Development and Application of Synthetic Receptors for Methylated Lysine and Arginine for Methyltransferase Assays

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Marcey Waters from the University of North Carolina at Chapel Hill. While every cell in an individual person has the same genes, not all genes in a cell are expressed. Gene expression is the process by which genetic instructions are used to synthesize genetic products. Differences in gene expression lead to differentiation, such that a skin cell is different from a liver cell, for example. Research into understanding how genes are expressed is an important area because the factors that control gene expression can lead to many diseases. One factor that controls gene expression, but that is poorly understood, is a phenomenon called protein methylation, which involves the "tagging" of certain proteins with a molecule, here a methyl group. Studies indicate that incorrect methylation is a critical component in many diseases, particularly cancer, and that the processes that lead to methylation are potential medicinal targets. However, the ability to detect methylation is currently severely limited. Dr. Waters is developing new detection tools for rapidly sensing methylation, and determining when incorrect methylation occurs. This project is also supporting continued efforts to increase diversity in science fields and provide undergraduate and graduate student research opportunities for those from underrepresented groups. This research project is developing synthetic receptors as molecular sensors for methylated lysine and arginine, which are being used to characterize the enzymes that install and remove these post-translational modifications. Dysregulation of lysine and arginine methylation has been linked to a wide range of diseases, yet the tools available for sensing these modifications are limited and this has hindered advancements in the field. These approaches include the use of antibodies, which are expensive and have been shown to give false negatives; radioactive labeling, which is a low-throughput single-timepoint assay and requires specialized equipment and safety protocols; and mass spectrometry, which is time consuming and requires very sensitive, expensive equipment. The approach taken in this proposal is providing a rapid, real-time, high throughput, fluorogenic sensing method, which is enabling a significant advancement in the ability to characterize lysine and arginine methylation.