Grant: Project Grant

Transposable elements (TEs) are selfish genes that copy themselves and jump around the genome. Sophisticated defense mechanisms prevent TEs from rampant replications and insertions causing devastating mutations that destroy genes, generate breaks in the DNA, and induce chromosomal rearrangements. TE regulation is therefore pivotal to the maintenance of genome stability, and failure to suppress them are associated with myriads of disease phenotypes and illness including tumorigenesis and sterility. Despite the robust and conserved defense mechanisms, TEs repeatedly developed means of evading control. This is evident from their overwhelming abundance across eukaryotes, including the human genome of which they occupy nearly 50%. Using the powerful model genetic organism, the Drosophila, this proposal aims to dissect the molecular bases for two strategies in which TEs adopt during a critical juncture of early embryonic development called zygotic genome activation. The first strategy to be elucidated is the timely activation of TEs during this critical time point allowing them to proliferate before silencing mechanisms are established. The second is for TEs to concentrate their activity at favorable locations to increase their chance to insert into the germline necessary for transmission to the next generation. To understand the mutational and disruptive impacts of individual insertions, we further aim to artificially induce TE insertions through multiple generations. Large numbers of novel TE insertions will allow exhaustive investigations of how individual insertions affect local epigenetic state, gene regulation, and chromatin architectures genome-wide. Understanding how TEs proliferate and how they disrupt genome architecture will critically inform preventative and treatment plans for the plethora of diseases caused by genome instability.