Current Opinion in Systems Biology最新文献

Neuropathic pain is a complex condition with a huge unmet medical need. Owing to our incomplete understanding of its perplexing pathology, current therapeutic strategies for treating neuropathic pain remain limited in their efficacy. Computational modeling has emerged as a promising methodology in unraveling the intricate neural mechanisms contributing to neuropathic pain. This review serves as a bridge that links traditional experimental research in neuropathic pain to computational neuroscience. We aim to fill in the gap of knowledge between these two fields by introducing the methodology of computational modeling as well as the neurophysiological background for neuropathic pain. We provide examples of recent advances in using computational modeling at the molecular, cellular, and neural network levels to harness the understanding of pain-associated neural signaling. This integration of computational modeling has yielded crucial insights into neuropathic pain pathophysiology, with great potential to inform novel pharmacological and neurostimulation-based treatments for the disease.

Concerns about environmental issues and limited fossil resources have increased interest and efforts in developing sustainable production of bio-based chemicals and fuels using microorganisms. Advanced metabolic engineering has developed microbial cell factories (MCFs) with the support of synthetic biology and systems biology. Isoprenoids are one of the largest classes of natural products and possess many practical industrial applications. However, it is challenging to meet the market demand for isoprenoids because of the current inefficient and unsustainable strategies for isoprenoid production such as chemical synthesis and plant extraction. Therefore, many efforts have been made to build isoprenoid-producing MCFs by applying metabolic engineering strategies, biological devices, and machinery from synthetic biology and systems biology. This review introduces recent studies of strain engineering and applications of biological tools and systems for developing isoprenoid MCFs. In addition, we also reviewed the isoprenoid fermentation strategies that lead to the best performance of isoprenoid-producing MCFs.

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.

Gas fermentation using autotrophic acetogenic bacteria has been industrialized, however, its full potential remains untapped, with only native products like ethanol being produced thus far. Advancements in synthetic biology have enabled the recombinant production of diverse biocommodities to broaden their limited natural product spectrum from C1-gases. Additionally, co-culturing acetogens with other microorganisms holds the potential for expanding the product spectrum further. However, commercialization remains challenging due to complex pathway and (co)culturing optimizations. To address this, novel synthetic biology tools, including the use of high throughput biopart screenings using reporter proteins, the deployment of cell-free systems to combine best-performing enzymes, and the identification and elimination of competing pathways, can be employed. Incorporating genetically engineered strains in co-cultures improves dependencies, directs product formation, and increases resilience, enhancing bioproduction efficiency. This review emphasizes using these tools to enhance the recombinant production of biocommodities, offering promising solutions to overcome existing challenges.

The successful use of mRNA vaccines during the Covid-19 pandemic has created a boom in mRNA therapeutic research and development. The efficacy of mRNA vaccines and therapies relies on the quality of the synthesized molecules – a key feature of which is the 5′-end cap modification. The development of analytical methods for assessing mRNA quality needs to be prioritized to enable manufacturing development, process control, and rapid assessment of batch quality before release. In this review, we provide an overview of the latest techniques in the analysis of mRNA 5′ capping. We also discuss future possibilities and challenges in quality control of mRNA products at scale.

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.

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.