Evolutionary genetics of tsetse and its symbionts

采采蝇及其共生体的进化遗传学

• 批准号: 7750618
• 负责人: Serap AKSOY
• 金额: $ 75.81万
• 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/7750618
• 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）：人类非洲锥虫（HAT）每年在撒哈拉以南非洲杀死数千人。这种疾病是由采采蝇传播的非洲锥虫引起的。HAT传播是复杂的，它需要哺乳动物和无脊椎动物宿主，并涉及国内和野生水库。目前还没有哺乳动物疫苗，治疗药物具有严重的副作用，患者的耐药性不断增加。相反，减少采采蝇种群对于疾病控制是非常有效的。然而，采采蝇控制方案的实施依赖于陷阱和目标，难以持续，因为它们不切实际，需要广泛的社区参与。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，已经开发出一种副转基因策略。在这种策略中，采采蝇的互惠共生体Sodalis被利用来表达锥虫抑制分子，以削弱锥虫的传播。通过舌蝇共生菌Wolbachia介导的细胞质不相容现象，可将转基因的耐抗性Sodalis细菌驱入自然舌蝇种群。我们建议调查人类疾病媒介物种，Glossina fuscipes fuscipes，它的锥虫寄生虫（S），以及它的Wolbachia和Sodalis共生体的传播学。使用实验室和现场实验相结合，我们将调查潜在的沃尔巴克氏体介导的基因驱动机制，以帮助应用的副转基因苍蝇。此外，我们将阐明这种人类病媒群体的基本遗传结构，对此没有任何信息。这些信息对于有效实施和监测传统或新型控制策略是必要的。共生体生物学，采采蝇的多个共生体，沃尔巴克氏体感染表型，沃尔巴克氏体介导的驱动器，人口遗传学和流行病学动态的潜在强度获得的知识将提供所需的参数，开发一个数学模型框架。该模型将使我们能够测试经验数据的预测性质，设计种群控制的最佳策略，并预测替代策略成功的可行性和鲁棒性。这种跨学科的应用将结合联合收割机流行病学，人口遗传学和模型参数化和验证从实验室和实地研究建模。