Approximately half of the sequence of human and mouse genomes is derived from mobile elements. Much of this DNA is no longer capable of mobilization but is likely “auditioning” for a function for example in homologous recombination or in regulation of gene expression. Modern mammalian genomes also contain numerous intact transposable elements, such as retrotransposon LINE-1, that utilize RNA intermediate to spread about the genome.
Given the crucial role of germ cells in the propagation of species, their genomes represent a particularly attractive target for the selfish propagation LINE-1. Uncontrolled activity of retrotransposons is known to cause new mutations and even kill germ cells necessitating existence of specialized defensive mechanisms regulating LINE-1 elements.
Our group focuses on:
1. Molecular mechanisms of restraining LINE-1 mobilization in mouse embryonic and adult germ cells.
We approach this problem through the analysis of function of Maelstrom, a conserved protein implicated in transposon silencing in flies and mice by means of specialized small RNAs known as Piwi-interacting RNAs (or piRNAs).
2. The impact of LINE-1 on the development, differentiation and function of mouse germ cells.
We posit that the never-ending battle between the genome and its selfish elements has profoundly influenced and shaped many aspects of germ cell biology in the course of evolution. We are trying to uncover and understand how LINE-1 elements impact germ cells in the course of their normal development and differentiation particularly during meiosis, a specialized cell cycle that generates haploid gametes.