, 5:3 | Cite as

Environmental metabolomics: a critical review and future perspectives

  • Jacob G. Bundy
  • Matthew P. Davey
  • Mark R. ViantEmail author
Orignal Article


Environmental metabolomics is the application of metabolomics to characterise the interactions of organisms with their environment. This approach has many advantages for studying organism–environment interactions and for assessing organism function and health at the molecular level. As such, metabolomics is finding an increasing number of applications in the environmental sciences, ranging from understanding organismal responses to abiotic pressures, to investigating the responses of organisms to other biota. These interactions can be studied from individuals to populations, which can be related to the traditional fields of ecophysiology and ecology, and from instantaneous effects to those over evolutionary time scales, the latter enabling studies of genetic adaptation. This review provides a comprehensive and current overview of environmental metabolomics research. We begin with an overview of metabolomic studies into the effects of abiotic pressures on organisms. In the field of ecophysiology, studies on the metabolic responses to temperature, water, food availability, light and circadian rhythms, atmospheric gases and season are reviewed. A section on ecotoxicogenomics discusses research in aquatic and terrestrial ecotoxicology, assessing organismal responses to anthropogenic pollutants in both the laboratory and field. We then discuss environmental metabolomic studies of diseases and biotic–biotic interactions, in particular herbivory. Finally, we critically evaluate the contribution that metabolomics has made to the environmental sciences, and highlight and discuss recommendations to advance our understanding of the environment, ecology and evolution using a metabolomics approach.


Ecotoxicology Metabolomics Metabonomics Ecotoxicogenomics Ecophysiology Environmental sciences 



MRV thanks the NERC for an Advanced Fellowship in Metabolomics (NER/J/S/2002/00618).


  1. Ankley, G. T., Miracle, A., Perkins, E. J., & Daston, G. P. (2008). Genomics in regulatory ecotoxicology: Applications and challenges. London: CRC.Google Scholar
  2. Arany, A. M., de Jong, T. J., Kim, H. K., van Dam, N. M., Choi, Y. H., Verpoorte, R., et al. (2008). Glucosinolates and other metabolites in the leaves of Arabidopsis thaliana from natural populations and their effects on a generalist and a specialist herbivore. Chemoecology, 18, 65–71. doi: 10.1007/s00049-007-0394-8.CrossRefGoogle Scholar
  3. Arany, A. M., de Jong, T. J., & van der Meijden, E. (2005). Herbivory and abiotic factors affect population dynamics of Arabidopsis thaliana in a sand dune area. Plant Biology, 7, 549–555. doi: 10.1055/s-2005-865831.PubMedCrossRefGoogle Scholar
  4. Atherton, H. J., Jones, O. A. H., Malik, S., Miska, E. A., & Griffin, J. L. (2008). A comparative metabolomic study of NHR-49 in Caenorhabditis elegans and PPAR-alpha in the mouse. FEBS Letters, 582, 1661–1666. doi: 10.1016/j.febslet.2008.04.020.PubMedCrossRefGoogle Scholar
  5. Blaise, B. J., Giacomotto, J., Elena, B., Dumas, M. E., Toullhoat, P., Segalat, L., et al. (2007). Metabotyping of Caenorhabditis elegans reveals latent phenotypes. Proceedings of the National Academy of Sciences of the United States of America, 104, 19808–19812. doi: 10.1073/pnas.0707393104.PubMedCrossRefGoogle Scholar
  6. Bon, D., Gilard, V., Massou, S., Peres, G., Malet-Martino, M., Martino, R., et al. (2006). In vivo 31P and 1H HR-MAS NMR spectroscopy analysis of the unstarved Aporrectodea caliginosa (Lumbricidae). Biology and Fertility of Soils, 43, 191–198. doi: 10.1007/s00374-006-0092-7.CrossRefGoogle Scholar
  7. Broeckling, C. D., Huhman, D. V., Farag, M. A., Smith, J. T., May, G. D., Mendes, P., et al. (2005). Metabolic profiling of Medicago truncatula cell cultures reveals the effects of biotic and abiotic elicitors on metabolism. Journal of Experimental Botany, 56, 323–336. doi: 10.1093/jxb/eri058.PubMedCrossRefGoogle Scholar
  8. Browse, J., & Lange, B. M. (2004). Counting the cost of a cold-blooded life: Metabolomics of cold acclimation. Proceedings of the National Academy of Sciences of the United States of America, 101, 14996–14997. doi: 10.1073/pnas.0406389101.PubMedCrossRefGoogle Scholar
  9. Bundy, J. G., Keun, H. C., Sidhu, J. K., Spurgeon, D. J., Svendsen, C., Kille, P., et al. (2007). Metabolic profile biomarkers of metal contamination in a sentinel terrestrial species are applicable across multiple sites. Environmental Science and Technology, 41, 4458–4464. doi: 10.1021/es0700303.PubMedCrossRefGoogle Scholar
  10. Bundy, J. G., Lenz, E. M., Bailey, N. J., Gavaghan, C. L., Svendsen, C., Spurgeon, D., et al. (2002a). Metabonomic assessment of toxicity of 4-fluoroaniline, 3, 5-difluoroaniline and 2-fluoro-4-methylaniline to the earthworm Eisenia veneta (Rosa): Identification of new endogenous biomarkers. Environmental Toxicology and Chemistry, 21, 1966–1972. doi:10.1897/1551-5028(2002)021<1966:MAOTOF>2.0.CO;2.PubMedCrossRefGoogle Scholar
