1. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Introduction to Systems Biology: Constraint-based Metabolic Reconstructions & Analysis 1

2. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University 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: 2

3. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Course Introduction Content Overview Course Content Course Learning Process Course Grading & Expectations 3

4. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 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 MetabolicRegulatorySignaling

5. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Cellular Machinery: Converting Matter Into Living Organisms Yeast (S. Cerevisiae) Bacteria (E. coli )

6. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Major Metabolic Pathways http://en.wikipedia.org/wiki/Portal:Metabolism

7. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Escherichia coli K-12 Metabolic Map http://www.biocyc.org/ECOLI/NEW-IMAGE?type=OVERVIEWhttp://www.biocyc.org/ECOLI/NEW-IMAGE?type=OVERVIEW Biosynthesis Signal Transduction Pathways Signal Transduction Pathways Energy Degradation Proteins & Compounds Proteins & Compounds

8. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Full E.coli model “ecoli_iaf1260.xml” (http://bigg.ucsd.edu/bigg/main.pl)

9. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University 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 9

10. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Opportunities Provided by Genome-scale Metabolic 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.

11. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Course Introduction Content Overview Course Content Course Learning Process Course Grading & Expectations 11

12. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Course Website http://systemsbiology.usu.edu

13. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Course Introduction Content Overview Course Content Course Learning Process Course Grading & Expectations 13

14. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University 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 14

15. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Course Introduction Content Overview Course Content Course Learning Process Course Grading & Expectations 15

16. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Grading Labs50% Final Project Proposal Presentation 5% Paper 30% Presentation 15% 16

17. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University 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. 17

18. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Course Introduction Content Overview Course Content Course Learning Process Course Grading & Expectations 18

19. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University Extra Slides 19

20. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University H. Sauro, “Systems and Synthetic Biology,” 499C, University of Washington, 2008, Lecture #2, p. 17 20 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

21. Constraint-based Metabolic Reconstructions & Analysis © 2015 H. Scott Hinton Lesson: Introduction BIE 5500/6500Utah State University H. Sauro, “Systems and Synthetic Biology,” 499C, University of Washington, 2008, Lecture #2, p. 18 21