Title: Investigating periodontitis host-related factors at molecular level: healthy-to-diseased periodontium single-cell characterisation and molecular dynamics of aging.
Funder: The Academy of Medical Sciences

Abstract: The aim of this research is to investigate host factors of periodontitis by establishing the cell states and transitions from healthy to chronic inflamed periodontal ligament (PDL) at a single-cell level, as well as the effect of aging on human periodontal cells (gingiva and PDL). Periodontitis is a widespread oral disease within the present UK and global adult population. The day-to-day treatment and prevention for periodontitis is mainly based on the removal of plaque, the primary risk factor causative of the disease. However, even though prevention and treatment of the disease has improved over the years, periodontists is still the 6th most common non-communicable disease worldwide. Therefore, further understanding of host factors such as cellular interaction dynamics, molecular pathways, and aging (an independent risk factor of the disease) is crucial for improving prevention and treatment of this common disease. We will use state-of-the-art single-cell RNA-seq analysis, never before used in human PDL, allowing us to investigate intra-population heterogeneity (potentially revealing cell subtypes), key gene expression, and cellular dynamics during health-to-disease transition. Also, we will investigate the transcriptomics and epigenetics differences between young and aged gingiva and PDL cells in vitro using high throughput RNAseq and ChIP-Seq. Allowing us to shed a light on the key molecular information of aging as a risk factor for periodontitis. Together, the data generated from this project will increase the understanding of periodontitis host risk factors resulting in knowledge that can be used to enhance periodontitis prevention and treatment.

Lay abstract: The aim of this project is to understand how human periodontal ligament cells behave in disease when compared to health, as well as understand how human gingival and periodontal ligament cells age at a molecular level. We want to understand that because gaining knowledge about those factors can help improve the prevention and treatment of periodontitis. Periodontitis is an advanced stage of the gum disease that is common in the UK and in the world. The way periodontitis prevention and treatment happens is based on removing dental plaque (a sticky substance that contains bacteria). Plaque attacks the tissues that hold teeth into place (gingiva and periodontal ligament) and once these are destroyed, bone is also lost, ultimately leading to tooth loss. Although we understand on how plaque starts the disease, little is known about how the periodontal ligament reacts to the attacks at a cellular and genetic level. Moreover, research has shown that as we age, the risks to have periodontitis increase, however, we do not fully understand the reasons behind it. In order to gain knowledge about these factors involved in periodontitis, we will use a cutting-edge molecular biology analysis called single-cell-RNA-seq capable to generate a map of cells and genes in the periodontal ligament. Also, we will age gingiva and periodontal ligament cells in the petri dish so that we can compare the genetic and epigenetic (nature/nurture) profiles of aged cells to young ones. We hope that this project gathers knowledge to help protecting people against periodontitis.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL;INFECTION