  11. Bundy, J. G., Osborn, D., Weeks, J. M., Lindon, J. C., & Nicholson, J. K. (2001). An NMR-based metabonomic approach to the investigation of coelomic fluid biochemistry in earthworms under toxic stress. FEBS Letters, 500, 31–35. doi: 10.1016/S0014-5793(01)02582-0.PubMedCrossRefGoogle Scholar
  12. Bundy, J. G., Ramlov, H., & Holmstrup, M. (2003). Multivariate metabolic profiling using 1H nuclear magnetic resonance spectroscopy of freeze-tolerant and freeze-intolerant earthworms exposed to frost. Cryo Letters, 24, 347–358.PubMedGoogle Scholar
  13. Bundy, J. G., Sidhu, J. K., Rana, F., Spurgeon, D. J., Svendsen, C., Wren, J. F., et al. (2008). ‘Systems toxicology’ approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus. BMC Biology, 6, 25. doi: 10.1186/1741-7007-6-25.PubMedCrossRefGoogle Scholar
  14. Bundy, J. G., Spurgeon, D. J., Svendsen, C., Hankard, P. K., Osborn, D., Lindon, J. C., et al. (2002b). Earthworm species of the genus Eisenia can be phenotypically differentiated by metabolic profiling. FEBS Letters, 521, 115–120. doi: 10.1016/S0014-5793(02)02854-5.PubMedCrossRefGoogle Scholar
  15. Bundy, J. G., Spurgeon, D. J., Svendsen, C., Hankard, P. K., Weeks, J. M., Osborn, D., et al. (2004). Environmental metabonomics: Applying combination biomarker analysis in earthworms at a metal contaminated site. Ecotoxicology (London, England), 13, 797–806. doi: 10.1007/s10646-003-4477-1.Google Scholar
  16. Bussell, J. A., Gidman, E. A., Causton, D. R., Gwynn-Jones, D., Malham, S. K., Jones, M. L. M., et al. (2008). Changes in the immune response and metabolic fingerprint of the mussel, Mytilus edulis (Linnaeus) in response to lowered salinity and physical stress. Journal of Experimental Marine Biology and Ecology, 358, 78–85. doi: 10.1016/j.jembe.2008.01.018.CrossRefGoogle Scholar
  17. Cao, M., Koulman, A., Johnson, L. J., Lane, G. A., & Rasmussen, S. (2008). Advanced data-mining strategies for the analysis of direct-infusion ion trap mass spectrometry data from the association of perennial ryegrass with its endophytic fungus, Neotyphodium lolii. Plant Physiology, 146, 1501–1514. doi: 10.1104/pp.107.112458.PubMedCrossRefGoogle Scholar
  18. Chaves, M. M., Maroco, J. P., & Pereira, J. S. (2003). Understanding plant responses to drought—from genes to the whole plant. Functional Plant Biology, 30, 239–264. doi: 10.1071/FP02076.CrossRefGoogle Scholar
  19. Cho, K., Shibato, J., Agrawal, G. K., Jung, Y., Kubo, A., Jwa, N., et al. (2008). Integrated transcriptomics, proteomics, and metabolomics analyses to survey ozone responses in the leaves of rice seedling. Journal of Proteome Research, 7, 2980–2998. doi: 10.1021/pr800128q.PubMedCrossRefGoogle Scholar
  20. Clegg, J. S. (2001). Cryptobiosis—a peculiar state of biological organization. Comparative Biochemistry and Physiology. B, Comparative Biochemistry, 128, 613–624. doi: 10.1016/S1096-4959(01)00300-1.CrossRefGoogle Scholar
  21. Coen, M., Holmes, E., Lindon, J. C., & Nicholson, J. K. (2008). NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology. Chemical Research in Toxicology, 21, 9–27. doi: 10.1021/tx700335d.PubMedCrossRefGoogle Scholar
  22. Cook, D., Fowler, S., Fiehn, O., & Thomashow, M. F. (2004). A prominent role for the CBF cold response pathway in configuring the low-temperature metabolome of Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America, 101, 15243–15248. doi: 10.1073/pnas.0406069101.PubMedCrossRefGoogle Scholar
  23. D’Auria, J. C., & Gershenzon, J. (2005). The secondary metabolism of Arabidopsis thaliana: Growing like a weed. Current Opinion in Plant Biology, 8, 308–316. doi: 10.1016/j.pbi.2005.03.012.PubMedCrossRefGoogle Scholar
  24. Darwin, C. (1881). The formation of vegetable mould, through the action of worms, with observations on their habits. London: Murray.Google Scholar
  25. Davey, M. P., Bryant, D. N., Cummins, I., Ashenden, T. W., Gates, P., Baxter, R., et al. (2004). Effects of elevated CO2 on the vasculature and phenolic secondary metabolism of Plantago maritima. Phytochemistry, 65, 2197–2204. doi: 10.1016/j.phytochem.2004.06.016.PubMedCrossRefGoogle Scholar
  26. Davey, M. P., Burrell, M. M., Woodward, F. I., & Quick, W. P. (2008). Population-specific metabolic phenotypes of Arabidopsis lyrata ssp. petraea. New Phytologist, 177(2), 380–388.PubMedGoogle Scholar
  27. Davey, M. P., Harmens, H., Ashenden, T. W., Edwards, R., & Baxter, R. (2007). Species-specific effects of elevated CO2 on resource allocation in Plantago maritima and Armeria maritima. Biochemical Systematics and Ecology, 35, 121–129. doi: 10.1016/j.bse.2006.09.004.CrossRefGoogle Scholar
  28. Davey, M. P., Woodward, F. I., & Quick, W. P. (in press). Intraspecific variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp. petraea. Metabolomics, 5(1). doi: 10.1007/s11306-008-0127-1.
