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middleton1

middleton1

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Reactions

re1

GA4-GID association

s1 + s2 > s65

re10

GA15-GA20ox association

s24 + s27 > s31

re11

GA15.GA20ox dissociation

s31 > s24 + s27

re12

GA24 production

s31 > s27 + s25

re13

GA24-GA20ox association

s25 + s27 > s30

re14

GA24.GA20ox dissociation

s30 > s25 + s27

re15

GA9 production

s30 > s27 + s26

re16

GA9-GA3ox association

s26 + s28 > s29

re17

GA9.GA3ox dissociation

s29 > s26 + s28

re18

GA4 production

s29 > s28 + s1

re19

GA4.GID lid closing

s65 > s62

re2

GA4.GID dissociation

s65 > s2 + s1

re20

GA4.GID-Closed lid opening

s62 > s65

re21

della translation

s7 > s16

re22

ga20ox translation

s6 > s27

re23

ga3ox translation

s5 > s28

re24

gid translation

s33 > s2

re27

ga20ox transcription (activated by DELLA)

s11 > s39

re28

gid transcription (activated by DELLA)

s15 > s42

re29

della transcription (repressed by DELLA)

s34 > s40

re3

GA4.GID-DELLA1 association

s62 + s16 > s45

re30

ga3ox transcription (activated by DELLA)

s35 > s41

re31

della decay

s40 > s34

re32

gid decay

s42 > s15

re33

ga20ox decay

s39 > s11

re34

ga3ox decay

s41 > s35

re35

GA20ox decay

s27 > s6

re37

GID decay

s2 > s33

re38

GA3ox decay

s28 > s5

re39

GA4.GID-DELLA2 association

s62 + s16 > s36

re4

GA4.GID.DELLA1 dissociation

s45 > s62 + s16

re40

GA4.GID.DELLA2 dissociation

s36 > s62 + s16

re41

GA4 supply

s66 > s1

re42

degradation of GA12

s23 > s67

re43

degradation of GA15

s24 > s68

re44

degradation of GA24

s25 > s69

re45

degradation of GA9

s26 > s70

re46

degradation of GA4

s1 > s71

re5

DELLA ubiquitination

s45 > s62 + s22

re6

GA12 supply

s3 > s23

re7

GA12-GA20ox association

s23 + s27 > s32

re8

GA12.GA20ox dissociation

s32 > s23 + s27

re9

GA15 production

s32 > s27 + s24

Parameters

Global parameters
re1
re10
re11
re12
re13
re14
re15
re16
re17
re18
re19
re2
re20
re21
re22
re23
re24
re27
re28
re29
re3
re30
re35
re37
re38
re39
re4
re40
re41
re46
re5
re7
re8
re9

Fixed species

Initial values

Functions and Rules

Assignment rules

omegaGA12 = R * omegaGA12ga13

Function definitions

Events

AddGA4

Trigger: gt(time, tGA4on)

Delay:

Assignments:

  • omegaGA4 = appliedGA4

RemoveGA4

Trigger: gt(time, tGA4off)

Delay:

Assignments:

  • omegaGA4 = 0

Constraints

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.


Species:

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Mathematical modeling elucidates the role of transcriptional feedback in gibberellin signaling.

  • Alistair M Middleton
  • Susana Úbeda-Tomás
  • Jayne Griffiths
  • Tara Holman
  • Peter Hedden
  • Stephen G Thomas
  • Andrew L Phillips
  • Michael J Holdsworth
  • Malcolm J Bennett
  • John R King
  • Markus R Owen
Proc. Natl. Acad. Sci. U.S.A. 2012; 109 (19): 7571-7576
Abstract
The hormone gibberellin (GA) is a key regulator of plant growth. Many of the components of the gibberellin signal transduction [e.g., GIBBERELLIN INSENSITIVE DWARF 1 (GID1) and DELLA], biosynthesis [e.g., GA 20-oxidase (GA20ox) and GA3ox], and deactivation pathways have been identified. Gibberellin binds its receptor, GID1, to form a complex that mediates the degradation of DELLA proteins. In this way, gibberellin relieves DELLA-dependent growth repression. However, gibberellin regulates expression of GID1, GA20ox, and GA3ox, and there is also evidence that it regulates DELLA expression. In this paper, we use integrated mathematical modeling and experiments to understand how these feedback loops interact to control gibberellin signaling. Model simulations are in good agreement with in vitro data on the signal transduction and biosynthesis pathways and in vivo data on the expression levels of gibberellin-responsive genes. We find that GA-GID1 interactions are characterized by two timescales (because of a lid on GID1 that can open and close slowly relative to GA-GID1 binding and dissociation). Furthermore, the model accurately predicts the response to exogenous gibberellin after a number of chemical and genetic perturbations. Finally, we investigate the role of the various feedback loops in gibberellin signaling. We find that regulation of GA20ox transcription plays a significant role in both modulating the level of endogenous gibberellin and generating overshoots after the removal of exogenous gibberellin. Moreover, although the contribution of other individual feedback loops seems relatively small, GID1 and DELLA transcriptional regulation acts synergistically with GA20ox feedback.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000422) Biomodels notes: This model corresponds to the full model that is described in the reference publication. The model parameter corresponds to wild-type and reproduces Figure 4C wild-type with R=1. The simulation runs for 500 time units (minutes) to allow the system to approach its steady state, then adds exogenous hormone for 120 time units, before removing the exogenous hormone until a total time of 800. So, the total run time is 800 minutes, having exogenous hormone between time points 500 and 620 (120 mins). In the paper, time is shifted so that t=0 corresponds to the addition of hormone, i.e. 500mins. The plot here show the time-course simulation between 500 mins(t=0 in the paper) and 800 mins (t=300 in the paper). The y-axis scale in the paper is in nM, whereas in the model it is in ?M. The plot date were obtained by simulating the model using Copasi v4.8 (Build 35). The plot was generated using Gnuplot. JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.