Registry of Standard Biological Models/CellML Practical

Scope of the abstract

• Demonstrate the use of CellML 1.1 to describe BioBricks [1](encapsulated and hierarchical assemblies)
  • building a modular Repressilator (see practicals)
• Define requested features of a Virtual BioBrick Repository
  • review on existing model repository
  • specific requirements for a virtual biobrick repository
  • toward a Synthetic Biology CAD system

Practical with CellML to describe BioBricks

List of models defining a CellML structure : Registry_of_Standard_Biological_Models/Basic_Component_Models

CellML 1.1 looks very flexible and could provide all the desired features that we are looking for in order to describe a BioBrick [2]. Some testing has to be done on real examples to see how far we can incorporate BioBrick concepts into CellML description capabilities.

• Practical 1: Describe a simple genetic assembly (promoter + RBS + protein coding region + stop codon) from the description of each sub-component.
  • example of such a part: <bbpart>BBa_I13522</bbpart>
    • It might be better to use <bbpart>BBa_I7101</bbpart> as this has been characterized quite extensively by Caitlin Conboy and Jennifer Braff (westerns, northerns etc.).
  • the concept of PoPS [3] could be used as a connection mechanism from a dynamical perspective
  • Each part could be represented as a CellML 'component' and then a group could be created to produce the final assembly

• Practical 2: Describe a standardized inverter as a CellML module (example found here <bbpart>BBa_Q04121</bbpart> )
  • NB: this is a non functional assembly as there is no promoter to the coding region
  • Define clear inputs and outputs to allow future assembly with counter parts (i.e. LacI protein with LacI promoter)

• Practical 3: From 3 standardized inverter build the Elowitz repressilator
  • part found here: <bbpart>BBa_I5610</bbpart>
  • demonstrate modularity and re-use offered by CellML
  • An abstraction could be created to encapsulate everything and define an oscillator device (use of group concept in CellML).

General aim

In this article, we are investigating the creation of a virtual equivalent to the DNA parts registry using CellML. Each physical DNA part would have one or multiple models to describe their properties. A model registry could be the core of a CAD system for synthetic biology where new assemblies of parts would be simulated and tested before starting the wetlab.

This problem has 2 main required features: a standardized description language and a structured repository for the created models

• Wish list for a BioBrick description language
  • standardized
  • machine and human readable
  • quantitative and/or qualitative description
  • modular
  • hierarchical

Wish list for a BioBrick model repository

• • store, curate and search models
  • reference DNA part registry
  • drag and drop mechanism to assemble new systems

Background and References

• Description language for bio-models
  • CellML [4]
  • SBML [5]
  • MML

• Databases of models
  • CellML repository [6]
  • BioModels [www.ebi.ac.uk/biomodels]

• Previous CAD system
  • BioJADE [7]
  • BioSPICE [8]

• BioBricks [9]
• Part registry[10]