  29. Day, T. A., Ruhland, C. T., & Xiong, F. S. (2001). Influence of solar ultraviolet-B radiation on Antarctic terrestrial plants: Results from a 4-year field study. Journal of Photochemistry and Photobiology B: Biology, 62, 78–87. doi: 10.1016/S1011-1344(01)00161-0.CrossRefGoogle Scholar
  30. Desbrosses, G. G., Kopka, J., & Udvardi, M. K. (2005). Lotus japonicus metabolic profiling. Development of gas chromatography-mass spectrometry resources for the study of plant–microbe interactions. Plant Physiology, 137, 1302–1318. doi: 10.1104/pp.104.054957.PubMedCrossRefGoogle Scholar
  31. Ekman, D. R., Teng, Q., Villeneuve, D. L., Kahl, M. D., Jensen, K. M., Durhan, E. J., et al. (2008). Investigating compensation and recovery of fathead minnow (Pimephales promelas) exposed to 17 alpha-ethynylestradiol with metabolite profiling. Environmental Science and Technology, 42, 4188–4194. doi: 10.1021/es8000618.PubMedCrossRefGoogle Scholar
  32. Falk, M. J., Zhang, Z., Rosenjack, J. R., Nissim, I., Daikhin, E., Nissim, I., et al. (2008). Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans. Molecular Genetics and Metabolism, 93, 388–397.PubMedCrossRefGoogle Scholar
  33. Gagneul, D., Ainouche, A., Duhaze, C., Lugan, R., Larher, F. R., & Bouchereau, A. (2007). A reassessment of the function of the so-called compatible solutes in the halophytic Plumbaginaceae Limonium latifolium. Plant Physiology, 144, 1598–1611. doi: 10.1104/pp.107.099820.PubMedCrossRefGoogle Scholar
  34. Gibb, J. O. T., Svendsen, C., Weeks, J. M., & Nicholson, J. K. (1997). 1H NMR spectroscopic investigations of tissue metabolite biomarker response to Cu(II) exposure in terrestrial invertebrates: Identification of free histidine as a novel biomarker of exposure to copper in earthworms. Biomarkers, 2, 295–302. doi: 10.1080/135475097231526.CrossRefGoogle Scholar
  35. Gidman, E., Goodacre, R., Emmett, B., Sheppard, L., Leith, I., & Gwynn-Jones, D. (2004). Applying metabolic fingerprinting to ecology: The use of fourier-transform infrared spectroscopy for the rapid screening of plant responses to N deposition. Water, Air, and Soil Pollution, 4, 251–258. doi: 10.1007/s11267-004-3035-z.CrossRefGoogle Scholar
  36. Gidman, E. A., Jones, M. L. M., Bussell, J. A., Malham, S. K., Reynolds, B., Seed, R., et al. (2007). A methodology for screening haemolymph of intertidal mussels, Mytilus edulis, using FT-IR spectroscopy as a tool for environmental assessment. Metabolomics, 3, 465–473. doi: 10.1007/s11306-007-0060-8.CrossRefGoogle Scholar
  37. Gidman, E. A., Royston, G., Emmett, B., Wilson, D. B., Carroll, J. A., Caporn, S. J. M., et al. (2005). Metabolic fingerprinting for bio-indication of nitrogen responses in Calluna vulgaris heath communities. Metabolomics, 1, 1573–3882. doi: 10.1007/s11306-005-0004-0.CrossRefGoogle Scholar
  38. Gidman, E. A., Stevens, C. J., Goodacre, R., Broadhurst, D., Emmett, B., & Gwynn-Jones, D. (2006). Using metabolic fingerprinting of plants for evaluating nitrogen deposition impacts on the landscape level. Global Change Biology, 12, 1460–1465. doi: 10.1111/j.1365-2486.2006.01190.x.CrossRefGoogle Scholar
  39. Glass, D. J., & Hall, N. (2008). A brief history of the hypothesis. Cell, 134, 378–381. doi: 10.1016/j.cell.2008.07.033.PubMedCrossRefGoogle Scholar
  40. Gong, P., Guan, X., Inouye, L. S., Pirooznia, M., Indest, K. J., Athow, R. S., et al. (2007). Toxicogenomic analysis provides new insights into molecular mechanisms of the sublethal toxicity of 2, 4, 6-trinitrotoluene in Eisenia fetida. Environmental Science and Technology, 41, 8195–8202. doi: 10.1021/es0716352.PubMedCrossRefGoogle Scholar
  41. Goodacre, R., York, E. V., Heald, J. K., & Scott, I. M. (2003). Chemometric discrimination of unfractionated plant extracts analyzed by electrospray mass spectrometry. Phytochemistry, 62, 859–863. doi: 10.1016/S0031-9422(02)00718-5.PubMedCrossRefGoogle Scholar
  42. Gray, G. R., & Heath, D. (2005). A global reorganization of the metabolome in Arabidopsis during cold acclimation is revealed by metabolic fingerprinting. Physiologia Plantarum, 124, 236–248. doi: 10.1111/j.1399-3054.2005.00507.x.CrossRefGoogle Scholar
  43. Griffin, J. L., Walker, L. A., Garrod, S., Holmes, E., Shore, R. F., & Nicholson, J. K. (2000a). NMR spectroscopy based metabonomic studies on the comparative biochemistry of the kidney and urine of the bank vole (Clethrionomys glareolus), wood mouse (Apodemus sylvaticus), white toothed shrew (Crocidura suaveolens) and the laboratory rat. Comparative Biochemistry and Physiology. B, Comparative Biochemistry, 127, 357–367. doi: 10.1016/S0305-0491(00)00276-5.CrossRefGoogle Scholar
  44. Griffin, J. L., Walker, L. A., Shore, R. F., & Nicholson, J. K. (2001). High-resolution magic angle spinning 1H NMR spectroscopy studies on the renal biochemistry in the bank vole (Clethrionomys glareolus) and the effects of arsenic (As3+) toxicity. Xenobiotica, 31, 377–385. doi: 10.1080/00498250110055938.PubMedCrossRefGoogle Scholar
  45. Griffin, J. L., Walker, L. A., Troke, J., Osborn, D., Shore, R. F., & Nicholson, J. K. (2000b). The initial pathogenesis of cadmium induced renal toxicity. FEBS Letters, 478, 147–150. doi: 10.1016/S0014-5793(00)01843-3.PubMedCrossRefGoogle Scholar
