SB3-2009

From BaderLab

580.429, Systems Bioengineering 3, Systems Biology from Molecules to Cells

Contents 1 Instructor Information 2 Openers 3 Linear Systems in Signal Transduction and Gene Regulation 4 Non-linear, Stochastic, and Spatial Systems 5 Large-Scale Networks 6 Supplemental Material 7 Discussion Sections 8 Homeworks 9 Quizzes 10 Exams 11 Final Exam

[edit] Instructor Information

Prof. Joel S. Bader, 201C Clark Hall

TAs, 1st half: Rahul Karnik, David Simcha

TAs, 2nd half: Rahul Karnik, An-Chi Wei

Office hours: TAs during recitation sections; Prof. after lecture and by appointment

Main Lecture: Maryland 110, Mon and Wed 12-1:15 PM

Key dates

• Exam 1: Wed. Oct. 14
• Exam 2: Wed. Nov. 18
• Final: Working to avoid conflict with Optimization

[edit] Openers

• Lecture 0, Sep. 2: Course policies. Grading. Intellectual honesty. Prerequisite knowledge. Software.
• Lecture 1, Sep. 2: MAPK signal transduction and review of signals and systems. The basic model for a biological switch. Reading: Hersen et al. PNAS 2008 Signal processing by the HOG MAP kinase pathway. Salt Vampire from Star Trek episode "The Man Trap".

[edit] Linear Systems in Signal Transduction and Gene Regulation

• Lecture 2, Sep. 7: No class (Labor Day)
• Lecture 3, Sep. 9: See Lecture 0 for an update on course policies. Why this class. Modeling cellular switches. Time-response of a linear switch. A problem-solving pattern: analytical, numerical, stochastic.
• Falls Road 15K, Sep. 13: Free breakfast for anyone who finishes ahead of Prof. Bader.
• Lecture 4, Sep. 14: Outline of L4. Inverse LTs using contour integrals. Gain and phase delay.
• Lecture 5, Sep. 16: System identification. Reverse engineering: components, structure, parameters.
• Lecture 5, continued, Sep. 21: Continue with Lecture 5 notes
• Lecture 6, Sep. 23: Model selection. Supplemental reading: Schwarz 1978.
• Lecture 8, Sep. 28: (no class)
• Lecture 9, Sep. 30: Caffeine signal transduction. Supplemental reading: Bastia, Lindskog
• Fri Oct 1: Discussion sections at 12 PM meet together in 111 Mergenthaler
• Lecture 10, Oct. 5: Generating functions. Sensitivity analysis. Will this be on the exam.
• Lecture 11, Oct. 7: Sensitivity analysis

[edit] Non-linear, Stochastic, and Spatial Systems

• Lecture 12, Oct. 12: Stem cells and cell fate as a model. Non-linearities from saturation, cooperativity / thresholds, and stochasticity.
• Lecture 13, Oct. 14: Exam 1
• Lecture 14, Oct. 19: Timescale separation and cooperativity. Reading: Alon Ch 1, 2, Appendix A.
• Lecture 15, Oct. 21: Hill functions as A/D or A/Binary converters, logic approximation. Nonlinear to piecewise linear. Serial circuit as a delay element. Evidence for positive feedback.
• Lecture 16, Oct. 26: Autoregulation. Positive autoregulation, strong and weak. Negative autoregulation and proportional control.
• Lecture 17, Oct. 28: Combinatorial regulation. Statistics / information theory. Biophysics.
• Lecture 18, Nov. 2: Mixed feedback. Lateral inhibition. Statistical cell fate. Delta-Notch signaling. Noise in gene expression. Gillespie algorithm.
• Lecture 19, Nov. 4: Stochastic models for open loop and closed loop gene regulation.
• Lecture 20, Nov. 9: Morphogen gradients and dorsal-ventral patterning. European Flag model. Stochastic model for diffusion.
• Lecture 21, Nov. 11: Diffusion PDE. Cell fate boundaries. Sensitivity analysis. Transients and diffusion times.
• Lecture 22, Nov. 16: Kinetic proofreading

[edit] Large-Scale Networks

• Lecture 23, Nov. 18: Exam 2
• Lecture 24, Nov. 23: Network models: small-world, scale-free, clustering, motifs
• Lecture 25, Nov. 25: No class (Thanksgiving Vacation)
• Lecture 26, Nov. 30: Network search, missing edges, graph diffusion. Metabolic networks, linear programming.
• Lecture 27, Dec. 2:
• Lecture 28, Dec. 7: Last class meeting

[edit] Supplemental Material

• Hersen et al. PNAS 2008 Signal processing by the HOG MAP kinase pathway.
• Mettetal et al. Science 2008 Frequency dependence of osmo-adaptation in Saccharomyces cerevisiae.
• Salt Vampire from Star Trek episode "The Man Trap".
• Schwarz Annals of Statistics 1978 Estimating the dimension of a model.
• Your brain on drugs.
• Your brain on caffeine: Lindskog et al. 2002 Nature, Bastia 2003 Science Signal Transduction.
• Embryonic / pluripotent stem cell reprogramming: Yu et al. Science 2007, Wisconsin group. Takahashi et al. Cell 2007, Kyoto group. Vogel and Holden Science 2007, mini-review.
• Delta/Notch signaling: Spyros A-K et al. Science 2009.
• Stochastic gene expression: Elowitz et al. Science 2002. McAdams and Arkin PNAS 1997. Raser and O'Shea Science 2005. Newman et al. Nature 2006.
• Gillespie algorithm: Gillespie J Comp Phys 1976. Friendly implementation in R, Pineda-Krch GillespieSSA 2008 J Stat Soft.

[edit] Discussion Sections

• Discussion 1, Sep. 4.
• Discussion 2, Sep. 11. Laplace transform review.
• Fri Oct 1: Discussion sections at 12 PM meet together in 111 Mergenthaler

[edit] Homeworks

1. HW1 Numerical solution of an ODE. HW1 key.
2. HW2 due Fri. Sep. 18 by 1 PM. HW2 key. HW2 bonus question, giving the full answer for the frequency-domain problem and the simplified result but not the method ("then a miracle happens" between pages 4 and 5) for the time-domain problem.
3. HW3 due Wed. Sep. 30 Mon. Oct. 5 by 12 PM. HW3 key.
4. HW4 due Mon. Oct. 5 Wed. Oct. 7 by 12 PM. HW4 key.
5. HW5 due Mon. Oct. 12 by 12 PM. HW5 key.
6. HW6 due Mon. Oct. 26 by 12 PM. HW6 key.
7. HW7 due Mon. Nov. 9 by 12 PM. HW7 key.
8. HW8 due Mon. Nov. 16 by 12 PM. HW8 part 1 key.

[edit] Quizzes

1. Quiz 1 key
2. Quiz 2 key
3. Quiz 4 key
4. Quiz 5 makeup
5. Quiz 6 key
6. Quiz 7 key
7. Quiz 8 key

[edit] Exams

1. Exam 1
   • Pre-exam: Exam 1 equation sheet, Exam 1 review sheet
   • Exam 1 questions
   • Exam 1 key
2. Exam 2, scheduled for Wed. Nov. 18
   • Exam 2 review

[edit] Final Exam

• Review Session: TBA
• Final Exam: TBA (being scheduled to avoid conflict with Optimization)