Realising Efficient and Robust Synthetic Biology Systems Using Systems and Control Engineering

Synthetic biology systems are as good as their reliability in terms of robustness and performance characteristics within a given host and an ever-changing environment. Progression to larger scale designs and higher order functionalities requires solid foundations for the design and implementation of robust and efficient biological systems. The lessons learned by the advancements made in more established engineering disciplines point to the fact that adapting and implementing systems and control theory principles to synthetic biology is crucial for meeting these robust performance requirements. To that effect, we study and work towards implementing and combining synthetic feedback control mechanisms within cells. In particular we focus on the design,  implementation and combination of synthetic biology feedbacks at various levels: (a) The first level focuses on the synthetic circuitry level, where feedback auto-regulation can be mediated directly through transcriptional regulation and implemented through various network topologies. (b) The second level focuses on engineering feedback in metabolic processes for optimizing the production of certain metabolites but more importantly, for balancing the flux of nutrients and ensuring a dynamically balanced allocation of cell resources when part of the native metabolic flux becomes diverted by synthetic branches. (c) At the population level we are working towards an extracellular environment sensor-actuator feedback control mechanism that can robustly keep extracellular concentrations around a desired setpoint. We study the above both from both a theoretical and an experimental viewpoint and consider combinations of these various feedbacks with the aim to deliver more resilient chasses for operating synthetic systems and to consequently reduce the host-imposed uncertainty on synthetic systems behaviour.