Comparative genomics of gene expression lab

Certain genes are translated with programmed exceptions to the genetic code used for the rest of the genome. This phenomenon is known as “translational recoding”, and it is widespread through life. Its most common form is stop codon readthrough, wherein a stop codon supports amino acid insertion instead of translation termination.

Selenocysteine (Sec) is a non-canonical amino acid found in oxidoreductases known as selenoproteins. Sec is encoded by the UGA codon, and its insertion is dependent on stop codon readthrough. Humans carry 25 selenoproteins, many of which have essential functions such as antioxidant defense, protein quality control, and hormone regulation. This makes Sec, and its component selenium, essential for human health.

Our lab investigates the biology of selenium utilization and selenoproteins. We are particularly interested in two selenoproteins central to selenium metabolism: selenophosphate synthetase (Sephs2), involved in Sec synthesis, and Selenoprotein P (Sepp1), involved in selenium transport.

In insects, selenoproteins are very rare, but other forms of stop codon readthrough are very abundant: evolutionary conservation analyses indicate that readthrough occurs in ~1000 Drosophila genes. The functions and mechanisms of this phenomenon, however, are poorly characterized.

Our lab investigates stop codon readthrough in insects through computational and experimental approaches. We detect occurrences of readthrough through analysis of ribosome profiling, which is a variant of high-throughput RNA sequencing. Then, we pinpoint and validate the sequence elements responsible for readthrough through reporter assays in cell culture.

Besides our main basic research goals, we are working on repurposing natural readthrough mechanisms for an innovative form of gene therapy. Our aim is to induce readthrough in a targeted manner, which will allow to rescue pathogenic non-sense mutations.