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Development of a biophysical model of translational coupling Tian Tian Salis Lab

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.

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Development of a biophysical model of translational coupling Tian Tian Salis Lab

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  1. Development of a biophysical modelof translational coupling TianTian Salis Lab Year 7 Fall Retreat September 23, 2012

  2. Metabolic Engineering E1 E2 E1: E2…En = a: b…n … … … En Many proteins work together to manufacture products

  3. Translational Coupling to Coordinate Protein Expression Translational coupling Upstream Downstream Intergenic region Examples: Translational Coupling NoCoupling Down- stream gene expression Escherichia. coli Escherichia. coli F(Upstream gene expression) Salmonella Typhimurium

  4. 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.

  5. Mechanism of Translational Coupling Upstream gene Downstream gene Ribosome Upstream gene Downstream gene

  6. Mechanism of Translational Coupling Ribosome Upstream Gene Downstream Gene De novo initiation

  7. Mechanism of Translational Coupling Ribosome Downstream Gene Upstream Gene Re - initiation

  8. Ribosome-assisted Unfolding of mRNA Hairpins Hairpin is never unfolded High Fcoupling Low downstream TIR Low upstream TIR Hairpin is unfolded 50% of time Medium Fcoupling Medium downstream TIR Medium upstream TIR Hairpin is always unfolded Low Fcoupling High downstream TIR High upstream TIR

  9. Translational Coupling Calculator Coming Soon !

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