An Exhibition of Applications: Molecular Computing Dr. Chrisantha Fernando Systems Biology Centre Birmingham University Dr. Chrisantha Fernando Systems Biology Centre Birmingham University

Don’t think we can escape from chemotaxis just yet…

Stochastic Modeling  So far we have been doing deterministic modeling.  Stochastic models consider individual molecules, undergoing discrete reaction events, i.e. chemical (autonomous) agents.  These models diverge from deterministic models when particle numbers are low, but also they allow “emergent” reactions…  To get a feel for stochastic modeling, try BioNetS.  So far we have been doing deterministic modeling.  Stochastic models consider individual molecules, undergoing discrete reaction events, i.e. chemical (autonomous) agents.  These models diverge from deterministic models when particle numbers are low, but also they allow “emergent” reactions…  To get a feel for stochastic modeling, try BioNetS.

BioNetS Easy to use

Here is a paper written using the tool…

Lets start with some simple chemical networks…

CheZ RCheZ R Rm Example of a Saturated Enzyme (CheZ) acting to methylate R

Applications  Development and Cellular Differentiation  A Molecular Machine: Bacteriorhodopsin  Molecular Self-Assembly  Liquid State Machines in Cellular Networks?  Development and Cellular Differentiation  A Molecular Machine: Bacteriorhodopsin  Molecular Self-Assembly  Liquid State Machines in Cellular Networks?

Development

eggblastoderm fate map larva T A Fly Development acron head thorax abdomen telson T1 T2 T3 A1 A2 A3 A4 A5 A6 A7 A8 (cuticle) “stripy” expression of segmentation gene fushi tarazu (ftz) anterior posterior dorsal epithelium (6,000 cells)

A diffusion gradient is set up by maternally expressed genes bcd mRNA Bcd protein anteriorposterior

The Reaction Diffusion Principle source of morphogen threshold blue threshold white Gradient cells

The Fly ‘French Flag’ colors are made like this… bcd protein binds differentially to enhancers of target (gap) genes target genes are zygotically expressed gap genes low affinity high affinity

bicoid Krüppel even-skipped (gap gene) (pair-rule gene) bicoid maternally expressed genes caudal > protein gradients > 7 stripes of protein expr. > distinct protein expr. domain zygotically expressed genes

From Bio to Techno  Can we make self-assembling, self- organizing machines that utilize the robust mechanisms displayed by multicellular development?

The French Flag Problem

MIT Amorphous Computing Lab  Printable computers   Printable computers  Asynchrony = Stochastic noise in/between cells Fault tolerance= Protein misfolding/non-specific binding Spatial constraints= Allostery and diffusion constraints Adaptable topology = Individual differences between cells/organs Code compactness = Slow protein conformation changes "A programming model employing a self-organizing ecology of mobile process fragments supports a variety of useful applications on a paintable computer” Inspired by biological development

Bacteriorhodipsin Archaebacteria Halobacteria Salinarium absorbs green light protons are pumped one at a time from the inside of the cell to the outside Photons react with a bound retinal group causing conformational change in BR 1. Retinal changes form when absorbing a photon

Agent Based Models of ‘Molecular’ Self-Assembly

Molecular Dynamics computer simulation is useful in designing molecular self-assembling systems

Now for a special guest…  Ben Jones (PhD student), will talk about our recent paper that we will present in Hawaii this weekend.  We model the gene transcription network of E.Coli, and ask if it works like a bucket of water.  Ben Jones (PhD student), will talk about our recent paper that we will present in Hawaii this weekend.  We model the gene transcription network of E.Coli, and ask if it works like a bucket of water.