Optimization based design of synthetic oscillators from standard biological parts

Abstract

We consider the problem of optimal design of synthetic biological oscillators. Our aim is, given a set of standard biological parts and some pre-specified performance requirements, to automatically find the circuit configuration and its tuning so that self-sustained oscillations meeting the requirements are produced. To solve this design problem, we present a methodology based on mixed-integer nonlinear optimization. This method also takes into account the possibility of including more than one design objective and of handling both deterministic and stochastic descriptions of the dynamics. Further, it is capable of handling significant levels of circuit complexity. We illustrate the performance of this method with several challenging case studies.