A fundamental challenge of synthetic biology and its clinical applications is the capability to control gene expression. Presently, gene expression systems for research and industry have several limitations, such as a small number of available systems, inconsistent behavior among systems, lack of sufficient dynamic range of expression, and the requirement for high concentrations of a signaling molecule to induce/repress a gene. Consequently, there is a strong need for a better and diverse array of gene expression systems.

Phages can infect bacteria either in a lytic cycle, which lyses the bacterial wall, or in a lysogenic cycle in which the phage genome integrates into the bacterial genome. The research team of Prof. Sorek discovered the novel Arbitrium communication system that enables lytic or lysogenic cycle (Fig. A). The Arbitrium system functions on the basis of three genes, aimR, aimP, and aimX. AimR is a dimeric receptor that binds and activates the transcription of gene aimX, whereby AimX inhibits lysogeny leading to lysis (Fig. B). AimP is a six amino acid pro-peptide (arbitrium peptide) that is expressed following infection, secreted extracellularly, and post-translationally modified. After the arbitrium peptide accumulates to a specific concentration, the arbitrium peptide is internalized and bound by the AimR receptor, which inhibits the expression of AimX and leads to lysogeny (Fig. C). The Sorek team further determined that when infected bacteria are incubated with the arbitrium peptide from the same phage that infected them, the bacterial growth curve changes due to a shift to a lysogenic cycle (Fig. D). However, when incubated with an arbitrium peptide from a different phage, the bacterial growth curve does not shift, regardless of peptide concentration (Fig. E).