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Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study

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Abstract

Various T-cell co-receptor molecules and calcium channel CRAC play a pivotal role in the maintenance of cell’s functional responses by regulating the production of effector molecules (mostly cytokines) that aids in immune clearance and also maintaining the cell in a functionally active state. Any defect in these co-receptor signalling pathways may lead to an altered expression pattern of the effector molecules. To study the propagation of such defects with time and their effect on the intracellular protein expression patterns, a comprehensive and largest pathway map of T-cell activation network is reconstructed manually. The entire pathway reactions are then translated using logical equations and simulated using the published time series microarray expression data as inputs. After validating the model, the effect of in silico knock down of co-receptor molecules on the expression patterns of their downstream proteins is studied and simultaneously the changes in the phenotypic behaviours of the T-cell population are predicted, which shows significant variations among the proteins expression and the signalling routes through which the response is propagated in the cytoplasm. This integrative computational approach serves as a valuable technique to study the changes in protein expression patterns and helps to predict variations in the cellular behaviour.

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Acknowledgments

We thank Department of Biotechnology, India (Project Code: BT/PR13689/BID/07/363/2010), and Council of Scientific and Industrial Research, XII Five Year Plan Project ‘GENESIS’ (BSC0121) for providing financial support to perform this work. SC acknowledges the research fellowship from DST-INSPIRE fellowship program. The authors also acknowledge Mr Shomeek Chowdhury for his effort to collate few pathway specific data used in this work.

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  1. Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune, 411 008, India

    Piyali Ganguli, Saikat Chowdhury, Rupa Bhowmick & Ram Rup Sarkar

  2. Academy of Scientific & Innovative Research (AcSIR), New Delhi, 110 001, India

    Saikat Chowdhury & Ram Rup Sarkar

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  1. Piyali Ganguli
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  2. Saikat Chowdhury
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[Ganguli P, Chowdhury S, Bhowmick R and Sarkar RR 2015 Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study. J. Biosci.] DOI 10.1007/s12038-015-9561-1

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Ganguli, P., Chowdhury, S., Bhowmick, R. et al. Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study. J Biosci 40, 769–789 (2015). https://doi.org/10.1007/s12038-015-9561-1

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