On March 20th the Wageningen Centre for Systems Biology (WCSB) will organise a seminar on systems biology. The seminar is free, will take an hour and will be followed by drinks. No registration is necessary, so feel free to come by!
prof. dr. Barbara Bakker, Professor of Medical Systems Biology, Systems Biology Centre for Energy Metabolism and Ageing, UMCG/RUG, Groningen
"Modelling of lipid metabolism for young and old"
Mitochondrial fatty-acid metabolism plays a key role in ageing as well as in acquired and inborn metabolic diseases. We use a variety of experimental and computational techniques to get an systems view on mitochondrial function in ageing and metabolic diseases. We constructed a detailed and dynamic computational model of the mitochondrial fatty-acid oxidation. The model contains reversible and saturable enzyme-kinetic equations and experimentally determined parameters for rat-liver enzymes. It has been validated by adding palmitoyl CoA or palmitoyl carnitine to isolated rat-liver mitochondria: without refitting of measured parameters, the model correctly predicts the b-oxidation flux as well as the time profiles of most acyl-carnitine concentrations. By simulating the response to increased fatty-acid substrate (a condition typical for fasting or obesity) we revealed an intrinsic vulnerability of the pathway to substrate overload. I will discuss the mechanism underlying this vulnerability and potential cellular protection mechanisms in the light of our ongoing projects into medium-chain acyl dehydrogenase (MCAD) deficiency and ageing.
More information about WCSB and the 14 different projects can be found on the website www.wur.nl/systemsbiology.