Objective
Genomic instability is a key hallmark of cancer. Chromosome translocations require the formation of pairs of double-strand breaks (DSB) and trans-chromosomal ligation of the broken ends. Members of the AID/APOBEC family of enzymes deaminate cytosine (C) to uracil (U) in the context of a polynucleotide substrate. Excision of the U residue from DNA produces an abasic site, leading to incision of the DNA strand containing the abasic site by the conventional base-excision repair pathway. The introduction of proximal incisions on both DNA strands can generate a DSB intermediate for chromosomal translocation. AID acts on C residues at immunoglobulin loci in activated B cells to trigger antibody gene diversification and is the only member of the AID/APOBEC family that is currently known to act physiologically on endogenous nuclear DNA. Off-target deamination by AID results in nucleotide substitutions and genomic rearrangements in B lymphocyte tumours. APOBEC1 edits mRNA transcripts in the small intestine. Liver-directed misexpression of APOBEC1 is oncogenic in transgenic mice. APOBEC3 enzymes are ubiquitously expressed and act on C residues in the cDNA viral replication intermediates as part of a host restriction pathway. APOBEC3A and APOBEC3B have been shown to be capable of causing genomic damage in mammalian cells. Access to the nucleus by APOBEC family members likely permits DNA deamination activity that introduces mutations and genomic instability during tumourigenesis. I have generated mice that harbour FLAG-tagged forms of AID, APOBEC1, APOBEC3A or APOBEC3B inserted at the ROSA26 locus, preceded by a floxed stop sequence for conditional expression. This system will be used to understand the role of cytosine deamination in tumour progression in tissue- and time-specific contexts in vivo through whole genome sequencing of tumours. The long-term goal is to initiate the development of reagents to regulate APOBEC activity in basic science and clinical oncology.
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 genetics mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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-2014
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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.
13125 Berlin
Germany
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.