Abstract
A dynamic model of prokaryotic gene expression is developed that makes
considerable use of gene sequence information. The main contribution
arises from the fact that the combined gene expression model allows us
to access the impact of altering a nucleotide sequence on the dynamics
of gene expression rates mechanistically. The high level of detail of
the mathematical model is considered as an important step towards
bringing together the tremendous amount of biological in-depth knowledge
that has been accumulated at the molecular level, using a systems level
analysis (in the sense of a bottom-up, inductive approach). This enables
to the model to provide highly detailed insights into the various steps
of the protein expression process and it allows us to access possible
targets for model-based design. Taken as a whole, the mathematical gene
expression model presented in this study provides a comprehensive
framework for a thorough analysis of sequence-related effects on the
stages of mRNA synthesis, mRNA degradation and ribosomal translation, as
well as their nonlinear interconnectedness. Therefore, it may be useful
in the rational design of recombinant bacterial protein synthesis
systems, the modulation of enzyme activities in pathway design, in vitro
protein biosynthesis, and RNA-based vaccination.
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