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Multistability in the lactose utilization network of Escherichia coli

Multistability in the lactose utilization network of Escherichia coli. Advisors: Tang Leihan & Namiko Mitarai Group two members: He Xiaojuan Bi Hongjie Wang Peng Wang Jinshui Li Xiang Li Mengyao Zheng Muhua Jiang Chongming. our photo & introduction. O utline.

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Multistability in the lactose utilization network of Escherichia coli

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  1. Multistability in the lactose utilization network of Escherichia coli Advisors: Tang Leihan & NamikoMitarai Group two members: He XiaojuanBi HongjieWang Peng Wang JinshuiLi Xiang Li Mengyao ZhengMuhua Jiang Chongming

  2. our photo&introduction

  3. Outline • Backgrounds • The lactose utilization network • Deterministic model • Deterministic model&Noise • Stochastic model • The lactose utilization network + lactose metabolism

  4. Backgrounds: • Regulatorynetwork: regulatorysystemthatconsistsofacollectionofnodes,pairsofwhichareconnectedbylinks. • Feedback loops: a cyclic chain of links in a regulatory network. • Positive feedback loops: self-activation or double negative feedback. • Multistability: thecapacity to achieve multiple internal states in response to a single set of external inputs. • Biological switch: cell fate, cell-cycle oscillations.

  5. Thelactoseutilizationnetwork Two external inputs: Glucose & TMG(thio-methylgalactoside) TMG: a non-metabolizable lactose analogue. Redlines:regulatoryinteractions. Black arrows: protein creation through transcription and translation. Dotted arrows: uptake process Operon: promoter + expressible genes

  6. Thelactoseutilizationnetwork and reportor system Bi-stability !!! Two transcriptional regulators: LacI: a repressor. CRP: an activator. GFP: green fluorescent protein, expressed at the lac promoter. HcRed: red fluorescent protein, expressed at the gat promoter. LacYcatalyses the uptake of TMG, which induces further expression of LacY, resulting in a positive feedback.

  7. Experimental results: b. Behavior of alarge cell population c. The phase diagram describing the state of the lactose utilization network in wild-type cells

  8. Deterministic model ρ: dissociation constant of LacI from its main DNA-binding site. ρ=1+RT/R0 : describes how tightly LacI is able to regulate the expression of the lacoperon.

  9. Our results

  10. Theoretical phase diagram

  11. Model analysis

  12. Model analysis & Add noise

  13. Stochastic model & Gillespie algorithm

  14. Stochastic model & Gillespie algorithm

  15. Lactose LacY (y) Lactose (x) Allolactose (w) LacZ (z) LacI Plac The lactose utilization network + lactose metabolism (S2) (S3) (S4) (S5)

  16. Lactose LacY (y) Lactose (x) Allolactose (w) LacZ (z) LacI Plac The lactose utilization network + lactose metabolism simplified model:

  17. The lactose utilization network + lactose metabolism steady state: Analyze the third equation, and let: We find:

  18. The lactose utilization network + lactose metabolism phase diagram

  19. Conclusion

  20. References: • Ertugrul M. Ozbudak, Mukund Thattai, Han N. Lim,Boris I. Shraiman& Alexander van Oudenaarden. 2004. Multistabilityin the lactose utilizationnetwork of Escherichia coli. • Kim Sneppen, Sandeep Krishna, and Szabolcs Semsey. 2010. Simplified models of biological networks. • Danlel T. Gillespie. 1977. Exact stochastic simulation of coupled chemical reactions. • Michael B. Elowitz et al. 2002. Stochastic gene expression in a single cell. • Jerome T. Mettetal, Dale Muzzey, Juan M. Pedraza, Ertugrul M. Ozbudak, and Alexander van Oudenaarden. Predicting stochastic gene expression dynamics in single cells.

  21. Thanks for your listening!

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