Design and implementation of a biomolecular concentration tracker.
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.
Division of Biology and Biological Engineering, California Institute of Technology , Pasadena, California United States.
Victoria
V
Hsiao
Emmanuel L C
EL
de los Santos
Weston R
WR
Whitaker
John E
JE
Dueber
Richard M
RM
Murray
D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D025461:Feedback, Physiological; D000071677:Histidine Kinase; D007700:Kinetics; D016350:Leucine Zippers; D008958:Models, Molecular; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism
D029968:Escherichia coli Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase; D010744:Phosphoric Monoester Hydrolases
feedback circuits; live-cell tracking; negative feedback; synthetic protein scaffolds; two-component systems