  46. Griffiths, W. (2007). Metabolomics, metabonomics and metabolite profiling. Cambridge: Royal Society of Chemistry.CrossRefGoogle Scholar
  47. Guy, C., Kaplan, F., Kopka, J., Selbig, J., & Hincha, D. K. (2008). Metabolomics of temperature stress. Physiologia Plantarum, 132, 220–235.PubMedGoogle Scholar
  48. Hannah, M. A., Wiese, D., Freund, S., Fiehn, O., Heyer, A. G., & Hincha, D. K. (2006). Natural genetic variation of freezing tolerance in Arabidopsis. Plant Physiology, 142, 98–112. doi: 10.1104/pp.106.081141.PubMedCrossRefGoogle Scholar
  49. Harrigan, G. G., & Goodacre, R. (2003). Metabolic profiling: Its role in biomarker discovery and gene function analysis. Boston: Springer.Google Scholar
  50. Hawes, T. C., Hines, A., Viant, M. R., Bale, J. S., Worland, M. R., & Convey, P. (2008). Metabolomic fingerprint of cryo-stress in a freeze-tolerant insect. Cryo Letters, 29(6), 505–515.PubMedGoogle Scholar
  51. Hernandez, G., Ramirez, M., Valdes-Lopez, O., Tesfaye, M., Graham, M. A., Czechowski, T., et al. (2007). Phosphorus stress in common bean: Root transcript and metabolic responses. Plant Physiology, 144, 752–767. doi: 10.1104/pp.107.096958.PubMedCrossRefGoogle Scholar
  52. Hines, A. (2008). The development and evaluation of NMR-based metabolomics as a tool for environmental monitoring using the common mussel, PhD thesis, University of Birmingham, UK.Google Scholar
  53. Hines, A., Oladiran, G. S., Bignell, J. P., Stentiford, G. D., & Viant, M. R. (2007a). Direct sampling of organisms from the field and knowledge of their phenotype: Key recommendations for environmental metabolomics. Environmental Science and Technology, 41, 3375–3381. doi: 10.1021/es062745w.PubMedCrossRefGoogle Scholar
  54. Hines, A., Yeung, W. H., Craft, J., Brown, M., Kenned, J., Bignell, J., et al. (2007b). Comparison of histological, genetic, metabolomics, and lipid-based methods for sex determination in marine mussels. Analytical Biochemistry, 369, 175–186. doi: 10.1016/j.ab.2007.06.008.PubMedCrossRefGoogle Scholar
  55. Hirai, M. Y., Yano, M., Goodenowe, D. B., Kanaya, S., Kimura, T., Awazuhara, M., et al. (2004). Integration of transcriptomics and metabolomics for understanding of global responses to nutritional stresses in Arabidopsis thaliana. Proceedings of the National Academy of Sciences of the United States of America, 101, 10205–10210. doi: 10.1073/pnas.0403218101.PubMedCrossRefGoogle Scholar
  56. Hjalten, J., Lindau, A., Wennstrom, A., Blomberg, P., Witzell, J., Hurry, V., et al. (2007). Unintentional changes of defence traits in GM trees can influence plant–herbivore interactions. Basic and Applied Ecology, 8, 434–443. doi: 10.1016/j.baae.2006.09.001.CrossRefGoogle Scholar
  57. Huang, C. Y., Roessner, U., Eickmeier, I., Genc, Y., Callahan, D. L., Shirley, N., et al. (2008). Metabolite profiling reveals distinct changes in carbon and nitrogen metabolism in phosphate-deficient barley plants (Hordeum vulgare L.). Plant and Cell Physiology, 49, 691–703. doi: 10.1093/pcp/pcn044.PubMedCrossRefGoogle Scholar
  58. Hurry, V., Strand, A., Furbank, R., & Stitt, M. (2000). The role of inorganic phosphate in the development of freezing tolerance and the acclimatization of photosynthesis to low temperature is revealed by the pho mutants of Arabidopsis thaliana. The Plant Journal, 24, 383–396. doi: 10.1046/j.1365-313x.2000.00888.x.PubMedCrossRefGoogle Scholar
  59. Jansen, M. A. K., Hectors, K., O’Brien, N. M., Guisez, Y., & Potters, G. (2008). Plant stress and human health: Do human consumers benefit from UV-B acclimated crops? Plant Science, 175, 449–458. doi: 10.1016/j.plantsci.2008.04.010.CrossRefGoogle Scholar
  60. Jeong, M. L., Jiang, H. Y., Chen, H. S., Tsai, C. J., & Harding, S. A. (2004). Metabolic profiling of the sink-to-source transition in developing leaves of quaking aspen. Plant Physiology, 136, 3364–3375. doi: 10.1104/pp.104.044776.PubMedCrossRefGoogle Scholar
  61. Johnson, H. E., Broadhurst, D., Goodacre, R., & Smith, A. R. (2003). Metabolic fingerprinting of salt-stressed tomatoes. Phytochemistry, 62, 919–928. doi: 10.1016/S0031-9422(02)00722-7.PubMedCrossRefGoogle Scholar
  62. Jones, O. A. H., Spurgeon, D. J., Svendsen, C., & Griffin, J. L. (2008). A metabolomics based approach to assessing the toxicity of the polyaromatic hydrocarbon pyrene to the earthworm Lumbricus rubellus. Chemosphere, 71, 601–609. doi: 10.1016/j.chemosphere.2007.08.056.PubMedCrossRefGoogle Scholar
  63. Jones, O. A. H., Walker, L. A., Nicholson, J. K., Shore, R. F., & Griffin, J. L. (2007). Cellular acidosis in rodents exposed to cadmium is caused by adaptation of the tissue rather than an early effect of toxicity. Comparative Biochemistry and Physiology D-Genomics & Proteomics, 2, 316–321. doi: 10.1016/j.cbd.2007.06.003.CrossRefGoogle Scholar
  64. Kahvejian, A., Quackenbush, J., & Thompson, J. F. (2008). What would you do if you could sequence everything? Nature Biotechnology, 26, 1125–1133. doi: 10.1038/nbt1494.PubMedCrossRefGoogle Scholar
  65. Kaplan, F., Kopka, J., Haskell, D. W., Zhao, W., Schiller, K. C., Gatzke, N., et al. (2004). Exploring the temperature-stress metabolome of Arabidopsis. Plant Physiology, 136, 4159–4168. doi: 10.1104/pp.104.052142.PubMedCrossRefGoogle Scholar
