Current Opinion in Systems Biology最新文献

A germline-soma distinction — irreversible differentiation from reproductive germline cells to sterile somatic cells — is a landmark of cellular cooperation in metazoans. Traditionally, this distinction was considered a property of only some metazoan taxa, such as vertebrates and insects. However, recent studies on a number of other metazoan taxa are challenging this traditional perspective, suggesting that a germline-soma distinction is widespread among metazoans. Here, we review recent molecular and cellular evidence supporting this suggestion and emphasise the difference between germline-soma distinction and germline segregation. We also outline the considerable diversity among metazoans in germline specification, segregation and regeneration. We finish by discussing how evolutionary explanations for this diversity can be investigated by harnessing theoretical modelling approaches.

In recent years, synthetic biology has provided many engineering approaches to reprogram and engineer cells in diverse applications including the development of novel therapeutics. Engineered cells provide advantages over small molecules or biologics, as these cells can be reprogrammed to have spatial and temporal control over the delivery of therapeutics in response to disease biomarkers. Herein, some of the recent applications of engineered live bacterial therapeutics against human diseases such as cancer, metabolic disorders, gastrointestinal diseases, and infections are reviewed. Furthermore, this review highlights active clinical trials on engineered cells with promising results.

To achieve a circular bioeconomy, carbon streams can be utilised through microbial conversion to produce value-added compounds. Although some microorganisms are naturally able to grow on these renewable carbon sources and generate desirable molecules, significant engineering is required to develop platform chassis exhibiting attractive performance parameters for industrial-scale processes. Here, we provide a brief overview of the core considerations in chassis engineering for autotrophic bioproduction, including carbon and energy supply, in addition to emerging standards for rewiring metabolic pathways to enhance growth and biosynthetic capabilities. We highlight examples of successful strategies, placing emphasis on recent advances in engineering autotrophic capabilities in both native autotrophs and heterotrophs.

The increased awareness of the pharmaceutical supply chain issues after the recent pandemic crisis has emphasized the need for innovative drug discovery. Natural products (NPs) have emerged as promising candidates to address pandemics due to their diverse structures and medicinal properties. However, development of novel NP-drugs in pharmaceutical supply chains has faced many challenges, including the absence of an efficient large-scale production platform to meet market demands. The advent of systems metabolic engineering has facilitated the efficient production of NPs in microorganisms compared with traditional plant-based and chemical-based production. In this article, we review recent strategies in systems metabolic engineering that have opened up new avenues for NP-drug discovery and production. In addition, we suggest viewpoints on how combinatorial approaches of systems metabolic engineering and synthetic chemistry will further enhance the diversity of NP-drugs and provide prospects for the development of NP-drugs in the pharmaceutical supply chain.

Many proteins begin to fold as they are being synthesized by the ribosome. Growing experimental evidence, supported by new theory, simulation and bioinformatics studies, suggests that many proteins rely on co-translational folding in order to fold efficiently and to avoid misfolded intermediates that arise posttranslationally. Consistent with these findings, complementary bioinformatics analyses have revealed widespread evolutionary selection for efficient co-translational folding kinetics. This perspective summarizes recent theoretical and experimental advances that have uncovered specific molecular mechanisms underlying the benefits of co-translational folding in vivo. We highlight studies involving single-domain proteins that begin adopting nativelike structure on the ribosome, which can help commit misfolding-prone domains to their native state. We emphasize the need for new experimental techniques to probe the molecular details underlying this process systematically.

After decades of development, DNA synthesis, assembly, and sequencing technologies have reached a high level, allowing faster and cheaper acquirements of synthetic genes or even de novo synthesis of an entire genome. Meanwhile, the value of synthetic genomes keeps increasing, and the target organisms have covered viruses, bacteria, and yeast and moved toward higher eukaryotes. However, as the length of genomes moves from kilobase to gigabase, the cost of synthetic genome projects increases sharply and requires years of effort to complete. Therefore, new DNA synthesis technology and a next-generation DNA synthesizer are urgently needed. In this review, we focus mainly on the advances in DNA and genome synthesis and discuss difficulties that need to be addressed in both areas.

High-throughput (HT) methodologies are extensively applied in synthetic biology for the rapid enrichment and selection of desired properties from a wide range of genetic diversity. In order to effectively analyze these vast variants, HT tools must offer parallel experiments and compact reaction capabilities to enhance overall throughput. Here, we discuss about various aspects of three representative high-throughput screening (HTS) systems: microwell-, droplet-, and single-cell-based screening. These systems can be categorized based on their reaction volume, which in turn determines the associated technology, machinery, and supporting applications. Furthermore, HT techniques that rapidly connect numerous genotypes and phenotypes have evolved to enhance the precision of predictions through the integration of digital technologies like machine learning and artificial intelligence. The use of advanced HT techniques within biofoundry will enable rapid selection and analysis from extensive genetic diversity, making it a driving force for the advancement of synthetic biology.

Cell-free synthetic biology is swiftly progressing and is poised to revolutionize multiple domains within synthetic biology. By departing from the constraints of living cells, it dramatically expands potential applications, surmounting the intrinsic limitations associated with cellular systems, especially where access to cytosolic conditions poses challenges. The open nature of cell-free systems means their potential applications are vast, limited only by creative imagination. A burgeoning number of studies underline its versatility across a broad spectrum of fields. This review article offers an insight into the recent advancements in this vibrant area, pinpointing key achievements and challenges in arenas such as biomanufacturing, pathway prototyping, and material sciences.

Traditional therapeutics aim to diagnose, treat, and cure diseases through various synthetic and natural approaches. The emerging field of engineered living therapeutics (ELTs) genetically functionalizes living cells to alter the paradigm of designed solutions. In this review, we focus on ELTs derived from microbial cell scaffolds. We propose three synergistic modalities for the rational design of ELTs: first, use of regulatory operations to regulate genetic expression; second, integration of alternative biosensing inputs for directed application; third, choice of microbial chassis to deliver solutions. We highlight the challenges and future opportunities within each group and conclude by providing a prospective outlook for ELTs.

The development of synthetic biology has resulted in the use of genetically engineered microbes (GEMs), becoming increasingly critical for addressing global issues such as health, food shortage, climate crisis, and environmental pollution. However, GEMs also pose a potential threat to the ecosystem, necessitating the implementation of biocontainment strategies. Synthetic genetic circuits have the potential to provide an additional level of safety and control beyond traditional physical containment measures. The development of biocontainment strategies is ongoing, including the use of kill switches, auxotrophy, and stringent response circuits, to control the viability of GEMs. This review discusses the application and future directions of genetic circuits for microbial biocontainment strategies.