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

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



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:



3

Course Introduction

• Content Overview

• Course Content

• Course Learning Process

• Course Grading & Expectations



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



Cellular Machinery: Converting Matter Into Living Organisms

Yeast (S. Cerevisiae)

Bacteria (E. coli )



Major Metabolic Pathways

http://en.wikipedia.org/wiki/Portal:Metabolism



Escherichia coli K-12 Metabolic Map http://www.biocyc.org/ECOLI/NEW-IMAGE?type=OVERVIEW

Biosynthesis

Signal TransductionPathways

En

erg

y

Degradation Proteins &Compounds

http://www.biocyc.org/ECOLI/NEW-IMAGE?type=OVERVIEW



Full E.coli model “ecoli_iaf1260.xml”

(http://bigg.ucsd.edu/bigg/main.pl)



9

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



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.



11

Course Introduction


• Course Content





Course Website

http://systemsbiology.usu.edu

https://systemsbiology.usu.edu/



13

Course Introduction


• Course Content





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



15

Course Introduction


• Course Content





16

Grading

Labs 50%

Final Project

Proposal Presentation 5%

Paper 30%

Presentation

15%



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.



18

Course Introduction


• Course Content





19

Extra Slides



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



21

H. Sauro, “Systems and Synthetic Biology,” 499C, University of Washington, 2008, Lecture #2, p. 18

Documents

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