Temperature dependence of biomolecular circuit designs

Sen, Shaunak; Murray, Richard M.

doi:10.1109/cdc.2013.6760078

Cited by 10 publications

(11 citation statements)

References 16 publications

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“…The computations for the negative feedback circuit suggest that, in addition to matched temperature dependencies, certain parameter regimes can also facilitate temperature robustness, at a performance cost, similar to what can be observed in a two-state model [8]. Experimental measurements seem consistent with this ( Fig.…”

Section: Discussion Of the Experimental Measurements In The Context Osupporting

confidence: 64%

“…Synthetic oscillator designs can also have temperature dependent periods [6], and relatively recently, it was shown how a temperature sensitive mutant transcription factor can be used to compensate for the effect of temperature [7]. We have investigated, primarily computationally, the propagation of temperature dependence in simple biomolecular circuit models, noting that in addition to matching temperature dependence of parameters, certain parameter regimes can also give temperature robustness [8,9]. More recently, a multiscale approach was used to explain the effects of temperature in simple negative and positive feedback circuits in yeast [10].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Robustness to Temperature in a Negative Feedback Loop and a Feedforward Loop

Patel

Murray

Sen

2019

Preprint

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Robustness to temperature variation is an important specification for biomolecular circuit design. While cancellation of parametric temperature dependences has been shown to improve temperature robustness of period in a synthetic oscillator design, the performance of other biomolecular circuit designs in different temperature conditions is relatively unclear. Using a combination of experimental measurements and mathematical models, we assess the temperature robustness of two biomolecular circuit motifs -a negative feedback loop and a feedforward loop. We find that the measured responses in both circuits can change with temperature, both in the amplitude and in the transient response. We find that, in addition to the cancellation of parametric temperature dependencies, certain parameter regimes can also facilitate temperature robustness for the negative feedback loop, although at a performance cost. We discuss these parameter regimes of operation in the context of the measured data for the negative feedback loop. These results should help develop a framework for assessing and designing temperature robustness in biomolecular circuits.

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Section: Discussion Of the Experimental Measurements In The Context Osupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Assessment of Robustness to Temperature in a Negative Feedback Loop and a Feedforward Loop

Patel

Murray

Sen

2019

Preprint

Self Cite

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“…First, they are based on fundamental and ubiquitous effects: The Arrhenius law applies for all chemical reactions, and growth rate changes affect protein half-lives ubiquitously. Second, they have already been shown to explain temperature-dependent gene network function in bacteria ( 30 ) and cell-free systems ( 31 ). Nonetheless, it will be interesting to test whether the first pillar (cell fate choice between growth arrest and resistance) might generalize to other stresses and other cell types, considering that findings in yeast often generalize to other organisms ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

“…For example, forward engineering temperature compensation made a synthetic genetic clock robust to temperature changes ( 30 ). Inspiration for such designs may come from nature, since temperature compensation appears to be an intrinsic property of natural circadian cycles ( 82 ) and certain gene-regulatory network motifs ( 31 ). Although temperature-induced changes in synthetic gene circuit function present some challenges, they may also present opportunities to exploit this environmental factor for control purposes.…”

Section: Discussionmentioning

confidence: 99%

“…In some cases, temperature provides a way to control synthetic gene circuits ( 29 ) and temperature compensation may be possible ( 30 ). However, since most synthetic gene circuits are developed and characterized under controlled laboratory conditions, it is unclear how temperature shifts affect their function ( 31 ), such as the gene expression noise they are designed to impose.…”

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confidence: 99%

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Multiscale effects of heating and cooling on genes and gene networks

Charlebois

Hauser

Marshall

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceFluctuating environments such as changes in ambient temperature represent a fundamental challenge to life. Cells must protect gene networks that protect them from such stresses, making it difficult to understand how temperature affects gene network function in general. Here, we focus on single genes and small synthetic network modules to reveal four key effects of nonoptimal temperatures at different biological scales: (i) a cell fate choice between arrest and resistance, (ii) slower growth rates, (iii) Arrhenius reaction rates, and (iv) protein structure changes. We develop a multiscale computational modeling framework that captures and predicts all of these effects. These findings promote our understanding of how temperature affects living systems and enables more robust cellular engineering for real-world applications.

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