Electron Cryomicroscopy

Lead Researcher: Marcus A. Brubaker

The structure of biological molecules like proteins and viruses play a critical role in understanding life at a cellular level and are important to the discovery of new medical treatments. However determining these structures is a difficult task due to their small size and delicate biological nature. Electron Cryomicroscopy (cryo-EM for short) is an emerging new technique for structure determination which uses large numbers of low-contrast, high-noise 2D images to attempt to estimate 3D structure.

Image processing for cryo-EM

This project aims to explore the computational aspects of this reconstruction and estimation problem. This includes a range of problems such as particle picking [Zhao et al. 2013], 3D reconstruction [Punjani et al. 2017; Punjani et al. 2016], image clustering, structural clustering, deconvolution [Zhao et al. 2015], motion estimation and correction [Rubinstein and Brubaker 2015] and others.

A single particle in Cryo-EM Ab Initio Structure Estimation with SGD High resolution structure
Sample image, ab initio estimation and a final refined structure.

The following is a selected list of publications related to this project:

  1. Zhao, J., Brubaker, M.A., and Rubinstein, J.L. 2013. TMaCS: A hybrid template matching and classification system for partially-automated particle selection. Journal of Structural Biology 181, 3, 234–242.
  2. Punjani, A., Rubinstein, J.L., Fleet, D.J., and Brubaker, M.A. 2017. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nature Methods 14, 3, 290–296.
  3. Punjani, A., Brubaker, M.A., and Fleet, D.J. 2016. Building Proteins in a Day: Efficient 3D Molecular Structure Estimation with Electron Cryomicroscopy. IEEE Transactions on Pattern Analysis and Machine Intelligence.
  4. Zhao, J., Brubaker, M.A., Benlekbir, S., and Rubinstein, J.L. 2015. Description and comparison of algorithms for correcting anisotropic magnification in cryo-EM images. Journal of Structural Biology 192, 2, 209–215.
  5. Rubinstein, J.L. and Brubaker, M.A. 2015. Alignment of cryo-EM movies of individual particles by optimization of image translations. Journal of Structural Biology 192, 2, 188–195.