Confronting risks of mirror life.

Broad discussion is needed to chart a path forward.

Organ-on-chip technology: Opportunities and challenges.

Organ-on-chip (OOC) technology is an innovative approach that reproduces human organ structures and functions on microfluidic platforms, offering detailed insights into intricate physiological processes. This technology provides unique advantages over conventional in vitro and in vivo models and thus has the potential to become the new standard for biomedical research and drug screening. In this mini-review, we compare OOCs with conventional models, highlighting their differences, and present several applications of OOCs in biomedical research.

Tunable cell differentiation via reprogrammed mating-type switching.

This study introduces a synthetic biology approach that reprograms the yeast mating-type switching mechanism for tunable cell differentiation, facilitating synthetic microbial consortia formation and cooperativity. The underlying mechanism was engineered into a genetic logic gate capable of inducing asymmetric sexual differentiation within a haploid yeast population, resulting in a consortium characterized by mating-type heterogeneity and tunable population composition. The utility of this approach in microbial consortia cooperativity was demonstrated through the sequential conversion of xylan into xylose, employing haploids of opposite mating types each expressing a different enzyme of the xylanolytic pathway.

Prodrug-conjugated tumor-seeking commensals for targeted cancer therapy.

Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery.

MFSD7c functions as a transporter of choline at the blood-brain barrier.

Mutations in the orphan transporter MFSD7c (also known as Flvcr2), are linked to Fowler syndrome. Here, we used Mfsd7c knockout (Mfsd7c) mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood-brain barrier (BBB). We performed comprehensive metabolomics analysis and detected differential changes of metabolites in the brains and livers of Mfsd7cembryos.

Establishing chromosomal design-build-test-learn through a synthetic chromosome and its combinatorial reconfiguration.

Chromosome-level design-build-test-learn cycles (chrDBTLs) allow systematic combinatorial reconfiguration of chromosomes with ease. Here, we established chrDBTL with a redesigned synthetic chromosome , . We designed and built to harbor strategically inserted features, modified elements, and synonymously recoded genes throughout the chromosome.

Engineering for diagnosis and management of hyperuricemia.

Uric acid disequilibrium is implicated in chronic hyperuricemia-related diseases. Long-term monitoring and lowering of serum uric acid levels may be crucial for diagnosis and effective management of these conditions. However, current strategies are not sufficient for accurate diagnosis and successful long-term management of hyperuricemia.

Synthetic biology: Learning the way toward high-precision biological design.

Since its inception, synthetic biology has overcome many technical barriers but is at a crossroads for high-precision biological design. Devising ways to fully utilize big biological data may be the key to achieving greater heights in synthetic biology.

Engineering of a probiotic yeast for the production and secretion of medium-chain fatty acids antagonistic to an opportunistic pathogen .

is an opportunistic pathogen, with its infection as one of the causes of morbidity or mortality. Notably, the probiotic yeast var. boulardii has shown the potential to fight against infections.

FELICX: A robust nucleic acid detection method using flap endonuclease and CRISPR-Cas12.

Nucleic acid detection is crucial for monitoring diseases for which rapid, sensitive, and easy-to-deploy diagnostic tools are needed. CRISPR-based technologies can potentially fulfill this need for nucleic acid detection. However, their widespread use has been restricted by the requirement of a protospacer adjacent motif in the target and extensive guide RNA optimization.

An Engineered Probiotic Produces a Type III Interferon IFNL1 and Reduces Inflammations in Inflammatory Bowel Disease Models.

The etiology of inflammatory bowel diseases (IBDs) frequently results in the uncontrolled inflammation of intestinal epithelial linings and the local environment. Here, we hypothesized that interferon-driven immunomodulation could promote anti-inflammatory effects. To test this hypothesis, we engineered probiotic Nissle 1917 (EcN) to produce and secrete a type III interferon, interferon lambda 1 (IFNL1), in response to nitric oxide (NO), a well-known colorectal inflammation marker.

Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies.

The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases.

Synthetic Biology Meets Machine Learning.

