A modular degron library for synthetic circuits in mammalian cells

H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, M. Fussenegger, Nature Communications 10 (2019) 2013.

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Journal Article | Published | English
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Abstract
Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells.
Publishing Year
Date Published
2019-05-01
Journal Title
Nature Communications
Volume
10
Issue
1
Article Number
2013
eISSN
IST-REx-ID

Cite this

Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 2019;10(1):2013. doi:10.1038/s41467-019-09974-5
Chassin, H., Müller, M., Tigges, M., Scheller, L., Lang, M., & Fussenegger, M. (2019). A modular degron library for synthetic circuits in mammalian cells. Nature Communications, 10(1), 2013. https://doi.org/10.1038/s41467-019-09974-5
Chassin, Hélène, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang, and Martin Fussenegger. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications 10, no. 1 (2019): 2013. https://doi.org/10.1038/s41467-019-09974-5.
H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, and M. Fussenegger, “A modular degron library for synthetic circuits in mammalian cells,” Nature Communications, vol. 10, no. 1, p. 2013, 2019.
Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. 2019. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 10(1), 2013.
Chassin, Hélène, et al. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications, vol. 10, no. 1, Springer Nature, 2019, p. 2013, doi:10.1038/s41467-019-09974-5.
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