Death from liver disease is rising in all age groups with significant impact on healthcare systems. In liver failure patients often die of infection due to dysfunctional immune systems and are difficult to treat in intensive care units.
Our group has developed an interest and global expertise in the control of immunity in liver failure by lipids describing phospholipid control of monocytes. These molecules turn off anti-inflammatory responses and are the basis of future therapies to restore immune function and prevent patients dying of sepsis. This project aims to interrogate how lipids control immune and liver cells and test therapies for future clinical trials. It utilises a broad gamut of immunometabolism techniques including cell culture, flow cytometry, metabonomics, transciptomics, ELISA and advanced statistics.
In year 1-2 the student will learn lipid biology, metabonomics and statistics and identify lipid pathways of interest and choose the target cell(s) of most relevance. They will also learn how to: a) isolate human hepatocytes from donor liver tissues (normal, and steatotic/fatty) unused/rejected for transplantation, b) in vitro maintenance of hepatocyte culture, c) carry out assays to assess the function and activity of hepatocytes including cell attachment, overall metabolic activity, urea synthesis (ammonia detoxification assay), albumin synthesis, and cytochrome P450 activity (drug metabolism assay).
In year 2-3 they will use cell culture and flow cytometry to determine the functional and phenotypic effects of lipids on immune and hepatic cells. This will also involve testing candidate drugs for immune restoration to form the basis of human experimental medicine clinical trials. The hepatocytes will be analysed at the molecular level to study the expression of key genes involved in lipid metabolism.
In year 3-4 transcriptomics of cells from year 2-3, pathway analysis and writing will be undertaken and immune cell/hepatocyte co-culture if time permits.