Bacterial gasdermin as a model system to study ancient immune mechanisms

• Applicant: Dr. Tanita Wein
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Microbial Ecology and Applied Microbiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 548292591

Prokaryotes are equipped with anti-phage defense genes that can be collectively termed bacterial immune system. The most widely studied bacterial immune mechanisms are CRISPR-Cas and restriction-modification systems, but many additional defense systems have been described in bacteria. Until very recently, it was assumed that eukaryotes and prokaryotes shared little in terms of immune mechanisms. This view was proven false upon the recent discovery of several novel prokaryotic anti-phage immune systems that appear to be present in major eukaryotic antiviral pathways. This includes gasdermins that are the executioners of pyroptosis and a crucial part of the human innate immune system. The recent discovery of bacterial gasdermin has dramatically shifted our perception of the evolutionary trajectory of the human pyroptosis pathway. However, many critical aspects of the mechanism and evolution of pyroptosis remain completely unknown: Do prokaryotic cells use gasdermins to deliver cytokine-like molecules in response to infection, and can gasdermin-mediated defense affect nearby cells? These questions will be addressed as part of my planned research program.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2330: New concepts in prokaryotic virus-host interactions - from single cells to microbial communities
• International Connection: Israel