Emergent genetic oscillations in a synthetic microbial consortium

Abstract

A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types – an “activator” strain and a “repressor” strain. These strains produce two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way towards engineering complex synthetic tissues and organs with multiple cell types.

Protein sequestration versus Hill‐type repression in circadian clock models

“…While Hill-type regulations have frequently been used in models of these biological oscillators [188][189][190][191][192][193][194][195][196], the critical roles of protein sequestration were also reported [71,197]. It would be interesting in future work to explore whether diverse biological oscillators show different properties depending on their key repression mechanisms, as presented in this review (Fig.…”

Synthetic biology platform technologies for antimicrobial applications

“…Early efforts focused on the development of model transcriptional networks to recapitulate and understand native gene regulation [7][8][9][10]. These works advanced our ability to engineer complex behavior such as memory encryption and oscillatory gene expression, and catalyzed advancements in the rapid design and implementation of synthetic gene networks [11][12][13][14][15][16][17][18][19][20]. The field has since moved towards repurposing natural biological processes for tunable and targetable synthetic gene regulation [21][22][23][24][25].…”

Population regulation in microbial consortia using dual feedback control

“…With different circuit components in different cells, the components have separate resource pools and thus cannot compete for resources. In addition, the Previously developed synthetic gene circuits that function at the population level and involve feedback include a population control circuit that regulates the number of cells in a culture [13], a predator prey system with two cell strains [14], a two strain system for programmed pattern formation [15], and a two strain population level oscillator [16]. However, there are challenges associated with implementing circuits at the population level across multiple cell strains.…”