Molecular Aspects of Tsetse and Trypanosome Transmission

项目摘要 这个应用程序是防止人类非洲锥虫病（HAT），杀死成千上万的人， 在撒哈拉以南的非洲。这种疾病是由采采蝇传播的非洲锥虫引起的。没有 存在哺乳动物疫苗或有效且可负担得起的治疗药物。相反，采采蝇的减少 尽管传统的策略很难 因为它们需要贫穷、偏远和饱受战争蹂躏地区的社区广泛参与 通常都患有这种疾病重组技术现在承诺开发新的 方法，包括修改的载体能力的苍蝇。本申请旨在调查 采采蝇免疫生物学的基本方面涉及其传播的致病性锥虫， 以及它赖以繁殖的互惠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--病原体的作用 识别分子，（2）了解舌蝇免疫系统的反应和进化动力学， 调节共生体内平衡和载体能力的反应。宿主免疫蛋白的鉴定 导致寄生虫抗性可以加强可以通过遗传减少采采蝇的媒介能力的努力， 改性了解对共生动物的耐受机制可能会导致新的病媒控制 减少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.