Molecular Aspects of Tsetse and Trypanosome Transmission

描述（由申请人提供）：本申请是关于预防非洲人类锥虫病（HAT），每年在撒哈拉以南非洲造成数千人死亡。这种疾病是由采采蝇传播的非洲锥虫引起的。没有哺乳动物疫苗或有效和负担得起的治疗药物。相比之下，减少采采蝇种群对疾病控制非常有效，尽管传统的战略难以维持，因为它们需要在通常受这种疾病影响的贫困、偏远和饱受战争蹂躏的地区广泛的社区参与。重组技术现在有望开发出新的方法，包括修饰苍蝇的载体能力。本申请旨在研究采采蝇免疫生物学的基本方面，因为它涉及到它传播的致病性锥虫，以及它依赖于繁殖力的专性互利共生体。该应用程序有两个目标：（1）研究采采蝇对锥虫传播的抗性的分子基础，重点是病原体识别分子的作用，以及（2）了解调节共生体内平衡和载体能力的采采蝇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蝇载体能力的努力。了解共生动物的耐受机制可能会导致新的病媒控制策略，旨在减少采采蝇的繁殖力。公共卫生相关性：该应用程序将调查昆虫采采蝇的分子和生化机制，使寄生虫非洲锥虫的传播成为可能，非洲锥虫是人类昏睡病的病原体。最终目标是能够干扰寄生虫在苍蝇中的传播。

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.