can reduce tsetse's vector competence via genetic modification. Understanding the mechanism of tolerance to symbiotic fauna may result in novel vector control strategies that aim to reduce tsetse's fecundity.