PhD Studentship - How do Oral Bacteria Initiate Cardiovascular Disease?

University of Sheffield - School of Clinical Dentistry

There is increasing evidence that bacteria, which normally reside in the mouth, can gain access to the bloodstream and cause systemic infection. This is particularly important for individuals suffering from chronic periodontitis, a serious oral disease that has been associated with increased risk of systemic conditions such as cardiovascular disease and rheumatoid arthritis and affects 700 million people worldwide. Recent work conducted at the School of Clinical Dentistry in Sheffield has shown that the bacterium Porphyromonas gingivalis, a key pathogen in periodontitis, can invade endothelial cells cultured in vitro and cause vascular damage in an in vivo zebrafish model of systemic infection (Widziolek et al. 2016, Scientific Reports). The damage appears to be mediated by proteins secreted by P. gingivalis called gingipains.

The aim of this project is to continue this work to determine the molecular mechanism by which P. gingivalis causes vascular damage in vitro and in vivo. To do this you will perform infection studies with wild-type or mutated forms P. gingivalis that lack gingipains or other virulence factors on cultured human microvascular endothelial cells and examine the integrity of cell surface receptors at endothelial junctions and measure vascular permeability in flow assays that mimic the circulation. In addition, you will use gingipain mutants along with specific gingipain inhibitors in our zebrafish systemic infection model along with real-time fluorescence microscopy to examine the mechanism by which this bacterium causes increased vascular permeability and damage in vivo.

You will gain experience of in vitro and in vivo zebrafish infection models alongside a range of cellular and molecular microbiology techniques to gain a multidisciplinary training that will be suited for a career in host-pathogen research.

Entry Requirements

Applications are invited from highly motivated and talented students holding, or expecting to obtain, the equivalent of at least an upper second (2:1) or First Class degree in a relevant subject area. You will join a vibrant and dynamic research environment with a good track record in journal publication by PhD students.

Funding Information

Covers fees and stipend

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Type / Role:

PhD

Location(s):

Northern England