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Transcriptional regulation by nuclease-deficient CRISPR/Cas is a popular and valuable tool for routine control of gene expression. CRISPR interference in bacteria can be reliably achieved with high efficiencies. Yet, options for CRISPR activation (CRISPRa) remained limited in flexibility and activity because they relied on σ 70 promoters. Here we report a eukaryote-like bacterial CRISPRa system based on σ 54 -dependent promoters, which supports long distance, and hence multi-input regulation with high dynamic ranges. Our CRISPRa device can activate σ 54 -dependent promoters with biotechnology relevance in non-model bacteria. It also supports orthogonal gene regulation on multiple levels. Combining our CRISPRa with dxCas9 further expands flexibility in DNA targeting, and boosts dynamic ranges into regimes that enable construction of cascaded CRISPRa circuits. Application-wise, we construct a reusable scanning platform for readily optimizing metabolic pathways without library reconstructions. This eukaryote-like CRISPRa system is therefore a powerful and versatile synthetic biology tool for diverse research and industrial applications. CRISPR activation strategies in bacteria are limited due to the reliance on σ 70 promoters. Here the authors demonstrate eukaryote-like gene activation with high dynamic ranges using σ 54 - dependent promoters.

Cell-based biosensors have great potential to detect various toxic and pathogenic contaminants in aqueous environments. However, frequently they cannot meet practical requirements due to insufficient sensing performance. To address this issue, we investigated a modular, cascaded signal amplifying methodology. We first tuned intracellular sensory receptor densities to increase sensitivity, and then engineered multi-layered transcriptional amplifiers to sequentially boost output expression level. We demonstrated these strategies by engineering ultrasensitive bacterial sensors for arsenic and mercury, and improved detection limit and output up to 5,000-fold and 750-fold, respectively. Coupled by leakage regulation approaches, we developed an encapsulated microbial sensor cell array for low-cost, portable and precise field monitoring, where the analyte can be readily quantified via displaying an easy-to-interpret volume bar-like pattern. The ultrasensitive signal amplifying methodology along with the background regulation and the sensing platform will be widely applicable to many other cell-based sensors, paving the way for their real-world applications. An engineered biosensor, which optimizes metal-sensing and couples it to transcriptional amplification cascades that produce a fluorescent protein, was applied to build a sensitive and easy-to-use sensor for the toxic metals As 3+ and Hg 2+ .

Versatile tools for gene expression regulation are vital for engineering gene networks of increasing scales and complexity with bespoke responses. Here, we investigate and repurpose a ubiquitous, indirect gene regulation mechanism from nature, which uses decoy protein-binding DNA sites, named DNA sponge, to modulate target gene expression in Escherichia coli . We show that synthetic DNA sponges can be designed to reshape the response profiles of gene circuits, lending multifaceted tuning capacities including reducing basal leakage by >20-fold, increasing system output amplitude by >130-fold and dynamic range by >70-fold, and mitigating host growth inhibition by >20%. Further, multi-layer DNA sponges for decoying multiple regulatory proteins provide an additive tuning effect on the responses of layered circuits compared to single-layer sponges. Our work shows synthetic DNA sponges offer a simple yet generalizable route to systematically engineer the performance of synthetic gene circuits, expanding the current toolkit for gene regulation with broad potential applications. Decoy binding sites are natural regulators of gene expression. Here the authors design synthetic DNA sponges that fine tune the performance of synthetic gene circuits in a simple yet systematic manner, expanding the synthetic biology toolkit for gene regulation.

