Discovering novel membrane fission catalysts and analyzing their cellular functions

Membrane fission of organelles requires the enclosing lipid bilayer to be brought to close proximity, which from theory represents a distance of separation of ~5 nanometers. Since organelles are of much larger dimensions, fission necessitates topological transformation of organelles into a highly curved tube-like intermediate. Using arrayed membrane nanotubes (see the Resource page for more details) that mimic such curved intermediates, we screen tissue lysates for fission activity and identify the sets of proteins that contribute to such activity. We then purify and reconstitute their functions to better understand how they work. The hits that emerge from our screen are tested for cellular function by making knock-out models and analysing morphological changes to various membrane compartments. Shown below is a schematic workflow of the discovery process.

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