Extracellular proteases are important signaling molecules in coagulation, inflammation, cell migration, and pain. Dysregulation of extracellular protease activity is common in diseases that perturb these critical functions. Engineering cells to sense and respond programmatically to protease activity has applications in biosensing, cell-based screening for protease activity, and therapeutics. Here we report synthetic protease-activated receptors (SynPARs) based on engineered, auto-inhibited G protein-coupled receptors (GPCRs). Relief of autoinhibition by proteolysis enables receptor activation by an exogenous or tethered agonist to generate transgene expression, real-time fluorescence, or endogenous G-protein signaling. We demonstrate SynPAR modularity with diverse secreted proteases, establish a cell-based SynPAR library selection to optimize protease recognition sequences, and control neuronal activity in response to protease activity. Finally, we use SynPARs in the dorsal root ganglion of mice to counteract hyperalgesia produced by trypsin activity, rewiring neurons to produce an analgesic response to a pain-inducing stimulus. Our study establishes SynPAR as a versatile and modular platform for recording, sensing, and responding to pericellular proteolysis. This fills a critical gap in protease-sensing tools and lays the groundwork for protease-activated genetic and cell-based medicines.

Among display technologies, mRNA display has emerged as a powerful approach to identify de novo ligands for proteins of interest. Applying the same methods to studying the substrates of protein/peptide-modifying enzymes has received much less attention, but progress in this area has accelerated rapidly over the last 5 years. In this article, we review the published literature to date (up to December 2025) of dedicated efforts to identify and understand enzyme substrate preferences using mRNA- or cDNA-display. We include observations of trends from these reports over time and reflections on where the area may go in the future. We hope this will serve as a useful primer for researchers in this and related areas.

Metabolic diseases, such as obesity and diabetes, have risen due to lifestyle changes. Traditional treatments, including dietary modifications and pharmacological interventions, are limited by low compliance and adverse effects, highlighting the need for alternative therapeutic approaches that offer improved patient compliance and long-term effectiveness. Engineered live biotherapeutic products (eLBPs) have emerged as a promising strategy that combines bacterial chassis with synthetic genetic circuits for precise and targeted disease treatment. Unlike conventional therapeutics, eLBPs can colonize the intestinal tract and enable localized and condition-responsive therapeutic activity while offering improved safety profiles through defined mechanisms of action. This review highlights key strategies for eLBP development, particularly chassis selection and genetic circuit design. Applications in metabolic diseases, including inherited disorders such as phenylketonuria (PKU), demonstrate how engineered gene circuits can modulate specific metabolic pathways. However, several challenges remain, including genetic stability, interindividual variability, biological safety, and production scalability. In addition, further research on host–microbiota interactions is required to improve therapeutic predictability and efficacy, supporting the development of safe and effective personalized eLBP-based therapies for metabolic diseases.

Plastic pollution is a major environmental challenge, given its widespread presence and potential risks to both ecosystems and human health. Microbial biodegradation offers a promising solution for managing plastic waste. However, research in this area remains fragmented, with varying reports on degradation efficiency, mechanisms, and practical applications. This review synthesizes recent developments in microbial taxonomy, enzymatic depolymerization, and multiomics functional analysis, highlighting the connections between microbial traits and the four key stages of plastic degradation: colonization, depolymerization, assimilation, and mineralization. It critically evaluates the robustness and comparability of reported degradation metrics, demonstrating that variability in polymer properties, experimental conditions and assessment methods severely hinders meaningful comparisons across studies and limits the translation of laboratory findings to real-world applications. Additionally, this review elaborates on emerging bioaugmentation strategies such as genetic modification, enzyme engineering and synthetic microbial consortia design, while identifying key translational bottlenecks involving scalability, environmental relevance and long-term stability. By integrating insights from multiomics research and synthetic biology, this work proposes a framework to bridge the gap between laboratory-based discoveries and practical biodegradation strategies. It aims to advance microbial plastic remediation research by identifying key knowledge gaps and offering actionable recommendations for future developments.

Soil microbial communities have a variety of mechanisms to deal with emerging drought stress. One well-documented mechanism is increased microbial production of extracellular polymeric substances which can potentially change the soil density and water holding capacity. Yet little is known about how microbial diversity influences the functional capacity of EPS formation and the resulting outcomes in water dynamics. To understand more about communal microbiome EPS production, we set up sterile mesocosms where we examined the effects of microbial diversity and nutrient input on these processes. To capture the microhydrology of the mesocosms, we measured water holding, infiltration, evaporation, and soil properties we believe microbes are altering. Our hypothesis stated that if diversity was artificially manipulated, then soil-water properties will be altered via production of EPS. We predicted that low diversity systems would have lower functional diversity, leading to less EPS production, moisture storage, and minimal changes from inert soil media. As predicted, we found that the high-diversity systems had a higher water retention and lower rates of water loss over time than low-diversity systems. This trend was magnified in the nutrient-supplemented treatment, suggesting that EPS production and subsequent water-holding traits are emergent features of the microbiome. Unexpectedly, we observed a correlation between the amount of water retained and the quantity of lipid EPS produced. This suggests that EPS composition, rather than quantity, is determinative of a biofilm's function. In conclusion, it appears that microbial diversity influences soil properties that are important to moisture retention within these systems. To date, the role that microbes and their diversity play in soil hydrology has been severely understudied, so this work aims to build ecological understandings of these systems. These findings are valuable, for if we learn how microbes manipulate soil moisture, we can apply these functions to advance sustainable agricultural practices and enhance ecosystem resilience to water scarcity in arid regions.

The development of functional nanomaterials with controlled morphologies is essential for advancements in medicine, electronics and computing, energy, catalysis, and environmental applications. However, conventional synthesis methods often demand high energy input and pose significant environmental challenges. Urease-based biomineralization presents an efficient, eco-friendly alternative for nanomaterial production under mild conditions. In this study, we engineered E. coli to express a urease gene cluster from Sporosarcina pasteurii using CRAGE-Duet technology. The engineered strain successfully synthesized calcium carbonate and calcium phosphate crystals. Expanding the approach, we synthesized metal oxide nanoparticles, including hematite (Fe2O3), and nanocrystalline anatase titanium dioxide (TiO2). These nanomaterials were characterized by electron microscopy, demonstrating the potential of E. coli as a sustainable and versatile platform for green nanomaterial synthesis.