AUTHOR=Kim Heonsu , Choi Gyuho , Suk Myung Eun , Kim Tae-Jin TITLE=Resource for FRET-Based Biosensor Optimization JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=Volume 10 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.885394 DOI=10.3389/fcell.2022.885394 ISSN=2296-634X ABSTRACT=After the development of Cameleon, the first fluorescence resonance energy transfer (FRET)-based calcium indicator, a variety of FRET-based genetically encoded biosensors (GEBs) have visualized numerous target players to monitor their cell physiological dynamics spatiotemporally. Many attempts have been made to optimize GEBs, which require labor-intensive effort, novel approaches, and precedents to develop more sensitive and versatile biosensors. However, researchers face considerable trial and error in upgrading biosensors because examples and methods of improving FRET-based GEBs are not well documented. In this review, we organize various optimization strategies after assembling the existing cases in which the components of biosensors are upgraded. In addition, promising areas to which optimized biosensors can be applied are briefly discussed. Therefore, this review could serve as a resource for researchers attempting FRET-based GEB optimization.