Human-specific Inflammasomes

Project Description

Immunological research often uses the laboratory mouse to understand human disease. Inflammasome research is no exception, and previous studies in mice have revealed important mechanisms of human inflammatory disease. But the immune responses of humans and mice are not identical, in part because of gene differences between these species. Recent technological advances (e.g. CRISPR/Cas9 gene editing) give us unprecedented precision in approaches for characterising immune processes in human cells.

 

Projects:

  • Activation mechanisms for human-specific caspases (e.g. caspase-4/5)
  • Molecular functions of human-specific NLRs
  • Intra-species divergence in human and mouse inflammasomes

 

Select Publications:

  1. Bierschenk D, Monteleone M, Moghaddas F, Baker PJ, Masters SL, Boucher D, Schroder K (2018).
    The Salmonella pathogenicity island-2 subverts human NLRP3 and NLRC4 inflammasome responses. Journal of Leukocyte Biology In press. Pubmed
     
  2. Bierschenk D, Boucher D, Schroder K. (2017).
    Salmonella-induced inflammasome activation in humans. Molecular Immunology Jun;86:38-43. Pubmed
     
  3. Baker PJ1, Boucher D1, Bierschenk D, Tebartz C, Whitney PG, D'Silva DB, Tanzer MC, Monteleone M, Robertson AA, Cooper MA, Alvarez-Diaz S, Herold MJ, Bedoui S, Schroder K2, Masters SL2 (2015).
    NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. European Journal of Immunology 45:2918-26. 1, 2Joint Contribution. Pubmed
     
  4. Schaale K, Peters KM, Murthy AM, Fritzsche A, Phan MD, Totsika M, Robertson AAB, Nichols KB, Cooper MC, Stacey KJ, Ulett GC, Schroder K, Schembri MA, Sweet MJ (2015). Strain-and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli. Mucosal Immunology 9(1):124-36. Pubmed
     
  5. Schroder K, Irvine KM, Taylor MS, Bokil NJ, Le Cao KA, Masterman KA, Labzin LI, Semple CA, Kapetanovic R, Fairbairn L, Akalin A, Faulkner GJ, Baillie JK, Gongora M, Daub CO, Kawaji H, McLachlan GJ, Goldman N, Grimmond SM, Carninci P, Suzuki H, Hayashizaki Y, Lenhard B, Hume DA, & Sweet MJ (2012) Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages. Proceedings of the National Academy of Science U S A 109(16):E944-953. Pubmed

 

Image: Artwork uses an image of Vitruvian Man circa 1492 by Leondardo da Vinci (photographed by Luc Viator) overlayed with the inflammasome symbol.

Categories: 
Genetics
Molecular biology
Cell biology