Project ID CM-HD2023_51

ThemeCM-HD

Co Supervisor 1A Centre for Craniofacial and Regenerative Biology (FoDOCS)Website

Co Supervisor 1B Centre for Host- Microbiome Interactions (FoDOCS)Website

Regulation of the junctional epithelium stem cell niche: a new stem cell population in the mouth

The junctional epithelium (JE) is an important group of epithelial cells that reside between the tooth and the oral mucosa. At the base of the JE is a putative epithelial stem cell niche (*) that replenishes the junctional epithelium. The region is defined by the expression of Wnt-responding cells. In periodontal disease, the JE can be damaged and regresses, breaking the connection between the tooth and surrounding gums. The regression of the JE is linked to the subsequent loss of bone around the tooth, ultimately leading to tooth loss. If the JE stem cell niche could be stimulated in periodontal disease, the regression of the JE could be reversed, providing a novel regenerative therapy for periodontal disease. For this we need to understand how the JE stem cell niche is regulated.

We Aim:
• To map the signals and cell populations that maintain the JE stem cell niche.
• To follow the impact of periodontal disease on the stem cell niche in a mouse model
• To rescue the regression of the JE in periodontal disease

We will use a range of transgenic mouse models, allowing us to address the molecular signals that control the JE, combined with mouse periodontal disease models. The student will be trained in molecular biology techniques, mouse transgenics, laser capture microdissection, bioinformatics (RNAseq), and imaging, and immersed in clinically relevant problems. Critical thinking, presentation and writing skills will be taught.

Objectives:
• Year 1: Mapping the JE niche
• Year 2: Impact of disease
• Year 3: Rescue of disease progression

One representative publication from each co-supervisor:

• Tucker, A.S., Dyer, C.J., Romero, J.M.F., Teshima, T.H.N., Fuchs, J.C., Thompson, H. (2018). Mapping the distribution of stem/progenitor cells across the middle ear during homeostasis and inflammation. Development Jan 11; 145. pii: dev.154393. doi: 10.1242/dev.154393. PMID: 29217752

• Lu, E. M. C., Hobbs, C., Dyer, C., Ghuman, M. & Hughes, F. J., Dec 2020, In: Journal of Periodontal Research. 55, 6, p. 859-867 9