  66. Kell, D. B., & Oliver, S. G. (2004). Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era. BioEssays, 26, 99–105. doi: 10.1002/bies.10385.PubMedCrossRefGoogle Scholar
  67. Kliebenstein, D. J. (2004). Secondary metabolites and plant/environment interactions: A view through Arabidopsis thaliana tinged glasses. Plant, Cell & Environment, 27, 675–684. doi: 10.1111/j.1365-3040.2004.01180.x.CrossRefGoogle Scholar
  68. Kontunen-Soppela, S., Ossipov, V., Ossipova, S., & Oksanen, E. (2007). Shift in birch leaf metabolome and carbon allocation during long-term open-field ozone exposure. Global Change Biology, 13, 1053–1067. doi: 10.1111/j.1365-2486.2007.01332.x.CrossRefGoogle Scholar
  69. Lee, R. E., & Denlinger, D. L. (1985). Cold tolerance in diapausing and non-diapausing stages of the flesh fly, Sarcophaga crassipalpis. Physiological Entomology, 10, 309–315. doi: 10.1111/j.1365-3032.1985.tb00052.x.CrossRefGoogle Scholar
  70. Lenz, E. M., Hagele, B. F., Wilson, I. D., & Simpson, S. J. (2001). High resolution 1H NMR spectroscopic studies of the composition of the haemolymph of crowd- and solitary-reared nymphs of the desert locust, Schistocerca gregaria. Insect Biochemistry and Molecular Biology, 32, 51–56. doi: 10.1016/S0965-1748(01)00078-9.PubMedCrossRefGoogle Scholar
  71. Li, P. H., Sioson, A., Mane, S. P., Ulanov, A., Grothaus, G., Heath, L. S., et al. (2006). Response diversity of Arabidopsis thaliana ecotypes in elevated [CO2] in the field. Plant Molecular Biology, 62, 593–609. doi: 10.1007/s11103-006-9041-y.PubMedCrossRefGoogle Scholar
  72. Lin, C. Y., Viant, M. R., & Tjeerdema, R. S. (2006). Metabolomics: Methodologies and applications in the environmental sciences. Journal of Pesticide Science, 31, 245–251. doi: 10.1584/jpestics.31.245.CrossRefGoogle Scholar
  73. Lindon, J. C., Nicholson, J. K., & Holmes, E. (2006). The handbook of metabonomics and metabolomics. London: Elsevier Science.Google Scholar
  74. Llusia, J., Penuelas, J., Alessio, G. A., & Estiarte, M. (2008). Contrasting species-specific, compound-specific, seasonal, and interannual responses of foliar isoprenoid emissions to experimental drought in a mediterranean shrubland. International Journal of Plant Sciences, 169, 637–645. doi: 10.1086/533603.CrossRefGoogle Scholar
  75. Lois, R. (1994). Accumulation of UV-absorbing flavonoids induced by UV-B radiation in Arabidopsis thaliana.1. Mechanisms of UV-resistance in Arabidopsis. Planta, 194, 498–503. doi: 10.1007/BF00714462.CrossRefGoogle Scholar
  76. Long, S. P., Ainsworth, E. A., Rogers, A., & Ort, D. R. (2004). Rising atmospheric carbon dioxide: Plants face the future. Annual Review of Plant Biology, 55, 591–628. doi: 10.1146/annurev.arplant.55.031903.141610.PubMedCrossRefGoogle Scholar
  77. MacKenzie, D. A., Defernez, M., Dunn, W. B., Brown, M., Fuller, L. J., de Herrera, S., et al. (2008). Relatedness of medically important strains of Saccharomyces cerevisiae as revealed by phylogenetics and metabolomics. Yeast (Chichester, England), 25, 501–512. doi: 10.1002/yea.1601.CrossRefGoogle Scholar
  78. Maharjan, R. P., & Ferenci, T. (2005). Metabolomic diversity in the species Escherichia coli and its relationship to genetic population structure. Metabolomics, 1, 235–242. doi: 10.1007/s11306-005-0002-2.CrossRefGoogle Scholar
  79. Malmendal, A., Overgaard, J., Bundy, J. G., Sorensen, J. G., Nielsen, N. C., Loeschcke, V., et al. (2006). Metabolomic profiling of heat stress: Hardening and recovery of homeostasis in Drosophila. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 291, R205–R212. doi: 10.1152/ajpregu.00867.2005.PubMedGoogle Scholar
  80. McKelvie, J., Yuk, J., Xu, Y., Simpson, A., & Simpson, M. (in press). 1H NMR and GC/MS metabolomics of earthworm responses to sub-lethal DDT and endosulfan exposure. Metabolomics, 5(1). doi: 10.1007/s11306-008-0122-6.
  81. Michaud, M. R., Benoit, J. B., Lopez-Martinez, G., Elnitsky, M. A., Lee, R. E., & Denlinger, D. L. (2008). Metabolomics reveals unique and shared metabolic changes in response to heat shock, freezing and desiccation in the Antarctic midge, Belgica antarctica. Journal of Insect Physiology, 54, 645–655. doi: 10.1016/j.jinsphys.2008.01.003.CrossRefGoogle Scholar
  82. Michaud, M. R., & Denlinger, D. L. (2007). Shifts in the carbohydrate, polyol, and amino acid pools during rapid cold-hardening and diapause-associated cold-hardening in flesh flies (Sarcophaga crassipalpis): A metabolomic comparison. Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology, 177, 753–763. doi: 10.1007/s00360-007-0172-5.PubMedCrossRefGoogle Scholar
  83. Miller, M. G. (2007). Environmental metabolomics: A SWOT analysis (strengths, weaknesses, opportunities, and threats). Journal of Proteome Research, 6, 540–545. doi: 10.1021/pr060623x.PubMedCrossRefGoogle Scholar
  84. Miller, G. A., Islam, M. S., Claridge, T. D. W., Dodgson, T., & Simpson, S. J. (2008). Swarm formation in the desert locust Schistocerca gregaria: Isolation and NMR analysis of the primary maternal gregarizing agent. The Journal of Experimental Biology, 211, 370–376. doi: 10.1242/jeb.013458.PubMedCrossRefGoogle Scholar
