Grant: Undergraduate Student Research Awards (USRA)

"REarranged during transfection (RET) is a cell surface receptor tyrosine kinase that transduces signals for cell growth and motility. RET is required for the growth and dissemination of cells during the normal development of the neural crest and the innervation of many tissues, but these processes can be co-opted to contribute to the invasion of cancer cells. Despite their known importance, the underlying mechanisms and signals involved in RET-mediated invasion are not well understood. Building on previous work, this project will use RNA sequencing (RNA-seq) data to investigate the specific genes and signalling pathways involved in RET-mediated cell motility and invasion. We hypothesize that RET promotes these processes by altering the expression of invasion-related genes. We aim to analyse the gene expression patterns in RNA-seq data from RET wildtype and RET knockout cell lines using the DESeq2 software package in R to identify differentially expressed genes (DEG). We will perform Gene Ontology (GO) enrichment analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to explore DEG functional clusters and pathways associated with RET-dependent invasion. We will confirm changes in gene expression when RET is depleted by RT-qPCR. Candidate genes and pathways with predicted roles in RET-mediated invasion will be validated in vitro using CRISPR knockout in cultured mammalian cells and cell-based assays for cell adhesion, migration, and invasion. This integrated approach through data analysis, molecular and cell-based techniques will provide insight into the mechanisms and signals by which RET can regulate invasion, with broad implications for cell growth and cancer development."