DRA Lecture: NMR-based metabonomics

Thursday, February 23rd, 2006 at 10:30-12:15 in Benzon Auditorium

The Danish University of Pharmaceutical Sciences Universitetsparken 2, 2100 Copenhagen O

Part 1. NMR-based metabonomics: principles and techniques

Part 2. Applications of metabonomics to pharmaceutical R&D

Biological Chemistry, Biomedical Sciences Division, Imperial College London, UK

The place that metabonomics has in systems biology will be introduced and the main types of sample that can be analysed will be shown. These comprise biofluids and tissue biopsies. The principal analytical methodologies that are used will be introduced, concentrating on those based on NMR spectroscopy. The potential problems of analytical and biological variation will also be covered. In order to interpret the resulting complex data sets, it is necessary to use multivariate statistics approaches (chemometrics) and the basic principles of these will be explained.  More advanced standard and new chemometric methods used in metabonomics will also be described, explaining the roles of unsupervised methods for ease of visualisation of complex data sets and supervised methods for building predictive models of outcome based on NMR spectra.  Interpretation of such models allows the identification of combinations of metabolites that change their concentrations in different classes of samples - these become biomarkers of the effect being studied. 

Some applications of the NMR-based metabonomics approach will be illustrated, including physiological variation such as the effects of both genetic and environmental factors, ageing, diet, herbal remedies and gut microflora on metabolic profiles.  Once an understanding of normal variation is obtained then it is possible to consider pathological effects.  The use of metabonomics as a tool for investigating drug toxicity will be highlighted.  Some studies will be employed to show how metabonomics can be used for disease diagnosis, including the study of large populations for screening investigations. This then leads to the use of metabonomics for measuring the therapeutic responses to drugs and an example of the use of statin drug treatment for hyperlipidaemia will be shown.  Metabonomics opens up the possibility, in an analogous fashion to pharmacogenomics, that there will be a signature in human metabolic profiles that predicts the predisposition for individuals to metabolise drugs differently or to show variable adverse effects to a drug.  This has been termed pharmaco-metabonomics and preliminary results of a study in both rats and man will be shown. 

The DRA-lecture is a part of a PhD course organised by: Jerzy Jaroszewski (the Danish University of Pharmaceutical Sciences) and is open for attendance by all interested parties.