Eukaryotic genomes are not static blueprints but dynamic conflict zones shaped by the ancient struggle between selfish genetic elements and their hosts. Transposable elements are the most prominent invaders, capable of copying and inserting themselves across the genome, disrupting genes and threatening genome stability. Yet, eukaryotes have evolved powerful defence systems to keep these elements in check. As a result, genomes can tolerate vast amounts of transposons, which make up half of the human genome and up to 80% of some plant genomes. Our group investigates the molecular principles of this conflict, focusing on how small RNA-guided genome immune systems silence transposons—and how transposons, in turn, evolve to escape suppression. Notably, this ongoing evolutionary arms race is one of the major drivers of molecular innovations in biology.
We use the fruit fly Drosophila melanogaster—a powerful genetic model—to explore the co-evolution of genome defence systems and transposable elements. By studying both host silencing pathways and transposon strategies, we aim to uncover the molecular mechanisms and principles that safeguard genome stability and to reveal the innovations that transposons use to evade these defences. Our work addresses fundamental questions about genome function, RNA biology, evolutionary innovation, and the molecular logic of genetic conflict.
We address these questions through collaborative, interdisciplinary research. By integrating genetics, comparative genomics, computational biology, imaging, biochemistry, and structural biology, we gain a comprehensive view of genome defence, uncovering novel biological processes and linking molecular mechanisms to broader evolutionary paradigms. Our lab focuses on two complementary research domains: genome defence mechanisms of the host and evolutionary strategies of transposable elements.
The host side: Molecular Mechanisms of the piRNA Pathway
The PIWI/piRNA pathway is a highly specific, small RNA-guided genome immune system—functionally analogous to CRISPR-Cas in prokaryotes. In animals, it safeguards the germline by silencing transposons and other foreign sequences.
Our lab has identified nearly forty core proteins of the piRNA pathway, laying the foundation for a molecular understanding of this defence system.
We investigate the genetic and mechanistic principles of piRNA biogenesis, piRNA-guided heterochromatin formation, and the transcriptional control of piRNA-producing loci. A central question is how this powerful system can selectively silence the vast array of transposons without disrupting normal gene expression.
The transposon side: Adaptation and Evolutionary Innovation
Transposons must continuously evolve to survive. To maximize their replication, they must evade host defences and adapt to the gonad ‘ecosystem’. With dozens of active transposon families employing different replication strategies, Drosophila offers a rich model to study transposon evolution.
We have developed sophisticated genetic systems that enable precise manipulation of both host and transposon biology, allowing us to dissect the molecular and evolutionary dynamics of this arms race.
By exploring how transposons adapt their traits to the cellular environment of the male and female host gonad, we are uncovering principles that not only explain their persistence but also provide insights into retroviral evolution and host-pathogen interactions.
Read more about our research here.
ERC Starting Grant (2010-2015)
ERC Consolidator Grant (2016-2021) more information
ERC Advanced Grant (2024-2029) more information
FWF Doctoral Program “RNA@CORE" (recurring)
Hohmann, U., Graf, M., Schellhaas, U (...) Brennecke, J., Plaschka, C. (2024). A molecular switch orchestrates the nuclear export of human messenger RNA BioRxiv.
Andreev, VI., Yu, C., Wang, J (...) Patel, DJ., Brennecke, J. (2022). Panoramix SUMOylation on chromatin connects the piRNA pathway to the cellular heterochromatin machinery. Nat Struct Mol Biol. 29(2):130-142
Baumgartner, L., Handler, D., Platzer, SW (...) Duchek, P., Brennecke, J. (2022). The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters. Elife. 11
ElMaghraby, MF., Andersen, PR., Pühringer, F (...) Tirian, L., Brennecke, J. (2019). A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production. Cell. 178(4):964-979.e20
Andersen, PR., Tirian, L., Vunjak, M., Brennecke, J. (2017). A heterochromatin-dependent transcription machinery drives piRNA expression. Nature. 549(7670):54-59
