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Resource Competition Shapes the Response of Genetic Circuits

Yili Qian, Hsin-Ho Huang, José I. Jiménez, View ORCID ProfileDomitilla Del Vecchio
doi: https://doi.org/10.1101/091306
Yili Qian
1Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
†These authors contributed equally to this work.
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Hsin-Ho Huang
1Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
†These authors contributed equally to this work.
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José I. Jiménez
1Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
2Faculty of Health of Medical Sciences, University of Surrey, Guildford, UK
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Domitilla Del Vecchio
1Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
3Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA
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  • ORCID record for Domitilla Del Vecchio
  • For correspondence: ddv@mit.edu
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Abstract

A common approach to design genetic circuits is to compose gene expression cassettes together. While appealing, this modular approach is challenged by the fact that expression of each gene depends on the availability of transcriptional/translational resources, which is in turn determined by the presence of other genes in the circuit. This raises the question of how competition for resources by different genes affects a circuit’s behavior. Here, we create a library of genetic activation cascades, where we explicitly tune the resource demand by each gene. We develop a general Hill-function-based model that incorporates resource competition effects through resource demand coefficients. These coefficients lead to non-regulatory interactions among genes that reshape circuit’s behavior. For the activation cascade, such interactions result in surprising biphasic or monotonically decreasing responses. Finally, we use resource demand coefficients to guide the choice of ribosome binding site (RBS) and DNA copy number to restore the cascade’s intended monotonically increasing response. Our results demonstrate how unintended circuit’s behavior arises from resource competition and provide a model-guided methodology to minimize the resulting effects.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 03, 2016.
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Resource Competition Shapes the Response of Genetic Circuits
Yili Qian, Hsin-Ho Huang, José I. Jiménez, Domitilla Del Vecchio
bioRxiv 091306; doi: https://doi.org/10.1101/091306
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Resource Competition Shapes the Response of Genetic Circuits
Yili Qian, Hsin-Ho Huang, José I. Jiménez, Domitilla Del Vecchio
bioRxiv 091306; doi: https://doi.org/10.1101/091306

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