Welcome to the max planck institute for dynamics of complex technical systems magdeburg
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WELCOME TO THE MAX PLANCK INSTITUTE FOR DYNAMICS OF COMPLEX TECHNICAL SYSTEMS MAGDEBURG. Program 14:30 p.m. Welcome to the institute and introduction of the Systems Biology Group (Ernst Dieter Gilles, Jörg Stelling) 15:00 p.m. Introduction of the group and purpose of study

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Welcome to the max planck institute for dynamics of complex technical systems magdeburg
WELCOME TO THEMAX PLANCK INSTITUTEFOR DYNAMICS OF COMPLEX TECHNICAL SYSTEMSMAGDEBURG

Program

14:30 p.m. Welcome to the institute and introduction of the Systems Biology Group

(Ernst Dieter Gilles, Jörg Stelling)

15:00 p.m. Introduction of the group and purpose of study

(Marvin Cassmann)

15:30 p.m. Refreshment and start of poster session

16:30 p.m. Viewing of the biological laboratories

17:30 p.m. End


Max planck institute for dynamics of complex technical systems magdeburg
MAX PLANCK INSTITUTEFOR DYNAMICS OF COMPLEX TECHNICAL SYSTEMSMAGDEBURG

  • Founded in 1996 as 1st Max Planck Institute of Engineering

  • Start of research activities in 1998

  • 4 departments:

    • Process Engineering (Sundmacher)

    • Bioprocess Engineering (Reichl)

    • Physical and Chemical Fundamentals (Seidel-Morgenstern)

    • System Theory (Gilles)


Broad spectrum of processes to deal with
BROAD SPECTRUM OF PROCESSES TO DEAL WITH:

Provides methods and tools

SYSTEM SCIENCES

(SYSTEM THEORY)

Integrating factor

Chemical

Processes

Biochemical

Processes

Biological

Networks

•••


Systems biology
SYSTEMS BIOLOGY

Biology Information Sciences

Quantitative

Measurement

Data-

bases

Hypo-

theses

Modeling

Tool

Virtual

Biological

Laboratory

Genetic

Modi-

fication

Visuali-

zation

Analysis

Synthesis

Modeling Concept

Systems Sciences

„Systems biology is the synergistic application of experiment, theory, and modeling towards understanding biological processes as whole systems instead of isolated parts.“

Systems Biology Group/Caltech

Interdisciplinary approach towards a quantitative and predictivebiology


Research group systems biology
RESEARCH GROUP: SYSTEMS BIOLOGY

  • Research activities started in 1998

  • 17 employees working in our group

  • Continuous extension of research activities on metabolic regulation and signal transduction

  • Interdisciplinary composition of research group

  • Close cooperation with a network of external biology groups

  • Fermentation laboratory to perform experiments for model validation and hypotheses testing

    • Quantitative determination of cellular components

    • Construction of isogenic mutant strains of E. coli and other microorganisms


Objectives of research
OBJECTIVES OF RESEARCH

  • Improved understanding of cellular systems

  • New solutions for biotechnological and medical problems

    (drug target identification)

APPROACH

  • Detailed mathematical modeling

  • Close interconnection between theory and experiment

    • Model validation

    • Model-based design of experiments

    • Formulation and testing of hypotheses

  • System-theoretical analysis of dynamics and structural properties

  • Decomposition into functional units of limited autonomy

  • Model reduction


Complexity and robustness
COMPLEXITY AND ROBUSTNESS

Complex Technical Processes

Powerful concepts to cope with increasing complexity

  • Modularity techniques

  • Hierarchical structuring

  • Redundancy and diversity

    Biological Systems

    Similar features of structuring

  • Natural modularity decomposition into functional units of limited autonomy

  • Hierarchical structuring of regulation

  • Redundancy and diversity of pathways, sensors and other key units

    Objectives of these concepts in both fields

  • Robustness of functionality

  • Reduction of fragilities

    Methods and tools developed in engineering, also appropriate for biological

    systems

    Control Theory, Nonlinear Dynamics, System Theory …


Projects of the group
PROJECTS OF THE GROUP

Biology Information Sciences

Data-

bases

Quantitative

Measurement

Modeling

Tool

Hypo-

theses

Virtual

Biological

Laboratory

Genetic

Modi-

fication

Visuali-

zation

Analysis

Synthesis

Systems Sciences

Modeling Concept

SIGNAL TRANSDUCTION

AND REGULATION

IN BACTERIAL CELLS

SIGNAL TRANSDUCTION

AND REGULATION

IN EUKARYOTES

COMPUTER AIDED MODELING

AND ANALYSIS

OF CELLULAR SYSTEMS


Project signal transduction and regulation in bacterial cells
PROJECT: SIGNAL TRANSDUCTION AND REGULATION IN BACTERIAL CELLS

Redox Control in

Photosynthetic Bacteria

(H. Grammel, S. Klamt)

Mathematical Modeling of

Catabolite Repression in E.coli

(K. Bettenbrock, S. Fischer, A. Kremling)

Phototaxis in

Halobacterium Salinarum

(T. Nutsch)

Uni Stuttgart (Prof. Gosh; ISR)

Uni Magdeburg (Prof. Reichl)

MPI Biochemie (Prof. Oesterhelt)

Uni Freiburg (Dr. Marwan)

Uni Osnabrück (Prof. Lengeler)

Biology Information Sciences

Regulation of Stress Sigma Factor σS

(T. Backfisch)

Two-component

Signal Transduction in E.coli

(A. Kremling)

Quantitative

Measurement

Data-

bases

Hypo-

theses

Modeling

Tool

Virtual

Biological

Laboratory

Genetic

Modi-

fication

Visuali-

zation

Analysis

Synthesis

FU Berlin (Prof. Hengge)

