Understanding how bile acids cause cognitive deficits in Primary Biliary Cholangitis (PBC)
This project aims to investigate the specific effects bile acids have on cell populations within the brain, as well as the ability of drug treatments to reverse these effects.
PBC is a chronic liver disease that causes debilitating symptoms of cognitive impairment and fatigue. These symptoms have a huge impact on quality of life, and aren’t improved by current therapies.
This project investigates the cell specific effects of cholestasis in the brain, as well as the potential improvement of health with either currently used or novel anti-cholestatic agents. The choice of optimal agent will be determined during the PhD project.
Through the link with our industrial partner Intercept, we aim to determine if an existing licenced therapy Obeticholic acid (OCA) or second-generation anti-cholestatic drugs can protect brain resident cell types from toxic effects of bile acids and other toxins.
Positive findings from this study would suggest that drug therapy could be used to alleviate the debilitating cognitive decline in PBC patients. This would have direct translational impact for the patient population.
- Use molecular and cellular approaches to interrogate the effects of PBC-relevant bile acids (and other toxins) on the phenotype, function and metabolism of human derived neuronal/astrocyte cell cultures.
- Modulate bile acid signalling pathways in these cells.
- Determine if anti cholestatic agents are able to modulate or limit the effect of PBC-relevant bile acids on neuronal/astrocyte cell biology.