PhD Studentship: Kiss and Tell: Determining how periodontal pathogens interact with and modulate human cells via Outer Membrane Protein interactions

University of Sheffield - School of Clinical Dentistry

During infection in the human body the interaction between invading bacteria and the surface of human cells is a key factor in determining establishment of colonization and infection. Some bacteria are able to enter epithelial cells, evade the immune system and manipulate cellular function- including innate immune responses. In the case of oral disease, it is periodontitis that is by far the most prominent and serious soft-tissue associated infection, with over 700 million sufferers globally and strong links to serious systemic conditions such as cardiovascular disease and rheumatoid arthritis.

Recent work by the team in Sheffield identified a set of genes that are upregulated during this cellular invasion process by the keystone periodontal pathogen Porphyromonas gingivalis, one of which, the OmpA2 protein, contains surface peptide loops that interact directly with human epithelial cells (Naylor et al., 2016, MicroOpen doi: 10.1002/mbo3.401).

The aim of this project is to continue our work on the OmpA protein and through a series of immunoprecipitation and affinity chromatography experiments coupled with Mass Spectrometry identify the human receptor that this protein binds to. Additionally, we will examine the consequences of OmpA interactions with human cells to identify how this interaction influences cellular behavior.

In parallel you will use peptide analogues of OmpA to ascertain if they might be useful as anti-infective agents against P. gingivalis using an in vitro cellular infection model and a zebrafish infection model that we have developed (Widziolek et al., Scientific Rep- in press). In addition, you will continue work on the invasive gene set examining how these genes play a role in infections using a combination of mutagenesis and in vitro and zebrafish models alongside molecular microbiological work into their mechanism of action.

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 stand you in good stead for a career in microbiological research.

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.

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Northern England