Abstract
Cells can encode information about their environment by modulating signaling dynamics and responding accordingly. Yet, the mechanisms cells use to decode these dynamics remain unknown when cells respond exclusively to transient signals. Here, we approach design principles underlying such decoding by rationally engineering a synthetic short-pulse decoder in budding yeast. A computational method for rapid prototyping, TopoDesign, allowed us to explore 4122 possible circuit architectures, design targeted experiments, and then rationally select a single circuit for implementation. This circuit demonstrates short-pulse decoding through incoherent feedforward and positive feedback. We predict incoherent feedforward to be essential for decoding transient signals, thereby complementing proposed design principles of temporal filtering, the ability to respond to sustained signals, but not to transient signals. More generally, we anticipate TopoDesign to help designing other synthetic circuits with non-intuitive dynamics, simply by assembling available biological components.
Highlights
Cells can encode information about their environment by modulating signaling dynamics and responding
A coherent feedforward (CFF) on c-Fos, a network motif in which a signal activates the target both directly and via an intermediary component[3], decodes the sustained output of MAPK signaling[4,5]. This architecture is consistent with proposed design principles of temporal filtering, which is the ability to respond to sustained signals, but not to transient signals[4,6]
Because decoder network architectures are not known, we develop a computational method for rapid prototyping of synthetic circuits with complex target dynamics, TopoDesign
Summary
Cells can encode information about their environment by modulating signaling dynamics and responding . A coherent feedforward (CFF) on c-Fos, a network motif in which a signal activates the target both directly and via an intermediary component[3], decodes the sustained output of MAPK signaling[4,5] This architecture is consistent with proposed design principles of temporal filtering, which is the ability to respond to sustained signals, but not to transient signals[4,6]. A comparatively simple signaling pathway to investigate decoding principles by synthetic circuit design is the mating pathway in the budding yeast Saccharomyces cerevisiae It is well-characterized, accepts a sustained stimulation with the α-factor pheromone as input[11], and was previously used, for example, to rationally tune G-protein coupled receptor signaling in this model eukaryote[12]
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