BIOMARKER DISCOVERY · Novel post-genomic bioanalytical techniques of metabonomics (metabolomics) in biomedical research and drug discovery

Final Activity Report Summary - BIOMARKER DISCOVERY (Novel post-genomic bioanalytical techniques of metabonomics (metabolomics) in biomedical research and drug discovery)

The scope of the project was the partnership of a big pharmaceutical company and a young academic group to perform research on the discovery of small molecule biomarkers in biological fluids developing systems biology studies (metabonomics). Biomarkers are molecules that characterise a disease (diagnostic markers), successful therapeutic intervention (drug efficacy markers), or unwanted effects caused by drug administration (toxicity markers). Drug Discovery represents one of the strongest drives and at the same time a bottleneck for the pharmaceutical industry. Discovery-development of new pharmaceuticals or diagnostics employs multidisciplinary research and state of the art technologies. Systems biology offers a multitude of platforms such as genomics, proteomics, metabonomics / metabolomics, which are inter-dependent and are influenced by several conditions such as the environment, food, or other stressors throughout life. Omics use powerful analytical methods to gather data on the physiology of the investigated system or organism. Extracting biochemical information needs a variety of chemometric / bioinformatics tools used to reduce the multi-dimensionality of the generated raw data. The aim is to suppress the noise (biochemical, electronic etc.) and reveal differences related to the investigated phenomena. For example, if we examine the effect of diet, we need to 'iron' the signal of other chemical components to study the signals of the chemicals related to the given diet. Unfortunately, we often have to deal with differences which are 'hidden in the grass' where the concentration or the signal of the 'markers' is much lower than the signal obtained from hundreds of other abundant chemicals. To overcome these problems in the current project we aimed: i) to validate the available technologies; ii) to use complementary technologies / tools; and iii) compare / correlate the obtained results. The research work of the project was divided in two major branches: 1) Fundamental research work Here, we worked towards the establishment / development of new methodologies and tools for metabonomics research in drug discovery. We worked with cutting-edge separation, mass spectrometry and NMR spectroscopy tools (often in direct cooperation with the instrument / software manufacturers). Research topics included validation of analytical tools (repeatability, cross-site validation, reproducibility and stability issues), evaluation of new technologies (ICP-MS, hot-water chromatography), sample preparation methods (solid phase extraction, sample dilution or centrifugation), evaluation / comparison of special peak picking algorithms used to treat data and find biomarkers. 2) Metabonomics or wider systems biology application oriented biomarker research to discover biomarkers of certain physiology states Characteristic studies included: the effect of diet on the physiology and metabolome, metabonomics on animal disease models (diabetes, arthritis, cancer and others) and studies with human population, administration of pharmaceuticals (statins, antibiotics, anti cancer drugs and others) to study therapeutic intervention or drug toxicity, effect of the living environment in the gut microbiota and urine metabolome. The project generated 40 man-months of exchange (38 to United Kingdom and 2 to Greece) and helped in the establishment of the Greek team in the metabolomics community. Important long-lasting synergies were created between the two partners and also with the wider academia and biotechnological research community. Result dissemination (by the end of the project) includes 11 publications and more than 30 presentations. To conclude we developed valid tools for mapping several biofluids and discovered biomarkers for disease (cancer, obesity, diabetes) and drug efficacy / toxicity.

Data: CORDIS, © European Union