Objective
Regulation of transcription is orchestrated by a complex combination of histone posttranslational modifications (PTMs), but how their co-occurrence in the same cell regulate gene expression is still poorly understood. Recently, novel histone acylations have been identified, namely propionylation (pr) and butyrylation (bu). They co-exist with acetylation (ac), arise from cellular metabolism, and are key candidates to fine-tune chromatin activity and transcription. This project will answer fundamental questions on the role of acylations in gene regulation and their co-occurrence in single cells, and provide novel insights into metabolic disorders (propionic acidemia; PA), where histone acylations are altered.
Through this project, I will generate the first genome-wide histone acylation map in single cells, functionally link their co-occurrence with gene expression, and establish the impact of a metabolic disease on histone acylations and transcription. Our preliminary data showed that histone H4K16ac/pr/bu play key roles in chromatin activity and could thus regulate transcription, and are impaired in livers of a PA mouse model. I hypothesize that acylations co-occurrence will regulate transcription, and altered propionyl-CoA metabolism in PA will impact H4K16 acylations, and consequently transcription.
To achieve this, I will develop an experimental and computational framework for single-cell Simultaneous Transcriptome and Epigenome Profiling (sc-STEP-seq). With this approach, I will map H4K16ac/pr/bu and the transcriptome in single-cells, and integrate epigenomic and transcriptomic changes, in liver samples from PA mice. This interdisciplinary project will address a fundamental question in epigenetics: the functional relevance of histone PTMs regulated by metabolic state in single cells, advance the technology for single-cell multimodal epigenomic profiling, and provide for the first-time molecular understanding of histone acylations in a clinically relevant model.
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.
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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.
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.
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.
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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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.
85764 Neuherberg
Germany
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.