Perforin-2 (Mpeg1) is an ancient, pore-forming protein of the membrane attack complex perforin/cholesterol-dependent cytolysin (MACPF/CDC) family with essential roles in immunity. Unlike perforin-1, which is secreted by cytotoxic T cells to kill diseased host cells, perforin-2 is expressed in dendritic cells and macrophages, where it is anchored in endosomal and phagosomal membranes. Intriguingly, perforin-2 is reported to perform two distinct functions during immune responses: attacking intravacuolar pathogens and forming pores in endocytic compartments to enable cytosolic delivery of antigens during cross‑presentation.
The aim of this project is to establish how these two functions are regulated at the molecular level and whether they involve the formation of pores in two different orientations – away and towards the host membranes. This work will help to establish how one effector can carry out two fundamentally different functions during immune responses.
The project will employ state-of-the-art microscopy techniques (including confocal, live, multispectral, and/or high-resolution approaches) using established as well as novel reagents (e.g. organelle markers delivered by in vitro-transcribed mRNAs, and de novo-designed protein binders). The position is best suited for an enthusiastic student interested in how immune responses are initiated at the molecular level.