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Shaping the transcriptome through autophagy

Objective

In the face of environmental stress, autophagy plays a crucial role in stress adaptation through the maintenance of cellular homeostasis. While extensively studied for its ability to degrade proteins, pathogens, and organelles, the potential of autophagy to degrade RNA remains largely unexplored. Recent findings from my team uniquely reveal that specific subsets of RNA are selectively sequestered and degraded by autophagy in a stress-responsive manner. However, the molecular mechanisms driving this process and its biological implications remain unknown. Based on our preliminary results, I hypothesize that autophagy represents a previously unrecognized, highly regulated RNA decay pathway capable of dynamically shaping the transcriptome in response to cellular stress.

Here, I propose a comprehensive approach to investigate autophagy's impact on transcriptome remodeling in response to hypoxia and UV irradiation in cellular models and during melanoma development in mice. To this end, I will integrate state-of-the-art sequencing technologies with subcellular proteomics, high-content screening, advanced biochemistry, and single molecule RNA imaging. In doing so, we will dissect the molecular signals and regulatory factors guiding this previously overlooked RNA decay pathway. Furthermore, we will determine the biological consequences of pathway dysfunction on transcriptome integrity, cellular fitness, and the shaping of cellular identity. Together, this work will provide crucial insights into the mechanisms governing RNA homeostasis during cellular stress. The findings will challenge our current view of autophagy and uncover fundamental new understanding of gene expression regulation in health and disease, with broad implications across the biological sciences.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2025-COG

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Host institution

KRAEFTENS BEKAEMPELSE
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.

€ 1 999 965,00
Address
STRANDBOULEVARDEN 49
2100 Koebenhavn
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Research Organisations
Links
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.

€ 1 999 965,00

Beneficiaries (1)

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