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Feedback mechanisms and systems medicine: Modeling cholesterol homeostasis for drug discovery

Feedback mechanisms and systems medicine: Modeling cholesterol homeostasis for drug discovery

This video was recorded at 20th International Symposium on Microsomes and Drug Oxidations (MDO), Stuttgart 2014. Feedback mechanisms are the key features of cellular organisation; however, they can cause severe misinterpretation of the data. Cholesterol biosynthesis is a robust and highly regulated pathway; nevertheless, hypercholesteremia is a prevalent disease in the western world, which is seemingly contradicting. Statins are common drugs to treat hypercholesteremia in humans, taken by millions of people worldwide. Even if in principle safe, stat ins are known also for some severe adverse effects in particular patients. In the tutorial the participants will first design a very simple model of hypothetic metabolic pathway and observe its response to various simulated treatments. Next, a feedback will be introduced to the pathway and the simulated treatments will be repeated, to illustrate effects of the feedback loop. In the second part, the participants will get acquainted with the cholesterol biosynthesis model and will learn to simulate the effects of statins on cholesterol biosynthesis pathway as well as test some other treatment strategies. OpenModelica software (https://www.openmodelica.org) will be used for the tutorial in combination with SysBio library for systems biology/medicine modelling.

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