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States and probabilities

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  1. States and probabilities TexPoint fonts used in EMF. Read the TexPoint manual before you delete this box.: AAAAAAA

  2. Gating mechanism?

  3. States and weights

  4. Gating mechanism! Applied voltage (mV)

  5. Thermodynamic model of gene regulation Gene expression/ p(RNAp bound to promoter)

  6. RNAp binding energetics

  7. Promoter-RNAp binding: States and weights

  8. Ligand-receptor binding

  9. Ligand gated channel Zhong et al. ‘98

  10. Gating mechanism!

  11. Measuring gene regulation

  12. Single molecule FISH A. Raj ‘09

  13. Repression of gene expression

  14. Repression of transcription Monod ‘47 Schlax et al.‘97

  15. Mechanism of repression by Lac repressor Open complex formation (single molecule) Transcription (bulk)

  16. Repression in the Lac operon

  17. Simple repression: States and weights

  18. Counting repressors two different ways

  19. The Lac Operon Our goal: Mathematize the story told by all of these cartoons!

  20. Combined repressor and activator

  21. DNA looping and gene regulation DNA Lac repressor (Goodsell) (Muller-Hill et al.)

  22. States and weights

  23. Operator quality Vilar and Leibler ‘03

  24. Why is Looping Useful? Vilar and Leibler ’03 • For in vivo concentrations (R≈10) repression is better than the strongest single site by a factor of ten. • For high number of repressors the state wins, giving the same repression as a single site. • The plateau between the two regimes is robust with respect to fluctuations in R.

  25. DNA looping

  26. Combinatorial control of a promoter Bintu et al. ’05