Grant: Master's Award: Canada Graduate Scholarships

Alternative Splicing; Cerebellar Development; Granule Neuron Precursor (Gnp) Cells; Phosphorylation; Phosphorylation-Specific Exon Regulation; Phosphorylation-Specific Exons; Post-Transcriptional Regulation; Sonic Hedgehog Medulloblastoma (Shh-Mb); Splice Variants; Tumorigenesis

Phosphorylation is a critical process in the body that plays an important role in controlling the development and progression of cancer. This process is done by molecules known as kinases, which add phosphate groups to proteins, thereby altering their functions. However, kinases often act as blunt instruments with the ability to phosphorylate a variety of proteins with similar binding sites, leading to multiple downstream effects. Consequently, a challenge arises in the kinase’s inability to precisely target and control the activity of a specific protein. To address this problem, we will be exploring the mechanism of alternative splicing (AS), which allows cells to produce different versions of proteins called splice variants using only a single set of genetic instructions. By including or excluding parts of the genetic code containing areas of phosphorylation, AS may act as an unconventional means of controlling phosphorylation in growth processes and cancer formation. Medulloblastoma (MB) is the most common childhood brain tumour, and acts as a good model to study this concept due to the large number of cells in the brain that can develop into a MB. Previous data from our lab will be used to find the splice variants and their associated phosphorylation sites (called phosphosites) that lead to MB growth. New experimental research will be performed to determine the effects of including or excluding phosphosites in normal brain and MB cells in mice. The proposed research will establish novel methodology via AS-mediated selective phosphorylation and may uncover new biological rules governing tumour development and initiation, potentially leading to innovative strategies for cancer treatment.