Natural regulatory networks have complex features to ensure robust cellular functions. However, robustness comes with a price: it requires cellular resources, imposing a metabolic burden on cells. The overarching goal of this project is to understand the principles of biological robustness by building genetic circuits from the bottom-up. The work will benefit society by providing design principles and engineering strategies to ensure that biological systems behave as designed over a long time scale. In addition, while the PI's focus is to apply design principles to biochemical production platforms, the same approach can be applied to other problems, such as environmental and health issues, by replacing the actuator modules with toxic chemical degrading pathways and pathogen killing mechanisms.
The overarching goal of this project is to understand the principles of biological robustness by building genetic circuits from the bottom-up. The intellectual merits of this project are threefold. First, it will enable the quantitative assessment of the burden imposed by individual genes, providing guidelines for part selection in synthetic biology. Second, it will help address the issues of metabolic burden and evolution by using genetic circuits. Last, by building functions from the bottom-up, hypotheses regarding the dynamics and evolution of highly interconnected natural regulatory networks will be tested. The research approach will involve (i) the identification and characterization of sensory and gene regulatory elements, (ii) the building of negative feedback loops and redundant circuits, and (iii) the implementation of these synthetic circuits in microbial cell factories for chemical and drug production.
