Programming cellular behaviors with biological circuits
Living cells use circuits of interacting genes and proteins to sense and respond to signals, communicate, remember information, and develop into multicellular organisms. These circuits often use non-intuitive designs. Making sense of those designs is essential for understanding, predicting, and controlling natural cellular behaviors. It is also essential for designing and building synthetic circuits that can program biomedically useful cellular behaviors.
Strategy: naturally inspired synthetic circuit design. Our lab combines two approaches to the design and analysis of biological circuits: First, we create and analyze fully synthetic molecular circuits that provide new cellular capabilities. Second, we reconstitute core pathways in minimal cell culture systems and quantitatively analyze their behavior at the single cell level. A key premise of the lab is that these two approaches are synergistic: Natural pathways inform the design of their synthetic counterparts by providing elegant and unexpected solutions to synthetic design challenges. Conversely, for synthetic circuits to interact predictably with natural pathways we need to know how those natural pathways sense, process, and respond to their inputs. By combining these approaches, we aim to establish a foundation for programmable cell-based therapeutics and develop conceptual frameworks for understanding biological systems. Our approaches blend synthetic biology, mathematical modeling, and dynamic single cell analysis.
Research focus: bringing synthetic biology to multicellular systems. We currently focus on capabilities required for natural mammalian development and synthetic therapeutic and developmental circuits. These include intercellular communication to allow coordination among cells; computation to allow signal processing within the cell; and memory to store information. We also develop new technologies that enable these systems. See our lab website for recent projects.