dorsal/arxiv
View SchemaNoise-based switches and amplifiers for gene expression
| Authors | Jeff Hasty, Joel Pradines, Milos Dolnik, J. J. Collins |
|---|---|
| Categories | |
| ArXiv ID | physics/0003105 |
| URL | https://arxiv.org/abs/physics/0003105 |
| DOI | 10.1073/pnas.040411297 |
| Journal | Proc. Natl. Acad. Sci. USA, Vol. 97, Issue 5, 2075-2080, February 29, 2000; http://www.pnas.org/cgi/content/full/97/5/2075 |
Abstract
The regulation of cellular function is often controlled at the level of gene transcription. Such genetic regulation usually consists of interacting networks, whereby gene products from a single network can act to control their own expression or the production of protein in another network. Engineered control of cellular function through the design and manipulation of such networks lies within the constraints of current technology. Here we develop a model describing the regulation of gene expression, and elucidate the effects of noise on the formulation. We consider a single network derived from bacteriophage $\lambda$, and construct a two-parameter deterministic model describing the temporal evolution of the concentration of $\lambda$ repressor protein. Bistability in the steady-state protein concentration arises naturally, and we show how the bistable regime is enhanced with the addition of the first operator site in the promotor region. We then show how additive and multiplicative external noise can be used to regulate expression. In the additive case, we demonstrate the utility of such control through the construction of a protein switch, whereby protein production is turned ``on'' and ``off'' using short noise pulses. In the multiplicative case, we show that small deviations in the transcription rate can lead to large fluctuations in the production of protein, and describe how these fluctuations can be used to amplify protein production significantly. These novel results suggest that an external noise source could be used as a switch and/or amplifier for gene expression. Such a development could have important implications for gene therapy.
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"abstract": "The regulation of cellular function is often controlled at the level of gene\ntranscription. Such genetic regulation usually consists of interacting\nnetworks, whereby gene products from a single network can act to control their\nown expression or the production of protein in another network. Engineered\ncontrol of cellular function through the design and manipulation of such\nnetworks lies within the constraints of current technology. Here we develop a\nmodel describing the regulation of gene expression, and elucidate the effects\nof noise on the formulation. We consider a single network derived from\nbacteriophage $\\lambda$, and construct a two-parameter deterministic model\ndescribing the temporal evolution of the concentration of $\\lambda$ repressor\nprotein. Bistability in the steady-state protein concentration arises\nnaturally, and we show how the bistable regime is enhanced with the addition of\nthe first operator site in the promotor region. We then show how additive and\nmultiplicative external noise can be used to regulate expression. In the\nadditive case, we demonstrate the utility of such control through the\nconstruction of a protein switch, whereby protein production is turned ``on\u0027\u0027\nand ``off\u0027\u0027 using short noise pulses. In the multiplicative case, we show that\nsmall deviations in the transcription rate can lead to large fluctuations in\nthe production of protein, and describe how these fluctuations can be used to\namplify protein production significantly. These novel results suggest that an\nexternal noise source could be used as a switch and/or amplifier for gene\nexpression. Such a development could have important implications for gene\ntherapy.",
"arxiv_id": "physics/0003105",
"authors": [
"Jeff Hasty",
"Joel Pradines",
"Milos Dolnik",
"J. J. Collins"
],
"categories": [
"physics.bio-ph",
"physics.med-ph",
"q-bio"
],
"doi": "10.1073/pnas.040411297",
"journal_ref": "Proc. Natl. Acad. Sci. USA, Vol. 97, Issue 5, 2075-2080, February\n 29, 2000; http://www.pnas.org/cgi/content/full/97/5/2075",
"title": "Noise-based switches and amplifiers for gene expression",
"url": "https://arxiv.org/abs/physics/0003105"
},
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