Bo Huang, UC San Francisco
Pharmaceutical Chemistry and Biochemistry and Biophysics
Title: Super-resolution microscopy for living cells
As one of the newest breakthroughs in light microscopy, the invention of super-resolution microscopy brings the spatial resolution towards the size of a protein molecule (~ 10 nm), thus generating enormous excitement in biologists. Among super-resolution microscopy techniques, the single-molecule-switching-based approach, commonly known as STORM or PALM, achieves super-resolution by activating and sampling small fractions of fluorophores in each camera frame. Despite the achievements in 3D and multicolor super-resolution imaging, the development of live cell STORM/PALM has been hindered by its requirement for a large number of camera frames and high excitation light intensity, the duration of observation becomes one of the final obstacles for it to be broadly applicable to the study of subcellular dynamic processes. Here, combining the expertise of Dr. Bo Huang at UCSF in super-resolution microscopy technique development and the expertise of hosting Dr. Laura Waller at UC Berkeley in computational imaging, we propose a computational approaches to address this issue. We will create new algorithms that can reconstruct high quality super-resolution images from noisy snapshots in a continuous movie, as well as algorithms to infer the underlying cellular structures from incompletely sampled snapshots utilizing prior knowledge of the structures. These methods should increase the observation duration of live STORM/PALM by more than one order of magnitude. We are confident that our research will have far reaching impact given the sheer number of biological problems awaiting visualization tools.