Drosophila model to investigate the tripartite relationship between symbiont, trypanosomes and tsetse flies

采采蝇(Glossina属)是非洲锥虫病的唯一传播者，这种疾病会导致人类昏睡病和动物纳格纳病。世界卫生组织(世卫组织)估计，目前在37个非洲国家有30万至50万锥虫病病例，6000万人面临感染该疾病的风险(世卫组织委员会，2001年)。除了人的代价之外，锥虫病还严重限制了非洲的牛和乳制品生产，造成了重大的经济损失。为了提高非洲的农业产量，牛被用作耕作的牵引物是非常重要的。在这项提议中，我们将研究苍蝇、锥虫和一种名为Sodalsglossinidius的共生细菌之间的三方相互作用。采采蝇中苏达利斯的存在被认为与苍蝇传播锥虫的能力更强有关。我们将通过分析Sodalis与昆虫细胞和肠道的相互作用来确定Sodalis使苍蝇成为更好的媒介的机制。我们预计Sodalis可以改变昆虫免疫系统对Sodalis的反应方式，这在昆虫的防御系统中创造了一个“盲点”，使寄生虫能够存活并在采采期分裂。这将通过观察昆虫基因表达的变化来进行研究，这些变化是由于接触苏打和锥虫造成的。这项工作将通过确定支持共生和寄生相互作用的关键基因，从根本上了解采采子作为疾病媒介的生物学。更好地了解昆虫肠道如何应对微生物的挑战将导致疾病控制战略的新目标。所获得的知识将与节肢动物传播的其他医疗、兽医和农业重要疾病的控制直接相关。例如，人畜共患疾病，如利什曼原虫，动物疾病，如蓝舌病，以及由蚜虫传播的植物疾病，如马铃薯卷叶病毒。

Tsetse flies (genus Glossina) are the sole vectors of the zoonotic disease African Trypanosomiasis, which causes sleeping sickness in humans and nagana in animals. The World Health Organisation (WHO) has estimated that there are currently 300,000 - 500,000 cases of trypanosomiasis with 60 million people at risk of contracting the disease in 37 African countries (WHO Committee, 2001). In addition to the human cost, trypanosomiasis has severely restricted cattle and dairy production in Africa, resulting in substantial economic losses. To increase agricultural production in Africa it is very important that cattle can be used for traction for ploughing. In this proposal we will investigate the tripartite interactions of the fly, trypanosome and a symbiotic bacterium called Sodalis glossinidius. The presence of Sodalis in tsetse has been linked to the fly being more capable of transmitting the trypanosome parasite. We will identify the mechanisms through which Sodalis makes the fly a better vector by analysing how Sodalis interacts with cells and guts of insects. We expect that Sodalis can change the way an insect's immune system responds to Sodalis and this creates a "blind spot" in the insect's defenses that allow the parasite to survive and divide in tsetse. This will be investigated by looking at how insect gene expression changes as a result of exposure to Sodalis and trypanosomes. The work will provide fundamental understanding of the biology of tsetse as a disease vector by identifying the key genes underpinning symbiotic and parasitic interactions. A greater understanding of how insect guts respond to challenge by microbes will lead to new targets for disease control strategies. The knowledge gained will be of direct relevance to the control of other medical, veterinary and agriculturally important diseases vectored by arthropods. For example zoonosis such as Leishmania, animal diseases like Bluetongue and plant diseases vectored by aphids such as Potato leaf roll virus.