Correlating single-molecule localization microscopy and cryo-electron tomography

This thesis decribes the development of new tools and methods for super-resolution correlative light and electron microscopy (SRcryoCLEM), specifically using cryo-single molecule localization microscopy (cryoSMLM) and cryo-electron tomography (cryoET) as the imaging modalities. The purpose of this technique is to study specific intracellular biomolecules at high resolution and within their native environments. Included in the thesis is the design for a dedicated cryoSMLM microscope, a full workflow for performing SRcryoCLEM, various chapters on sample optimization and validation, and describes new open-source software packages for cryoSMLM reconstruction and SRcryoCLEM correlation and for tomogram segmentation.