Dudziuk2019 - Biologically sound formal model of Hsp70 heat induction

  public model
Model Identifier
BIOMD0000000843
Short description 
This is a mathematical model of Hsp70 induction. To model heat shock effects, the model incorporates temperature dependencies in transcirption to Hsp70 mRNA and in dissociation of transcriptional complexes, in addition to a formal expression relating temperature to protein denaturation.
Format
SBML (L2V4)
Related Publication
  • Biologically sound formal model of Hsp70 heat induction.
  • Dudziuk G, Wronowska W, Gambin A, Szymańska Z, Rybiński M
  • Journal of theoretical biology , 10/ 2019 , Volume 487 , pages: 74-101 , PubMed ID: 31181241
  • ICM, University of Warsaw, ul. Tyniecka 15/17, Warsaw 02-630, Poland. Electronic address: g.dudziuk@icm.edu.pl.
  • A proper response to rapid environmental changes is essential for cell survival and requires efficient modifications in the pattern of gene expression. In this respect, a prominent example is Hsp70, a chaperone protein whose synthesis is dynamically regulated in stress conditions. In this paper, we expand a formal model of Hsp70 heat induction originally proposed in previous articles. To accurately capture various modes of heat shock effects, we not only introduce temperature dependencies in transcription to Hsp70 mRNA and in dissociation of transcriptional complexes, but we also derive a new formal expression for the temperature dependence in protein denaturation. We calibrate our model using comprehensive sets of both previously published experimental data and also biologically justified constraints. Interestingly, we obtain a biologically plausible temperature dependence of the transcriptional complex dissociation, despite the lack of biological constraints imposed in the calibration process. Finally, based on a sensitivity analysis of the model carried out in both deterministic and stochastic settings, we suggest that the regulation of the binding of transcriptional complexes plays a key role in Hsp70 induction upon heat shock. In conclusion, we provide a model that is able to capture the essential dynamics of the Hsp70 heat induction whilst being biologically sound in terms of temperature dependencies, description of protein denaturation and imposed calibration constraints.
Contributors
Submitter of the first revision: Grzegorz
Submitter of this revision: Tung Nguyen
Modellers: Tung Nguyen, Grzegorz, Krishna Kumar Tiwari, Johannes Meyer

Metadata information

is (2 statements)
BioModels Database BIOMD0000000843
BioModels Database MODEL1807160001

isDescribedBy (1 statement)
PubMed 31181241

isDerivedFrom (2 statements)
PubMed 19327370
PubMed 23985732

hasProperty (3 statements)
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Heat-Shock Response
UniProt Knowledgebase Heat shock protein 72

Curation status
Curated
Tags

Connected external resources

Name Description Size Actions

Model files
Dudziuk2019.xml SBML L2V4 Representation of Dudziuk2019 - Biologically sound formal model of Hsp70 heat induction 76.44 KB Preview | Download

Additional files
Dudziuk2019.cps COPASI file of Dudziuk2019 - Biologically sound formal model of Hsp70 heat induction 102.61 KB Preview | Download
Dudziuk2019.sedml SED-ML file of Dudziuk2019 - Biologically sound formal model of Hsp70 heat induction 6.82 KB Preview | Download

  • Model originally submitted by : Grzegorz
  • Submitted: Jun 28, 2019 10:38:23 AM
  • Last Modified: Apr 22, 2021 10:53:48 AM
Revisions
  • Version: 9 public model Download this version
    • Submitted on: Apr 22, 2021 10:53:48 AM
    • Submitted by: Tung Nguyen
    • With comment: Automatically added model identifier BIOMD0000000843
  • Version: 7 public model Download this version
    • Submitted on: Nov 7, 2019 12:49:15 PM
    • Submitted by: Johannes Meyer
    • With comment: Automatically added model identifier BIOMD0000000843
  • Version: 5 public model Download this version
    • Submitted on: Jun 28, 2019 10:38:23 AM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Submitted for public release

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
HSP

Benzylpenicilloic acid 		52.06 μmol
S

MI:0908 ; Protein 		8.122E-8 μmol
HSP S

Benzylpenicilloic acid 		5.268E-4 μmol
HSF

CCO:37068 		0.001363 μmol
HSF 3

CCO:37068 		9.082E-6 μmol
HSE

SO:0001850 		3.996E-6 μmol
Reactions
Reactions Rate Parameters
=> HSP; mRNA compartment*k4*mRNA k4 = 18.85
HSP + S => HSP_S compartment*k1*HSP*S k1 = 12.6
HSP_S => HSP + P compartment*k10*HSP_S k10 = 0.09813
HSP + HSF_3 => HSF + HSP_HSF compartment*I3*HSP*HSF_3 I3 = 2.392
HSP => compartment*k9*HSP k9 = 0.001888
HSE + HSF_3 => HSE_HSF_3 compartment*k7*HSE*HSF_3 k7 = 5892.0
HSF + HSP => HSP_HSF compartment*k2*HSF*HSP k2 = 0.218
Curator's comment:
(added: 07 Nov 2019, 12:48:51, updated: 07 Nov 2019, 12:48:51)
Reproduced plot of Figure D3 in the original publication. Model simulated and data obtained using COPASI 4.24 (Build 197). Plot produced using Wolfram Mathematica 11.3.