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Are we ready for… Genome-scale Metabolic Modeling in plants

Are we ready for… Genome-scale Metabolic Modeling in plants. Yoav Teboulle October 2012 Collakova , E . et al. (2012). Are we ready for genome-scale modeling in plants? Plant Science , 1–18. Outline. Motivation What’s been done… Why is it tough to model plants?

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Are we ready for… Genome-scale Metabolic Modeling in plants

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  1. Are we ready for… Genome-scale Metabolic Modeling inplants YoavTeboulle October 2012 Collakova, E. et al. (2012). Are we ready for genome-scale modeling in plants? Plant Science, 1–18.

  2. Outline • Motivation • What’s been done… • Why is it tough to model plants? • What are we doing about it? • The future…

  3. Motivation: Why genome-scale modeling? • Reductionist studies of individual reactions and pathways • Tinkering approaches to metabolic engineering • An integrated view of metabolism • Rational design approach to metabolic engineering

  4. Motivation: Why plants?

  5. Motivation: Why plants? Hibberd, J. M., & Weber, A. P. M. (2012). Plant metabolism and physiology. Current opinion in plant biology, 15(3), 225–227.

  6. So far: existing plant models • Arabidopsis(Poolman, 2009) • Barley • (Grafahrend-Belau, 2009) • C4 Plants: maize, sugarcane, sorghum • (Dal’Molin, 2010) • Oilseed rape • (Hay, 2011) • Zea mays • (Saha, 2011) • Tomato…Rice…Lemna…?

  7. Is that it?! What’s so hard about modeling plants? • Plant cell metabolism is complex… • Collectively, plants produce over 200,000 (primary and secondary) metabolites

  8. Is that it?! What’s so hard about modeling plants? • The complexity of plant cell metabolism means that little is known… • Experimental data is of limited coverage & bad quality • …which subsequently leads to poor annotation • Experimentally determined molecular function ~15% • Computationally determined molecular function ~40% • ??? ~45% • …which leave us with relatively poor models Zhu et al., Elements of a dynamic systems model of canopy photosynthesis, Current Opinion in Plant Biology, Volume 15, Issue 3, June 2012, Pages 237-244 Hibberd, J. M., & Weber, A. P. M. (2012). Plant metabolism and physiology. Current opinion in plant biology, 15(3), 225–227.

  9. Is that it?! What’s so hard about modeling plants? • Enzyme sub-cellular compartmentalization presents another challenge in plant modeling • Duplicated pathways of central carbon metabolism, such as glycolysis • Different organelles provide different conditions for metabolism in terms of • pH • Salt concentrations • Energy/redox status • Transporters between organelles and cytosol need to be identified de Oliveira Dal’Molin, C. G., & Nielsen, L. K. (2012). Plant genome-scale metabolic reconstruction and modeling. Current Opinion in Biotechnology, 1–7.

  10. Is that it?! What’s so hard about modeling plants? • Photosynthesis & photorespiration also contribute to the complexity… • Model assurance is unclear when dealing with tissues whose photosynthesis is not clear-cut • Different pathways active in light and dark • …as do the diversity of plant cell and tissue types… • …which causes difficulty in the selection of appropriate objective functions de Oliveira Dal’Molin, C. G., & Nielsen, L. K. (2012). Plant genome-scale metabolic reconstruction and modeling. Current Opinion in Biotechnology, 1–7.

  11. Excuses, you say…?

  12. So what CAN the models do…? • Existing models are predictive where central metabolism is concerned, less so in secondary metabolism These models demonstrate the applicability of metabolic modeling approaches to plant cells… …but still have difficulty in providing meaningful metabolic and mutant predictions

  13. What are WE doing about it? Zea Mays Arabidopsis

  14. What are WE doing about it? • Two newer Arabidopsis models

  15. What are WE doing about it? • Model improvement • Apply existing datasets • Apply novel datasets: AsaphAharoni’s Lab, Weizmann • biomass measurements • organelle-specific ‘omics • gene essentiality data • flux measurements

  16. What are WE doing about it? • Searching for ways to augment the production of: • Tocopherol(vitamin E) – antioxidant function • Thiamine (vitamin B1) – prevention of neural and other disorders

  17. What are WE doing about it? • Mays model • Verification and improvement of the existing model Saha, R., Suthers, P. F., & Maranas, C. D. (2011). Zea mays iRS1563: a comprehensive genome-scale metabolic reconstruction of maize metabolism. PloS one, 6(7), e21784. • Progress to a tissue-specific model • Use transcriptome and proteome data to extract a subset of reactions • Define tissue-specific biomass composition and metabolite exchange • Increased yield in target pathways based on bacterial gene transformation

  18. The FUTURE • Focus on secondary metabolism • Progress in ‘omics technologies • Better use of what we know! • Choose model systems we can experimentally validate • Apply known constraints • Define appropriate objective functions • Integrate regulatory mechanisms

  19. The FUTURE Rational Plant Metabolic Engineering

  20. So, are we ready for genome-scale modeling in plants? Definitely!

  21. Questions...?

  22. THANKS!

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