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Systems and Synthetic Biology

Winter 2011

Start Date for Spring Term: January 3th
End Date for Spring Term: March 11th

This page describes the systems and synthetic biology elective course, 524/424.

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.

One day a week (except for the first week) will be devoted to a journal club where students are expected to discuss the latest research and application papers in synthetic biology.

General Introduction

List of Possible Papers for Journal Club

Discussed papers:

Syllabus (Updated for 2011)

Week

Lecture Topics

1

Introductory Week: Lambda Phage; Assembly Methods

2

Stoichiometry and the Compact Notation; Flux constraints, Elementary modes; Flux Balance Analysis

3

Stoichiometry: Moiety Conservation Behavioral effects, Modeling

4

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

5

Stochastic Systems in Synthetic Biology: Stochastic switching, Stochastic focusing, Single events and Multiplicative noise effects.

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, Control and other Strategies in Metabolic Engineering

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

 

 

 

Videos

These are short (< 5 min) videos.

Basic Concepts

Software Tutorials

Stoichiometric Networks

Lecture Notes

Weeks 1, 2, 3 and 4

Slides: Structural Analysis: Flux Relationships

Slides Structural Analysis: Moiety Conservation

Assembly Methods in Synthetic Biology

Additional Reading:

Definition of a Pathway

Trends in Biotechnology Article on Elementary Modes

The incorrect result in Wednesday's class was due to attempting to minimizing the objective function rather than maximize, here is the corrected LP code:

/* Objective function */
max: 0.5*v9 + 0.75*v8;

/* Steady State Constraints */
v1 - v2 - v3 = 0;   /* A */
v2 - v4 - v6 = 0;   /* B */
v3 + v6 - v7 = 0;   /* C */
v6 - v9 = 0;        /* F */
v5 - v4 = 0;        /* E */
2 v4 - v8 + v7 = 0; /* D */

/* Variable bounds */
v1 = 10;
v5 = 6;
v3 >= 1;

Optimal distribution is: v1 = 10; v2 = 9; v3 = 1; v4 = 6; v5 = 6; v7 = 4; v8 = 16; v9 = 3

The optimal flux of 16 and 3 going through v8 and v9 respectively is correct given that the computed maximum flux was 13.5. This matches the objective function: 0.5*v9 + 0.75*v8

Assignment:

  1. Read sections 4.5 and 4.6
  2. Do exercises at end of chapter 2
Week 5

Modeling Standards, Software and Repositories

  • SBML
  • CellML
  • BioModels
  • SBOL Semantic
  • SBOl Visual

Introduction to Design Motifs

Week 6
Reading material
Toggle Switches:
Oscillator Circuits:
Week 7

TinkerCell

Week 8
Week 9

Basic Control in Metabolic Pathways

MidTerm

MidTerm will be on the 11th of February

The following topics that will be in the test:

  1. Stoichiometry
  2. Left Null Space (Gamma)
  3. Right Null Space (K)
  4. Flux Balance Analysis
  5. Acronyms
  6. Elementary Modes

There will be two simple computer related questions on:

  1. Flux Balance Analysis
  2. Elementary Modes

Assignments

Lambda Phage Project (Due before the midterm)

Develop a means to explain the regulatory operation of Lambda phage. A selection of approaches to this includes:

  1. Computer Animation or Simulation
  2. Lego model of a simple regulated gene circuit
  3. Electrical analog of part of the circuit
  4. Paper, wooden etc model to explain lambda phage
  5. Flip book (i.e a movie)
  6. Skit (if you must) - must provide script

Any materials required (eg Lego parts, electrical components) will be reimbursed to the student provided receipts are kept.

For an example of a Lego model explaining a complex mechanism see the following video (Lego Antikythera Mechanism):

http://www.youtube.com/watch?v=RLPVCJjTNgk

An another example (Simple Arithmetic Computer):

http://www.youtube.com/watch?v=SYi9sJkS19Q

What you can't do is create a poster but you may work in a team of up to two people.

Reverse Engineer a Gene Regulatory Circuit

Given the following gene regulatory circuit:

Circuit Diagram

answer the questions:

  • Identify the various parts in the circuit and indicate what they do.
  • Determine the overall function of the circuit.

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.
  • Introductory Enzyme Kinetics for Systems Biology. Sauro HM (http://sysbiobooks.com/)

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 Download

Course Grading:

  • 20% Homework
  • 20% Lambda Phage Project
  • 20% Midterm plus Journal Club Participation
  • 40% Design Project

Course Schedule:

Two hours of lecture per week plus one hour of journal club

 
sysbio/labmembers/498a_systems_and_synthetic_biology_winter_2011.txt · Last modified: 2011/03/01 17:36 (external edit)
 

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