Dr J Konkel, Dr J Grainger, Prof A Barton
No more applications being accepted
About the Project
For decades a link between periodontitis and rheumatoid arthritis (RA) has been proposed. Recently epidemiologic association between RA and periodontitis has been demonstrated, heralding the potential for treatments targeted at the relatively accessible oral barrier to mediate positive outcomes in RA. Indeed, initial studies have indicated that treatment of periodontitis can improve RA severity and that RA patients with active periodontitis are less responsive to conventional therapeutic interventions. Thus, understanding the cellular/molecular links between periodontitis and RA is vital not only to promote development of novel strategies for RA treatment, to both delay onset and reduce severity, but also to ensure effective delivery of therapy.
Most research to date has focused on the roles of periodontal pathogens in driving the inflammatory consequences of periodontitis in RA. However, non-bacterial links between these two diseases remain minimally explored. This is surprising given their similar aetiology, the common immune dysfunction in both the inflamed synovium and oral barrier, and that aberrant inflammation results in bone destruction in both pathologies. Key mediators of pathology in both diseases are CD4+ T-cells producing the cytokine IL-17, called Th17-cells. This project will explore possible links between periodontitis and RA mediated by Th17 cells, determining whether Th17 cells generated at the oral barrier could mediate pathological consequences in the joint microenvironment. Given the interdisciplinary nature of this project undertaking these studies will lead to training in many cutting-edge immunology techniques including: in vivo models of inflammation, in vitro culture of immune cells, multicolour flow-cytometry, and genome-wide transcriptional profiling.
This project requires a multi-disciplinary approach to achieve its objectives, and will therefore provide comprehensive training in a plethora of immunological, biological, microbiological, and in vitro and in vivo approaches. This will be complimented by basic training in bioinformatics. Moreover, our experimental approach will utilize both in vivo experimental animal models and samples from well-defined patient cohorts, allowing the student to become proficient in both animal and human sample research. Each of the distinct aspects of the project will be supported by the supervisory team.
http://www.mig.ls.manchester.ac.uk/people/joannekonkel/
Funding Notes
This project is funded by Arthritis Research UK and will cover fees and stipend. If you are interested please make contact with the Supervisor. You must also submit an online application - https://www.bmh.manchester.ac.uk/study/research/apply/. Please select Immunology as the programme. Applications will close once a suitable candidate is found.
Applications are invited from UK/EU nationals only. Applicants are to hold a minimum upper second class undergraduate degree (or equivalent) in Immunology or directly related subject area. A Masters degree in a relevant subject and/or extensive laboratory experience, such as a year in industry or previous employment as a technician, is desirable.
References
• Dutzan N, Abusleme L, Bridgeman H, Greenwell-Wild T, Zangerle-Murray T, Fife ME, et al. On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity. 2017;46(1):133-47.
• Moutsopoulos NM, Konkel JE. Tissue-specific immunity at the oral mucosal barrier. Trends Immunol. 2017; S1471-4906(17).
• Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nature Rev Immunol. 2015; 15(1):30-44.