Molecular mechanisms of pore formation by Gasdermin D in pyroptosis (P26)

Subject Area Cell Biology
Term from 2020 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 180879236
 

Project Description

Pyroptosis is a form of regulated cell death triggered by caspases in response to pathogens or endogenous danger signals in the cell. Gasdermin D (GSDMD) has recently been identified as a key factor in plasma membrane (PM) permeabilization during pyroptosis. GSDMD may form oligomers with specific lipids and proteins. The aim of this project is to elucidate the exact composition, assembly and dynamics of GSDMD microcompartments and to investigate their functional role in pyroptosis. The following objectives will be pursued: 1) Identification and characterization of PM components responsible for the recruitment and function of GSDMD. 2) Study of the assembly mechanisms of GSDMD oligomers and the structural characterization of GSDMD , and 3) correlation of protein stoichiometry with pore functionality to understand pyroptosis in detail. These studies will provide important insights into the role of GSDMD in the modulation of inflammatory cell death, with possible clinical implications for infectious and inflammatory diseases.
DFG Programme Collaborative Research Centres
Subproject of SFB 944:  Physiology and Dynamics of Cellular Microcompartments
Applicant Institution Universität Osnabrück
Project Head Professorin Dr. Katia Cosentino