Browsing by Author "Reichart, Thomas"

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    DNA microarray based gene expression profiling in human hepatocyte cells to serve as a basis for dynamic modelling of the human liver : a systems biology approach
    (2008) Reichart, Thomas; Schmid, Rolf D. (Prof. Dr.)
    This thesis provides a holistic overview over the gene expression pattern in human hepatocyte cells after induction with rifampicin. The expression levels of all human genes were determined using full genome microarrays from Affymetrix after several points in time (6, 24 and 72 h) after induction in three individual patients. In addition 151 liver specific genes were monitored more frequently using sub-genome Arrays from Eppendorf. The results were confirmed by Realtime PCR and Western-Blot analysis. Identified genes play a role in carbon metabolism (gluconeogenesis), in heme biosynthesis, in bulirubin-, bile acid- and lipid metabolism as well as xenobiotic-metabolism and transport. The observed cell response on RNA level over time allowed new insights in the regulation of this complex system. Next to the network reconstruction, based on the full genome array data, the highly time resolved measurements enable dynamic modelling of expression and therefore a mathematical reproduction of the cellular response upon the stimulus. Using the developed models predictions concerning the behaviour of the "system hepatocyte" and the associated regulations will be possible in the future. This model based prognosis will especially allow improved drug development and personalized medicine.