Group: Vilardo

Research Focus

To date, more than 150 chemical RNA modifications have been described, most of them found in tRNAs. However, the pathways leading to the synthesis of many modifications, and their impact on the RNA molecule itself and on the cell remain poorly understood. Remarkably, mutations in about a half of the currently known RNA modification enzymes are associated with human diseases, manifested with diverse phenotypes, ranging from mild metabolic disorders to severe neuropathies. Among all RNA modifications, methylations constitute the vast majority of modifications identified.

In our lab we investigate the process of tRNA methylation from its multiple faces and aim to address the following fundamental questions: how do modification enzymes work to recognize their substrate? what is the effect of the modification on the tRNA structure/function? what are the consequences of modification, and of its absence, on cellular function?

To address these questions we use a range of diverse approaches including genetic manipulation by CRISPR/Cas editing, cutting edge Next-Generation Sequencing, classical biochemistry and protocols developed ad hoc in our lab to investigate RNA modification. We ultimately aim to translate our mechanistic findings from the molecular to the organismal level, and shed light on the role of RNA modifications in physiology and disease.