Evolutionary genetics of tsetse and its symbionts

采采蝇及其共生体的进化遗传学

• 批准号: 8004935
• 负责人: Serap AKSOY
• 金额: $ 69.07万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-15 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8004935
• 关键词: Acute; Adverse effects; Affect; Africa South of the Sahara; African; African Trypanosomiasis; Bacteria; Biology; Chronic; Community Participation; Competence; Complex; Data; Development; Diagnostic; Disease; Disease Vectors; Engineering; Epidemiology; Equilibrium; Fright; Future; Genes; Genetic; Genetic Drift; Genetic Models; Genetic Structures; Genotype; Goals; Human; Infection; Inherited; Knowledge; Laboratories; Mediating; Midgut; Mitochondrial DNA; Modeling; Monitor; Nature; Outcome; Parasites; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Population; Population Control; Population Genetics; Prevalence; Public Health; Recombinants; Refractory; Research; Research Personnel; Resistance; Structure; System; Technology; Testing; Therapeutic; Time; Transgenic Organisms; Trypanosoma; Trypanosomiasis; Tsetse Flies; Uganda; Vaccines; Wolbachia; base; design; disorder control; fly; human disease; invertebrate host; killings; novel; novel strategies; population genetic structure; programs; reconstitution; research study; success; tool; transmission process; vector

DESCRIPTION (provided by applicant): Human African trypanosomiasis (HAT) kills thousands of people each year in sub-Saharan Africa. The disease is caused by African trypanosomes transmitted by the tsetse fly. HAT transmission is complex; it requires mammalian and invertebrate hosts and involves domestic and wild reservoirs. No mammalian vaccines exist and therapeutic drugs have serious side effects with increasing resistance seen in patients. In contrast, reduction of tsetse populations is highly efficacious for disease control. However, the implementation of the tsetse control programs, which rely on traps and targets, have been difficult to sustain because they are not practical and require extensive community participation. A paratransgenic strategy has been developed which exploits the unique biology of tsetse and its maternally inherited bacterial symbionts. In this strategy, tsetse's mutualist symbiont Sodalis is harnessed to express trypanosome inhibitory molecules in tsetse's midgut to impair trypanosome transmission. Transgenic Sodalis bacterium conferring refractoriness may be driven into natural tsetse populations by cytoplasmic incompatibility phenomenon mediated by tsetse's symbiont, Wolbachia. We propose to investigate the biogeography of the human disease vector species, Glossina fuscipes fuscipes, its Trypanosoma parasite(s), and its Wolbachia and Sodalis symbionts. Using a combination of laboratory and field experiments, we will investigate the potential for a Wolbachia mediated gene-drive mechanism to aid in the application of paratransgenic flies. In addition, we will elucidate the basic genetic structure of this human disease vector population, for which no information exists. This information is necessary for the efficacious implementation and monitoring of either the traditional or novel control strategies. Knowledge obtained on symbiont biology, maternal linkage of tsetse's multiple symbionts, Wolbachia infection phenotype, potential strength of Wolbachia mediated drive, population genetics and epidemiological dynamics will provide the parameters needed to develop a mathematically based model framework. This model will allow us to test the predictive nature of the empirical data, design the optimal strategies for population control, and predict feasibility and robustness for the success of the replacement strategy. This interdisciplinary application will combine epidemiology, population genetics and modeling with model parameterization and verification from laboratory and field research.

描述（由申请人提供）：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。该病由采采蝇传播的非洲锥虫引起。HAT传输复杂；它需要哺乳动物和无脊椎动物宿主，包括家养和野生宿主。目前还没有哺乳动物疫苗，治疗药物有严重的副作用，患者的耐药性也在增加。相反，减少采采蝇种群对疾病控制非常有效。然而，依靠诱捕器和目标的采采蝇控制规划的实施很难持续下去，因为它们不实际，需要广泛的社区参与。利用采采蝇及其母系遗传细菌共生体的独特生物学特性，开发了一种准转基因策略。在这种策略中，利用采采蝇的共生共生菌Sodalis在采采蝇的中肠中表达锥虫抑制分子来破坏锥虫的传播。具有抗逆性的转基因Sodalis细菌可能是通过采采的共生体沃尔巴克氏体介导的细胞质不相容现象进入天然采采群体的。我们建议调查人类疾病媒介物种fuscipes fuscipes，其锥虫寄生虫及其Wolbachia和Sodalis共生体的生物地理学。利用实验室和现场实验相结合的方法，我们将研究沃尔巴克氏体介导的基因驱动机制在准转基因果蝇应用中的潜力。此外，我们将阐明这种人类病媒种群的基本遗传结构，目前尚无相关资料。这些信息对于有效实施和监测传统或新型控制策略都是必要的。关于共生体生物学、采采蝇多种共生体的母系连锁、沃尔巴克氏体感染表型、沃尔巴克氏体介导驱动的潜在强度、群体遗传学和流行病学动态的知识将为开发基于数学的模型框架提供所需的参数。该模型将允许我们检验经验数据的预测性，设计最优的人口控制策略，并预测替代策略成功的可行性和鲁棒性。这个跨学科的应用将结合流行病学、群体遗传学和模型参数化以及实验室和实地研究的验证。