title: Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: a computational study.
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.
authors.affiliation: Chemical Engineering and Process Development Division, CSIR-National Chemical Laboratory, Pune 411 008, India.
authors.forename: Piyali
authors.initials: P
authors.lastname: Ganguli
authors.forename: Saikat
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Rupa
authors.initials: R
authors.lastname: Bhowmick
authors.forename: Ram Rup
authors.initials: RR
authors.lastname: Sarkar
mesh_terms: D015220:Calcium Channels / Q000235:genetics / Q000276:immunology; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics*; D046228:Microarray Analysis; D000071740:ORAI1 Protein; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D015220:Calcium Channels; D061025:Costimulatory and Inhibitory T-Cell Receptors; D036341:Intercellular Signaling Peptides and Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D014157:Transcription Factors