Research in my lab is primarily focussed on host-pathogen interactions of intracellular bacteria. I am using Salmonella and Listeria as model bacteria that invade human cells and subvert normal cellular processes. I am interested in understanding the role of certain proteins so that we may identify novel methods to inhibit their action, or to exploit their activities for therapeutic processes. My lab is based in the School of Applied Sciences at Edinburgh Napier University.
Host-pathogen interactions during Salmonella infection
Current research is focused on two areas of Salmonella pathogenesis:
- Cobalt homeostasis in Salmonella enterica. This metal ion is required for cobalamin (Vitamin B12) which in turn is an important cofactor for anaerobic metabolism in the gut. My lab is characterising genes & proteins involved in cobalt transport and elucidating their roles in homeostasis, cobalt-dependent gene expression and their contributions to virulence. Interestingly, one of these genes has been shown to be expressed inside tumour cells and we are looking at the potential use of the Salmonella gene promoter to control the differential expression of heterologous anti-tumour proteins directly inside tumours. Such a mechanism could be exploited for the selective delivery of potent anti-tumour therapies.
- Role of PgtE protease. The protease is thought to be involved in the degradation of host tissues during infection. Our work aims to understand the regulation of expression of this protease to enable us to develop a novel antimicrobial strategy based on PgtE-dependent cleavage of antibiotic prodrugs. One way to describe this would be to say that we are trying to design Salmonella ‘suicide bombers’ that would trigger the destruction of other Salmonella.
Infection during pregnancy
I have had a long-standing interest in Listeria monocytogenes pathogenicity and a recent PhD student investigated factors in the pregnant host that may contribute to increased susceptibility to infection by this pathogen, including modulation of gene expression by pregnancy hormones. We have identified a Listeria protein which may degrade steroid hormones such as progesterone, and would thus have implications for infection during pregnancy.
I am also engaged in collaborative research with a number of colleagues in the broad category of infection control. This includes clinical, industrial and environmental settings.