One of the most exciting ideas in modern biology is the notion that cells can be “programmed” to execute a desired complex behavior. We can imagine a future where cells—as advanced therapeutics—are programmed to repair damaged tissue or eradicate a pathogen. Indeed, recent pioneering examples such as chimeric antigen receptor-modified T cells1 have cured diseases which, just a few years ago, were incurable. Considering their potential to regenerate every cell in the body and create full tissues de novo, pluripotent stem cells have lagged behind in this cell therapy revolution.
To accomplish this goal, we leverage our unique expertise in working with cellular optogenetic tools. These tools utilize light-sensitive proteins, often from plants, which are engineered to control the activity of a protein or signaling pathway with the simple application of a particular wavelength of light. We pair these tools with a suite of modern light-delivery devices, to gain an unprecedented level of spatiotemporal control over cell signaling, especially in contrast to ligand or drug-based stimulation. Thus, we can dissect the impact of signaling dynamics and the organization of underlying pathway components by assessing the cellular responses to light¬ stimuli. Ultimately, by combining input control with live-cell reporters of cell state we hope to advance predictive models of stem cell behavior