Building synthetic memory

Abstract

Cellular memory - conversion of a transient signal into a sustained response - is a common feature of biological systems. Synthetic biologists aim to understand and re-engineer such systems in a reliable and predictable manner. Synthetic memory circuits have been designed and built in vitro and in vivo based on diverse mechanisms, such as oligonucleotide hybridization, recombination, transcription, phosphorylation, and RNA editing. Thus far, building these circuits has helped us explore the basic principles required for stable memory and ask novel biological questions. Here we discuss strategies for building synthetic memory circuits, their use as research tools, and future applications of these devices in medicine and industry.

Figure 1

Cellular memory circuits can be built in many ways. (A) The change in state of synthetic memory circuits can be either reversible or irreversible. (B) In vitro memory circuits rely on hybridization of nucleic acids. Interlocking negative and positive feedback loops form the bistable core (in box) of such devices (C-F) In vivo memory circuits are built using diverse strategies. (C) Recombination-based memory circuits can be based on excision or inversion of DNA sequences. (D) Both positive and double negative transcriptional feedback loops can be used to engineer cellular memory. Novel memory circuits based on (E) protein phosphorylation and (F) RNA editing have also been proposed.

Figure 2

Engineered cellular memory circuits can be used to study biology and may be used to diagnosis and treat disease, as well as solve unmet industrial needs. (A) Memory circuits can be used to study heterogeneously responding cell populations. (B) When a cell changes from a healthy to a disease state, memory circuits can detect and report this change or treat the underlying condition. (C) Memory circuits will allow long-term expression by transient addition of inducer.