Project description
Research sheds light on silencer’s role on gene expression
Gene expression is controlled by genomic regions called regulatory elements. While much is known about enhancers, which activate genes, silencers, which turn genes off, remain poorly understood. With the support of the Marie Skłodowska-Curie Actions programme, the SIRENseek project aims to identify and characterise silencers and the proteins that bind to them to gain further insight into their underlying mechanisms. SIRENseek will combine advanced methods to identify these proteins, assess how they interact with silencers and explore how silencers change the 3D structure of DNA to turn off genes. This proposed research will sistematically map silencers, thereby improving understanding of gene control and potentially leading to new treatments
Objective
"Distal regulatory elements in the genome play a key role in orchestrating tissue- and context- specific transcriptional programs. While activating elements (enhancers) have been broadly studied in the last decades, repressive elements (silencers) remain a ‘mysterious’ class of regulatory regions of the genome, whose characteristics have never been systematically elucidated.
In the ""seeking the SIlencer-associated REpressive protein Network” (SIRENseek) project, I aim to identify and functionally characterize silencers and silencer-binding proteins (SBPs) to gain insight into their mechanism of action and ultimately unlock their untapped potential for gene regulation and targeted therapy. To this aim, I will combine state-of-the-art proteomic analyses and high-throughput epigenomic profiling to identify SBPs and assess their relevance in shaping the chromatin landscape. First, I will focus on a repressive transcription factor known to bind silencers and I will use novel proximity labeling technologies to isolate its interacting proteins, thus unveiling other chromatin factors involved in silencer functions. Then, I will interrogate multiple candidate SBPs via a CRISPR screening and test their ability to rewire the chromatin landscape via ATAC-seq. Finally, by integrating this information with epigenomic data, I will identify SBPs with a functional role at silencers and test their ability to establish long-range chromatin interactions via 3D genomic approaches.
Together, this interdisciplinary proposal will allow me to map for the first time silencer elements, their associated chromatin factors and the potential 3D interactions that they mediate to repress target genes, thus addressing the existing gap in our understanding of repressive elements."
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
- natural sciences biological sciences genetics genomes
You need to log in or register to use this function
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
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
See all projects funded under this funding scheme
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-2024-PF-01
See all projects funded under this callCoordinator
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.
20121 Milano
Italy
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.