Project title: Development of novel in vitro models to investigate the role of pathogens in the aetiology of feline chronic gingivostomatitis and to test therapeutic interventions

Supervisors:    Dr Marcello Riggio (Marcello.Riggio@glasgow.ac.uk)

                        Dr Christopher Nile (Christopher.Nile@glasgow.ac.uk)

                        Dr David Lappin (David.Lappin@glasgow.ac.uk)

                        Professor David Bennett (David.Bennett@glasgow.ac.uk)

Application deadline: 21st November 2014

Stipend: Tax-free stipend (MRC UK rate) of £13863 (year 1), £14002 (year 2) and £14142 (year 3), which will also over the cost of home tuition fees.

Eligibility: UK/EU

Start date: Up to 1st February 2015 (negotiable)

Project description: The Dental School and School of Veterinary Medicine (University of Glasgow) are seeking applications for a three-year PhD scholarship funded by the Petplan Charitable Trust. The student will be based at the Dental School.

Feline chronic gingivostomatitis (FCGS) is a severe inflammation in the oral cavity of cats that causes much pain and distress that can be serious enough to lead to euthanasia of affected animals. It presents as a proliferative and ulcerative inflammation of the oral cavity, mostly on the palatoglossal folds and the buccal gingiva. Other areas that can be affected are the pharynx, tongue and lips. The palate can become inflamed at the sites of the molar and premolar teeth, with varying amounts of plaque and calculus present. Clinical signs, generally caused by the inflammation that induces pain when opening the mouth, are dysphagia, weight loss, loss of grooming behaviour, excessive salivation, pawing at the mouth and halitosis.

Although FCGS is the most challenging of the oral inflammatory diseases to treat, its aetiology remains largely unknown. Full dental extraction, which is commonly used in severe cases, has a recovery success rate of only 50 to 60%. The disease is assumed to have a multifactorial aetiology and both viruses and bacteria have been implicated. We have previously shown that a number of pathogenic organisms are associated with FCGS including Tannerella forsythiaPorphyromonas circumdentaria and, to a lesser extent, feline calicivirus. The underlying hypothesis is that these organisms are, in part, responsible for the increased cytokine and Toll-like receptor (TLR2, TLR4, TLR7) expression that we have previously demonstrated in the gum/palate of affected cats and a target for potentially novel treatments.

The aim of the current study is to test the hypothesis that therapeutic intervention to reduce inflammation and microbial activity will ultimately lead to improvement of the health status of cats with FCGS.  In vitro model systems will be developed to investigate the aetiology and pathogenesis of FCGS and to test potential pharmacological interventions. The initial innate immune responses to identified pathogens in isolation or in combination will be investigated in vitro. A 3D in vitro model of the feline gingival stroma will be developed and used to interrogate the initial activation of the mucosal inflammatory response, following challenge with putative pathogens and including the effect of commensal oral bacteria identified in the healthy oral cavity. The 3D model will also provide a platform for investigating the efficacy of both existing and potentially novel antimicrobial, anti-inflammatory and anti-viral therapies, in isolation or in combination. This will include the use of liposomes as a local delivery vehicle for antimicrobial agents.

This project will give an ideal opportunity for training in a wide range of laboratory skills. These include microbiological and immunological laboratory techniques, which are applicable to many areas of research. The successful applicant would also be trained in many generic research skills.

If you would like to discuss the post or require further information, please contact Dr Marcello Riggio (Marcello.Riggio@glasgow.ac.uk), to whom applications comprising a CV and covering letter should also be sent.

Applicants must have at least a 2(i) in a life sciences or related degree and should demonstrate an interest in host-pathogen interactions in oral inflammatory diseases.

17 October 2014