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A Microfluidics Approach for the Functional Investigation of Signaling Oscillations Governing Somitogenesis

A Microfluidics Approach for the Functional Investigation of Signaling Oscillations Governing Somitogenesis

Published on: March 19, 2021

A self-regulating biomolecular comparator for processing oscillatory signals.

Deepak K Agrawal¹, Elisa Franco², Rebecca Schulman³

¹Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.

Journal of the Royal Society, Interface

|September 18, 2015

Summary

This study presents a synthetic biochemical device that converts noisy biological oscillator signals into clear on/off outputs, enabling precise control of cellular processes.

Keywords:

biomolecular comparator dynamical systems modular oscillator synthetic biology

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Area of Science:

Synthetic Biology
Biochemical Engineering
Systems Biology

Background:

Biomolecular oscillators drive cellular processes but offer imprecise control due to continuous signal variation and noise.
Downstream processes require well-defined on/off signals, similar to electronic comparators, which are challenging to achieve with biological oscillators.

Purpose of the Study:

To develop a synthetic biochemical device that generates a reliable square-wave output from oscillatory biomolecular inputs.
To demonstrate the device's ability to process various in vitro and in vivo biological oscillators.

Main Methods:

Constructed a synthetic biochemical device utilizing a separation of timescales between slow signal production and fast molecular interactions.
Engineered the device to convert continuous, noisy oscillatory signals into discrete, on/off biomolecular outputs.
Validated the device's performance with different biomolecular oscillators, including the p53-Mdm2 system.

Main Results:

The synthetic device successfully produced a square-wave-type biomolecular output from diverse oscillatory inputs.
Output characteristics were controllable by adjusting species concentrations and reaction rates.
Demonstrated applicability to both in vitro and in vivo biological oscillators.

Conclusions:

This method provides a robust way to process biomolecular oscillator signals, enabling precise control of downstream cellular functions.
The modular design facilitates the construction of complex biological circuits.
Natural biological systems may employ similar mechanisms for processing oscillator outputs.