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E-CELL: Towards integrative modeling of cellular processes
M. Tomita
E-CELL Project (http://www.e-cell.org) was launched in 1996 at Keio University
in order to model and simulate various cellular processes with the ultimate
goal of simulating the cell as a whole. E-CELL System, a generic software
package we have developed, enables us to model not only metabolic pathways
but also other higher-order cellular processes such as protein synthesis and
signal transduction.
Using the system, we have successfully constructed a virtual
cell with 127 genes sufficient for ``self-support''. The gene set was
selected from the genome of Mycoplasma genitalium, and the metabolisms include
transcription, translation, membrane transport, the glycolysis pathway for
energy production, and the phospholipid biosynthesis pathway for membrane
structure. Since all its proteins and membrane structure are modeled to degrade
spontaneously over time, the virtual cell must keep synthesizing proteins
and phospholipid bilayer to sustain its life. It thus uptakes glucose
as its energy source, and emptying glucose in the environment would result
in “cell death from hunger”.
Modeling Group in our institute is now developing many
different models of cellular processes, including bacterial chemotaxis, circadian
rhythms, photosynthesis, as well as cell cycle and cell division. For organelles,
a quantitative model of mitochondria is nearly complete, and we will be soon
developing chloroplasts in the context of e-Rice Project funded by Japanese
ministry of agriculture. For human cells, we have already developed a quantitative
model of erythrocytes, and being used in pathological analyses of enzyme deficiencies
causing anemia. Other human cells now being developed include myocardial
cells, neural cells, and pancreatic beta-cells.
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