Evolutionary genetics of tsetse and its symbionts

在撒哈拉以南非洲，人类非洲锥虫病(HAT)每年导致数千人死亡。这个 这种疾病是由非洲锥虫通过采采蝇传播引起的。 需要哺乳动物和无脊椎动物宿主，涉及家养和野生水库。没有哺乳动物 疫苗是存在的，治疗药物有严重的副作用，患者的耐药性增加。在……里面 相比之下，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期控制程序的执行一直难以持续 因为它们不切实际，需要广泛的社区参与。一种异基因策略已经 开发了利用采采子及其母体遗传的细菌共生体的独特生物学。 在这个策略中，采采族的互惠共生体苏打被利用来表达锥虫抑制 采采人中肠中的分子会破坏锥虫的传播。转基因苏打菌种的研究 细胞质不亲和现象可能导致天然采采子种群产生抗逆性 由采采子的共生菌沃尔巴克氏菌介导。我们建议研究人类的生物地理学 病媒物种，浮游丝虫，其锥虫寄生虫(S)，其沃尔巴克氏菌和 苏丹花共生体。结合实验室和野外实验，我们将研究这种潜力。 用于沃尔巴克氏菌介导的基因驱动机制，以辅助转基因果蝇的应用。此外, 我们将阐明这种人类疾病媒介种群的基本遗传结构，对于这种种群，没有 信息是存在的。这些信息对于有效实施和监测以下任何一项都是必要的 传统的或新型的控制策略。在共生生物生物学、母体连锁等方面获得的知识 采采族多种共生菌、沃尔巴克氏菌感染表型、沃尔巴克氏菌介导驱动力的潜在强度 人口遗传学和流行病学动态将提供制定 基于数学的模型框架。这个模型将允许我们测试经验数据的预测性。 数据，设计最优人口控制策略，并预测人口控制的可行性和稳健性 更替战略的成功。这项跨学科的建议将结合流行病学、人口 遗传学和模型模型化，以及实验室和现场研究的模型参数化和验证。

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.