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Sep 15, 2009 (Vol. 29, No. 16)

Metabolic Profiling Crucial to Unveiling Cellular Complexity

Ability to Dynamically Integrate Intracellular Networks Emerging as Principal Benefit

  • Metabologeography

    A fascinating new field that became possible thanks to metabolic profiling where other approaches failed is metabologeography, or the differentiation of geography-related metabotypes. Philippe Schmitt-Kopplin, Ph.D., leader of the department of biogeochemistry and analytics at the German Research Center for Environmental Health in Munich, and his French collaborators at the UNSECO Chair Culture et Traditions du Vin and University of Burgundy in Dijon, used a nontargeted metabolomics approach primarily based on ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to demonstrate that it is possible not only to differentiate red from white wine, but also to determine the type of grapes that were used.

    “The challenges in metabolic profiling are the same and are independent of the question you are exploring. The primary challenge is to get an ideal experimental sample setup and to combine the right high-resolution analytical and statistical/mathematical tools,” says Dr. Schmitt-Kopplin.

    Using a combination of multidimensional separation techniques to spectrometry (FTICR-MS, 12 Tesla) and spectroscopy (Cryo-NMR, 500 & 800 MHz), his department recently embarked on various studies related to environmental issues (meta-metabolome and C-cycling in the oceans, terrestrial environments, and atmosphere related to global climate change), food chemistry (GMO, beverage metabotyping), nutrition and health (new noninvasive sampling techniques such as exhaled breath condensates and pathogen interactions).

    Recently, Dr. Schmitt-Kopplin and collaborators used FTICR mass spectrometry to examine the metabolic profiles of fecal water extracts from twins with Crohn’s disease. Comparing healthy, concordant and discordant twins revealed that there are differences in the metabolome/microbiome, not only between healthy- and Crohn’s-disease individuals but even between patients in whom inflammatory changes were localized primarily in the colon versus ileum.

    Besides unveiling new metabolites that are differentially present in patients with the disease and could provide important noninvasive diagnostic or monitoring biomarkers, the approach revealed that not only specific metabolites, but also metabolic pathways, are important to be considered as potential biomarker or therapeutic targets.

  • Interpretation and Description

    The ability to meaningfully interpret information provided by several approaches represents a cornerstone of metabolomics. “We need to integrate all the information, understand how molecules interact with each other, and establish mathematical models that can be validated by experimental approaches,” says Kazuki Saito, Ph.D., group leader of the metabolic function research group at the RIKEN Plant Science Center.

    Recently, by using Arabidopsis thaliana as a model, Dr. Saito and collaborators established a link between mitochondrial function and circadian rhythms in plants. Circadian clocks, described in organisms ranging from bacteria to mammals, were implicated in blood-pressure regulation, hormone-level homeostasis, and drug metabolism.

    Dr. Saito and collaborators focused on three Arabidopsis genes and, by using transcriptomic and metabolomic analyses, found a link between circadian rhythms, mitochondrial homeostasis and stress response, pointing toward the possibility that mitochondrial physiology and circadian clocks might be linked across several species.

    While many omics approaches comprehensively describe various components of the cellular network, the most accurate description of cellular processes is provided by metabolic fluxes, which emerge from the complex interaction of all cellular components.

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