Current Opinion in Systems Biology最新文献

Chronotherapy aims at optimising the time of day and dosing of drugs administration. This is a promising perspective because the toxicity and efficacy of many drugs show a dependence on the time of the day at which they are administrated. Efficient cancer chronotherapy requires a good understanding of the interplay between the cell cycle and the circadian clock. Computational models offer a way to study the dynamics resulting from the coupling between these two biological oscillators and to predict successful therapeutic protocols. We review here recent advances and highlight key challenges for further developments of predictive mathematical models.

Plastic waste has become one of the most pressing environmental issues with rapidly increased their production that also has a severe impact on individual species and ecosystem functioning.

With recycling technologies in place, the waste plastic will become a valuable resource and hence less material will be lost to the environment. In the pursuit of a sustainable approach to the treatment of plastic waste, biological processes have emerged as an eco-friendly method with significant potential. In this review, we summarize previous research on the biodegradation of polystyrene (PS) as major plastics, including a review of the analytical methods used to investigate the plastic biodegradation, the isolation of PS-degrading microbes from various environment, and the identification of potential enzymes for PS biodegradation. Based on this, we propose a potential PS biodegradation pathway, even though the specific biochemical mechanisms associated with certain enzymes have not yet been fully identified. Finally, we discuss how PS-biodegrading enzymes can be identified using a systems biology-based screening approach that combines culture-based genomic and culture-independent metagenomic methods. This strategy can be applied to searching biodegrading enzymes for other plastics.

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.

The epigenome, comprising DNA and histone modifications alongside intricate chromatin structures, has emerged as pivotal players in disease development. These factors offer promising opportunities for therapeutic interventions, expanding the avenues traditionally explored within genetic elements. Eukaryotic chromatin exhibits an impressive capacity for computation and information storage, fueled by the dynamic interplay of factors that modify the physicochemical states of chromatin. With its unique attributes, chromatin emerges as a compelling candidate for synthetic intervention and therapeutic reprogramming. In this review, we explore pioneering initiatives aimed at synthetically manipulating the epigenome, a relatively uncharted domain with transformative potential for both diagnostics and treatments.

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.

How does genetic sequence give rise to biological function? Answering this question is key to our understanding of life and the construction of synthetic biosystems that fight disease, resource scarcity and climate change. Unfortunately, the virtually infinite number of possible sequences and limitations in their functional characterization limit our current understanding of sequence-function relationships. To overcome this dilemma, several high-throughput methods to experimentally link sequences to corresponding functional properties have been developed recently. While all of these share the goal to collect sequence-function data at large scale, they differ significantly in their technical approach, functional readout and application scope. Herein, we highlight recent developments in the aspiring field of high-throughput sequence-function mapping providing a critical assessment of their potential in synthetic biology.

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.

Integration of cell-free systems with genetic biosensors is emerging as an advantageous platform for small molecule detection. This biosensor-coupled cell-free system simplifies an assay-and-detection procedure by combining the advantages of rapid and efficient protein expression through a cell-free system and the in situ detection capabilities provided by genetic biosensors. Moreover, this system is easy to assay multiple conditions at once, as the open environment of the cell-free systems enhances overall ease of handling. In this review, we focus on the acceleration of enzyme and pathway prototyping using cell-free biosensors, as well as strategies to improve the sensitivity and specificity of biosensors. High-throughput screening tools that can expand the prototyping process by generating massive data sets for rapid evaluation were also described.

Synthetic biology has promoted a conceptual shift in metabolic engineering for the microbial production of industrial chemicals toward a sustainable economy. Engineering principles from synthetic biology and metabolic engineering are integrated to redesign cellular metabolism to create microbial cell factories with emerging and programmable functionalities. Combining metabolic engineering with programmed spatial control is a promising approach that enables deep rewiring of microbial cell factory metabolism for the efficient production of bio-based chemicals. In this review, we discuss metabolic compartmentalization approaches for programmable control of cellular metabolism, including intracellular or intercellular partitioning-based organization of biosynthetic pathways. We also examine the designs and applications of cellular compartments and their analogs, highlighting selected examples for creating efficient and sustainable microbial cell factories.