Objective
The discovery of RNA interference (RNAi) has revolutionized biology. As a technology it opened up new experimental and therapeutic avenues. As a biological phenomenon it changed our view on a diverse array of cellular processes. Among those are the control of gene expression, the suppression of viral replication, the formation of heterochromatin and the protection of the genome against selfish genetic elements such as transposons.
I propose to study the molecular mechanism and the biological impact of a recently discovered RNAi pathway, the Piwi interacting RNA pathway (piRNA pathway).
The piRNA pathway is an evolutionarily conserved small RNA pathway acting in the animal germline. It is the key genome surveillance system that suppresses the activity of transposons. Recent work has provided a conceptual framework for this pathway: According to this, the genome stores transposon sequences in heterochromatic loci called piRNA clusters. These provide the RNA substrates for the biogenesis of 23-29 nt long piRNAs. An amplification cycle steers piRNA production predominantly to those cluster regions that are complementary to transposons being active at a given time. Finally, piRNAs guide a protein complex centered on Piwi-proteins to complementary transposon RNAs in the cell, leading to their silencing.
In contrast to other RNAi pathways, the mechanistic framework of the piRNA pathway is largely unknown. Moreover, the spectrum of biological processes impacted by it is only poorly understood. piRNAs are for example not only derived from transposon sequences but also from various other genomic repeats that are enriched at telomeres and in heterochromatin.
We will systematically dissect the piRNA pathway regarding its molecular architecture as well as its biological functions in Drosophila. Our studies will be a combination of fly genetics, proteomics and genomics approaches. Throughout we aim at linking our results back to the underlying biology of germline development.
Fields of science
Call for proposal
ERC-2010-StG_20091118
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Funding Scheme
ERC-SG - ERC Starting GrantHost institution
1030 Wien
Austria