The Rubinstein laboratory studies the structure and function of macromolecular assemblies using electron cryomicroscopy (cryo-EM), image analysis, molecular biology and molecular genetics. We also develop the tools of cryo-EM so that we can answer questions that are not amenable to the techniques that currently exist. Method development usually occurs on several levels: (1) Development of new algorithms and computational approaches for image analysis (e.g. Rubinstein and Brubaker, 2015); and (2) Nanofabrication to improve specimen preparation (e.g. Marr et al., 2014). For computational method development we collaborate closely with colleagues in the Department of Computer Sciences at the University of Toronto. Recent biological projects have included the structural study of the mitochondrial ATP synthase (Zhou et al., 2015), the Vacuolar-type ATPase (Zhao et al., 2015), and the V/A-ATPase (Lau and Rubinstein, 2012). These rotary ATPases have important roles in cancer, osteoporosis, the immune system, and ischemia-reperfusion injury. We have numerous collaborative projects studying other aspects of the molecular biology of the cell from a structural perspective. Our work on the rotary ATPases and other ongoing projects has illustrated how cryo-EM can be used not only to elucidate the high-resolution structures of macromolecular assemblies, but also to understand the dynamics of biomolecular systems.
At A Glance
- Electron cryomicroscopy (cryo-EM) of macromolecular machines
- Cryo-EM method development including algorithm and software development and nano-fabrication for specimen preparation
- Study of rotary ATPases and other biomedically significant protein complexes
- Bioenergetics and pH control in intracellular compartments
- Targeted destruction of proteins
- Vacuolar ATPases in cancer, osteoporosis, cell cycle control, and the immune system
Dr. Rubinstein is a Senior Scientist in the Molecular Structure and Function Program at the Hospital for Sick Children, where he has worked since 2006. He is a Professor in the Departments of Medical Biophysics and Biochemistry at the University of Toronto, and a Tier 1 Canada Research Chair in Electron Cryomicroscopy. He received his PhD from Cambridge University for work done at the Medical Research Council laboratories. His accomplishments have been recognized by awards including a CIHR New Investigator Award, the GE Healthcare New Investigator Award from the Canadian Society for Molecular Biosciences, and the Burton Medal from the Microscopy Society of America.