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Light-activated Reversible Inhibition by Assembled Trap (LARIAT) Technology

A unique optogenetic technology to uncover the secrets of the brain

“Optogenetics represent the best technology for understanding the numerous functions of neurons and new neural networks in the brain. However, its application to the studies of signaling in neurons has been limited. The optogenetic technology we developed can not only activate neurons but also induce their growth and differentiation through light, presenting the possibility of a fundamental cure for senile dementia, depression, and Parkinson's disease. Currently, studies are being conducted in the fields of tumor metastasis and neuroscience in various animal models using Light-Activated Reversible Inhibition by Assembled Trap (LARIAT) technology. We are hopeful that it will ultimately play a crucial role in the discovery of tumor treatment methods and in revealing the role of neurons within the complex neural network."

Utilization in research of cells and signaling in tumors

Synapses, which are connectors between neurons in the neural network, are configured differently according to individual memories, experiences, and ailments. The amount, size, and shape of synapses greatly affect human actions, thoughts, and emotions at all times. Optogenetics is a new field of neuroscience that studies the activation of synapses in specific pathways when humans think, feel emotions, or suffer certain ailments.
Optogenetics aims to control signaling in cells using light and can be used to control protein functions and even animal behavior. This is possible due to the application of channelrhodopsin (blue light photoreceptor proteins in green algae necessary for inducing phototaxis in reaction to blue light) in neurons. By activating channelrhodopsin in neurons, the molecule senses light and converts it into electric signals that activates the neuron as if external stimulation was applied. As channelrhodopsin reacts sensitively, blue light-emitting lasers or blue LEDs can be used.

Professor Karl Deisseroth's study, which activated channelrhodopsin expressed in the neurons of mice with light to control mice behavior opened the field of optogenetics. A system by which light (remote control) can be used to control synapses (receiver) had been made possible. However, his method activates the target neurons in the mouse brain through ion channel proteins. If light can be used to activate desired neurons, there should also be a way to control target proteins within neuron or neural synapses. That is the light-activated reversible inhibition by assembled trap (LARIAT) technology developed by Professor Won Do Heo's team at KIB.

In this technology, when light is irradiated onto cells, a protein complex called LARIAT is formed instantaneously within the cell to trap certain proteins and inhibit the functions of the target proteins. Professor Won Do Heo's team observed that when light is irradiated onto a small area of several micrometers in a single cell, protein functions in that area are inhibited rapidly and specifically, with functions returning quickly when the light is switched off. Using these findings, they were able to inhibit target protein functions by trapping various proteins that affect cell division, growth, and movement within the LARIAT.
Until now, studies were focused on genetic or medicinal methods for the inhibition of specific protein functions in animals. However, the LARIAT technology developed by Professor Won Do Heo's team enabled the deactivation of important bio phenomena, such as cell division and movement, without the administration of any substance other than light with easy and reversible control by switching a light on and off. This discovery has drawn widespread interest around the world. LARIAT technology's ability to prevent cell division through human control has strong potential for application to cancer cells with widespread implications for tumor cell structure and signaling studies.

Professor Won Do Heo's team is currently working on technologies in the field of neuroscience to control various protein functions and discover their roles in the brain. This involves the process of imaging neural signaling in the cognition and social behavior of mice. Going beyond the field of optogenics, the team aims to discover sensor proteins for other effective stimulation such as heat, ultrasound, and magnetic fields to develop new technologies such thermogenetics and magnetogenetics. The results of this study were published in the June issue of Nature Methods (IF 23.565), the world's most influential journal in the field of biochemical research methods, published by the Nature Publishing Group.
2014 Annual Report

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