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Development of a biophysical model of translational coupling Tian Tian Salis Lab Year 7 Fall Retreat September 23, 2012. Metabolic Engineering. E 1. E 2. E 1 : E 2 …E n = a: b…n. …. …. …. E n. Many proteins work together to manufacture products. - PowerPoint PPT Presentation
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Development of a biophysical modelof translational coupling
Tian TianSalis Lab
Year 7 Fall RetreatSeptember 23, 2012
Metabolic Engineering
… … …E1
En
E2
Many proteins work together to manufacture products
E1: E2…En = a: b…n
Translational Coupling to Coordinate Protein Expression
Translational coupling
Upstream Downstream
Intergenic region
Examples:
F(Upstream gene expression)
Escherichia. coli
Escherichia. coli
Salmonella Typhimurium
Translational Coupling No Coupling
Down-stream
geneexpression
Objectives Develop a biophysical model of translational coupling that
can predict the downstream mRNA translation initiation rate;
Engineer metabolic pathway with optimal stoichiometries to coordinate protein expression and improve the pathway function.
Mechanism of Translational Coupling
Ribosome
Upstream gene Downstream gene
Upstream gene Downstream gene
Mechanism of Translational CouplingRibosome
Upstream Gene Downstream Gene
De novo initiation
Mechanism of Translational CouplingRibosome
Upstream Gene Downstream Gene
Re - initiation
Low upstream TIR
High upstream TIR
Medium upstream TIR
Hairpin is never unfolded
Hairpin is always unfolded
Hairpin is unfolded 50% of time
High Fcoupling
Ribosome-assisted Unfolding of mRNA Hairpins
Medium Fcoupling
Low Fcoupling
Medium downstream TIR
High downstream TIR
Low downstream TIR
Translational Coupling Calculator
Coming Soon !
