A Systems Approach to Dissecting Immunity

Alan Aderem, The Institute for Systems Biology

Macrophages represent one of the cornerstones of the innate immune system. They detect infectious organisms via a plethora of receptors; they phagocytose them; and then they orchestrate an appropriate host response to them. To precisely define the nature of the threat, the immune cell needs to read the molecular barcode that is displayed on the specific pathogen. Recent work from a number of laboratories has indicated that the family of Toll-like receptors (TLRs) plays a key role in defining the invading microorganism. Thus, activation of TLR4, which detects LPS, and TLR5, which detects flagellin, would indicate the presence of a Gram-negative, flagellated bacterium. This precise recognition triggers a specific, highly regulated, response to the pathogen by the host. We are using genomic and proteomic tools to define branch points in the signaling pathways, and computational methods to define regulatory points. Biological results and technological developments will be discussed. Technological developments include a microfluids/nanosensor approach to single-cell analysis.