Post on 30-Jun-2015
description
Segmenting the fly embryo: by means of non-linear dynamics or Boolean logic?
Joseph X. Zhou
Konrad Loetzsch
Presentations on lecture "Introduction to Mathematical Biology II", Jan. 29, 2008
Group advisor:
Group member:
Lutz Brusch
Pattern formation during embryonic development
• Central problem: 1D genetic information 3D complex structure
• Gradients pattern formation
• Intracellular signaling
Genetic network controlling segmentation in fly Drosophila
• Drosophila - easily cultured in mass in lab
- short generation time (7 – 60 days)
- easily genetically manipulated
• The genetic hierarchy controls segmentation in the fly Drosophila
Conventional physics Law
A B
Akdt
dBAB
It is to easy to guess the law in a simple system, such as:
Newton’s Gravity Law,
Coulomb's Law,
Schrodinger equation, etc.
When network plays a role
B
- “Bringing cartoons to life”, John J. Tyson, Nature, 445, 823
A
DC• It is harder to guess the law from a complex system.
• To bridge molecular biology to cell physiology, we need to build a network of interacting genes and proteins as a dynamic system .
A dynamical model of the segment polarity gene network
• The segment polarity gene network is modeled by kinetic equations
• It needs 50 free parameters, mRNA, proteins, rates & coop coef.
• Ask two questions:- How to build the network more systematically and quickly?- How to share these models more efficiently?
Pathways Database Network models
World-wide Pathways Database 1
Extract a sub-model
World-wide Pathways Database n
… … Integrate them to Network model
Coupled ODEs
Stochastic Model
Boolean Dynamics
SBML CellML
• Identify the nodes of the network
- ask experts, or go to websites: GO, KEGG, GenMAPP, PID
• Start qualitative network, identify sub-circle that
involve the process
• Build a network model involving markers and
interactions
• Build a kinetic model with parameters available
Build a Gene network modelfor early wing development of Drosophila
Build a Gene network modelfor early wing development of Drosophila
Build a Gene network modelfor early wing development of Drosophila
• By fixing the values of the nodes in the
network, simulate mutations
• Verified by phenotype observed in Exp.
• Study the robustness of gene network
Conclusion
• Network model is a powerful mathematical tool
to model interacting genes and proteins as a
dynamic complex system
• A network model can be built from WWW
pathways databases quickly
• SBML, CellML etc. make it more efficient to build
and share network models