An investigation of the credentials of a novel lysine deacetylase as an age-related biomarker for periodontitis
The aim of the project is to investigate the role of SIRT2 in periodontitis in cell culture models in vitro and as a diagnostic measure in vivo.
Periodontitis is chronic inflammation of the tissues that surround and support the teeth which is common in older people. The inflammation of these tissues can cause pain and can lead to tooth loss. Another issue is the rising number of people suffering from this disorder as the proportion of the elderly in our society increases. Our research group previously identified that high levels of an unusual protein (an enzyme that alters the structure of other proteins) are present in the saliva of patients with periodontitis whereas saliva from healthy individuals has a lot less of this protein. This project will investigate how this novel protein contributes to inflammation in periodontitis and whether or not measuring this protein in saliva can be useful in the dental clinic where patients with periodontitis are cared for. If the results of this project are positive then this may allow the dentist to diagnose periodontitis earlier and predict which patients might not respond so well to treatment.
- Investigation of SIRT2 protein and mRNA expression and regulation in leukocytes and periodontal cells using immunohistochemistry (IHS), western blotting and qPCR.
- Establishment of assays (immunoblot and IHS) for protein acetylation (NF-κB and histones H3 & H4-known targets for SIRT2). Development of SIRT2 knockdowns using SiRNA.
- Functional studies of SIRT2 activity in response to inflammatory signals and the effect of knockdown on inflammatory responses: cytokines and matrix metalloproteinases analysed by low density expression arrays TLDA & ELISA.
- Analysis of salivary SIRT2 protein levels in 2 independent, longitudinal clinical trials of periodontitis.
- Analysis and modelling of biomarker data in the context of other biomarker information and clinical and demographic information