Synthetic circuit for exact adaptation and fold-change detection

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Jongmin Kim, Ishan Khetarpal, Shaunak Sen and Richard M. Murray
Nucleic Acids Research, 42(9):6078-6089, 2014

Biological organisms use their sensory systems to detect changes in their environment. The ability of sensory systems to adapt to static inputs allows wide dynamic range as well as sensitivity to input changes including fold-change detection, a response that de- pends only on fold changes in input, and not on ab- solute changes. This input scale invariance underlies an important strategy for search that depends solely on the spatial profile of the input. Synthetic efforts to reproduce the architecture and response of cellu- lar circuits provide an important step to foster under- standing at the molecular level. We report the bottom- up assembly of biochemical systems that show exact adaptation and fold-change detection. Using a malachite green aptamer as the output, a synthetic tran- scriptional circuit with the connectivity of an incoherent feed-forward loop motif exhibits pulse generation and exact adaptation. A simple mathematical model was used to assess the amplitude and duration of pulse response as well as the parameter regimes required for fold-change detection. Upon parameter tuning, this synthetic circuit exhibits fold-change detection for four successive rounds of two-fold input changes. The experimental realization of fold-change detection circuit highlights the programmability of transcriptional switches and the ability to obtain predictive dynamical systems in a cell-free environment for technological applications.