The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Emergent bistability by a growth-modulating positive feedback circuit
Open accessAbstract
A synthetic gene circuit is often engineered by considering the host cell as an invariable “chassis”. Circuit activation, however, may modulate host physiology, which in turn can drastically impact circuit behavior. We illustrate this point by a simple circuit consisting of mutant T7 RNA polymerase (T7 RNAP*) that activates its own expression in bacterium Escherichia coli. Although activation by the T7 RNAP* is noncooperative, the circuit caused bistable gene expression. This counterintuitive observation can be explained by growth retardation caused by circuit activation, which resulted in nonlinear dilution of T7 RNAP* in individual bacteria. Predictions made by models accounting for such effects were verified by further experimental measurements. Our results reveal a novel mechanism of generating bistability and underscore the need to account for host physiology modulation when engineering gene circuits.
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Cited by
Interdependence of Cell Growth and Gene Expression: Origins and Consequences
Scott, M., Gunderson, C. W., Mateescu, E. M., Zhang, Z., & Hwa, T. (2010) · Science · doi:10.1126/science.1192588 · Cited by 1,470
Five hard truths for synthetic biology
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Bacterial growth laws and their applications
Scott, M., & Hwa, T. (2011) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2011.04.014 · Cited by 309
Positive Feedback Between PU.1 and the Cell Cycle Controls Myeloid Differentiation
Kueh, H. Y., Champhekar, A., Nutt, S. L., Elowitz, M. B., & Rothenberg, E. V. (2013) · Science · doi:10.1126/science.1240831 · Cited by 273
Engineered microbial consortia: strategies and applications
Duncker, K. E., Holmes, Z. A., & You, L. (2021) · Microbial Cell Factories · doi:10.1186/s12934-021-01699-9 · Cited by 196
Self-citation
Metadata
- Authors
- Tan, C., Marguet, P., & You, L.
- Venue
- Nature Chemical Biology
- Published
- 2009-10-04
- Volume
- 5
- Issue
- 11
- Pages
- 842-848
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2135783707
- Cited by
- 339
- References
- 48
- FWCI
- 9.00
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
