A modular degron library for synthetic circuits in mammalian cells

Hélène Chassin, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang and Martin Fussenegger ()
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Hélène Chassin: ETH Zürich
Marius Müller: Cilag AG
Marcel Tigges: Cilag AG
Leo Scheller: ETH Zürich
Moritz Lang: Institute of Science and Technology Austria
Martin Fussenegger: ETH Zürich

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09974-5

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