**SSA** Functional biology of small RNAs secreted by the parasitic nematode Trichinella spiralis

许多关于宿主-寄生虫通讯的研究都集中在蛋白质的作用上，但最近小RNA已经成为一类可能参与这些事件的新型分子。特别是一类微小RNA（miRNAs），已被假定在寄生虫操纵宿主功能中发挥作用。我将探讨的作用，小RNA在寄生线虫旋毛虫和它的哺乳动物宿主之间的通信。这种线虫寄生虫非常适合作为宿主-寄生虫通信的模型，因为它在其生命周期的成体阶段期间占据肠上皮中的假细胞内生态位，并且在其幼虫阶段期间占据骨骼肌中的真正细胞内生态位。已知它调节宿主免疫力，也诱导骨骼肌重塑，尽管负责后一种现象的试剂尚不清楚。 我将利用T.啮齿动物的螺旋体感染作为模型系统。该项目的目的是研究寄生虫不同阶段分泌的miRNAs，研究它们的分泌途径和进入宿主细胞的模式，并确定它们是否以及如何被纳入宿主小RNA途径。我的目标是确定选定的寄生虫分泌的miRNA的目标，并检查它们在骨骼肌重塑中的可能作用。这个项目将解决分泌RNA的基本机制问题，提供深入了解宿主-寄生虫相互作用的潜在作用。

Much of the research on host-parasite communication has focussed on the role of proteins, but recently small RNAs have emerged as a novel class of molecules which might participate in these events. One class in particular, microRNAs (miRNAs), have been posited to play a role in parasite manipulation of host function. I will explore the role that miRNAs play in communication between the parasitic nematode Trichinella spiralis and its mammalian host. This nematode parasite is well suited as a model for host-parasite communication in that it occupies a pseudo-intracellular niche in the gut epithelium during the adult phase of its life cycle, and a true intracellular niche in skeletal muscle during its larval phase. It is known to modulate host immunity and also induce remodelling of skeletal muscle, although the agents responsible for the latter phenomenon are unknown. I will investigate potential roles for miRNAs in parasite-host communication using T. spiralis infection of rodents as a model system. The aim of the project is characterise miRNAs secreted by different stages of the parasite, investigate their pathway of secretion and mode of entry into host cells, and determine whether and how they are incorporated into the host small RNA pathway. I will aim to determine the targets of selected parasite secreted miRNAs and examine their possible role in remodelling of skeletal muscle. This project will address fundamental mechanistic questions on secretory RNAs, providing insight into potential roles in host-parasite interactions.