Meaningful microbiomes: Investigation of host-microbiome interactions in liver fluke infections

问题：抗药性目前威胁着食用动物寄生虫感染的控制，对全球粮食安全构成严重威胁。肝片吸虫是一种感染牛、绵羊和山羊的高致病性吸虫，已有广泛耐药报道。因此，研究的重点是确定新的战略来改善对这些感染的控制。一个关键的方法是确定影响宿主对感染的免疫反应的因素；特别是肠道共生细菌已被确定在调节这种反应中发挥重要作用。方法：在这个项目中，学生将首次详细研究肝片吸虫感染对绵羊胃肠道(GI)微生物区系、代谢物和宿主免疫反应的影响。学生将使用一系列最先进的测序技术(微生物16S rRNA扩增和RNA序列)和代谢物检测技术(核磁共振光谱、气/液相色谱-质谱仪)来描述宿主对感染的反应。随后，将开发生物信息学分析和先进的生物统计数据集成技术，以确定肝片吸虫感染不同阶段的宿主-寄生虫-微生物组关联。这项研究将有助于我们了解GI微生物群在肝片吸虫感染的免疫反应中的作用，并将为未来旨在改善我们对这种重要经济寄生虫的控制的研究奠定基础。

The problem: Drug resistance currently threatens the control of helminth parasite infections in food producing animals, constituting a serious threat to global food security. Liver fluke (Fasciola hepatica) is a highly pathogenic trematode parasite infecting cattle, sheep and goats, to which widespread drug resistance has been reported. As a result, research is focusing on the identification of novel strategies to improve control of these infections. One key approach is the identification of factors which impact upon the host's immune response to infection; in particular, gut commensal bacteria have been identified as playing an important role in regulating such responses. The approach: In this project the student will, for the first time, provide a detailed examination of the impact of F. hepatica infection on the gastrointestinal (GI) microbiota, metabolites and host immune responses in sheep. A range of state-of-the-art sequencing (microbial 16S rRNA amplicon and RNA seq), and metabolite detection techniques (nuclear magnetic resonance spectroscopy, gas/liquid chromatography-mass spectrometry) will be employed by the student to profile host responses to infection. Following this, bioinformatics analyses and advanced biostatistical data integration techniques will be developed to identify host-parasite-microbiome associations at different stages of F. hepatica infection. This study will contribute significantly to our knowledge of the role of the GI microbiome in immune responses to F. hepatica infection, and will form the basis of future studies aimed at improving our control of this economically important parasite.