Learning to Program Cellular Machines: Engineering Cells to Treat Disease, Build Tissues, and Elucidate Design Principles

The ability to use living cells as a powerful new platform for therapeutics has the potential to transform medicine. With newfound capabilities in genetic engineering and an encyclopedic knowledge of molecular components, we have the potential to engineer cells as smart sense-and-response systems that can be tailored to address the unmet needs of complex tissue-based diseases such as cancer, autoimmunity, and degeneration. Living cells, particularly immune cells, have the unique capability to infiltrate, recognize, coax and kill diseased tissues. Conversely, this cell engineering framework also presents a powerful way to test and systematically understand the general principles by which molecular components are networked to create regulatory circuits capable of precise and robust decision making. In the new science of cellular engineering, many of the most exciting challenges and roadblocks lie in developing general modules for cell sensing, recognition, communication, feedback control and decision making -- modules that could be flexibly used to program diverse cellular behaviors rapidly and predictably. I will describe our efforts to construct such modular cell engineering platforms and to use them to build smarter immune cell therapies, as well as to build self-organizing multi-cellular systems.