A novel optogenetically tunable frequency modulating oscillator

Abstract

Synthetic biology has enabled the creation of biological reconfigurable circuits, which perform multiple functions monopolizing a single biological machine; Such a system can switch between different behaviours in response to environmental cues. Previous work has demonstrated switchable dynamical behaviour employing reconfigurable logic gate genetic networks. Here we describe a computational framework for reconfigurable circuits in E.coli using combinations of logic gates, and also propose the biological implementation. The proposed system is an oscillator that can exhibit tunability of frequency and amplitude of oscillations. Further, the frequency of operation can be changed optogenetically. Insilico analysis revealed that two-component light systems, in response to light within a frequency range, can be used for modulating the frequency of the oscillator or stopping the oscillations altogether. Computational modelling reveals that mixing two colonies of E.coli oscillating at different frequencies generates spatial beat patterns. Further, we show that these oscillations more robustly respond to input perturbations compared to the base oscillator, to which the proposed oscillator is a modification. Compared to the base oscillator, the proposed system shows faster synchronization in a colony of cells for a larger region of the parameter space. Additionally, the proposed oscillator also exhibits lesser synchronization error in the transient period after input perturbations. This provides a strong basis for the construction of synthetic reconfigurable circuits in bacteria and other organisms, which can be scaled up to perform functions in the field of time dependent drug delivery with tunable dosages, and sets the stage for further development of circuits with synchronized population level behaviour.

Steering Molecular Activity with Optogenetics: Recent Advances and Perspectives

“…[ 125 ] Also, several other in silico optogenetic systems were developed for the dynamic control of transcription intensity [ 126 ] and reconfiguration of gene circuits with logic gates. [ 127 ]…”

Programming Bacteria With Light—Sensors and Applications in Synthetic Biology

“…Hardware shares an essential three-part architecture: (a) an adapted cell culture system; (b) a real-time quantification system; and (c) a computer-controlled light delivery system (Figure 2C ) (Milias-Argeitis et al, 2016 ; Hennemann et al, 2018 ; Mahajan and Rai, 2018 ). The cell culture system is supposed to be designed according to experimental purposes.…”