Molecular Aspects of Tsetse and Trypanosome Transmission

描述(申请人提供)：这份申请是关于预防人类非洲锥虫病(HAT)的，这种疾病每年在撒哈拉以南非洲导致数千人死亡。这种疾病是由采采蝇传播的非洲锥虫引起的。目前还没有哺乳动物疫苗或有效且负担得起的治疗药物。相比之下，减少采采树种群对疾病控制可能是非常有效的，尽管传统的战略难以持续，因为它们需要贫困、偏远和受战争蹂躏的地区的广泛社区参与，这些地区通常受到这种疾病的影响。重组技术现在有望开发新的方法，包括修改苍蝇的载体能力。这项申请建议研究采采赛免疫生物学的基本方面，因为它与其传播的致病锥虫以及其繁殖力所依赖的专性互惠共生体有关。这项应用有两个目标：(1)研究采采赛对锥虫传播的抵抗力的分子基础，重点是病原体识别分子的作用；(2)了解采采赛调节共生稳态和媒介能力的免疫反应的反应和进化动力学。鉴定导致寄生虫抗性的宿主免疫蛋白可以加强通过遗传修饰降低采采子媒介能力的努力。了解对共生动物的耐受机制可能会导致新的媒介控制策略，旨在减少采采族的繁殖力。公共卫生相关性：这项应用将研究采采蝇中能够传播寄生虫非洲锥虫的分子和生化机制，非洲锥虫是人类睡眠病的病原体。最终目标是能够干扰寄生虫在飞行中的传播。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: This application will investigate the molecular and biochemical mechanisms in the insect tsetse fly that enable the transmission of the parasite African trypanosome, the causative agents of Sleeping Sickness disease in humans. The ultimate goal is to be able to interfere with parasite transmission in the fly.