Team:Chalmers-Gothenburg/Detection

Detection

The detection system is used so allow Saccharomyces cerevisiae to detect a foreign peptide. The system couples a signaling pathway, the pheromone pathway with a receptor in from a species from a different another Subphylum. The pheromone pathway starts with a ligand receptor association followed by disassociation of g proteins associated to the receptor. The disassociated g- protein starts a phosphorylation cascade (MAPK) leading to a activation of a transcriptionfactor.

Model Formation

There are significant work on modeling the pheromone pathway, there is even a database dedicated to yeast pheromone pathway modeling (http://yeastpheromonemodel.org/). The receptor is a G - protein coupled receptor (GPCR), the G-proteins are the Gα, Gβ, and Gγ, the Gβ and Gγ proteins interactions are neglected in the model and the proteins are assumed to always be associated. A similar assumption is made on the Gα protein and its associated GDP, however, the GDP can still me phosphorylated to GTP. All the monomers present in the MAPK-cascade complexes were assumed not to be associated all the time. Also all MAPK-cascade were assumed to irreversible reactions except from the last reaction where Fus3 can re associate with the complex and then reenter the cascade. The activation Ste12 by the inhibition of Dig1 and Dig2 is a one-step reaction between Fus3pp and inactive Ste12. The Protein expression were assumed to be linear to the amount of active transcription factor.


Chalmersgothenburgmodelreaktion.png

The reactions was defines as:

ChalmersGothenburgModellingDasEq3.png

ChalmersGothenburgModellingDasEq4.png


Yielding the following differential equations:

ChalmersGothenburgModellingDasEq1.png

ChalmersGothenburgModellingDasEq2.png



ChalmersGothenburgModellingDas1.png
ChalmersGothenburgModellingDas2.png
ChalmersGothenburgModellingDas3.png
ChalmersGothenburgModellingDas4.png
ChalmersGothenburgModellingDas5.png
ChalmersGothenburgModellingDas6.png
ChalmersGothenburgModellingDas7.png
ChalmersGothenburgModellingDasKaskad.png

Parameters

[Ste5] 158.33 nM
[Ste11] 158.33 nM
[Ste7] 36.40 nM
[Fus3] 686.40 nM
[Ste12] 200 nM
[Ste20] 1000 nM
[Gαβγ] 1666.67 nM
[Ste5/Ste11] 105.94 nM
[Ste7/Fus3] 77.87 nM
[Ste5/Ste11/Ste7/Fus3] 235.72 nM
Rest 0
k1 0.03min−1 nM−1 [1],[2]
k2 0.0012 min−1 nM−1 [1],[2]
k3 0.6 min−1 [1],[2]
k4 0.24 min−1 [1],[2]
k5 0.024 min−1 [1],[2]
k6 0.0036 min−1 nM−1 [1],[2]
k7 0.24 min−1 [1],[2]
k8 0.33min−1 nM−1 [1],[2]
k9 2000 min−1 nM−1 [1],[2]
k10 0.1 min−1 nM−1 [1]
k11 5min−1 [1]
k12 1min−1 nM−1 [1]
k13 3min−1 [1]
k14 1min−1 nM−1 [1],[3]
k15 3min−1 [1],[3]
k16 3min−1 nM−1 [1]
k17 100 min−1 [1]
k18 5min−1 nM−1 [1]
k19 1min−1 [1]
k20 10 min−1 [1]
k21 5min−1 [1]
k22 47 min−1 [1],[4]
k23 5min−1 [1],[4]
k24 345 min−1 [1],[4]
k25 5min−1 [1]
k26 50 min−1 [1]
k27 5min−1 [1]
k28 140 min−1 [1],[5]
k29 10 min−1 nM−1 [1]
k30 1min−1 [1]
k31 250 min−1 [1]
k32 5min−1 [1],[5]
k33 50 min−1 [1]
k34 18 min−1 nM−1 [1,[6]]
k35 10 min−1 [1]