KC Huang (Stanford University)
KC Huang was an undergraduate Physics and Mathematics major in Page House at Caltech, and spent a year as a Churchill Scholar at Cambridge University working with Dr. Guna Rajagopal on Quantum Monte Carlo simulations of water cluster formation. He received his PhD from MIT working with Prof. John Joannopoulos on electromagnetic flux localization in polaritonic photonic crystals and the control of melting at semiconductor surfaces using nanoscale coatings. During a short summer internship at NEC Research Labs, he became interested in self-organization in biological systems, and moved on to a postdoc with Prof. Ned Wingreen in the Department of Molecular Biology at Princeton working on the relationships among cell shape detection, determination, and maintenance in bacteria. His lab is currently situated in the departments of Bioengineering and Microbiology&Immunology at Stanford, and his current interests include cell division, membrane organization, cell wall biogenesis, and collective motility of bacterial communities. His lab is a force to be reckoned with in pickup basketball.
Structural Dynamics Reveal New Mechanisms of Feedback Between Cell Geometry and Intracellular Organization
The assembly of protein filaments drives many cellular processes, from nucleoid segregation, growth, and division in single cells to muscle contraction in animals. In eukaryotes, shape, motility, and cytokinesis are regulated through cycles of polymerization and depolymerization of actin and microtubule cytoskeletal networks. In bacteria, the actin homolog MreB and the tubulin homolog FtsZ form filaments that coordinate the cell-wall synthesis and division machineries, respectively. A fundamental challenge in cell biology is to link the structural properties of these filaments to cellular behaviors and morphogenesis. We have used all-atom molecular dynamics simulations to reveal the nucleotide-dependent polymer mechanics of these cytoskeletal filaments. For FtsZ, our simulations predict that small changes at the monomer-monomer interface result in a large hinge-opening leading to filament bending upon GTP hydrolysis, which was confirmed solving the structure of an FtsZ-GDP filament by X-ray crystallography. Next, I will demonstrate that similarly subtle modifications to the interprotofilament interface in microtubules due to acetylation are responsible for perturbing the quinary structure of the microtubules enervating touch receptor neurons in C. elegans, leading to a defect in mechanosensation. We observe that MreB exhibits actin-like polymerization-dependent structural changes, wherein polymerization induces flattening of MreB subunits, and hydrolyzed polymers favored a straighter conformation. Taken together, our results provide molecular-scale insight into the diversity of structural states and the relationships among polymerization, hydrolysis, and filament properties within the actin and tubulin families. I will close by demonstrating a novel curvature-sensing strategy of the protein SpoVM, which initializes the formation of the spore coat in Bacillus subtilis. Taken together, our results highlight the expanding utility of molecular dynamics to link the atomic scales of protein function and the cellular scales of behavior.
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