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Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
1
Introduction to Systems Biology: Constraint-based Metabolic Reconstructions & Analysis
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
2
Learning Objectives
• Explain flux balance analysis
• Explain the basic E.coli core metabolic model
• Demonstrate the ability to effectively use the Cobra Toolbox
• Explain and demonstrate robustness analysis
• Explain and demonstrate flux variability analysis
• Explain and demonstrate phenotype phase plane analysis
• Explain and demonstrate the process of determining gene knockouts for optimizing bioproduct production
• Explain and demonstrate the process of optimizing bioproduct production
• Explain transcriptional regulated models
• Explain the process of creating genome-scale metabolic reconstructions
Each student should be able to:
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
3
Course Introduction
• Content Overview
• Course Content
• Course Learning Process
• Course Grading & Expectations
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
Biological Networks
• Biological networks are made up of chemical transformations
• Biological networks are composed of nodes and links
• Biological networks produce biological/physiological functions
Metabolic Regulatory Signaling
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
Cellular Machinery: Converting Matter Into Living Organisms
Yeast (S. Cerevisiae)
Bacteria (E. coli )
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
Major Metabolic Pathways
http://en.wikipedia.org/wiki/Portal:Metabolism
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
Escherichia coli K-12 Metabolic Map http://www.biocyc.org/ECOLI/NEW-IMAGE?type=OVERVIEW
Biosynthesis
Signal TransductionPathways
En
erg
y
Degradation Proteins &Compounds
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
Full E.coli model “ecoli_iaf1260.xml”
(http://bigg.ucsd.edu/bigg/main.pl)
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
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This figure shows a phylogenetic tree of all species for which metabolic genome-scale reconstructions have been built. Sections are colored by superkingdom, and phyla are noted on the outer ring of the tree.
Oberhardt, M. A., B. O. Palsson, et al. (2009). "Applications of genome-scale metabolic reconstructions." Molecular Systems Biology 5: 320.
Phylogenetic Tree of Reconstructed Species
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
Opportunities Provided
by Genome-scaleMetabolic
Reconstructions
Feist, A. M. and B. O. Palsson (2008). "The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli." Nature biotechnology 26(6): 659-667.
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
11
Course Introduction
• Content Overview
• Course Content
• Course Learning Process
• Course Grading & Expectations
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
Course Website
http://systemsbiology.usu.edu
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
13
Course Introduction
• Content Overview
• Course Content
• Course Learning Process
• Course Grading & Expectations
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
14
Course Learning Process
• Weekly class periods
• Attend class (attendance is expected)
• Tuesdays will typically be lectures.
• Thursdays will typically be labs covering the material learned in previous
lectures.
• Class project
• Each student must complete a class project.
• A project proposal presentation, a final paper, and final presentation will be
required for each project
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
15
Course Introduction
• Content Overview
• Course Content
• Course Learning Process
• Course Grading & Expectations
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
16
Grading
Labs 50%
Final Project
Proposal Presentation 5%
Paper 30%
Presentation
15%
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
17
Expectations
• Estimated homework for a B student– ~3 hours out-of-class work for every hour in class
• All assignments and materials will be provided through the course
website.• Computer compatibility is your responsibility.• Students are expected to attend every class.• Students will check the course website at least three times per week. • Students are expected to know (or re-learn on their own) material
covered in prerequisite courses.
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
18
Course Introduction
• Content Overview
• Course Content
• Course Learning Process
• Course Grading & Expectations
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
19
Extra Slides
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
20
H. Sauro, “Systems and Synthetic Biology,” 499C, University of Washington, 2008, Lecture #2, p. 17
David S. Goodsell, “Escherichia coli,” Biochemistry and Molecular Biology Education, Volume 37, Issue 6, pages 325–332, November/December 2009
Average space between proteins: 7 nm/molecule
Average diameter of a protein: 5 nm
Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton
Lesson: IntroductionBIE 5500/6500Utah State University
21
H. Sauro, “Systems and Synthetic Biology,” 499C, University of Washington, 2008, Lecture #2, p. 18