Jonathan Krook: Geometric regularisation for 3D reconstruction in cryogenic electron microscopy

Cryogenic electron microscopy (Cryo-EM) single particle analysis refers to tomographic imaging methods used for recovering the 3D structure of a rigid biomolecule, such as a protein, from many 2D electron microscopy images of it taken from differing views. A common approach is to first reconstruct a 3D volume representing an electrostatic potential associated to the biomolecule, and then assemble a (pseudo) atomic model that represents its 3D structure. Thanks to recent developments, one can perform these two steps jointly. This means it is possible to directly reconstruct the 3D (pseudo) atomic model (structure) of the biomolecule from the 2D electron microscopy images. In the case of proteins, AlphaFold lets us generate an initial template for the 3D structure. Combined with recent work in protein geometry, and methods from the field of image registration using tools from differential geometry, we can construct geometric regularisers that penalise non-physical deformations of such a template, which is challenging to enforce when reconstructing a 3D volume. In this talk I will present two different approaches to geometric regularisation in Cryo-EM. The first part is based on joint work with Erik Jansson (Chalmers), Ozan Öktem (KTH), and Klas Modin (Chalmers). The second part is based on joint work with Willem Diepeveen (University of Cambridge & UCLA).