Purpose of the Experiment  Fluxes in central carbon metabolism of a genetically engineered, riboflavin-producing Bacillus subtilis strain were investigated.

Slides:

Advertisements

Similar presentations

Metabolic Modeling - Why? Models - why? Building models of a system helps us improve our understanding. It is also a way of checking our understanding,

Advertisements

Lets begin constructing the model… Step (I) - Definitions We begin with a very simple imaginary metabolic network represented as a directed graph: Vertex.

Regulation of Gene Expression in Flux Balance Models of Metabolism.

Lecture #10 Metabolic Pathways. Outline Glycolysis; a central metabolic pathway Fundamental structure (m x n = 20 x 21) Co-factor coupling (NAD, ATP,

General Concepts of Bioprocess Modeling &

Darwinian Genomics Csaba Pal Biological Research Center Szeged, Hungary.

Effect of oxygen on the Escherichia coli ArcA and FNR regulation systems and metabolic responses Chao Wang Jan 23, 2006.

The (Right) Null Space of S Systems Biology by Bernhard O. Polson Chapter9 Deborah Sills Walker Lab Group meeting April 12, 2007.

Computational Modelling of Biological Pathways Kumar Selvarajoo

E.coli aerobic/anaerobic switch study Chao Wang, Mar

Flux Balance Analysis. FBA articles Advances in flux balance analysis. K. Kauffman, P. Prakash, and J. Edwards. Current Opinion in Biotechnology 2003,

Energy Balance Analysis Reference Paper: Beard et al. Energy Balance for Analysis of Complex Metabolic Networks. Biophysical Journal 83, (2002) Presented.

Integration of enzyme activities into metabolic flux distributions by elementary mode analysis Kyushu Institute of Technology Hiroyuki Kurata, Quanyu Zhao,

Models and methods in systems biology Daniel Kluesing Algorithms in Biology Spring 2009.

1 2 Extreme Pathway Lengths and Reaction Participation in Genome Scale Metabolic Networks Jason A. Papin, Nathan D. Price and Bernhard Ø. Palsson.

Systems Biology Existing and future genome sequencing projects and the follow-on structural and functional analysis of complete genomes will produce an.

The activity reaction core and plasticity of metabolic networks Almaas E., Oltvai Z.N. & Barabasi A.-L. 01/04/2006.

Mathematical Representation of Reconstructed Networks The Left Null space The Row and column spaces of S.

Regulated Flux-Balance Analysis (rFBA) Speack: Zhu YANG

Flux balance analysis in metabolic networks Lecture notes by Eran Eden.

Metabolic network analysis Marcin Imielinski University of Pennsylvania March 14, 2007.

Evolution of minimal metabolic networks WANG Chao April 11, 2006.

In silico aided metaoblic engineering of Saccharomyces cerevisiae for improved bioethanol production Christoffer Bro et al

Adaptive evolution of bacterial metabolic networks by horizontal gene transfer Chao Wang Dec 14, 2005.

The global transcriptional regulatory network for metabolism in Escherichia coli exhibits few dominant functional states Speaker: Zhu Yang

Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism Ref: Eliane Fischer & Uwe Sauer, Nature Genetics.

A synthetic gene- metabolic oscillator Fung et al

1 Escheria coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth Rafael U. Ibarra, Jeremy S. Edwards and Bernhard Ø. Palsson.

Humboldt- Universität zu Berlin Edda Klipp Systembiologie 3 - Stoichiometry Sommersemester 2010 Humboldt-Universität zu Berlin Institut für Biologie Theoretische.

Constraint-Based Modeling of Metabolic Networks Tomer Shlomi School of Computer Science, Tel-Aviv University, Tel-Aviv, Israel March, 2008.

Humboldt- Universität Zu Berlin Edda Klipp, Humboldt-Universität zu Berlin Edda Klipp Systembiologie 4 – Flux Balance Analysis Sommersemester 2010 Humboldt-Universität.

