affinity based model of multicellular development oisn mac aodha 4ece 02/04/2007
DESCRIPTION
As the drive towards nano-scale fabrication continues we may soon reach a point where physical manipulation of atomic scale components will become impossible. A possible alternative to the current top-down lithographic process would be a bottom up manufacturing process where the pre-existing components of a system can automatically self assemble to produce the desired behavior. Background Affinity Based Model of Multicellular DevelopmentTRANSCRIPT
Affinity Based Model of Multicellular Development
Oisín Mac Aodha 4ECE
02/04/2007
This project investigates if it is possible to model the development of multicellular organisms.
Presentation Structure: - Background - Brief introduction to genetic algorithms (GAs) - Introduction to development
- Modelling development - Experimental results
- Conclusions
Introduction
Affinity Based Model of Multicellular Development
As the drive towards nano-scale fabrication continues we may soon reach a point where physical manipulation of atomic scale components will become impossible.
A possible alternative to the current top-down lithographic process would be a bottom up manufacturing process where the pre-existing components of a system can automatically self assemble to produce the desired behavior.
Background
Affinity Based Model of Multicellular Development
Genetic Algorithms
Affinity Based Model of Multicellular Development
Generation
0 5 10 15 20 25 30 35 40 45 50
Ave
rage
Fitn
ess
5
6
7
8
9
10
11
The goal is to evolve an a population whose individuals comprise of just 1s.
Ones Max Problem
Affinity Based Model of Multicellular Development
Development
Affinity Based Model of Multicellular Development
http://www.microscopy-uk.org.uk/
Development is the process by which organisms grow and develop.
As the problem becomes more complex so will the processing time required by a GA to find the best solution.
Development allows a more complex genotype to phenotype mapping compared to the one to one mapping provided by a GA.
May contribute to achieving the levels of complexity as seen in nature.
Why Use Development?
Affinity Based Model of Multicellular Development
Development was modelled using Java by creating a gene regulatory network.
Corresponding classes were created for the objects found in nature including: Protein, Gene, Chromosome, Cell and Phenotype. GA was used to evolve the genome (configuration) used data for development.
Modelling Development
Affinity Based Model of Multicellular Development
10.5
20.8
30.3
Cell
Genome
Protein
In a GRN, a gene produces a protein. The protein produced subsequently affects other genes and ultimately cell behavior.
Gene Regulatory Network
Affinity Based Model of Multicellular Development
1 3 2 2 4 2 1 3 2 3 4 1
Gene 1 Gene 2 Gene 3
Cis – Reg Site Coding Region
The affinity matrix contains the protein-gene interaction
strengths.
The gene transcribes a new protein when the evolved threshold for the gene is exceeded.
Affinity Matrix
Affinity Based Model of Multicellular Development
ON
OFF
OutputInputs
0
0.3 X 0.45
1.2 X -0.25
0.4 X 0.1
The following results were obtained using the configuration data below.
Single Cell Results
Affinity Based Model of Multicellular Development
Development Step
0 2 4 6 8 10 12 14 16 18 20
Con
cent
ratio
n
0
1
2
3
4
5
Protein 0Protein 1Protein 2Protein 3Protein 4
Flat Concentration
Affinity Based Model of Multicellular Development
Development Step
0 2 4 6 8 10 12 14 16 18 20
Con
cent
ratio
n
0
1
2
3
Protein 0Protein 1Protein 2Protein 3Protein 4
Linear Concentration
Affinity Based Model of Multicellular Development
Development Step
0 2 4 6 8 10 12 14 16 18 20
Con
cent
ratio
n
0
1
2
3
Protein 0Protein 1Protein 2Protein 3Protein 4
Development Step
0 2 4 6 8 10 12 14 16 18 20
Con
cent
ratio
n
0
1
2
3
Protein 0Protein 1Protein 2Protein 3Protein 4
Heterochrony
Affinity Based Model of Multicellular Development
Next stage was to expand the current single cell modelto allow for multicellular development.
Cells have the ability to: - Divide - Die - Communicate (via signalling proteins)
Multicellular Development
Affinity Based Model of Multicellular Development
Cell division is the process by which a parent cell divides into two cells.
The genome of the parent cell is transferred is copied and transferred to the new cell.
Protein concentrations are distributed between the cells.
Cell Division
Affinity Based Model of Multicellular Development
10.6
20.8
30.2
10.3
20.4
30.1
10.3
20.4
30.1
Genome Replicates
Proteins Divide
10.6
20.8
30.2
Cell
Genome
Protein
The direction a cell divides in is based on the concentration of the direction protein.
The direction around the unitcircle corresponds to the eightpossible neighbouring locations acell has in a 2D grid.
Cell Direction
Affinity Based Model of Multicellular Development
0
12
3
74
5 6
0
π/4
π/23π/4
π
5π/4
3π/27π/4
2π
3 2 1
4 cell 0
5 6 7
The multicellular model has nine proteins with the following functions:
Protein Functions
Affinity Based Model of Multicellular Development
For the multicellular experiments the fitness was based on the position of the cells.
Multicellular Results
Affinity Based Model of Multicellular Development
Line
Affinity Based Model of Multicellular Development
Step 1 Step 10 Step 20
fitness = (1/cellsInside) + (cellsOutside/desiredLength)
Square
Affinity Based Model of Multicellular Development
Step 7 Step 15 Step 20
fitness = (size*size) – cellsInside + cellsOutside
A morphogen is a substance which governs thepositions of the various specialized cell types within anorganism.
It spreads from a localised source and forms a concentration gradient across a developing organism.
Based on Wolpert’s French flag model.
Morphogens
Affinity Based Model of Multicellular Development
Blue Threshold
Red Threshold
Source
Sink
Cells
Distance
0 5 10 15 20
Mor
phog
en C
once
ntra
tion
-0.2
0.0
0.2
0.4
0.6
0.8
1.0
1.2
morphogenConc = sourceConc x (1 / (sourceConc + distanceFromSource))
Morphogen Gradients
Affinity Based Model of Multicellular Development
French Flag
Affinity Based Model of Multicellular Development
Research: - Inter cell communication - More complex development model - 3D organisms - Environmental effects during development
Possible Applications: - Self developing systems - Fault repairing circuits
Future Research
Affinity Based Model of Multicellular Development
Questions
Affinity Based Model of Multicellular Development
http://ohm.nuigalway.ie/0607/03macaodha