Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Gene nomenclature wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Point mutation wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Helitron (biology) wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
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