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See detailModeling metabolism of the human gut microbiome
Magnusdottir, Stefania UL; Thiele, Ines UL

in Current Opinion in Biotechnology (2018)

The human gut microbiome plays an important part in human health. The complexity of the microbiome makes it difficult to determine the detailed metabolic functions and cross-talk occurs between the ... [more ▼]

The human gut microbiome plays an important part in human health. The complexity of the microbiome makes it difficult to determine the detailed metabolic functions and cross-talk occurs between the individual species. In silico systems biology studies of the microbiome can help to identify metabolite exchanges among gut microbes. Constraint-based reconstruction and analysis methods use biochemically accurate genome-scale metabolic networks of microorganisms to simulate metabolism between species in a given microbiome and help generate novel hypotheses on microbial interactions. Here, we review metabolic modeling studies that have investigated metabolic functions of the gut microbiome. [less ▲]

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See detailCritical transitions in chronic disease: transferring concepts from ecology to systems medicine
Trefois, Christophe UL; Antony, Paul UL; Goncalves, Jorge UL et al

in Current Opinion in Biotechnology (2015), 34

Ecosystems and biological systems are known to be inherently complex and to exhibit nonlinear dynamics. Diseases such as microbiome dysregulation or depression can be seen as complex systems as well and ... [more ▼]

Ecosystems and biological systems are known to be inherently complex and to exhibit nonlinear dynamics. Diseases such as microbiome dysregulation or depression can be seen as complex systems as well and were shown to exhibit patterns of nonlinearity in their response to perturbations. These nonlinearities can be revealed by a sudden shift in system states, for instance from health to disease. The identification and characterization of early warning signals which could predict upcoming critical transitions is of primordial interest as prevention of disease onset is a major aim in health care. In this review, we focus on recent evidence for critical transitions in diseases and discuss the potential of such studies for therapeutic applications. [less ▲]

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See detailHow metabolites modulate metabolic flux
Wegner, André UL; Meiser, Johannes UL; Weindl, Daniel UL et al

in Current Opinion in Biotechnology (2015), 34

Adaptation to metabolic needs and changing environments is a basic requirement of every living system. These adaptations can be very quick and mild or slower but more drastic. In any case, cells have to ... [more ▼]

Adaptation to metabolic needs and changing environments is a basic requirement of every living system. These adaptations can be very quick and mild or slower but more drastic. In any case, cells have to constantly monitor their metabolic state and requirements.In this article we review general concepts as well as recent advances on how metabolites can regulate metabolic fluxes. We discuss how cells sense metabolite levels and how changing metabolite levels regulate metabolic enzymes on different levels, from specific allosteric regulation to global transcriptional regulation. We thereby focus on local metabolite sensing in mammalian cells and show that several major discoveries have only very recently been made. [less ▲]

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See detailA roadmap for interpreting (13)C metabolite labeling patterns from cells.
Buescher, Joerg M.; Antoniewicz, Maciek R.; Boros, Laszlo G. et al

in Current opinion in biotechnology (2015), 34

Measuring intracellular metabolism has increasingly led to important insights in biomedical research. (13)C tracer analysis, although less information-rich than quantitative (13)C flux analysis that ... [more ▼]

Measuring intracellular metabolism has increasingly led to important insights in biomedical research. (13)C tracer analysis, although less information-rich than quantitative (13)C flux analysis that requires computational data integration, has been established as a time-efficient method to unravel relative pathway activities, qualitative changes in pathway contributions, and nutrient contributions. Here, we review selected key issues in interpreting (13)C metabolite labeling patterns, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments. [less ▲]

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See detailLipid-based biofuel production from wastewater
Muller, Emilie UL; Sheik, Abdul UL; Wilmes, Paul UL

in Current Opinion in Biotechnology (2014), 30

Increasing world population, urbanization and industrialization are driving global increases in wastewater production. Wastewater comprises significant amounts of chemical energy primarily in the form of ... [more ▼]

Increasing world population, urbanization and industrialization are driving global increases in wastewater production. Wastewater comprises significant amounts of chemical energy primarily in the form of organic molecules (in particular lipids), which are currently not being recovered comprehensively. Within biological wastewater treatment (BWWT) systems, specialized microorganisms assimilate and store lipids anaerobically. These intracellular stores represent interesting feedstocks for biofuel synthesis. Here, we review our current understanding of the genetic and functional basis for bacterial lipid accumulation and processing, and relate this to lipid accumulating bacterial populations which occur naturally in BWWT plants. A grand challenge for microbial ecologists and engineers now lies in translating this knowledge into the design of new BWWT processes for the comprehensive recovery of lipids from wastewater streams and their subsequent conversion into biofuel. [less ▲]

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See detailProfiling metabolic networks to study cancer metabolism
Hiller, Karsten UL; Metallo, Christian M.

in Current Opinion in Biotechnology (2013)

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See detailFrom multi-omics to basic structures of biological systems.
Müller, Susann; Hiller, Karsten UL

in Current Opinion in Biotechnology (2013), 24

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See detailA systems biology approach to studying the role of microbes in human health.
Thiele, Ines UL; Heinken, Almut Katrin UL; Fleming, Ronan MT UL

in Current Opinion in Biotechnology (2013), 24(1), 4-12

Host-microbe interactions play a crucial role in human health and disease. Of the various systems biology approaches, reconstruction of genome-scale metabolic networks combined with constraint-based ... [more ▼]

Host-microbe interactions play a crucial role in human health and disease. Of the various systems biology approaches, reconstruction of genome-scale metabolic networks combined with constraint-based modeling has been particularly successful at in silico predicting the phenotypic characteristics of single organisms. Here, we summarize recent studies, which have applied this approach to investigate microbe-microbe and host-microbe metabolic interactions. This approach can be also expanded to investigate the properties of an entire microbial community, as well as single organisms within the community. We illustrate that the constraint-based modeling approach is suitable to model host-microbe interactions at molecular resolution and will enable systematic investigation of metabolic links between the human host and its microbes. Such host-microbe models, combined with experimental data, will ultimately further our understanding of how microbes influence human health. [less ▲]

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See detailFrom multi-omics to basic structures of biological systems.
Hiller, Karsten UL

in Current Opinion in Biotechnology (2012)

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See detailFrom Systems Biology to Systems Biomedicine
Antony, Paul UL; Balling, Rudi UL; Vlassis, Nikos UL

in Current Opinion in Biotechnology (2012), 23(4), 604-8

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to ... [more ▼]

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients’ quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multiscale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine. [less ▲]

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See detailDiseases as network perturbations
del Sol Mesa, Antonio UL; Balling, Rudi UL; Hood, Leroy UL et al

in Current Opinion in Biotechnology (2010), 21(4), 566-571

The tremendous amount of the data obtained from the study of complex biological systems changes our view on the pathogenesis of human diseases. Instead of looking at individual components of biological ... [more ▼]

The tremendous amount of the data obtained from the study of complex biological systems changes our view on the pathogenesis of human diseases. Instead of looking at individual components of biological processes, we focus our attention more on the interaction and dynamics of biological systems. A network representation and analysis of the physiology and pathophysiology of biological systems is an effective way to study their complex behavior. Specific perturbations can trigger cascades of failures, which lead to the malfunctioning of cellular networks and as a result to the development of specific diseases. In this review we discuss recent developments in the field of disease network analysis and highlight some of the topics and views that we think are important for understanding network-based disease mechanisms. [less ▲]

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