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A genetic time-delay circuitry in mammalian cells
Wilfried Weber1, Beat P Kramer, Martin Fussenegger
1Institute for Chemical and Bio-Engineering, ETH Zurich, HCI F115, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Biotechnology and Bioengineering
|April 28, 2007
Summary
Scientists engineered a synthetic gene circuit with tunable time-delayed gene expression in mammalian cells. This novel circuit, mimicking natural biological processes, offers precise control over cellular functions for synthetic biology applications.
Area of Science:
- Synthetic Biology
- Genetic Engineering
- Systems Biology
Background:
- Gene expression circuitries with time-delayed profiles are crucial for biological processes like oscillations and noise reduction in organisms.
- Understanding and engineering these time-delayed systems is fundamental for advancing synthetic biology and creating novel cellular functions.
Purpose of the Study:
- To rationally synthesize a genetic circuit that exhibits controllable time-delayed gene expression.
- To characterize the in silico and in vivo performance of this synthetic time-delay circuit in mammalian cells.
- To explore the potential of this tunable circuitry as a building block for artificial gene networks.
Main Methods:
- Designed a synthetic gene network utilizing a tetracycline-responsive transactivator (tTA) to control a repressor (PIP-KRAB).
- The repressor PIP-KRAB silences the expression of a reporter gene (SEAP).
- Characterized the time-delayed expression kinetics in silico and in mammalian cells, analyzing the impact of repressor buffer size and stability.
Main Results:
- Successfully synthesized a genetic circuit demonstrating predictable time-delayed gene expression in mammalian cells.
- Demonstrated that the addition of tetracycline abolishes repressor synthesis, leading to a delay in reporter gene expression until the repressor is degraded.
- Showcased the tunability of the response kinetics by altering the size and stability of the repressor (PIP-KRAB) buffer.
Conclusions:
- The developed tunable time-delay circuitry serves as a versatile biologic building block.
- This synthetic circuit can emulate fundamental circuit topologies for integrated artificial gene networks.
- Enables the design of tailor-made cell types and organisms with precise temporal control over gene expression.
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