  85. Mittler, R. (2002). Oxidative stress, antioxidants and stress tolerance. Trends in Plant Science, 7, 405–410. doi: 10.1016/S1360-1385(02)02312-9.PubMedCrossRefGoogle Scholar
  86. Morgan, A. J., Kille, P., & Sturzenbaum, S. R. (2007). Microevolution and ecotoxicology of metals in invertebrates. Environmental Science and Technology, 41, 1085–1096. doi: 10.1021/es061992x.PubMedCrossRefGoogle Scholar
  87. Morrison, N., Bearden, D., Bundy, J. G., Collette, T., Currie, F., Davey, M. P., et al. (2007). Standard reporting requirements for biological samples in metabolomics experiments: Environmental context. Metabolomics, 3, 203–210. doi: 10.1007/s11306-007-0067-1.CrossRefGoogle Scholar
  88. Noaksson, E., Gustavsson, B., Linderoth, M., Zebuhr, Y., Broman, D., & Balk, L. (2004). Gonad development and plasma steroid profiles by HRGC/HRMS during one reproductive cycle in reference and leachate-exposed female perch (Perca fluviatilis). Toxicology and Applied Pharmacology, 195, 247–261. doi: 10.1016/j.taap.2003.11.017.PubMedCrossRefGoogle Scholar
  89. OECD. (1984). OECD guidelines for testing of chemicals. No 207. Earthworm acute toxicity tests. Organisation for Economic Cooperation and Development.Google Scholar
  90. OECD. (2004). OECD guidelines for testing of chemicals. No 222. Earthworm reproduction test (Eisenia foetida/Eisenia andrei). Organisation for Economic Cooperation and Development.Google Scholar
  91. Orlando, E. F., & Guillette, L. (2001). A re-examination of variation associated with environmentally stressed organisms. Human Reproduction Update, 7, 265–272. doi: 10.1093/humupd/7.3.265.PubMedCrossRefGoogle Scholar
  92. Ossipov, V., Ossipova, S., Bykov, V., Oksanen, E., Koricheva, J., & Haukioja, E. (2008). Application of metabolomics to genotype and phenotype discrimination of birch trees grown in a long-term open-field experiment. Metabolomics, 4, 39–51. doi: 10.1007/s11306-007-0097-8.CrossRefGoogle Scholar
  93. Overgaard, J., Malmendal, A., Sorensen, J. G., Bundy, J. G., Loeschcke, V., Nielsen, N. C., et al. (2007). Metabolomic profiling of rapid cold hardening and cold shock in Drosophila melanogaster. Journal of Insect Physiology, 53, 1218–1232. doi: 10.1016/j.jinsphys.2007.06.012.PubMedCrossRefGoogle Scholar
  94. Owen, J., Hedley, B. A., Svendsen, C., Wren, J., Jonker, M. J., Hankard, P. K., et al. (2008). Transcriptome profiling of developmental and xenobiotic responses in a keystone soil animal, the oligochaete annelid Lumbricus rubellus. BMC Genomics, 9, 266. doi: 10.1186/1471-2164-9-266.PubMedCrossRefGoogle Scholar
  95. Parsons, H. M., Ludwig, C., Günther, U. L., & Viant, M. R. (2007). Improved classification accuracy in 1- and 2-dimensional NMR metabolomics data using the variance stabilising generalised logarithm transformation. BMC Bioinformatics, 8, 234. doi: 10.1186/1471-2105-8-234.PubMedCrossRefGoogle Scholar
  96. Paules, R. (2003). Phenotypic anchoring: Linking cause and effect. Environmental Health Perspectives, 111, A338–A339.PubMedGoogle Scholar
  97. Peiris, D., Dunn, W. B., Brown, M., Kell, D. B., Roy, I., & Hedger, J. N. (2008). Metabolite profiles of interacting mycelial fronts differ for pairings of the wood decay basidiomycete fungus, Stereum hirsutum with its competitors Coprinus micaceus and Coprinus disseminatus. Metabolomics, 4, 52–62. doi: 10.1007/s11306-007-0100-4.CrossRefGoogle Scholar
  98. Penuelas, J., & Estiarte, M. (1998). Can elevated CO2 affect secondary metabolism and ecosystem function? Trends in Ecology & Evolution, 13, 20–24. doi: 10.1016/S0169-5347(97)01235-4.CrossRefGoogle Scholar
  99. Penuelas, J., Llusia, J., & Gimeno, B. S. (1999). Effects of ozone concentrations on biogenic volatile organic compounds emission in the Mediterranean region. Environmental Pollution, 105, 17–23. doi: 10.1016/S0269-7491(98)00214-0.CrossRefGoogle Scholar
  100. Pincetich, C. A., Viant, M. R., Hinton, D. E., & Tjeerdema, R. S. (2005). Metabolic changes in Japanese medaka (Oryzias latipes) during embryogenesis and hypoxia as determined by in vivo 31P NMR. Comparative Biochemistry and Physiology C, 140, 103–113.Google Scholar
  101. Pinheiro, C., Passarinho, J. A., & Ricardo, C. P. (2004). Effect of drought and rewatering on the metabolism of Lupinus albus organs. Journal of Plant Physiology, 161, 1203–1210. doi: 10.1016/j.jplph.2004.01.016.PubMedCrossRefGoogle Scholar
  102. Pope, G. A., MacKenzie, D. A., Defemez, M., Aroso, M., Fuller, L. J., Mellon, F. A., et al. (2007). Metabolic footprinting as a tool for discriminating between brewing yeasts. Yeast (Chichester, England), 24, 667–679. doi: 10.1002/yea.1499.CrossRefGoogle Scholar
  103. Rasmussen, S., Parsons, A. J., Fraser, K., Xue, H., & Newman, J. A. (2008). Metabolic profiles of Lolium perenne are differentially affected by nitrogen supply, carbohydrate content, and fungal endophyte infection. Plant Physiology, 146, 1440–1453. doi: 10.1104/pp.107.111898.PubMedCrossRefGoogle Scholar
  104. Riipi, M., Haukioja, E., Lempa, K., Ossipov, V., Ossipova, S., & Pihlaja, K. (2004). Ranking of individual mountain birch trees in terms of leaf chemistry: Seasonal and annual variation. Chemoecology, 14, 31–43. doi: 10.1007/s00049-003-0256-y.CrossRefGoogle Scholar