This chapter outlines the myriad applications of machine learning (ML) in synthetic biology, specifically in engineering cell and protein activity, and metabolic pathways. Though by no means comprehensive, the chapter highlights several prominent computational tools applied in the field and their potential use cases. The examples detailed reinforce how ML algorithms can enhance synthetic biology research by providing data-driven insights into the behavior of living systems, even without detailed knowledge of their underlying mechanisms.

Dominant Negative TRAF3 Variant With Recurrent Infection and Bronchiectasis.

Host factors leading to pulmonary nontuberculous mycobacteria (PNTM) disease are poorly understood compared with disseminated NTM disease, which is linked to the interleukin 12-interferon gamma signaling pathway. We investigated the tumor necrosis factor receptor associated factor 3 (TRAF3) R338W variant in a patient with recurrent PNTM infection, demonstrating TRAF3- and TNF-α-deficient phenotypes via ex vivo immune and cloning-transfection cellular studies.

Engineering probiotics to inhibit Clostridioides difficile infection by dynamic regulation of intestinal metabolism.

Clostridioides difficile infection (CDI) results in significant morbidity and mortality in hospitalised patients. The pathogenesis of CDI is intrinsically related to the ability of C. difficile to shuffle between active vegetative cells and dormant endospores through the processes of germination and sporulation.

Potential use of microbial engineering in single-cell protein production.

Single-cell proteins (SCPs) have been widely used in human food and animal feed applications, still, there are challenges in their production and commercialization. Recently, advances in microbial synthetic biology, genomic engineering, and biofoundry technologies have offered capabilities to effectively and rapidly engineer microorganisms for improving the productivity, nutritional, and functional quality of SCPs. In this review, we discuss various synthetic biology, genomic engineering, and biofoundry tools that can be harnessed for SCP production and genetic modification.

Engineered microbial systems for advanced drug delivery.

The human body is a natural habitat for a multitude of microorganisms, with bacteria being the major constituent of the microbiota. These bacteria colonize discrete anatomical locations that provide suitable conditions for their survival. Many bacterial species, both symbiotic and pathogenic, interact with the host via biochemical signaling.

Design and fabrication of field-deployable microbial biosensing devices.

Biosensors could enable a wide range of applications in environmental monitoring, pathogen detection, and biomarker diagnostics. While conventional diagnostic platforms like chemical sensors and PCR-based assays are capable of highly sensitive detection in laboratory conditions, their configurations, production cost, and operational requirements are not suitable for applications beyond the laboratory. Recent advances in synthetic biology, bioelectronics, and materials sciences have paved the way for the creation of novel microbial biosensing devices, which integrate core synthetic biosensors with state-of-the-art deployment platforms to create unique biosensor products.

Transporter-Driven Engineering of a Genetic Biosensor for the Detection and Production of Short-Branched Chain Fatty Acids in .

Biosensors can be used for real-time monitoring of metabolites and high-throughput screening of producer strains. Use of biosensors has facilitated strain engineering to efficiently produce value-added compounds. Following our recent work on the production of short branched-chain fatty acids (SBCFAs) in engineered , here we harnessed a weak organic acid transporter Pdr12p, engineered a whole-cell biosensor to detect exogenous and intracellular SBCFAs and optimized the biosensor's performance by varying expression.

Heterologous expression of cyanobacterial gas vesicle proteins in Saccharomyces cerevisiae.

Given the potential applications of gas vesicles (GVs) in multiple fields including antigen-displaying and imaging, heterologous reconstitution of synthetic GVs is an attractive and interesting study that has translational potential. Here, we attempted to express and assemble GV proteins (GVPs) into GVs using the model eukaryotic organism Saccharomyces cerevisiae. We first selected and expressed two core structural proteins, GvpA and GvpC from cyanobacteria Anabaena flos-aquae and Planktothrix rubescens, respectively.

The Divergent Immunomodulatory Effects of Short Chain Fatty Acids and Medium Chain Fatty Acids.

Fatty acids are derived from diet and fermentative processes by the intestinal flora. Two to five carbon chain fatty acids, termed short chain fatty acids (SCFA) are increasingly recognized to play a role in intestinal homeostasis. However, the characteristics of slightly longer 6 to 10 carbon, medium chain fatty acids (MCFA), derived primarily from diet, are less understood.