Circuits of Unknown Function

Cells use circuits of interacting genes and proteins to control their behaviors, but the design principles that govern genetic circuit architecture usually remain mysterious. In order to figure out these design principles we combine three synergistic approaches: First, we apply time-lapse movies and quantitative image analysis to follow the dynamics of genetic circuits in individual cells. Second, we develop synthetic biology approaches in which we design and construct new genetic circuits (or re-wire natural ones) to implement specific functions in cells. Finally, we use mathematical models to explore the dynamics of actual and potential genetic circuit architectures. We work in bacteria, yeast, and mammalian cells, model systems that enable precise genetic manipulation and measurement of the dynamics of cellular gene circuits. In this talk, I will discuss recent work on design principles of the mammalian Notch signaling pathway.