Objective
The human genome is largely composed of non-coding DNA, only 3-5% codes for exons. The majority of the non-coding DNA is however fundamental for the correct functioning and regulation of the genome. Transposable elements (TEs) like LINEs generated up to 50% of the human genome during evolution. They can mobilize, causing mutations but also conferring genomic plasticity. The generation of new insertions in the germ line led to the concept of TEs as ‘selfish’ DNA. However, inconsistent with their hereditary transmission, it was recently shown by the host lab and others that most of the action of TEs occurs in somatic cells during early embryogenesis.
Thus, to deeply understand the impact of the somatic activity of LINE elements, we propose to develop and use an in vivo mouse model for LINE transposition. We will use human embryonic stem cells (hESCs) and tissue-specific iPSCs, containing an eGFP-marked LINE reporter cassette. Once injected into immuno-suppressed mice these cells will develop teratomas containing tissues of the 3 germ layers (endo, meso, ectoderm). For the proof of principle, the host lab has injected human embryonic carcinoma cells (hECs). With this model, we aim to answer the following: 1) Are LINEs active in all three germ layers?; 2) Are LINEs differentially regulated, depending on the germ layer?; 3) What’s the impact of LINE activity in the somatic tissues?
To answer these questions, we will FACS-sort parts of the teratoma into ecto-, meso-, and endoderm-like cells and map the site of new LINE insertions during development, using deep sequencing. We aim to detect hot spots of LINE integration, allowing the analysis of possible genetic and phenotypic consequences. Imaging of the rest of the teratoma will further show us cell types where transposition occurs with higher frequency and possible phenotypic alterations. We therefore hope to detect new principles of genomic plasticity that could regulate gene expression.
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 developmental biology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- 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.
FP7-PEOPLE-2011-IEF
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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.
Coordinator
41092 Sevilla
Spain
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.