Registry of Standard Biological Models/CellML Practical/Practical 1

Goal: Describe a simple genetic assembly (promoter + RBS + protein coding region + stop codon) from the description of each sub-component.

Example of such a part: BBa_I7101

=Simple Modeling=

Assumptions: > Central Dogma: Gene --> mRNA --> Protein > unlimited resources to produce mRNA and proteins (i.e. excess of Polymerases, Ribosomes, tRNA ...) > No stochastic effect taken into account, continous approach

\frac{d[mRNA]}{dt} = k_M*[Gene] - \gamma_M*[mRNA]

\frac{d[Protein]}{dt} = k_P*[mRNA] - \gamma_P*[Protein]

Where,

\emph [Gene] = number of gene copies per cell, [Gene] \emph [mRNA] = mRNA concentration per cell, [mRNA] \emph [Protein] = Protein concentration per cell, [Protein] \emph k_{M} = mRNA production rate (PoPS), unit:[mRNA]/[DNA]/s \emph k_{P} = Protein production rate (RiPS), unit:[Protein]/[mRNA]/s \gamma_M = mRNA degradation rate, 1/s \gamma_P = Protein degradation rate., 1/s

=BioBrick matching=

=CellML matching=

>>>>Comments
 * About the Promoter:
 * Characterized by nb gene copies + transcription rate
 * PoPs is defined as a MathML expression. Can easily define repression, activation or constitutive expression behaviour.
 * Inputs: none. BC: Should numbers of copies be here? VR: true.
 * Output: PoPs (Polymerases per second). It is used to feed a Protein component. BC: Although it feeds into a protein component here, more generally it could feed into other components, such as tRNA. VR: Not too sure to understand how you define PoPs for tRNAs. Can you explain ?  BC:I mean that PoPS should be independent of whatever piece of DNA you are sitting on when you measure it.  So the polymerases could be transcribing an mRNA or a tRNA or whatever.  Since we can easily imagine wanting to transcribe non-protein components such as tRNA, we need to keep the output of the promoter general in my opinion. VR: I am a bit confused. To me polymerases are only binding DNA (chromosomal or plasmid). tRNA are compounds formed by an anti-codon and amino-acid site, to me they onlyinteract with the ribosome during translation of the protein. Am I missing something ?


 * About the RBS:
 * Characterized by translation rate
 * RiPS is defined by a MathML expression. Could describe limited resource at this point.
 * Inputs: needs [mRNA]
 * Ouputs: RiPs (Ribosomes per second). It is used to feed a Protein component.


 * About the Protein:
 * I felt the need to encapsulate in the same component the concept of mRNA and protein. mRNA is not a BioBrick anyway. This component might benefit being implemented as a group, or maybe simply an import of a 'protein_molecule' component and a 'mRNA_molecule' component.
 * We should think about riboswitch parts which are affecting mRNA behaviour
 * Characterized by degradation rate of mRNA and Protein
 * Inputs: need PoPs from a promoter + RiPs from a RBS
 * BC:Do we really need PoPS as an input to a protein component. I feel that the PoPS defines the numbers of mRNA and after that, it doesn't really affect the protein component.  What do you think?  VR: I have to admit that I haven't found yet a design with which I am happy. My problem comes from the fact that the mRNA component is not a BioBrick, so I would like to hide it some how. I have also tried to encapsulate it with the RBS component here.
 * Outputs: [mRNA] + [Protein]


 * The overall part:
 * Inputs: none BC:Number of DNA copies of the part? VR: true.
 * Outputs: Protein and mRNA expression levelss
 * Import all the other components: Promoter + RBS + Protein