2024 Michael Smith Health Research BC, Sept 17, 2024:
Molecular mechanisms and genomic consequences of transposable element hijack strategies during embryogenesis
Year 2024
Type Scholar Award
Principal investigator Kevin Wei
Host institution University of British Columbia
Research location University of British Columbia
Transposable elements (TEs) are selfish genes that self-copy and move around the genome. Robust defense mechanisms silence TEs to prevent them from causing devastating mutations that break DNA and destroy genes. Failed TE suppression is associated with myriads of disease phenotypes including tumorigenesis and sterility. But the defense is not failsafe; TEs repeatedly acquire evasion tactics, enabling them to amplify at the expense of the genome. Using the powerful model organism, the Drosophila, this proposal aims to dissect hijack strategies TEs adopt during embryonic development. The first strategy is the timely activation of TEs before silencing is fully established. The second is for TEs to concentrate their activity near cells to increase the chance of passage to the next generation. To further reveal the full mutational impacts of TEs, we will artificially induce TE activity across multiple generations. Large numbers of new TE insertions will enable us to determine the deleterious impact on epigenetic state, gene regulation, and nuclear organization. Elucidating how TEs “cheat” and disrupt the genome will critically inform preventative and treatment plans for diseases caused by genome instability.