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A Short Introduction To System Biology

Systems biology is the study of how biological functions emerge from molecular and cellular interactions. It uses an interdisciplinary approach involving experiments, mathematical modeling, and computer simulations. The document discusses key concepts in systems biology including cellular processes, network representations, multilevel organization, and modeling approaches to understand biological complexity and nonlinear dynamics.

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272 views

A Short Introduction To System Biology

Systems biology is the study of how biological functions emerge from molecular and cellular interactions. It uses an interdisciplinary approach involving experiments, mathematical modeling, and computer simulations. The document discusses key concepts in systems biology including cellular processes, network representations, multilevel organization, and modeling approaches to understand biological complexity and nonlinear dynamics.

Uploaded by

AsemSaleh
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Complex Systems

A Short Introduction to Systems Biology


Olaf Wolkenhauer
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Cell Functions

Growth

Differentiation
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Proliferation

Apoptosis
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The Systems Biology APPROACH

Systems Biology

Systems biology is an emerging research field,


which aims at understanding the dynamic interactions between components of a
living system [].

Systems biology is an approach by which biological questions are addressed


through integrating experiments in iterative cycles with computational modelling,
simulation and theory.

Systems biology is the science that studies how biological


function emerges from the interactions between the
components of living systems

Modelling is not the final goal, but is a tool to increase understanding of the
system, to develop more directed experiments and finally allow predictions.

and how these emergent properties enable/constrain


the behavior of these components.
Systems Biology in the European Research Area, p.9, www.erasysbio.net
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Key cellular processes and the network concept


Metabolism

Gene expression

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Examples of signaling pathways


Cell signalling

Pathway, Network
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Complex Systems

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Yes, this is state-of-the-art

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Why Mathematical Modeling?

The Systems (Biology) Approach

R"
S+

R"

S+

dR
= k0E * (R)+ k1S k2R
! dt

t+

(time-varying) dynamics,

dx
= f (x ; t)
dt

Rss+

frequency)

Biological complexity:

Observa(ons+
Experiments+

nonlinearity,

self-organization,

multilevelness.

Hypothesis+

Modeling+

Contextual*
Assump/ons**

Predic'ons+

Simula(on+
Analyses+

S+

Explana(on+
Concepts+

Narra/ve*

R+
E*+
Claim+

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The Network Approach to Systems Biology

E+
e.g.+Feedback+regula(on,+Bistability+

Rebu>al+
Understanding+

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Biological Complexity: Nonlinear Dynamics


S=8
S=14

0.6

0.5
0.4

0.4

R(t)
R(t)

R(t)
R(t)

0.5

0.3

0.2

0.2

0.1

0.1
0
0

0.3

10

15
time t

20

0
0

25

time t

10

15

0.5
0.5

Response RSS

R(t)

0.4
0.3
0.2
0.1
0
0

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0.4
0.3
0.2
Scrit
0.1

4
time t

0
0

10

15

Signal S

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Multilevelness

Multilevel Tissue Organization


crypt

107 crypts (14000 / cm2)


2000 cells per crypt
<20 stem cells per crypt
3-5 days for renewal

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Complex Systems

Functional Organization of Intestinal Crypts


intestinal tract
dys/hyper/neo-plasia
leading up to a tumor.
(cell death)

(mature tissue specific cells)

(transit, amplifying cells)

stem cell niche


(cell cycle)

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Multilevelness of Tissue Organization

Tissue Self-Organization Principle

In a tissue, every cell owes


its presence to the behavior
of all the remaining cells,
and also functions for the
sake of the others.

Reactions

Mutations

Lumen
Crypt

Molecules

Structural Organisation

Cell
Functions

Large
Intestine

Stress

EMERGENCE

Tissue
Function

COORDINATION

Functional Organisation

progressive determination

Maurits C. Escher: Drawing Hands, 1948

The whole (tissue) and its parts (cells) reciprocally


produce each other; determine the functioning of
each other.

regressive determination
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Emergence

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How do I model and simulate a system?

Statistics and Probability Theory


Machine-learning
Clustering and Classification
Dynamical Systems Theory
ODE-based mechanistic modeling
Stochastic modeling & simulation
Simulation/Agent-based modeling
Logical Representations

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Kinds of Modeling

Kinds of modeling (contd)

25

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There is nothing more practical than a good theory!

Mechanistic Modeling

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Why model?

Explain (very distinct from predict!)


Guide data collection
Illuminate core dynamics
Suggest dynamical analogies
Discover new questions
Promote scientific habit of mind
Bound outcomes to plausible ranges
Illuminate core uncertainties
Formulate hypotheses
Reveal simplicity in complexity
Ren Magritte: La Clairvoyance, 1936

cf. JM Epstein JASSS 11 (4) 2008

Modelling is a means for theorizing: We construct and analyse models


in order to formulate hypotheses about general law-like (organising) principles.
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Omnis cellular e cellula

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CDK proteins control the cell cylce by binding

Rudolf Virchow

CDK2
G2: Preparation for division

M: Cell division (mitosis)

Cyclin

G1: Cell growth

CDK-Protein

G0
S: DNA replication/synthesis

Cyclin
Go: Cell cycle arrest
(senescence)

CDK = Cyclin-abhngige
Protein-Kinase

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3D-Visualisierung fr CDK2_HUMAN

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Steps in the cell cycle


M: Division

G2: Synthesis

Modelling the Cell Cycle


G1: Growth

S: DNA-Doubling

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Simulating the cell cycle

Changing the binding properties of Cdc25 und Wee1

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Brahe

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Newton

Kepler

Brahes universe

Large scale data gathering

First data-driven models


(strongly context-dependent)
Systems Biology

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Copernicus universe

Generalisation into
universal laws
general principles

Idea for this slide from J.E.Ferrell, who got it from Stas Shvartsman

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Johannes Kepler

Tycho Brahe

(1571-1630)

(1546-1601)
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Take Home Messages


Cellular Systems:
Cell functions: growth, proliferation, differentiation, apopotosis.
The network/pathway concept.
Systems Biology:
Studying how biological function emerges from molecular and cellular interactions.
An interdisciplinary approach addressing biological and biomedical questions with
the help of mathematical modeling and computer simulations.
Biological Complexity:
Nonlinear spatio-temporal interactions of molecules and cells: Feedback.
Multilevelness: Self-organisation, emergence.
Mathematical modeling:
Statistics, machine learning: Clustering, classification.
Dynamical systems theory: Rate equations, logic representations, stochastic
processes.
Modeling as a way of thinking.
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The Teaching Crew

Dr Shailendra Gupta

Dr Anu R Jauhan

Faiz Khan

Dr Dagmar Waltemath

Florian Wendland

Haus 3, Ulmentrae 69
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