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Metabolomics is the systematic study of the unique metabolite (small-molecule) fingerprints of biological systems. The Metabolomics Laboratory uses state-of-the-art tandem mass spectrometry to obtain metabolic profiles (primarily lipids and fats) from cell and animal models in addition to clinically relevant human samples to better characterise the dyslipidemia associated with obesity, diabetes and cardiovascular disease and its relationship to the pathogenesis of these disease states. These studies are leading to new approaches to early diagnosis, risk assessment and therapeutic monitoring of these most prevalent diseases in our society.

- Metabolomics analytical platform

Analytical platform - Liquid chromatography, electrospray ionisation triple quadrapole mass spectrometer. Incorporating an Agilent 1200 series liquid chromatography system and an Applied Biosystems API 4000 QTRAP mass spectrometer.

Our approach and capabilities

- Our Research - MetabolomicsWe have developed a comparative lipidomics approach that enables to semi-quantification of approximately 400 lipid species across 22 lipid classes and subclasses (see Table 1). The analysis is performed by liquid chromatography tandem mass spectrometry on one of two instruments within the Metabolomics Laboratory. We use stable isotope dilution (with 23 different internal standards) to provide quantitative data on each of the over 400 lipid species.

This analysis typically required only small amounts of biological material (10 μL plasma or 50 μg cellular protein from cell or tissue homogenates).

Study design: We can advise on appropriate experimental design to minimise variance across the experiment and maximise statistical power. Experiments can comprise anywhere from one to over 1,000 samples. The appropriate use of quality control samples provides for standardisation across and between analytical runs.

Lipid extraction: We have developed SOPs for lipid extraction from biological fluids, cells and tissues that provide high recoveries and reproducibility.

Liquid chromatography mass spectrometry: Our experienced researchers maintain and run the mass spectrometers for the analysis of in-house and external samples.

Data extraction and analysis: Data processing is performed on specialised software available within the Metabolomics Laboratory. Analysis of lipidomic data presents some specific challenges. We can also advise on, and support, subsequent statistical analysis with our established lipidomic workflow utilising MATLAB statistical software. These analyses can extend to multivariate modelling utilising machine learning approaches within a cross validation framework to create and evaluate classification or prediction models.

Table 1. Lipid classes included in our current lipidomic profile.

Lipid class
No Species
Parent ion
MRM type
dihydroceramide (dhCer)  6 [M+H]+  PIS, 284.3 m/z
ceramide (Cer)
 7 [M+H]+ 
PIS, 284.3 m/z
monohexosylceramide (MHC)
 7 [M+H]+
PIS, 284.3 m/z
dihexosylceramide (DHC)
 7 [M+H]+
PIS, 284.3 m/z
trihexosylcermide (THC)
 7 [M+H]+
PIS, 284.3 m/z
GM3 ganglioside (GM3)
 6 [M+H]+
PIS, 284.3 m/z
modified ceramide (modCer)
 14 [M+H]+
PIS, 284.3 m/z
sphingomyelin (SM)
 12 [M+H]+
PIS, 184.1 m/z
phosphatidylcholine (PC)
 48 [M+H]+
PIS, 184.1 m/z
alkylphosphatidylcholine (PC(O))  20 [M+H]+
PIS, 184.1 m/z
alkenylphosphatidylcholine (PC(P))
 14 [M+H]+
PIS, 184.1 m/z
lysophosphatidylcholine (LPC)
 25 [M+H]+
PIS, 184.1 m/z
lysoalkylphosphatidylcholine (LPC(O))
 8 [M+H]+
PIS, 184.1 m/z
modified phosphatidylcholine (modPC)
 44 [M+H]+
PIS, 184.1 m/z
phosphatidylethanolamine (PE)
 20 [M+H]+
NL, 141 Da
alkylphosphatidylethanolamine (PE(O))
 12 [M+H]+
NL, 141 Da
alkenylphosphatidylethanolamine (PE(P))
 12 [M+H]+
NL, 141 Da
lysophosphatidylethanolamine (LPE)
 6 [M+H]+
NL, 141 Da
phosphatidylinositol (PI)
 17 [M+ NH4]+ PIS, 184.1 m/z
phosphatidylserine (PS)
 7 [M+H]+
NL, 185 Da
phosphatidylglycerol (PG)
 4 [M+ NH4]+
NL, 189 Da
bis(monoacylglycerol)phosphate (BMP)
 1 [M+ NH4]+ PIS, 339.3 m/z
free cholesterol (COH)
 1 [M+ NH4]+ PIS, 369.3 m/z
cholesteryl ester (CE)
 30 [M+ NH4]+ PIS, 369.3 m/z
modified cholesteryl ester (modCE)
 4 [M+ NH4]+ PIS, 369.3 m/z
diacylglycerol (DG)  27 [M+ NH4]+ NL, fatty acid
triaclyglycerol (TG)  44 [M+ NH4]+ NL, fatty acid
TOTAL
 415    

Training and collaborations

We work with both internal and external groups on collaborative projects. Training can be provided to collaborating laboratories to facilitate the processing and analysis of biological samples. Development of additional capabilities is ongoing and we are happy to discuss project specific needs.

