麻省理工大学：《Systems Biology》Wrapping up E coli chemotaxis (L7& L8)

Wrapping up E coli chemotaxis (L7& L8) Main points of last 2 lectures L7: Biological background what is the function of the individual molecules L8: modeling of all possible chemotactic reactions why doesn't this model reproduce experimentally observed perfect adaptation L8-9: strip down full model to essentials based on assumptions that are experimentally justified (or sometimes not

Wrapping up E. coli Chemotaxis (L7 & L8) Main points of last 2 lectures: L7: Biological background what is the function of the individual molecules ? L8: modeling of all possible chemotactic reactions why doesn’t this model reproduce experimentally observed perfect adaptation ? L8-9: strip down full model to essentials based on assumptions that are experimentally jus tified (or sometimes not) reduction 1

Figure 1A in Mittal, N, E.O. Budrene M. P. Brenner, and A. van oudenaarden Motility of Escherichia coli cells in clusters formed by chemotactic aggregation. "Proc Nat/ Acad SciUSA 100,no.23(NoV11,2003):13259-63 Copyright(2003)National Academy of Sciences, U.S.A

100, no. 23 (Nov 11, 2003): 13259-63. Copyright (2003) National Academy of Sciences, U. S. A. Figure 1A in Mittal, N., E. O. Budrene, M. P. Brenner, and A. Van Oudenaarden. "Motility of Escherichia coli cells in clusters formed by chemotactic aggregation." Proc Natl Acad Sci U S A

Images removed due to copyright considerations

Images removed due to copyright considerations. 3

Absence of chemical attractant Tumble Run Image by MIT OCW

Absence of chemical attractant 4 Image by MIT OCW. Tumble Run

Presence of chemical attractant Attractant Tumble Run Chemical Gradient Sensed in a Temporal manner Image by MIT OCW

Presence of chemical attractant 5 Image by MIT OCW. Tu m ble C h e mic al Gra die nt S e n s e d in a Te m p oral M a n n er R u n Attracta nt

+ATT ATT flagellar +cH3- 器 motor MCPs MCPs CW -CH3 ATP ATP ADP B P Figure 1 of Spiro, P A, J. S. Parkinson and H. G. othmer A model of excitation and adaptation in bacterial chemotaxis Proc Nat/ Acad SciUSA 94, no 14 (Jul 8, 1997): 7263-8 Copyright(1997) National Academy of Sciences, U.S.A key player: Tar-CheA-CheW complex

6 Figure 1 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8. "A model of excitation and adaptation in bacterial chemotaxis." key player: Tar-CheA-CheW complex Copyright (1997) National Academy of Sciences, U. S. A

Phosphorylation Methylation Bindingintermediate gand 午T SLOW-T2 4 fast 3p·FLT4 Y B Figure 2 of Spiro, P. A, J. S. Parkinson, and H. G. Othmer A model of excitation and adaptation in bacterial chemotaxis Proc Nat/ Acad SciUSA94, no 14 ( Jul 8, 1997): 7263-8 Copyright (1997) National Academy of Sciences, U.S.A

fast slow intermediate Copyright (1997) National Academy of Sciences, U. S. A. Figure 2 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8. "A model of excitation and adaptation in bacterial chemotaxis

First reduction ff4 p p LT LT Kfrr(l) f effl (L) Kff(L) f2 KffA (L e 3 LT LT 3 keffi(L) ff [3] in steady state C≡ [2]+[3] k,=(1-c)k eff1 (L)+ak pnos eff2

T2 LT2 T3 LT3 T2p LT2p T3p LT3p keff1(L) keff2(L) keff3(L) keff4(L) keff3(L) keff4(L) kpt kpt First reduction 1-α α [2] [3] [3] α + in steady state: ≡ 8 (L) eff2 (L) αk eff1 (1 α)k phos k = − +

perfect adaptation for small L K/k ef128 safe zone perfect adaptation for large L K/ eff18 0 6 8 10 K. L fine-tune: net phoshorylation rate and keff and keff2 so that a falls in safe zone

safe zone net phosphorylated rate perfect adaptation for large L perfect adaptation for small L 9 fine-tune: net phoshorylation rate and keff1 and keff2 so that α falls in safe zone

no safe zone never perfect adaptation K/ eff2 8 K/K eff18 0 10

net phosphorylated rate no safe zone never perfect adaptation 10