Transcript Final Presentation

Affinity Based Model of
Multicellular Development
Oisín Mac Aodha 4ECE
02/04/2007
Introduction
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
Affinity Based Model of Multicellular Development
Background
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.
Affinity Based Model of Multicellular Development
Genetic Algorithms
Affinity Based Model of Multicellular Development
Ones Max Problem
The goal is to evolve an a population whose
individuals comprise of just 1s.
11
Average Fitness
10
9
8
7
6
5
0
5
10
15
20
25
30
Generation
Affinity Based Model of Multicellular Development
35
40
45
50
Development
Development is the process by which organisms
grow and develop.
http://www.microscopy-uk.org.uk/
Affinity Based Model of Multicellular Development
Why Use Development?
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.
Affinity Based Model of Multicellular Development
Modelling Development
Development was modelled using Java by creating a
gene regulatory network.
Cell
2
Corresponding classes were
created for the objects found in
nature including: Protein, Gene, Genome
Chromosome, Cell and Phenotype.
1
0.5
0.8
3
0.3
GA was used to evolve the genome (configuration)
used data for development.
Affinity Based Model of Multicellular Development
Protein
Gene Regulatory Network
In a GRN, a gene produces a protein. The protein
produced subsequently affects other genes and
ultimately cell behavior.
Gene 1
1
3
Cis – Reg Site
Gene 2
2
2
4
2
Coding Region
Affinity Based Model of Multicellular Development
Gene 3
1
3
2
3
4
1
Affinity Matrix
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 Based Model of Multicellular Development
Inputs
Output
ON
0.3 X 0.45
1.2 X -0.25
0.4 X 0.1
0
OFF
Single Cell Results
The following results were obtained using the
configuration data below.
Affinity Based Model of Multicellular Development
Flat Concentration
5
Concentration
4
3
2
1
0
0
2
4
6
8
10
12
14
Development Step
Protein 0
Protein 1
Protein 2
Protein 3
Protein 4
Affinity Based Model of Multicellular Development
16
18
20
Linear Concentration
3
Concentration
2
1
0
0
2
4
6
8
10
12
14
Development Step
Protein 0
Protein 1
Protein 2
Protein 3
Protein 4
Affinity Based Model of Multicellular Development
16
18
20
3
3
2
2
Concentration
Concentration
Heterochrony
1
0
1
0
0
2
4
6
8
10
12
14
16
18
20
0
2
4
6
Development Step
Protein 0
Protein 1
Protein 2
Protein 3
Protein 4
Affinity Based Model of Multicellular Development
8
10
12
Development Step
Protein 0
Protein 1
Protein 2
Protein 3
Protein 4
14
16
18
20
Multicellular Development
Next stage was to expand the current single cell model
to allow for multicellular development.
Cells have the ability to:
- Divide
- Die
- Communicate (via signalling proteins)
Affinity Based Model of Multicellular Development
Cell Division
Protein
Cell
Cell division is the process by which
a parent cell divides into two cells.
2
1
0.8
3
0.6
0.2
Genome
Genome Replicates
The genome of the parent cell is
transferred is copied and transferred
to the new cell.
1
3
0.6
0.2
2
0.8
Proteins Divide
Protein concentrations are
distributed between the cells.
Affinity Based Model of Multicellular Development
2
2
1
0.3
1
0.4
3
0.1
0.3
0.4
3
0.1
Cell Direction
π/2
The direction a cell divides in
is based on the concentration
of the direction protein.
3π/4
π/4
2
π
1
3
0
0
4
7
2π
5
6
5π/4
7π/4
3π/2
The direction around the unit
circle corresponds to the eight
possible neighbouring locations a
cell has in a 2D grid.
Affinity Based Model of Multicellular Development
3
2
1
4
cell
0
5
6
7
Protein Functions
The multicellular model has nine proteins with the
following functions:
Affinity Based Model of Multicellular Development
Multicellular Results
For the multicellular experiments the fitness was based
on the position of the cells.
Affinity Based Model of Multicellular Development
Line
Step 1
Step 10
Step 20
fitness = (1/cellsInside) + (cellsOutside/desiredLength)
Affinity Based Model of Multicellular Development
Square
Step 7
Step 15
Step 20
fitness = (size*size) – cellsInside + cellsOutside
Affinity Based Model of Multicellular Development
Morphogens
A morphogen is a substance which governs the
positions of the various specialized cell types within an
organism.
Source
Blue Threshold
It spreads from a localised
source and forms a
concentration gradient
across a developing organism.
Red Threshold
Sink
Cells
Based on Wolpert’s French flag model.
Affinity Based Model of Multicellular Development
Morphogen Gradients
morphogenConc = sourceConc x (1 / (sourceConc + distanceFromSource))
1.2
Morphogen Concentration
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
0
5
10
Distance
Affinity Based Model of Multicellular Development
15
20
French Flag
Affinity Based Model of Multicellular Development
Future Research
Research:
- Inter cell communication
- More complex development model
- 3D organisms
- Environmental effects during development
Possible Applications:
- Self developing systems
- Fault repairing circuits
Affinity Based Model of Multicellular Development
Questions
http://ohm.nuigalway.ie/0607/03macaodha
Affinity Based Model of Multicellular Development