Project: Investigating how OCNDS variants affect cell signaling and whether suppressor tRNA therapy can help restore normal function

Lead Investigator: David Litchfield, PhD | University of Western Ontario

Grant Details:

Project funded for one year starting in 2026 for a total of $50,000.

Aims of Grant: 



Most cases of OCNDS are caused by de novo (spontaneous, non-inherited) mutations in CSNK2A1, the gene that encodes the catalytic subunit of the CK2 protein, the part of the protein that carries out its primary functions. CK2 is a kinase, a protein that regulates hundreds of other proteins by phosphorylation, which acts like a molecular on/off switch. Collectively, the thousands of phosphorylation events occurring throughout the cell make up the phosphoproteome, a map of which proteins are switched on or off. 

Some disease-associated mutations in CSNK2A1 do not impair the catalytic activity of CK2, meaning its ability to phosphorylate proteins. Instead, they disrupt the location of CK2 within the cell, what proteins it partners with, and which proteins it phosphorylates. 

This project will characterize how OCNDS-associated CSNK2A1 variants alter CK2 signaling in cell models, focusing on how these variants change the phosphoproteome, as well as the set of proteins that CK2 associates with, known as the interactome. 

The mutations in CSNK2A1 will then be corrected using transfer RNA (tRNA)-based therapeutics. tRNAs are molecules that normally deliver amino acids, the building blocks that cells use to assemble proteins. tRNA-based therapeutics help the cells’ protein-building machinery “read through” or correct an error caused by a mutation, allowing a normal, functional protein to be produced. The effect of functional CK2 on the phosphoproteome and interactome will then be examined.  

The results from this project will support identification of OCNDS biomarkers, inform how OCNDS disrupts normal biological function, and help identify and develop personalized tRNA therapeutics.