Understanding processes and mechanisms affecting the oral microbiome using OMICs approaches

Strategic Priority Area: Bascis Bioscience underpinning health
Keywords: Biofilm, metabolomics, oral

Abstract:
Our groups overall interest lies in understanding the dynamic interactions between complex oral biofilms, their role in human health, and how chemotherapeutic intervention impacts the interactome and reactome. The metabolome and proteome are the small molecule and protein outputs of a cell, respectively, and unlike the genome, the metabolome and proteome can provide readouts of the current phenotype of the cell. Using these approaches it is possible to obtain very detailed information about the evolution of small molecules and lipids excreted by culture systems during their growth phases. Coupled to rapid proteomic analysis at key time points, we would have the opportunity to observe the production of biomarkers and metabolites as they are produced over time. With this in mind we aim to use our models and his technologies to make strides into oral health improvements. The aim of this PhD studentship is to use complex biofilm models associated with host-microbial interactions in the healthy oral cavity and to use to undertake profiling of the interactome. It is our hypothesis that biomarkers or molecular signatures are expressed under certain conditions that influence biofilm dysbiosis and ultimately host immunity.

In year 1 will use existing oral biofilm models, developed in our laboratory to evaluate the secreteome (metabolic and proteomic) of complex biofilms during their development and maturation. Once methodology is standardized and validated we will investigate the effects on metabolic and proteomic profiles through the exchange of key microbial species within the biofilms to delineate their influence on the key pathways involved in biofilm homeostasis. These studies will inform us of quantifiable target molecules associated with oral health.

In year 2 will initially use exogenous analogues of metabolites identified in year 1 and apply these to a range of important cells associated with the oral cavity, including epithelia (cell line and primary cells), monocytes and macrophages, and a 3-D model. We will undertake inflammatory profiling of these cells in order to understand the dominant patterns of the host response. We will then use this as the basis to investigate whether these are expressed under co-culture conditions with complex biofilms, as outlined in year 1, and simultaneously evaluate the secreteome under these conditions. These studies will provide a comprehensive assessment of inflammatory mediators associated with biofilm secreteome.

In year 3 the biofilm and cells models described in years 1 and 2 we will then assess how these are impacted by the addition of actives. We will assess exogenously applied molecules and intact biofilm co-culture systems actives, assessing the dynamics of the biofilms, downstream inflammatory effects, and secreteome outputs. These applied studies will enable us to evaluate the direct impact of important oral hygiene actives within a complex system.