Feedback mechanisms play a critical role in the maintenance of cell homeostasis in the presence of disturbances and uncertainties. Motivated by the need to tune the dynamics and improve the robustness of gene circuits, biological engineers have proposed various designs that mimic natural molecular feedback control mechanisms. However, practical and predictable implementations have proved challenging because of the complexity of synthesis and analysis of complex biomolecular networks. Here, we analyze and experimentally validate a synthetic biomolecular controller executed in vitro. The controller ensures that gene expression rate tracks an externally imposed reference level, and achieves this goal even in the presence of certain kinds of disturbances. Our design relies upon an analog of the well-known principle of integral feedback in control theory. We implement the controller in an
Stochastic pulsatile dynamics have been observed in an increasing number of biological circuits with known mechanism involving feedback control and bistability. Surprisingly, recent single-cell experiments in
- NSF-PAR ID:
- 10197914
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 117
- Issue:
- 43
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- p. 26608-26615
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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