What we do
A BIT OF BACKGROUND
Our research interest is to understand the role of post-transcriptional gene regulation during germline development. Dysregulation of gene expression at the post-transcriptional level leads to growth defects and cancer. Normal tissue development depends on RNA binding proteins and non-coding RNAs; however, more recently, modifications to the RNAs have also been shown to be critical in this process. The functional relevance of RNA modifications in vivo is largely unexplored, and their role in organogenesis and disease remains to be established.
A critical type of post-transcriptional modification is the non-templated addition of nucleotides to the 3’ end of RNAs. These 3’ additions of nucleotides are catalysed by enzymes known as terminal nucleotidyl transferases (TENTs). There are eleven mammalian TENTs each one with a preference for one or more of the four ribonucleotides; A, C, G or U. When a TENT adds several Us to an mRNA, a process known as oligo-uridylation, the RNA becomes unstable. Instead, when an mRNA is poly-adenylated, it becomes translationally active. The roles of C terminal additions (cytidylation) and G terminal additions (guanylation) are only now beginning to be explored ex vivo.
By systematically studying the TENTs using animal models and advanced molecular biology techniques, we will begin to understand the physiological relevance of terminal modifications in tissue development and start to bridge the gap between our mechanistic knowledge of gene regulation at the cellular level and the principles that define multicellular organization.