Elhanan Borenstein Spring 2011 Complex (Biological) Networks Some slides are based on slides from courses given by Roded Sharan and Tomer Shlomi Analyzing.

Seminar in Bioinformatics (236818) Ron Y. Pinter Fall 2007/08.

Metabolic Networks Describe cellular reactions at the biochemical level –kinetics –thermodynamics –stoichiometry Several levels of hierarchy; the most.

Extreme Pathways introduced into metabolic analysis by the lab of Bernard Palsson (Dept. of Bioengineering, UC San Diego). The publications of this lab.

VL Netzwerke, WS 2007/08 Edda Klipp 1 Max Planck Institute Molecular Genetics Humboldt University Berlin Theoretical Biophysics Networks in Metabolism.

Richard Notebaart Systems biology / Reconstruction and modeling large biological networks.

Biological Network Analysis: Introduction to Metabolic Networks Tomer Shlomi Winter 2008.

Metabolic Model Describing Growth of Substrate Uptake By Idelfonso Arrieta Anant Kumar Upadhyayula.

Lecture #23 Varying Parameters. Outline Varying a single parameter – Robustness analysis – Old core E. coli model – New core E. coli model – Literature.

Local Parametric Sensitivity Analysis AMATH 882 Lecture 4, Jan 17, 2013.

Flux Balance Analysis Evangelos Simeonidis Metabolic Engineering.

Genetic modification of flux (GMF) for flux prediction of mutants Kyushu Institute of Technology Quanyu Zhao, Hiroyuki Kurata.

Transcriptional Regulation in Constraints-based metabolic Models of E. coli Published by Markus Covert and Bernhard Palsson, 2002.

Metabolic pathway alteration, regulation and control (5) -- Simulation of metabolic network Xi Wang 02/07/2013 Spring 2013 BsysE 595 Biosystems Engineering.

The Optimal Metabolic Network Identification Paula Jouhten Seminar on Computational Systems Biology

Solution Space? In most cases lack of constraints provide a space of solutions What can we do with this space? 1.Optimization methods (previous lesson)

Reconstruction of Transcriptional Regulatory Networks

Steady-state flux optima AB RARA x1x1 x2x2 RBRB D C Feasible flux distributions x1x1 x2x2 Max Z=3 at (x 2 =1, x 1 =0) RCRC RDRD Flux Balance Constraints:

A chemostat approach to analyze the distribution of metabolic fluxes in wine yeasts during alcoholic fermentation Quirós, M. 1, Martínez-Moreno, R. 1,

BIOINFORMATICS ON NETWORKS Nick Sahinidis University of Illinois at Urbana-Champaign Chemical and Biomolecular Engineering.

1 Departament of Bioengineering, University of California 2 Harvard Medical School Department of Genetics Metabolic Flux Balance Analysis and the in Silico.

Lecture # 1 The Grand Schema of Things. Outline 1.The grand scheme of things 2.Some features of genome-scale science 3.The systems biology paradigm 4.Building.

10 AM Tue 20-Feb Genomics, Computing, Economics Harvard Biophysics 101 (MIT-OCW Health Sciences & Technology 508)MIT-OCW Health Sciences & Technology 508.

Introduction to biological molecular networks

Metabolic pathway alteration, regulation and control (3) Xi Wang 01/29/2013 Spring 2013 BsysE 595 Biosystems Engineering for Fuels and Chemicals.

In silico gene targeting approach integrating signaling, metabolic, and regulatory networks Bin Song Jan 29, 2009.

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

20. Lecture WS 2006/07Bioinformatics III1 V20 Extreme Pathways introduced into metabolic analysis by the lab of Bernard Palsson (Dept. of Bioengineering,

Essence of Metabolic Engineering

Source Bohringer-Mannheim. The History of Biological Networks Structures Strings, Physical Structures,…. Networks: Objects with relationships or discrete.

