Cell and Systems Modeling - Fall, 2018

Course Directors 

Jim Faeder (University of Pittsburgh) - faeder@pitt.edu - BST3 3082 - Office hours: Fridays, 1-2 pm.
Robin Lee (University of Pittsburgh) - robinlee@pitt.edu - BST3 3083 - Office hours: after class, 2-3 pm on Friday Sep. 21 & 28.
Jianhua Xing (University of Pittsburgh) - xing1@pitt.edu - BST3 3084 - Office hours: by appointment.

For discussion of homework or course content, please use our Piazza page
To reach course instructors directly, please send email to csm2018-instructors@googlegroups.com

Teaching Assistants

Jonathan King - jok120@pitt.edu  - BST3 3076 Cubicle #14 - Office hours: Tuesdays, 12-1 pm. 
Laura Tung - ltung@andrew.cmu.edu - GHC 7409 - Office hours: Fridays, 2-3 pm.

Course Description

CMU 02-730 & PITT CMPBIO/MSCBIO 2040

This course will introduce students to the theory and practice of modeling biological systems from the molecular to the population level with an emphasis on intracellular processes. Topics covered include kinetic and equilibrium descriptions of biological processes, systematic approaches to model building and parameter estimation, analysis of biochemical circuits modeled as differential equations, modeling the effects of noise using stochastic methods. A range of biological models and applications will be considered including gene regulatory networks cell signaling, molecular motors, and developmental biology. Weekly recitations will introduce computational skills and provide students hands-on experience with methods and models presented in class. Course requirements include weekly homework assignments, a final project, and a take-home exam.

Prerequisites

The course is designed for graduate and upper-level undergraduate students with a wide variety of backgrounds.  The course is intended to be self-contained but students may need to do some additional work to gain fluency in core concepts.  Students should have a basic knowledge of calculus, differential equations, and chemistry as well as some previous exposure to molecular biology and biochemistry.  Experience with programming and numerical computation is useful but not mandatory.  Laboratory exercises will use Matlab as the primary modeling and computational tool augmented by additional software as needed.

Course Requirements

  • Homework (30%) 
    • Weekly graded assignments based on class lectures and readings.
    • Lateness policy: 25% credit deducted per day for late assignments. Each student will receive 3 days of grace period credit to be distributed over assignments throughout the semester.  Further extensions will be granted only under extreme circumstances.  All assignments must be completed to pass the course.
    • Cheating policy: All work must be your own.  Unauthorized collaboration or plagiarism will result in a failing grade and will be reported to your academic advisor and dean. 
  • Project (40%) 
    • Model and analyze a biological network; or 
    • Design and implement a simulation or analysis tool for biological modeling.
    • A project proposal will be due mid-semester. See Proposals for more information.
    • The project will be graded by peer-review panels in the final week of the course and participation in this review process will count for 25% of the project grade.
    • Cheating policy: All work must be your own and novel.  Unauthorized collaboration, falsified data, or plagiarism will result in a failing grade and will be reported to your academic advisor and dean.
    • Double dipping policy:  You may not re-use data, reports, manuscripts, or publications from your research or from other courses. However, you  may extend your previous work, as long as you inform the instructors that you are doing so. Please contact the instructors if you have any questions regarding this policy.
  • Take-Home Exam (30%) 
    • One week for a problem set covering course topics. 

Meeting Times

First day of class: Tuesday, August 28, 2018
Lectures: Tu,Th 10:30am - noon, BST3 3073* 
Recitation/Lab: Fr 3:30-5 pm, 
BST3 3073*


* BST3 = Biomedical Science Tower 3 (click to see on Google maps). Building is access-controlled. If you have a Pitt ID with and RFID chip, you can ask to have building access added. If you are not a Pitt student, you will have to arrange to meet someone with access to escort you or have the guard call the main department number.

Required Text

Physical Biology of the Cell, 2nd edition (PBOC2). Reading and homework assignments will be drawn from this book. It has not been pre-ordered at campus bookstores, so we suggest you order it from your favorite online purveyor.

Recommended Texts

The following books may be useful as supplements to the main text and lectures.

  • Uri Alon, An Introduction to Systems Biology: Design Principles of Biological Networks, Chapman and Hall/CRC, ISBN-13: 978-1584886426.
  • Chris Myers, Engineering Genetic Circuits, Chapman and Hall/CRC, ISBN-13: 978-1420083248.
  • E. Klipp, R. Herwig, A. Kowald, C. Wierling, and H. Lehrach, Systems Biology in Practice: Concepts, Implementation, and Application, Wiley-VCH, ISBN-13: 978-3527310784. (Note: an updated version called Systems Biology: A Textbook is also now available.)
  • D. Kaplan and L. Glass, Understanding Nonlinear Dynamics. Springer. 1995. ISBN-13: 978-0387944401.
  • Eberhard Voit, A First Course in Systems Biology, Garland Science. 2012. ISBN-13: 9780815344674
  • Sarah Otto and Troy Day, A Biologist's Guide to Mathematical Modeling in Ecology and Evolution Princeton University Press,  ISBN-13: 978-0691123448
  • Athel Cornish-Bowden, Fundamentals of Enzyme Kinetics, 4th Edition (publisher's web site).

