Molecular Aspects of Tsetse and Trypanosome Transmission

项目摘要 这个应用程序是关于预防人类非洲锥虫病(HAT)，每种疾病都会导致数千人死亡 撒哈拉以南非洲的一年。这种疾病是由采采蝇传播的非洲锥虫引起的。不是 哺乳动物疫苗，或有效的和负担得起的治疗药物。相反，采采率的降低 人口对疾病控制可以非常有效，尽管传统的策略很难做到 可持续，因为它们需要贫困、偏远和饱受战争蹂躏的地区的广泛社区参与 典型的受这种疾病折磨的。重组技术为新技术的发展提供了保证 方法，包括修改苍蝇的媒介能力。此应用程序建议调查 采采氏免疫生物学的基本方面与其传播的致病性锥虫有关， 以及它赖以繁衍后代的专职互惠共生体。该应用程序有两个目标：(1)调查 采采子对锥虫传播耐药的分子基础及病原体的作用 识别分子，以及(2)了解采采族免疫的反应和进化动力学 调节共生动态平衡和媒介能力的反应。宿主免疫蛋白的鉴定 导致寄生虫抗药性的努力可能会加强通过遗传降低采采氏病媒能力的努力 修改。了解对共生动物的耐受机制可能会导致新的媒介控制 旨在减少采采人繁殖力的策略。

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.