1. Place, date, unit, occasion etc. Slide 1 Nikoline Juul Nielsen, Post Doc Soil and Environmental Chemistry (present) Bioorganic Chemistry (previous) Exploratory Chemometrics and Analytical Chemistry – Looking for the Needle in the Haystack

2. Place, date, unit, occasion etc. Slide 2 PhD in Natural Product Research Developing analytical tools (ways of measuring) and data processing tools (ways of interpreting data) for discovery of novel natural products

3. Place, date, unit, occasion etc. Slide 3 Natural Products I - Drugs S:de novo synthetic N:Natural product NM: Natural product mimic ND: Natural product derived S*: Synthetic, but NP pharmacophore Newman and Cragg (2007): Journal of Natural Products, 70, 461- Small molecule drugs approved 1981-2006 sorted by origin

4. Place, date, unit, occasion etc. Slide 4 Natural Products II – Establishing biosynthetic pathways Compound A Compound B Compound C Aurofusarin Enz. 1Enz. 2Enz. 3 Compound C Frandsen et al. (2006): Molecular Microbiology, vol. 61(4), pp. 1069-

5. Place, date, unit, occasion etc. Slide 5 Natural Products III – Insect resistance factors in plants Shinoda et al. (2002): J. Chem Ecol., 28(3), 587- Agerbirk et al. (2003): J. Chem Ecol., 29(6), 1417- Kuzina et al. (2009): Plant Phys., 151, 1977- Nielsen et al. (in press): J. Agric. Food. Chem.

6. Place, date, unit, occasion etc. Slide 6 Natural Products IV – Small molecule endpoints from genes of unknown function C Mycelia C Liquid media Intensity Overexpression Wildtype Transporter deletion Wildtype Deletion m/z 683.5 rt 8.9 min m/z 774.5 rt 14.1 min rt 9.4 min. Nielsen et al. (in press): Metabolomics

7. Place, date, unit, occasion etc. Slide 7 Natural Products V – Plant biomarkers of environmental contamination

8. Place, date, unit, occasion etc. Slide 8 How?  Meauring the organisms fingerprint i.e. as many analyte signal as possible and ideally all metabolites  Relating the fingerprints to a target vector i.e.  expected level of gene expression  plant resistance to herbivores  contaminant exposure level

9. Place, date, unit, occasion etc. Slide 9 Measuring the organism metabolite fingerprints - Instrumentation FLRDADUPLC ESI-TOF-MS Chromatogram UV spectrum Mass-to-charge spectrum

10. Place, date, unit, occasion etc. Slide 10 Measuring the organism metabolite fingerprints - Data 1000 scans > 10 4 m/z values Spectrum Chromatogram samples

11. Place, date, unit, occasion etc. Slide 11 Relating the metabolite fingerprints to the target vector Multivariate models can visualize the major variations in data e.g. Principal Component Analysis (PCA)

12. Place, date, unit, occasion etc. Slide 12 Relating the metabolite fingerprints to the target vector Noise Baseline Retention time shifts Varying detector sensitivity Artefacts in the chromatographic dimension

13. Place, date, unit, occasion etc. Slide 13 My prime areas of interest  How to measure the entire set of metabolites i.e. increasing the information content of the data sets  How to fix up messy data i.e. for subsequent multivariate modelling And this applies to a wide range of applications...  To characterize and identify targeted analytes from each application using e.g. NMR Basically what we can do is finding out what metabolites from an organism are related to a treatment or an effect

14. Place, date, unit, occasion etc. Slide 14 Acknowledgements: The Research School of Environmental Chemistry, Microbiology and Toxicology Any Questions? TYFYA