We use Shigella infection to discover new roles for the cytoskeleton in host defence, and use zebrafish to study the cell biology of infection in vivo. This work is supported by a Wellcome Trust Senior Research Fellowship, ERC Consolidator Grant, and the Lister Institute of Preventive Medicine.
The results generated from our work will provide fundamental advances in understanding cellular immunity, and could suggest the development of new strategies aimed at combating infectious diseases.
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. We recently established the antibacterial activity of septin caging, and discovered a fundamental link between mitochondria and the assembly of septin cages around Shigella. 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 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 this research will provide fundamental advances in understanding cellular immunity. This information should provide vital clues towards understanding bacterial disease and for illuminating new therapeutic strategies.
Bacterial infections continue to be responsible for immense human suffering and mortality throughout the world. More research is required to bring deeper and more complete understanding of the processes that govern bacterial infections. In our lab we have illuminated new roles for autophagy and the cytoskeleton in host defence and cellular homeostasis, and have also developed the zebrafish to investigate the cell biology of infection in vivo. Results generated by this novel research programme will significantly improve our understanding of pathogenesis by discovering more important concepts in infection biology and inspiring new avenues for further research. A comprehensive understanding of septin functions in innate immunity at the molecular, cellular, and whole organism level will have important consequences for enhancing host defence. These insights can suggest the development of new strategies aimed at combating infectious diseases, and may be helpful to decipher the molecular mechanisms underlying human diseases in which septins have been implicated.
Selected Publications (see all Serge's publications on Pubmed)