Metabolomics core facility
Metabolomics, or metabonomics, refers to the measurement of metabolites (compounds with a molecular mass < 1000 daltons) in biological materials such as blood, urine, cells.
In the Faculty we are able to perform both untargeted and targeted metabolomics. Untargeted metabolomics, also referred to as global metabolite profiling, is used to identify metabolic pathways that can be linked to biological mechanisms or clinical outcomes. Targeted metabolomics focuses on specific compounds (or pathways) and is usually more quantitative than untargeted metabolomics.
The FHMS metabolomics facility contains 2 liquid chromatography mass spectrometers (LC-MS) and one gas chromatography MS (GC-MS).
We routinely use targeted LC-MS metabolomics to investigate 24 h rhythms, circadian and sleep/wake processing in a range of species, including humans. Our targeted method (AbsoluteIDQ® p180 Kit, Biocrates) measures amino acids, biogenic amines, acylcarnitines, glycerophospholipids and sphingolipids.
The 5975C is a single quadrupole mass spectrometer coupled to a 7890A Gas Chromatograph. The mass spectrometer is equipped with an Electron Ionisation (EI) source and has a mass range 2-1050 Da with unit mass resolution. The instrument has the capability of performing Synchronous SIM/Scans, it captures SIM data and full scan data in the same acquisition, with no compromise in analytical performance.
Used for analysing relatively small volatile non-polar compounds.
The LCQ Deca XP Plus is a 3D quadrupole ion trap mass spectrometer coupled to a Surveyor HPLC with a Photodiode array detector. The instrument is equipped with Electrospray Ionisation (ESI) and Atmospheric Pressure Chemical Ionisation (APCI) sources and has a mass range of 50 – 4,000 Da. The instrument can perform MS, MS/MS and MSnacquisitions.
Used for analysing relatively low molecular weight compounds and for identifying unknown compounds.
The Q-TOF Premier™ is a hybrid quadrupole Time-of-Flight (oaToF) tandem mass spectrometer coupled to a Waters Acquity UPLC system and UV detector. The instrument has both Electrospray ionisation (ESI) and ESCi™ Multi-Mode Ionisation sources. ESCi ™ allows high speed switching between Electrospray ionisation and Atmospheric Pressure Chemical Ionisation acquisitions in a single run. The instrument also utilises LockSpray™ technology to ensure good mass accuracy (3 ppm RMS).
Used for metabolite profiling and good for the accurate mass analysis of relatively polar compounds.
The Xevo TQ-S is a tandem quadrupole mass spectrometer coupled to a Waters Acquity binary UPLC and a TUV detector. An optional Acquity H-Class quaternary UPLC is available to be used together with the Acquity binary UPLC to give orthogonal separations (2D-LC). Using a 2D-LC set up has the potential of allowing greater sensitivity and an improved selectivity by allowing orthogonal chromatographic separations. The mass spectrometer has a multi-mode ionisation probe allowing Electrospray Ionisation (ESI) and Atmospheric Pressure Chemical Ionisation (APCI). The mass range of the instrument is 2-2048 m/z and can be used either in full scan or four different MS/MS modes – precursor ion, product ion, Selected Reaction Monitoring (SRM) or neutral loss mode.
Used for analysing relatively polar low molecular weight compounds. This instrument is particularly good for the analysis of low concentration analytes and for quantitation.
In recent years we have chosen to focus on LC/MS metabolomics in health and disease in both human and animal studies.
- Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation
- Metabolic profiling of presymptomatic Huntington's disease sheep reveals novel biomarkers
- Modulation of Plasma Metabolite Biomarkers of the MAPK Pathway with MEK Inhibitor RO4987655: Pharmacodynamic and Predictive Potential in Metastatic Melanoma
- Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes
- Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism
- A systems genetics resource and analysis of sleep regulation in the mouse
- Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females
- Effect of sleep deprivation on the human metabolome
- Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers
- Abnormalities in the Polysomnographic, Adenosine and Metabolic Response to Sleep Deprivation in an Animal Model of Hyperammonemia
Dr Dovile Lingaityte
Senior Research Technician (LC-MS), Chronobiology