Development of low-dose cryo-scanning transmission electron tomography using sparse images to study whole eukaryotic cells at the nanometre scale – C-STET-4-E-Cells

The project C-STET-4-E-Cells aims to develop an original cryo-scanning transmission electron tomography (cryo-STET) imaging method using sparse images for low dose applications in biology. The goal is to propose to the structural biology community a new imaging method to study in 3D large complexes in their cellular environment. Current state-of-the-art electron cryo-tomography methods are limited to the study of sample thinner than about 300 nm. By using cryo-STET, we will bring the new thickness limitation to more than 1 µm explore whole eukaryotic cells. To respect the sample integrity, low electron doses will be achieved by collecting incomplete images, also known as sparse images. The missing information (i.e. the uncollected pixels) will be reconstructed using state-of-the-art shearlets-based inpainting methods and artificial intelligence. We will apply the method on the study of the distribution and structure of intraflagellar transport particles of a unicellular eukaryotic parasite, T. brucei, to show the various applications of the method.