Molecular Aspects of Tsetse and Trypanosome Transmission

采采蝇和锥虫传播的分子方面

• 批准号: 7770552
• 负责人: Serap AKSOY
• 金额: $ 46.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7770552
• 关键词: Africa South of the Sahara; African; African Trypanosomiasis; Animals; Antiparasitic Agents; Bacteria; Binding; Biochemical; Biology; Blood; Community Participation; Competence; Computer Systems Development; Development; Disease; Drosophila genus; Engineering; Exhibits; Exposure to; Female; Fertility; Foundations; Gene Expression; Genetic; Goals; Grant; Homeostasis; Human; Immune; Immune response; Immune system; Immunity; Infection; Inherited; Insecta; Investigation; Knowledge; Mediating; Microbe; Midgut; Modification; Molecular; Nature; Nutrient; Organism; Parasite resistance; Parasites; Peptidoglycan; Pharmaceutical Preparations; Population; Prevention; Process; Proteins; Reaction; Recombinants; Refractory; Research; Resistance; Role; Staging; Sterility; System; Technology; Testing; Therapeutic; Transgenic Organisms; Trypanosoma; Tsetse Flies; Vaccines; War; Wolbachia; base; dietary restriction; disorder control; feeding; fitness; fly; invertebrate host; killings; male; microbial; novel; novel strategies; pathogen; peptidoglycan recognition protein; prevent; programs; public health relevance; receptor; reproductive; resistance mechanism; response; transmission process; vector; vector control

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.

描述（由申请人提供）：此申请是针对预防人类非洲锥虫病（HAT），该pan虫病（HAT）每年在撒哈拉以南非洲杀死数千人。该疾病是由采摘蝇传播的非洲锥虫引起的。不存在哺乳动物疫苗或有效且负担得起的治疗药物。相比之下，尽管传统策略很难维持，但采用采集人群的减少可能是高效的，因为它们需要广泛的社区参与通常遭受这种疾病折磨的被剥夺，偏远和饱受战争的地区。重组技术现在承诺开发新方法，包括修改苍蝇的向量能力。该应用建议研究TSETSE免疫生物学的基本方面，因为它与它所传播的致病性锥虫有关，以及它依赖于生产力的强大互助者。该应用程序有两个目标：（1）研究采采对锥体传播的磨性性的分子基础，重点是病原体识别分子的作用，以及（2）了解TSETSE免疫反应的反应和进化动力学，这些反应调节了Symbioticsocicsostostostostasis和vector的能力。鉴定导致寄生虫抗性的宿主免疫蛋白可以加强可以通过遗传修饰来降低TSETSE载体能力的努力。了解对共生动物群的耐受性的机制可能会导致新颖的矢量控制策略，旨在降低采摘繁殖力。公共卫生相关性：该应用将调查昆虫采集蝇中的分子和生化机制，使寄生虫非洲锥体能够传播，非洲锥虫是人类睡眠病的病因。最终的目标是能够干扰苍蝇的寄生虫传播。