Project 2 Flux Balance Analysis of Mitochondria Energy Metabolism Suresh Gudimetla Salil Pathare.

V15 Flux Balance Analysis – Extreme Pathways

BT8118 – Adv. Topics in Systems Biology

DR.MITHAL ABD UL-KAREEM College of dentistry/Ibn sina university

Emerging Frontiers of Science Information

System Biology ISA5101 Final Project

MENTOS: A Statistical Thermodynamic Approach for Modeling Metabolism

BT8118 – Adv. Topics in Systems Biology

A DOLMN flux solution of E. coli core carbon metabolism.

Presentation transcript:

Purpose of the Experiment  Fluxes in central carbon metabolism of a genetically engineered, riboflavin-producing Bacillus subtilis strain were investigated in glucose-limited chemostat cultures at low (0.11 h -1 ) and high (0.44 h -1 ) dilution rates.

Introduction A metabolic network could be defined as a set of enzymatic reactions that biochemically process metabolites within the cell and transport processes that convert extra-cellular metabolites to intracellular metabolites and vice versa.

E. Coli Metabolic Network The E.Coli metabolic network.

Ultimate Goal Development of complete models simulating every aspect of cellular metabolism Absence of kinetic information on some of the reactions and the dynamics and regulation of metabolic reactions is the major hindrance. Many researchers have tried various approaches towards the ultimate goal with varying degrees of success. Some of them are :

Simulation Models Biochemical systems theory (Savageau, 1969a, 1969b, 1970), Metabolic control analysis (Kacser and Burns, 1973), Temporal decomposition (Palsson et al., 1987). Pathway analysis (Clark, 1988), Flux balance analysis (Varma and Palsson, 1994b), Cybernetic modeling (Ramakrishna et al., 1996;),

Flux Balance Analysis Flux balance analysis has gained a greater degree of acceptance with researchers. It describes the metabolic physiology in a quantitative manner It is based on the fundamental law of mass conservation. It is based on the fundamental physicochemical constraints on metabolic networks. It only requires information about the stoichiometry of metabolic pathways and on metabolic demands.

Flux Balance Analysis (contd.)

Metabolic Flux Analysis Metabolic flux analysis(MFA) is similar to flux balance analysis (FBA) but instead of the optimization techniques used in FBA experimentally measured/estimated fluxes are used to reduce the underdetermined nature of a metabolic system.

Modeling through MFA A model was developed through metabolic flux analysis to comprehensively describe the central metabolism of Bacillus subtilis The model was based on previously developed exhaustive biochemical reactions models developed by Dauner and Sauer

Problems with MFA  A typical problem of metabolic flux analysis using such metabolite balances are underdetermined equation systems.  These are caused by alternative pathways and redundant reactions in central metabolism, an inherent feature of biological systems.

MFA Process  Metabolic net fluxes are determined from an initial, randomly chosen set of parameters, and the corresponding isotopomer balances are calculated.  From this isotopomer distribution, synthetic NMR signals are simulated and compared to the experimentally determined 13 C- 13 C scalar coupling fine structures in cellular amino acids.

Flow chart of flux estimation procedure

System Trying to Model

Model Estimation  Net and exchange fluxes were estimated on the basis of the physiological data from Dauner and Sauer

Initial Basis Fluxes

Determined Exchange Fluxes

References  Metabolic Flux Analysis with a Comprehensive Isotopomer Model in Bacillus subtillis. Michael Dauner, James E. Bailey, Uwe Sauer.Institute of Biotechnology, ETH Zurich, CH 8093 Zurich, Switzerland.

References  Robustness Analysis of the Escherichia coli Metabolic Network. Jeremy S. Edwards and Bernhard O. Palsson. 927 Biotechnol. Prog. 2000, 16, 92  -939  Combining Pathway Analysis with Flux Balance Analysis for the Comprehensive Study of Metabolic Systems. Christopher H. Schilling, Jeremy S. Edwards, David Letscher, Bernhard Ø. Palsson