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
14-1 Baba-cho, Tsuruoka-shi
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.