Analysis of the role of trans-membrane molecules for T cell calcium dynamics
Triggering of T cell receptors induces a nonlinear calcium response necessary for T cell-activation. The contribution of various trans-membrane ion currents and of intracellular organelles to the calcium signal is controversial. We developed an ordinary-differential-equation model for T cell calcium electrophysiology based on measured single trans-membrane protein properties. This reduces the number of tunable parameters and increases predictive power.
In cooperation with Andreas Guse and Ralf Fliegert (Hamburg, Germany) the model was validated with experimental data for calcium dynamics under different conditions. The model proposed that Calcium Release-Activated Channels rather than inducing an early calcium increase supports a long-term sustained calcium enhancement. Currently, we extend this model with the aim to understand pharmacological interventions that target ion-conducting trans-membrane molecules, in particular in the context of transplantation and graft rejection.
Sahamoddin Khailaie, Phillipe A. Robert, Alexey Uvarovskii (since 2016 in Heidelberg)
Schmeitz C, Hernandez-Vargas EA, Fliegert R, Guse AH, Meyer-Hermann M. A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties. Front Immunol4 (2013) 277.
T lymphocyte calcium dynamics derived from single transmembrane protein properties. Front Immunol 4 (2013) 277.
- Systems Immunology- Prof. Dr. Michael Meyer-Hermann