"The proposed project aims to identify the dynamics of RNA-protein interactions during DNA damage response (DDR) using high-throughput “omics” approaches.
The mechanistic basis of DDR has been classically thought to consist of an ""early"" post-translational response, which results in activation of several signalling pathways and transciption factors. These activate the ""late"" transcriptional reprogramming influencing DNA repair, cell cycle regulation and apoptosis. However, for an immediate and effective response, global post-transcriptional control of mRNA stability, splicing and translation may be crucial during “immediate-to-early” DDR.
In this project, I will employ biochemical, cell, systems biology and computational approaches to study the relevance of post-transcriptional regulators such as RNA-binding proteins and microRNAs in DDR. Quantitative proteomics will be applied to identify the differentially mRNA-bound proteins after the exposure of human cultured cells to ionizing radiation. Validation of protein candidates will be carried out by biochemical and deep sequencing approaches. In addition, I will characterize the transcriptome-wide response of existing RNA molecules as well as the newly synthesized transcripts. This will provide a global insight into the dynamics of RNAs and proteins during DDR.
The proposed project explores a previously uncharacterized link between post-transcriptional RNA operons and DDR. The results and implementations of this project will significantly contribute to the understanding of the regulation of DDR, as well as have potential clinical and translational impact. Novel tumour-specific RNA-protein interacting partners may serve as candidates to selectively induce cell death in tumour cells.
The proposed project will enable a focused career development period in the scope of European mobility for the researcher who will gain a high level of expertise in systems biology and establish several international collaborations."
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