Proteins are nanometer-scale molecules whose composition and shape are specified by genes. Inside the cell, they catalyze chemical reactions, perform mechanical work, and assemble into larger structures. The collective action of very many proteins drives cell growth, division, and movement. Proteins are often controlled by external signals – for example, adding a nutrient to the cellular environment might turn a protein “on” or “off” by binding to the protein and altering its shape or dynamics. Such allosteric control provides a basic mechanism for cells to sense and respond to the environment and is a building block for intracellular communication. A complete understanding of how allosteric control works, and how it is encoded in the genetic sequence of proteins, would allow biologists to engineer proteins that respond to artificial cues. In this project, the PI’s research team will use computation and experiment to understand how allosteric regulation in a protein is optimized, define physical properties distinguishing allosteric surfaces, and construct a set of synthetic allosteric switches that enable control of cell growth rate with light. This work will establish a practical, general toolkit for engineering allosteric regulation, and provide fundamental insights into how natural allosteric regulation might evolve. This proposal will train graduate, undergraduate, and bio-oriented high school students to improve their skills in basic programming and research experimenta