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September 01, 2009 (Vol. 29, No. 15)

Using Metabolomics to Optimize Bioprocessing

Systems Biology Tool Strives to Help Scientists Increase Knowledge of Cellular Changes

  • Click Image To Enlarge +
    Figure 1. The central dogma of biology showing the flow of information from DNA to the phenotype. Associated with each stage is the corresponding systems biology tool.

    Cells can be grown in cultured media for a variety of scientific applications. One common use is the production of recombinant proteins in cell-based bioreactors. Determining the optimal growth conditions in order for these cells to achieve the highest product quantity and quality involves a complex series of experiments that modify the hundreds of components in the media, the feeding schedule, and a wide variety of other variables such as temperature and dissolved oxygen.

    New tools are emerging to better characterize cellular growth and production of recombinant proteins. These tools provide insight into the mechanisms involved in growth and production, as well as uncover biomarkers that can be used to monitor the key mechanisms involved. Given the complex nature of cells growing in a cultured environment, systems biology tools (Figure 1) are well-adapted for understanding cell growth on a comprehensive basis.

  • Understanding Cellular Phenotype

    Metabolomics, a systems biology tool, is defined as the comprehensive profiling of all the biochemicals and metabolites in a biological sample. It is nonhypothesis driven so that no specific class of biochemicals or particular pathways is targeted. The majority of metabolomics studies are done using mass spectrometry, often coupled with another chromatographic method for better resolution of components. This analysis reveals changes in biochemicals and their associated pathways that are related to the experimental design, including drug, disease, diet, or environmental effects. Because these changes are closely related to the biological phenotype (Figure 1), a metabolomic analysis can provide insight into mechanism (e.g., drug toxicity) as well as markers related to the phenotype (e.g., diagnostic markers of disease).

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