Tymber Moody

The WARS2 gene encodes the mitochondrial tryptophanyl-tRNA synthetase responsible for charging mitochondrial tRNA with tryptophan – an essential step in mitochondrial protein synthesis. Pathogenic variants in WARS2 cause a rare mitochondrial disorder characterized by impaired mitochondrial translation and neurological symptoms including movement abnormalities and seizures. Despite the severe impact this disorder has on patients, there are currently no curative treatment options available. This research therefore aims to identify drugs – screened from a large library of FDA and EMA approved, repurposed drugs in Drosophila melanogaster – that can alleviate symptoms associated with WARS2 deficiency. Using such a “drug repurposing” screen will potentially lead to faster translation of treatments to affected patients. We are also investigating the molecular mechanisms contributing to the effects of these compounds in Drosophila melanogaster to determine whether the observed phenotypic rescue is due to their known pathway or a different one. Together, this work integrates genetics and pharmacology to discover drug candidates and mechanistic insights to advance the treatment of WARS2-related mitochondrial disorders.