Light is the most widely employed tool to interrogate biological specimens. Starting with the first optical microscopes through present-day super-resolution tools. Visible light has provided a vast amount of information about the state of living systems. The wavelength and intensity of incident light can also be precisely tuned and measured, enabling applications in quantitative regulation and single molecule detection. The goal of this proposal is to develop new, more sensitive molecular tools for manipulating central molecules in live tissues with superb spatial and temporal resolution.
Ribonucleic acid, or RNA is one of the three major biological macromolecules that are essential for all known forms of life (along with DNA and proteins). The flow of genetic information in a cell is from DNA through RNA to proteins. There are many chemical tools to study RNA structure and function in the laboratory. However, the tools to study RNAs in live tissue is limited and RNA activity with light has not been achieved yet. This project will isolate photo-riboswitches that will regulate gene expression in response to a single photo-isomer of a photoactive ligand, creating an RNA-based optogenetic tool. These molecular tools will be clonable modules that can be fused to other transcripts, act through secondary and tertiary interactions with target RNAs for optogenetic applications
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
