Mol2013 - Immune Signal Transduction in Leishmaniasis

Model Identifier
BIOMD0000000477
Short description

Created by The MathWorks, Inc. SimBiology tool, Version 3.3
Format
SBML (L2V4)
Related Publication
  • Immune signal transduction in leishmaniasis from natural to artificial systems: role of feedback loop insertion. Click here to expand
  • Milsee Mol, Milind S Patole, Shailza Singh
  • Biochimica et biophysica acta , 1/ 2014 , Volume 1840 , Issue 1 , pages: 71-79 , PubMed ID: 23994140
  • National Centre for Cell Science, NCCS Complex, Ganeshkhind, Pune University Campus, Pune 411007, India.

  • Background

    Modulated immune signal (CD14-TLR and TNF) in leishmaniasis can be linked to EGFR pathway involved in wound healing, through crosstalk points. This signaling network can be further linked to a synthetic gene circuit acting as a positive feedback loop to elicit a synchronized intercellular communication among the immune cells which may contribute to a better understanding of signaling dynamics in leishmaniasis.

    Methods

    Network reconstruction with positive feedback loop, simulation (ODE 15s solver) and sensitivity analysis of CD14-TLR, TNF and EGFR was done in SimBiology (MATLAB 7.11.1). Cytoscape and adjacency matrix were used to calculate network topology. PCA was extracted by using sensitivity coefficient in MATLAB. Model reduction was done using time, flux and sensitivity score.

    Results

    Network has five crosstalk points: NIK, IκB-NFκB and MKK (4/7, 3/6, 1/2) which show high flux and sensitivity. PI3K in EGFR pathway shows high flux and sensitivity. PCA score was high for cytoplasmic ERK1/2, PI3K, Atk, STAT1/3 and nuclear JNK. Of the 125 parameters, 20% are crucial as deduced by model reduction.

    Conclusions

    EGFR can be linked to CD14-TLR and TNF through the MAPK crosstalk points. These pathways may be controlled through Ras and Raf that lie upstream of signaling components ERK ½ (c) and JNK (n) that have a high PCA score via a synthetic gene circuit for activating cell-cell communication to elicit an inflammatory response. Also a disease resolving effect may be achieved through PI3K in the EGFR pathway.

    General significance

    The reconstructed signaling network can be linked to a gene circuit with a positive feedback loop, for cell-cell communication resulting in synchronized response in the immune cell population, for disease resolving effect in leishmaniasis.
Contributors
Submitter of the first revision: Shailza Singh
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modellers: administrator, Shailza Singh

Metadata information

is (2 statements)
BioModels Database BIOMD0000000477
BioModels Database MODEL1308080000

isDescribedBy (1 statement)
PubMed 23994140

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (1 statement)
hasPart (1 statement)
hasProperty (2 statements)
Human Disease Ontology leishmaniasis
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model

Connected external resources