Project description
The role of small RNAs in genome stability
Small RNAs such as microRNAs are known to play a central role in the regulation of gene expression. With the support of the Marie Skłodowska-Curie Actions programme, the sRNAUR project aims to explore whether small RNAs and particularly piwi-interacting RNAs (piRNAs) regulated DNA copy number in Drosophila. Evidence so far indicates that piRNAs protect the germline genome by facilitating heterochromatin formation at repetitive DNA regions. The project will investigate whether piRNAs regulate the amount of centromeric DNA and they influence how traits are inherited. By using advanced sequencing and imaging techniques, sRNAUR is expected to uncover new insights into how small RNAs help maintain genome stability.
Objective
Small RNA-mediated gene regulation and DNA replication are fundamental genome-regulatory pathways essential for cellular life, organismal development, and disease prevention. While small RNA pathways are known to sequence-specifically regulate DNA copy number in some unicellular animals, such connections have yet to be found in multicellular animals. With this project, I will investigate and mechanistically characterize such a potential connection in the Drosophila animal model system.
Piwi-interacting RNAs (piRNAs), a class of animal small RNAs, safeguard the germline genome against repetitive DNA proliferation by guiding repressive heterochromatin formation at target loci. In Drosophila melanogaster ovarian nurse cells, heterochromatic (peri)centromeric DNA repeats undergo selective local suppression of DNA replication thus lowering their relative copy number. Interestingly, abundant piRNAs able to target to these 'underreplicated' regions have been found, yet the potential functional interactions between small RNA genome defense and DNA replication remain unexplored. With this project, I will bridge this gap by investigating the role of satellite piRNAs in Drosophila melanogaster, focusing on the interplay between regulated DNA replication and small RNA genome defense. Two interconnected hypotheses will be examined: (1) piRNA-directed heterochromatin formation regulates centromeric DNA copy number, and (2) piRNA-regulated heterochromatin sinks alter epigenetic inheritance. To do so, I will apply advanced sequencing- and imaging-based methods for DNA copy number quantification and leverage the powerful Drosophila genetics to uncover underlying molecular mechanisms.
In sum, my investigation of small RNA-based regulation of DNA replication holds the promise to reveal a new paradigm in animal genome regulation and to provide deeper insights into the mechanisms regulating genome stability and the role of piRNAs in maintaining it.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesgeneticsDNA
- engineering and technologymechanical engineeringvehicle engineeringaerospace engineeringsatellite technology
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesbiological sciencesgeneticsgenomes
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Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
8000 Aarhus C
Denmark