Download Systems Biology: history of a grand challenge

The Context of Systems Biology
Michele Griffa
Dept. of Physics, Polytechnic of Torino
[email protected]
The Role of Mathematical Modeling and Numerical Simulation in the
Systems Biology Era
Workshop
Bioindustry Park of Canavese, Colleretto Giacosa
February 28th, 2006
Systems Biology: history of a grand challenge
since ‘910s
since ‘950s
2000
t
Institute for Systems Biology, Seattle
• Concept of
(www.systemsbiology.org)
Homeostasys (Cannon)
• General Systems Theory (von
Leroy Hood
• Predator- Prey Bertalanffy, 1967)
Dynamics
•Biological
“The Cybernetics
HGP has given us a parts list.
(Volterra/Lotka) (Wiener/Rosenbluth)
• system-level
understanding
grounded
The next step
is to capture the
information from one
all the elements in a
in molecular-level
•Automata Theory
(von
biological system: DNA, proteins,
Neumann)
• function
and dynamics
understanding
cells, tissues
and organs,
and then
of acreate
wholenew
biosystem
• Compartmental
models
mathematical
in
models
Physiology
that will represent the relationships
• prediction and control
between them”
•Biochemical oscillators
The Economist Technology Quaterly,
september 17-23 2005
Systems Biology: history of a grand challenge
1990s: a leap forward
t
Post Genomic Era
theory, modelling,
computational
power (hardware,
algorithms)
microtechs,
total analysis-onone device
1 gene
networks paradigms
high throughput tools
developed for
genomes sequencing
databases,
WWW access
and data
mining
1 protein
• gene regulatory networks
• transcriptional pathways
• metabolic pathways
Systems Biology
approach needed !
Systems Biology: goals
Biosystems structure:
• networks of gene
• components
interactions
• modules that implement
functions
• interplay between
modules, relationships
between components
whole-biosystem dynamics:
how a whole-system behaves
over time under various
(boundary) conditions
• biochemical pathways
• mechanisms through which
such interactions modulate
physical properties of
intracellular and multicellular
structures
• control of the system
 robustness
• (evolutionary) design:
how to construct or
modify biosystems
having desired
properties
Multi-Scale Modeling of the Heart,
from Genes to Cells to the Whole-Organ:
an example of Systems Biology-like result
• 1952: Hodgkin/Huxley’s model, study of the dynamical behaviour of the voltage dependent
conductivity of a nerve cell membrane for Na+ and K+ ions, prediction of the dynamics of
action potential and of axon conduction in giant squibb.
• electrophysiological activity of miocytes (oscillators models)
•emergence of synchronization in sets of coupled non-linear oscillators (pacemakers cell
population dynamics, Winfree, 1980s)
• genetic mutations, protein expression and cardiac sodium channel dynamic behaviour
(Clancy, Rudy, 1999)
• propagation of action potential wavefield in excitable media (incorporation of cellular models
into whole-organ ones)
• mechanical-electrical feedback (how the contraction of the heart influences its electrical
conduction properties)
• blood fluid dynamics around cardiac valves surfaces (immerse boundary methods for the
solution of PDEs problems involving dynamic fluid-structure interaction, McQueen/Peskin,
1980s)
Multi-Scale Modeling of the Heart,
from Genes to Cells to the Whole-Organ
Spread of the electrical
activation potential wavefield in
an anatomically detailed cardiac
model (P. Kohl et al., Philos.
Trans. R. Soc. London Ser. A
358, 579, 2000)
red: activation potential wavefront; blue: endocardial surface
Transmural pressure
on coronary vessels
from the myocardial
stress (dark blue=0
press., red=peak
press.)
end-diastole
early systole
(N.P. Smith, G.S. Kassab, Philos. Trans. R. Soc. London Ser. A 359, 1315, 2001)
late systole
Systems Biology: a knowledge-management goal !
Integration and Scaling of Knowledge, Information,
Data, Models, Simulation Tools:
Integrative Biology !
large-scale
measurements
collection
large-scale data/knowledge
sharing
modeling and simulation
• KEGG (www.genome.ad.jp)
• SBML (www.sbml.org)
• STKE (www.stke.org)
• CellML (www.cellml.org)
• Alliance for Cellular Signaling
• BioUML (www.biouml.org)
(www.signaling-gateway.org)
• BioSpice
(https://community.biospice.org)
• BioCyc (www.biocyc.org)
• BIND (www.bind.ca/Action?pg=0)
• R-DBMS, WWW
• data and text mining
• Semantic Web (XML-enabled techs)
• XML-based computer readable model
definition languages;
• toolboxes for analysis, synthesis and
simulation;
The Context of Systems Biology
Michele Griffa
Dept. of Physics, Polytechnic of Torino
[email protected]
The Role of Mathematical Modeling and Numerical Simulation in the
Systems Biology Era
Workshop
Bioindustry Park of Canavese, Colleretto Giacosa
February 28th, 2006