Systems Biology ___ Toward Systemlevel Understanding of Biological Systems

1
Systems Biology___ Toward System-levelUnderstand
ing of Biological Systems
Hou-Haifeng
2
What 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
• ...

3
Dynamic 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

4
Dynamic Systems
5
What 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

6
The 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.
7
What 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

8
What exactly is Systems Biology?
9
(No Transcript)
10
History

• Term coined at 1960s, however theoretical people
  and experimental biologists diverged
• Renaissance at 1990s
• Biology becoming cross-disciplinary, information
  based, high throughput science

11
A systems biology view...
12
Systems Biology Research Cycle Vision
In vitro, In vivo experiments
In silico experiments
13
(No Transcript)
14
SYSTEMS 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

15
(No Transcript)
16
(No Transcript)
17
Protein 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
18
What 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
19
What 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
21
What needs to be accomplished

• System Control

22
What 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

23
Biological 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.
25
Robustness 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)
26
Modularity 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
27
Biological 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

28
Conclusion

• 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.

29
Thank you very much for listening