A team of researchers has developed groundbreaking instruments that use light to accurately manipulate proteins in real-time within living cells. This significant advancement could transform how we study complex cellular functions and may lead to significant progress in medicine and synthetic biology.
A group of scientists at Umeå University has created cutting-edge light-controlled tools that provide real-time precision in controlling proteins within living cells. This innovative research offers new avenues for investigating complex cellular mechanisms and could lead to major advancements in both the fields of medicine and synthetic biology.
“Cellular mechanisms are complex and constantly change based on timing and spatial context within the cell. Our new chemical tool, which features light switches, will make it easier to control these cellular processes, allowing for real-time study of cellular functions. We can also define the regulation point within a cell or tissue at a micrometer level,” says Yaowen Wu, a chemistry professor at Umeå University.
The intricate activities of a cell are dependent on the precise distribution and interactions of proteins throughout time and space. Effectively managing the roles of proteins or genes is crucial for modern biological research. However, traditional genetic techniques such as CRISPR-Cas9 often operate on extended timelines, which may lead to cellular adaptations. These methods also lack the necessary spatial and temporal accuracy for exploring the dynamic processes inside cells.
To address these challenges, researchers have employed innovative chemo-optogenetic systems as powerful tools. These systems combine chemical substances, optical techniques, and genetically modified proteins to accurately control protein functions at specific locations within cells using light-sensitive molecules. Professor Yaowen Wu’s lab is at the forefront of developing these chemo-optogenetic technologies.
In their earlier work, Wu’s lab introduced systems that utilize a type of molecular glue to connect two proteins, thereby altering a protein’s location or activity. These molecular glues can be activated or deactivated using light that removes or cleaves a light-sensitive component. Although these advancements were significant, they had limitations in application and lacked adequate stability in light and chemicals.
In two recent publications recognized as hot papers in the journals Angewandte Chemie International Edition and Chemistry – A European Journal, Wu’s team has crafted next-generation chemo-optogenetic instruments featuring photoswitchable molecular glues. These improvements tackle the shortcomings of earlier systems. The newly designed molecular glues can be toggled “on” or “off” just like a light switch using specific light wavelengths, enabling multiple activation cycles that can either boost or suppress protein functions.
”The new modular design provides exceptional flexibility within the system, offering adaptable properties and enhanced stability,” explains Jun Zhang, a research scientist in the Department of Chemistry at Umeå University.
“Our experiments have shown precise management of various cellular functions, which includes regulating protein activity, positioning organelles, and controlling protein levels,” comments Laura Herzog, a postdoctoral researcher in Umeå University’s Department of Chemistry.
