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.
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.
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TinkerCell
Systems Biology Workbench
Jarnac notes including stochastic simulations
Basic concepts:
Differential Equation (ODE) Models
Concept of state variables and boundary species
Stoichiometry and stoichiometry matrices
Time course behavior and steady states
Taking into account stoichiometry when writing out the ODEs
More advanced concepts:
Sensitivity Analysis
Frequency Analysis
Stability and Bifurcation Analysis
Observability
Network Structure Properties from Stoichiometry
The midterm will be held on 8th of February in class at the normal time of 11.30am.
Midterm Content:
Gene regulatory kinetics
Building models including, constructing the stoichiometry matrix
Motifs and their properties
Reading material for the midterm:
PowerPoint slides
Handout on gene regulatory kinetics
Handout on model building
The following papers:
Network motifs: theory and experimental approaches, Nature Reviews Genetics, 8, 450 (2007)
On schemes of combinatorial transcription logic, Nicolas E. Buchler, Ulrich Gerland, and Terence Hwa, PNAS April 29, 2003 vol. 100 no. 9 51365141
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 11291133
Synthetic biology: understanding biological design from synthetic circuits, Shankar Mukherji and Alexander van Oudenaarden, Nature Reviews Genetics 10, 859871 (December 2009)
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, FanOut 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)
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.
No official text book but the following can be recommended:
An Introduction to Systems Biology: Design Principles of Biological Circuits (ISBN10: 1584886420), U Alon
Systems Biology: A Textbook. (ISBN10: 3527318747) Klipp et al
Engineering Genetic Circuits (ISBN10: 1420083244) Myers.
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.
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 multidisciplinary teams
k. An ability to use the techniques, skills, and modern engineering tools necessary for engineering practice (i.e. computer and analytical equipment)
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
And one of the following:
* 50% Design Project
* 50% Final exam
Three hours of lecture per week