Research Report

 

Research Title: Mathematical and Statistical Approaches on Metabolic flux Analysis and Metabolic Control Analysis.

 

M. Aminul Hoque

Ph.D student

Institute for Advanced Bioscience

Keio University(TTCK)

14-1 Baba-cho, Tsuruoka-shi

Yamagata: 997-0035, Japan

Enail: aminul@sfc.keio.ac.jp

 

 

As soon as I entered into my Ph.D program I fixed up my research after consulted with my supervisor Professor Kazuyuki Shimizu and Professor Masaru Tomita. After fixed up my research title I was familiar with reference articles and some computer software including E.cell model related with my research analysis. As all of my research works are based on computer but unfortunately I had no laptop of my own. As soon as I got Mori grant I bought a laptop and other related research materials. Then I have selected my research methodologies and started my research. We established some formulae to compute metabolic flux distributions based on measured isotopomer distributions using a simple example. Later a computer simulation was made to study the dynamics of the intracellular metabolites concentrations in E.coli in particular for glycolysis and pentose-phosphate pathways based on the kinetic reactions developed by Chassagnole et al., (2002). The model successfully simulates the main features of the time course without alteration of the experimentally determined parameters.

 

Recently we made sensitivity analysis and flux control coefficients using inverse flux analysis method. We also found the impact in change of flux on acetate production and cellmass growth when pre-specific gene gets knock-out in E.coli. We identified some of the genes in E.coli that are very essential and they have grate impact on the other genes in E.coli whether some of the genes are not so essential to survive for E.coli. We also succeeded  to include the Entner-Doudoroff pathway using gluconate as carbon source and gene gnd was knocked out. We studied yet only for single mutant blocked gene but we would continue our study to see the results if double mutants were blocked and will compare the calculated results with experimental data.

 

Our next target would be focused on the analysis of isotopomer flux distribution using Atom Mapping Matrix (AMM) and then we would do statistical tests for the estimated parameters for their goodness of fit. We also wrote an article entitled “Metabolic Control Analysis Based on the Sensitivities of the Metabolic Flux Values with Respect to Gene Knockout in Escherichia coli” for publication in an International journal.