Oral Presentation Australian and New Zealand Metabolomics Conference 2018

We all like sheep – and worms, bugs, and maths. NMR-based metabolomics, systems biology and genome-scale modelling in livestock science, insects, and C. elegans. (#2)

Horst Joachim Schirra 1 , Denni Currin-Ross 1 , Alexandra Gloria 1 , Luke Husdell 1 , Jake P. Hattwell 1 , Angelo H. C. Chan 1 , Gene Wijffels 2 , Christopher McSweeney 2 , Paul R. Ebert 1
  1. University of Queensland, Brisbane, QLD, Australia
  2. CSIRO Agriculture, St Lucia, QLD, Australia

We will show several applications of NMR-based metabolomics in systems biology, livestock, and environmental science:

1) As part of a large livestock science research program in collaboration with colleagues at CSIRO Agriculture, we have investigated various conditions, such as road transport of sheep [1], parasite infections in sheep, and ruminal methane production as well as heat stress in cattle.

2) Application in insects center on the infection of insects with pipientis.

3) We have identified dihydrolipoamide dehydrogenase (DLD) as the enzyme responsible for phosphine resistance [2]. Progress in elucidating the role of DLD in phosphine resistance and general metabolic regulation includes the recent detailed characterization of the phosphine response, which shows that DLD preadapts elegans to phosphine toxicity by triggering global metabolic suppression in the resistant nematode strain [3]. DLD is a core metabolic enzyme, central to metabolic regulation, and a new class of resistance factor. DLD participates in four key steps of core metabolism, and this position in the metabolic network makes it a highly likely candidate for a central regulator of metabolism. We have developed CeCon, a genome-scale metabolic model of C. elegans metabolism that enables further characterization of DLD’s role in these processes through computational modelling of the nematode’s metabolism [3]. CeCon comprises 225 pathways, 1923 reactions, 1394 metabolites and 73 transporters. The model forms the basis for creating a C. elegans consensus genome-scale model as part of a multinational consortium [4]. DLD is an exceptional case in which a combination of systems biology methods has identified a single genetic cause of phenotypic change that can subsequently be studied with a wide range of methods from classical biochemistry to systems biology.

[4] Hastings et al.: Worm 6:e1373939, 1-4. (2017).

  1. Li, J., Wijffels, G., Yu, Y.-H., Nielsen, L. K., Niemeyer, D., Fisher, A., Ferguson, D. & Schirra, H. J. (2011): Altered fatty acid metabolism in long duration road transport: an NMR-based metabonomics study in sheep. J. Proteome Res. 10, 1073-1087.
  2. Schlipalius, D. I., Valmas, N., Tuck, A. G., Jagadeesan, R., Ma, L., Kaur, R., Goldinger, A., Anderson, C., Kuang, J., Zuryn, S., Mau, Y. S., Cheng, Q., Collins, P. J., Nayak, M. K., Schirra, H. J.^, Hilliard, M. A.^, Ebert, P. R.^ (2012): A core metabolic enzyme mediates resistance to phosphine gas. Science 338, 807-810.
  3. Li, M., Chan, A. H. C., Hattwell, J. P. N., Ebert, P. R.#, Schirra, H. J.# (2017): Systems biology analysis using a genome-scale metabolic model shows that phosphine triggers global metabolic suppression in a resistant strain of C. elegans. BioRXiv:144386.
  4. Hastings, J., Mains, A., Artal-Sanz, M., Bastos Lourenço, A., Bergmann, S., Braeckman, B., Bundy, J., Cabreiro, F., Dobson, P., Ebert, P., Hattwell, J., Hefzi, H., Houtkooper, R., Jelier, R., Joshi, C., Kothamachu, V. B., Lewis, N., Nie, Y., Norvaisas, P., Pearce, J., Riccio, C., Rodriguez, N., Santermans, T., Scarcia, P., Schirra, H. J., Sheng, M., Smith, R., Suriyalaksh, M., Towbin, B., Tuli, M. A., van Weeghel, M., Weinkove, D., Zečić, A., Zimmerman, J., le Novère, N., Kaleta, C., Witting, M., Casanueva, O. (2017): WormJam: Consensus C. elegans Metabolic Reconstruction and Metabolomics Community. Worm 6:e1373939, 1-4.