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                       BIOINFORMATICS COLLOQUIUM
                    School of Computational Sciences
                        George Mason University
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      Modeling the Calcium-dependent Activation of T-lymphocytes

                             Saleet Jafri
                                 GMU

                       Tuesday, January 20, 2004
                               4:30 pm
               Verizon Auditorium, Prince William Campus

The activation of T-lymphocytes is the primary response of the immune
system to foreign proteins (antigens).  When thus stimulated at the cell
surface, a intracellular signalling cascade results in elevated
intracellular calcium concentration in the form of calcium
oscillations. Recent experimental studies have shown that two
calcium-dependent transcription factors, NFAT and NFkB which activate
the genes that code for two different interleukins that are involved in
activation of the immune system, are differentially activated depending
on the frequency of the calcium oscillations.  In this study, a
mathematical model of the biochemical reaction pathways involved in the
activation of these two transcription factors is developed.  Kinetic
parameters for the models are determined by experimental estimates.  The
models faithfully reproduce a variety of experimental data and suggest a
mechanism for calcium-dependent activation of transcription factors.
Furthermore, these two pathways contain the target for all of the
commonly used immunosuppressants.  The model can help to suggest future
drug targets for modulation of the immune response.

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