Objective
In any organism, the need to reproduce is paramount, with genome replication being the earliest step in the process. The machinery and mechanisms of DNA replication are widely conserved, with initiation occurring at defined bi-directional DNA synthesis sites termed origins. Though origins may not be conserved DNA sequences, they are defined through binding conserved replication initiator factors. In some circumstances, such as after DNA damage or origin deletion, origin-independent replication can be observed in cellular organisms and can be driven by recombination. However, origin-independent replication is not normally considered to be a genome-wide, central reaction of genome replication. Very recently, genome-wide mapping of DNA replication initiation in two species of the kinetoplastid parasite Leishmania revealed only a single locus-specific origin per chromosome. Analyses of Leishmania S phase length and DNA synthesis speed suggest that a single origin-based strategy is insufficient for complete genome duplication, indicating replication in these eukaryotic microbes relies on origin-independent initiation to support origin-directed initiation. In this proposal, I will test the hypothesis that stochastic origin-independent DNA synthesis initiation events occur throughout the Leishmania genome due to homologous recombination acting on DNA lesions. If correct, this work will reveal the first example of a cellular organism that uses origin-independent replication as a core feature of genome duplication. The genome-wide use of recombination-driven replication would alter our view of DNA replication evolution and would explain the remarkable genome plasticity of Leishmania, with implications for how the parasite adapts genome structure and gene expression in the face of changing environments. Such adaptive change is seen during acquisition of resistance to anti-leishmanial drugs, and so this work will provide insight into the use and development of therapies.
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 microbiology protozoology
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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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-EF-ST - Standard EF
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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-2016
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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.
G12 8QQ Glasgow
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.