Evolutionary genetics of tsetse and its symbionts

采采蝇及其共生体的进化遗传学

• 批准号: 8204829
• 负责人: Serap AKSOY
• 金额: $ 54.48万
• 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 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8204829
• 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

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 proposal will combine epidemiology, population genetics and modeling with model parameterization and verification from laboratory and field research.

人类非洲锥虫（HAT）每年在撒哈拉以南非洲杀死数千人。的 这种疾病是由采采蝇传播的非洲锥虫引起的。HAT的传播很复杂， 需要哺乳动物和无脊椎动物宿主，并涉及家庭和野生水库。无哺乳动物 现有的疫苗和治疗药物具有严重的副作用，在患者中观察到越来越多的耐药性。在 相反，减少采采蝇种群对疾病控制非常有效。但 采采蝇控制计划的实施依赖于诱捕器和目标， 因为它们不切实际，需要广泛的社区参与。一种副转基因策略 利用采采蝇独特的生物学特性及其母系遗传的细菌共生体， 在这种策略中，采采蝇的互利共生体Sodalis被利用来表达锥虫抑制因子， 采采蝇中肠中的分子来削弱锥虫的传播。转基因Sodalis细菌 舌蝇自然种群的不应性可能是由细胞质不亲和现象引起的 由采采蝇的共生体沃尔巴克氏体介导我们打算研究人类的神经系统 病媒种，Glossina fuscipes fuscipes，其锥虫属寄生虫，及其沃尔巴克氏体， 苏打共生体使用实验室和现场实验相结合，我们将调查的潜力 沃尔巴克氏体介导的基因驱动机制，以帮助应用副转基因苍蝇。此外，本发明还提供了一种方法， 我们将阐明这种人类疾病媒介群体的基本遗传结构， 信息存在。这一信息对于有效实施和监测 传统的或新的控制策略。获得关于共生生物学的知识， 采采蝇多种共生体，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， 人口遗传学和流行病学动态将提供制定一个 数学模型框架。这个模型将使我们能够测试经验的预测性质， 数据，设计人口控制的最佳策略，并预测可行性和鲁棒性， 替代战略的成功。这个跨学科的建议将结合联合收割机流行病学，人口 遗传学和建模与模型参数化和验证实验室和实地研究。