London School of Hygiene & Tropical Medicine

The intracellular bacterium Shigella flexneri has emerged as an exceptional model pathogen to address key issues in biology, including how bacteria can move inside host cells or be recognized by the immune system. We discovered that host cells employ septins, a poorly understood component of the cytoskeleton, to restrict the motility of Shigella and target them for destruction by autophagy, an important mechanism of innate immune defence. A major issue is now to fully decipher the underlying molecular and cellular mechanisms, and to validate these events in vivo using relevant animal models. We developed zebrafish (Danio rerio) infection models to study the cell biology of Shigella infection in vivo and to discover new roles for septins in host defence against bacterial infection. This approach has enabled a cutting edge platform for in vivo studies both at the single cell and whole animal level. Collectively, the results generated from our research can provide fundamental advances in understanding cellular immunity. This information should provide vital clues towards understanding bacterial disease and for illuminating new therapeutic strategies.