Environmental acclimation in the cephalopod nervous system through RNA editing

A-to-I RNA editing is an endogenous biochemical process with which cells dynamically and reversibly adapt mRNA sequences, affecting protein diversity and function.

Cephalopods have by far the highest RNA editing levels among animals, which may help them maintain their incomparably high neural functions even in the sometimes-inhospitable environment of the sea.

The precise underlying mechanisms however remain unknown, partly due to the complete lack of transgenic models.This project will elucidate the role and regulation of RNA editing in response to environmental factors using the bobtail squid Euprymna berryi.

I will use novel CRISPR-Cas9 knockout models of the RNA editing enzymes ADAR1 and ADAR2 to study the biological role of each enzyme, and explore the temperature-dependent regulation of RNA editing in this species. I will also assess whether RNA editing is regulated in response to different oxygen levels.

I will carry out the experiments at the Marine Biological Laboratory in Woods Hole, Massachusetts, and visit Tel Aviv University to acquire the necessary bioinformatic skills.

The project is an active collaboration with Lund University.Since the project pioneers the use transgenic CRISPR-Cas9 squid as a model organism, we expect the project to impact other fields that use cephalopods as a model, such as neurobiology and engineering. Our findings are also predicted to fuel efforts to adapt RNA editing for therapeutic purposes in a medical context.