Designing with living systems in the synthetic yeast project

Synthetic biology is challenged by the complexity and the unpredictability of living systems. While one response to this complexity involves simplifying cells to create more fully specified systems, another approach utilizes directed evolution, releasing some control and using unpredictable change to achieve design goals. Here we discuss SCRaMbLE, employed in the synthetic yeast project, as an example of synthetic biology design through working with living systems. SCRaMbLE is a designed tool without being a design tool, harnessing the activities of the yeast rather than relying entirely on scientists’ deliberate choices. We suggest that directed evolution at the level of the whole organism allows scientists and microorganisms to “collaborate” to achieve design goals, suggesting new directions for synthetic biology. Synthetic biology often views the organism as a chassis into which a circuit can be inserted. Here the authors explore the idea of the organism as a core aspect of design, aiding researchers in navigating the genetic space opened up by SCRaMbLE.