1. BCB 570 Spring 20081 Signal Transduction Julie Dickerson Electrical and Computer Engineering

2. BCB 570 Spring 20082 Seminar Dr. Craig Benham, Department of Mathematics, Department of Biomedical Engineering, University of California, Davis, Title: "DNA Structural Transitions and Transcriptional Regulation in E. coli" Date: Thursday, April 3 Time: 2:10 - 3:00 p.m. Place: 1652 Gilman Hall

3. BCB 570 Spring 20083 Outline What are signal transduction networks? Basic Motifs in modeling Stochastic modeling

4. BCB 570 Spring 20084 Readings Chapter 6 in Textbook

5. BCB 570 Spring 20085 Introduction Cells sense extracellular signals Stimuli: heat, light, drought Signals: hormones, pheromones Concentration levels of key metabolites, glucose, cAMP, calcium ions Chemically looks similar to metabolic modeling: modify, produce or degrade substances, activation or inhibition

6. BCB 570 Spring 20086 Modeling: flow of information Metabolism Based on mass transfer. Characterized by enzymes Involves large quantities of material (  Signaling Basis of modeling is information transfer Complex formation and change Based on number of molecules (10-10 4)

7. BCB 570 Spring 20087 Components of signaling Signal, what is being sent Receptor: way to sense a signal Target molecules that mediate cellular response

8. BCB 570 Spring 20088 From course text, figure 6.1 Signal Transduction Animation

9. BCB 570 Spring 20089

10. 10 Key Mechanism Receptor-Ligand Interactions

11. BCB 570 Spring 200811 Receptor-Ligand Interactions Dissociation Constant, range 10 -12 -10 -6 M In reality, this can be regulated by cell to modulate the response and receptor activity

12. BCB 570 Spring 200812 More Detailed Model: Receptor Dynamics Notation R i Inactive Receptor R S Susceptible R a Active

13. BCB 570 Spring 200813 Discussion Model degradation terms as linearly dependent on substrate concentration Receptor activation may depend on ligand concentration.

14. BCB 570 Spring 200814 Dimer Receptors For example: Dimeric protein with two identical binding sites. Binding of first ligand facilitates binding of second ligand

15. BCB 570 Spring 200815 If Receptor Dimer/Oligomer Equation for cooperative binding n is the Hill coefficient Implies complete cooperativity (every protein is either empty or fully bound)

16. BCB 570 Spring 200816 Key Components G protein Cycles Phosphorelay systems MAP kinase cascades Jak-Stat pathways

17. BCB 570 Spring 200817 Basic mathematical motifs Represent action pairs of protein synthesis and degradation Phosphorylation and dephosphorylation General Form, change in responder, R, depends on concentration of signal, S and responder, R:

18. BCB 570 Spring 200818 Linear Synthesis and degradation

19. BCB 570 Spring 200819 Single Loop Phosphorylation, dephosporylation

20. BCB 570 Spring 200820 Double Loop

21. BCB 570 Spring 200821 Combinations Perfect Adaptation: signal pathway has a transient response to changes in signal strength, steady state response is independent of S. Combining linear response with a second pathway

22. BCB 570 Spring 200822 Positive Feedback (e) R activates protein E, EP enhances synthesis of R (f) R inhibits E and E promotes degradation of R

23. BCB 570 Spring 200823 Positive Feedback Negative Feedback R inhibits protein E that catalyzes its synthesis of R Signal, S, is the demand for R, maintains a constant response

24. BCB 570 Spring 200824 Examples

25. BCB 570 Spring 200825 G Proteins Bind Guanine Nucleotides GDP and GTP 3 different subunits Cell surface receptor Movie G protein Movies

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27. BCB 570 Spring 200827 Phosphorelay System Phosphate is passed down the chain

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30. BCB 570 Spring 200830 Regulating immune responses and cellular homeostatis Jakstat Movies