CryoMinflux-guided In-situ Visual Proteomics and Structure Determination

This group of physicists and structural cell biologists will build a novel cryo-superresolution (SR) microscope, based on the Minflux concept, for protein localization in natively preserved cells with single-digit nanometer 3D-precision, providing an accurate molecular census of the labelled proteins. The team will devise workflows to correlate cryo-SR and cryo-electron-tomography (cryo-ET) at nanometer accuracy to contextualize protein locations. They will develop open-source computational tools to guide structure determination and visual proteomics of uncharted proteins in crowded cellular environments. This will solve one of the biggest limitations of in-situ structural biology, where the low signal-to-noise-ratio of cryo-ET data and cellular complexity interfere with protein identification, specifically for molecules where no a priori contextual and structural information exists. The group’s synergistic expertise in optical and low-temperature molecular physics, methods development in SR-imaging, cryo-ET, and image processing will enable researchers to study structurally unknown proteins and their interactions in cells and determine their structure at potentially near-atomic resolution, bringing in-situ structural biology closer to true visual proteomics.