Current Opinion in Systems Biology最新文献

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.

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.

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.

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.

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.

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.