Mesoscopic models of neurotransmission as intermediates between disease simulators and tools for discovering design principles.

Two grand challenges have been declared as premier goals of computational systems biology. The first is the discovery of network motifs and design principles that help us understand and rationalize why biological systems are organized in the manner we encounter them rather than in a different fashion. The second goal is the development of computational models supporting the investigation of complex systems, in particular, as simulation platforms in personalized medicine and predictive health. Interestingly, most published systems models in biology contain between a handful and a few dozen variables. They are usually too complicated for systemic analyses of organizing principles, but they are at the same time too coarse to allow reliable simulations of diseases. While it may thus appear that the modeling efforts of the past have missed the declared targets of systems biology, we argue in this article that midsized mesoscopic models are excellent starting points for pursuing both goals in computational systems biology. © Georg Thieme Verlag KG Stuttgart · New York.