(MRC DTP) Manipulating macrophages to improve oral inflammation
Dr J Konkel
Dr J Grainger
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
State-of-the-art immunology research has revealed that immune-mediated inflammation of the mouth (periodontitis) is linked to development of bowel cancer, cardiovascular disease and rheumatoid arthritis (RA). Manipulating the mouth immune system could be a powerful but unexplored mechanism to improve patient outcome in a number of life-threatening or life-limiting diseases. Despite this the immune system of the mouth is not well understood, presenting a critical knowledge gap that if overcome could have profound medical implications.
The immune system of the gums (termed gingiva) has different activities to the immune system in other organs. It must protect against the risk of commensal bacteria breaking through the gingival epithelial barrier, while also healing the damage that is continuously experienced in the mouth due to chewing and tooth brushing. Indeed, the wound repair process that occurs in the mouth is much faster than in the skin. A failure in this wound repair process underlies periodontal disease. Cells that are crucial to this different type of wound repair, but also in controlling commensal bacteria, are mouth monocytes and macrophages. Modulating the activities of these cells could be one possible mechanism to control and resolve periodontal inflammation.
Although well explored in other tissue, how monocytes and macrophages develop and are locally adapted to the gingiva has not been determined. Here we will employ pre-clinical models of inflammation, alongside samples from patient cohorts to define: (1) the developmental pathways of gingival monocytes and macrophages; and (2) the transcriptional networks and molecular pathways that underlie the functional diversity of these barrier resident immune mediators. Our research approach will utilize cutting-edge immunological techniques including multi-dimensional flow cytometry and transcriptional profiling of bulk and single-cell populations. Ultimately this work will provide much needed insight into how the myeloid network present in the gingiva is locally educated to ensure effective induction of both defensive and reparative mechanisms.
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.