Objective
"Accurate DNA replication is key to maintaining genomic stability. Replication is immensely complex requiring error-free duplication of several billion bases each time a human cell divides. The DNA replication machinery must deal with a wide range of DNA damage, aberrant secondary structures and DNA:protein complexes; obstacles that cause replication forks to arrest. Arrested replication complexes are actively stabilised by checkpoint pathways, but in some cases component proteins still dissociate from the site of DNA incorporation, resulting in fork ¿collapse¿. Collapsed forks can be restarted by homologous recombination (HR)-based processes, but are strongly associated with gross chromosomal rearrangements. Thus, the advantage gained by restarting a collapsed fork comes at the expense of an increased potential for genome instability.
Structural, biochemical, and molecular techniques identified the main components and regulators of these processes, but are inherently limited to studying the system in bulk, thereby averaging events and limiting our understanding of the dynamics and behaviour of molecular participants. To overcome these limitations and to study single molecules at a single arrested or collapsed fork I propose to develop an nTIRF-PALM ¿super-resolution¿ microscopy platform that will allow the identification of individual protein molecule as well as very small numbers of molecules at <50 nanometer resolution inside the nucleus of a living eukaryotic cell. I propose to apply this methodology to the model organism fission yeast (S. pombe) to study the organization and structure of normal and restarted replication forks. To achieve this I propose to extend the development of site-specific and temporally controlled replication fork arrest systems to manipulate a single replication fork at a defined DNA locus. By creating a variety of fluorescent protein tags we will record ""molecular movies"" to provide insight into the dynamics and reaction mechanisms."
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
- humanities arts modern and contemporary art cinematography
- 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.
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.
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.
ERC-2010-AdG_20100317
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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.
Host institution
BN1 9RH BRIGHTON
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.