Objective
                                DNA replication is essential to cellular function. During a lifetime, each of us synthesizes a light-year’s length of DNA, but this process is so robust that few of us will develop cancer. In eukaryotes, DNA is packed into chromatin, a hierarchical DNA-protein assembly of which the nucleosome forms the basic unit. Chromatin replication convolves DNA replication with the duplication and reassembly of all DNA-associated proteins. Understanding the coupling between these processes has fundamental implications for epigenetic inheritance and cancer.
The goal of this proposal is to gain spatiotemporal insight into chromatin replication by using our biophysical expertise in replication and chromosomal dynamics to build up a mechanistic timeline of the process. We will harness recent advances in the reconstitution of the yeast replisome alongside our novel, high-throughput single-molecule approach to visualize and quantify the collaboration between a single yeast replisome and the histone chaperones to achieve chromatin replication. We will:
•Monitor the assembly of the replisome on chromatin and visualize how nucleosomes impact its progression.
•Quantify how the replisome and histone chaperones disrupt nucleosomes and retain histones for further processing.
•Detect the deposition of newly synthesized histones behind the replisome and reveal the interactions between replisome components and histone chaperones that couple replication to nucleosome assembly.
•Report on the phenomenon of epigenetic inheritance by imaging histone recycling between parental and daughter DNA. We will examine its timing and efficiency, the conformations of reassembled nucleosomes, and any preferential recycling to either daughter DNA.
This proposal places us in a unique position to make major contributions to the field of chromatin replication, and to provide the field with a powerful tool to investigate topics from fundamental questions in molecular biology to the performance of new cancer drugs.
                            
                                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.
- engineering and technology environmental engineering waste management waste treatment processes recycling
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences molecular 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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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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.
ERC-ADG - Advanced Grant
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              Call for proposal
                
                  
                  
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(opens in new window) ERC-2017-ADG
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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.
2628 CN DELFT
Netherlands
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