WeekDayDateTitlePresenterReadingTopics
1Tuesday8/28/2018Intro to systems biologyLeepapersIntros, course requirements, definitions, issues, examples
Thursday8/30/2018BionumbersXing3,4
Friday8/31/2018RecitationTAIntroduction to Matlab
2Tueday9/4/2018HW 1 due
Tuesday9/5/2018Introduction to thermodynamics of cellsFaeder5
Thursday9/7/2018Equilibrium Binding 1Faeder6.1-6.2Statistical mechanics: counting and the Boltzmann distribution.
Friday9/8/2018RecitationTAMatlab: solving equations numerically & symbolically
3
Tuesday9/11/2018Equilibrium Binding 2Faeder6.3-6.4Thermodynamics, law of Mass Action, Shannon entropy
Thursday9/13/2018Equilibrium Binding 3Faeder7.1-7.3Cooperativity, two-state systems, MWC model
Friday9/14/2018RecitationTA
4Monday9/17/2018HW 2 due
Tuesday9/18/2018Dynamics of Transcriptional Motifs 1LeeAlon Ch 1-3Selected topics of transcriptional networks and 1-node motifs  
Thursday9/20/2018Dynamics of Transcriptional Motifs 2LeeAlon Ch 4-6Larger network motifs
Friday9/21/2018RecitationTA
5Monday9/24/2018
Tuesday9/25/2018Dynamics of Transcriptional Motifs 3LeeAlon Ch 4-6Biological perception and fold-change detection
Thursday9/27/2018Project overview / avidity / dimerizationFaeder15.1-15.2Project overview, antibody binding and avidity, ligand-induced dimerization model
Friday9/28/2018RecitationTA
6Monday10/1/2018
Tuesday10/2/2018Biochemical Kinetics 1Faeder15.3-15.4Avidity calculation, elementary kinetics and building blocks
Thursday10/4/2018Boolean modeling
Miskov-Zivanov
Friday10/5/2018RecitationTA
7Monday10/8/2018HW 3 due
Tuesday10/9/2018Enzyme kinetics19.3Enzyme kinetics, 
Thursday10/11/2018Phosphorylation mechanismsFaeder19.3Phosphorylation cascades, toggle switch
Friday10/12/2018RecitationTA
8Monday10/15/2018Project proposals due
Tuesday10/16/2018ODE's in 2D, linear and nonlinear  Faeder  19.3
 
Stability analysis, toggle switch, limit cycle oscillator
Thursday10/18/2018No class (Science 2018)


Friday10/19/2018Recitation
9Monday10/22/2018
Tuesday10/23/2018Parameter estimation GuptaBayesian methods
Thursday10/25/2018Stochastic dynamicsFaeder19.3Chemical master equation, Gillespie algorithm, stochastic switching
Friday10/26/2018RecitationTA
10Monday10/29/2018Proposal resubmissions due
Tuesday10/30/2018Macromolecules 1Xing8
Thursday11/1/2018DiffusionXing13
Friday11/2/2018RecitationTA
11Monday11/5/2018HW 4 due
Tuesday11/6/2018Cell fate decisionsXing
Thursday11/8/2018Cell fate decisions 2Xing
Friday11/9/2018RecitationTA
12Monday11/12/2018
Tuesday11/13/2018Spatial dynamics/ robust patterningFaeder20.1-20.3Reaction-diffusion, morphogen gradients, Turing patterns
Thursday11/15/2018Robust sensing in bacterial chemotaxisFaeder  Alon, Ch. 7 
Friday11/16/2018RecitationTA
13Monday11/19/2018HW 5 due
Tuesday11/20/2018TBDLee/Xing/Faeder
Thursday11/22/2018No class (Thanksgiving)
Friday11/23/2018No recitation (Thanksgiving)
14Monday11/26/2018No HW (Projects)
Tuesday11/27/2018Case study Xing
Thursday11/29/2018No class
Friday11/30/2018Final Projects Reports Due
15Monday12/3/2018Preliminary project scores due
Tuesday12/4/2018Project reviewingLee/Xing/Faeder
Thursday12/6/2018Project reviewingLee/Xing/Faeder
Friday12/7/2018Take home exam distributed
16Wednesday12/12/2018Take home exam due

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