|
|
*Timo Lubitz*
|
|
|
|
|
|
***
|
|
|
|
|
|
1. [Modules](#modules)
|
|
|
2. [Output](#output)
|
|
|
3. [Issues](#issues)
|
|
|
4. [References](#references)
|
|
|
|
|
|
***
|
|
|
|
|
|
## Modules
|
|
|
We have decided to initially start by modelling the **HOG pathway** and the **Calcineurin pathway**. We can add more if we get these running.
|
|
|
|
|
|
### HOG Pathway Submodule
|
|
|
The implementation is based on the model of [Klipp *et al.*, 2005](http://www.ncbi.nlm.nih.gov/pubmed/16025103).
|
|
|
We are receiving the turgor from the [volume](vol) module and we deliver nuclear, double phosphorylated *Hog1* as output to the gene regulation. As an effect, the expression of target gene *GPD1* (needed for glycerol synthesis and then turgor adaptation) is induced.
|
|
|
|
|
|
### Pheromone Pathway submodule
|
|
|
The implementation is based on the model of [Schaber *et al.*, 2006](http://www.ncbi.nlm.nih.gov/pubmed/16884493). The interface of the transport module to the pathway (G-protein coupled) is described in more detail in [Kofahl *et al.*, 2004](http://www.ncbi.nlm.nih.gov/pubmed/15300679), so we rather use this for the interface (not yet implemented). The output is the transcription factor *Ste12*, which can be part of two different dimers: *Ste12-Ste12-P* and *Ste12-Tec1-P*. In the former case, it induces the expression of PREP genes (in our case *BAR1*, *FAR1*, *FUS1*). In the latter case it induces FREP genes (in our case *FLO11*).
|
|
|
The feedback and crosstalk of this module will be interesting: it regulates the *BAR1* expression, which is transported to the extracellular medium to counteract the pheromone activation of the pathway. There are some more direct feedbacks to the pathway (*STE12*?). Furthermore, the pathway will interact with the cell cycle module via *Fus3*, *Ste5* and *Kss1* (not implemented yet).
|
|
|
|
|
|
### Calcineurin Pathway Submodule
|
|
|
The implementation is based on an old model of Falko Krause (*ENa1*) [unpublished].
|
|
|
Anyway, it is not tested for its behaviour yet.
|
|
|
|
|
|
### Following Submodules
|
|
|
We are planning to extend the Signalling module for the following pathways (list not neccessarily complete):
|
|
|
*PKA* (Totta Kasemo), *Snf1* (Timo Lubitz), *TORC1/2* (Ruben Vasquez-Uribe), *CWI* (Mareike Simon), *Snf3/Rgt2*, *PKC*
|
|
|
|
|
|
***
|
|
|
|
|
|
## Output
|
|
|
The output of each module needs to be an extensive list of the transcription factors that are regulated. Also, the affected genes.
|
|
|
|
|
|
***
|
|
|
|
|
|
## Issues
|
|
|
* UV, heat shock, DNA damage --> include more stresses? How?
|
|
|
* what about crosstalk between signalling pathways (e.g. between HOG and MAT: Ste11)? Right now, this is excluded.
|
|
|
* a general issue for the pathways is always the granularity. How detailled are they supposed to be modelled. Often this depends on the interfaces and what the other modules expect from the pathways, e.g. the cell cycle.
|
|
|
|
|
|
***
|
|
|
|
|
|
##References
|
|
|
* [Klipp *et al.*, 2005](http://www.ncbi.nlm.nih.gov/pubmed/16025103)
|
|
|
* [Kofahl *et al.*, 2004](http://www.ncbi.nlm.nih.gov/pubmed/15300679)
|
|
|
* [Schaber *et al.*, 2006](http://www.ncbi.nlm.nih.gov/pubmed/16884493) |
|
|
\ No newline at end of file |