Biological signal generators: integrating synthetic biology tools and in silico control

Abstract

Biological networks sense extracellular stimuli and generate appropriate outputs within the cell that determine cellular response. Biological signal generators are becoming an important tool for understanding how information is transmitted in these networks and controlling network behavior. Signal generators produce well-defined, dynamic, intracellular signals of important network components, such as kinase activity or the concentration of a specific transcription factor. Synthetic biology tools coupled with in silico control have enabled the construction of these sophisticated biological signal generators. Here we review recent advances in biological signal generator construction and their use in systems biology studies. Challenges for constructing signal generators for a wider range of biological networks and generalizing their use are discussed.

A yeast optogenetic toolkit (yOTK) for gene expression control in Saccharomyces cerevisiae

“…Engineering efforts benefit greatly from the ability to tune the concentration of individual components to test and adjust circuit function. Additionally, tunability can allow circuits to be temporally and spatially adjusted to match dynamic constraints, such as the external environment or bioprocess phase (Scott, Sweeney, & McClean, ).…”

“…Additionally, tunability can allow circuits to be temporally and spatially adjusted to match dynamic constraints, such as the external environment or bioprocess phase (Scott, Sweeney, & McClean, 2019).…”

Embedded control of cell growth using tunable genetic systems

“…To mitigate this problem, a promising solution may be to add an additional external feedback control loop which compensates for the heterogeneity by adjusting the reference fed to the inner system. This can be implemented in vivo by using the external control strategies 34–39 .…”

Functional roles of microbial cell-to-cell heterogeneity and emerging technologies for analysis and control

“…For example, optogenetically controlled components could be used for precise manipulation of the temporal dynamics associated with sporulation, competence, and timesharing of sigma factors [34••,35,36,38,40]. Optogenetic methods also offer excellent potential for manipulating dynamics to reveal underlying properties of regulatory networks via comprehensive system identification studies; we point the reader to two recent reviews for further discussion on these opportunities [65,66].…”