Pathway engineering via quorum sensing and sRNA riboregulators—Interconnected networks and controllers

The advent of genetic engineering has elevated our level of comprehension of cellular processes and functions. A natural progression of these findings is determining not only how these processes function within individual cells but also within a community. Bacterial cells monitor the conditions and microorganisms in their vicinity by producing, releasing and sensing chemical-signaling molecules. When a specific cell-density threshold is reached, a quorum is perceived, gene expression profiles are altered and the community orchestrates activities that are more effective en masse. This communication mechanism, in the language of autoinducers (AI), is referred to as quorum sensing (QS). It has become increasingly evident that while scientists attempt to decipher the intricacies of cellular communication and quorum sensing networks, we must remain conscious of the broader context of how a cell may identify itself in the environment and how this also impacts QS. Importantly, these phenomena span time and length scales by several orders in magnitude. Though the revelation of small RNAs, as both sensing and regulatory elements participating in the quorum sensing cascade, has connected new pieces of the puzzle, it has also added a new tier of uncertainty. The complexity of quorum sensing networks makes resolution of its diverse mechanisms difficult. The ability to design simpler networks with defined, more predictable or even “modular” elements will help elucidate these actions. Because it embraces innovative concepts of biological design accommodating the many length and time scales at play, synthetic biology serves as one of the most promising platforms for describing QS phenomena as well as enabling novel implementation strategies for biotechnological application.