Design and implementation of a synthetic biomolecular concentration tracker

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Victoria Hsiao, Emmanuel LC de los Santos, Weston R Whitaker, John E Dueber, Richard M Murray
10.1021/sb500024b, (preprint posted on BioRxiv 10.1101/000448, 15 Nov 2013)

As a field, synthetic biology strives to engineer increasingly complex artificial systems in living cells. Active feedback in closed loop systems offers a dynamic and adaptive way to ensure constant relative activity independent of intrinsic and extrinsic noise. In this work, we use synthetic protein scaffolds as a modular and tunable mechanism for concentration tracking through negative feedback. Input to the circuit initiates scaffold production, leading to colocalization of a two-component system and resulting in the production of an inhibitory antiscaffold protein. Using a combination of modeling and experimental work, we show that the biomolecular concentration tracker circuit achieves dynamic protein concentration tracking in Escherichia coli and that steady state outputs can be tuned.