English

Welcome to the Heolab (Bio-Imaging and Optogenetics Lab)!

 

Bio-Imaging technology in combination with the optogenetics toolkit will allow us not only to discover a large number of potential drugs and their targets for disease therapy, but also to understand the development of human diseases. Bio-Imaging technologies that we have developed can lead us to a better understanding of different model organisms and can be used for “drug discovery” through screening of chemical libraries. We have also developed new optogenetics toolkit, which will be very powerful tools for investigations of cell signaling networks in mammalian cells as well as for controlling behaviors in animal models.

Bio-Imaging and Optogenetics Group investigates fundamental cellular processes by developing and utilizing novel bio-imaging technologies using diverse bio-imaging instruments. Recently, the research group initiated exploiting the next generation optogenetic toolkits on in vivo mouse models to understand mechanisms to control synaptic plasticity and learning and memory. Bio-Imaging and Optogenetics Group investigates fundamental cellular processes by developing and utilizing novel bio-imaging technologies using diverse bio-imaging instruments. Recently, the research group initiated exploiting the next generation optogenetic toolkits on in vivo mouse models to understand mechanisms to control synaptic plasticity and learning and memory.

Research Overview/Research Interests (to be updated)

 

 

 

Recently Publihsed Research Topics 

 

Spatiotemporal control of fibroblast growth factor receptor signals by blue light.

Fibroblast growth factor receptors (FGFRs) regulate diverse cellular behaviors that should be exquisitely controlled in space and time. We engineered an optically controlled FGFR (optoFGFR1) by exploiting cryptochrome 2, which homointeracts upon blue light irradiation. OptoFGFR1 can rapidly and reversibly control intracellular FGFR1 signaling within seconds by illumination with blue light. At the subcellular level, localized activation of optoFGFR1 induced cytoskeletal reorganization. Utilizing the high spatiotemporal precision of optoFGFR1, we efficiently controlled cell polarity and induced directed cell migration. OptoFGFR1 provides an effective means to precisely control FGFR signaling and is an important optogenetic tool that can be used to study diverse biological processes both in vitro and in vivo.

 

Light-inducible receptor tyrosine kinases that regulate neurotrophin signalling.

Receptor tyrosine kinases (RTKs) are a family of cell-surface receptors that have a key role in regulating critical cellular processes. Here, to understand and precisely control RTK signalling, we report the development of a genetically encoded, photoactivatable Trk (tropomyosin-related kinase) family of RTKs using a light-responsive module based on Arabidopsis thaliana cryptochrome 2. Blue-light stimulation (488 nm) of mammalian cells harbouring these receptors robustly upregulates canonical Trk signalling. A single light stimulus triggers transient signalling activation, which is reversibly tuned by repetitive delivery of blue-light pulses. In addition, the light-provoked process is induced in a spatially restricted and cell-specific manner. A prolonged patterned illumination causes sustained activation of extracellular signal-regulated kinase and promotes neurite outgrowth in a neuronal cell line, and induces filopodia formation in rat hippocampal neurons. These light-controllable receptors are expected to create experimental opportunities to spatiotemporally manipulate many biological processes both in vitro and in vivo. 

We present a versatile platform to inactivate proteins in living cells using light, light-activated reversible inhibition by assembled trap (LARIAT), which sequesters target proteins into complexes formed by multimeric proteins and a blue light-mediated heterodimerization module. Using LARIAT, we inhibited diverse proteins that modulate cytoskeleton, lipid signaling and cell cycle with high spatiotemporal resolution. Use of single-domain antibodies extends the method to target proteins containing specific epitopes, including GFP.