Untersuchung der molekularen Mechanismen des Protein-Zusammenbaus und der Membran-Permeabilisierung im programmierten Zelltod anhand hochentwickelter Mikroskopie

01/03/2018 to 28/02/2021

Pore-forming proteins (PFPs) comprise a broad group of proteins that are involved in many biological processes related to infection and immunity, as well as cancer and neurodegeneration. These proteins induce cell-death by pore formation upon membrane permeabilization. A well-known class of PFPs involved in cell death is the Bcl-2 family, which plays a key role in apoptosis. In fact, dysregulation of this function is a hallmark of cancer.
Recent advances in the cell death research have brought to discover additional, completely uncharacterized, forms of regulated cell death. Although the understanding and control of regulated necrosis (RN) is still in its early days, it is clear that all RN pathways are characterized by cellular leakage, likely following membrane permeabilization. A prominent example is inflammation-related pyroptosis, where lytic activity has been attributed to the Gasdermin (GSDM) family of proteins. However, little is known about the molecular mechanisms involved in membrane permeabilization by PFPs.
In this project we aim to elucidate the molecular details of PFPs membrane permeabilization in the context of regulated cell death by an innovative combination of advanced microscopy and biophysical tools. This will help refining therapeutic strategies and drug development in the treatment of apoptosis and pyroptosis related diseases, like infection, inflammation, cancer and neurodegeneration.