Evolutionary genetics of tsetse and its symbionts

描述(申请人提供)：非洲人类锥虫病(HAT)每年在撒哈拉以南非洲导致数千人死亡。这种疾病是由采采蝇传播的非洲锥虫引起的。HAT的传播是复杂的；它需要哺乳动物和无脊椎动物宿主，并涉及家养和野生水库。目前尚不存在哺乳动物疫苗，治疗性药物具有严重的副作用，患者的耐药性不断增加。相反，采采树种群的减少对疾病控制是非常有效的。然而，依赖陷阱和目标的采采物控制方案的执行一直难以持续，因为它们不切实际，需要社区的广泛参与。开发了一种副转基因策略，该策略利用采采赛及其母系遗传的细菌共生体的独特生物学特性。在这一策略中，采采族的互惠共生体苏打被利用来在采采族的中肠表达锥体抑制分子，以破坏锥体的传播。在采采子共生菌Wolbachia介导的细胞质不亲和现象的作用下，产生抗性的转基因苏打细菌可能被引入天然采采子种群。我们建议调查人类疾病媒介物种--融合舌虫、其锥虫寄生虫(S)及其沃尔巴克氏和苏丹斯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菌介导的基因驱动机制在辅助转基因果蝇应用方面的潜力。此外，我们还将阐明这一人类疾病媒介种群的基本遗传结构，目前尚无相关信息。这些信息对于有效实施和监测传统或新型控制战略是必要的。在共生菌生物学、采采族多种共生菌的母系连锁、沃尔巴克氏菌感染表型、沃尔巴克氏菌介导的驱动力的潜在强度、种群遗传学和流行病学动力学方面获得的知识将为开发基于数学的模型框架提供所需的参数。这一模型将使我们能够检验经验数据的预测性，设计人口控制的最优策略，并预测替代策略成功的可行性和稳健性。这一跨学科的应用将把流行病学、人口遗传学和建模与模型的参数化和实验室和实地研究的验证结合起来。

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.