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Use of the cytoskeleton to control Shigella infection

Use of the cytoskeleton to control Shigella infection

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.

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About us

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.

Mission statement

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.

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About
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Research overview

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.

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Mission statement
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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.

Publications

Selected Publications (see all Serge's publications on Pubmed)

 

Publications List Block
Septins Recognize and Entrap Dividing Bacterial Cells for Delivery to Lysosomes
Krokowski S, Lobato-Márquez D, Chastanet A, Pereira PM, Angelis D, Galea D, Larrouy-Maumus G, Henriques R, Spiliotis ET, Carballido-López R, Mostowy S
2018
Cell Host Microbe. 2018 Dec 12;24(6):866-874.e4. doi: 10.1016/j.chom.2018.11.005. PMID: 30543779
Cell scientist to watch
Serge Mostowy
2018
J Cell Sci. 2018 Sep 17;131(18). pii: jcs223958. doi: 10.1242/jcs.223958
Septins suppress the release of vaccinia virus from infected cells
Pfanzelter J, Mostowy S, Way M
2018
J Cell Biol. 2018 Aug 6;217(8):2911-2929. doi: 10.1083/jcb.201708091. Epub 2018 Jun 19. PMID: 29921601 Free PMC Article
Shigella-Induced Emergency Granulopoiesis Protects Zebrafish Larvae from Secondary Infection
Willis AR, Torraca V, Gomes MC, Shelley J, Mazon-Moya M, Filloux A, Lo Celso C, Mostowy S
2018
MBio. 2018 Jun 26;9(3). pii: e00933-18. doi: 10.1128/mBio.00933-18. PMID: 29946048
Zebrafish Infection: From Pathogenesis to Cell Biology
Torraca V, Mostowy S
2018
Trends Cell Biol. 2018 Feb;28(2):143-156. doi: 10.1016/j.tcb.2017.10.002. Epub 2017 Nov 21. Review. PMID: 29173800 Free PMC Article