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Peridontal PhD

“Microbiology of Periodontal Pathogens”


Co-supervisors; Dr. D.H.Edwards, Prof. P. Mossey & Dr. A. Gilbert.

Contact: David Edwards

Background; 

The two most common diseases of the mouth are both precipitated by bacteria. Caries involves the dissolution of the tooth surface by bacterially produced acid, while Periodontal disease is known to involve the action of a wide range of bacteria whose cumulative effect is to promote inflammation and cause direct damage to the gingiva and supporting tissue. For both these diseases a community, or biofilm, of bacteria is key to disease progression. In the case of Caries two species of mutans Streptococci are considered the main bacterial source of acid. In the case of Periodontal disease a group of organisms collectively referred to as Gram negative anaerobic bacteria (GNABs) are the major mediators of disease. One of the best understood GNAB is Porphymonas gingivalis, a major pathogen that can survive intracellularly and encodes a variety of potent virulence factors. The project proposed is aimed at developing specific drugs and improved targeting of existing antibiotics to kill another important Periodontal Pathogen Fusobacterium nucleatum, the earliest colonising and most abundant GNAB in plaque. This microorganism has a unique role in promoting the adhesion of different species of bacteria due to is large surface area; a result of its long filamentous shape (5-25 µMs), and uniquely its ability to coaggregate with all of the oral bacteria so far investigated. This role as a ‘bridging’ organism is key to the accumulation and diversification of bacterial species in dental plaque. Importantly F. nucleatum is considered a Periodontal pathogen and the aetiological agent of specific conditions that include Acute Ulcerative Gingivitis. Consequently a method of specifically controlling F. nucleatum offers the opportunity not only to reduce the accumulation of plaque, but also to intervene in destructive oral infections where F. nucleatum is a key mediator of disease.

Research Outline; 

The first year of this laboratory based project will involve characterising the cell cycle of the four sequenced strains. These will include the three sequenced subspecies (F. nucleatum nucleatum (FNN), F. nucleatum vincentii (FNV), and F. nucleatum polymorphum (FNP), and the one genetically tractable strain of F. nucleatum (ATCC23726). Genetic tools to construct mutants already exist for ATCC23726, and these will be used to inactivate important cell wall proteins. Resulting bacteria will be analysed for alterations in cell growth, antibiotic sensitivity and adhesive properties. Subsequently the project will investigate the proteins identified as key to the survival and adhesive properties of F. nucleatum. The ultimate aim of this work will be the construction of new strains of bacteria that can be used to screen existing drugs and commercially available chemical libraries for new therapies that could be used in a clinical setting.

With the assistance of Dr. Gilbert from year two onwards, the student will handle samples obtained from a stratified group of patients suffering from different degrees of periodontal disease. Ethical consent will need to be obtained, but as this will involve the non-invasive collection of bacteria colonising a patient this should be routine. These samples will analysed in the laboratory for the presence of F. nucleatum strains by direct PCR and microbiological culturing. This will provide information on the variety of subspecies, and if this varies at different stages of disease. Importantly these samples will also be analysed for the carriage of the key protein targets identified during the molecular microbiology component of the project. In this way it is intended to validate the hypothesis that key strains of F. nucleatum are widely conserved in the samples isolated from patients suffering Periodontal disease. 

Entry Requirements

The normal requirements are a First Class or Upper Second Class Honours Degree (or equivalent) at undergraduate level in a relevant discipline.

Applications including


This is a self funding project only.