Photo credit: www.sciencedaily.com
Umeå University Develops Advanced Light-Controlled Tools for Protein Study
A research team at Umeå University has pioneered innovative light-controlled tools that facilitate real-time manipulation of proteins within living cells. This significant advancement not only enhances the methods utilized in cellular biology but may also lead to crucial developments in both medical and synthetic biology fields.
“The processes occurring within cells are intricate and continually vary based on timing and location. Our newly developed chemical tool with light switches simplifies the regulation of cellular activities and allows us to observe the dynamics of cellular functions in real time. We can precisely define the areas of regulation within a cell or tissue down to micrometre resolution,” remarked Yaowen Wu, a professor in the Department of Chemistry at Umeå University.
The functioning of a cell hinges on the accurate distribution and interaction of proteins over both space and time. Manipulating protein or gene activities is foundational to contemporary biological research. Nonetheless, conventional genetic methods such as CRISPR-Cas9 often unfold over extended periods, thereby risking cellular adaptation. Furthermore, these techniques typically lack the necessary precision in spatial and temporal resolution required to analyze the fluidity of cellular processes effectively.
To navigate these limitations, researchers have developed what are known as chemo-optogenetic systems. These systems integrate chemical compounds, optical technologies, and genetically engineered proteins, allowing for the targeted control of protein functions at specific locations in cells through the application of light-sensitive molecules. Professor Yaowen Wu’s lab is a leader in the advancement of these chemo-optogenetic systems.
Prior work in Wu’s lab revolved around systems utilizing a form of molecular glue. These systems operate by bringing two proteins into proximity to alter either their localization or activity. The activation or deactivation of these molecular glues occurs in response to light, which cleaves or removes light-sensitive groups. While these advancements marked progress, they were hindered by limitations such as insufficient chemical stability and photostability.
In two recent publications highlighted as hot papers in the journals Angewandte Chemie International Edition and Chemistry – A European Journal, researchers from Wu’s lab have introduced next-generation chemo-optogenetic tools grounded in photoswitchable molecular glues. These advancements address previous limitations, allowing researchers to activate or deactivate molecular glues akin to flipping a switch, utilizing specific light wavelengths to toggle between promoting or inhibiting protein functions.
”The new modular design offers exceptional versatility with adaptable properties and improved stability,” stated Jun Zhang, a staff scientist in the Department of Chemistry at Umeå University.
“Our experiments showcased the ability to exert precise control over various cellular processes, including not only protein function and localization but also the positioning of organelles and the regulation of protein levels,” added Laura Herzog, a postdoctoral fellow in the same department.
Source
www.sciencedaily.com