Network Modelling of Macrophage Systems

We are currently developing new strategies for understanding macrophage biology, particularly with respect to its role in infectious and inflammatory disease. Using a powerful new network-based approach to analysing microarray data, we have been examining the transcriptional response of these cells to various factors and pathogens in order to identify cohorts of genes activated in the macrophage by proinflammatory stimuli. These data are then been used to direct the construction of a large integrated pathway diagram which aims to describe the network of interactions between known components of the signalling cascades and the effector systems they regulate. These pathways function as a knowledge-base with which to model and visualize the consensus view on the regulation of these pathways and the potential functional significance of the transcriptional profiles we observe. Finally, having established a working model of these molecular systems, we are beginning to use RNAi technology to manipulate their activity thereby testing our view of events.