Project Overview
Our DNA contains remnants of ancient viral infections, sequences called endogenous retroviruses (ERVs), that make up roughly 8% of the human genome. Long dismissed as "junk DNA," ERVs are actively expressed in human neurons, yet their role, if any, remains largely unknown.
This project investigates a bold new idea: that neurons use ERVs as a form of communication. Cells routinely release tiny membrane-enclosed packages called extracellular vesicles (EVs) that carry molecules to neighbouring cells, influencing their behaviour. Recent discoveries have shown that certain proteins derived from retroviral sequences can package RNA into EVs for transfer between cells. We hypothesize that ERVs participate in this same process and that they do so in a regulated, activity dependent manner, meaning neurons may adjust what ERV cargo they package into EVs depending on how electrically active they are.
To test this, we will use human stem cell-derived neurons and subject them to different levels of electrical activity. We will then isolate the EVs they produce and comprehensively profile their ERV content at both the RNA and protein levels. This will generate the first open-access atlas of ERVs in neuronal EVs. We will also use CRISPR gene-editing to remove specific ERVs and test whether receiving ERV-containing EVs changes gene expression, electrical activity, or survival of recipient neurons. Beyond fundamental neuroscience, this work has translational implications: aberrant ERV expression is linked to neurodegenerative diseases such as ALS and multiple sclerosis. Understanding how ERVs participate in normal neuronal communication could explain how their dysregulation contributes to disease, and open new therapeutic avenues. Results from this project will directly inform future studies in spontaneous animal disease models, creating a pipeline toward clinical applications in both human and veterinary medicine.
Partners & Donors
Azrieli Foundation
