KC Huang (Stanford University)
MolBio Seminar Series
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 IM basketball.
Mapping the structural dynamics of cytoskeletal filaments onto behavior
Determining how cells, tissues, and organisms determine their structure, and how this structure affects behavior, is a fundamental challenge for modern cell biology. In prokaryotes and eukaryotes alike, cytoskeletal proteins such as tubulin and actin form filaments that have been implicated in a vast array of cellular processes. The mechanisms by which cytoskeletal filaments generate force and affect cell morphology are often dynamic and require techniques that address both the submolecular and cellular scales. I will demonstrate that all-atom molecular dynamics (MD) simulations can be used to infer the properties of filaments, and to discover molecular mechanisms connecting mutations in these proteins to their phenotype. I will illustrate how MD can be used to probe the effects of nucleotide binding on the structure of the essential division protein FtsZ, a homolog of eukaryotic tubulin. We found that nucleotide hydrolysis induced a dramatic bending of a dimer, and determined that this transition can generate the 20-30 pN per monomer necessary to constrict the cell wall. Next, I will demonstrate that similarly subtle modifications to the interprotofilament interface in microtubules due to acetylation are responsible to perturbing the quinary structure of the microtubules enervating touch receptor neurons in C. elegans, leading to a defect in mechanosensation. Finally, I will show that polymerization of the bacterial actin homolog MreB induces ATP hydrolysis and alters filament stiffness, with mutations near the ATP binding pocket resulting in altered cell size. These studies illustrate that advanced computational methods with molecular resolution, in combination with emerging structural data, offer the potential to reveal the functional mechanisms of cytoskeletal proteins.
Free and open to the university community and the public