Zonal distribution and molecular regulation of apoptosis in organotypic hepatocyte cultures.

Initially, this research project deals with the investigation of the molecular regulation mechanisms of apoptosis occuring in cultivated hepatocytes. Various organotypical culture systems such as the co-culture of hepatocytes with primitive biliary epithelial cells and the collagen gel sandwich configuration will be tested. Especially the effect of trichostatin A, which is a prototype of histone deacetylase inhibitor, but also structure analogues, on apoptosis will be examined in order to develop a hepatocyte culture system that is more stable (maintenance of biotransformation capacity) and has a longer lifespan via inhibition of apoptosis. Measurements will be done at the activity, protein and mRNA levels. At a later stage, it will also be investigated in vitro whether apoptosis is zonally distributed across the liver and if so, how this is regulated.