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

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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.