In engineering, the use of mathematical modeling for design purposes has a long history. Long before any technical realization, a system is planned, simulated, and tested extensively on the computer. In biosciences, however, the application of model-based design before going to the wet lab is still rather rare but has particularly high potential in synthetic biology. We demonstrate exemplarily how mathematical modeling and numerical optimization can be used for the design of a circadian rhythm that is supposed to oscillate robustly with respect to uncertainty in system parameters.