In type II CRISPR systems, the guide RNA (gRNA) comprises a CRISPR RNA (crRNA) and a hybridized trans-acting CRISPR RNA (tracrRNA), both being essential in guided DNA targeting functions. Although tracrRNAs are diverse in sequence and structure across type II CRISPR systems, the programmability of crRNA-tracrRNA hybridization for Cas9 is not fully understood. Here, we reveal the programmability of crRNA-tracrRNA hybridization for Streptococcus pyogenes Cas9, and in doing so, redefine the capabilities of Cas9 proteins and the sources of crRNAs, providing new biosensing applications for type II CRISPR systems. By reprogramming the crRNA-tracrRNA hybridized sequence, we show that engineered crRNA-tracrRNA interactions can not only enable the design of orthogonal cellular computing devices but also facilitate the hijacking of endogenous small RNAs/mRNAs as crRNAs. We subsequently describe how these re-engineered gRNA pairings can be implemented as RNA sensors, capable of monitoring the transcriptional activity of various environment-responsive genomic genes, or detecting SARS-CoV-2 RNA in vitro, as an Atypical gRNA-activated Transcription Halting Alarm (AGATHA) biosensor.

Though evaporation‐driven electricity generation has emerged as a novel eco‐friendly energy and attracted intense interests, it is typically demonstrated in pure water or a very low salt concentration. Integrating evaporation‐driven electricity generation and solar steam desalination simultaneously should be more promising. Herein, a polyaniline coated metal‐organic frameworks (MOFs) nanorod arrays membrane is synthesized which inherits the merits of both polyaniline and MOFs, demonstrating nice stability, good interfacial solar steam desalination, and evaporation‐driven electricity generation. Moreover, an integrated system based on this hybrid membrane achieves good interfacial solar‐heating evaporation and prominently enhanced evaporation‐driven electricity generation under one sun. Notably, the realization of effective seawater desalination and efficient evaporation‐driven electricity generation simultaneously by the non‐carbon‐based materials is reported for the first time, which provides a new alternative way for cogenerating both freshwater and electricity by harvesting energy from seawater and solar light. The integration of interfacial solar‐heating evaporation and evaporation‐driven electricity generation is achieved based on a rationally designed hybrid membrane with polyaniline coating on the metal‐organic frameworks’ nanorod arrays. This membrane demonstrates effective sea water desalination and efficient evaporation‐driven electricity generation simultaneously under solar light.

Summary Synthetic biology offers new tools and capabilities of engineering cells with desired functions for example as new biosensing platforms leveraging engineered microbes. In the last two decades, bacterial cells have been programmed to sense and respond to various input cues for versatile purposes including environmental monitoring, disease diagnosis and adaptive biomanufacturing. Despite demonstrated proof‐of‐concept success in the laboratory, the real‐world applications of microbial sensors have been restricted due to certain technical and societal limitations. Yet, most limitations can be addressed by new technological developments in synthetic biology such as circuit design, biocontainment and machine learning. Here, we summarize the latest advances in synthetic biology and discuss how they could accelerate the development, enhance the performance and address the present limitations of microbial sensors to facilitate their use in the field. We view that programmable living sensors are promising sensing platforms to achieve sustainable, affordable and easy‐to‐use on‐site detection in diverse settings. Synthetic biology offers new tools and capabilities of engineering microbes with defined functions as new biosensing platforms for environmental monitoring, disease diagnosis and adaptive biomanufacturing. Here, we summarize the latest advances in synthetic biology and discuss how they could accelerate the development, enhance the performance and address the present limitations of microbial sensors to facilitate their use in the field. We view that programmable living sensors are promising sensing platforms to achieve sustainable, affordable, and easy‐to‐use on‐site detection in diverse settings.

Plastic photoreforming offers a compelling technology to address the global issue of the large amount cumulative plastic waste by converting it into valuable fuels and chemical feedstocks. However, constrained by insufficient mass and energy transfers, the existing hydrophilic plastic photoreforming systems heavily rely on the unsustainable chemical pre-treatments in corrosive solutions. Herein, we demonstrate a conceptual plastic photoreforming system based on a floatable hydrophobic organic-inorganic hybrid-TiO 2 photocatalyst, which unlocks superoxide radical as the major oxidizing species and forms a four-phase interface among photocatalyst, plastic substrate, water and air, thus greatly enhancing the mass and energy transfers. Consequently, the photoreforming yield rates in neutral aqueous solutions are increased by 1–2 orders of magnitude for typical plastic including polyethylene, polypropylene, and polyvinyl chloride without applying pre-treatments, whilst producing high-value C 2 H 5 OH with a selectivity of over 40%. We believe this work reveals a feasible route to sustainable plastic photoreforming. Plastic photoreforming offers a promising route for recycling plastic waste but typically depends on unsustainable, corrosive conditions. Here, the authors present a floatable organic–inorganic hybrid TiO 2 material that enables efficient conversion of common plastics such as PE, PP, and PVC under neutral conditions.

