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Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
Published on: September 29, 2016
A synthetic metabolite-based mammalian inter-cell signaling system
Wilfried Weber1, Marco Schuetz, Nicolas Dénervaud
1Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Molecular Biosystems
|June 30, 2009
Summary
Researchers engineered synthetic signaling systems for mammalian cells. This metabolite-controlled device enables precise timing of gene expression between engineered cell lines for future synthetic hormone applications.
Area of Science:
- Synthetic biology
- Cellular engineering
- Biotechnology
Background:
- Modular transcription units are key for designing synthetic gene networks within mammalian cells.
- Interconnecting cells into multicellular assemblies requires synthetic signaling systems for computational functions.
- Current systems lack robust methods for metabolic information synchronization between cells.
Purpose of the Study:
- To design and characterize a metabolite-controlled intercellular signaling device.
- To enable communication and synchronized metabolic information transfer between mammalian cells.
- To lay the groundwork for synthetic hormone systems in multicellular assemblies.
Main Methods:
- Engineered a human sender cell line for constitutive expression of human liver-type arginase.
- Developed a transgenic receiver cell line with a synthetic circuit for glycoprotein production.
- Utilized L-arginine levels in culture medium to control intercellular communication.
Main Results:
- Demonstrated functional interoperability between two independent transgenic cell lines.
- Quantitatively characterized system components for precise prediction of L-arginine degradation and gene expression kinetics.
- Showcased the ability to precisely time target gene expression via metabolite control.
Conclusions:
- Metabolite-controlled intercellular signaling devices can be designed using synthetic gene circuits.
- This approach enables precise timing of gene expression across engineered cell lines.
- Synthetic signaling systems can facilitate the development of synthetic hormone systems for multicellular communication.
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