Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of excess fat in the liver, termed steatosis. NAFLD encompasses simple steatosis and its inflammatory state called non-alcoholic steatohepatitis (NASH) which is a core driver of liver cirrhosis, and hepatocellular carcinoma (HCC). This project will focus on the generation of colon and liver organoid culture systems to study the interaction between intestinal immunity and permeability with liver inflammation in NASH.
Organoids are three dimensional structures grown in vitro from primary tissue that retain the characteristics of their primary source, including self-renewal, organisation, and differentiation. As such, they are an optimal model to study the influence of genetic and environmental factors on disease progression and treatment. Using in vitro co-culture systems, this project will examine the factors that contribute to “leaky gut” in NASH, and how translocating microbes influence liver inflammation. In addition to enteric bacterial, fungal and human viruses, this project will contain a unique focus on bacteriophages, and theircontribution to chronic immune stimulation in both the gut and liver. This study utilises cutting edge primary cell culture, flow cytometry and molecular biology techniques to discover unknown connections between gut and liver immunity, and will enable a better understanding of inter-organ interactions that contribute to NASH pathogenesis.
Student level: PhD
Supervisor: Professor Golo Ahlenstiel