Histone marks, carriers of epigenetic information, regulate gene expression. In mammalian cells, H3K36me3 is mainly catalyzed by SETD2 at gene body regions. Here, we find that in addition to gene body regions, H3K36me3 is enriched at promoters in primary cells. Through screening, we identify SMYD5, which is recruited to chromatin by RNA polymerase II, as a methyltransferase catalyzing H3K36me3 at promoters. The enzymatic activity of SMYD5 is dependent on its C-terminal glutamic acid-rich domain. Overexpression of full-length Smyd5 , but not the C-terminal domain-truncated Smyd5 , restores H3K36me3 at promoters in Smyd5 knockout cells. Furthermore, elevated Smyd5 expression contributes to tumorigenesis in liver hepatocellular carcinoma. Together, our findings identify SMYD5 as the H3K36me3 methyltransferase at promoters that regulates gene expression, providing insights into the localization and function of H3K36me3. SETD2 methylates histone H3K36me3 in gene bodies in mammalian cells. Here the authors show H3K36me3 is also enriched at the promoter regions, and that this methylation is carried out by SMYD5, which is recruited by RNA polymerase II. They furthermore show SMYD5 is elevated in liver cancer and is correlated with changes in gene expression.

Constructing moiré superlattices has been demonstrated to be a powerful approach for tailoring the electronic properties of two-dimensional van der Waals materials. However, the periodic moiré potential diminishes rapidly away from the interface between the two stacked layers, restricting the moiré modulation only at the superlattice interface. Here, we present an alternative strategy to extend the influence range of the moiré tuning through drag interaction, a dynamic process involving inter-layer momentum/energy transfer mediated by Coulomb scatterings. By fabricating a unique electronic double-layer structure comprising a graphene moiré superlattice and a pristine graphene layer, we observe several intriguing inter-layer drag behaviors dominated by moiré physics. Notably, measuring the drag voltage within the pristine graphene layer, located distant from the moiré superlattice, reveals clear moiré tuning effects on the drag signal, including self-similar mapping spectra and the Hofstadter’s butterfly spectra of drag resistance in the presence of a magnetic field. The realization of such moiré drag effect thus establishes a new paradigm for remote moiré engineering, offering a gateway to explore rich moiré physics in the emerging two-dimensional systems. This study demonstrates that the influence range of moiré tuning can be significantly extended beyond the moiré superlattice to a distant conductor through inter-layer drag interaction, presenting a novel strategy for remote moiré engineering.

The distinguishing feature of a quantum system is interference arising from the wave mechanical nature of particles which is clearly central to macroscopic electronic properties. Here, we report the signature of quantum interference effect in inter-layer transport process. Via systematic magneto-drag experiments on graphene-based electronic double-layer systems, we observe low-field correction to the Coulomb-scattering-dominated inter-layer drag resistance in a wide range of temperature and carrier density, with its characteristics sensitive to the band topology of graphene layers. These observations can be attributed to a new type of quantum interference between drag processes, with the interference pathway comprising different carrier diffusion paths in the two constituent conductors. The emergence of such effect relies on the formation of superimposing planar diffusion paths, among which the impurity potentials from intermediate insulating spacer play an essential role. Our findings establish an ideal platform where the interplay between quantum interference and many-body interaction is essential. Previous demonstrations of quantum interference in solids have mainly been limited to intra-layer transport within single conductors. Zhu et al. report a new type of inter-layer quantum interference in graphene-based double-layer devices, due to interference between carrier diffusion paths across the constituent layers.