Yeast Systems Biology
The yeast Saccharomyces cerevisiae is perhaps the best model organism to establish new techniques and methodologies due to its easy growth, non-pathogenicity, and the wide availability of genetic and molecular tools. This is also the case for systems biology, so yeast is used in many projects in our group.
Yeast Metabolic Reconstruction
We update the most comprehensive and documented reconstruction of yeast metabolism. This stemmed from a community-wide collaborative project from which a consensus model emerged. We have subsequently continued to update this reconstruction by filling in gaps and adding parts of metabolism that were previously not well covered by reconstructions. The most up to date reconstruction is available in SBML format from yeast.sf.net.
We are part of the Manchester Centre for Integrative Systems Biology (MCISB). During its first period of funding, the Centre engaged in the development of bottom-up systems biology using yeast as a model organism. This included methods for systematic protein purification, enzyme kinetics, quantitative metabolomics, quantitative proteomics, flux-balance analysis, kinetic modelling with ODEs, metabolic control analysis, data standards and web services. This work resulted in several dynamic models of biochemical pathways of yeast central metabolism.
Oxidative stress response
We carried out a comprehensive gene expression study of the dynamic response to oxidative stress in yeast. We use these data to develop reverse engineering methods for top-down systems biology.
mRNA translation machinery
Together with the group of John McCarthy, we created a detailed model of yeast mRNA translation (protein synthesis by the ribosome). This model helped decide between alternative mechanisms in some of the steps of initiation.
- Smallbone K, Messiha HL, Carroll KM, Winder CL, Malys N, Dunn WB, Murabito E, Swainston N, Dada JO, Khan F, Pir P, Simeonidis E, Spasić I, Wishart J, Weichart D, Hayes NW, Jameson D, Broomhead DS, Oliver SG, Gaskell SJ, McCarthy JEG, Paton NW, Westerhoff HV, Kell DB, Mendes P (2013) A model of yeast glycolysis based on a consistent kinetic characterization of all its enzymes. FEBS Letters 587:2832–41 [full text]
- Sha W, Martins AM, Laubenbacher R, Mendes P, Shulaev V (2013) The genome-wide early temporal response of Saccharomyces cerevisiae to oxidative stress induced by cumene hydroperoxide. PLOS One 8: e74939. [full text] [supplementary data]
- Mensonides FIC, Bakker BM, Cremazy F, Messiha HL , Mendes P, Boogerd FC, Westerhoff HV (2013) A new regulatory principle for in vivo biochemistry: pleiotropic low affinity regulation by the adenine nucleotides – illustrated for the glycolytic enzymes of Saccharomyces cerevisiae. FEBS Letters 587: 2860-7. [abstract]
- Firczuk H, Kannambath S, Pahle J, Claydon A, Beynon R, Duncan J, Westerhoff H, Mendes P, McCarthy JEG (2013) An in vivo control map for the eukaryotic mRNA translation machinery. Molecular Systems Biology 9:635 [full text]
- Lee D, Smallbone K, Dunn WB, Murabito E, Winder CL, Kell DB, Mendes P, Swainston N (2012) Improving metabolic flux predictions using absolute gene expression data BMC Systems Biology 6:73 [full text]
- Heavner BD, Smallbone K, Barker B, Mendes P, Walker LP (2012) Yeast 5 - an expanded reconstruction of the Saccharomyces cerevisiae metabolic network BMC Systems Biology 6:55 [full text]
- Li, P, Dada, JO, Jameson, D, Spasic, I, Swainston, N, Carroll, K, Dunn, W, Khan, F, Messiha, HL, Simeonidis, E, Weichart, D, Winder, C, Broomhead, D, Goble, CA, Gaskell, SJ, Kell, DB, Westerhoff, HV, Mendes, P, Paton, NW (2010) Systematic integration of experimental data and models in systems biology BMC Bioinformatics 11, 582 [full text]
- Dobson, PD, Smallbone, K, Jameson, D, Simeonidis, E, Lanthaler, K, Pir, P, Lu, C, Swainston, N, Dunn, WB, Fisher, P, Hull, D, Brown, M, Oshota, O, Stanford, NJ, Kell, DB, King, RD, Oliver, SG, Stevens, RD, Mendes, P (2010) Further developments towards a genome-scale metabolic model of yeast BMC Systems Biology 4,145. [full text]
- Mendes, P, Messiha, H, Malys, N, Hoops, S (2009) Enzyme kinetics and computational modeling for systems biology. Methods Enzymol. 467, 583-99. [abstract] [ full text]
- Herrgård MJ, Swainston N, Dobson P, Dunn WB, Arga KY, Arvas M, Blüthgen N, Borger S, Costenoble R, Heinemann M, Hucka M, Le Novère N, Li P, Liebermeister W, Mo ML, Oliveira AP, Petranovic D, Pettifer S, Simeonidis E, Smallbone K, Spasić I, Weichart D, Brent R, Broomhead DS, Westerhoff HV, Kirdar B, Penttilä M, Klipp E, Palsson BØ, Sauer U, Oliver SG, Mendes P, Nielsen J, Kell DB (2008) A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology, Nature Biotechnol. 26, 1155-1160. [abstract] [full text].
- Martins, A.M., Sha, W., Evans, C., Martino-Catt, S., Mendes, P., Shulaev, V. (2007) Comparison of sampling techniques for parallel analysis of transcript and metabolite levels in Saccharomyces cerevisiae. Yeast 24, 181-188. [abstract]
- Martins, A.M., Camacho, D., Shuman, J., Sha, W., Mendes, P. & Shulaev, V. (2004) A systems biology study of two distinct growth phases of Saccharomyces cerevisiae. Current Genomics 5, 649-663. [abstract]