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Elucidating the functional basis of membrane-transforming machineries by studying the archaeal ESCRTs

Subject Area Biophysics
Term since 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 509862298
 
Membrane transformation, up to the complete scission of compartments during cell and organelle division, is among the most crucial tasks to be executed by sophisticated protein machineries in living organisms. The endosomal sorting complex required for transport (ESCRT), which has first been reported to initiate a budding of vesicles from cellular membranes, appears to be a paradigm for the execution of membrane scission. The widespread representation of ESCRTs in all domains of life places them as ideal candidates for identifying key motifs in cellular membrane remodelling machines. In particular, ESCRTs from the recently identified Asgard superphylum which according to current evolutionary theories are the closest archaeal relatives to eukaryotes, appear to constitute a predecessor machinery to eukaryotic ESCRTs with reduced complexity, and thus are ideal candidates for detailed quantitative studies. In this joint initiative that brings together expertise in the biology of eukaryotes and archaea, biochemistry, and biophysics, we propose to functionally reconstitute archaeal ESCRT proteins for interaction with sophisticated membrane model systems. Our multidisciplinary study will combine (i) an investigation ot the assembly of purified proteins on membranes at single moelcule resolution in space and time, (ii) a probing of their ability to deform membranes of different geometries in vitro, (iii) a detailed characterization of their spatiotemporal behaviour in model cell systems (archaea / bacteria). Through these, we aim to unravel the functional core of membrane remodelling machines preserved through evolution.
DFG Programme DIP Programme
International Connection Israel
 
 

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