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Medical diagnosis and the resulting treatment will improve the results significantly when a more personalized system for health assessment is implemented. This can be achieved by providing detailed information about the metabolic status of individuals. The use of metabolomic data to predict the health trajectories of individuals will require bioinformatic tools and quantitative reference databases. For example protein phosphorylation is probably the most important regulatory event in eukaryotes. Many enzymes and receptors are switched 'on' or 'off' by phosphorylation and dephosphorylation. Antibodies can be used as powerful tools to detect whether a protein is phosphorylated at any particular site. Such antibodies are called phospho-specific antibodies; hundreds of such antibodies are now available. They are becoming critical reagents both for basic research and for clinical diagnosis. Approaches to identify and more importantly quantify phosphorylated proteins, like mass spectrometry-based proteomics, are becoming increasingly important for the systematic analysis of complex phosphorylation networks. However, most of them lack the ability to identify the phosphorylation status rapidly and accurately. Furthermore, other post translational modification such as sulphurylation and the redox status of translational proteins and selenoproteins could give vital information about the metabolic status of an individual. Two challenges lie ahead for the bioanalytical community; the separation of the complex mixtures of metabolites, peptides and proteins and their quantitative determination. Most methods can only cover one of the challenges. Here, with this proposal, we seek funding to complete the world-wide unique set-up the SCOttish Trace element Speciation & Metabolomics Analytical Network (SCOTSMAN), a new combination of chromatography and/or electrophoresis and dual mass spectrometry to develop a rapid separation technique which is capable of online identification and quantification of metabolites and proteins which have been labelled or tagged in a complex matrix of organic compounds which do not contain an hetero-element. Hence, this method is able to pick out the needles in the haystack. This set-up will be able to quantify biomolecules containing a hetero-element such as phosphorous or sulphur or metals and metalloids such as copper, selenium and arsenic. Using element-specific detection coupled with high resolution mass separation, the requested instrument is capable of quantifying the compounds at ultra-trace level which is relevant for background studies and non diseased individuals. Since the instrument response is not dependant on the compound itself, it can be used to quantify the element in the introduced sample without having the exact compound as a standard. If that analyser is now coupled to a separation method online, the unambiguous quantification of the compound carrying the tag or label can be done directly. When identification of certain metabolites is of importance, the second complementary molecular mass analyser (already in place) will provide accurate data on the mass of the molecule simultaneously. This information is vital to deduce molecular formula. Altogether this proposal, supported by the manufacturer and a charity organisation has an extremely good add on value, since the requested instrument will be coupled directly with additional complementary mass analyser with similar calibre to built this unique analytical set-up for biologists, plant physiologists, microbiologists, researcher interested in systems biology and pharmacologists.
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