Invited Speaker The 48th Lorne Conference on Protein Structure and Function 2023

Optogenetics and Synthetic Protein Condensates for Controlling and Visualizing Cell Signaling in Living Cells and Animals (#16)

Won Do Heo 1
  1. Korea Advanced Institute for Science and Technology, Korea, Korea, Democratic People's Republic of

My group have developed various synthetic phase separation tools and optogenetic technologies for visualizing and controlling diverse molecules in live cells and animals. Synthetic phase separation tools were applied to monitor protein-protein interactions. We found synthetic phase separation tools were very pewful and sensitive to discovering many meaningful unknown protein-protein interactions. These provided new insights into understanding cell signalling to induce specific cellular processes. Our optogenetic tools, based on mostly plant light sensing elements, allow finely manipulated molecules and cells in a spatial and temporal resolution. We are applying the new technologies to study the spatiotemporal roles of signalling proteins and second messengers in living cells and the mouse brain. For example, we developed ultra-light-sensitive optogenetic Ca2+ modulators named OptoSTIM1 and monSTIM1, encompassing engineered cryptochrome2 for manipulating Ca2+ signalling in the brain of awake mice. With an mRNA-modulating optogenetic tool called mRNA-LARIAT, light induces the sequestration of specific exogenous or endogenous mRNAs into large protein clusters, altering mRNA localization and interfering with translation by limiting the ribosome interaction with trapped mRNA. Our ultimate goal is to provide new paradigms for future therapeutics through our optogenetics. I will talk about new approaches in cell biology studies and new strategies for therapeutics for neuronal diseases through remotely and non-invasively delivered light.