Macrophage manipulation by peridontopathogens and other oral microflora

Supervisors: Dr M Grant (Dentistry), Dr R Sammons (Dentistry), Dr R May (Biosciences)

Periodontitis is a highly prevalent, human chronic inflammatory disease. Bacteria within the dental plaque biofilm initiate the disease and progression is associated predominantly with the presence of anaerobic, Gram-negative bacteria within subgingival plaque and an aberrant inflammatory response. Phagocytes are one of the first cell types to respond to the plaque biofilm.

We have undertaken a body of research to understand the role of neutrophils in periodontitis, unveiling the role of reactive oxygen species in their hyper-responsive state (Matthews et al 2007a&b) and a role for type-1 Interferons in that process (Wright et al 2008; Dias et al 2011).

Here we propose to examine the role of macrophages in the destruction of periodontopathogens and other oral microflora, through phagocytosis and production of reactive oxygen species. It is already known that the periodontal pathogen Porphyromonas gingivalis enters macrophages in a lipid raft (caveolin 1) dependant manner and is directed to lysosomes for destruction (Wang & Hajishengallis, Cellular Microbiology 2008, 10, 2029–2042) and that it can induce intracellular changes (Zhou & Amar, Infect Immun. 2006 74:1204-14). Do these changes accommodate survival of P. gingivalis within macrophages? And do other plaque bacteria cause similar adaptations? Answers to these questions, amongst others, through cell culture models (Cumley et al 2012) and bacterial challenge could give rise to novel pathways for therapeutic intervention for periodontal disease.

At present, we would only consider applications from prospective students with:
- a first class biomedical degree, with interests in any of the areas outlined above,
- excellent command of the English language as outlined in the postgraduate prospectus,
- a source of funding to cover fees and living expenses.

To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in each school, the funding opportunities for each subject, and guidance on making your application, you can now order your copy of the new Doctoral Research Prospectus, at: www.birmingham.ac.uk/students/drp.aspx