Modeling the effects of a Staphylococcal Enterotoxin B (SEB) on the apoptosis pathway

We explore this through the modeling and simulation of the Fas-mediated apoptotic pathway under normal and SEB influenced conditions. We stimulated human Jurkat cells with an anti-Fas antibody in the presence and absence of SEB and determined the relative levels of seven proteins involved in the core pathway at five time points following exposure. These levels were used to impute relative rate constants and build a quantitative model consisting of a series of ordinary differential equations (ODEs) that simulate the network under both normal and pathogen-influenced conditions. Experimental results show that cells exposed to SEB exhibit an increase in the rate of executioner caspase expression (and subsequently apoptosis) of 1 hour 43 minutes (± 14 minutes), as compared to cells undergoing normal cell death.Our model accurately reflects these results and reveals intervention points that can be altered to restore SEB-influenced system dynamics back to levels within the range of normal conditions.Apoptosis is a naturally occurring mechanism by which a cell undergoes programmed death in response to external or internal signals. It has been shown that many potential biowarfare agents including Staphylococcal Enterotoxin B (SEB) improperly activate the pathways controlling this process in a variety of cell types [1-4]. These agents target specific components of these pathways, inducing a cascade of reactions that modify the rate at which apoptosis occurs. The large scale cell death that ensues brings about a state of unrecoverable shock.Since the induction of apoptosis underlies the lethality of SEB, this pathway presents a good target for therapeutic intervention. Previous results have shown that SEB treatment affects the expression of proteins involved in the Fas-mediated apoptotic pathway [2,4]. However, the mechanisms by which these agents interact with this pathway, and the cellular components most advantageous for potential therapies, is unclear. In order to establis