Gillian Douce

Biography

Gillian Douce is currently working as a Senior Lecturer in the Department of Infection, Immunity & Inflammation

Research Interest

Clostridium difficile: C. difficile is a bacterium that particularly affects elderly and hospitalised patients, causing chronic and relapsing diarrhoea, which can kill. Infection occurs when indigenous bacteria are destroyed as a consequence of antibiotic use, given to treat other unrelated infections. The removal of these ‘friendly’ bacteria leaves the colon vulnerable to C. difficile colonisation and provides a niche in which they can flourish. Once established, the bacterium releases two powerful toxins which are responsible for damaging the gut and causing diarrhoea. In addition, the bacteria produce spores which are metabolically inactive and can survive long term in the environment. It is the subsequent contamination of inanimate surfaces that leads to the further spread of the infection to vulnerable patients. Our research programmes focus on two aspects of this infection; firstly pathogenesis or the study of the infection process and secondly translation of this information to improve treatment. In particular, we are interested in where and how the organism interacts with the host (localisation of the organism) and the specific genes that are involved in this process. To improve our understanding of these interactions, we have marked the bacteria with a tag that makes them fluoresce. This tag has been adapted from a protein previously found in plants, which is involved in light capture. The advantage of this domain known as LOV (light, oxygen or voltage) is that it is functionally active in the anaerobic environment of the gut. Currently, we are coupling this methodology with the creation of genetic mutants of C. difficile to allow us to determine which specific genes are essential for binding to and multiplication within the colon. We can also mark individual proteins with this tag. This is allowing us to more clearly define when particular virulence traits are made and their contribution to the disease process. We are also considering whether specific by–products of C. difficile growth can modify the ‘friendly bacteria’ or microbiome of the gut and as a consequence influence susceptibility to subsequent infections. A second focus remains the development of preventative or therapeutic treatments for C. difficile. In collaboration with Novartis we have generated and tested several vaccines based on combinations of specific fragments from the two dominant toxins, Toxin A and B. This work has led to the identification of a formulation that appears to prevent or limit diarrhoeal symptoms. In addition, we are testing whether inclusion of possible ‘adhesion’ proteins within this formulation could limit colonisation and prevent infection initiation. In collaboration with the Scottish Salmonella Shigella and C. difficile Reference Laboratory (SSSCDRL), we are considering the changing epidemiology of this infection, including the appearance and tracking of new virulent strains of the organism.