Control Theory for Synthetic Biology: From Fundamentals to Application
Domitilla Del Vecchio
Associate Professor, Department of Mechanical Engineering, MIT
Friday October 13, 4:00pm, 3-270
Synthetic biology has tremendous potential for tackling pressing societal problems from energy, to environment, to medicine. The success of the field hinges on the critical ability to design genetic circuits that perform as intended once interacting with each other inside the cell. Today, this ability is still largely missing. Genetic circuits rarely perform as specified because they are poorly robust to context: a circuit’s input/output behavior is affected by surrounding systems, in ways that can be very subtle.
In this talk, I will take a control theoretic approach to this lack of robustness and describe a mathematical framework, along with experimental validations, to predict and mitigate effects of context-dependence. I will address two main sources of context-dependence: direct connectivity of a circuit module to other systems and competition among different circuit modules for limited cellular resources, focusing mostly on the latter problem. For this, I will introduce a decentralized feedback control approach for decoupling circuit modules from the effects of resource competition. Finally, I will transition to application and introduce our preliminary work towards establishing a control theoretic framework for gene-based stem cell reprogramming. Overall, our results contribute to the progress of synthetic biology by aiding designs that are sufficiently robust for practical use.