Project description
G4 multimers under the microscope
G-quadruplex (G4) multimers are unique DNA structures found in higher eukaryotes. They are believed to play essential roles in biological processes. Their ability to inhibit telomerase in telomeres has generated interest in them as potential targets for anticancer medications. With the support of the Marie Skłodowska-Curie Actions programme, the MCG-QUAD project will conduct an integrative study of G4 multimers, developing a framework for interpreting experimental data and connecting microscopic views with macroscopic observables through the use of an innovative multiscale in silico approach. These solutions will help expand our understanding of G4 multimers and their dynamics in telomeric sequences, thereby allowing for many key breakthroughs.
Objective
MCG-QUAD is an integrative study of G-quadruplex (G4) multimers—noncanonical DNA structures—providing a framework to interpret experimental data and connect a microscopic view to macroscopic observables through a novel multiscale in silico approach. G4s are ubiquitous in the genomes of higher eukaryotes and are believed to play key roles in various biological processes. The presence of G4s in the telomeric region has been shown to inhibit telomerase, opening the possibility for G4-stabilizing compounds to be used as anticancer medications. Sequences that form G4s exhibit long folding timescales. G4s are highly polymorphic structures with long-living quasi-stable topologies, a complexity further compounded in multimers. Structural information on G4 multimers is limited, and existing data often lack physiological context. A novel computational approach is necessary to address open questions about the folding/unfolding dynamics of telomeric sequences into G4 multimers, their structure, topological phase space, the role of crowders, and the effects of ligands on G4 formation, stabilization, and properties. Through a combination of classical bottom-up coarse-graining and recent developments in machine learning, MCG-QUAD provides scalable and accurate models that enable bulk, long-timescale simulations. These simulations will be combined with in vitro observables to elucidate previously inaccessible phenomenology, forming an integrative study of G4 multimers in crowded environments. Furthermore, MCG-QUAD explores the interaction of G4 multimers with ligands to inform the design of new anticancer drugs, pushing beyond the limitations of existing in vitro and in silico studies. In collaboration with leading experts and institutions, MCG-QUAD will generate knowledge for the development of effective G4-targeting therapies and a broader understanding of biomolecular behaviour in complex environments, extending beyond cancer research.
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.
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs
- natural sciences biological sciences genetics DNA
- natural sciences mathematics pure mathematics topology
- medical and health sciences clinical medicine oncology
- 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)
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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
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-PF-01
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00185 Roma
Italy
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