Date post: | 17-Jan-2016 |
Category: |
Documents |
Upload: | penelope-weaver |
View: | 215 times |
Download: | 0 times |
Systems Biology___ Toward System-level
Understanding of Biological Systems
Hou-HaifengHou-Haifeng
What is Systems Theory?What is Systems Theory?
By By “system”“system”, we mean a bunch of parts that a, we mean a bunch of parts that are connected to one another and work togetherre 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 ...
Dynamic SystemsDynamic Systems- Definition- 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
Dynamic SystemsDynamic Systems
What exactly is Systems What exactly is Systems Biology?Biology?
Biology went top-down for the last 50 Biology went top-down for the last 50 yearsyears From cell to protein to gene ..From cell to protein to gene .. Huge amounts of data producedHuge amounts of data produced
Challenge: put the pieces back together Challenge: put the pieces back together againagain
Attempts to create predictive models of Attempts to create predictive models of cells, organs, biochemical processes and cells, organs, biochemical processes and complete organismscomplete organisms
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.
What exactly is Systems What exactly is Systems Biology? 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
What exactly is Systems What exactly is Systems Biology?Biology?
HistoryHistory
Term coined at 1960s, however Term coined at 1960s, however theoretical people and experimental theoretical people and experimental biologists divergedbiologists diverged
Renaissance at 1990sRenaissance at 1990s Biology becoming cross-disciplinary, Biology becoming cross-disciplinary,
information based, high throughput information based, high throughput sciencescience
A systems biology view...A systems biology view...
Components
BuildingBlocks
FunctionalModules
System
Life‘s Complexity Pyramid (Oltvai-Barabasi, Science 10/25/02)
Systems Biology Research Cycle VisionSystems Biology Research Cycle Vision
In vitro, In vivo experiments
In silico experiments
SYSTEMS BIOLOGY: SYSTEMS BIOLOGY: ProjectsProjects
Multi-scale modeling and analysis of Multi-scale modeling and analysis of adaptive cellular and system processesadaptive cellular and system processes
Mammalian systems – neurons, brains, Mammalian systems – neurons, brains, brain functions and diseasesbrain functions and diseases
a model benchmark tool, and a matrix of a model benchmark tool, and a matrix of solutions for Genetic Regulatory Circuits. solutions for Genetic Regulatory Circuits.
Development and Analysis of kinetic signaling Development and Analysis of kinetic signaling modelsmodels
Link of signaling models to Genetic Regulatory Link of signaling models to Genetic Regulatory CircuitsCircuits
Genetic Regulatory Circuits to neuronal Genetic Regulatory Circuits to neuronal electrical behaviorelectrical behavior
IonChannels
Receptors
mRNA
TranscriptionFactors
Ligands
ELECTROPHYSIOLOGY
Extracellularspace
Cytoplasm
NucleusTranslation +
processing
cis sites
IntracellularSignaling
GeneticRegulatory
Network
Expression profiles
Cellularprocesses
Proteins
Nucleus
mRNAsTFsIntracellular
signals
Cytosol
Genomicsequences
cis bindingactivities
Protein interaction network 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 protein–protein interactions based on yeast two-hybrid method
What needs to be What needs to be accomplished?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
What needs to be What needs to be accomplishedaccomplished
System Behavior Analysis Computer simulation and a set of theoretical
analyses are essential to provide in-depth understanding on the mechanisms behind the circuits
Figure:Software tools for systems biology and their workflow
• 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.
What needs to be What needs to be accomplishedaccomplished
System Control
What needs to be What needs to be accomplishedaccomplished
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
Biological RobustnessBiological 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
| Explaining robustness — the aeroplane example.
System control consists of negative and positive feedback to attain a robust dynamic response in the regulatory networks (cell cycle, circadian clock and chemotaxis)
Robustness as an Robustness as an organizationalorganizational principleprinciple
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
Biological RobustnessBiological 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
ConclusionConclusion System biology is a new and emerging System biology is a new and emerging
field in biologyfield in biology A long ways to go before understanding A long ways to go before understanding
biological systemsbiological systems We believe that systems biology will be We believe that systems biology will be
the dominant paradigm in biology, and the dominant paradigm in biology, and many medical applications as well as many medical applications as well as scientific discoveries are expected.scientific discoveries are expected.
Thank you very much for listening