Pulse modulation of optical signals for programming gene expression dynamics

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Eric Davidson, Travis S. Bayer

Imperial College London, United Kingdom

Precise control of gene expression is critical for living cells and for many applications in synthetic biology. We have developed a combined genetic, hardware, and control strategy for programming gene expression dynamics in the bacterium E. coli that relies on modulation of an oscillating input pattern, rather than modulation of input intensity as is conventional. This strategy depends on the signal transduction process functioning as a low-pass filter, in which the oscillating input signal is ‘passed’ at low frequencies, resulting in an oscillating output, and attenuated at high frequencies, resulting in a constant output. Above a cut-off frequency, the pathway output can be scaled continuously between the ‘off’ and ‘on’ states through pulse width modulating the input signal. This strategy allows fine-tuning of expression rates, levels and temporal dynamics, as well as the control of bacterial physiology by direct control of expression of a key metabolic enzyme.