Perturbing human TCR signaling pathway through superantigen from Staphylococcus aureus: Multi objective optimization under FBA

Abstract

Event Abstract Back to Event Perturbing human TCR signaling pathway through superantigen from Staphylococcus aureus: Multi objective optimization under FBA Namrata Tomar1* and Rajat K. De1 1 Indian Statistical Institute, Machine Intelligence Unit, India It is necessary to understand the dynamics of a cellular system to evaluate the capacity of an immune response at the time of infection. An integrated system was constructed that included Superantigen (SAg) expression regulatory and TCR signaling pathways of Homo sapiens to compare the pathogen (Staphylococccs aureus) perturbed and unperturbed system. A conflicting/multi objective optimization formalism under Flux Balance Analysis (FBA) was developed, and analyzed in four ways: (1) Implemented on an unperturbed TCR signaling pathway of H. sapiens, with the objective to maximize the concentrations of the regulators (c-values) that synthesizes the inhibitory molecules (CBL and SHP1), and observed their concentration values, which were later used as a base line for comparison. (2) The pathogen perturbed TCR signaling pathway (an integration of SAg expression regulatory pathway of S. aureus and TCR signaling pathway of H. sapiens), was studied with the objective of maximizing the c-values for stimulatory molecules (ZAP70, LCK and FYN). (3) The same integrated pathway was studied on optimization of two conflicting objectives (minimization of SAg expression and maximization of the c-values for TCR:CD3 complex and ZAP70). (4) Perturbation of the concentrations of regulators for some of the molecules (ZAP70, LCK, FYN) was performed, under pathogen perturbed and unperturbed conditions to check the effects of perturbation on CBL, SHP1 and Interleukins. Here, we figured out a relation between the TCR signaling inhibitory and stimulatory molecules - balance between these two keeps the system into resting/stimulating stage. Model predictions were validated through experimental evidences. Acknowledgements Acknowledgement - Ms. Namrata Tomar, one of the authors, gratefully acknowledges CSIR, India for providing her a Senior Research Fellowship (9/93 (0145)/12, EMR-I). Keywords: staphylococcal enterotoxin, Pathogen perturbation, Flux balance analysis, Staphylococcal superantigen expression regulatory pathway, optimization techniques Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Tomar N and De RK (2013). Perturbing human TCR signaling pathway through superantigen from Staphylococcus aureus: Multi objective optimization under FBA. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00695 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 13 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Ms. Namrata Tomar, Indian Statistical Institute, Machine Intelligence Unit, Kolkata, West Bengal, 700108, India, namrata.tomar@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract Supplemental Data The Authors in Frontiers Namrata Tomar Rajat K De Google Namrata Tomar Rajat K De Google Scholar Namrata Tomar Rajat K De PubMed Namrata Tomar Rajat K De Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.