Computational Systems Biology
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University of Washington
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Systems and Synthetic Biology

Start Date for Spring Term: January 4th

End Date for Spring Term: March 12th.

This page describes the systems and synthetic biology elective course, 424.

UW General Catalog Course Description:

This course offers an advanced course on system and synthetic biology. The course is designed for seniors and/or graduates who have an interest in bioengineering at the cellular network level. Topics include kinetics, modeling, stoichiometry, control theory, metabolic systems, signaling, motifs and a one week project. All topics are set against problems in synthetic biology.

To access pdf or download material, right click and save-as. Direct clicking over the item does not appear to work on this wiki.

General

Intro Slides

Recent General Review Article, Dec 2009

Initial Assignment: Prepare a poster on Phage Lambda, explaining the parts, life cycle and control systems.

Due by 22 Jan, 2010 at 11.45. For those who have access to the drop box on catalyst, use that, otherwise email me the assignment.

I found a section of reasonable posters at this site, they may give you ideas:

http://www.apple.com/ca/science/poster/

Gene Expression Kinetics

Reading Material

Modeling

TinkerCell

Systems Biology Workbench

Jarnac notes including stochastic simulations

Basic concepts:

  1. Differential Equation (ODE) Models
  2. Concept of state variables and boundary species
  3. Stoichiometry and stoichiometry matrices
  4. Time course behavior and steady states
  5. Taking into account stoichiometry when writing out the ODEs

More advanced concepts:

  1. Sensitivity Analysis
  2. Frequency Analysis
  3. Stability and Bifurcation Analysis
  4. Observability
  5. Network Structure Properties from Stoichiometry

Modules and Motifs

Reading material

Feed forward and other configurations:

Network motifs: theory and experimental approaches, Nature Reviews Genetics, 8, 450 (2007)

Uri Alon's very nice book: “An Introduction to Systems Biology”. Hint: some parts of the book are on google books.

Miscellaneous Circuits:
Toggle Switches:
Oscillator Circuits:

Synthetic Oscillator

Mammalian Synthetic Biology - Review

Another Review on Mammalian Synthetic Biology

Mammalian Oscillator

Ecoli Oscillator

Synchronized Genetic Clocks: Hasty

Slides describing Competence Circuit in Bacillus

Hint for final project: As you look at these and other papers, make a list of the parts that the authors have used in building their networks. In your final project you will have to suggest some real parts to build your device, such a list will therefore be useful.

Control Analysis

Midterm

The midterm will be held on 8th of February in class at the normal time of 11.30am.

Midterm Content:

  1. Gene regulatory kinetics
  2. Building models including, constructing the stoichiometry matrix
  3. Motifs and their properties

Reading material for the midterm:

  1. PowerPoint slides
  2. Handout on gene regulatory kinetics
  3. Handout on model building
  4. The following papers:
    1. Network motifs: theory and experimental approaches, Nature Reviews Genetics, 8, 450 (2007)
    2. On schemes of combinatorial transcription logic, Nicolas E. Buchler, Ulrich Gerland, and Terence Hwa, PNAS April 29, 2003 vol. 100 no. 9 5136-5141
    3. Quantitative model for gene regulation by lambda phage repressor, G K Ackers, A D Johnson, and M A Shea, PNAS February 1, 1982 vol. 79 no. 4 1129-1133
    4. Synthetic biology: understanding biological design from synthetic circuits, Shankar Mukherji and Alexander van Oudenaarden, Nature Reviews Genetics 10, 859-871 (December 2009)

Syllabus

Week

Lecture Topics                                                  

1

Introductory Week: Genetic Circuits; Parts; Assembly Methods; Standards and Software; Introductory Case Studies

2

Kinetics: Michaelian, Gene Regulatory and Allosteric Kinetics; Generalized Kinetics

3

Stoichiometry and the Compact Notation; Modeling Techniques, ODE, Stochastic; Steady State and Bifurcation Analysis

4

Stoichiometry: Flux constraints, Elementary modes; Flux Balance Analysis, Moiety Conservation and Impact on Modeling

5

Control Theory for Synthetic Biology: Small Signal Analysis; Frequency Analysis; Application of Microfluidics; Phase Shifts and Amplification

6

Control Theory: Introducing Domain, Impedance, Fan-Out and Modularity in Synthetic Biology. Stability Analysis, Robustness, Oscillations and Bistability

7

Control of Metabolic Systems: Basic Principles of Flow Control; Front Loading of Control; Optimal Allocation of Protein in Flow Control; Tracking and Control Strategies.

8

Control of Metabolic Systems: Effects of Feedback in Simple and Complex Architectures; Metabolic Engineering Case Studies

9

Signaling and Motifs: Introduction to Signaling Pathways; Design Issues In Protein Pathways; Case studies

10

Term Design Project

 

 

 

Prerequisites: Basic Biology, Math (Basic Calculus and Matrices) and Programming (eg Matlab)

Overview:

This course offers an introduction and advanced course on system and synthetic biology. The course is designed for seniors and/or graduates who have an interest in bioengineering at the cellular network level. The first week will include a basic introduction to synthetic biology. The remainder of the course will then cover a variety of more advanced topics including metabolic engineering, control engineering theory applied to biology and signaling networks. The course will be interspersed with case studies illustrating the work. Students will be introduced to the field of synthetic biology and its application in systems biology and applied engineering. Students will understand in quantitative terms the basic principles of operation of regulation at the cellular level, including metabolic, signaling and gene networks; discover how cellular networks can be reengineered, taking examples from the iGEM competitions and applications such as metabolic engineering; learn how to build computer models of cellular networks; appreciate that cellular systems are very noisy and how these can be modeled and studied experimentally.

Possible Textbooks:

No official text book but the following can be recommended:

  • An Introduction to Systems Biology: Design Principles of Biological Circuits (ISBN-10: 1584886420), U Alon
  • Systems Biology: A Textbook. (ISBN-10: 3527318747) Klipp et al
  • Engineering Genetic Circuits (ISBN-10: 1420083244) Myers.

Learning Objectives:

  • To understanding the basic principles of building models of cellular networks.
  • Be able to choose and apply appropriate analytical and numerical tools to solve a given problem.
  • Be able to go from a functional requirement to a concrete design.
  • To apply principles of control theory to problems in synthetic biology.
  • To understand the operating principles of genetic, signal and metabolic systems.

ABET Outcomes

  • a. An ability to apply knowledge of mathematics, science, and engineering
  • c. An ability to design a system, component, or process to meet desired needs within realistic constraints such as economic, environmental, social, political, ethical, health and safety, manufacturability, and sustainability
  • d. An ability to function on multi-disciplinary teams
  • k. An ability to use the techniques, skills, and modern engineering tools necessary for engineering practice (i.e. computer and analytical equipment)

Design Component:

The course incorporates a team based design component. Teams are expected to provide the designs for a novel cellular molecular device. Teams will work in pairs and present their work in class and in the form of a final report. The report will be expected to include the following sections (See design project template for details): Title, Author names and date; Abstract; Introduction; Overview; Product Design Spec; Internal Design Spec; Validation and Test Implementation (in silico); in vivo Implementation Details including estimated construction costs, time lines and suggested assembly methods; Conclusion; References.

Format document for design project final_project_report_2010.pdf

Course Grading:

  • 30% Homework
  • 20% Midterm

And one of the following:

* 50% Design Project
* 50% Final exam

Course Schedule:

Three hours of lecture per week

 
sysbio/labmembers/498a_systems_and_synthetic_biology_winter_2010.txt · Last modified: 2010/03/03 11:10 (external edit)
 

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