Build Synthetic Circuits at Different Scales

Multicellular organisms rely on the coordinated actions of diverse organs to sustain life. Each organ comprises cells that communicate with each other to execute physiological functions, and each cell encodes gene regulatory networks that shape its gene expression programs. The intrinsic complexity of biological systems, including features such as redundancy that endow them with robustness, also makes them difficult to study using reductionist approaches alone. To elucidate quantitative design principles underlying multicellular organization, I adopted a bottom-up approach and built synthetic circuits at multiple scales. In the first project, I engineered a single-gene incoherent feedforward circuit that leverages multispecific microRNA targeting to achieve dosage-invariant and tunable protein expression across wide ranges of gene copy numbers. In the second project, I constructed a multicellular reaction–diffusion circuit that integrates juxtacrine and paracrine signaling to generate self-organized, periodic Turing patterns. Together, these studies introduce new tools for engineering regulatory behaviors, reveal general principles that govern biological organization across scales, and pave the way for potential translational applications.