**Acknowledgements**

*Gene Expression and Control*

used in their system, it is responsible for translating electrical signals into a biochemical redox signal that, in turn, can be sensed by SoxR and in sequence, initiate the expression from *psoxS* promoter. Strikingly, gene expression controlled by this device is functionally reversible on relatively short time scales (30–45 min). It was also found to be quite robust, as oscillatory behaviors were shown over many cycles. Accordingly, both optogenetic and electrogenetic systems will require that an entirely new 'suite' of genetic elements be developed that respond to and coordinate these environmental cues. In the recent study, the expression of AHL-synthesizing enzyme LuxI was electronically actuated, resulting in electronic control of QS behavior of nearby cells. Analogously, motility regulator CheZ was also electronically stimulated demonstrating the electronic initiation of cell motility. This study is the first in which electronic signals guided engineered cells and those, in turn, guided others. While this chapter has focused on gene expression in *E. coli*, it also attempts to show how the simultaneous coordination of gene expression and of the

*Electrogenetic induction system scheme. Pyo (O) initiates gene induction and Fcn (R/O), through interactions with respiratory machinery, allows electronic control of induction level. Fcn (R/O), ferro/ferricyanide; Pyo, pyocyanin. Encircled 'e<sup>−</sup>'and arrows indicate electron movement (adapted from Tschirhart et al. [89]).*

Researchers in biotechnology are constantly seeking novel platforms or techniques from which to address problems: those that in a broad sense, have enhanced efficacy, while maintaining or intensifying specificity. In this chapter, innovative means that focus on controlling environmental cues to regulate gene expression are introduced. To optimize heterologous protein expression, methods seeking to repress stress responses and retain cells in a 'productive' state are carried out by carefully engineering host cells to respond to various cues that are either introduced exogenously or endogenously. QS systems have appeared that provide targets for controlling bacterial behavior. They are also shown to report on the prevailing metabolic state of a product-producing cell. Early methodologies such as RNAi, genetic mutation, product protein-directed evolution, all successful means to enhance yield, can be reexamined based on new understanding of how cells communicate with one another. That is, QS systems enable the rewiring of endogenous metabolism for the coordinated control of entire populations of cells. This ushers in a new way of viewing protein or product-producing cells as a cell 'collective' rather than as individual cells each identical to one another, responding to cues or inducers such as

host cells can result in interesting and new application areas.

**180**

**5. Conclusion**

**Figure 6.**

This work was supported by DTRA (HDTRA1-13-0037) and NSF (DMREF #1435957) and by the National Institutes of Health (R21EB024102).
