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Bridging temporal resolution gaps to dissect RNA silencing at the molecular and genomic scale

Project description

Regulatory role of RNA silencing at molecular and genomic levels

Establishing distinct gene expression profiles is essential for organism development and physiological response to external stimuli or pathogens, as well as for our understanding of human diseases. Controlling different aspects of RNA regulation and function has emerged recently as a critical element, with immediate biotechnological and biomedical implications. The EU-funded RiboTrace project proposes to study the molecular principles of RNA silencing, the least understood aspect of post-transcriptional gene regulation, in fruit flies and mammals. Researchers will study the mechanisms and biological functions of RNA 3´end uridylation, to determine the role of RNA modifications in the regulation of gene expression; and elucidate principles of RNA turnover at the genomic scale by time-resolved transcriptomics. By combining in vivo genetics, cell-free biochemical experiments, bioinformatics, and cell culture methods, RiboTrace will delineate post-transcriptional gene regulatory pathways at the molecular and genomic scale.

Objective

The implementation of distinct gene expression profiles is essential for organismal development, physiological responses to external stimuli or pathogens, and defines a primary cause for human disease. While much attention has been paid to the regulation of transcription, the control over RNA fate and function has only recently emerged as a central hallmark of gene regulation with enormous biological, technological and biomedical implications.
Here, we propose to study the molecular principles of RNA silencing, the least understood aspect of post-transcriptional gene regulation. We aim to systematically dissect the mechanisms and biological functions of RNA 3end uridylation to determine the emerging role of RNA modifications in the regulation of gene expression; we will elucidate fundamental principles of RNA turnover at the genomic scale by time-resolved transcriptomics; and we will use functional genomics and haploid genetics to systematically delineate post-transcriptional gene regulatory pathways. Throughout, we will link our results back to the established function of RNA silencing in the control of organismal development, physiology and disease. Our goal is to acquire fundamental insights into the processes that survey the quality and quantity of the transcriptome to determine possible molecular causes for aberrant RNA levels that have been associated with diverse human diseases.
Because of its genetic and biochemical tools, we will use Drosophila melanogaster as a model organism. We will employ a combination of in vivo genetics, cell-free biochemical experiments, bioinformatics, and cell culture methods. What we learn in flies we will test for its conservation in mammalian cell extracts and cultured cells.
Overall, we will determine fundamental biological mechanisms of gene regulation trough pathways with enormous biological impact in health and disease.

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Topic(s)

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Funding Scheme

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ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2019-COG

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Host institution

UNIVERSITAT WIEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 448 149,50
Address
UNIVERSITATSRING 1
1010 WIEN
Austria

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Region
Ostösterreich Wien Wien
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 448 149,50

Beneficiaries (2)

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