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2013 Fiscal Year Research-status Report

Fluxomic approaches for Yeast metabolism

Research Project

Project/Area Number 24510268
Research InstitutionKeio University

Principal Investigator

MURRAY Douglas  慶應義塾大学, 政策・メディア研究科, 特任講師 (50458965)

Keywords国際的研究者交流 / Germany / Austria / UK / 計算上の結果と実験結果の交換
Research Abstract

We calculated the synthesis and degradation rates for many metabolites from Mass spectrometry data obtained from dynamic isotopically non-stationary 13C labelling data. We are currently collating the data and have identified the requirement for isotopically stationary 13C labelling to calculate the fluxes in the network using metabolic flux analyses (MFA).
We are produced a carbon atom transition metabolic model of Saccharomyces cerevisiae. The plan is to expand our methods to produce software that is applicable to other species. This work is in collaboration with Glasgow and Vienna Universities.
Dynamic Flux balance analyses (FBA) tools have been developed for large scale metabolic networks. This work has been carried out in collaboration with Humboldt University.
Our results show that CO2 assimilation and lipid mobilisation play important roles in cellular energetics during high oxygen uptake rates. Therefore, we have conducted 13CO2 labelling experiments and produced mutants in lipid degradation.
We are currently analysing the data and testing the mutant physiology. This work has been carried out in collaboration with Exeter University.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

We have developed Dynamic Flux balance analyses (FBA) and have implemented them in FASIMU and are simulating large scale yeast networks based on constraints from our experiments.
We have processed ~500 spectra encompassing intracellular, extracellular and biomass digestions, and are collating the results.
We have calculated synthesis and degradation rates for many metabolites from Mass spectrometry data.
We have produced mutants in lipid degradation.
We are in the latter stages of producing a carbon atom transition model that encompasses most of our measured data.

Strategy for Future Research Activity

New isotopically stationary data needs to be obtained and analysed for effective MFA analysis. All the data will be collated and integrated. FBA and MFA simulations will be integrated.
Present data at Metabolomics 2014, Tsuruoka. I also plan to present results Exeter, Glasgow and Humboldt Universities.
I am working on a lipidomics article based on the results obtained in this study. We are writing an article based on our FBA work. A manuscript based on a theoretical study on the role of temporal and physical (at the organelle level) in metabolic network optimisation is nearing completion.
I plan to use the excess balance of last years budget to buy consumables for the project. In particular, labelled glucose to carry out isotopically stationary dynamic metabolic flux analysis.

Expenditure Plans for the Next FY Research Funding

I underspent the budget because I managed to locate a cylinder of 13CO2 in our department.
I plan to use the excess balance of last years budget to buy consumables for the project. In particular, labelled glucose to carry out isotopically stationary dynamic metabolic flux analysis.

  • Research Products

    (3 results)

All 2013

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results) Book (1 results)

  • [Journal Article] The dynamics of cellular energetics during continuous yeast culture.2013

    • Author(s)
      Amariei C, Machne R, Sasidharan K, Gottstein W, Tomita M, Soga T, Lloyd D, Murray DB.
    • Journal Title

      Conf Proc IEEE Eng Med Biol Soc.

      Volume: 2013 Pages: 2708-2711

    • DOI

      10.1109/EMBC.2013.6610099

    • Peer Reviewed
  • [Presentation] The dynamics of cellular energetics during continuous yeast culture.2013

    • Author(s)
      Douglas Murray
    • Organizer
      Engineering in Medicine and Biology Society (EMBC), 2013 35th Annual International Conference of the IEEE
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      20130703-20130707
  • [Book] Systems Biology of Metabolic and Signalling Networks2013

    • Author(s)
      Temporal Partitioning of the Yeast Cellular Network.
    • Total Pages
      375 (323-351)
    • Publisher
      Douglas B. Murray, Cornelia Amariei, Kalesh Sasidharan, Rainer Machne´, Miguel A. Aon, and David Lloyd

URL: 

Published: 2015-05-28  

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