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Mechanisms of pathogenicity of periodontal bacteria in patients presenting with acute myocardial infarction.


School of Medicine, Medical Sciences & Nutrition

Aberdeen United Kingdom Dentistry Microbiology

About the Project

Periodontal disease (PD) is a major health issue in Scotland and 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 adversely influence the coronary atherosclerosis processes already present, thus leading to the hypothesis that periodontitis may participate in the triggering or exacerbation of coronary artery inflammatory processes 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 overall bacterial mechanisms which regulate the expression profile of these factors, and the 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 1. A recent genomic study indicate that these systems exist in most major periodontal bacteria 2.

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 acute myocardial infarction.

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 enthusiatic team of clinicians and clinical researchers at the Institute of Dentistry as well as a vibrant research group in the Infection & Immunity research programme at the Institute of Medical Sciences. 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:

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.


Funding Notes

This project is for self-funded applicants only – there is no funding attached.
Minimum eligibility criteria: candidates should hold the equivalent to a 1st class Bachelor in Dental Surgery (BDS) degree OR the equivalent of a 2.1 BDS degree alongside a Masters with Commendation or Distinction.
Desirable criteria: postgraduate degree in Periodontology; undergraduate degree in molecular biology / biomedical science

References

1. Manso et al. A random six-phase switch regulates pneumococcal virulence via global epigenetic changes. Nature Communications 2014 Sep 30;5:5055.
2. Haigh RD, Crawford L, Ralph J, Wanford JJ, Vartoukian SR, Hijazi K, Wade W and Oggioni MRO. Phase variable restriction modification systems in periodontal pathogens Prevotella intermedia, Tannerella forsythia and Porphyromonas gingivalis. Genome Announc 2017 Nov 16;5(46).

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