place, date, unit, occasion etc. slide 1 nikoline juul nielsen, post doc soil and environmental...
TRANSCRIPT
Place, date, unit, occasion etc.Slide 1
Nikoline Juul Nielsen, Post DocSoil and Environmental Chemistry (present)Bioorganic Chemistry (previous)
Exploratory Chemometrics and Analytical Chemistry – Looking for the Needle in the Haystack
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
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
Place, date, unit, occasion etc.Slide 4
Natural Products II – Establishing biosynthetic pathways
Com
poun
d A
Com
poun
d B
Com
poun
d C
Aurof
usar
inEnz. 1 Enz. 2 Enz. 3
Com
poun
d C
O
OOHOH
O O
OOHO
OO
O
O OH O
OO
O
OOHOH
HO
Frandsen et al. (2006): Molecular Microbiology, vol. 61(4), pp. 1069-
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.
Place, date, unit, occasion etc.Slide 6
Natural Products IV – Small molecule endpoints from genes of unknown function
CMycelia CLiquid media
Overexpression Overexpression
Wildtype
Transporter deletion
Transporter deletion
Wildtype
DeletionDeletion
8.6 8.7 8.8 8.9 9 9.1 9.2 9.30
1000
2000
3000
4000
5000
6000
a
13.9 14 14.1 14.2 14.3 14.4 14.50
0.5
1
1.5
2
2.5
3
x 104
b
m/z 683.5 rt 8.9 min
m/z 774.5 rt 14.1 min
Nielsen et al. (in press): Metabolomics
Place, date, unit, occasion etc.Slide 7
Natural Products V – Plant biomarkers of environmental contamination
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
Place, date, unit, occasion etc.Slide 9
Measuring the organism metabolite fingerprints - Instrumentation
FLRDADUPLC ESI-TOF-MS
Chromatogram UV spectrum Mass-to-charge spectrum
Place, date, unit, occasion etc.Slide 10
Measuring the organism metabolite fingerprints - Data
0 2000 4000 6000 8000 10000 12000 140000
2000
4000
6000
8000
10000
12000
10
00
sca
ns
> 104 m/z values
Spectrum
Chromatogram0 200 400 600 800 1000 1200
0
500
1000
1500
2000
2500
3000
3500
4000
samples
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)
Place, date, unit, occasion etc.Slide 12
Relating the metabolite fingerprints to the target vector
NoiseBaseline
Retention time shifts
Varying detector sensitivity
Artefacts in the chromatographic dimension
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
Place, date, unit, occasion etc.Slide 14
Acknowledgements:
The Research School of Environmental Chemistry, Microbiology and Toxicology
Any Questions?
TYFYA