Project description DEENESFRITPL RNA and ribonucleoprotein aggregates in neurons Recent studies implicate the pathogenic relevance of altered RNA metabolism and aberrant ribonucleoprotein (RNP) assembly in several neurodegenerative diseases. How defective RNPs form, what their integral components are and which events trigger their appearance late in life are still unsolved issues. The EU-funded ASTRA project will combine sophisticated imaging-derived RNP complex purification, genetic tools and innovative computational approaches to investigate the biophysical properties and composition of the complexes and how they are modified in disease conditions. The development of new imaging and optical methods will allow scientists to study the separation of RNPs in liquid and solid phases in cells, in tissues and animal models, and to characterise their RNA and protein components in physiological and pathological states. Show the project objective Hide the project objective Objective Recent works indicate the pathogenic relevance of altered RNA metabolism and aberrant ribonucleoprotein (RNP) assembly in several neurodegenerative diseases, such as Amyotrophic lateral sclerosis. How defective RNPs form, what are their integral components and which events trigger their appearance late in life are still unsolved issues. While emerging evidence indicates that mutations and post-translational modifications of specific RNA-binding proteins (RBPs) induce liquid-solid phase transition in vitro, much less is known about the in vivo properties of RNP assemblies and which role RNA plays in their formation. ASTRA will combine sophisticated imaging-derived RNP complex purification with innovative computational approaches and powerful genetic tools to unravel the biophysical properties and composition of RBP complexes and how they are modified in disease conditions. Through the development of new imaging and optical methods we plan to study how RNPs separate in liquid and solid phases in cells, in tissues (retina) and animal models and to characterize their RNA and protein components in physiological and pathological states.Exploiting the novel finding that non-coding RNAs act as scaffolding molecules for RNP assembly, we will investigate how such RNAs control the dynamic link between RNP formation, intracellular sorting and function. In a genuine interdisciplinary team effort, we will reveal how the architecture and localization of cytoplasmic RNP complexes are controlled in motor neurons and affected in neurodegeneration.We plan to develop novel advanced microscopy methods to monitor formation of aberrant RNPs in vivo and we will explore new molecules to impede pathological cascades driven by RNP assemblies. In conclusion, ASTRA will allow us to gain a comprehensive understanding of RNP function and dysfunction; we will use this knowledge to develop new therapeutic strategies that will impact on several protein-misfolding neurodegenerative diseases. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineophthalmologymedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis Keywords long non coding RNAs and circular RNAs Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2019-SyG - ERC Synergy Grant Call for proposal ERC-2019-SyG See other projects for this call Funding Scheme ERC-SyG - Synergy grant Coordinator UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA Net EU contribution € 2 138 904,45 Address Piazzale aldo moro 5 00185 Roma Italy See on map Region Centro (IT) Lazio Roma Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA Italy Net EU contribution € 2 138 904,45 Address Piazzale aldo moro 5 00185 Roma See on map Region Centro (IT) Lazio Roma Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA Italy Net EU contribution € 5 602 894,55 Address Via morego 30 16163 Genova See on map Region Nord-Ovest Liguria Genova Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
