Supervisor: Dr Ansgar Zoch We study how the mammalian germline defends genome integrity against jumping genes called transposons. The germline, the cell lineage that will eventually make sperm and egg cells, passes on our genetic information to the next generation. Maintaining the integrity of the germline genome is thus paramount to the continuation of life. Transposons threaten genome integrity through mutagenic transposition and deregulation of chromatin. During foetal development, transposons reactivate in mammalian germ cells, creating an existential challenge. The piRNA pathway identifies active transposon loci using small non-coding piRNAs and induces epigenetic silencing by de novo DNA methylation. Yet, the mechanisms of how target-recognition leads to silencing are not understood. We recently discovered essential effector proteins required for piRNA-mediated DNA methylation. We also demonstrated the relevance of the pathway for human fertility. In this project we will build upon these discoveries to investigate how the piRNA pathway controls the chromatin environment at transposon. The aim is to understand piRNA-mediated regulation of chromatin remodelling complexes from the nano-scale of protein interactions to relevance in the organism. Therefore, this project will involve a wide range of molecular biology tools in cell culture and mouse models as well as recombinant approaches. Ansgar Zoch Research Group This article was published on 2024-11-05
