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EMBO Fellowship Broglia

Aggregation of RNA binding proteins (RBPs) is a pathological hallmark of neurodegenerative pathologies such as Amyotrophic Lateral Sclerosis. The mechanism of RBP aggregation relies on the ability of these proteins to transition into separate compartments such as stress granules. As RBPs are intrinsically prone to coalesce in large assemblies, their accumulation, if unregulated, can lead to cell toxicity. While the effects of amino acid mutations on RBP aggregation have been extensively investigated, recent studies indicate that nucleotide variants in untranslated regions (UTRs) can strongly impact RBP expression by altering the interactions with specific regulatory proteins. The research objective of my project is to reveal interactions in regulatory regions of RBPs and to understand their effects on phase separation in physiology and pathology. Firstly, the effect of disease-linked mutations on UTRs of RNAs encoding RBPs will be studied in silico. Secondly, I will characterize the RBP interactome of specific UTRs mutated in neurodegenerative diseases. Lastly, functional characterization of these interactions will be shed light on the contribution of regulatory regions in RBP phase transition and aggregation. Successful completion of this project will not only lead to new insights into RBP biology, but will also pave the way to understand early events of neurodegeneration.

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Project information
EMBO Fellowship Broglia
Start date
End date
People involved
Laura Broglia
RNA Systems Biology
Total budget: 66.000,00€
Total contribution: 66.000,00€