Super-resolution Cryo-Correlative Light and Electron Microscopy to studying macromolecular structure in the cell nanocontext

To understand complex biological structure and function, we need more comprehensive imaging strategies. Cryo-correlative light and electron microscopy (cryo-CLEM) has been put into the frontline of bio-imaging method and development. Cryo-electron microscopy (cryo-EM) is a powerful tool to obtain up to sub-nanometre resolution molecular and cellular ultrastructure. Cryo-fluorescence microscopy (cryo-FM) takes the leading role to study the distribution and organisation of specific biomolecules in cells. Cryo-CLEM is a powerful way to link function to structure in complex biological systems; however a major drawback is the discrepancy in resolving power between cryo-EM (nanometre scale) and cryo-FM (a few hundred number scale). We propose to develop super-resolution cryo-FM, leading to the development of a new imaging method offering macromolecular level optical resolution on bio-samples preserved in a near-native state. The development will pave the way for the deployment of highly demanded super-resolution cryo-CLEM, enabling a variety of correlative biological structure and function studies.