Uni München (Prof. Jung)

Systems Sciences

Modeling Concept


Sub project catabolite repression in e coli
SUB-PROJECT:CATABOLITE REPRESSION IN E. coli


Sub project redox control of photosynthetic bacteria
SUB-PROJECT:REDOX CONTROL OF PHOTOSYNTHETIC BACTERIA

Fructose

Fructose

-

6

-

EMP

phosphate

C4/C5/C6/C7

-

Glyceraldehyde

-

Intermediates

3

-

phosphate

CBB

-

ATP

Glyceraldehyde

-

Cycle

3

-

phosphate

Ribulose

-

1,5

-

NADH

NADH

bisphosphate

3

-

Phospho

-

glycerate

Formiate

3

-

Phospho

-

Acetate

glycerate

NADH

CO

2

2

-

OG

TCA

-

OA

Cycle

SCoA

NADH

FADH

NADH

ATP



Block diagram of phototaxis
BLOCK-DIAGRAM OF PHOTOTAXIS

MOLECULAR ORIENTED:

SIGNAL ORIENTED:



Projects of the group1
PROJECTS OF THE GROUP

Biology Information Sciences

Data-

bases

Quantitative

Measurement

Modeling

Tool

Hypo-

theses

Virtual

Biological

Laboratory

Genetic

Modi-

fication

Visuali-

zation

Analysis

Synthesis

Systems Sciences

Modeling Concept

SIGNAL TRANSDUCTION

AND REGULATION

IN BACTERIAL CELLS

SIGNAL TRANSDUCTION

AND REGULATION

IN EUKARYOTES

COMPUTER AIDED MODELING

AND ANALYSIS

OF CELLULAR SYSTEMS


Project signal transduction and regulation in eukaryotes
PROJECT:SIGNAL TRANSDUCTION AND REGULATION IN EUKARYOTES

Mathematical Modeling of Cell Cycle Regulation in Eukaryotes

(J. Stelling)

Catabolite Repression in Yeast

(J. Stelling)

Biology Information Sciences

Quantitative

Measurement

Data-

bases

Modeling

Tool

Hypo-

theses

Virtual

Biological

Laboratory

Uni Halle (Prof. Breunig)

Uni Stuttgart (Prof. Seufert)

Genetic

Modi-

fication

Visuali-

zation

TCR Signaling Pathway

(J. Saez-Rodriguez, X. Wang)

HGF/c-Met Signaling Pathway

and H. pylori

(S. Ebert)

Analysis

Synthesis

TNF-induced Apoptosis

(H. Conzelmann, T. Sauter)

Modeling Concept

Systems Sciences

Uni Stuttgart (Prof. Pfizenmaier)

Uni Magdeburg (Prof. Schraven)

MIT/Merrimack (B. Schoeberl)

Uni Magdeburg (Prof. Naumann)


Sub project cell cycle of s cerevisiae
SUB-PROJECT: CELL CYCLE OF S. CEREVISIAE

cell division

M

4n

DNA

mass

growth

G2

CLN1-3

SIC1

2n

DNA

CLB1-4

G1

CLB3-6

replication

control

2...4n

DNA

S

START

DNA-Replication

  • The cell cycle of the yeast consists of discrete phases (G1, S, G2, M)

  • The transition from one phase to the next strictly depends on a successful termination of all functions of the preceding phase and is always irreversible

  • The cell cycle can be interpreted as a sequential controller on the highest level of regulation


SUB-PROJECT:CELL CYCLE OF S. CEREVISIAE

Molecular Interactions

Undisturbed Cell Cycle

cell growth

Complex interconnection of gene expression and proteolysis of 9 cyclins and the inhibitor Sic 1 leads to periodic cyclin-kinase activities

Nocodazole arrest



BMBF: SYSTEMS BIOLOGY – SYSTEMS OF LIFE

Interaction of Signal Transduction and Cell Cycle Regulation

in Eukaryotes

T-cell

Receptor

Hepatocyte

Growth

Factor

Epidermal

Growth

Factor

Tumor

Necrosis

Factor

Insulin

Cell cycle


  • Cooperation with experimental groups

    • Uni Magdeburg:

      • Immunology (Prof. Schraven): TCR

      • Experimental Internal Medicine (Prof. Naumann): c-Met (HGFR) and H. pylori

    • Uni Leipzig:

      • Cell Techniques and Applied Stem Cell Biology (Prof. Bader): EGF, HGF, Insulin and TNF in hepatocytes

    • Uni Stuttgart:

      • Cell Biology and Immunology (Prof. Pfizenmaier): TNF

  • Methods

    • Phosphorylation Assays (Western Blots), Microscopical Methods, ELISA, microarrays, FACS

  • Cellular systems

    • cell lines: HeLa (EGF, TNF), MDCK (HGF), HepG2

    • primary cells: mouse-Tcells (TCR), mouse/pig/man-hepatocytes

      The projects are supported by the German Research Foundation (DFG), German Ministery for Education and Research (BMBF) and State of Saxony-Anhalt


Future objectives
FUTURE OBJECTIVES

  • Decomposition of signaling network into modules

    • Criteria and system theoretical methods to demarcate modules in complex signaling networks

    • Analysis of signal transfer of modules

    • Building-up of a construction-kit containing a complete set of elementary and disjunctive modules of signal transfer

  • Analysis of crosstalk phenomena among signaling systems (EGF, HGF, TNF, Insulin, ...)

  • Analysis of differentiation processes

  • Interaction between signaling processes and cell cycle control



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