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Engineered molecular circuits encoded in RNA can act as programmable therapeutics that sense cellular states and elicit precise responses within diseased cells. Here, the authors introduce a model delivery system with layered control of targeted infection, conditional replication, drug-inducible viral clearance, and molecular circuit-based cargo regulation, demonstrating a versatile platform for precise RNA viral vector delivery.

Michael Elowitz and colleagues demonstrate that dynamic correlations in gene expression noise, as revealed using single-cell time-lapse microscopy showing time lags due to regulation, can be used to characterize active regulatory links in a synthetic and an endogenous network.

Many gene-regulatory proteins have been shown to activate in pulses, but whether cells exploit the dynamic interaction between pulses of different regulatory proteins has remained unexplored; here single-cell videos show that yeast cells modulate the relative timing between the pulsatile transcription factors Msn2 and Mig1—a gene activator and a repressor, respectively—to control the expression of target genes in response to diverse environmental conditions.

Five experts discuss their views on the main achievements and challenges of synthetic biology in basic and applied science, consider potential ethical issues, and describe how synthetic biology relates to disciplines such as systems biology and computational modelling.

A new system, termed MEMOIR, allows cells to record lineage and gene expression history within their own genome in a format that can be read out in single cells in situ.

Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.

To program intercellular communication for biomedicine, it is crucial to regulate the secretion and surface display of signaling proteins. Here the authors develop RELEASE, a modular approach to control intercellular signals using protein-based circuits.

Movies, made possible by the combination of time-lapse microscopy, quantitative image analysis and fluorescent protein reporters, are allowing us to directly observe various cellular components over time in individual cells. As such, movies are providing powerful insights into the behaviour of genetic circuit behaviours in diverse microbial systems.

Synthetic mouse embryos assembled from embryonic stem cells, trophoblast stem cells and induced extraembryonic endoderm stem cells closely recapitulate the development of wild-type and mutant natural mouse embryos up to embryonic day 8.5.

The spatial location and sequence of DNA barcodes are detected with high sensitivity in fixed tissues.

Temporally dynamic extraembryonic and embryonic BMP4 signalling shapes mouse embryo lineage choices.

Time-lapse imaging is used to follow the activity of several promoters that regulate competence genes in Bacillus subtilis, and the data used to develop a mathematical model of the gene circuitry — revealing that excitable dynamics underlies the positive and negative feedback loops that regulate entry into, and exit from, competence in an individual cell.

A 16-year-old synthetic genetic circuit that produces gene-expression oscillations in bacterial cells has been given an upgrade, making it an exceptionally precise biological clock. See Letter p.514

A single-molecule FISH-based method to quantify splicing efficiency at active transcription sites in single cells reveals an unexpected ‘economy of scale’ behavior in which splicing efficiency increases with transcription rate.

Kueh, Rothenberg and colleagues describe distinct, asynchronous and stage-specific mechanisms of T cell commitment mediated by the transcription factors Notch, TCF-1, GATA-3 and Runx1.

A new study reports the development of the 'morbidostat', a device that allows for continuous culture of bacteria under a constant drug selection pressure using computer feedback control of antibiotic concentration. This device, together with bacterial whole-genome sequencing, allowed the authors to follow the evolution of resistance-conferring mutations in Escherichia coli populations in real time, providing support for deterministic evolution of resistance in some situations.

Notch and Delta are transmembrane proteins that allow neighbouring cells to communicate during development. Here, quantitative time-lapse microscopy has been used to show that the response of Notch to Delta on a neighbouring cell is graded, whereas its response to Delta on the same cell is sharp and occurs at a fixed threshold. A mathematical model explores how this new design principle enhances the sharpness of developmental boundaries set by classical lateral inhibition.

Why do cells of the same type, grown in the same conditions, look and behave so differently? Studying fluctuations in a well-characterized genetic pathway in yeast hints at how such variation arises.

Individuals with exactly the same genetic make-up can differ from one another in their development and resulting phenotype when the genome contains a mutation — a phenomenon called 'partial penetrance'. Exploration of the genetic and stochastic factors controlling the proportion of abnormal 'twin' spores in mutant populations of the bacterium Bacillus subtilus now reveals how mutations affecting DNA replication and cell division may act in synergy to significantly increase the penetrance of twin sporulation.

Recent advances in genome engineering are enabling the recording of cellular histories into genomes, with single-cell and spatial omics technologies enabling their reconstruction into cellular lineages, states and exposures. This Perspective explores the rationale and technical basis of DNA recording, what aspects of cellular biology can be recorded and how, and the types of discovery that DNA recording will enable when studying development and disease.

Intermediate colistin production in E. coli maximizes the benefit of inhibiting sensitive neighbours while minimizing competition from resistant cheaters.