Project description
DNA sequences shape chromosomal organisation through mechanical properties
DNA sequences influence both protein encoding and their mechanical properties, affecting gene regulation and chromatin organisation. However, the impact of these mechanical features on biological functions remains largely unexplored. Supported by the Marie Skłodowska-Curie Actions programme, the MECHGEN project will develop a molecular dynamics model to investigate how DNA sequences affect chromosomal organisation. The project will examine how sequences influence topological strains and DNA damage in supercoiled DNA, as well as their effect on chromatin structure and function. By combining simulations with experimental data, it aims to deepen our understanding of genomic stability and gene regulation, with potential implications for treating genetic diseases.
Objective
Beyond its role in encoding the primary structure of proteins, the sequence of DNA also determines its mechanical properties such as shape and flexibility. This sequence-specific mechanical code significantly influences interactions between the cellular machinery and the genome, affecting critical processes such as gene regulation and chromatin organization. However, the extent to which this MECHanical GENome drives biological function remains largely unexplored. MECHGEN seeks to bridge this gap by leveraging a recently developed coarse-graining methodology to construct a multi-resolution molecular dynamics (MD) model that integrates sequence-dependent elastic properties of DNA. This model will enable efficient simulations of genomic length DNA, chromatin, and other biologically relevant systems.
Using this new methodology, we propose to study two aspects of chromosomal organization. The first will investigate how DNA sequence influences the distribution of topological strains and how sequence context determines the exposure of DNA damage in supercoiled DNA, offering new insights into genomic stability and repair mechanisms. The second line of investigation will explore how DNA sequence shapes chromatin structure and function, focusing on nucleosome positioning and higher-order chromatin architectures. By combining coarse-grained simulations with experimental data, MECHGEN aims to clarify the role of sequence variations in chromosomal organization and gene regulation. These findings could significantly impact our understanding of genomic function and stability, with potential applications in the study and treatment of genetic diseases.
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 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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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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.
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-2024-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.
EH8 9YL Edinburgh
United Kingdom
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.