Current Opinion in Systems Biology最新文献

The human immune system is determined by the functionality of the human lymph node. With the use of high-throughput techniques in clinical diagnostics, a large number of data is currently collected. The new data on the spatiotemporal organization of cells offer new possibilities to build a mathematical model of the human lymph node - a virtual lymph node. The virtual lymph node can be applied to simulate drug responses and may be used in clinical diagnosis. Here, we review mathematical models of the human lymph node from the viewpoint of cellular processes. Starting with classical methods, such as systems of differential equations, we discuss the values of different levels of abstraction and methods in the range of artificial intelligence techniques formalism.

Biological recycling and valorization of plastics are promising approaches to solve global plastic waste accumulation. Out of diverse plastic materials, polyethylene terephthalate (PET) is one of the most abundant polymers with rapid development in both biodegradation and product upcycling. In this perspective, we review recent discoveries and engineering of PET-degrading enzymes together with plausible auxiliary pathways, and provide insights on how to construct better parts through systematic bioengineering (metagenome mining, protein design, and directed evolution). Then, we discuss the potential of microbial-based PET degradation and upcycling in either a single host or consortia, as well as bottom-up and top-down methods of microbial consortia engineering using novel synthetic biology tools for enhanced PET circularization.

Host immune responses play a pivotal role in defending against influenza viruses. The activation of various immune components, such as interferon, macrophages, and CD8⁺ T cells, works to limit viral spread while maintaining lung integrity. Recent mathematical modeling studies have investigated these responses, describing their regulation, efficacy, and movement within the lung. Here, we discuss these studies and their emphasis on identifying nonlinearities and multifaceted roles of different cell phenotypes that could be responsible for spatially heterogeneous infection patterns.

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.

The growing numbers of cancer cases represent a medical and societal burden worldwide. More than half of all cancer patients are treated with chemotherapy. Yet, chemotherapeutic drugs kill not only cancer cells, but also healthy tissue, causing massive adverse side effects. Recent research on circadian medicine suggests that side-effects can be reduced, and treatment efficacy increased, by considering the biological clock of patients. Integrating circadian profiles of molecular clock markers in personalized mathematical models can simulate individual circadian dynamics of drug uptake, drug action and cellular response to chemotherapy. This requires advanced computational tools that balance prediction quality with overfitting. Personalized mathematical models will eventually lead to an optimal alignment of treatment timing with the inner circadian clock of the patient, reducing side effects, increasing efficacy and enhancing patient well-being.

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.

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.

Naïve CD4+ T cells can polarize into diverse functionally distinct effector cell types such as Th1, Th2, Th17 and Treg. These cell types can also interconvert among one another. The dynamics of T-cell differentiation and plasticity is driven by complex interactions involving many feedback loops among cytokines, intracellular signalling and lineage-determining transcription factors. In the past two decades, mechanistic computational models have played an instrumental role in understanding the underlying emergent dynamics. Here, we highlight the key concepts elucidated from such modelling efforts – a) multistability in underlying gene regulatory networks, b) the (co-) existence of stable hybrid cell states (Th1/Th2, Th1/Th17, Th2/Th17), and c) population-level dynamics of T-cell differentiation. These models, in close integration with experimental data, have improved our understanding of cell-state transitions and trajectories implicated in intracellular and population dynamics of T-cell plasticity.