Title: Systems Biology ___ Toward Systemlevel Understanding of Biological Systems
1Systems Biology___ Toward System-levelUnderstand
ing of Biological Systems
Hou-Haifeng
2What is Systems Theory?
- By system, we mean a bunch of parts that are
connected to one another and work together - Mathematical Systems Theory is oncerned with the
description and understanding of systems by the
means of mathematics - Analysis
- Modeling
- Simulation
- ...
3Dynamic Systems- Definition
- A system is an object in which variables of
different kinds interact and produce observable
signals - In a dynamic system the current output value
depends not only on the current input value but
also on its earlier values
4Dynamic Systems
5What exactly is Systems Biology?
- Biology went top-down for the last 50 years
- From cell to protein to gene ..
- Huge amounts of data produced
- Challenge put the pieces back together again
- Attempts to create predictive models of cells,
organs, biochemical processes and complete
organisms
6The scope of systems biology is potentially very
broad and different sets of techniques may be
deployed for each research target. It requires
collective efforts from multiple research areas,
such as molecular biology, high-precision
measurement, computer science, control theory,
and other scientific and engineering fields.
7What exactly is Systems Biology?
- a new field in biology that aims at system-level
understanding of biological systems - to understand biological systems grounded in the
molecular level as a consistent framework of
knowledge - to investigate the behaviour and relationships of
all the elements in a particular biological
system
8What exactly is Systems Biology?
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10History
- Term coined at 1960s, however theoretical people
and experimental biologists diverged - Renaissance at 1990s
- Biology becoming cross-disciplinary, information
based, high throughput science
11A systems biology view...
12Systems Biology Research Cycle Vision
In vitro, In vivo experiments
In silico experiments
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14SYSTEMS BIOLOGY Projects
- Multi-scale modeling and analysis of adaptive
cellular and system processes - Mammalian systems neurons, brains, brain
functions and diseases - a model benchmark tool, and a matrix of solutions
for Genetic Regulatory Circuits. - Development and Analysis of kinetic signaling
models - Link of signaling models to Genetic Regulatory
Circuits - Genetic Regulatory Circuits to neuronal
electrical behavior
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17Protein interaction network
The colour of a node indicates the phenotypic
effect of removing the corresponding protein (red
lethal, green non-lethal, orange slow
growth, yellow unknown).
Yeast map of proteinprotein interactions based
on yeast two-hybrid method
18What needs to be accomplished?
- System Structure Identification
-
- BOTTOM-UP APPROACH
- TOP-DOWN APPROACH make use of
high-throughput data and other new measurement
technologies to deduce the properties of the
systems - PARAMETER IDENTIFICATION brute force
exhaustive search, genetic algorithms, simulated
annealing
Systems
Components
19What needs to be accomplished
- System Behavior Analysis
- Computer simulation and a set of theoretical
analyses are essential to provide in-depth
understanding on the mechanisms behind the
circuits
20 a database for storing experimental data a
cell and tissue simulator, parameter
optimization software, bifurcation and systems
analysis software, hypotheses generator and
experiment planning advisor software, and
data visualization software.
FigureSoftware tools for systems biology and
their workflow
21What needs to be accomplished
22What needs to be accomplished
- System Design the strategies to modify and
construct biological systems having desired
properties can be devised based on definite
design principles and simulations, instead of
blind trial-and-error
23Biological Robustness
- Robustness is a ubiquitously observed property of
biological systems - Robustness is a property that allows a system to
maintain its functions despite external and
internal perturbations
24 Explaining robustness the aeroplane example.
25Robustness as an organizational principle
System control consists of negative and positive
feedback to attain a robust dynamic response in
the regulatory networks (cell cycle, circadian
clock and chemotaxis)
26Modularity an effective Mechanism for containing
perturbations and damage locally to minimize the
effects on the whole system
Decoupling isolates low-level variation from
high-level functionalities
27Biological Robustness
- Cancer is an extremely complex and heterogeneous
disease that exhibits a high level of robustness
against a range of therapeutic efforts - Heterogeneity among tumour cells provides a high
level of redundancy, and hence increased chances
of survival and growth - Hunt for fragility weaknesses in tumour growth
dynamics could yield new anti-cancer therapies
28Conclusion
- System biology is a new and emerging field in
biology - A long ways to go before understanding biological
systems - We believe that systems biology will be the
dominant paradigm in biology, and many medical
applications as well as scientific discoveries
are expected.
29Thank you very much for listening