Tissues by Design
Our project focuses on tissue self-construction to achieve specific patterns of cell differentiation (initially with fluorescence, ultimately with cell fate regulators) with genetic circuits. To accomplish this, we focused on three components: cell-cell communication pathways, intracellular information processing circuits, and cell-cell adhesion. Through engineered control of these mechanisms, we are investigating how programmed local rules of interactions between cells can lead to the emergence of desired global patternings.
Above is the result of a simulation run, starting with undifferentiated cells and ending with a pattern.
Specifically, for cell-cell signaling, we developed a modular juxtacrine platform, using Notch and Delta proteins. For intracellular information processing circuits, as a proof of concept, we build a 2-input AND gate. For cell-cell adhesion, the final output of our system, we used cadherin. Below is an animation depicting our project components. The cell-cell signaling of Notch-Delta interaction leads to the cleavage of the Notch intracellular domain, which enters the nucleus and after logic processing, expresses cadherins, which cause cells to adhere to similarly expressing cells.
We developed software tools to model the behavior of our system. Below is a sample of a simulation of cells with genetic circuits and how they differentiate.