In the laboratory there are three major projects.
1). The role of capsular polysaccharides in extra-intestinal infections caused by Escherichia coli.
Escherichia coli cause a number of extra-intestinal infections such as urinary tract infections, blood poisoning (septicemia) and meningitis in new born children. A key virulence factor is the expression of a polysaccharide capsule that coats the outside of the E. coli and protects it from host defences. The research has two broad objectives-first to understand how capsular polysaccharide expression is regulated in E. coli during an infection. This research will not only elucidate at the molecular level the mechanisms by which the genes encoding for capsular polysaccharide synthesis are regulated but also shed light on the role of the capsular polysaccharide during different stages of an infection. This project primarily uses molecular genetic approaches. The second objective is to understand how capsular polysaccharides are transported out of the bacterial cell. The export of large polysaccharide molecules out of the cell represents a fascinating challenge to the bacterium. In addition, understanding how this process is mediated will allow the synthesis of transport inhibitors that could potentially be used to treat infections. Moreover, we should be able to exploit the transport process to export polysaccharides of biomedical importance that have been engineered in Escherichia coli. This project combines molecular biology and structural biology.
2). The growth of the food borne pathogen Listeria monocytogenes inside the host.
Listeria monocytogenes is a food borne pathogen responsible fro a number of infections including intra-uterine infections of the unborn foetus. A key characteristic of L. monocytogenes is its ability to grow inside host cells, a process which represents a nutritional challenge to the bacterium. The intracellular life cycle of L. monocytogenes has been well studied. In my laboratory we are studying the ability of intracellular L. monocytogenes to acquire zinc a key element for growth the availability of which tightly regulated within the host cell. Recently my group has initiated research on the growth of L. monocytogenes in the intestine prior to invasion. Both project involve combining molecular, genetic and biochemical approaches with tissue culture and cell biology.
3). Studies on the gut microbiota during long-term chronic parasitic infections.
The microbiota of the large intestine play key roles in the health of the host including maturation of the host immune system, digestion of dietary molecules, prevention of infection and generation of important signaling molecules to the host. Changes in the host microbiota have been implicated in a number of disorders including obesity, cancer and behavior. In my laboratory in collaboration with the Grencis laboratory we are looking at how the microbiota of the host is affected by chronic parasite infection (Trichuris muris) and crucially the implications to the host of such changes. The project involves metagenomics, bioinformatics, molecular microbiology and metabolomics.