Within the past decades biochemical data of single processes, metabolic and signaling pathways were collected and advances in technology led to improvements of sensitivity and resolution of bioanalytical techniques. These achievements build the bases for the so called ‘genome wide biochemistry’. In this context the aim of our group is to apply metabolomics and proteomics techniques for absolute quantification and to analyze turnover rates of proteins and metabolites using stable isotopes. Furthermore we analyze posttranslational modifications of proteins e.g. by quantitative phospho-proteomics.

Our core interest is the characterization of post-transcriptional and post-translational regulatory mechanisms which play an important role in metabolic regulation. Therefore we have developed new techniques to measure the metabolic fluxes within the central metabolism using stable isotope labeled substrates e.g. glucose, glutamine, pyruvate or palmitate and combine this technology with state of the art proteomics methods. Using these techniques we could analyze the translational regulation of an RNA binding protein (Jungkamp et al. 2011) in vivo and could resolve the mode of action of a synthetic lethal interaction between MYC and the protein kinase ARK5 (Liu et al. 2012).

In frame of future projects we will apply phospho-proteomics, in combination with pulsed stable isotope resolved metabolomics (pSIRM) to identify new targets of metabolic regulation in cancer cells.

Scheme of the central metabolism of cancer cells

Distribution of isotopomers resulting from pulsed stable isotope resolved metabolomics after labeling with 13C-glucose or 13C-glutamine.