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Origination of novel gene regulatory networks in the evolution of mammalian pregnancy

Objective

One of the deepest unanswered biological questions is how new phenotypes arise in evolution. To address this question, I propose to investigate a major mammalian innovation: pregnancy. Phenotypic novelties of pregnancy include efficient placental delivery of nutrients and internal fetal development. When being established, these novelties were associated with major gene regulatory changes in the endometrium of the uterus. My preliminary studies in human endometrial cells suggest that aryl hydrocarbon receptor (AHR) regulates genes that are essential for placental development and maternal immunotolerance of the fetus. It is also known that AHR evolved endometrium-specific expression early in the mammalian ancestor and acquired the ability to repress estrogen signalling necessary for implantation only in placental mammals. Here, I propose to study the origination of novel endometrial gene regulatory networks of AHR. I will establish the full endometrial target gene sets of AHR in major placental lineages and a non-placental out-group (opossum). Potential AHR targets will be validated in endometrial cells using knockdowns and reporter assays. The results of this study will provide a paradigm for understanding how transcription factors integrate into a new cell-signalling network. The findings will also expand our knowledge of the mechanisms of AHR-mediated toxicity of dioxins in mammalian reproduction and may reveal new therapeutic targets for the treatment of female reproductive disorders such as preeclampsia and endometriosis.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

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.

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.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

TURUN YLIOPISTO
Net EU contribution

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.

€ 191 325,60
Total cost

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.

€ 191 325,60
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