Registry of Standard Biological Models/BioSysBio Abstract Draft

Registry of BioBricks Models using CellML

Author(s): Vincent Rouilly¹, Barry Canton², Poul Nielsen³, Richard Kitney¹
Affiliations: ¹Imperial College London, ²MIT, ³The University of Auckland
Contact:email: vincent.rouilly@ic.ac.uk
Keywords: 'synthetic biology' 'biobrick' 'cellML' 'model database'

Background/Introduction

One of the main goal in Synthetic Biology is to assess the possibility of building biological systems from interchangeable and standardized parts. In order to provide building blocks, a Registry of physical DNA BioBricks[1] has been established at the MIT. BioBrick[2] can then be assembled[3] to form devices or more complicated systems in living cells.

As in most engineering fields, the challenge begins with a comprehensive description and understanding of the problem. This involves qualitative and quantitative analysis: clear physical interpretation of the problem followed by an adequate mathematical description. Therefore, alongside the effort of characterizing experimentaly the BioBricks , a logical extension to the Registry would be to build a Registry of Biobrick Models to complement the wetlab work.

Motivations behind a Registry of BioBrick Models

to store, search and curate models related to physical DNA Biobricks. to gain a deeper understanding in the way BioBricks work. to promote the re-useability of BioBrick models. to explore through simulations the properties of de-novo assemblies between parts. to go towards a faster/cheaper development process. to complement the open-source spirit in Synthetic Biology and open-up a new form of "dry-work" contributions.

image

A key aspect in this effort is the use of a description language being able to describe and support the BioBrick concepts.

Properties needed for BioBrick description language
Human and machine readable. Enable the describtion of qualitative and quantitative models of biochemical networks. Enable the definition of modules (as biobricks have inputs/outputs). Enable the definition of hierachies between modules (as a system will be composed of sub-systems or devices). Enable a minimum annotation scheme to comply with MIRIAM[4], for example.	image

Results

In this article, is demonstrated that such Registry of BioBrick Models is achievable. A mock-up is provided based on the great flexibility and modularity offered by CellML [5].

Generic CellML architecture for BioBricks
generic model architectures in CellML are defined for most of the types of the parts encountered in the DNA registry (plasmid, promoter, RBS, proteins, riboswitch ...).	image
Catalog of quantitative BioBrick models
A catalog of quantitative models based on already characterized parts is presented.	image
Building simulations from modular BioBrick models
the versatility of the approach is demonstrated by simulating different sytems from a set of pre-defined models [to be defined].	image

Conclusion

Using CellML, a basic Registry of BioBrick models has been built. It takes advantage of CellML flexibility and modularity to provide a catalog of quantitative models which are standardized and reuseable. With the growth of the physical DNA parts and their characterization, such a repository will help to gain a deeper understanding of the BioBrick properties as well a speeding up the process of building-up new devices and systems. But more importantly, it will help to federate the growing number of contributions from the modeling community.

Stuff that we might want to include too

• synergy between the definition of a biobrick model and the way its characterization is done (validation scheme between simulation and experiment)
• future work: CAD system with drag and drop of biobricks and use of 'CellML units' to validate connections between modules,
• elaborate on MIRIAM compliance + touch on linking model with gene and protein databases.
• conclusion is not great ...

References

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