Objective
The replication of DNA and therefore of the genetic information is realized at the molecular level in three steps: helicases open the DNA, primases initiate the replication and polymerases use this primer to duplicate the DNA strand. The precise mechanism of action of primases has up to now remain quite elusive and thus a better understanding of how primase works would be of great interest to fully understand the process of DNA replication.
Primases are classed into two groups, bacterial and archeal/eukaryal, and some archeal primase have the particularity to carry their biological function without requiring the association in a larger molecular complex, making them an accessible target to Nuclear Magnetic Resonance (NMR) spectroscopy.
In this project we propose to exploit the unique capacity of NMR spectroscopy for determining structure and dynamics of biomolecules in solution to investigate the ORF904 primase, free and in complex with its DNA template and the cofactors necessary for primer synthesis. We aim to characterize how this system assembles and to provide an atomic resolution picture of its mechanism of action, just before the creation of the first phosphodiester bound that initiate primer formation. We will also investigate the conformational changes occurring during the primer synthesis using Electron Paramagnetic Resonance (EPR) spectroscopy. Spectroscopic and computational innovative approaches will be developed to describe this complex dynamic system and complementary integrative structural biology will be used to support our findings.
By this study we aim to provide an accurate description of a primase accomplishing its biological function and therefore significantly deepen our knowledge of DNA replication. This in turn could be used in cancer biology to develop new therapeutic approaches.
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 physical sciences optics spectroscopy absorption spectroscopy
- natural sciences biological sciences genetics nucleotides
- natural sciences biological sciences molecular biology structural biology
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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-2015
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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.
8092 Zuerich
Switzerland
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.