Project description
The role of transposons in placenta development
Development of the placenta largely depends on genetics of both the foetus and the mother. Understanding the underlying mechanisms will provide important knowledge on pregnancy complications such as preeclampsia and growth restriction. The EU-funded InvADeRS project is investigating the role of transposable elements (TEs), mobile DNA elements found in mammalian genomes that have emerged during evolution from viral infections. Researchers are interested to understand whether TEs regulate gene expression in the placenta of humans driving placental invasion into the maternal uterus. Identification of specific TEs with regulatory potential points towards key pathways implicated in normal pregnancy and may fuel further research in the field.
Objective
Aberrant epigenetic regulation of placental function is implicated in several complications of pregnancy, such as preeclampsia, recurrent pregnancy loss and fetal growth restriction. Notably, the placenta has a unique epigenetic landscape, permissive for the activity of transposable element (TE) derived DNA sequences. TEs are often co-opted by the host genome as cis-regulatory elements, driving tissue- and species-specific gene expression programs. Indeed, TEs contribute many placental-specific enhancers in mouse trophoblast. However, the presence and role of a similar TE-derived regulatory network has not been explored in human trophoblast. As TEs are highly species-specific, such a network in humans would be expected to regulate species-specific placental characteristics, such as the deep interstitial invasion unique to great apes. TE-derived regulatory elements may therefore be important for placental homeostasis and be involved in diseases characterised by aberrant placental invasion. I propose to map TE-derived cis-regulatory sequences in human trophoblast ex vivo using their histone modification signatures. I will assess the regulatory potential of candidate TEs through transcriptomic analyses and motif analysis to reveal transcription factor binding sites, highlighting promising candidates of importance in the human placenta. I will then directly test the function of top TE candidates using CRISPR-Cas9 genome editing of the TEs in trophoblast in vitro, and measuring changes in expression of target genes. Finally, I will elucidate epigenetic and coding differences between complicated and normal control placentas at the functional regulatory TE loci I find, to identify correlations with disease. This project will provide a comprehensive analysis of an as-yet unexplored aspect of human placental epigenetic regulation, and potentially identify novel causes of common unexplained complications of human pregnancy.
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 zoology mammalogy primatology
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences clinical medicine obstetrics fetal medicine
- natural sciences biological sciences genetics genomes
- medical and health sciences basic medicine physiology homeostasis
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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-RI - RI – Reintegration panel
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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-2018
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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.
E1 4NS LONDON
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.