Molecular engineering, fluorescence resonance energy transfer (FRET), live cell imaging, and bio-nanotechnology to visualize and elucidate the molecular mechanisms by which live cells perceive the environment and to engineer machinery molecules for the reprogramming of cellular functions. Specifically, our research includes the development of genetically-encoded molecule biosensors based on fluorescence resonance energy transfer (FRET) and the application of these biosensors for the visualization and quantification of molecular signals in live cells with high spatiotemporal resolution under physical/mechanical environment. We are also interested in integrating the cutting-edge technologies in molecular engineering, live cell imaging, and nanotechnology for the engineering of machinery molecules to reprogram cellular functions. Our research interests include:
"A Drunk Cell Dancing" - Airport Art Exhibit
Description of the image
This image shows the activation process of a kinase in a live cell. Initially the cell shows a blue color indicating low activity (2 o'clock position). After stimulation, the cell turns green and then turns red counterclockwise, indicating kinase activation.
1) Developing genetically-encoded reporters based on fluorescent resonance energy transfer (FRET) to visualize and quantify signaling transduction in live cells with high tempo-spatial resolution;
The 3D structures of the Src reporter before Src activation.
The 3D structures of the Src reporter after Src activation.
The movie shows effects of EGF stimulation and washout on FRET responses of the monomeric Src reporter in HeLa cells.
The EGF-induced FRET response in HeLa cells expressing the Src reporter.
PP1 reversed the EGF-induced FRET responses of the membrane-targeted Src reporter in HeLa cells.
2) Combining red fluorescence protein (RFP) together with CFP/YFP-based FRET reporters to simultaneously visualize multiple signaling events and elucidate the molecular hierarchy involved in cellular signaling transduction;
3) Integrating Nano-fabrication, Laser-Tweezer, and Multi-photon Microscopy, together with fluorescence probes, to manipulate and visualize the regulatory signaling cascades in live cell motility and migration.
The movie shows a highlighted cell with a clear FRET wave propagation away from the stimulation site upon force application.
The laser-tweezer-traction induced directional and long-range propagation of FRET responses of the membrane-targeted Src reporter in HUVECs.
The laser-tweezer-traction on a polylysine-coated bead did not induce FRET responses in HUVECs.
4) Detecting early cancer development in biopsy samples with FRET-based reporters.
5) Image-driven system biology: Intra-cellular transport and diffusion by finite-element-analysis
6) High throughput image analysis software for automatic quantification of molecular activities and statistical inference.