Interpreting the signaling dynamics of innate immune cells using E-Cell

Our immune system is a highly sophisticated process that cannot be well understood using the wet-bench facility alone. I will focus on the innate immune system, the activation of Toll-like receptor (TLR) 4 to lipopolysaccaride stimuli that leads to the induction of typical proinflammatory cytokines such as TNF-α and IL-1β. The understanding of such complex signaling process requires i) the dynamic measurements of biological entities such as NF-κB and AP-1 transcriptional activation and ii) appropriate computational tools that will be able to interpret the temporal results. I will introduce the E-Cell simulation platform, developed at our institute, suited for this kind of analysis and show how one can successfully use such in silico tools to address some key issues in biology that could otherwise take a longer time to resolve. In particular, I will demonstrate the utility of my TLR4 in silico model of the macrophage cell-type, developed using ordinary differential equations, which predicts the existence of unknown intermediates in the TLR4 signaling system.