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Natural transcription factors are often regulated in a pulsatile fashion unlike many synthetic systems. Here the authors show that dynamic pulsatile signals reduce cell-to-cell gene expression variability in an optogenetic construct.

Creating synthetic biological circuits can be maddeningly difficult because of unpredictable stimuli and unknown variability in the system. Milias-Argeitis et al. circumvent these problems by moving control functions outside the cell—to a computer—and connecting computer and cell through optogenetics.

Recent advances in tissue engineering have been remarkable, yet the precise control of cellular behavior in 2D and 3D cultures remains challenging. Here by using light signals, they spatially regulated programmed cell death pathways and cell-cell communication cascades in 2- and 3-dimensional designer tissues.

In the field of tissue engineering, achieving precise spatiotemporal control over engineered cells is critical for sculpting functional 2D cell cultures into intricate morphological shapes. Here the authors introduce μPatternScope (μPS), a modular system for precise, automated light-based control of cell patterning in 2D cultures.

To identify intracellular dynamics at the single-cell level, authors develop a scalable method via a divide-and-conquer strategy and apply it to a yeast transcription system. The results underscore the heterogeneity in isogenic cells, which is validated by a noise-decomposition method.

Practical implementation of genetic circuits is difficult due to low predictability and time-intensive troubleshooting. Here the authors present Cyberloop, which interfaces a computer with single cells to enable cell-in-the-loop testing and optimization of circuit designs before they are built.

Anhydrotetracycline and tetracycline are commonly used chemicals to regulate transcription and translation, respectively. Here the authors exploit the natural photosensitivity of these molecules to place their activity under optical control.

The design of genetic networks in mammalian cells is still slow and often fails. Here the authors show that miRNA-based incoherent feedforward loop circuits can be used to alleviate cellular burden.

Synthetic biological pattern formation is challenging to engineer due to theoretical complexity and practical limitations. Here, the authors introduce a cell-in-the-loop approach in which cells interact through in silico signaling.

Homeostasis and robust perfect adaptation are remarkable features of living cells. Here, to synthetically achieve this, the authors present a theoretical and experimental framework using inteins to implement compact biomolecular integral feedback controllers.

Communities of microbes play important roles in natural environments and hold great potential for deploying division-of-labor strategies in synthetic biology and bioproduction. Here, in a community of two competing E. coli strains, the authors show that the relative abundances of the strains can be stabilized and steered dynamically with remarkable precision by coupling the cells to an automated computer-controlled feedback-loop.

The invention of the Fourier integral in the 19th century laid the foundation for modern spectral analysis methods. Here the authors develop frequency-based methods for analyzing the reaction mechanisms within living cells from distinctively noisy single-cell output trajectories and present forward engineering of synthetic oscillators and controllers.

Engineering of a blue light-inducible AraC dimerization system in E. coli permits light-dependent, rather than arabinose-based, regulation of gene expression from standard P_BAD promoters, enabling temporal and spatial control of bacterial systems.

The design of feedback biomolecular controllers is essential to synthetically regulate biological processes in a robust and timely fashion. Here the authors introduce a wide array of biomolecular Proportional-Integral-Derivative (PID) controllers that are capable of enhancing stability and dynamic performance, and also reducing stochastic noise.

Optogenetics has emerged as a promising means to achieve gene expression control in bioprocess engineering, but current systems cannot respond to fluctuations in growth conditions. Here the authors overcome this limitation and develop an automated optogenetic feedback control system for precise and robust control of protein production in E. coli.

A synthetic gene circuit implementing an integral feedback topology is shown to achieve robust perfect adaptation in living cells--mathematical analysis proves this topology is necessary for adaptation in networks with noisy dynamics.