Project description
Dynamic remodelling of transcription upon oxidative stress
Oxidative stress is an imbalance between reactive oxygen species (free radicals) and the antioxidants that counteract them. In humans, it plays an essential role in cardiovascular and neurodegenerative diseases, cancer and diabetes. All organisms have an adaptive response to oxidative stress, typically the activation of so-called stress genes. A brief exposure to oxidative stress also leads to a rapid and transient global repression of transcription, but the molecular mechanism underlying this response is unknown. Funded by the European Research Council, the TranscriptStress project will investigate the transcriptome-wide oxidative stress response in human cells and in mice. State-of-the art sequencing, time-resolved proteomics and a novel screening approach should help fill this important knowledge gap.
Objective
Environmental stress triggers a cellular response to promote adaptation and survival, typically through activation of stress genes. What is less appreciated is that various types of cellular stress at the same time induce widespread transcriptional repression at most other genes. Although such transcriptional reprogramming is common to various kinds of cellular stress, recent evidence suggests it is governed by different stress-specific mechanisms. A brief exposure to oxidative stress leads to a rapid and transient global repression of transcription. However, our current knowledge about the oxidative stress response is extremely limited. Based on our preliminary results, I hypothesise that the transcriptional response to oxidative stress involves both regulation of transcription elongation as well as termination and that these are connected to post-translational modifications of RNA polymerase II (RNAPII) itself.
Here, I propose an ambitious approach to investigate the transcriptome-wide oxidative stress response in human cells and following physiologically induced oxidative stress in mice. To this end, we will use a combination of state-of-the art sequencing techniques coupled with time-resolved proteomics and a novel screening approach. Together, our work will provide important new knowledge about the transcriptional response to oxidative stress and the factors involved – in an area that is currently not well understood. Such knowledge is also crucial to understand the fundamental mechanisms allowing RNAPII to stop transcribing and restart again. Finally, we will investigate how factors involved in the transcriptional response influence transcription-associated genome instability and neuronal cell identity. This will be relevant for diseases in which oxidative stress has been implicated, such as neurological disorders and cancer.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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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.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-STG
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1165 KOBENHAVN
Denmark
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