Exploring phospholipase C-coupled Ca 2+ signalling networks using boolean modelling

G. Bhardwaj, C. P. Wells, R. Albert, D. B. Van Rossum, R. L. Patterson

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In this study, the authors explored the utility of a descriptive and predictive bionetwork model for phospholipase C-coupled calcium signalling pathways, built with non-kinetic experimental information. Boolean models generated from these data yield oscillatory activity patterns for both the endoplasmic reticulum resident inositol-1,4,5-trisphosphate receptor (IP 3R) and the plasma-membrane resident canonical transient receptor potential channel 3 (TRPC3). These results are specific as randomisation of the Boolean operators ablates oscillatory pattern formation. Furthermore, knock-out simulations of the IP3R, TRPC3 and multiple other proteins recapitulate experimentally derived results. The potential of this approach can be observed by its ability to predict previously undescribed cellular phenotypes using in vitro experimental data. Indeed, our cellular analysis of the developmental and calcium-regulatory protein, DANGER1a, confirms the counter-intuitive predictions from our Boolean models in two highly relevant cellular models. Based on these results, the authors theorise that with sufficient legacy knowledge and/or computational biology predictions, Boolean networks can provide a robust method for predictive modelling of any biological system.

Original languageEnglish (US)
Pages (from-to)174-184
Number of pages11
JournalIET Systems Biology
Volume5
Issue number3
DOIs
StatePublished - May 2011

Fingerprint

Transient Receptor Potential Channels
Boolean Networks
Type C Phospholipases
Receptor
Boolean Model
Calcium
Inositol 1,4,5-Trisphosphate Receptors
Calcium Signaling
Random Allocation
Computational Biology
Modeling
Endoplasmic Reticulum
Protein
Predictive Modeling
Proteins
Plasma Membrane
Signaling Pathways
Prediction
Cell Membrane
Predictive Model

ASJC Scopus subject areas

  • Biotechnology
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Modeling and Simulation

Cite this

Bhardwaj, G., Wells, C. P., Albert, R., Van Rossum, D. B., & Patterson, R. L. (2011). Exploring phospholipase C-coupled Ca 2+ signalling networks using boolean modelling. IET Systems Biology, 5(3), 174-184. https://doi.org/10.1049/iet-syb.2010.0019

Exploring phospholipase C-coupled Ca 2+ signalling networks using boolean modelling. / Bhardwaj, G.; Wells, C. P.; Albert, R.; Van Rossum, D. B.; Patterson, R. L.

In: IET Systems Biology, Vol. 5, No. 3, 05.2011, p. 174-184.

Research output: Contribution to journalArticle

Bhardwaj, G, Wells, CP, Albert, R, Van Rossum, DB & Patterson, RL 2011, 'Exploring phospholipase C-coupled Ca 2+ signalling networks using boolean modelling', IET Systems Biology, vol. 5, no. 3, pp. 174-184. https://doi.org/10.1049/iet-syb.2010.0019
Bhardwaj, G. ; Wells, C. P. ; Albert, R. ; Van Rossum, D. B. ; Patterson, R. L. / Exploring phospholipase C-coupled Ca 2+ signalling networks using boolean modelling. In: IET Systems Biology. 2011 ; Vol. 5, No. 3. pp. 174-184.
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