  105. Robertson, D. G. (2005). Metabonomics in toxicology: A review. Toxicological Sciences, 85, 809–822. doi: 10.1093/toxsci/kfi102.PubMedCrossRefGoogle Scholar
  106. Robinson, A. R., Ukrainetz, N. K., Kang, K. Y., & Mansfield, S. D. (2007). Metabolite profiling of Douglas-fir (Pseudotsuga menziesii) field trials reveals strong environmental and weak genetic variation. The New Phytologist, 174, 762–773. doi: 10.1111/j.1469-8137.2007.02046.x.PubMedCrossRefGoogle Scholar
  107. Rosenblum, E. S., Tjeerdema, R. S., & Viant, M. R. (2006). Effects of temperature on host-pathogen-drug interactions in Red Abalone, Haliotis rufescens, determined by 1H NMR metabolomics. Environmental Science and Technology, 40, 7077–7084. doi: 10.1021/es061354e.PubMedCrossRefGoogle Scholar
  108. Rosenblum, E. S., Viant, M. R., Braid, B. M., Moore, J. D., Friedman, C. S., & Tjeerdema, R. S. (2005). Characterizing the metabolic actions of natural stresses in the California red abalone, Haliotis rufescens using 1H NMR metabolomics. Metabolomics, 1, 199–209. doi: 10.1007/s11306-005-4428-3.CrossRefGoogle Scholar
  109. Samuelsson, L. M., Forlin, L., Karlsson, G., Adolfsson-Eric, M., & Larsson, D. G. J. (2006). Using NMR metabolomics to identify responses of an environmental estrogen in blood plasma of fish. Aquatic Toxicology (Amsterdam, Netherlands), 78, 341–349. doi: 10.1016/j.aquatox.2006.04.008.Google Scholar
  110. Samuelsson, L. M., & Larsson, D. G. J. (2008). Contributions from metabolomics to fish research. Molecular BioSystems, 4, 974–979. doi: 10.1039/b804196b.PubMedCrossRefGoogle Scholar
  111. Sanchez, D. H., Siahpoosh, M. R., Roessner, U., Udvardi, M., & Kopka, J. (2008). Plant metabolomics reveals conserved and divergent metabolic responses to salinity. Physiologia Plantarum, 132, 209–219.PubMedGoogle Scholar
  112. Semel, Y., Schauer, N., Roessner, U., Zamir, D., & Fernie, A. R. (2007). Metabolite analysis for the comparison of irrigated and non-irrigated field grown tomato of varying genotype. Metabolomics, 3, 289–295. doi: 10.1007/s11306-007-0055-5.CrossRefGoogle Scholar
  113. Smirnoff, N. (1998). Plant resistance to environmental stress. Current Opinion in Biotechnology, 9, 214–219. doi: 10.1016/S0958-1669(98)80118-3.PubMedCrossRefGoogle Scholar
  114. Smith, A. R., Johnson, H. E., & Hall, M. (2003). Metabolic fingerprinting of salt-stressed tomatoes. Bulgarian Journal of Plant Physiology, 153–163.Google Scholar
  115. Snape, J. R., Maund, S. J., Pickford, D. B., & Hutchinson, T. H. (2004). Ecotoxicogenomics: The challenge of integrating genomics into aquatic and terrestrial ecotoxicology. Aquatic Toxicology (Amsterdam, Netherlands), 67, 143–154. doi: 10.1016/j.aquatox.2003.11.011.Google Scholar
  116. Solanky, K. S., Burton, I. W., MacKinnon, S. L., Walter, J. A., & Dacanay, A. (2005). Metabolic changes in Atlantic salmon exposed to Aeromonas salmonicida detected by 1H nuclear magnetic resonance spectroscopy of plasma. Diseases of Aquatic Organisms, 65, 107–114. doi: 10.3354/dao065107.PubMedCrossRefGoogle Scholar
  117. Southam, A. D., Easton, J. M., Stentiford, G. D., Ludwig, C., Arvanitis, T. N., & Viant, M. R. (2008). Metabolic changes in flatfish hepatic tumours revealed by NMR-based metabolomics and metabolic correlation networks. Journal of Proteome Research, 7, 5277–5285. doi: 10.1021/pr800353t.CrossRefPubMedGoogle Scholar
  118. Spurgeon, D. J., Weeks, J. M., & Van Gestel, C. A. M. (2002). A summary of eleven years progress in earthworm ecotoxicology. Pedobiologia, 47, 588–606.Google Scholar
  119. Stentiford, G. D., Viant, M. R., Ward, D. G., Johnson, P. J., Martin, A., Wei, W., et al. (2005). Liver tumours in wild flatfish: A histopathological, proteomic and metabolomic study. OMICS—Journal of Integrative Biology, 9, 281–299.CrossRefGoogle Scholar
  120. Stewart, G. R., Larher, F., Ahmed, I., & Lee, J. A. (1979). Nitrogen metabolism and salt-tolerance in higher plant halophytes. In R. Jefferies & A. Davy (Eds.), Ecological processes in coastal environments (pp. 211–227). Oxford: Blackwell Scientific Publications.Google Scholar
  121. Stitt, M., & Hurry, V. (2002). A plant for all seasons: Alterations in photosynthetic carbon metabolism during cold acclimation in Arabidopsis. Current Opinion in Plant Biology, 5, 199–206. doi: 10.1016/S1369-5266(02)00258-3.PubMedCrossRefGoogle Scholar
  122. Sumner, L. W., Amberg, A., Barrett, D., Beale, M. H., Beger, R., Daykin, C. A., et al. (2007). Proposed minimum reporting standards for chemical analysis. Metabolomics, 3, 211–221. doi: 10.1007/s11306-007-0082-2.CrossRefGoogle Scholar
  123. Svendsen, C., Owen, J., Kille, P., Wren, J., Jonker, M. J., Headley, B. A., et al. (2008). Comparative transcriptomic responses to chronic cadmium, fluoranthene, and atrazine exposure in Lumbricus rubellus. Environmental Science and Technology, 42, 4208–4214. doi: 10.1021/es702745d.PubMedCrossRefGoogle Scholar
  124. Taylor, N. S., Weber, R. J. M., Southam, A. D., Payne, T. G., Hrydziuszko, O., Arvanitis, T. N., & Viant, M. R. (in press). A new approach to toxicity testing in Daphnia magna: Application of high throughput FT-ICR mass spectrometry metabolomics. Metabolomics, 5(1). doi: 10.1007/s11306-008-0133-3.
