Identification of factors contributing to group behavior in African Trypanosomes

描述（由申请人提供）：布鲁氏锥虫是一种鞭毛原虫寄生虫，是人类和牛的非洲昏睡病的病原体。昏睡病是撒哈拉以南非洲的一种重新出现的疾病，那里约有6000万人面临感染的风险。昏睡病如果不治疗是致命的，而且没有疫苗可用。目前的药物陈旧、有毒且难以施用，耐药性的发展使这种情况更加恶化。因此，迫切需要了解寄生虫生物学的新特征并确定新的药物靶点。布氏绦虫通过受感染的采采蝇媒介的叮咬传播到哺乳动物宿主的血液中。在这两个宿主体内，布氏体与组织表面密切接触，并表现出对感知和信号传导的隐性需求，以指导寄生虫的迁移和分化。这在采采中尤为明显。目前，关于表面接触如何调节锥虫生物学知之甚少。最近，我们报道了在半固态琼脂糖培养皿上培养布鲁氏体的社会行为。这种行为被称为社会运动，其特征是形成多细胞社区，感知外部刺激并相互沟通以协调人口的运动。布鲁氏体社会行为的发现揭示了原生动物行为的复杂性和合作性，这是以前未被认识到的。在其他微生物病原体中，社会行为提供了许多优势，细菌社会相互作用的研究彻底改变了我们对微生物发病机制的理解。我们假设布鲁氏锥虫的社会行为为锥虫的发育和发病提供了类似的优势，并且布鲁氏锥虫在社会运动中用于细胞-细胞信号传导的系统与用于感知和响应宿主信号的系统重叠。目前的建议将确定锥虫社会行为的基因和机制。鉴于其他微生物之间广泛的社会相互作用，我们希望我们的研究在寄生原生动物中具有广泛的相关性。

DESCRIPTION (provided by applicant): Trypanosoma brucei is a flagellated protozoan parasite that is the causative agent of African sleeping sickness in humans and nagana in cattle. Sleeping sickness is a reemerging disease in sub-Saharan Africa where ~60 million people live at risk of infection. Sleeping sickness is fatal if untreated and no vaccines are available. Current drugs are antiquated, toxic and difficult to administer, a situation that is exacerbated by the development of drug resistance. Thus, there is a critical and urgent need to understand novel features of parasite biology and identify new drug targets. T. brucei is transmitted to the bloodstream of a mammalian host through the bite of an infected tsetse fly vector. In both hosts, T. brucei is in intimate contact with tissue surfaces and exhibits an implicit requirement for sensing and signaling to guide parasite migration and differentiation. This is especially apparent in the tsetse. Currently, little is known about how surface contact modulates trypanosome biology. Recently, we reported that T. brucei engages in social behavior when cultivated on semi-solid agarose plates. This behavior, termed social motility, is characterized by the formation of multicellular communities that sense external stimuli and communicate with one another to coordinate movement of the population. The discovery of social behavior in T. brucei reveals a level of complexity and cooperativity in protozoan behavior that was previously unrecognized. In other microbial pathogens social behaviors offer numerous advantages and studies of social interactions in bacteria have revolutionized our understanding of microbial pathogenesis. We hypothesize that social behavior in T. brucei provides similar advantages for trypanosome development and pathogenesis and that systems used by T. brucei for cell-cell signaling in social motility overlap with systems used to sense and respond to host signals. The current proposal will identify genes and mechanisms underlying social behavior in trypanosomes. Given the widespread social interactions among other microbes we expect our studies to have broad relevance among parasitic protozoa.