Head: Gillian Mackay
The Metabolomics facility employs state-of-the-art mass spectrometry techniques to measure small molecule (metabolite) changes in cancer cells, to support cancer metabolism research projects within the Institute.
Using high-resolution Thermo Scientific Q-Exactive mass spectrometers and HILIC chromatography, we have well-established LC-MS methods for both targeted and untargeted analysis of small polar molecules. With our targeted approach to metabolomics, we measure approximately 100 metabolites per sample, encompassing a broad range of metabolites of different classes. Experiments using stable isotope tracers (often 13C glucose) enable us to examine the intracellular kinetics of many metabolites produced from the tracer. Using an untargeted approach, metabolomics is used to look for novel metabolic changes, by identifying compounds showing altered abundances in cancer cells.
Our Thermo Scientific Altis triple quad mass spectrometer is used for specific targeted LC-MS/MS analysis, such as the measurement of lysophosphatidic acids. Our LC-MS systems are complemented with our Agilent Technologies GC-MS/MS triple quad instrument, for measuring compounds such as fatty acids and acetate.
We provide advice for sample preparation for a range of sample types, including cell extracts, plasma, urine and tumour tissue, and support for data analysis, based on Thermo Scientific TraceFinder and Compound Discoverer software.
Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, Dhayade S, Schug ZT, Vande Voorde J, Blyth K, Gottlieb E, Vazquez A, Kamphorst JJ. Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Cell Rep 2017; 18: 647–58
Dolfi SC, Medina DJ, Kareddula A, Paratala B, Rose A, Dhami J, Chen S, Ganesan S, Mackay G, Vazquez A, Hirshfield KM. Riluzole exerts distinct antitumor effects from a metabotropic glutamate receptor 1-specific inhibitor on breast cancer cells. Oncotarget 2017; 8: 44639–53
Dornier E, Rabas N, Mitchell L, Novo D, Dhayade S, Marco S, Mackay G, Sumpton D, Pallares M, Nixon C, Blyth K, MacPherson I, Rainero E, Norman JC. Glutaminolysis drives membrane trafficking to promote cancer invasion. Nat Comms 2017; 8: 2255
Maddocks ODK, Athineos D, Cheung EC, Lee P, Zhang T, van den Broek NJF, Mackay GM, Labuschagne CF, Gay D, Kruiswijk F, Blagih J, Vincent DF, Campbell KJ, Ceteci F, Sansom OJ, Blyth K, Vousden KH. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 2017; 544: 372-6
Susanto O, Koh YWH, Morrice N, Tumanov S, Thomason PA, Nielson M, Tweedy L, Muinonen-Martin AJ, Kamphorst JJ, Mackay GM, Insall RH. LPP3 mediates self-generation of chemotactic LPA gradients by melanoma cells. J Cell Sci 2017; 130: 3455–66
Meiser J, Tumanov S, Maddocks O, Labuschagne CF, Athineos D, Van Den Broek N, Mackay GM, Gottlieb E, Blyth K, Vousden K, Kamphorst JJ, Vazquez A. Serine one-carbon catabolism with formate overflow. Science Advances 2: e1601273, 2016
Tweedy L, Knecht DA, Mackay GM, Insall RH. Self-Generated Chemoattractant Gradients: Attractant Depletion Extends the Range and Robustness of Chemotaxis. PLoS Biol. 2016 Mar 16;14(3):e1002404
Cardaci S, Zheng L, MacKay G, van den Broek NJ, MacKenzie ED, Nixon C, Stevenson D, Tumanov S, Bulusu V, Kamphorst JJ, Vazquez A, Fleming S, Schiavi F, Kalna G, Blyth K, Strathdee D, Gottlieb E. Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis. Nat Cell Biol 17: 1317-26, 2015
Mackay GM, Zheng L, van den Broek NJ, Gottlieb E. Analysis of Cell Metabolism Using LC-MS and Isotope Tracers. Methods Enzymol 561: 171-96, 2015
Patella F, Schug ZT, Persi E, Neilson LJ, Erami Z, Avanzato D, Maione F, Hernandez-Fernaud JR, Mackay G, Zheng L, Reid S, Frezza C, Giraudo E, Fiorio Pla A, Anderson K, Ruppin E, Gottlieb E, Zanivan S. Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability. Mol Cell Proteomics 14: 621-34, 2015
Schug ZT, Peck B, Jones DT, Zhang Q, Grosskurth S, Alam IS, Goodwin LM, Smethurst E, Mason S, Blyth K, McGarry L, James D, Shanks E, Kalna G, Saunders RE, Jiang M, Howell M, Lassailly F, Thin MZ, Spencer-Dene B, Stamp G, van den Broek NJ, Mackay G, Bulusu V, Kamphorst JJ, Tardito S, Strachan D, Harris AL, Aboagye EO, Critchlow SE, Wakelam MJ, Schulze A, Gottlieb E. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 27: 57-71, 2015
Tedeschi PM, Johnson-Farley N, Lin H, Shelton LM, Ooga T, Mackay G, Van Den Broek N, Bertino JR, Vazquez A. Quantification of folate metabolism using transient metabolic flux analysis. Cancer Metab 3: 6, 2015
Principal Scientific Officer
Senior Scientific Officer