Professor Ian Wilson Seminar and Bruker Prize Ceremony

The development of the so called “omics” technologies (genomics/proteomics/metabonomics etc, etc) has been promised as providing the potential to revolutionize areas such as personalized medicine by providing new, mechanistic diagnostic and prognostic biomarkers of disease and response to therapy. In the context of metabolic phenotyping (generally known as metabonomics /metabolomics)  the application of modern NMR and MS (the latter usually hyphenated to separations such as UHPLC-MS and GC-MS), has greatly increased the potential of this technology for “global” untargeted metabolic profiling (metabotyping) in the search for biomarkers. We are now in the transistion from small scale “proof of principle” studies to mainstream investigations in e.g., human disease and epidemiology. The high information content analytical platforms at our disposal are clearly capable of discovering metabolites that might be biomarkers of particular conditions, but identifying them, and then actually understanding what they are really biomarkers of, still poses significant problems.

At its simplest the question that these disease-correlated metabolites pose is, “are they really a set of useful mechanistic biomarkers delivering real insight to the biology of the disease being studied?”,  or merely a more general, non-specific, response?, or worse, are they just an artefact of the experimental design?.  One of the legacies of the London Olympics has been the repurposing of the drug testing laboratory, with its advanced analytical capabilities, for metabolic profiling as the UK’s “National Phenome Centre” (the NPC).  The NPC is, thanks to grants from the UK Medical Research Council and the NIHR, plus strong support from instrument manufacturers, is performing metabolic phenotyping on an “industrial” scale. This work, covering both clinical and epidemiological endpoints, will be described. Particular emphasis will be placed on the opportunities and challenges posed by the use of LC-MS-based techniques for metabolic profiling, illustrated with examples showing how metabolite-centred biomarker discovery can be performed.  Finally, the opportunities provided by some emerging technological developments, for both targeted and untargeted metabolic profiling, will be considered.