A small RNA-based immune system guards germ cell genomes

The PIWI-interacting RNA (piRNA) pathway is a small RNA-based innate immune system that guards the germ cell genomes of animals from the potentially deleterious consequences of the unfettered activity of mobile genetic elements. The integrity of this pathway is important for maintaining germ cell function and reproductive fitness throughout the animal kingdom. We propose to use Drosophila as a model system to deepen our mechanistic understanding of piRNA biology, drawing upon genetics, biochemistry, molecular and structural biology, high resolution and live-cell imaging, and computational and evolutionary biology. We seek to understand how piRNA clusters are defined and expressed, how their long non-coding RNA products are fated for biogenesis, how they are processed on the surface of mitochondria, and how the resultant piRNAs elicit co-transcriptional silencing, as well as the timelines and dynamics of the underlying processes. Finally, we will draw upon the expertise built in other areas of focus within our group to study the spatial and temporal interactions between transposons and host defence, as the relationship between mobile elements and their host are likely much more nuanced than can be reveal by bulk analyses which collapse multiple developmental stages into a single averaged measurement.