The main research focus of my group is the pathogenesis of Escherichia coli, in particular zoonoses caused by enterohaemorrhagic E. coli (EHEC). We study the colonization of cattle by EHEC strains and aim to understand the genetic factors that lead to infections in humans. Specifically, our recent work is making use of whole genome sequencing to define the subset of animal strains that are a threat to human health. By analyzing the accessory genome content of both human and cattle strains we are able to predict the strains more likely to cause serious human disease. This work can then be combined with our other main research area, the development of vaccines to prevent EHEC excretion from cattle. Our vaccine research has been built on our studies of surface organelle expression in Escherichia coli, in particular of flagella and type III secretion systems. As we are now able to predict which farms carry strain with a high zoonotic threat then targeted interventions are possible. Our ongoing work is aiming to licence the vaccine. We are also developing flagellin-based fusions for stimulation of mucosal immunity. The vaccine and adjuvant work is in partnership with Dr Tom McNeilly as the Moredun Research Institute. Our main research funding at the moment is a two million pound EHEC research programme from Food Standards Scotland and the Food Standards Agency that is studying the epidemiology and molecular biology of EHEC strains across the UK in partnership with researchers at: the Universities of Glasgow and Edinburgh; the Scottish E. coli Reference Laboratory (SERL); the Moredun Research Institute (MRI); Scotland’s Rural College (SRUC); Public Health Scotland; Public Health England; USDA and University of Brisbane.
At a fundamental level we study how key factors such as Shiga toxins are expressed during infection and how bacteriophage variation and integration into the E. coli genome impact on isolate virulence and their capacity to colonise and be excreted from animal hosts. This includes control by small RNA molecules expressed from integrated prophages. We also have three projects focused on antimicrobial resistance in E. coli. Two of these are using sequencing and bioinformatic approaches to examine the genetic context of resistance genes, especially on plasmids and how acquisition of these leads to other changes in the bacterial cell. A recently awarded NERC project aims to quantify how antibiotic use on a commercial pig farm alters the copy number of specific resistance genes in animals and the local environment, where the concept is to consider the resistance genes as pollutants that need to be monitored and controlled.
The group therefore uses a wide-range of techniques with expertise in genetic manipulation and we encourage applications from individuals interested in PhD or MSc positions.