Periodontal disease (PD) is a major health issue worldwide with ever-increasing prevalence due to the increasing age of the population. If left untreated, long-standing periodontal disease leads not only to the destruction of the tooth-supporting tissues but may also initiate and sustain systemic inflammation as shown by the elevated levels of serum inflammatory markers in affected patients. Additionally, bacterial species associated with periodontitis have been known to invade the periodontal tissues and enter the bloodstream thereby gaining access to coronary arteries. In vivo pre-clinical studies have demonstrated that such bacteria can promote coronary atherosclerosis, thus leading to the hypothesis that periodontitis may participate in the triggering or exacerbation of coronary artery disease and lead to acute myocardial infarction.
All bacterial species implicated in PD colonise the mouth of healthy individuals and the mere presence of these species does not promote disease. Many virulence factors of periodontal bacteria have been well characterised, for example fimbriae and gingipains in Porphyromonas gingivalis. However, the molecular mechanisms which regulate the expression profile of these bacterial factors and the overall transition from harmless bacteria to opportunistic pathogens in PD are unknown. This project will study an important biological phenomenon that has been completely ignored in periodontal bacteria, namely the phase variations of clonal bacterial populations and their role in disease initiation and progression. Some bacteria are capable of “switching” to a pathogenic status that is genetically unstable. This occurs via epigenetic phase variations controlled by rearrangement of genes contained in a type I restriction-modification (R-M) system. Our genomic studies indicate that these systems exist in most major periodontal bacteria.
The overall aim of this project is to investigate expression of known virulence factors and regulatory mechanisms of pathogenicity of periodontal bacteria in patients who have acutely presented with myocardial infarction. Mechanisms identified in isolates from acute myocardial infarction patients will be compared to those identified in matched control patients. Findings are expected to make a substantive contribution to the understanding of the molecular mechanisms that underpin the ability of periodontal bacteria to promote coronary atherosclerosis.
Breadth of training and benefits – The programme will provide training in a range of transferable skills and experience that can be taken forward into several career paths. The candidate will receive exposure to the clinical setting (wards and outpatient clinics). They will receive training in relevant aspects of molecular microbiology, statistics, bacterial genetics techniques as well as next-generation sequencing.
The candidate will join an enthusiastic team of clinicians and clinical researchers at the Institute of Dentistry and the Aberdeen Cardiovascular and Diabetes Centre. The candidate will benefit of the mentorship and support of senior peers involved in clinical research studies ongoing in these units, albeit on different population groups.
APPLICATION PROCEDURE:
Please note the lead supervisor for this project is Dr Karolin Hijazi, and their name should be noted on your application form. Informal enquiries can be sent to Dr Hijazi via the form below.
Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php.
You should apply for Degree of Doctor of Philosophy in Dentistry, to ensure that your application is passed to the correct person for processing.
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