1. From Steady State to Kinetics
Glucose Transport Regulatory Network in S. cerevisiae as a case study
Sooraj Kuttykrishnan
Brent Lab
Center For Genome Sciences
Washington University in St. Louis
29 October 2008

2. Goals
To model and parameterize each component in the network individually.
To model and parameterize the promoter region of each individual gene.
To predict and test steady state levels and time course of various species in the network.

3. Model Framework
Each regulatory interaction is modeled using an appropriate differential equation.
The system is assumed to be well mixed.
mRNA and protein degradation rates are assumed to be constant.
Stochastic variations are ignored.

4. Qualitative properties are well studied, but kinetics is poorly understood.
Number of genes and their regulators is relatively small.
Saccharomyces cerevisiae is genetically tractable.

5. Transcription Translation DNA mRNA1 + DNA TF1, TF2 mRNA1
mRNA1 + Protein1
Translation

8. Holstege FC et al. 1998, Cell., Vol. 95, pp. 717-728.
Yulei Wang et al , Proc Natl Acad Sci U S A., Vol. 99, pp. 5860–5865.
Belle A et al. 2006, Proc Natl Acad Sci U S A., Vol. 103, pp
Reifenberger E et al. 1997, Eur J Biochem , Vol. 245, pp

9. Snf1 Std1 Mth1 Mig1 Rgt1 Mig2 Glucose Low Glucose Hi Glucose Hxt2,3,4
Glucose metabolism
Low Glucose
Hi Glucose
Rgt2
Snf3
Glucose signal
Std1
Mth1
Mig1
Rgt1
MTH1
SNF3
Mig2
STD1
MIG2
MIG1
SUC2 et al.
HXT2,HXT4
HXT1,HXT3

10. Topology Is Important
WT(2% Glu)
ΔRGT1
(2% Gal)

11. Steady State Predictions

12. Predicted
Observed
HXT4 was observed to be induced in 0.1% Glucose using
β- galactosidase assays.
Long half life of LacZ impedes observation of the fall in HXT4 levels.

13. Conclusions
Modelled and parameterized individual components of the network independently.
Useful to predict kinetics of rewirings.
Model generated novel and testable hypotheses.
Steady state predictions are in good agreement with observations.

14. Acknowledgements Brent Lab Johnston Lab Michael Brent Laura Langton
Brian Haynes
Johnston Lab
Jeff Sabina
Mark Johnston