Molecular Biophysics; Electron cryomicroscopy of macromolecular assemblies
Our work, at the intersection of biology, biochemistry, and physics, is centered on imaging of macromolecular assemblies. Knowledge of the three-dimensional structure of a biological complex is a prerequisite for understanding its function. Single particle electron cryomicroscopy plays an increasingly important role in determining the structures of assemblies that are too large, unstable, scarce or hydrophobic to be studied by other methods.
Our group both uses and develops the technique of electron cryomicroscopy. Modern electron microscopes are capable of atomic resolution imaging. However, the electron beam used to obtain images destroys biological molecules as the image is recorded. Consequently, images must be obtained with an extremely low exposure of electrons, which results in low signal-to-noise ratios in the images. Computational analysis is then employed to determine the viewing angle for different copies of the molecule, so that images of molecules that present the same pose can be averaged and images of molecules presenting different views can be combined to produce a 3-D map of the complex. Our research on method development for electron cryomicroscopy has emphasized methods of specimen preparation and computational analysis of the resulting images.
For more information, please see www.sickkids.ca/research/rubinstein
