Domitilla Del Vecchio, a professor at the Massachusetts Institute of Technology (MIT), has been at the forefront of integrating control systems engineering with synthetic biology. Her work, recently published in a comprehensive paper, explores how control systems engineering can be applied to synthetic biology, with a focus on cell therapy and cell fate reprogramming for regenerative medicine.
The paper highlights a critical challenge in these fields: the need to accurately control the concentration of specific regulatory factors within cells, despite environmental uncertainties and perturbations. These perturbations can significantly affect the dynamics of the biomolecular processes within cells, which Del Vecchio refers to as the “biomolecular plant.” Understanding and mitigating these perturbations is essential for achieving precise control over cellular behavior.
Del Vecchio delves into various biomolecular control implementations designed to enhance the robustness of the biomolecular plant’s output against perturbations. These control strategies are categorized into feedback and feedforward control architectures. While modern computers can implement sophisticated control laws, translating these into biomolecular processes within cells presents unique challenges. The constraints of biomolecular processes limit the feasible control laws to those that can be engineered through synthetic biology.
The paper reviews different biomolecular feedback and feedforward control implementations, with a particular focus on Del Vecchio’s own research. These control strategies are then applied to the context of cell fate reprogramming. Specifically, the paper illustrates how controlling a master regulatory factor at a specific level within a cell can reprogram skin cells into pluripotent stem cells. This application underscores the potential of control systems engineering in advancing regenerative medicine.
Del Vecchio concludes the paper by highlighting ongoing challenges and future research directions for biomolecular control design. Her work not only advances the field of synthetic biology but also opens new avenues for developing precise and robust control systems that can be applied to various biomedical applications. Read the original research paper here.