Organelle structure-function: We investigate how proteins self-organize in the birth, life and death of cellular compartments. Our goal is to understand how coupled, coordinated Ångstrom-scale motions propagate into micron-scale cellular rearrangements. The current focus in our group is the mitochondrial membrane, where morphology is tightly coupled to metabolic function. We are investigating this relationship by asking:
How is organelle shape specialized for a particular function? How are signals transduced and propagated between membranes? What is the role of allosteric control in membrane-protein assemblies? How have organelles evolved to define tissue-specific metabolic niches?
Our approach draws from structural, biophysical, chemical and cellular methods to understand macromolecular assemblies in action, in situ. We enjoy reconstituting protein assembly activity to dissect molecular mechanisms. We use a variety of structural approaches, including electron cryo-microscopy (Cryo-EM), to visualize key conformational states, with an eye to developing new tools to manipulate protein conformational change.