Current projects within the Metabolomics Laboratory

  • Metabolomic studies into the pathogenesis and risk assessment of type 2 diabetes.
  • Pathogenesis and risk assessment of coronary artery disease.
  • The relationship between dairy food, insulin resistance and the risk of type 2 diabetes.
  • Lipidomic analysis of the FIELD Trial: mechanism of action and prediction of response to fenofibrate treatment in type 2 diabetes.
  • Lipidomic analysis of the ADVANCE Trial: the relationship between dyslipidemia and cardiovascular disease outcomes in diabetes.
  • The differences in composition and oxidation of LDL in type 2 diabetes, and their effect on vascular endothelial cell function and contribution to atherosclerosis.
  • High density lipoprotein lipid composition and function: toward lipid composition manipulation.
  • Assessment of the role of plasmalogens as lipoprotein anti-oxidants in atherosclerosis.
  • Dyslipidaemia resulting from obesity is a major contributor to the onset and progression of Type 2 diabetes.

References

Rasmiena AA, Ng TW, Meikle PJ. Metabolomics and ischaemic heart disease. Clin Sci 2013;124:289-306.

Kulkarni H, Meikle PJ, Mamtani M, Weir JM, Barlow CK, Jowett JB, Bellis C, Dyer TD, Johnson MP, Rainwater DL, Almasy L, Mahaney MC, Comuzzie AG, Blangero J, Curran JE. Variability in associations of phosphatidylcholine molecular species with metabolic syndrome in Mexican-American families. Lipids 2013;48:497-503.

Nestel PJ, Pally S, MacIntosh GL, Greeve MA, Middleton S, Jowett J, Meikle PJ. Circulating inflammatory and atherogenic biomarkers are not increased following single meals of dairy foods. Eur J Clin Nutr 2012;66:25-31.

Meikle PJ, Wong G, Tsorotes D, Barlow CK, Weir JM, Christopher MJ, MacIntosh GL, Goudey B, Stern L, Kowalczyk A, Haviv I, White AJ, Dart AM, Duffy SJ, Jennings GL, Kingwell BA. Plasma lipidomic analysis of stable and unstable coronary artery disease. Arterioscler Thromb Vasc Biol 2011;31:2723-32.

Boslem E, MacIntosh G, Preston AM, Bartley C, Busch AK, Fuller M, Laybutt DR, Meikle PJ, Biden TJ. A lipidomic screen of palmitate-treated min6 beta-cells links sphingolipid metabolites with endoplasmic reticulum (ER) stress and impaired protein trafficking. Biochem J 2011;435:267-76.

Ng TW, Khan AA, Meikle PJ. Investigating the pathogenesis and risk of type 2 diabetes: clinical applications of metabolomics. Clin Lipidol 2012;7(6):641-59.

Meikle PJ, Christopher MJ. Lipidomics is providing new insight into the metabolic syndrome and its sequelae. Curr Opin Lipidol 2011;22(3):210-5.

Lab Head Profile

Associate Professor Peter Meikle
Head, Metabolimics Laboratory and Metabolomic (Lipidomic) Profiling Facility

Peter Meikle completed his PhD in 1986 at James Cook University of North Queensland. Following postdoctoral positions at the National Research Council in Ottawa, Canada, and La Trobe University, Melbourne, he joined the Lysosomal Diseases Research Unit (LDRU) at the Women's and Children's Hospital in Adelaide and established a metabolomics research group focused on the screening diagnosis and pathogenesis of lysosomal storage diseases. In 2000, he was appointed Head of the Metabolic and Therapeutics Program, within the Department of Genetic Medicine, while still maintaining his research program within the LDRU.

In 2007, Associate Professor Meikle moved to the Baker Heart and Diabetes Institute where he established the Metabolomics Laboratory. In 2008 he was awarded a NHMRC Senior Research Fellowship. The Metabolomics Laboratory uses state of the art tandem mass spectrometry techniques to obtain metabolic profiles from cell and animal models in addition to clinically relevant human samples. This approach is combined with cell biology studies to improve our understanding of disease mechanisms and develop new diagnostic, prognostic and monitoring strategies in the areas of obesity, diabetes and cardiovascular disease.

Associate Professor Meikle holds affiliate positions at Bio21, University of Melbourne; the Department of Medicine, Monash Medical School, Monash University; and the NHMRC Clinical Trials Centre, University of Sydney.

Contact

Metabolomics Laboratory
Lipidomics Profiling Facility
Baker Heart and Diabetes Institute
Lab: +61 3 8532 1698

Associate Professor Peter Meikle
T: +61 3 8532 1770
E: peter.meikle@baker.edu.au

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