John Rubinstein

Macromolecular structure, electron cryomicroscopy, computational image analysis; Membranes and Transport Mechanisms, Protein Structure and Dynamics; Electron Cryomicroscopy of Macromolecular Machines; Our group studies the structure and function of macromolecular assemblies using electron cryomicroscopy (cryo-EM), as well as other biophysical and biochemical approaches. We also develop cryo-EM methods so that we can answer questions that are not amenable to the techniques that currently exist. There are two main biological research directions in the laboratory, both of which relate to how energy is transformed and stored in cells. First, we are investigating membrane protein complexes like the V-ATPase and its interaction partners, which drive neurotransmitter loading into synaptic vesicles in the brain and energize the membranes of lysosomes. These studies are aimed at understanding the molecular basis of neurological disorders and the role of V-ATPases in cancer and other diseases. Second, we are studying oxidative phosphorylation in mycobacteria, which has emerged as important target space for the development of new drugs to treat tuberculosis and other mycobacterial infections. This work is providing a fundamental understanding of energy metabolism in these pathogens, and through a collaborative network looking for new therapeutics to treat mycobacterial infections.