About the Project
The main aims of this project will be to analyse interactions between microbiome sequence data (tissue analyses) and antibodies to bacterial species (blood screening), metabolites such as bile acids and short chain fatty acids (human and microbiota-derived), and markers of gut barrier function, to assess their contribution to the risk of microbial-mediated gastrointestinal cancer development. A secondary aim will be to study the interactions with host genetics and nutritional factors as potential mediators of microbiota disease pathogenesis. The project will highlight the importance of the interaction between microbial infection, dysbiosis (including bacterial, viral, and fungal), gut barrier function, and metabolism in the aetiology of hepatobiliary and pancreatic cancers.
The PhD project will benefit from a collection of European human cohort studies, including case-control and nested case control studies of hepatocellular carcinoma (the main type of liver cancer) and other cancers of the hepatobiliary tract (together termed hepatobiliary cancers) and pancreatic cancers to analyse metagenomic sequences, antigen serology data, metabolite data, and markers of gut barrier function to test the hypothesis of a major contribution from microbial dysbiosis and metabolic dysfunction to gastrointestinal cancer aetiology.
This PhD will involve both laboratory assays such as ELISA assays, qPCR, metagenomic sequencing, mass spectrometry, but there will be a major focus on biostatistical and bioinformatic approaches. These analytical methods will be used to examine modification of microbial associations by gut permeability and microbial and human metabolites, nutrient levels, host genetic variation and other dietary/lifestyle factors.
The project will add to our existing data on hepatitis infection status and a host of other biomarker data on the hepatobiliary cancer cases and controls from a prospective cohort, including targeted and untargeted metabolomics and Metabolic Syndrome Score assessments. These analyses will be combined with metagenomic data and human host genetic data (e.g., immune gene variants, bile acid receptors gene variants, etc) that are available in data repositories. This project will be nested within a larger ongoing examination of the aetiology of gastrointestinal cancers related to the same factors.
For further details and application procedure see https://www.ucd.ie/sbbs/research/researchvacancies/
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