Understanding the viral interactome in the mammalian gut for novel therapeutic discovery

人类肠道微生物区系估计超过1014个细胞，由数百种细菌组成。这个微生物区系的总基因组信息量是人类基因组的100倍。入侵的肠道病毒，如诺沃克病毒，是全球急性病毒性胃肠炎的主要原因，必须协商这种复杂的混合物才能开始感染宿主。虽然这种微生物区系混合物中的一些生物被假设为对病毒感染具有保护作用，但其他生物被认为促进了感染。因此，微生物的组成被认为是决定致病的因素。这个项目的目的是研究这一假说和复杂的“互动组”，即肠道微生物区系和传入的病毒病原体之间的相互作用。在这样做的过程中，我们将回答这样的问题，即肠道病毒在健康的微生物区系中附着在哪些细菌物种上，这些相互作用的分子基础是什么，它们如何预防感染？了解这些问题有助于发现未来治疗胃肠道病毒感染的方法。这个跨学科的项目包括利兹大学和纽卡斯尔大学的小组，将使用荧光标记病毒成像、结构生物学、体外哺乳动物模型系统和纳米级分类的尖端方法。这一博士学位具有高度的协作性，需要与阿斯特伯里结构生物学中心、利兹大学生物科学学院和医学院以及纽卡斯尔大学成像负责人进行互动。这项研究包括摩根·希罗德博士(病毒学家)、卡罗琳·奇尔顿博士(细菌学家、临床微生物学)和安德鲁·菲尔比博士(纳米成像和细胞学)。该项目还将受益于结构和分子生物学以及细胞生物学的现有合作者，并提供跨学科科学培训，为学生提供一套独特的尖端技术技能和专业知识。

The human intestinal microbiota is estimated to exceed 1014 cells and is composed of hundreds of bacterial species. The total genomic information of this microbiota is >100-times more than the human genome. Invading enteric viruses such as norovirus, the leading cause of acute viral gastroenteritis worldwide, must negotiate this complex mixture to start infecting the host. Whilst some organisms within this mixture of microbiota have been hypothesised to be protective against viral infection, others are thought to promote infection. Thus, the microbial composition is believed to dictate pathogenesis.This project aims to study this hypothesis and the complex "interactome", the interaction between the gut microbiota and incoming viral pathogens. In doing so we will answer questions such as, which bacterial species do enteric viruses latch onto in a healthy microbiota, what are the molecular bases of these interactions and how do they protect against infection? Understanding these questions could help discover future therapies to tackle gastroenteric virus infections.This interdisciplinary project includes groups at Universities of Leeds and Newcastle and will use cutting edge methodologies on imaging with fluorescently-labelled viruses, structural biology, in vitro mammalian model systems, and nano-scale sorting. This PhD is highly collaborative and will require interaction with researchers in the Astbury Centre of Structural Biology, Faculties of Biological Science and Faculty of Medicine at the University of Leeds and Imaging leaders at the University of Newcastle. The research spans the groups of Dr Morgan Herod (virologist), Dr Caroline Chilton (bacteriologist, clinical microbiology) and Dr Andrew Filby (nano-imaging and cytometry). The project will also benefit from existing collaborators in structural and molecular biology and cell biology, and provide training in interdisciplinary science to give the student a unique set of skills and expertise with cutting-edge technology.