Isocost Lines Describe the Cellular Economy of Genetic Circuits

Andras Gyorgy, José I. Jiménez, John Yazbek, Hsin Ho Huang, Hattie Chung, Ron Weiss, Domitilla Del Vecchio

Research output: Contribution to journalArticle

Abstract

Genetic circuits in living cells share transcriptional and translational resources that are available in limited amounts. This leads to unexpected couplings among seemingly unconnected modules, which result in poorly predictable circuit behavior. In this study, we determine these interdependencies between products of different genes by characterizing the economy of how transcriptional and translational resources are allocated to the production of proteins in genetic circuits. We discover that, when expressed from the same plasmid, the combinations of attainable protein concentrations are constrained by a linear relationship, which can be interpreted as an isocost line, a concept used in microeconomics. We created a library of circuits with two reporter genes, one constitutive and the other inducible in the same plasmid, without a regulatory path between them. In agreement with the model predictions, experiments reveal that the isocost line rotates when changing the ribosome binding site strength of the inducible gene and shifts when modifying the plasmid copy number. These results demonstrate that isocost lines can be employed to predict how genetic circuits become coupled when sharing resources and provide design guidelines for minimizing the effects of such couplings.

Original languageEnglish (US)
Pages (from-to)639-646
Number of pages8
JournalBiophysical Journal
Volume109
Issue number3
DOIs
StatePublished - Aug 6 2015

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Plasmids
Ribosomes
Reporter Genes
Genes
Libraries
Proteins
Binding Sites
Guidelines

ASJC Scopus subject areas

  • Biophysics

Cite this

Gyorgy, A., Jiménez, J. I., Yazbek, J., Huang, H. H., Chung, H., Weiss, R., & Del Vecchio, D. (2015). Isocost Lines Describe the Cellular Economy of Genetic Circuits. Biophysical Journal, 109(3), 639-646. https://doi.org/10.1016/j.bpj.2015.06.034

Isocost Lines Describe the Cellular Economy of Genetic Circuits. / Gyorgy, Andras; Jiménez, José I.; Yazbek, John; Huang, Hsin Ho; Chung, Hattie; Weiss, Ron; Del Vecchio, Domitilla.

In: Biophysical Journal, Vol. 109, No. 3, 06.08.2015, p. 639-646.

Research output: Contribution to journalArticle

Gyorgy, A, Jiménez, JI, Yazbek, J, Huang, HH, Chung, H, Weiss, R & Del Vecchio, D 2015, 'Isocost Lines Describe the Cellular Economy of Genetic Circuits', Biophysical Journal, vol. 109, no. 3, pp. 639-646. https://doi.org/10.1016/j.bpj.2015.06.034
Gyorgy A, Jiménez JI, Yazbek J, Huang HH, Chung H, Weiss R et al. Isocost Lines Describe the Cellular Economy of Genetic Circuits. Biophysical Journal. 2015 Aug 6;109(3):639-646. https://doi.org/10.1016/j.bpj.2015.06.034
Gyorgy, Andras ; Jiménez, José I. ; Yazbek, John ; Huang, Hsin Ho ; Chung, Hattie ; Weiss, Ron ; Del Vecchio, Domitilla. / Isocost Lines Describe the Cellular Economy of Genetic Circuits. In: Biophysical Journal. 2015 ; Vol. 109, No. 3. pp. 639-646.
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