research

Projects developed at Helmholtz Center Munich (HMGU)

Metabolomics research

  • At the Helmholtz Center Munich - German Research Center for Environmental Health(HMGU), I started a research program on genetically determined human metabotypes and their link to complex disease. Metabolomics studies in animal models, such as mice and bovine are used in complement to studies in a human population. As a bioinformatician, I combine data from different sources, many of them from HelmholtzMuenchen instruments, such as targeted quantitative metabolomics from a API Q TRAP 4000, non-targeted metabolomics from a Bruker 12 Tesla APEX FT-ICR, and genotyping information using Affymetrix 500k and 6.0 GeneChip arrays on the KORA population.
  • I have set up a group in metabolic research, with partners from the Helmholtz Zentrum München institutes GAC (J. Adamski), EPI (T. Illig), and IOEC (P. Schmitt-Kopplin). Our group is providing different bioinformatics resources, which are available through this metabolomics web server. On that site, a Wiki for the metabolic initiative Wiki for the metabolic initiative MetaP is available for registered users.

  • We have organized the conference Metabolomics & More : The Impact of Metabolomics on the Life Sciences, which will be held on March 10-12, 2010 in Freising-Weihenstephan, Germany.

  • MassTRIX: Mass TRanslator into Pathways is a web server for the annotation of high precision mass spectrometry data. It is available at www.masstrix.org.

German Centre for Diabetes Research

DZD e.V.
  • The "Deutsches Zentrum fuer Diabetesforschung e.V." (DZD) is an intertdisciplinary cooperation of the Helmholtz Association and the Leibniz Association with strong contributions from the University of Tuebingen and the University Clinic Dresden. The managing office is at the Helmholtz Centre Munich.

Genome Analysis Centre (GAC)

  • Greifswald Approach to Individualized Medicine (BMBF-research project). The objective of Gani_Med is to use state-of-the-art diagnostics and novel therapeutic interventions that take into account the specific requirements and characteristics of the individual patient in order to increase the effectiveness of treatments, avoid unwanted adverse reactions and significantly reduce health care costs.

SysMBo

  • Systems Biology of Metabotypes (BMBF-research project). SysMBo is an interdisciplinary research consortium aiming to unravel the complex relations between genetic predisposition, environmental stimuli and disease. With the help of high-throughput metabolite profiling and powerful modelling tools, the researchers take a system based approach in order to understand the complex interplay between numerous factors leading to a pathophenotype.

SysMBo

  • The Metabolomic Platform (metaP) is a scientific interdisciplinary cooperation of Institutes of the Helmholtz Zentrum München. The activities include both profiling (analyses of all measurable analytes to identify differences) and targeted analyses (quantification of a chosen set of analytes). These activities are possible by the unique contributions of participating Helmholtz Zentrum München institutes in the GAC.

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What are genetically determined metabotypes?

Common genetic polymorphisms induce major differentiations in the metabolic make-up of the human population. We conducted a genome-wide association study with metabolomics, identifying genetic variants in genes involved in the breakdown of fats (Gieger et al., PLoS Genetics, 2008). The resulting differences in metabolic capacity can affect individuals' susceptibility to complex diseases such as diabetes and hyperactivity. In the rapidly evolving field of metabolomics, scientists aim to measure all endogenous metabolites in a cell or body fluid. These measurements provide a functional readout of the physiological state of the human body. Investigation into these so-called "genetically determined metabotypes" in their biochemical context may help determine the pathogenesis of common diseases and gene-environment interactions. We identified four single nucleotide polymorphisms (SNPs) located in genes coding for well-characterized enzymes of the lipid metabolism. Individuals with different genotypes in these genes have significantly different metabolic capacities with respect to the synthesis of some polyunsaturated fatty acids, the beta-oxidation of short- and medium-chain fatty acids and the breakdown of triglycerides. By simultaneous measurements of both SNPs and serum concentrations of endogenous metabolites, the researchers determined the metabolome of several hundred healthy individuals and compared it to their genetic inheritance. The results suggest that most individuals carry one or more risk alleles in their genetic inheritance that may determine a certain medical phenotype, the response to a given drug treatment, or the reaction to a nutritional intervention or environmental challenge. These findings may lead to more targeted approaches to health care based on a combination of genotyping and metabolic characterization. To achieve this goal, it will be necessary to identify the major genetically determined metabotypes and their association to complex diseases.

A much larger study has been published in Nature Genetics (Illig, Gieger et al., 2010). This study identifies a number of new genetically determined metabotypes.

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