  125. Thomashow, M. F. (1999). Plant cold acclimation: Freezing tolerance genes and regulatory mechanisms. Annual Review of Plant Physiology and Molecular Biology, 50, 571–599. doi: 10.1146/annurev.arplant.50.1.571.CrossRefGoogle Scholar
  126. Turner, M. A., Viant, M. R., Teh, S. J., & Johnson, M. L. (2007). Developmental rates, structural asymmetry, and metabolic fingerprints of steelhead trout (Oncorhynchus mykiss) eggs incubated at two temperatures. Fish Physiology and Biochemistry, 33, 59–72. doi: 10.1007/s10695-006-9117-2.CrossRefGoogle Scholar
  127. Urbanczyk-Wochniak, E., & Fernie, A. R. (2005). Metabolic profiling reveals altered nitrogen nutrient regimes have diverse effects on the metabolism of hydroponically-grown tomato (Solanum lycopersicum) plants. Journal of Experimental Botany, 56, 309–321. doi: 10.1093/jxb/eri059.PubMedCrossRefGoogle Scholar
  128. van Gestel, C. A. M., Vandis, W. A., Vanbreemen, E. M., & Sparenburg, P. M. (1989). Development of a standardized reproduction toxicity test with the earthworm species Eisenia fetida andrei using copper, pentachlorophenol, and 2, 4-dichloroaniline. Ecotoxicology and Environmental Safety, 18, 305–312. doi: 10.1016/0147-6513(89)90024-9.PubMedCrossRefGoogle Scholar
  129. van Straalen, N. M., & Roelofs, D. (2008). Genomics technology for assessing soil pollution. Journal of Biology (Online), 7, 19. doi: 10.1186/jbiol80.Google Scholar
  130. Viant, M. R. (2003). Improved methods for the acquisition and interpretation of NMR metabolomic data. Biochemical and Biophysical Research Communications, 310, 943–948. doi: 10.1016/j.bbrc.2003.09.092.PubMedCrossRefGoogle Scholar
  131. Viant, M. R. (2007). Metabolomics of aquatic organisms: The new ‘omics’ on the block. Marine Ecology Progress Series, 332, 301–306. doi: 10.3354/meps332301.CrossRefGoogle Scholar
  132. Viant, M. R. (2008). Recent developments in environmental metabolomics. Molecular BioSystems, 4, 980–986. doi: 10.1039/b805354e.PubMedCrossRefGoogle Scholar
  133. Viant, M. R., Bearden, D. W., Bundy, J. G., Burton, I. W., Collette, T. W., & Ekman, D. R., et al. (in press). International NMR-based environmental metabolomics intercomparison exercise. Environmental Science & Technology. doi: 10.1021/es802198z.
  134. Viant, M. R., Bundy, J. G., Pincetich, C. A., de Ropp, J. S., & Tjeerdema, R. S. (2005). NMR-derived developmental metabolic trajectories: An approach for visualizing the toxic actions of trichloroethylene during embryogenesis. Metabolomics, 1, 149–158. doi: 10.1007/s11306-005-4429-2.CrossRefGoogle Scholar
  135. Viant, M. R., Pincetich, C. A., Hinton, D. E., & Tjeerdema, R. S. (2006a). Toxic actions of dinoseb in medaka (Oryzias latipes) embryos as determined by in vivo 31P NMR, HPLC-UV and 1H NMR metabolomics. Aquatic Toxicology (Amsterdam, Netherlands), 76, 329–342. doi: 10.1016/j.aquatox.2005.10.007.Google Scholar
  136. Viant, M. R., Pincetich, C. A., & Tjeerdema, R. S. (2006b). Metabolic effects of dinoseb, diazinon and esfenvalerate in eyed eggs and alevins of Chinook salmon (Oncorhynchus tshawytscha) determined by 1H NMR metabolomics. Aquatic Toxicology (Amsterdam, Netherlands), 77, 359–371. doi: 10.1016/j.aquatox.2006.01.009.Google Scholar
  137. Viant, M. R., Rosenblum, E. S., & Tjeerdema, R. S. (2003a). NMR-based metabolomics: A powerful approach for characterizing the effects of environmental stressors on organism health. Environmental Science and Technology, 37, 4982–4989. doi: 10.1021/es034281x.PubMedCrossRefGoogle Scholar
  138. Viant, M. R., Werner, I., Rosenblum, E. S., Gantner, A. S., Tjeerdema, R. S., & Johnson, M. L. (2003b). Correlation between heat-shock protein induction and reduced metabolic condition in juvenile steelhead trout (Oncorhynchus mykiss) chronically exposed to elevated temperature. Fish Physiology and Biochemistry, 29, 159–171. doi: 10.1023/B:FISH.0000035938.92027.81.CrossRefGoogle Scholar
  139. Warne, M. A., Lenz, E. M., Osborn, D., Weeks, J. M., & Nicholson, J. K. (2000). An NMR-based metabonomic investigation of the toxic effects of 3-trifluoromethyl-aniline on the earthworm Eisenia veneta. Biomarkers, 5, 56–72. doi: 10.1080/135475000230541.CrossRefGoogle Scholar
  140. Warne, M. A., Lenz, E. M., Osborn, D., Weeks, J. M., & Nicholson, J. K. (2001). Comparative biochemistry and short-term starvation effects on the earthworms Eisenia veneta and Lumbricus terrestris studied by 1H NMR spectroscopy and pattern recognition. Soil Biology and Biochemistry, 33, 1171–1180. doi: 10.1016/S0038-0717(01)00021-9.CrossRefGoogle Scholar
  141. Waters, M., Boorman, G., Bushel, P., Cunningham, M., Irwin, R., Merrick, A., et al. (2003). Systems toxicology and the Chemical Effects in Biological Systems (CEBS) knowledge base. Environmental Health Perspectives, 111, 811–824.Google Scholar
  142. Widarto, H. T., Van der Meijden, E., Lefeber, A. W. M., Erkelens, C., Kim, H. K., Choi, Y. H., et al. (2006). Metabolomic differentiation of Brassica rapa following herbivory by different insect instars using two-dimensional nuclear magnetic resonance spectroscopy. Journal of Chemical Ecology, 32, 2417–2428. doi: 10.1007/s10886-006-9152-6.PubMedCrossRefGoogle Scholar
  143. Wishart, D. S., Tzur, D., Knox, C., Eisner, R., Guo, A. C., Young, N., et al. (2007). HMDB: The human metabolome database. Nucleic Acids Research, 35, D521–D526. doi: 10.1093/nar/gkl923.PubMedCrossRefGoogle Scholar
  144. Woodward, F. I. (1987). Climate and plant distribution. Cambridge: Cambridge University Press.Google Scholar
  145. Zhen, Y., & Ungerer, M. C. (2008). Clinal variation in freezing tolerance among natural accessions of Arabidopsis thaliana. The New Phytologist, 177, 419–427.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Jacob G. Bundy
    • 1
  • Matthew P. Davey
    • 2
  • Mark R. Viant
    • 3
    Email author
  1. 1.Department of Biomolecular MedicineImperial College London, Sir Alexander Fleming Building, Faculty of MedicineSouth Kensington, LondonUK
  2. 2.Department of Animal and Plant SciencesUniversity of SheffieldWestern Bank, SheffieldUK
  3. 3.School of BiosciencesUniversity of BirminghamEdgbaston, BirminghamUK

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