The Chao Lab explores structural and biophysical mechanisms underlying membrane dynamics and ultrastructure. A central goal for our team is to understand the mitochondrion’s morphology, a question filled with fascinating puzzles of how conformational change across scales generates diverse subcellular forms and functions.

We integrate structural and biophysical methods to understand how macromolecular assemblies generate responsive, pleomorphic shapes. Using electron cryo tomography (cryo-ET), we visualized how mitochondrial inner-membrane ultrastructure and architecture is regulated (Fry, Navarro et al., EMBO J 2024). Applying in vitro reconstution, we uncovered a mechanism for regulating mitochondrial inner-membrane fusion, revealing how proteolytic processing controls gating the final pore-opening step (Ge et al., eLife 2020). In other exploration of mitochondrial morphogenesis, we revealed interactions coordinating outer/inner-mitochondrial membrane fusion, and using phylogenetic approaches, identified a conserved sequence signature for an ancient membrane-shaping protein's respiratory function (Boopathy et al., JBC 2024; Benning, Bell, Nguyen et al., BioRxiv 2024).

Finally, our research team has made contributions to understanding macromolecular (ultra)structure/function in other systems. We revealed mechanisms regulating cell wall organization central for bacterial cell division (Navarro, Vettiger et al., Nat. Micro. 2022), and determined a cryo-EM helical reconstruction revealing baculovirus nucleocapsid assembly (Benning et al., Nat. Comm. 2024). We have also made contributions to understanding mechanisms of curvature-induction at the plasma membrane important in the generation of extracellular vesicles (Bell et al., eLife 2024).