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Engineering signalling pathways in mammalian cells

Abstract

In mammalian cells, signalling pathways orchestrate cellular growth, differentiation and survival, as well as many other processes that are essential for the proper functioning of cells. Here we describe cutting-edge genetic-engineering technologies for the rewiring of signalling networks in mammalian cells. Specifically, we describe the recombination of native pathway components, cross-kingdom pathway transplantation, and the development of de novo signalling within cells and organelles. We also discuss how, by designing signalling pathways, mammalian cells can acquire new properties, such as the capacity for photosynthesis, the ability to detect cancer and senescent cell markers or to synthesize hormones or metabolites in response to chemical or physical stimuli. We also review the applications of mammalian cells in biocomputing. Technologies for engineering signalling pathways in mammalian cells are advancing basic cellular biology, biomedical research and drug discovery.

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Fig. 1: Synthetic signalling pathways.
Fig. 2: Rewiring endogenous signalling pathways.
Fig. 3: Cross-kingdom transplantation of bacterial and fungi signalling pathways into mammalian cells.
Fig. 4: Cross-kingdom transplantation of plant signalling pathways into mammalian cells.
Fig. 5: Engineering signalling pathways de novo.
Fig. 6: Applications of engineered cells.
Fig. 7: Biocomputing.

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Acknowledgements

This work was supported by research grants from the US National Institutes of Health (GM122567), the Finland Cancer Foundation and the Jane and Aatos Erkko Foundation (220011).

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A.V.L. analysed the papers, wrote the paper and drew the figures. V.V.V. conceived the idea and revised the paper and figures.

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Leopold, A.V., Verkhusha, V.V. Engineering signalling pathways in mammalian cells. Nat. Biomed. Eng 8, 1523–1539 (2024). https://doi.org/10.1038/s41551-024-01237-z

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