Project description
3D ultrastructure of DNA organisation in single cells
Understanding how genetic information is regulated inside the cell represents an intriguing challenge of modern biology. Genome-wide studies have revealed a hierarchical genome organisation by structuring proteins, which regulates fundamental processes such as transcription, replication and DNA repair. Topologically associating domains (TADs) are functional building blocks of chromatin organisation above the nucleosome level. The now available super-resolution microscopy set-ups allow the study of genomic structures and their dynamics in situ at a resolution of 10 nm, which is comparable to the size of a nucleosome. The aim of the EU-funded ChromaSTORM project is to reveal the principles of TAD organisation in human cells using an imaging-based approach to visualize its genomic component as well as the architectural proteins. The project will provide the first 3D description of this central chromatin super-structure.
Objective
How can phenotypic variations emerge from cells that carry the same genetic information? It is one of today’s great challenges to understand how genetic information is modulated inside the cell. Over the last decade, insight from genome-wide proximity-based ligation approaches revealed that the genome is organised in a hierarchical manner with the help of structuring proteins, and that this spatial organisation regulates the core functions of the genome, such as transcription, replication and repair. In this context, topologically associating domains (TADs) were identified as fundamental and functional building blocks of chromatin organisation above the nucleosome level. Despite its vital importance, our current understanding of the spatial organisation of TADs remains largely enigmatic. With the advent of super-resolution microscopy, tools are now available for studying genomic structures and their functional dynamics in situ at a resolution of 10 nm which corresponds to the size of a few nucleosomes.
The goal of this project is to reveal the principles of TAD organisation in human cells. To achieve this, I will employ a multidisciplinary imaging-based approach. I will simultaneously visualise the DNA backbone of TADs and architectural proteins involved in TAD structure applying 3D super-resolution microscopy. I will focus on the key TAD organisers CTCF and Cohesin, as well as on Mediator and Condensin II. Additionally, I will directly study their individual structuring function for TADs by their acute depletion. Integrating these data with quantitative measurements of absolute protein copy numbers, I will derive a data-driven model of inner TAD organisation in cells. These studies will provide the first 3D description of this fundamental chromatin super-structure and will further our understanding of genome architecture which is a prerequisite for understanding genome function.
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 genetics DNA
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- 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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2018
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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.
69117 Heidelberg
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.