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Lecture 6: The Mathematics of Recruitment

Lecture 6: The Mathematics of Recruitment. Rob Phillips California Institute of Technology. (Beautiful work of David Goodsell). The Case of Activation. (Nissley et al.). All Together Now: The Lac Operon. Our goal: mathematize the story told by all of these cartoons.

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Lecture 6: The Mathematics of Recruitment

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  1. Lecture 6: The Mathematics of Recruitment Rob Phillips California Institute of Technology (Beautiful work of David Goodsell)

  2. The Case of Activation (Nissley et al.)

  3. All Together Now: The Lac Operon Our goal: mathematize the story told by all of these cartoons. In particular, compute the probability of RNAP binding as a function of concentration of all the other molecular actors.

  4. Repression in the Lac Operon: The Experimental Backdrop (Muller et al.)

  5. Oehler et al. (1994) Repression • Single operator case We fit the first point of each set

  6. Lac Repressor: Different Views (Beautiful work of David Goodsell)

  7. This is the only point used to fit the looping energy Repression and Looping I

  8. Operator quality Vilar and Leibler ‘03

  9. Operator distance

  10. Beta-Galactosidase Activity (Dove et al.) (Lawrence et al.) Ian B. Dodd et al. Genes Dev. 2004; 18: 344-354

  11. The Regulation Factor

  12. Synergistic Activation Interaction through DNA bending No interaction

  13. DNA in a Tight Squeeze: Case Studies (Goodsell) (Bustamante et al.) Viral DNA Packing Eukaryotic DNA Packing Gene Regulation 15 microns of data confined to 50nm capsid. Packing forces related to infection mechanism. DNA in nucleus wound around protein – histone octamer. Radius of curvature comparable to DNA thickness. DNA-binding proteins such as Lac repressor loop DNA. Ubiquitous in prokaryotes and eukaryotes.

  14. Genes in Eukaryotes

  15. Nucleosomes

  16. Beams and Biology

  17. Kinematics of Beam Bending

  18. Nucleosome Structure Continued (Richmond and Davey)

  19. Experiments on Nucleosome Accessibility

  20. Accessibility vs Burial Depth

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