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Metabolomics

Prof. RNDr. Zdeněk Glatz, CSc. Research Group Leader   email: glatz[at]chemi.muni.cz

THEMATIC RESEARCH FOCUS

RESEARCH AREAS

• Metabolomics
• Metabolism
• Metabolites
• Biomarkers
• Drug metabolism
• Nuclear magnetic resonance
• Mass spectrometry
• Liquid chromatography
• Gas chromatography
• Capillary electrophoresis

MAIN OBJECTIVES

• Using bacterial metabolomics as a model for systems biology.
• Establishing metabolite biomarkers for diagnostics.
• Development of a miniaturised drug metabolism system based on capillary electrophoresis.

CONTENT OF RESEARCH

Metabolomics is one of the newest “omics” in the field of systems biology. The subject of its study – metabolome is the complete set of metabolites that are present in cells under particular physiological or developmental ircumstances. Although the number of metabolites in a given organism is projected to be less than those of genes and proteins, the metabolome analysis presents a difficult analytical task. It is given not only by the wide diversity in physico-chemical properties of metabolites but also by the large differences in their abundance.

The main analytical techniques employed for metabolomic studies are based on NMR spectroscopy and mass spectrometry (MS). Besides the direct injection MS, this technique usually requires pre-separation of the metabolic components using either gas (GC) or liquid chromatography (LC). In addition to these well-established methodologies capillary electrophoresis (CE) even in combination with MS is gaining a position in this field.

Since the metabolites are downstream of all genome and proteome regulatory structures, they provide valuable information about the regulatory and catalytic properties of a gene product. In this consequence there is a growing interest in an application of metabolomics for functional genomics studies, for detection of metabolic dysfunctions and diseases and for study of drug metabolism.

As a result the metabolomic research will be focused on three key outcomes:

• Comprehensive development of metabolomic analytical tools for purpose of systems biology
• New diagnostic tools based on metabolomic biomarkers discovery for detection of metabolic dysfunctions and diseases
• High throughput analytical tools for drug development processes especially for drug metabolism studies

All above-mentioned analytical techniques should be applied for these research tasks.

KEY RESEARCH EQUIPMENT

PLANNED RESEARCH INFRASTRUCTURE

Technology Units

Metabolomics

CURRENT RESEARCH INFRASTRUCTURE

The metabolomic laboratoriy is equipped with three capillary electrophoresis (CE) instruments; one of them is connected to the new Agilent 6320 Ion Trap for mass spectrometry detection. In addition a new analytical HPLC system HP 1200 is available that could also be connectable to the above-mentioned MS system. The laboratories are further equipped with combined gradient HPLC systems (Shimadzu, ESA, Ecom) with an autosampler, column oven and diode-array, fluorescence and coularray detectors, UV VIS microtiter plate spectrophotometer and luminometer.

MAIN PROJECTS

• Miniaturized on-line drug-metabolism system based on capillary electrophoresis (GAP206/10/0057), Czech Science Foundation, 2010-2013, Z. Glatz, Masaryk University.
• Capillary electrophoresis as a member of the metabolomic analytical toolbox (GAP206/11/0009), Czech Science Foundation, 2011-2015, Z. Glatz, Masaryk University.
• Integrated bioanalytical technologies for microanalyses and diagnostics with laser induced fluorescence and mass spektrometry coupling (LC06023), Ministry of Education, Youth and Sports, 2006-2011, Z. Glatz, Masaryk University, L. Fajkusova, University Hospital Brno, F. Foret, Institute of Analytical Chemistry AS CR.

SELECTED PUBLICATIONS

• ZEISBERGEROVA, M., REMINEK, R., MADR, A., et al. On-line drug metabolites generation and their subsequent target analysis by capillary zone electrophoresis with UV-absorption detection. Electrophoresis. 2010, 31(19), p. 3256-3262.
• MUSILOVA, J., SEDLACEK, V., KUCERA, I., et al. Capillary zone electrophoresis with field enhanced sample stacking as a tool for targeted metabolome analysis of adenine nucleotides and coenzymes in Paracoccus denitrifi cans. Journal of separation science. 2009, 32(14), p. 2416-2420.
• ZEISBERGEROVA, M., ADAMKOVA, A., GLATZ, Z. Integration of on-line protein digestion by trypsin in CZE by means of electrophoretically mediated microanalysis. Electrophoresis. 2009, 30(13), p. 2378-2384.
• KONECNY, J., MICIKOVA, I., REMINEK, R., et al. Application of micellar electrokinetic capillary chromatography for evaluation of inhibitory effects on cytochrome P450 reaction. Journal of chromatography A. 2008, 1189(1-2), p. 274-277.
• ZHANG, J., KONECNY, J., GLATZ, Z., et al. Application of capillary electrophoresis in drug metabolism studies. Current analytical chemistry. 2007, 3(3), p. 197-217.